gigachad-library/autonomic-systems.html

<!DOCTYPE html>
<html lang="en">
<head>
    <meta charset="UTF-8">
    <meta name="viewport" content="width=device-width, initial-scale=1">
    <title>Autonomic systems — GigaChad</title>
    <link rel="icon" href="/favicon.ico">
    <link rel="stylesheet" href="/style.css?v=1">
    <meta property="og:type" content="website">
    <meta property="og:title" content="Autonomic systems — GigaChad">
    <meta property="og:description" content="The greatest website on the interwebz!">
    <meta property="og:image" content="/icons/chads/chad.png">
</head>
<body>
<script>
const setTheme = () => {
    const root = document.documentElement
    const storage = localStorage.length > 0 ? localStorage : sessionStorage
    for (let key in storage) {
        if (storage.hasOwnProperty(key)) {
            root.style.setProperty(key, storage.getItem(key))
        }
    }
}
setTheme()
document.addEventListener('visibilitychange', () => { if (!document.hidden) setTheme() })
</script>
    <h1>Autonomic systems</h1>
    <div style="text-align: center;">
        <a href="/"><img class="epic" src="/icons/chads/chad.png"></a>
    </div>
    <hr>
<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
<p>From the <a href="https://raypeat.com/articles/other/autonomic-systems.shtml" target="_blank">original article</a> in 2006. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
  <p><em>Historically, 
functions such as reason, emotion, and instinct were associated with 
particular nervous structures, and there was a reluctance to think that 
consciousness, like instinct, could be based on "reflexes." Eventually, 
this led to the idea of an autonomous nervous system which produced 
emotions and adjusted the body's functions, while the "central nervous 
system" was the seat of conscious thought, perception, and behavior.</p>
<p>Our individual 
cells have a degree of autonomy, consisting of the ability to sense 
their situation, integrate stimuli, and act adaptively. Their behavior 
is intelligently adaptive. The cells that make up the nervous system 
have this basic capacity for complex adaptive integration, but they 
also have the specialized role of serving as links between cells, and 
between cells and the environment. </p>
<p>The integration 
of the organism is most complete when the energy of each cell is optimal. 
The "autonomic nervous system," including nerves that are closely 
associated with the diverse organs and tissues, is easiest to understand 
as a system for integrating and optimizing energy throughout the organism.</p>
<p>This view 
suggests new ways of understanding imbalance in these nervous functions, 
and the diseases that develop under the imbalanced conditions--e.g., 
asthma, polycystic ovaries, menopausal symptoms, some skin diseases, 
multiple sclerosis, heart disease, and tumors.</p>
<p>Every organ 
has its own intrinsic nerve net, and the cortex of the brain adjusts 
each system to meet the adaptive needs of the organism.</p>

<p>When every 
cell is functioning optimally, and the organism is adapted to its environment, 
there is little need for intervention by the "transmitter substances."</em> </p>

<p>
<p>   
People 
like Walter Cannon and Wilhelm Reich popularized the idea of the autonomic 
nervous system, but they were just systematizing ideas that had been 
developing since the beginning of the century. Their views were the 
context in which Selye’s idea of stress developed.</p>

<p>The 
anatomical components of the nervous system that were called the sympathetic 
(“fight or flight,” adrenergic) system and the parasympathetic (“vegetative”) 
system are still important factors in physiological thinking, and despite 
the great complexity that has grown up around them, there is still a 
tendency to identify the systems with polarities of mood or emotion. 
The idea of polarities is useful, but it easily leads to error.</p>
<p>(The 
sympathetic system includes a chain of ganglia along the spine, and 
its functions include dilating the pupils and accelerating the heart. 
The parasympathetic system is also called the cranio-sacral system, 
from the location of its ganglia, and among its functions are slowing 
the heart and constricting the pupils. However, despite several decades 
of research, the actions of “sympathetic” and “parasympathetic” 
nerves in most organs aren’t understood.)</p>
<p>If 
the “adrenaline side” of the nervous system is responsible for the 
reactions to pain and threat, reactions of fear and rage, then the opposite 
side tends to be given attributes such as peace and pleasure, and the 
fact that these oppositions are often true has led to a climate in which 
the adrenergic reactions are seen as “bad,” and the opposite reactions 
as “good.” When adrenalin was identified as an agent of the sympathetic 
nervous system, there was a search for the “opposing” agent of the 
parasympathetic system. Histamine was an early candidate, before acetylcholine 
was discovered to be the main parasympathetic agent. This view of histamine 
was fostered by the older idea of “trophic nerves,” which easily 
became identified with the parasympathetic system. When acetylcholine 
was identified as the transmitter or agent of the parasympathetic system, 
it tended to take on many of the qualities, including the “trophic” 
functions, that had grown up around the idea of the parasympathetic 
system, but the emphasis on acetylcholine led to a general neglect of 
the associations of histamine, and the mast cells that produce much 
of it, with the autonomic nervous system. (The current trend seems to 
be emphasizing a close integration of mast cell function with nervous 
function.)  Nitric oxide has recently been identified as another 
parasympathetic “transmitter.” Nitric oxide and histamine are both 
very important factors in degenerative inflammatory diseases, but their 
association with the parasympathetic nervous system has given them an 
aura of benevolence.</p>
<p>I 
think it’s useful to compare the autonomic nervous system with the 
pituitary, not just because some of the pituitary hormones are called 
“trophic” hormones (e.g., luteotrophic, adrenocorticotrophic), but 
because their important adaptive functions can themselves be the cause 
of serious problems. An excess of the thyroid stimulating hormone, for 
example, causes degeneration and cancer development in the thyroid gland, 
and animals deprived of their pituitary gland, but given thyroid, live 
longer than intact animals. </p>
<p>If 
slaves are starved and beaten frequently, they aren’t very productive, 
they don’t live long, and they might rebel. Workers that are healthy 
and working for a common goal that they understand are more productive. 
Cells that are well energized perform their functions with minimal cues, 
but deprived cells that have to be forced to function are likely to 
die unexpectedly, or to reproduce inappropriately, or to change their 
identity.</p>
<p>Professors 
often make a strong impression on their students, but, especially in 
technical or scientific fields, they usually do this by controlling 
the discourse, so that radical questioning is excluded. What they don’t 
know “isn’t knowledge.” Under the pressure of “getting a professional 
education,” students appreciate organizing principles and mnemonic 
devices, but this gives traditional ways of systematizing knowledge 
tremendous power that, in practice, is far more important than mere 
experimental results. (Experiments that don’t acknowledge the ruling 
metaphors are almost universally considered inadmissable, 
unpublishable.)</p>

<p>Some 
obvious questions about the autonomic system have been commonly ignored 
or minimized by physiologists. If “stress” is the stimulus that 
causes the sympathetic system to increase its activity, what is the 
stimulus for increased activity of the parasympathetic system? What 
accounts for the relative balance between the two sides of the system, 
or their imbalance? The fact that the answers aren’t obvious has left 
the questions largely to psychiatrists and psychologists. Wilhelm Reich, 
who tried to provide answers in terms of developmental interactions 
between the organism and its environment, found that the question led 
him to investigate psychosomatic disease, sexual repression, cancer, 
and fascism, with disastrous results for himself. </p>
<p>Chinese 
medicine was familiar with many of the functions of the autonomic nervous 
system at a time when western medicine was organized around “the humors.” 
It’s easy for contemporary “western” people to see that the “winds” 
and the hot and cold principles of Chinese tradition are metaphors, 
but they are reluctant to see that their own system has grown up within 
very similar traditional metaphoric polarities.</p>
<p>The 
successes of even a good metaphor can cause people to neglect details 
that could support a more complete and accurate image of reality.</p>
<p>Contemporary 
science carries a load of bad metaphors, because the educational system 
doesn’t tolerate a critical attitude. Potentially, a good metaphor 
(e.g., Vernadsky’s suggestion that an organism is “a whirlwind of 
atoms”) could blow away many bad metaphors, but the present organization 
of science is tending in the other direction<strong>:</strong> Commercial interests 
are creating a culture in which their metaphors are replacing the traditional 
science in which there was a certain amount of honest intellectual exploration.
</p>

<p>In 
talking about consciousness, sleep, stress, biological rhythms, aging, 
and energy, I have often focussed on the efficient use of oxygen for 
energy production by the mitochondria, i.e., cellular respiration. Every 
situation demands a special kind of adaptation, and each kind of adaptation 
requires a special distribution of cellular and organic activity, with 
its supporting local respiratory activity.</p>
<p>There 
is a lot of local self-regulation in the adapting organism, for example 
when the activated tissue produces increased amounts of carbon dioxide, 
which dilates blood vessels, delivering more oxygen and nutrients to 
the tissue. But the distribution of excitation, and the harmonious balancing 
of the organism’s resources and activities, is achieved by the actions 
of the cortex of the brain, acting on the subordinate nerve nets, adjusting 
many factors relating to energy production and use.</p>
<p>On 
the level of the mitochondria, adrenaline and acetylcholine have slightly 
different effects. (Metabolic studies with isolated mitochondria are 
so remote from the normal cellular condition that their results are 
nothing more than a hint of what might be occurring in the cell.) Acetylcholine 
appears to shift the proportion of the fuels used (increasing the oxidation 
of alpha-ketoglutarate, with the production of carbon dioxide) and increasing 
the efficiency of energy conservation (phosphorylation, producing ATP) 
so that less oxygen is needed, while adrenaline increases the rate of 
oxygen consumption (and succinate oxidation). This would be consistent 
with F. Z. Meerson’s conception of the parasympathetic function as 
one of the “stress limiting” systems.</p>
<p>On 
the level of the whole cell, organ, and organism, the parasympathetic 
function limits oxygen consumption in a variety of ways, including the 
reduction of blood flow. Acetylcholine, like histamine and serotonin, 
activates glycolysis, the conversion of glucose to lactic acid, which 
provides energy in the absence of oxygen.  </p>
<p>The 
effects of a little adrenaline, and a lot of adrenaline, are very different, 
with a high concentration of adrenaline decreasing the efficiency of 
phosphorylation. In the stressed heart, this effect of excess adrenaline 
can be fatal, especially when it is combined with adrenaline’s acceleration 
of clotting, liberation of fatty acids, and frequently of calcium, and 
constriction of blood vessels. </p>
<p>Seventy 
years ago, autonomic control of blood vessels seemed to be a matter 
of nerve fibers that constrict them, and other fibers that cause them 
to dilate, but that idea hasn’t worked for a long time.</p>

<p>Ever 
since I noticed that the students in our physiology lab who tried to 
use adrenaline to revive their rats weren’t successful, I have wondered 
about the television shows in which adrenaline is given to patients 
with heart problems. Under some conditions adrenaline does increase 
circulation to the heart, but extreme stress doesn’t seem to be among 
those conditions.</p>
<p>Too 
much serotonin, histamine, acetylcholine, and polyunsaturated fatty 
acids, like too much adrenalin, can cause spasms of the coronary arteries, 
along with disturbances of mitochondrial respiration. In stress, these 
substances are almost sure to be present in excess. (Anti-serotonin 
drugs are effective for a variety of heart problems, and other degenerative 
diseases.)</p>
<p>By 
increasing the production of lactic acid and the loss of carbon dioxide, 
exaggerated nervous stimulation (especially the excess of acetylcholine, 
histamine, and serotonin) can cause a variety of problems, including 
generalized vasoconstriction and systemic alkalosis, as well as increased 
intracellular alkalinity.  This metabolic pattern is characteristic 
of many kinds of stress, including cancer. (Elsewhere, I have referred 
to this pattern as “relative hyperventilation.”) The metabolic effects 
probably account for some of the “paradoxical” effects of the autonomic 
agents.</p>
<p>When 
nutrition and thyroid function, light, atmospheric pressure, and other 
conditions are favorable, the autonomic transmitters (e.g., acetylcholine, 
histamine, serotonin, adrenalin) and pituitary hormones and other “signal 
substances” are kept within safe limits.</p>
<p>Because 
the substances released from various cells under the influence of the 
autonomic nerves (histamine and serotonin, for example) stimulate cell 
division, injuries which produce clots and vascular spasms will also 
stimulate the formation of new blood vessels, a process that is essential 
for the adaptation of tissues to prolonged stress.</p>
<p>These 
stress-induced agents are appropriately included in the “vegetative” 
(parasympathetic) nervous system, because they promote vegetation, i.e., 
the proliferation of substance.</p>

<p>Adrenaline, 
and the sympathetic nerves, have the opposite function, of restraining 
cell division, and they also oppose the pro-inflammatory functions of 
those parasympathetic agents.</p>
<p>Estrogen 
tends to shift autonomic balance toward the parasympathetic side, away 
from the sympathetic/adrenergic. Recalling that stress, hypothyroidism, 
and aging increase the activity of aromatase in various tissues, with 
local production of estrogen, and that tissue-bound estrogen stays at 
a high level in postmenopausal women despite the lower level of estrogen 
in the serum, it’s worthwhile looking at the effects of estrogen on 
the various components of the so-called autonomic nervous system.</p>
<p>One 
injection of estrogen can induce a large increase in the number of sympathetic 
nerves in the ovaries. At menopause, a similar “invasion” of sympathetic 
nerves occurs. The polycystic ovary (which is even more common after 
menopause than before, and some studies have found the condition in 
20% of premenopausal women) responds to estrogen by producing nerve 
growth factor(s), and growing a large number of new sympathetic nerves. 
Although the hyperestrogenism associated with the polycystic ovary syndrome 
has many harmful effects, the invasion of the ovary by adrenergic nerves 
apparently protects it from the development of cancer. </p>
<p>Parasympathetic 
nerves, pituitary hormones and mast cells activate the ovaries. The 
number of mast cells in the ovaries is increased by the pituitary hormones 
(including the thyroid stimulating hormone), and by estrogen (Jaiswal 
and Krishna, 1996). Estrogen is the most potent of these hormones in 
causing the cells to release histamine. The overgrowth of the sympathetic 
nerves in the polycystic 
ovary causes the number and activity of mast cells to decrease, possibly 
as a protective adaptation against excessive stimulation from the many 
pro-inflammatory factors. The mast cells are needed for the follicles 
to rupture, so their suppression prevents ovulation. </p>
<p>The 
nervous system is closely involved in controlling the growth of tissues, 
and it has been argued (R.E. Kavetsky reviewed the subject in his book, 
emphasizing the role of depression in development of cancer) that cancer 
results from reduced activity of the sympathetic nerves, or unopposed 
action of the parasympathetic system. That stress has a role in cancer 
is acknowledged by the scientific establishment, but the nervous system’s 
direct involvement in the regulation of cellular metabolism, cell division, 
and other processes that are central to the cancerous state is either 
flatly denied or simply ignored.</p>
<p>Although 
mast cells have been known to be a common component of tumors for many 
years, it is only recently that antihistamines and other antiinflammatory 
drugs have been recognized as valuable therapies in cancer. The whole 
issue of the role of nerves in tumor development and physiology has 
been submerged by the mystique of the “intrinsically bad cancer cell.”</p>

