Risperidone and lactic acid bacteria

[Harry Horton]

Risperidone and other AAP's blockading of the histamine receptor 1 involves metabolic syndrome attribute developments. Inflammation and allergic reaction processes in histamine receptor 1 activity are two categories that are exactly like the activities of lactic acid bacteria (LAB) in the gut flora; that is, LAB is found to modulate inflammatory and hypersensitivity responses. Activity exactly like the H 1 receptor and thus indicative of a possible intimate connection of H 1 Receptor
activity with LAB that evolved down through the earlier geo-historical eras. Wikipedia - entry:'probiotics' carries this and other info. on LAB activity. Additionally LAB could keep a normal pH balance at least in the gut. THis process could play a major role in preventing anaerobic glycolysis from emerging, bringing with it fasting hyperglycemia, elevated glucose levels and essentially diabetes if pH levels elevate to alkaline areas. WIkipedia entry:'histamine'- designates gut physiology regulation by histamine. Since h 1 is comprised of histamine, AAP blockading og h 1 could dysregulate gut physiology via histamine disruption. Additional articles along these lines can be found in Richard Fiddian Green's January 2007 article on glibenclamide and acne, especially pH levels in insulin release. Wikipedia - histamine receptor 1 is another good source for info. LAB's role for lowering pH in the gut and its activity in the gut solely in itself could be comprised to some extent by AAP h 1 R blockading. This is a future research area to consider perhaps. Risperidone is known for lactation disturbances.

[Harry Horton]

The Richard Fiddian Green article, from June 28 2004:'pH regulation of ATP synthase activity: evolutionary biochemical bedrock?"

A quote from the article goes as follows and could have some relevance to the above previous commentary on Risperidone and LAB---
"The demonstration that alkali stimulates lactate production, referenced in my earlier communication
is intriguing for implies that it stimulates anaerobic glycolysis. How might it do so? By limiting the availability of H for ATP synthesis? If so might an increase in cytosolic pH also make ATP synthase catalyse the pumping of protons out of the mitochondrial matrix? Consider the biological implications if this were the case. ATP resynthesis by oxidative phosphorylation would be inhibited by the rise in cytosolic pH." ENd of quote.

Risperidone increases lactation processes and brings on hyperglycemia, the latter a feature of stimulated anaerobic glycolysis. So it would seem the above Green principle gets validated by risperidone usage, perhaps. In any case, the h1 Receptor is possibly responsible for the hyperglycemia and hence increased anaerobic glycolysis prominence and activity increase. If h 1 receptor also affects gut physiology then LAB which is involved in lactose production could be affected also. Particularly since LAB tends to lower gut pH to the direction of acidic status, keeping gut pH out of the higher alakline regions. As Green stated above alkali stimulates lactate leaving the issue, what would LAB's relevance be to this Green assertion? Would LAB and gut tissue pH have anything to do with anaerobic glycolysis development, bringing with it hyperglycemia and diabetes in AAP usage.That could be a relevant question and issue perhaps. Alkali stimulates lactate production with such action, bringing on an eventual regulatory like reduction of