<p>In 
Alzheimer’s disease, there has been a great investment in the doctrine 
that drugs to promote the function of cholinergic (acetylcholine forming) 
nerves will restore lost mental function, or at least retard the progression 
of the disease. The success of <strong><em>anti</em></strong>cholinergic drugs in 
treating several degenerative brain diseases is probably embarrassing 
to the companies whose cholinergic-intensifying drugs aren’t very 
successful. Conveniently for them, these formerly “anticholinergic” 
drugs are now being called anti-excitotoxic or anti-glutamatergic drugs. 
There is no serious conflict in the terminology, since the cholinergic 
processes (like the serotonergic processes) are closely associated with 
excitotoxic nerve damage. The cholinergic drugs will probably be sold 
as long as their patents are effective, and then will be quietly forgotten.</p>
<p>The 
modern conception of pharmacology, with receptors and transmitters turning 
functions on or off, has turned into an unproductive and dangerous scholasticism. 
No one will ever successfully count the number of transmitter angels 
dancing on the variable sites of the variable receptor molecules. The 
functional “meaning” of a receptor or transmitter changes according 
to circumstances, and the effect of activating a particular nerve depends 
on surrounding conditions, and on preceding conditions. Each cell integrates 
stimuli adaptively.</p>
<p>If 
no reflex is simply mechanical and innate, then all reflexes are conditional. 
(M. Merleau-Ponty argued against the validity of the reflex concept 
itself, because of this conditionality.) P. K. Anokhin’s concept of 
the “Acceptor of Action” (described in my book, <strong><em>Mind and Tissue</em></strong>) 
provides an image in which we can see the “set-points” for the relatively 
“autonomic” reflexes as reflections of the general needs of the 
organism. The local tissue reflexes, the organ reflexes, the spinal 
reflexes, etc., are variable, according to their energetic resources, 
and according to the way in which they are organized under the influence 
of the cerebral cortex and the environment. </p>
<p>The 
reality is more complex than the philosophy of the drug industry imagines, 
but the solutions of problems can be much simpler, if we think in terms 
of energetic support, rather than the over-concretized interventions 
of the pharmacologists. In hypothyroidism, it is common for there to 
be an excess of adrenalin/noradrenalin, serotonin, histamine, and some 
of the pituitary hormones.  Correcting thyroid function can immediately 
correct many problems, but especially when the energy deficiency has 
caused anatomical adjustments (redistribution of blood vessels and mast 
cells, for example) it’s important to make the environment supportive 
in as many ways as possible.</p>
<p>In 
polycystic ovaries, menopausal symptoms, arthritis, angina pectoris, 
multiple sclerosis, some kinds of dementia, migraine, and emphysema, 
the relief achieved with a simple improvement of cellular energy can 
be rapid and complete. Presumably a similar process of biological reorganization 
is involved in the occasional spontaneous regression of tumors. </p>

<p>Although 
I don’t think the autonomic nervous system, with its sympathetic and 
parasympathetic divisions, exists in the way it has traditionally been 
conceived, the idea can be useful if we think of using drugs and other 
factors in ways that tend to <strong><em>“quiet an overactive autonomic 
nervous system.” </em></strong></p>
<h2>References</h2>
<small>
<p>Am 
J Emerg Med 1989 Sep;7(5):485-8. <strong>Coronary artery spasm induced by 
intravenous epinephrine overdose.</strong> Karch SB. A 27-year-old man was 
accidentally given 2 mg intravenous epinephrine instead of 2 mg naloxone. 
He immediately developed chest pain, nausea, and diaphoresis. An ECG 
taken shortly after the epinephrine administration showed widespread 
ischemia. Forty-five minutes later the tracing still showed an early 
repolarization pattern, but ST elevation was less marked and the patient 
was asymptomatic. Serum potassium was 3.2 mEq/L and serum catecholamines, 
drawn approximately 20 minutes after the epinephrine administration, 
were 10 times normal (dopamine, 173 ng/L; epinephrine, 1,628 ng/L; norepinephrine, 
1,972 ng/L). There are seven other reports of intravenous epinephrine 
overdose in the English literature. Two of the previously reported cases 
had 12-lead ECGs within the first hour. In both there was evidence of 
transient ischemia similar to that observed in this case. Most of the 
patients had symptoms consistent with angina,<strong> and several developed 
pulmonary edema. These findings suggest that, in humans, large intravenous 
doses of epinephrine are likely to produce coronary artery spasm and 
may decrease coronary artery perfusion.</strong></p>

<p>Res 
Exp Med (Berl) 1987;187(5):385-93. <strong>Possible interaction of platelets 
and adrenaline in the early phase of myocardial infarction.</strong> Seitz 
R, Leising H, Liebermann 
A, Rohner I, Gerdes H, Egbring R. “<strong>It is known that in most cases 
of transmural acute myocardial infarction a platelet clot originates 
within a coronary artery. In acute myocardial infarction patients increased 
levels of the plasma catecholamines adrenaline and 
noradrenaline as well as the platelet release proteins platelet factor 
4 and beta-thromboglobulin have been reported.” </strong>
</p>
<p>Anesthesiology 
1991 Jun;74(6):973-9. Comment in:  Anesthesiology. 1992 Mar;76(3):475. <strong>
Magnesium inhibits the hypertensive but not the 
cardiotonic actions of low-dose epinephrine.</strong> Prielipp RC, Zaloga 
GP, Butterworth JF 4th, Robertie PG, Dudas LM, Black KW, Royster RL. 
Intravenous magnesium supplementation is often used to control cardiac 
arrhythmias and coronary artery vasospasm resulting from disturbances 
of magnesium homeostasis after coronary artery bypass surgery. Many 
such patients also require inotropic drug support of depressed myocardial 
function. However, increased serum magnesium concentrations directly 
depress cardiac contractility in animals and may interfere with catecholamine 
actions. To determine whether small intravenous doses of magnesium sulfate 
(MgSO4) interfere with the cardiotonic actions of epinephrine, we examined 
the hemodynamic effects of MgSO4 and epinephrine infusion in 17 cardiac 
surgical patients on their 1st postoperative day in a prospective, controlled 
study. In 11 patients, infusion of MgSO4 (7-mg.kg-1 bolus followed by 
10 mg.kg-1.h-1 as a continuous infusion) increased serum magnesium concentrations 
by 44% (mean +/- standard error of the mean [SEM] of 0.8 +/- 0.1 to 
1.2 +/- 0.1 mM; P less than 0.01) but had no significant effect on heart 
rate; mean arterial, central venous, or pulmonary arterial occlusion 
pressures; or cardiac output. Epinephrine infusion (30 ng.kg-1.min-1) 
significantly increased cardiac index (2.7 +/- 0.1 to 3.1 +/- 0.21.min-1.m-2; 
P less than 0.05); this effect was not altered by MgSO4 administration 
(n = 11). However, MgSO4 significantly blunted epinephrine's hypertensive 
action and prevented a significant increase in mean arterial pressure 
during concurrent MgSO4-epinephrine administration. Six placebo control 
patients were given two sequential infusions of epinephrine separated 
by a placebo infusion to rule out an effect of time on the hemodynamic 
response to epinephrine. Mean arterial pressure and cardiac index responses 
to epinephrine were identical before and after placebo infusion.

</p>
<p>Jpn 
Heart J 1979 Jan;20(1):75-82. <strong>Inhibition of constrictor responses 
of dog coronary artery by atropine. A possible effectiveness of atropine 
on variant form of angina pectoris.</strong> Sakanashi M, Furukawa T, Horio 
Y. A possible effectiveness of atropine on variant form of angina pectoris 
was investigated using the left circumflex coronary arterial strips 
of dogs. Acetylcholine 10(-5)--10(-3) Gm/ml dose-dependently constricted 
the isolated arterial strips during potassium-contracture in 6 cases, 
and repetitive applications of acetylcholine could produce the similar 
contractions to the control. In 18 strips atropine 10(-6) Gm/ml significantly 
depressed the contractions of coronary arteries induced by acetylcholine 
10(-5)--10(-3) Gm/ml. In 5 arterial strips atropine 10(-6) Gm/ml <strong>
significantly inhibited norepinephrine-induced responses</strong> of these 
arteries, and by 10(-5) Gm/ml further suppression of the responses was 
obtained. The <strong>results suggest that atropine may suppress the contractile 
responses of the coronary artery induce by 
acetylcholine and nonrepinephrine through a 
muscarinic-receptor blocking action and simultaneously partly through 
an adrenergic alpha-receptor blocking action.</strong>
</p>
<p>Eur 
J Clin Pharmacol 1981;20(4):245-50. <strong>Effect of long-term beta-blockade 
with alprenolol on platelet function and 
fibrinolytic activity in patients with coronary heart disease.</strong> Jurgensen 
HJ, Dalsgaard-Nielsen J, Kjoller E, Gormsen J.</p>

<p>C 
R Seances Soc Biol Fil 1987;181(3):242-8.<strong> [Adrenaline activates oxidative 
phosphorylation of rat liver mitochondria through alpha 1-receptors].</strong> 
Breton L, Clot JP, Bouriannes J, Baudry M. We studied the effects and 
mode of action of epinephrine on the oxidative phosphorylation of rat 
liver mitochondria. With either succinate or beta-hydroxybutyrate as 
substrate, i.v. injection of 1.5 microgram/100 g epinephrine increased 
the respiratory rates by 30-40% in state 3 (with ADP), and by 20-30% 
in state 4 (after ADP phosphorylation), so that the respiratory control 
ratio (state 3/state 4) changed little. The respiratory stimulation 
by epinephrine was maximal 20 minutes after its injection. The action 
of epinephrine on mitochondria was blocked by pretreatment of the animals 
with the alpha 1-antagonist prazosin but not by treatment with the beta-antagonist 
propranolol. I. v. injection of 10 micrograms/100 g phenylephrine evoked 
the same mitochondrial response as epinephrine. I. v. administration 
of 50 micrograms/100 g dibutyryl cyclic AMP enhanced glycaemia but did 
not affect mitochondrial respiration. Epinephrine therefore has an alpha 
1-type of action on mitochondrial oxidative phosphorylation.
</p>
<p>Biochimie 
1975;57(6-7):797-802. <strong>Effects of 
catecholamines on rat myocardial metabolism. I. Influence of 
catecholamines on energy-rich nucleotides and 
phosphorylated fraction contents.</strong> Merouze P, Gaudemer Y. 1. The 
influence of catecholamines (adrenaline and noradrenaline) on energy 
metabolism of the rat myocardium has been studied by incubating slices 
of this tissue with these hormones and by following the levels of the 
different phosphorylated fractions and adenylic nucleotides. 2. Similar 
effects are obtained with both hormones, adrenaline being more effective. 
3<strong>. Catecholamines decrease significantly the total amount of phosphate 
while Pi content increases during the first 10 minutes of incubation; 
labile and residual phosphate contents increase at the beginning of 
incubation and decrease to the initial values afterwards. 4. ATP and 
ADP levels decrease significantly</strong> with both hormones; however, the 
effect of noradrenalin on the ATP level needs a longer time of incubation. <strong>

The ATP/ADP ratios decrease after 5 minutes incubation and the total 
adenylic nucleotide content is severely decreased (35 per cent with 
adrenalin, after 20 minutes incubation). 5. Similar results have been 
obtained with other tissues; these results can explain the decrease 
of aerobic metabolism we observed under the same conditions.</strong>
</p>
<p>Eur 
J Pharmacol 1982 Jul 30;81(4):569-76<strong>. Actions of 
serotonin antagonists on dog coronary artery.</strong> Brazenor RM, Angus 
JA. <strong>“Serotonin released from platelets may initiate coronary 
vasospasm</strong> in patients with variant angina. If this hypothesis is 
correct, serotonin antagonists without constrictor activity may be useful 
in this form of angina. We have investigated drugs classified as serotonin 
antagonists on dog circumflex coronary artery ring segments in vitro. 
Ergotamine, dihydroergotamine,<strong> bromocriptine, 
lisuride, ergometrine, ketanserin, 
trazodone, cyproheptadine and pizotifen caused 
non-competitive antagonism of serotonin concentration-response</strong> curves. 
In addition, ketanserin, trazodone, bromocriptine and pizotifen inhibited 
noradrenaline responses in concentrations similar to those required 
for serotonin antagonism. All drugs with the exception of ketanserin, 
cyproheptadine and pizotifen showed some degree of intrinsic constrictor 
activity.” “Of the<strong> drugs tested, 
ketanserin may be the most useful in variant angina since it is a potent 
5HT antagonist, lacks agonist activity and has 
alpha-adrenoceptor blocking activity.”</strong></p>

<p>Arch 
Mal Coeur Vaiss 1983 Feb;76 Spec No:3-6.<strong> Role of autonomic nervous 
system in the pathogenesis of angina pectoris.</strong> Yasue H. “The attacks 
of vasospastic angina or coronary spasm can be induced by injection 
of epinephrine, cold pressor test, Valsalva maneuver, and exercise.” 
“The attacks of vasospastic angina can also be induced by injection 
of methacholine, a parasympathomimetic agent, and this reaction is suppressed 
by atropine, a parasympathetic blocking agent. Thus,<strong> parasympathetic 
nervous system also seems to play a role in the production of 
vasospastic angina. The attacks of 
vasospastic angina can be easily induced by 
adrenergic or parasympathetic stimuli from midnight to early morning 
but is</strong> usually not provoked by these stimuli in the daytime. Thus, 
there is circadian variation in the reactivity of coronary arteries 
to adrenergic or parasympathetic stimuli. There are also weekly, monthly 
and yearly variations of the reactivity of coronary arteries to these 
stimuli. Thus, <strong>alpha adrenergic or parasympathetic activity is not 
the sole factor in the production of 
vasospastic angina.</strong> Angina pectoris caused by increased myocardial 
oxygen demand is induced by infusion of isoproterenol, a beta adrenergic 
stimulant, and is suppressed by propranolol but not by phentolamine.”
</p>
<p>Nippon 
Yakurigaku Zasshi 1986 Mar;87(3):281-90. <strong>[Vasoconstrictor responses 
of isolated pig coronary arteries].</strong> [Article in Japanese] Ikenoue 
K, Kawakita S, Toda N.<strong> “In helical strips of pig coronary arteries, 
histamine, serotonin, acetylcholine and a stable analogue of 
thromboxane A2 (9, 11-epithio-11, 12-methano 
TXA2: s-TXA2) produced a dose-dependent contraction. The histamine-induced 
contraction</strong> was suppressed by treatment with chlorpheniramine, suggesting 
an involvement of H1 receptors. <strong>Contractile responses to 
serotonin were attenuated by not only 
ketanserin, an S2 antagonist, but also by 
cinanserin and methysergide.</strong>” “Contractile responses to histamine 
were potentiated by treatment with low concentrations of serotonin or 
s-TXA2. Contractile responses to serotonin were also potentiated by 
low concentrations of histamine or s-TXA2. Removal of the endothelium 
from pig coronary arterial strips potentiated contractions induced by 
serotonin, histamine and norepinephrine. These results suggest that, 
in addition to damaged endothelium, <strong>integrating action of endogenous 
vasoconstrictors, including histamine, 
serotonin, TXA2 and norepinephrine, may play an important role in producing 
coronary vasospasm.”</strong></p>

<p>Jpn 
Heart J 1987 Sep;28(5):649-61<strong>. The role of parasympathetic nerve 
activity in the pathogenesis of coronary 
vasospasm.</strong> Suematsu M, Ito Y, Fukuzaki H. To evaluate the role of 
the autonomic nervous system, especially the parasympathetic nervous 
system, in the initiation mechanism of vasospastic angina pectoris (AP), 
the coefficient of R-R interval variation (CV) on the electrocardiogram 
(ECG) and plasma catecholamine concentration were measured in 25 patients 
with vasospastic AP, 10 patients with effort AP and 12 control subjects. 
CV which has been recognized as reflecting parasympathetic nervous system 
activity was calculated from 100 consecutive heart beats on the ECG 
and represented as the percentage of standard deviation of the R-R interval 
per mean R-R interval. Repeated measurements of <strong>plasma 
catecholamine concentration revealed higher values at any sampling point 
throughout a day in patients with vasospastic AP than those in </strong>
control subjects. A distinctly higher CV was observed at night in the 
vasospastic AP group. <strong>This elevated CV was abolished by atropine 
sulfate (1.5 mg/day per os). Pilocarpine injection (1.3 mg/10 kg 
B.W. subcutaneously) induced a marked increase</strong> in CV that preceded 
the occurrence of chest pain and/or ischemic ECG changes in 5 patients 
with vasospastic AP. The<strong> increment in CV at 10 min after 
pilocarpine administration was greater in 
vasospastic AP than in control subjects (p less than 0.05). It is concluded 
that enhanced parasympathetic activity may play a role in the initiation 
of coronary vasospasm associated with sympathetic hyperactivity.</strong>
</p>
<p>Science 
1984 Mar 30;223(4643):1435-7.<strong> Coronary arteries of cardiac patients 
are hyperreactive and contain stores of amines: a mechanism for coronary 
spasm.</strong> Kalsner S, Richards R. Coronary arteries from hearts of cardiac 
patients contain significantly higher concentrations of histamine than 
do those from noncardiac patients. The coronary vessels of cardiac patients 
are also hyperresponsive to histamine and serotonin. These differences 
between groups of patients suggest an explanation for coronary artery 
spasm in heart disease.</p>

<p>Fed 
Proc 1985 Feb;44(2):321-5. <strong>Coronary artery reactivity in human vessels: 
some questions and some answers.</strong> Kalsner S. “It is now clear that 
human coronary arteries in vitro contract to acetylcholine but that 
relaxation is the only response observed in dog coronary vessels. <strong>
Acetylcholine is as powerful a constrictor of human coronary arteries, 
in terms of tension induced, as 5-hydroxytryptamine (5-HT) or histamine 
and is a substantially more powerful constrictor than 
norepinephrine.</strong> Field stimulation of coronary artery strips caused 
a vasoconstriction that was partially antagonized by atropine (3.45 
X 10(-6) M).” “Coronary tissue from cardiac patients also contains 
stores of 5-HT and histamine, and the histamine levels are substantially 
increased above the values in vessels from noncardiac patients. Coronary 
artery spasm or contraction<strong> probably can be initiated by diverse 
intrinsic and extrinsic influences, including autonomic discharge from 
either the parasympathetic or sympathetic nervous system or from histamine 
or 5-HT, and probably no one agent or entity is causative in all cases.”</strong>
</p>
<p>Ann 
N Y Acad Sci 1969 Oct 14;164(2):517-9. <strong>Induced 
carcinogenesis under various influences on the hypothalamus.</strong> Kavetsky 
RE, Turkevich NM, Akimova RN, Khayetsky IK, Matveichuck YD.  </p>

<p>Kavetsky 
RE, (editor) <strong><em>The Neoplastic Process and the Nervous 
System,</em></strong>Kiev, 1958.</p>
<p>Ann 
N Y Acad Sci 1966 Jan 21;125(3):933-45. <strong>On the 
psychophysiological mechanism of the organism's resistance to tumor 
growth.</strong> Kavetsky RE, Turkevich NM, Balitsky KP.
</p>
<p>Patol 
Fiziol Eksp Ter 1971 Sep-Oct;15(5):3-10. <strong>[Role of disorders in 
intra-cellular and neuro-humoral regulation in the development of the 
tumor process]. </strong>[Article in Russian] Kavetskii RE, Balitskii KP.

</p>
<p>Mil’man, 
M.S., <strong>The sympathetic nervous system and the source of tumors,</strong> 
Problems of Oncology IX, 162-173, 1936.</p>
<p>Obstet 
Gynecol Surv 1977 May;32(5):267-81. <strong>Estrogen and 
endometrial carcinoma. </strong>Knab DR. “1. It has become evident that 
the estrogen secreting tumors of the ovary are associated with endometrial 
carcinoma, but this association is most easily observed in the postmenopausal 
patient where the incidence of carcinoma has been<strong> reported at 10.3% 
(1.  02) to 24% (83). 2. The most consistent association of 
endometrial carcinoma is with polycystic ovarian disease, where 19 (34), 
21 (152), and 25% (150) of young women with 
endometrial carcinoma had Stein-Leventhal syndrome (67). </strong>
3. A very significant discovery became known in 1967 when the peripheral 
aromatization of delta4 androstenedione to estrone was reported by Kase 
(94) and MacDonald (111,112). Since that time we have learned that endometrial 
carcinoma patients have an increased peripheral conversion (139) (0.1% 
compared to 0.027%), which is similar to that found in obese and aging 
patients, by Hemsell, et al (77). This can be 2 to 4 times greater than 
the young adult or the patient without cancer.” “Similarly patients 
with polycystic ovary disease, hyperthecosis and lipoid cell tumors 
of the ovary demonstrate androgen excess with extraglandular conversion 
to estrone (2). 4. It has become apparent that the principal estrogen 
in the postmenopausal patient is estrone and that the estrone-estradiol 
ratio in the serum is higher in postmenopausal women with corpus cancer 
than similar patients without cancer (135).” “5. With the lack of 
ovarian estrogen there is a relative excess of adrenal testosterone, 
dihydrotestosterone and delta4 androstenedione, the available precursors 
of extraglandular estrone (1). 6. With the passage of time <strong>it appears 
that endometrial carcinoma is associated with hypothalamic &quot;hyperactivity&quot;</strong> 

(31)....” </p>
<p>Endocrinology 
2000 Mar;141(3):1059-72.<strong> An increased 
intraovarian synthesis of nerve growth factor and its low affinity receptor 
is a principal component of steroid-induced 
polycystic ovary in the rat.</strong> Lara HE, Dissen GA, Leyton V, Paredes 
A, Fuenzalida H, Fiedler JL, Ojeda SR. A form of polycystic ovary (PCO) 
resembling some aspects of the human PCO syndrome can be induced in 
rats by a single injection of estradiol valerate (EV). An increase in 
sympathetic outflow to the ovary precedes, by several weeks, the appearance 
of cysts, suggesting the involvement of a neurogenic component in the 
pathology of this ovarian dysfunction. The present study was carried 
out to test the hypotheses that this change in sympathetic tone is related 
to an augmented production of ovarian nerve growth factor (NGF), and 
that this abnormally elevated production of <strong>NGF contributes to the 
formation of ovarian cysts induced by 
EV. Injection of the steroid resulted in increased 
intraovarian synthesis of NGF</strong> and its low affinity receptor, p75 
NGFR. The increase was maximal 30 days after EV, coinciding with the 
elevation in sympathetic tone to the ovary and preceding the appearance 
of follicular cysts. Intraovarian injections of the retrograde tracer 
fluorogold combined with in situ hybridization to detect tyrosine hydroxylase 
(TH) messenger RNA-containing neurons in the celiac ganglion revealed 
that these changes in NGF/p75 NGFR synthesis are accompanied by selective 
activation of noradrenergic neurons projecting to the ovary. The levels 
of RBT2 messenger RNA, which encodes a beta-tubulin presumably involved 
in slow axonal transport, were markedly elevated, indicating that EV-induced 
formation of ovarian cysts is preceded by functional activation ofceliac 
ganglion neurons, including those innervating the ovary. Intraovarian 
administration of a neutralizing antiserum to NGF in conjunction with 
an antisense oligodeoxynucleotide to p75 NGFR, via Alzet osmotic minipumps, <strong>
restored estrous cyclicity and ovulatory capacity in a</strong> majority 
of EV-treated rats. These functional changes were accompanied by restoration 
of the number of antral follicles per ovary that had been depleted by 
EV and a significant reduction in the number of both precystic follicles 
and<strong> follicular cysts. The results indicate that the 
hyperactivation of ovarian sympathetic nerves seen in 
EV-induced PCO is related to an overproduction of 
NGF and its low affinity receptor in the gland. They also suggest that 
activation of this neurotrophic-neurogenic regulatory loop is a component 
of the pathological process by which 
EV induces cyst formation and anovulation in rodents. The</strong> possibility 
exists that a similar alteration in neurotrophic input to the ovary 
contributes to the etiology and/or maintenance of the PCO syndrome in 
humans.</p>

<p>Acta 
Physiol Hung 1996;84(2):183-90.<strong> Effects of hormones on the number, 
distribution and degranulation of mast cells in the ovarian complex 
of mice.</strong> Jaiswal K, Krishna A. The changes in the number and degranulation 
pattern of mast cells varied with the types of hormonal treatment and 
ovarian compartment. <strong>Luteinizing hormone 
(LH), follicle stimulating hormone 
(FSH), thyroid stimulating hormone 
(TSH) and 17-beta estradiol (E2) treatment caused increase (P &lt; 0.05) 
in the number of mast cells</strong> in the hilum as compared with the controls. 
Increase (P &lt; 0.05) in the number of mast cells in the whole ovarian 
complex was observed only following FSH and E2 treatment. All the hormones 
used in the present study increased the percentage degranulation of 
mast cells in the hilum. However, only LH, FSH and E2 increased the 
percentage degranulation of mast cells in other compartments of the 
ovary (medulla, bursa and cortex). TSH and ACTH failed to cause any 
increase in the percentage degranulation of mast cells in these compartments. 
The present findings indicate E2 to be the most potent among the hormones 
tested in causing degranulation of mast cells in all ovarian compartments.
</p>
<p>Fertil 
Steril 2001 Jun;75(6):1141-7. <strong>Increase in nerve fibers and loss of 
mast cells in polycystic and postmenopausal ovaries.</strong> Heider U, Pedal 
I, Spanel-Borowski K. OBJECTIVE: To quantify nerve fibers and mast cells 
in human ovaries at different functional stages. DESIGN: Retrospective 
study. SETTING: Research laboratory of the university. SPECIMEN(S): 
8 human ovaries in the follicular (cyclic) phase, 7 polycystic ovaries, 
and postmenopausal ovaries with (n=5) or without (n=7) hyperthecosis. 
MAIN OUTCOME MEASURE(S): Single- and double immunohistology for the 
S100 antigen in glial cells of autonomic nerve fibers, for chymase and 
tryptase in mast cells, and for the common leukocyte antigen on leukocytes. 
Histometric evaluation was also performed. INTERVENTION(S): None. RESULT(S): 
Polycystic ovaries contained significantly more S100-positive nerve 
fibers in the corticomedullary region than did cyclic ovaries (mean 
+/- SD per 2-mm(2) area, 476 +/- 136 and 224 +/- 133; P&lt;.01). Postmenopausal 
ovaries with or without hyperthecosis had the highest density of nerve 
fibers. In cyclic and polycystic ovaries, more tryptase-positive mast 
cells than chymase-positive mast cells were found in the interstitial 
cortex and the medulla. In cyclic ovaries, areas with a moderate density 
of nerve fibers contained many mast cells. Hence, <strong>with increasing 
nerve fiber density in polycystic ovaries, the number of mast cells 
decreased strikingly compared with cyclic ovaries (p&lt;.001). Almost 
no mast cells were seen in postmenopausal ovaries</strong> with and without 
hyperthecosis. The number of leukocyte antigen-positive leukocytes was 
similar in all groups. CONCLUSION(S): The high density of nerve fibers 
in polycystic and postmenopausal ovaries, together with a conspicuous 
decrease in mast cells, indicates altered neuroimmune communication.

</p>
<p>Endocrinology 
1993 Dec;133(6):2696-703. <strong>Ovarian 
steroidal response to gonadotropins and 
beta-adrenergic stimulation is enhanced in 
polycystic ovary syndrome: role of sympathetic 
innervation.</strong> Barria A, Leyton V, Ojeda SR, Lara HE. Experimental 
induction of a polycystic ovarian syndrome (PCOS) in rodents by the<strong> 
administration of a single dose of 
estradiol valerate (EV) results in activation of the peripheral sympathetic 
neurons that innervate the ovary. This activation is evidenced by an 
increased capacity of ovarian nerve terminals to incorporate and release 
norepinephrine (NE), an increase in ovarian NE content, and a</strong> decrease 
in ovarian beta-adrenergic receptor number in the ovarian compartments 
receiving catecholaminergic innervation. The present experiments were 
undertaken to examine the functional consequences of this<strong> enhanced 
sympathetic outflow to the ovary.</strong> The steroidal responses of the 
gland to beta-adrenergic receptor stimulation and hCG were examined 
in vitro 60 days after EV administration, i.e. at the time when follicular 
cysts are well established. EV-treated rats exhibited <strong>a remarkable 
increase in ovarian progesterone and androgen responses to 
isoproterenol, a beta-adrenergic receptor 
agonist, with no changes in estradiol responsiveness. Basal 
estradiol release was, however, 50-fold higher than the highest levels 
released from normal ovaries at any phase of the estrous cycle.</strong> 
The ovarian progesterone and androgen responses to hCG were enhanced 
in EV-treated rats, as were the responses to a combination of isoproterenol 
and hCG. Transection of the superior ovarian nerve (SON), which carries 
most of the catecholaminergic fibers innervating endocrine ovarian cells, 
dramatically reduced the exaggerated responses of all three steroids 
to both beta-adrenergic and gonadotropin stimulation. SON transection 
also reduced the elevated levels of ovarian NE resulting from EV treatment 
and caused up-regulation of beta-adrenoreceptors. Most importantly, 
SON transection restored estrous cyclicity and ovulatory capacity. The 
results indicate that the increased output of ovarian steroids in PCOS 
is at least in part due to an enhanced responsiveness of the gland to 
both catecholaminergic and gonadotropin stimulation. The ability of 
SON transection to restore a normal response indicates that the alteration 
in steroid output results from a deranged activation of selective components 
of the noradrenergic innervation to the ovary. These findings support 
the concept that <strong>an alteration in the 
neurogenic control of the ovary contributes to the etiology of 
PCOS.</strong></p>

<p>Wilderness 
Environ Med 2001 Spring;12(1):8-12. <strong>Alterations in autonomic nervous 
control of heart rate among tourists at 2700 and 3700 m above sea level.</strong> 
Kanai M, Nishihara F, Shiga T, Shimada H, Saito S. “RESULTS: Both 
HF and LF heart rate variability <strong>decreased according to the elevation 
of altitude</strong>.” “CONCLUSIONS: <strong>At 2700 and 3700 m, the activity 
of the autonomic nervous system measured by heart rate variability was 
decreased</strong> in untrained office workers. The sympathetic nervous system 
was dominant to the parasympathetic at 3700 m. These alterations in 
the autonomic nervous system might play some role in physical fitness 
at high altitudes.”</p>
<p>Acta 
Neuroveg (Wien) 1967;30(1):557-63. <strong>[Neuroautonomic reactivity of 
the skin during high mountain climate treatment of skin diseases].</strong> 
[Article in German] Chlebarov S.</p>

<p>Munch 
Med Wochenschr 1966 Mar 18;108(11):589-92. <strong>[Changes of the 
neurovegetative reactivity of the skin after Alpine climatic therapy].</strong> 
[Article in German] Borelli S, Chlebarov S.</p>
<p>J 
Appl Physiol 1978 May;44(5):647-51. <strong>Mechanism of the attenuated cardiac 
response to beta-adrenergic stimulation in chronic 
hypoxia.</strong> Maher JT, Deniiston JC, Wolfe DL, Cymerman A.<strong> “A blunting 
of the chronotropic and inotropic responses of the heart to 
beta-adrenergic stimulation occurs following chronic exposure to 
hypobaric hypoxia.</strong>” “Neither monoamine oxidase activity nor 
norepinephrine level of any region of the heart was altered by chronic 
hypoxia. However, a twofold increase (P less than 0.001) <strong>in 
catechol O-methyltransferase activity above sea-level values was found 
in both the atria and ventricles of the 
hypoxic animals.</strong> Thus, the attenuation in cardiac responsiveness 
to beta-adrenoceptor stimulation in chronic hypoxia appears unrelated 
to the level of vagal activity, but may be attributable to enhanced 
enzymatic inactivation of catecholamines.”</p>

<p>Acta 
Physiol Scand 1976 Jun;97(2):158-65. <strong>Effects of respiratory alkalosis 
and acidosis on myocardial excitation.</strong> Samuelsson RG, Nagy G. In 
anesthetized dogs electrocardiogram and monophasic action potentials 
(MAPs) were recorded from the right atrium and the right ventricle by 
intracardiac suction electrode technique. The animals were subjected, 
by means of ventilation with CO2 and hyperventilation, to periods of 
respiratory acidosis and respiratory alkalosis, respectively.<strong> Pronounced 
respiratory acidosis induced an increased sympathetic activity </strong>
followed by a decrease in heart rate and prolongation of the A-V conduction 
time whereas the shape and duration of the atrial and ventricular MAPs 
remained unaltered. Arterial hypoxia in combination with pronounced 
respiratory acidosis did not influence the MAP durations. Respiratory <strong>
alkalosis resulted in an increased sympathetic influence on the heart 
activity</strong> whereas the shape and duration of the atrial and the ventricular 
MAPs remained unaffected. <strong>During pronounced hyperventilation with 
increasing central venous pressure an increased parasympathetic influence </strong>
on the heart activity with decrease in the heart rate, prolongation 
of the A-V conduction time and shortening of the atrial MAP duration 
was recorded.</p>

<p>Biull 
Eksp Biol Med 1978 Nov;86(11):525-8. <strong>[Effect of 
neuromediators on acid-base status].</strong> [Article in Russian] Lazareva 
LV, Bazarevich GI, Makarova LV. A relationship between the state of 
adrenergic, cholinergic, and serotoninergic systems, on the one hand, 
and the acid-alkaline balance of the organism, on the other hand, was 
revealed in sharp and chronic experiments on dogs. A surplus of each 
of the mediators was accompanied by respiratory alkalosis, and its deficiency--by 
combined respiratory and metabolic acidosis.</p>
<p>Can 
J Physiol Pharmacol 1987 May;65(5):1078-85. <strong>Pathophysiology of pH 
and Ca2+ in bloodstream and brain.</strong> Somjen GG, Allen BW, Balestrino 
M, Aitken PG. The highlights of the literature and our work on tetany 
and hyperventilation are reviewed. Our studies concern the following: 
(1) the changes of [Ca2+] in circulating plasma caused by respiratory 
and &quot;metabolic&quot; acidosis and alkalosis; (2) critical plasma 
[Ca2+] levels associated with signs of tetany and neuromuscular blockade; 
(3) changes in cerebral [Ca2+]o caused by hypo- and hyper-calcaemia, 
and the changes in cerebral [Ca2+]o and pHo caused by acute systemic 
acidosis and alkalosis; and (4) effects of changing [Ca2+]o and pHo 
levels on synaptic transmission in hippocampal formation. Our main conclusions 
are (1) changes of plasma [Ca2+] caused by &quot;metabolic&quot; pH 
changes are greater than those associated with varying CO2 concentration; 
(2) acute systemic [Ca2+] changes are associated with small cerebral 
[Ca2+]o changes; (3) the decreases in systemic and cerebral [Ca2+]o 
caused by hyperventilation are too small to account for the signs and 
symptoms of hypocapnic tetany; (4) moderate decrease of [Ca2+]o depresses 
and its increase enhances synaptic transmission in<strong> 

hippocampal formation; and (5) H+ ions in 
extracellular fluid have a weak depressant effect on neuronal excitability. 
CO2 is a strong depressant, which is only partly explained by the acidity 
of its solution. CO2 concentration is a significant factor in controlling 
cerebral function.</strong></p>
<p>J 
Hirnforsch 1991;32(5):659-664. <strong>Normalization of protein synthesis 
and the structure of brain dystrophic neurons after the action of 
hypoxia, 10% NaCl and organ-specific RNA.</strong> Polezhaev LV, Cherkasova 
LV, Vitvitsky VN, Timonin AV N. I. Vavilov Institute of General Genetics, 
USSR Academy of Sciences, Moscow. It was shown previously (Polezhaev 
and Alexandrova, 1986) that hypoxic hypoxia causes mass (up to 30%) 
diffuse dystrophy of brain cortex and hippocamp neurons in rats, disturbances 
in the higher nervous activity, reduction of protein, RNA synthesis 
in neurons and of DNA synthesis in the whole brain cortex. Transplantation 
of embryonic nervous tissue (ENT) in one of the hemispheres normalizes 
all the above abnormalities observed in some neurologic and mental diseases 
in humans. However, transplantation may entail injuries of parenchyma 
and brain blood vessels. This forces researchers to search for another 
biological method similar by its action but safer and simpler. ENT transplantation 
has a dual action: 1) formation of biologically active substances (BAS) 
releasing from the ENT transplant and from the host brain nervous tissue 
upon operation; 2) establishment of synaptic connections between the 
transplant and host neurons. Previously we (Vitvitsky, 1987) described 
the isolation of BAS from rat forebrain in the form of organ-specific 
RNA. The latter was injected intraperitoneally several times to post-hypoxic 
rats in which 30 min prior to that the blood-brain barrier (BBB) was 
opened by injecting intravenously and intraperitoneally 10% NaCl solution 
without damaging the host brain. At the beginning 10% NaCl increased 
the destruction of brain cortical neurons and then stimulated protein 
synthesis in them. RNA injections stimulated the synthesis in cortical 
neurons and normalized their structure. Thus, we propose a safe and 
simple method for normalization of dystrophic neurons which can be used 
after certain improvement for curing neurodegenerative and neuropsychic 
diseases in humans.  </p>

<p>Group 
processes</p>
<p>The 
trouble with writing and painting is that they are considered to be 
solitary and individualistic activities. In the 20th century, the idea 
developed that they were “expressive,” rather than communicative, 
as if there could be any sane distinction between those. The result 
was that much of 20th century poetry and painting was insane. The products 
of insanity aren’t necessarily worthless, but they are less than they 
could be. </p>

<p>When 
the writer and painter are in close contact with responsive people, 
their product is adjusted to, and enriched by, the reactions they evoke. </p>
<p>J 
Cardiovasc Pharmacol 1987;10 Suppl 2:S94-8; discussion S99. <strong>The effect 
of beta-blockade on platelet function and 
fibrinolytic activity.</strong> Winther K. Department of Clinical Chemistry, 
Rigshospitalet, Copenhagen, Denmark. Two groups of hypertensives and 
a group of migraine sufferers were tested during treatment with the 
nonselective beta-blocker propranolol 
and the beta 1-selective metoprolol. During treatment with propranolol, 
an increased platelet aggregability and a decrease in platelet content 
of cyclic AMP were seen when compared with metoprolol treatment. In 
addition, propranolol treatment increased the plasma level of adrenaline 
as well as the euglobulin clot lysis time. types of monoamine oxidase, 
adrenaline </p>

<p>45: 
Br J Pharmacol 1982 Feb;75(2):269-86
Coronary 
vasoconstrictor and vasodilator actions of arachidonic acid in the
isolated perfused heart of the rat.
Belo 
SE, Talesnik J.
The 
administration of arachidonic acid (AA) to the isolated perfused heart 
of
the 
rat usually produced biphasic coronary responses characterized by initial

vasoconstriction 
followed by prolonged vasodilatation. However, some responses
were 
predominantly vasoconstrictor or vasodilator. The non-steroidal
anti-inflammatory 
agents (NSAA) indomethacin (1-5 mg/l) and naproxen (12.5-25
mg/1) 
reversibly inhibited both phases of the response induced by AA.
Pretreatment 
of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg)
daily, 
resulted in unaltered coronary response to AA. Subsequent addition of

NSAA 
to the perfusate produced inhibition of the AA effect. Short infusions 
of
acetylsalicylic 
acid at low concentrations (2.9 micrograms/ml), dipyridamole
(0.6 
micrograms/ml) and sulphinpyrazone (28.7 micrograms/ml) selectively
inhibited 
the vasoconstrictor phase of the response to AA. It was confirmed that
metabolic 
coronary dilatation induced by cardiostimulation was inhibited by
prolonged 
AA administration; this effect was prevented by NSAA pretreatment.

Reactive 
hyperaemic responses to short lasting occlusions of coronary inflow
<strong>were 
unaffected by NSAA. Linolenic, linoleic, 
dihomo-gamma-linolenic and oleic</strong>
<strong>acid 
usually produced decreases in coronary flow which were unaffected by 
NSAA,</strong>
<strong>dipyridamole 
or sulphinpyrazone. Intra-aortic injections of AA, 
prostacyclin</strong>
<strong>(PGI2) 
and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent</strong>
<strong>decrease 
in blood pressure with the AA response inhibited by 
indomethacin. PGI2</strong>

and 
PGE2 produced long lasting coronary vasodilatation in the isolated heart.
The 
coronary actions of AA appear to be due to its transformation, within 
the
easily 
accessible vascular wall, into prostaglandin and thromboxane-like
<strong>substances. 
We suggest that a vasoconstrictor thromboxane 
A2-like substance may</strong>
<strong>be 
responsible for coronary vasospasm. Coronary insufficiency may also 
result</strong>
<strong>from 
an inhibition of compensatory metabolic coronary dilatation by increased</strong>

<strong>synthesis 
of PGE2 within the myocardial cell.</strong></p>
<p>42: 
Br Heart J 1983 Jan;49(1):20-5
<strong>Platelet 
reactivity and its dependence on alpha-adrenergic receptor function 
in</strong>
<strong>patients 
with ischaemic heart disease.</strong>
Yokoyama 
M, Kawashima S, Sakamoto S, Akita H, Okada T, Mizutani T, Fukuzaki H.
We 
studied 57 patients admitted to hospital with ischaemic heart disease,

including 
nine patients with variant angina, to evaluate platelet reactivity and
its 
dependence on alpha-adrenergic receptor function. The threshold
concentration 
for biphasic platelet aggregation in response to adrenaline and
adenosine 
diphosphate was measured in fresh platelet rich plasma. There were age
related 
alterations in platelet responsiveness to adrenaline. In 27 age matched
control 
subjects platelets showed adrenaline induced aggregation at a

concentration 
higher than 0.1 mumol. The threshold concentrations for adrenaline
and 
adenosine diphosphate were 0.91 mumol and 4.68 mumol. In 16 patients 
with
acute 
infarction, 14 with old infarction, nine with effort angina, and nine 
with
rest 
angina, mean values of platelet aggregation threshold for both adrenaline
and 
adenosine diphosphate were not altered significantly when compared with
control 
subjects. In contrast, the values for adrenaline and adenosine

diphosphate 
in nine patients with variant angina were 0.012 mumol and 2.24 mumol
and 
seven of them showed obvious platelet hyperactivity to adrenaline at 
a concentration lower than 0.1 mumol. The threshold concentration for 
adrenaline induced aggregation did not correlate with serum cholesterol 
and triglyceride
levels.
</p>
<p>Am 
Heart J 1985 Jun;109(6):1264-8. Reduction of plasma norepinephrine levels 
in response to brief coronary occlusion in experimental dogs. Haneda 
T, Arai T, Kanda H, Ikeda J, Takishima T. Although an increased plasma 
norepinephrine (NE) level is sometimes observed
during 
angina pectoris, it is difficult to say whether sympathetic overflow 
is

its 
cause. The left anterior descending coronary artery was occluded by
intracoronary 
balloon for 3 minutes in 12 closed-chest anesthetized dogs. During
occlusion, 
heart rate did not change but aortic pressure slightly decreased.
Occlusion 
caused a significant reduction in both NE levels in the aorta (177 +/-
17 
to 134 +/- 16 pg/ml, p less than 0.01) and in the great cardiac vein 
(GCV)
296 
+/- 44 to 249 +/- 44 pg/ml, p less than 0.01). After surgical vagotomy, 
the

occlusion 
increased NE levels in the aorta (227 +/- 44 to 278 +/- 43 pg/ml, p
less 
than 0.01) and in GCV (384 +/- 76 to 444 +/- 81 pg/ml, p less than 0.01),
showing 
the release of vagal inhibition. These results may be applicable to
<strong>patients 
with transient anterior myocardial 
ischemia; if plasma NE increases</strong>
<strong>without 
marked hemodynamic changes, it is suggested that the sympathetic</strong>
<strong>overflow 
is not a result but a possible cause of the 
ischemia.</strong></p>

<p>25: 
Exp Mol Pathol 1986 Apr;44(2):138-46
<strong>Intimal 
thickening and the distribution of vasomotor nerves in the mechanically</strong>
<strong>injured 
dog coronary artery.</strong>
Taguchi 
T, Ishii Y, Matsubara F, Tanaka K.
Intimal 
injury and atherosclerotic change seem to be causative factors linked 
to
spasm 
of the coronary artery. Intimal thickening was produced by mechanical

injury 
to the endothelium of the canine coronary artery and we investigated 
the
distribution 
of adrenergic, cholinergic, and peptidergic nerves in the coronary
arteries. 
Although adrenergic and cholinergic nerves were not altered in
<strong>density, 
neuron specific enolase positive nerve fibers were increased in number</strong>
<strong>in 
dogs killed 1 and 3 months after injury. Substance 
P-containing fibers were</strong>
<strong>also 
increased at 3 months after the induced injury.</strong>

</p>
<p>24: 
J Am Coll Cardiol 1986 Jul;8(1 Suppl A):42A-49A
<strong>Mechanisms 
of coronary spasm of isolated human 
epicardial coronary segments</strong>
<strong>excised 
3 to 5 hours after sudden death.</strong>
Vedernikov 
YP.
Isolated 
segments of epicardial coronary artery with and without severe

atherosclerotic 
lesions excised from human hearts 3 to 5 hours after sudden
coronary 
death demonstrated spontaneous contractile activity that was dependent
on 
the external calcium level and was inhibited by calcium antagonists 
and
activation 
of beta-adrenoceptors (isoproterenol and high concentrations of
norepinephrine). 
Isoproterenol, with a median effective dose (ED50) of 6.3 X
10(-7) 
M, relaxed coronary segments that had been precontracted with 30 mM

<strong>potassium. 
Stimulation of the alpha-adrenoceptors activated spontaneous</strong>
<strong>contractions 
and increased tension. Norepinephrine 
ED50 (in the presence of</strong>
<strong>10(-6) 
M propranolol) was 2.3 X 10(-7) M, and tension at a maximal concentration</strong>
<strong>of 
10(-4) M was 385.4 +/- 51.4 mg. The 
ED50 for acetylcholine and histamine, the</strong>
<strong>potent 
activators of coronary segment tone and 
phasic contractility, was 3.98 X</strong>
10(-7) 
and 8.9 X 10(-7) M, respectively; the maximal increase in tension was

1,079.5 
+/- 175 (at 10(-4) M) and 1,131.3 +/- 302 mg (at 10(-5) M),
respectively. 
Acetylcholine and histamine increased whereas high concentrations
of 
norepinephrine failed to inhibit rhythmic activity and tension of coronary
artery 
segments with severe atherosclerotic lesions. Membrane electrogenic
mechanisms 
and ways of activating the contractile elements of human coronary
artery 
smooth muscle are discussed.</p>

<p>Pharmacol 
Rev 2000 Dec;52(4):595-638. <strong>The sympathetic 
nerve--an integrative interface between two 
supersystems: the brain and the immune system.</strong> Elenkov IJ, Wilder 
RL, Chrousos GP, Vizi ES. Inflammatory Joint Diseases Section, Arthritis 
and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal 
and Skin Diseases, National Institutes of Health, Bethesda, Maryland, 
USA. The brain and the immune system are the two major adaptive systems 
of the body. During an immune response the brain and the immune system 
&quot;talk to each other&quot; and this process is essential for maintaining 
homeostasis. Two major pathway systems are involved in this cross-talk: 
the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous 
system (SNS). This overview focuses on the role of SNS in neuroimmune 
interactions, an area that has received much less attention than the 
role of HPA axis. Evidence accumulated over the last 20 years suggests 
that <strong>norepinephrine (NE) fulfills the criteria for 
neurotransmitter/neuromodulator in lymphoid organs.</strong> Thus, primary 
and secondary lymphoid organs receive extensive sympathetic/noradrenergic 
innervation. Under stimulation, NE is released from the sympathetic 
nerve terminals in these organs, and the target immune cells express 
adrenoreceptors. Through stimulation of these receptors, locally released 
NE, or circulating catecholamines such as epinephrine, affect <strong>lymphocyte 
traffic, circulation, and proliferation, and modulate 
cytokine production and the functional activity of different lymphoid 
cells.</strong> Although there exists substantial sympathetic innervation 
in the bone marrow, and particularly in the thymus and mucosal tissues, 
our knowledge about the effect of the sympathetic neural input on <strong>
hematopoiesis, thymocyte development, and 
mucosal immunity</strong> is extremely modest. In addition, recent evidence 
is discussed that <strong>NE and epinephrine, through stimulation of the 
beta(2)-adrenoreceptor-cAMP-protein 
kinase A pathway, inhibit the production of type 
1/proinflammatory cytokines,</strong> such as interleukin (IL-12), tumor 
necrosis factor-alpha, and interferon-gamma by antigen-presenting cells 
and T helper (Th) 1 cells, whereas they <strong>stimulate the production 
of type 2/anti-inflammatory cytokines such as IL-10</strong> and transforming 
growth factor-beta. Through this<strong> mechanism, systemically, endogenous 
catecholamines may cause a selective suppression of 
Th1 responses and cellular immunity, and a 
Th2 shift toward dominance of humoral immunity. On the other hand, in 
certain local responses, and under certain conditions, 
catecholamines may actually boost regional immune</strong> responses, through 
induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production. 
Thus, the activation of SNS during an immune response might be<strong> aimed 
to localize the inflammatory response, through induction of 
neutrophil accumulation and stimulation of more specific 
humoral immune responses, although systemically it may suppress 
Th1 responses, and, thus protect the organism from the detrimental effects 
of proinflammatory cytokines and other products of activated macrophages.</strong> 

The above-mentioned immunomodulatory effects of catecholamines and the 
role of SNS are also discussed in the context of their clinical implication 
in certain <strong>infections, major injury and sepsis, 
autoimmunity, chronic pain and fatigue syndromes, and tumor growth.</strong> 
Finally, the pharmacological manipulation of the sympathetic-immune 
interface is reviewed with focus on new therapeutic strategies using 
selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists 
and inhibitors of phosphodiesterase type IV in the treatment of experimental 
models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.
</p>
<p>Am 
J Physiol Cell Physiol 2000 Nov;279(5):C1665-74.<strong> 
beta-adrenergic receptor/cAMP-mediated signaling and 
apoptosis of S49 lymphoma cells.</strong> Yan L, Herrmann V, Hofer JK, Insel 
PA. Department of Pharmacology, University of California, San Diego, 
La Jolla, California 92093-0636, USA.<strong> 
beta-Adrenergic receptor (betaAR) activation and/or increases in 
cAMP regulate growth and proliferation of a variety of cells and, in 
some cells, promote cell death. In the current studies we addressed 
the mechanism of this growth reduction </strong>
by examining betaAR-mediated effects in the murine T-lymphoma cell line 
S49. Wild-type S49 cells, derived from immature thymocytes (CD4(+)/CD8(+)) 
undergo growth arrest and subsequent death when treated with agents 
that increase cAMP levels (e.g., betaAR agonists, 8-bromo-cAMP, cholera 
toxin, forskolin). Morphological and biochemical criteria indicate that 
this cell death is a result of apoptosis. In cyc(-) and kin(-) S49 cells, 
which lack G(s)alpha and functional protein kinase A (PKA), respectively, 
betaAR activation of G(s)alpha and cAMP action via PKA are critical 
steps in this apoptotic pathway. S49 cells that overexpress Bcl-2 are 
resistant to cAMP-induced apoptosis. We conclude that betaAR activation 
induces apoptosis in immature T lymphocytes via G(s)alpha and PKA, while 
overexpression of Bcl-2 prevents cell death. betaAR/cAMP/PKA-mediated 
apoptosis may provide a means to control proliferation of immature T 
cells in vivo.</p>

<p>Carcinogenesis 
2001 Mar;22(3):473-9. <strong>Beta-adrenergic growth regulation of human 
cancer cell lines derived from pancreatic 
ductal carcinomas.</strong> Weddle DL, Tithoff P, Williams M, Schuller HM. 
Carcinogenesis and Developmental Therapeutics Program, College of Veterinary 
Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, 
USA. Exocrine ductal carcinoma of the pancreas has been associated with 
smoking, and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone 
(NNK) causes this cancer type in laboratory rodents. Current knowledge 
on the growth regulation of this malignancy is extremely limited. Recent 
studies have shown overexpression of cyclooxygenase 2 (COX 2) and 5-lipoxygenase 
(5-lipox) in exocrine pancreatic carcinomas, <strong>suggesting a potential 
role of the arachidonic acid (AA) cascade in the regulation of this 
cancer type. In support of this interpretation, our data show high basal 
levels of AA release in two human cell lines derived from exocrine 
ductal pancreatic carcinomas.</strong> Both cell lines expressed m-RNA for 
beta2-adrenergic receptors and beta1-adrenergic receptors. Radio-receptor 
assays showed that beta2-adrenergic receptors predominated over beta1-adrenergic 
receptors. beta2-Adrenergic antagonist ICI118,551 <strong>significantly reduced 
basal AA release and DNA synthesis</strong> when the cells were maintained 
in complete medium. DNA synthesis of the cell line (Panc-1) with an 
activating point mutation in codon 12 of the ki-ras gene was significantly 
stimulated by NNK when cells were maintained in complete medium and 
this <strong>response was inhibited by the 
beta-blocker ICI118,551, the COX-inhibitor aspirin, or the 
5-lipox-inhibitor MK-886.</strong> The cell line without ras mutations (BXPC-3) 
did not show a significant response to NNK in complete medium. When 
the assays were conducted in serum-free medium, both cell lines demonstrated 
increased DNA synthesis in response to NNK, an effect inhibited by the 
beta2-blocker, aspirin, or MK-886. Panc-1 cells were more sensitive 
to the stimulating effects of NNK and less responsive to the inhibitors 
than BXPC-3 cells. Our findings are in accord with a recent report which 
has identified NNK as a beta-adrenergic agonist and suggest beta-adrenergic, 
AA-dependent regulatory pathways in pancreatic cancer as a novel target 
for cancer intervention strategies. </p>
<p>Shock 
2000 Jul;14(1):60-7. Terbutaline prevents circulatory failure and mitigates 
mortality in rodents with endotoxemia. Wu CC, Liao MH, Chen SJ, Chou 
TC, Chen A, Yen MH. Department of Pharmacology, National Defense Medical 
Center, Taipei, ROC, Taiwan. Septic shock is characterized by a decrease 
in systemic vascular resistance. Nevertheless, regional increases in 
vascular resistance can occur that may<strong> predispose mammals to organ 
dysfunction, including the acute respiratory</strong> distress syndrome. 
In the host infected by endotoxin (lipopolysaccharide, LPS), the expression 
and release of proinflammatory tumor necrosis factor-alpha (TNFalpha) 
rapidly increases, and this cytokine production is regulated by agents 
elevating cyclic AMP. In this report, we present evidence that<strong> 

terbutaline, a beta2-agonist, inhibits 
TNFalpha production and enhances interleukin-10 (IL-10) release in the 
anesthetized rat treated with LPS. In addition, an overproduction of 
nitric oxide (NO, examined by its metabolites nitrite/nitrate) by 
inducible NO synthase (iNOS, examined by western blot analysis) is attenuated 
by pretreatment of LPS rats with terbutaline. Overall,</strong> pretreatment 
of rats with terbutaline attenuates the delayed hypotension and prevents 
vascular hyporeactivity to norepinephrine. In addition, pretreatment 
of mice with terbutaline also improves the survival in a model of severe 
endotoxemia. The infiltration of polymorphonuclear neutrophils into 
organs (e.g., lung and liver) from the surviving LPS mice treated with 
terbutaline was reduced almost to that seen in the normal controls. 
These findings suggest that the inhibition of TNFalpha and NO (via iNOS) 
production as well as the increment of IL-10 production contribute to 
the beneficial effect of terbutaline in animals with endotoxic shock.</p>
<p>Ann 
Endocrinol (Paris) 1977;38(6):421-6. [Hyperestrogenism in the woman 
during the reproductive period]. [Article in French] Kuttenn F.
</p>
<p>Br 
J Obstet Gynaecol 1976 Aug;83(8):593-602. Polycystic ovarian disease. 
Duignan NM.<strong> Sex hormone binding globulin 
(SHBG) capacity was reduced in 9 of 31 patients with 
polycystic ovarian (PCO) disease and the mean level in 
PCO patients was significantly less (p less than 0.001) than normal. 
Serum testosterone levels</strong> were elevated in 21 of 32 PCO patients 
and the mean level was significantly elevated (p less than 0.001). Serum 
androstenedione values were raised in 17 of 31 patients and the mean 
value was also significantly raised (p less than 0.001). Serum dehydroepiandrosterone 
sulphate (DHAS) concentrations were elevated in only 2 of 14 patients. 
Urinary 17-oxo and 17-oxogenic steroids were normal in all patients 
studied. Basal follicle-stimulating hormone (FSH) and luteinizing hormone 
(LH) levels were normal but LH release following injection of luteinizing 
hormone-releasing hormone (LH-RH) was enhanced. A highly significant 
negative correlation (r=--0.449; p less than 0.01) was found between 
the logarithm of testosterone and the logarithm of LH levels. Serum 
prolactin concentrations were elevated in 4 of 21 PCO patients. Thyroid-stimulating 
hormone (TSH) values were normal. Eighteen of 20 patients ovulated following 
treatment with clomiphene and nine became pregnant. Five of 12 of patients 
treated with oestrogen/progesterone preparations noticed an improvement 
in their hirsutism. It is<strong> suggested that the normal cyclical release 
of LH is inhibited in PCO </strong>disease by a negative feedback by androgens 
to the hypothalamus or the pituitary, and that wedge resection should 
be reserved for patients in whom other forms of treatment have failed.</p>

<p>Nouv 
Presse Med 1976 Apr 10;5(15):975-9. [Secretion of gonadotropins during 
sleep. Changes during secondary amenorrheas]. [Article in French] Passouant 
P, Crastes de Paulet A, Descomps B, Besset A, Billiard M. 4 females 
with secondary amenorrheas underwent sleep polygraphic recordings together 
with blood samples for measurements of LH, FSH and  GH, 3 normal 
females served as controls.  Among normal subjects LH and FSH secretion 
showed a pulsating pattern around the time of ovulation, appearing as 
secretory episodes throughout the night, without any relationship with 
sleep stages. In amenorrheas, 3 types of abnormalities could be identified: 
the first was a lack<strong> of secretory episodes of 
LH and FSH associated with an abnormal pattern of 
GH (9 subjects). The second was an 
hypersecretion of LH and a decrease of 
FSH secretion together with a normal secretion of 
GH in 4 subjects with a Stein-Leventhal syndrome. The last one was an 
hypersecretion of LH and FSH</strong> together with a normal pattern of GH 
in a subject with an early menopause. These results are discussed according 
to the present data on the part of neurotransmission in the regulation 
of ovulation and the 2 types of sleep. Furthermore secretory abnormalities 
of LH and FSH together with a disconnection between GH secretion and 
the stages of sleep lead to question the possibility of interrelationships 
in the secretory mechanisms of these different hormones.
</p>
<p>Cancer 
1997 Feb 1;79(3):494-9. Comment in:  Cancer. 1997 Oct 1;80(7):1360-2. 
Association of Stein-Leventhal syndrome with the incidence of postmenopausal 
breast carcinoma in a large prospective study of women in Iowa. Anderson 
KE, Sellers TA, Chen PL, Rich SS, Hong CP, Folsom AR. Division of Epidemiology, 
School of Public Health, University of Minnesota, Minneapolis, USA. 
BACKGROUND: The Stein-Leventhal syndrome (SLS), first described in 1935, 
is characterized by infertility, hyperandrogenization, and obesity. 
Because this phenotype represents an aggregation of risk factors for 
postmenopausal breast carcinoma, and because in general, a hormonal 
imbalance underlies the disorder, the authors examined the association 
between self-reported SLS and breast carcinoma incidence in a cohort 
of 34,835 cancer-free women assembled in 1986 and followed through 1992. 
METHODS: All participants were between the ages of 55 and 69 and held 
a valid Iowa driver's license. A total of 472 women in the cohort (1.35%) 
reported a history of SLS at baseline. Incident cases of breast carcinoma 
were identified annually using the State Health Registry of Iowa. Data 
were analyzed using Cox proportional hazards regression. RESULTS: During 
the follow-up period, there were 883 incident breast carcinomas, 14 
among women reporting a history of SLS. Women with SLS were more likely 
than women without SLS to report fertility problems and menstrual irregularities, 
but there were no significant differences observed regarding body mass 
index (BMI). Although women with SLS were 1.8 times as likely to report 
benign breast disease than women without SLS (P &lt; 0.01), they were 
not more likely to develop breast carcinoma (relative risk [RR] = 1.2; 
95% confidence interval [CI] = 0.7-2). Adjustment for age at menarche, 
age at menopause, parity, oral contraceptive use, BMI, waist-to-hip 
ratio, and family history of breast carcinoma lowered the RR to 1 (95% 
CI = 0.6-1.9. CONCLUSIONS: Despite the high risk profiles of some women 
with SLS, these results do not suggest that the syndrome per se is associated 
with an increased risk of postmenopausal breast carcinoma.</p>
<p>Am 
J Epidemiol 1991 Oct 15;134(8):818-24. Comment in:  Am J Epidemiol. 
1992 Aug 1;136(3):372-3. Polycystic ovaries and the risk of breast cancer. 
Gammon MD, Thompson WD. Division of Epidemiology, Columbia University 
School of Public Health, New York, NY. Data from a case-control study 
that was conducted between 1980 and 1982 were analyzed to investigate 
the possible association between polycystic ovaries and the risk of 
breast cancer. The multicenter, population-based study included in-home 
interviews with 4,730 women with breast cancer and 4,688 control women<strong> 

aged 20-54 years. The age-adjusted odds ratio for breast cancer among 
women with a self-reported history of physician-diagnosed 
polycystic ovaries was 0.52 (95% confidence interval 0.32-0.87). The 
inverse association was not an artifact of infertility, age at first 
birth, or surgical menopause. Because women with this syndrome have 
abnormal levels of certain endogenous hormones, the observation of a 
low risk of breast cancer in this group may provide new insights into 
hormonal influences on breast cancer.</strong></p>
<p>Clin 
Endocrinol (Oxf) 1996 Mar;44(3):269-76. Polycystic ovaries in pre and 
post-menopausal women. Birdsall MA, Farquhar CM. Department of Obstetrics 
and Gynaecology, National Women's Hospital, Auckland, New Zealand.<strong> 
OBJECTIVE: Polycystic ovaries have been diagnosed in more than 20% of 
premenopausal women using ultrasound. The aim of this study was to determine 
whether polycystic ovaries exist in post-menopausal women. DESIGN: Two 
groups of</strong> women were studied; group 1 consisted of 18 post-menopausal 
volunteers and group 2 comprised 142 women, 94 of whom were post-menopausal 
who had recently undergone coronary angiography. MEASUREMENTS: Transabdominal 
and transvaginal ultrasound scans were performed and measurements made 
of uterine area, endometrial thickness and ovarian volume. The morphological 
appearance of the ovaries was also noted. Fasting blood samples were 
taken. Medical and menstrual questionnaires were completed. RESULTS: 
Polycystic ovaries were found in 8/18<strong> (44%) of group 1 and 60/142 
(42%) in group 2. Polycystic ovaries were detected in 35/94 (37%) of 
the post-menopausal women in group 2. Post-menopausal women with 
polycystic ovaries had larger ovaries containing more follicles compared 
with post-menopausal women with normal ovaries. Post-menopausal women 
with</strong> polycystic ovaries had higher serum concentrations of testosterone 
and triglycerides than had post-menopausal women with normal ovaries. 
CONCLUSIONS: Polycystic ovaries can be detected in post-menopausal women 
and have some of the same endocrine abnormalities which are evident 
in premenopausal women with polycystic ovaries, that is, raised serum 
concentrations of testosterone and triglycerides.
</p>
<p>Cancer 
Causes Control 1996 Nov;7(6):605-25. Comment in:  Cancer Causes 
Control. 1996 Nov;7(6):569-71. Nutrition, hormones, and breast cancer: 
is insulin the missing link? Kaaks R. International Agency for Research 
on Cancer, Lyon, France. Breast cancer incidence rates are high in societies 
with a Western lifestyle characterized by low levels of physical activity, 
and by an energy-dense diet rich in total and saturated fat and refined 
carbohydrates. Epidemiologic studies, so far mostly on postmenopausal 
women, have shown that breast cancer risk is increased in hyperandrogenic 
women, with decreased levels of plasma sex-hormone binding globulin, 
and with increased levels of testosterone and of free estrogens. This 
paper describes the role of hyperinsulinemia as a hysiologic link between 
nutritional lifestyle factors, obesity, and the development of a hyperandrogenic 
endocrine profile, and reviews evidence that may or may not support 
the theory that chronic hyperinsulinemia is an underlying cause of breast 
cancer. An hypothesis is presented, stipulating that breast cancer risk 
is increased not only in hyperandrogenic postmenopausal women, but also 
in premenopausal women with mild hyperandrogenism and normal (ovulatory) 
menstrual cycles. The author suggests further investigation as to whether 
there is a positive association between risk of breast cancer before 
menopause and ubclinical forms of the polycystic ovary syndrome (PCOS), 
and to what extent iet and physical activity during childhood, by modulating 
the degree of insulin esistance during adolescence, may or may not be 
determinants of a PCO-like hyperandrogenic endocrine profile persisting 
into adulthood.</p>

<p>Akush 
Ginekol (Mosk) 1990 Sep;(9):61-3. [The therapeutic effect of parlodel 
in the polycystic ovary syndrome]. [Article in Russian] Soboleva EL, 
Komarov EK, Potin VV, Svechnikova FA. Parlodel (2.5-50 mg/day) has been 
given for 1 to 7 days to 33 patients with the polycystic ovary syndrome 
(POS). The ovulatory menstrual cycle returned in 10 (30%) patients and 
4 of them conceived. Pretreatment cycle disturbance persisted in 6 (18%) 
patients. <strong>Parlodel reduced mid-follicular mean blood 
LH levels</strong> to values of normal women. Some decrease in blood testosterone 
levels occurred only in the second phase of the cycle. Estradiol test 
in 6 patients showed normal positive and negative feedbacks in the hypothalamic-pituitary-ovarian 
axis. Parlodel treatment reduced basal and estradiol stimulated pituitary 
gonadotropin secretion. It is suggested that parlodel may be used in 
ovulation induction in a proportion of POS patients.
</p>
<p>polycystic 
menopausal sympathetic
estrogen parasympathetic, antimitochondrial, both can have a protective 
function, though in excess the inhibition itself is toxic.</p>
<p>  

</p>
<p>Mast 
cells: hair growth, angiogenesis, cancer, MS, asthma. Nervous control 
of insulin,7: </p>
<p>Am 
J Obstet Gynecol 1993 Nov;169(5):1223-6. Comment in:  Am J Obstet 
Gynecol. 1994 Dec;171(6):1673 <strong>Excessive 
estradiol secretion in polycystic ovarian disease.</strong> Benjamin F, Toles 
AW, Seltzer VL, Deutsch S. Department of Obstetrics and Gynecology, 
Queens Hospital Center, Jamaica, NY 11432. Polycystic ovarian disease 
is both a hyperestrogenic and a hyperandrogenic syndrome, and all studies 
have shown that hyperestrogenemia is the result of an elevation of estrone 
with plasma estradiol levels in the normal follicular range. Because 
a literature search failed to reveal any report of polycystic ovarian 
disease with significantly elevated estradiol levels, we report a case 
in which the plasma estradiol was so massively elevated as to mimic 
an estrogen-producing neoplasm. This case also suggests that although 
polycystic ovarian disease is a very rare cause of such excessive estradiol 
production, it should be included in the differential diagnosis of estrogen-producing 
neoplasms.</p>
<p>Nephron 1983;33(4):253-6. <strong>Influence of 
inhibitor of glucose utilization on the blood platelet function.</strong> 
Tison P, Kubisz P, Cernacek P, Dzurik R. The <strong>inhibition of 
glycolysis</strong> by an inhibitor of glucose utilization isolated from 
urine of the uremic subjects reflects in: (1) decreased platelet<strong> 

aggregation induced by adenosine diphosphate, adrenaline, or collagen,</strong> 
respectively; (2) decreased platelet factor 4 release induced by the 
same inductors; (3) decreased availability of platelet factor 3, and 
(4) inhibition of retraction of reptilase clot. It is concluded that 
the inhibition of glycolysis by 'inhibitor of glucose utilization' contributes 
to the functional changes of platelets and thus to the alteration of 
hemostasis in uremic patients.</p>
<p>Energy: 
vasodilate, bronchoconstrict, secrete/leak, swell, grow, tumefy. Invasion 
by sympathetic balances the chronic stimulation by mast cells, platelets, 
pituitary hormones, locally formed estrogen, and the other mediators 
of stress.</p>
<p>Res 
Exp Med (Berl) 1987;187(5):385-93. <strong>Possible interaction of platelets 
and adrenaline in the early phase of myocardial infarction.</strong> Seitz 
R, Leising H, Liebermann A, Rohner 

I, Gerdes H, Egbring R. <strong>It is known that in most cases of 
transmural acute myocardial infarction a platelet clot originates within 
a coronary artery. In acute myocardial infarction patients increased 
levels of the plasma catecholamines adrenaline and 
noradrenaline as well as the platelet release proteins platelet factor 
4 and beta-thromboglobulin have been reported. </strong>
In this study, significantly higher values were found of platelet factor 
4 (P less than 0.0001) and beta-thromboglobulin (P less than 0.002) 
in 17 acute myocardial infarction patients as compared to 17 control 
patients (on intensive care due to non-cardiac disorders), while the 
plasma levels of adrenaline and noradrenaline were not different. Positive 
correlations were obtained between the two catecholamines and the platelet 
products in the control group and between adrenaline and both platelet 
factor 4 (r = 0.715, P less than 0.01) and beta-thromboglobulin (r = 
0.547, P less than 0.05) in the acute myocardial infarction patients. 
The data suggest that a stimulation of the platelets by adrenaline may 
facilitate in vitro activation during sampling in patients with high 
catecholamine load. On the other hand, a &quot;preactivation&quot; of 
the platelets by an increase of adrenaline might be of significance 
for thrombus formation in acute myocardial infarction.</p>
<p>Anesthesiology 
1991 Jun;74(6):973-9. Comment in:  Anesthesiology. 1992 Mar;76(3):475. 
Magnesium inhibits the hypertensive but not the cardiotonic actions 
of low-dose epinephrine. Prielipp RC, Zaloga GP, Butterworth JF 4th, 
Robertie PG, Dudas LM, Black KW, Royster RL. Intravenous magnesium supplementation 
is often used to control cardiac arrhythmias and coronary artery vasospasm 
resulting from disturbances of magnesium homeostasis after coronary 
artery bypass surgery. Many such patients also require inotropic drug 
support of depressed myocardial function. However, increased serum magnesium 
concentrations directly depress cardiac contractility in animals and 
may interfere with catecholamine actions. To determine whether small 
intravenous doses of magnesium sulfate (MgSO4) interfere with the cardiotonic 
actions of epinephrine, we examined the hemodynamic effects of MgSO4 
and epinephrine infusion in 17 cardiac surgical patients on their 1st 
postoperative day in a prospective, controlled study. In 11 patients, 
infusion of MgSO4 (7-mg.kg-1 bolus followed by 10 mg.kg-1.h-1 as a continuous 
infusion) increased serum magnesium concentrations by 44% (mean +/- 
standard error of the mean [SEM] of 0.8 +/- 0.1 to 1.2 +/- 0.1 mM; P 
less than 0.01) but had no significant effect on heart rate; mean arterial, 
central venous, or pulmonary arterial occlusion pressures; or cardiac 
output. Epinephrine infusion (30 ng.kg-1.min-1) significantly increased 
cardiac index (2.7 +/- 0.1 to 3.1 +/- 0.21.min-1.m-2; P less than 0.05); 
this effect was not altered by MgSO4 administration (n = 11). However, 
MgSO4 significantly blunted epinephrine's hypertensive action and prevented 
a significant increase in mean arterial pressure during concurrent MgSO4-epinephrine 
administration. Six placebo control patients were given two sequential 
infusions of epinephrine separated by a placebo infusion to rule out 
an effect of time on the hemodynamic response to epinephrine. Mean arterial 
pressure and cardiac index responses to epinephrine were identical before 
and after placebo infusion.(</p>
<p>Jpn 
Heart J 1979 Jan;20(1):75-82. <strong>Inhibition of constrictor responses 
of dog coronary artery by atropine. A possible effectiveness of atropine 
on variant form of angina pectoris.</strong> Sakanashi M, Furukawa T, Horio 
Y. A possible effectiveness of atropine on variant form of angina pectoris 
was investigated using the left circumflex coronary arterial strips 
of dogs. Acetylcholine 10(-5)--10(-3) Gm/ml dose-dependently constricted 
the isolated arterial strips during potassium-contracture in 6 cases, 
and repetitive applications of acetylcholine could produce the similar 
contractions to the control. In 18 strips atropine 10(-6) Gm/ml significantly 
depressed the contractions of coronary arteries induced by acetylcholine 
10(-5)--10(-3) Gm/ml. In 5 arterial strips atropine 10(-6) Gm/ml <strong>

significantly inhibited norepinephrine-induced responses</strong> of these 
arteries, and by 10(-5) Gm/ml further suppression of the responses was 
obtained. The <strong>results suggest that atropine may suppress the contractile 
responses of the coronary artery induce by 
acetylcholine and nonrepinephrine through a 
muscarinic-receptor blocking action and simultaneously partly through 
an adrenergic alpha-receptor blocking action.</strong></p>
<p>Eur 
J Clin Pharmacol 1981;20(4):245-50. <strong>Effect of long-term beta-blockade 
with alprenolol on platelet function and 
fibrinolytic activity in patients with coronary heart disease.</strong> Jurgensen 
HJ, Dalsgaard-Nielsen J, Kjoller E, Gormsen J. In 14 patients with coronary 
heart disease the effect of long-term treatment (mean 16 months, range 
12-33) with alprenolol on platelet function and fibrinolytic activity 
was studied. While on the beta-blocker and two weeks after gradual withdrawal 
of it, the patients performed a bicycle-ergometer test and blood samples 
were obtained before and following exercise. Pre-exercise fibrinolytic 
activity, assessed by the euglobulin clot lysis time, was 183 +/- 27 
min (mean +/- SEM) while on alprenolol as compared to 111 +/- 18 min 
(p less than 0.01) after its withdrawal. Activation of fibrinolysis 
following exercise was not significantly influenced by alprenolol. In 
patients treated with alprenolol, the pre-exercise threshold level of 
ADP, producing platelet aggregation was 3.3 muM (geometric mean) and 
5.1 muM after stopping treatment (p less than or equal to 0.05). In 
patients receiving the beta-blocker, the ADP- threshold value dropped 
from 3.3 muM before exercise to 2.3 muM immediately after exercise (not 
significant). The corresponding values after withdrawal of alprenolol 
were 5.1 muM and 2.7 muM (p less than or equal to 0.02). Adrenaline 
- stimulated aggregation was not significantly influenced by alprenolol. 
Serotonin release from platelets following maximal ADP- and adrenaline 
stimuli was not significantly changed by exercise in patients on beta-blockade. 
After stopping treatment, ADP-induced serotonin release was 22 +/- 4.1% 
before and 15 +/- 4.7% after exercise (p less than 0.02). the corresponding 
values using the adrenaline stimulus were 29 +/- 5.7% and 17 +/- 4.7% 
(p less than 0.05). It is suggested that during physical stress alprenolol 
may protect platelets against aggregatory stimuli.</p>
<p>C 
R Seances Soc Biol Fil 1987;181(3):242-8.<strong> [Adrenaline activates oxidative 
phosphorylation of rat liver mitochondria through alpha 1-receptors].</strong> 
Breton L, Clot JP, Bouriannes J, Baudry M. We studied the effects and 
mode of action of epinephrine on the oxidative phosphorylation of rat 
liver mitochondria. With either succinate or beta-hydroxybutyrate as 
substrate, i.v. injection of 1.5 microgram/100 g epinephrine increased 
the respiratory rates by 30-40% in state 3 (with ADP), and by 20-30% 
in state 4 (after ADP phosphorylation), so that the respiratory control 
ratio (state 3/state 4) changed little. The respiratory stimulation 
by epinephrine was maximal 20 minutes after its injection. The action 
of epinephrine on mitochondria was blocked by pretreatment of the animals 
with the alpha 1-antagonist prazosin but not by treatment with the beta-antagonist 
propranolol. I. v. injection of 10 micrograms/100 g phenylephrine evoked 
the same mitochondrial response as epinephrine. I. v. administration 
of 50 micrograms/100 g dibutyryl cyclic AMP enhanced glycaemia but did 
not affect mitochondrial respiration. Epinephrine therefore has an alpha 
1-type of action on mitochondrial oxidative phosphorylation.</p>

<p>Biochimie 
1975;57(6-7):797-802. <strong>Effects of 
catecholamines on rat myocardial metabolism. I. Influence of 
catecholamines on energy-rich nucleotides and 
phosphorylated fraction contents.</strong> Merouze P, Gaudemer Y. 1. The 
influence of catecholamines (adrenaline and noradrenaline) on energy 
metabolism of the rat myocardium has been studied by incubating slices 
of this tissue with these hormones and by following the levels of the 
different phosphorylated fractions and adenylic nucleotides. 2. Similar 
effects are obtained with both hormones, adrenaline being more effective. 
3<strong>. Catecholamines decrease significantly the total amount of phosphate 
while Pi content increases during the first 10 minutes of incubation; 
labile and residual phosphate contents increase at the beginning of 
incubation and decrease to the initial values afterwards. 4. ATP and 
ADP levels decrease significantly</strong> with both hormones; however, the 
effect of noradrenalin on the ATP level needs a longer time of incubation. <strong>
The ATP/ADP ratios decrease after 5 minutes incubation and the total 
adenylic nucleotide content is severely decreased (35 per cent with 
adrenalin, after 20 minutes incubation). 5. Similar results have been 
obtained with other tissues; these results can explain the decrease 
of aerobic metabolism we observed under the same conditions.</strong></p>
<p>Eur 
J Pharmacol 1982 Jul 30;81(4):569-76<strong>. Actions of 
serotonin antagonists on dog coronary artery.</strong> Brazenor RM, Angus 
JA. Serotonin released from platelets may initiate coronary vasospasm 
in patients with variant angina. If this hypothesis is correct, serotonin 
antagonists without constrictor activity may be useful in this form 
of angina. We have investigated drugs classified as serotonin antagonists 
on dog circumflex coronary artery ring segments in vitro. Ergotamine, 
dihydroergotamine,<strong> bromocriptine, 
lisuride, ergometrine, ketanserin, 
trazodone, cyproheptadine and pizotifen caused 
non-competitive antagonism of serotonin concentration-response</strong> curves. 
In addition, ketanserin, trazodone, bromocriptine and pizotifen inhibited 
noradrenaline responses in concentrations similar to those required 
for serotonin antagonism. All drugs with the exception of ketanserin, 
cyproheptadine and pizotifen showed some degree of intrinsic constrictor 
activity. Methysergide antagonized responses to serotonin competitively 
but also constricted the coronary artery. The lack of a silent competitive 
serotonin antagonist precludes a definite characterization of coronary 
serotonin receptors at this time. However, the profile of activity observed 
for the antagonist drugs in the coronary artery differs from that seen 
in other vascular tissues. Of the<strong> drugs tested, 
ketanserin may be the most useful in variant angina since it is a potent 
5HT antagonist, lacks agonist activity and has 
alpha-adrenoceptor blocking activity.</strong></p>

<p>Arch 
Mal Coeur Vaiss 1983 Feb;76 Spec No:3-6.<strong> Role of autonomic nervous 
system in the pathogenesis of angina pectoris.</strong> Yasue H. The attacks 
of vasospastic angina or coronary spasm can be induced by injection 
of epinephrine, cold pressor test, Valsalva maneuver, and exercise. 
The attacks induced by these procedures can be suppressed by injection 
of phentolamine, an alpha adrenergic blocking agent in 80 per cent of 
the patients. On the other hand, propranolol, a beta adrenergic blocking 
agent, is not only ineffective in suppressing the attacks but aggravates 
the attacks in 50 per cent of the patients. Thus, alpha adrenergic receptors 
seem to play an important role in the production of vasospastic angina. 
The attacks of vasospastic angina can also be induced by injection of 
methacholine, a parasympathomimetic agent, and this reaction is suppressed 
by atropine, a parasympathetic blocking agent. Thus,<strong> parasympathetic 
nervous system also seems to play a role in the production of 
vasospastic angina. The attacks of 
vasospastic angina can be easily induced by 
adrenergic or parasympathetic stimuli from midnight to early morning 
but is</strong> usually not provoked by these stimuli in the daytime. Thus, 
there is circadian variation in the reactivity of coronary arteries 
to adrenergic or parasympathetic stimuli. There are also weekly, monthly 
and yearly variations of the reactivity of coronary arteries to these 
stimuli. Thus, <strong>alpha adrenergic or parasympathetic activity is not 
the sole factor in the production of 
vasospastic angina.</strong> Angina pectoris caused by increased myocardial 
oxygen demand is induced by infusion of isoproterenol, a beta adrenergic 
stimulant, and is suppressed by propranolol but not by phentolamine. 
So, beta adrenergic receptors play an important role in the production 
of angina pectoris caused by increased myocardial oxygen demand or organic 
angina pectoris.</p>
<p>Nippon 
Yakurigaku Zasshi 1986 Mar;87(3):281-90. [Vasoconstrictor responses 
of isolated pig coronary arteries]. [Article in Japanese] Ikenoue K, 
Kawakita S, Toda N.<strong> In helical strips of pig coronary arteries, histamine, 
serotonin, acetylcholine and a stable analogue of 
thromboxane A2 (9, 11-epithio-11, 12-methano 
TXA2: s-TXA2) produced a dose-dependent contraction. The histamine-induced 
contraction</strong> was suppressed by treatment with chlorpheniramine, suggesting 
an involvement of H1 receptors. Contractile responses to serotonin were 
attenuated by not only ketanserin, an S2 antagonist, but also by cinanserin 
and methysergide. Relaxation induced by serotonin in preparations treated 
with high concentrations of ketanserin were inhibited by cinanserin 
and methysergide. Norepinephrine contracted coronary arteries treated 
with propranolol. Contractile responses to norepinephrine were reversed 
to relaxations by prazosin, which were abolished by treatment with yohimbine. 
Contractile responses to histamine were potentiated by treatment with 
low concentrations of serotonin or s-TXA2. Contractile responses to 
serotonin were also potentiated by low concentrations of histamine or 
s-TXA2. Removal of the endothelium from pig coronary arterial strips 
potentiated contractions induced by serotonin, histamine and norepinephrine. 
These results suggest that, in addition to damaged endothelium, integrating 
action of endogenous vasoconstrictors, including histamine, serotonin, 
TXA2 and norepinephrine, may play an important role in producing coronary 
vasospasm.</p>

<p>Jpn 
Heart J 1987 Sep;28(5):649-61<strong>. The role of parasympathetic nerve 
activity in the pathogenesis of coronary 
vasospasm.</strong> Suematsu M, Ito Y, Fukuzaki H. To evaluate the role of 
the autonomic nervous system, especially the parasympathetic nervous 
system, in the initiation mechanism of vasospastic angina pectoris (AP), 
the coefficient of R-R interval variation (CV) on the electrocardiogram 
(ECG) and plasma catecholamine concentration were measured in 25 patients 
with vasospastic AP, 10 patients with effort AP and 12 control subjects. 
CV which has been recognized as reflecting parasympathetic nervous system 
activity was calculated from 100 consecutive heart beats on the ECG 
and represented as the percentage of standard deviation of the R-R interval 
per mean R-R interval. Repeated measurements of <strong>plasma 
catecholamine concentration revealed higher values at any sampling point 
throughout a day in patients with vasospastic AP than those in </strong>
control subjects. A distinctly higher CV was observed at night in the 
vasospastic AP group. <strong>This elevated CV was abolished by atropine 
sulfate (1.5 mg/day per os). Pilocarpine injection (1.3 mg/10 kg 
B.W. subcutaneously) induced a marked increase</strong> in CV that preceded 
the occurrence of chest pain and/or ischemic ECG changes in 5 patients 
with vasospastic AP. The<strong> increment in CV at 10 min after 
pilocarpine administration was greater in 
vasospastic AP than in control subjects (p less than 0.05). It is concluded 
that enhanced parasympathetic activity may play a role in the initiation 
of coronary vasospasm associated with sympathetic hyperactivity.</strong></p>
<p>Science 
1984 Mar 30;223(4643):1435-7.<strong> Coronary arteries of cardiac patients 
are hyperreactive and contain stores of amines: a mechanism 
for coronary spasm.</strong> Kalsner S, Richards R. Coronary arteries from 
hearts of cardiac patients contain significantly higher concentrations 
of histamine than do those from noncardiac patients. The coronary vessels 
of cardiac patients are also hyperresponsive to histamine and serotonin. 
These differences between groups of patients suggest an explanation 
for coronary artery spasm in heart disease.</p>

<p>Fed 
Proc 1985 Feb;44(2):321-5. <strong>Coronary artery reactivity in human vessels: 
some questions and some answers.</strong> Kalsner S. Spasm of a conduit coronary 
artery, converting it into a major resistance vessel impeding myocardial 
blood flow, may have severe short- or long-term effects on cardiac rhythm 
and systolic ejection of blood. It is now clear that human coronary 
arteries in vitro contract to acetylcholine but that relaxation is the 
only response observed in dog coronary vessels. <strong>Acetylcholine is 
as powerful a constrictor of human coronary arteries, in terms of tension 
induced, as 5-hydroxytryptamine (5-HT) or histamine and is a substantially 
more powerful constrictor than norepinephrine.</strong> Field stimulation 
of coronary artery strips caused a vasoconstriction that was partially 
antagonized by atropine (3.45 X 10(-6) M). An enhanced reactivity of 
the epicardial arteries of cardiac and older patients to several agonists 
was also observed and appears to provide a background against which 
a number of vasoactive agents might induce spasm. Coronary tissue from 
cardiac patients also contains stores of 5-HT and histamine, and the 
histamine levels are substantially increased above the values in vessels 
from noncardiac patients. Coronary artery spasm or contraction<strong> probably 
can be initiated by diverse intrinsic and extrinsic influences, including 
autonomic discharge from either the parasympathetic or sympathetic nervous 
system or from histamine or 5-HT, and probably no one agent or entity 
is causative in all cases.</strong></p>
<p>Ann 
N Y Acad Sci 1969 Oct 14;164(2):517-9. <strong>Induced 
carcinogenesis under various influences on the hypothalamus.</strong> Kavetsky 
RE, Turkevich NM, Akimova RN, Khayetsky IK, Matveichuck YD.</p>

<p>Ann 
N Y Acad Sci 1966 Jan 21;125(3):933-45. <strong>On the 
psychophysiological mechanism of the organism's resistance to tumor 
growth.</strong> Kavetsky RE, Turkevich NM, Balitsky KP.</p>
<p>Patol 
Fiziol Eksp Ter 1971 Sep-Oct;15(5):3-10. [Role of disorders in intra-cellular 
and neuro-humoral regulation in the development of the tumor process]. 
[Article in Russian] Kavetskii RE, Balitskii KP.</p>
<p>Obstet 
Gynecol Surv 1977 May;32(5):267-81. <strong>Estrogen and 
endometrial carcinoma. </strong>Knab DR. 1. It has become evident that the 
estrogen secreting tumors of the ovary are associated with endometrial 
carcinoma, but this association is most easily observed in the postmenopausal 
patient where the incidence of carcinoma has been<strong> reported at 10.3% 
(1.  02) to 24% (83). 2. The most consistent association of 
endometrial carcinoma is with polycystic ovarian disease, where 19 (34), 
21 (152), and 25% (150) of young women with 
endometrial carcinoma had Stein-Leventhal syndrome (67). 3. A very significant 
discovery became known in</strong> 1967 when the peripheral aromatization 
of delta4 androstenedione to estrone was reported by Kase (94) and MacDonald 
(111,112). Since that time we have learned that endometrial carcinoma 
patients have an <strong>increased peripheral conversion (139) (0.1% compared 
to 0.027%), which is similar to that found in obese and aging patients, 
by Hemsell, et al (77).</strong> This can be 2 to 4 times greater than the 
young adult or the patient without cancer. Estrone produced peripherally 
in normal postmenopausal women can amount to 40-60 microng/day and rise 
as high as 120-180 microng/day in the endometrial neoplasia group (39). 
Similarly patients with polycystic ovary disease, hyperthecosis and 
lipoid cell tumors of the ovary demonstrate androgen excess with extraglandular 
conversion to estrone (2). 4. It has become apparent that the principal 
estrogen in the postmenopausal patient is estrone and that the <strong>estrone-estradiol 
ratio in the serum is higher in postmenopausal women with corpus cancer 
than similar patients without cancer</strong> (135). Clearly, we must find 
the effect of this estrone excess at the nuclear &quot;acceptor&quot; 

level; and does this imbalance create a hormonal environment conducive 
to the development of endometrial carcinoma when age (an extremely important 
factor) and an oncogenic agent are added? 5. With the lack of ovarian 
estrogen there is a relative excess of adrenal testosterone, dihydrotestosterone 
and delta4 androstenedione, the available precursors of extraglandular 
estrone (1). 6. With the passage of time <strong>it appears that 
endometrial carcinoma is associated with hypothalamic &quot;hyperactivity&quot;</strong> 
(31) which exhibits immunologic-biologic dissociation of LH as previously 
observed in persistent trophoblastic disease when measuring hCG. The 
significance of this is still unknown. In a like fashion a significant 
number of the at risk polycystic ovary disease patients have an increased 
LH secretion. 7. Patient susceptibility is required as seen in animal 
experiments where prolonged administration of stilbestrol is used and 
still only rabbits and mice developed a malignant change. 8. Long term 
exogenous estrogen appears to have caused malignant changes in the endometrium, 
but it was universally given over  a prolonged period (4 or more 
years). The recent retrospective studies demonstrate an association 
of oral estrogen therapy with endometrial cancer, but prospective studies 
investigating dose and duration of all estrogen preparations need to 
be undertaken. 9...</p>
<p>Endocrinology 
2000 Mar;141(3):1059-72.<strong> An increased 
intraovarian synthesis of nerve growth factor and its low affinity receptor 
is a principal component of steroid-induced 
polycystic ovary in the rat.</strong> Lara HE, Dissen GA, Leyton V, Paredes 
A, Fuenzalida H, Fiedler JL, Ojeda SR. A form of polycystic ovary (PCO) 
resembling some aspects of the human PCO syndrome can be induced in 
rats by a single injection of estradiol valerate (EV). An increase in 
sympathetic outflow to the ovary precedes, by several weeks, the appearance 
of cysts, suggesting the involvement of a neurogenic component in the 
pathology of this ovarian dysfunction. The present study was carried 
out to test the hypotheses that this change in sympathetic tone is related 
to an augmented production of ovarian nerve growth factor (NGF), and 
that this abnormally elevated production of <strong>NGF contributes to the 
formation of ovarian cysts induced by 
EV. Injection of the steroid resulted in increased 
intraovarian synthesis of NGF</strong> and its low affinity receptor, p75 
NGFR. The increase was maximal 30 days after EV, coinciding with the 
elevation in sympathetic tone to the ovary and preceding the appearance 
of follicular cysts. Intraovarian injections of the retrograde tracer 
fluorogold combined with in situ hybridization to detect tyrosine hydroxylase 
(TH) messenger RNA-containing neurons in the celiac ganglion revealed 
that these changes in NGF/p75 NGFR synthesis are accompanied by selective 
activation of noradrenergic neurons projecting to the ovary. The levels 
of RBT2 messenger RNA, which encodes a beta-tubulin presumably involved 
in slow axonal transport, were markedly elevated, indicating that EV-induced 
formation of ovarian cysts is preceded by functional activation ofceliac 
ganglion neurons, including those innervating the ovary. Intraovarian 
administration of a neutralizing antiserum to NGF in conjunction with 
an antisense oligodeoxynucleotide to p75 NGFR, via Alzet osmotic minipumps, <strong>
restored estrous cyclicity and ovulatory capacity in a</strong> majority 
of EV-treated rats. These functional changes were accompanied by restoration 
of the number of antral follicles per ovary that had been depleted by 
EV and a significant reduction in the number of both precystic follicles 
and<strong> follicular cysts. The results indicate that the 
hyperactivation of ovarian sympathetic nerves seen in 
EV-induced PCO is related to an overproduction of 
NGF and its low affinity receptor in the gland. They also suggest that 
activation of this neurotrophic-neurogenic regulatory loop is a component 
of the pathological process by which 
EV induces cyst formation and anovulation in rodents. The</strong> possibility 
exists that a similar alteration in neurotrophic input to the ovary 
contributes to the etiology and/or maintenance of the PCO syndrome in 
humans.</p>

<p>Acta 
Physiol Hung 1996;84(2):183-90.<strong> Effects of hormones on the number, 
distribution and degranulation of mast cells in the ovarian complex 
of mice.</strong> Jaiswal K, Krishna A. The changes in the number and degranulation 
pattern of mast cells varied with the types of hormonal treatment and 
ovarian compartment. <strong>Luteinizing hormone 
(LH), follicle stimulating hormone 
(FSH), thyroid stimulating hormone 
(TSH) and 17-beta estradiol (E2) treatment caused increase (P &lt; 0.05) 
in the number of mast cells</strong> in the hilum as compared with the controls. 
Increase (P &lt; 0.05) in the number of mast cells in the whole ovarian 
complex was observed only following FSH and E2 treatment. All the hormones 
used in the present study increased the percentage degranulation of 
mast cells in the hilum. However, only LH, FSH and E2 increased the 
percentage degranulation of mast cells in other compartments of the 
ovary (medulla, bursa and cortex). TSH and ACTH failed to cause any 
increase in the percentage degranulation of mast cells in these compartments. 
The present findings indicate E2 to be the most potent among the hormones 
tested in causing degranulation of mast cells in all ovarian compartments.</p>
<p>Fertil 
Steril 2001 Jun;75(6):1141-7. <strong>Increase in nerve fibers and loss of 
mast cells in polycystic and postmenopausal ovaries.</strong> Heider U, Pedal 
I, Spanel-Borowski K. OBJECTIVE: To quantify nerve fibers and mast cells 
in human ovaries at different functional stages. DESIGN: Retrospective 
study. SETTING: Research laboratory of the university. SPECIMEN(S): 
8 human ovaries in the follicular (cyclic) phase, 7 polycystic ovaries, 
and postmenopausal ovaries with (n=5) or without (n=7) hyperthecosis. 
MAIN OUTCOME MEASURE(S): Single- and double immunohistology for the 
S100 antigen in glial cells of autonomic nerve fibers, for chymase and 
tryptase in mast cells, and for the common leukocyte antigen on leukocytes. 
Histometric evaluation was also performed. INTERVENTION(S): None. RESULT(S): 
Polycystic ovaries contained significantly more S100-positive nerve 
fibers in the corticomedullary region than did cyclic ovaries (mean 
+/- SD per 2-mm(2) area, 476 +/- 136 and 224 +/- 133; P&lt;.01). Postmenopausal 
ovaries with or without hyperthecosis had the highest density of nerve 
fibers. In cyclic and polycystic ovaries, more tryptase-positive mast 
cells than chymase-positive mast cells were found in the interstitial 
cortex and the medulla. In cyclic ovaries, areas with a moderate density 
of nerve fibers contained many mast cells. Hence, <strong>with increasing 
nerve fiber density in polycystic ovaries, the number of mast cells 
decreased strikingly compared with cyclic ovaries (p&lt;.001). Almost 
no mast cells were seen in postmenopausal ovaries</strong> with and without 
hyperthecosis. The number of leukocyte antigen-positive leukocytes was 
similar in all groups. CONCLUSION(S): The high density of nerve fibers 
in polycystic and postmenopausal ovaries, together with a conspicuous 
decrease in mast cells, indicates altered neuroimmune communication.</p>

<p>Endocrinology 
1993 Dec;133(6):2696-703. <strong>Ovarian 
steroidal response to gonadotropins and 
beta-adrenergic stimulation is enhanced in 
polycystic ovary syndrome: role of sympathetic 
innervation.</strong> Barria A, Leyton V, Ojeda SR, Lara HE. Experimental 
induction of a polycystic ovarian syndrome (PCOS) in rodents by the<strong> 
administration of a single dose of 
estradiol valerate (EV) results in activation of the peripheral sympathetic 
neurons that innervate the ovary. This activation is evidenced by an 
increased capacity of ovarian nerve terminals to incorporate and release 
norepinephrine (NE), an increase in ovarian NE content, and a</strong> decrease 
in ovarian beta-adrenergic receptor number in the ovarian compartments 
receiving catecholaminergic innervation. The present experiments were 
undertaken to <strong>examine the functional consequences of this enhanced 
sympathetic outflow to the ovary.</strong> The steroidal responses of the 
gland to beta-adrenergic receptor stimulation and hCG were examined 
in vitro 60 days after EV administration, i.e. at the time when follicular 
cysts are well established. EV-treated rats exhibited a remarkable increase 
in ovarian progesterone and androgen responses to isoproterenol, a beta-adrenergic 
receptor agonist, with no changes in estradiol responsiveness. Basal 
estradiol release was, however, 50-fold higher than the highest levels 
released from normal ovaries at any phase of the estrous cycle. The 
ovarian progesterone and androgen responses to hCG were enhanced in 
EV-treated rats, as were the responses to a combination of isoproterenol 
and hCG. Transection of the superior ovarian nerve (SON), which carries 
most of the catecholaminergic fibers innervating endocrine ovarian cells, 
dramatically reduced the exaggerated responses of all three steroids 
to both beta-adrenergic and gonadotropin stimulation. SON transection 
also reduced the elevated levels of ovarian NE resulting from EV treatment 
and caused up-regulation of beta-adrenoreceptors. Most importantly, 
SON transection restored estrous cyclicity and ovulatory capacity. The 
results indicate that the increased output of ovarian steroids in PCOS 
is at least in part due to an enhanced responsiveness of the gland to 
both catecholaminergic and gonadotropin stimulation. The ability of 
SON transection to restore a normal response indicates that the alteration 
in steroid output results from a deranged activation of selective components 
of the noradrenergic innervation to the ovary. These findings support 
the concept that an alteration in the neurogenic control of the ovary 
contributes to the etiology of PCOS. 
</p>
</small>
    <hr>
    <p class="C">Library of GigaChad | <a href="/" target="_blank">GigaChad</a></p>
</body>
</html>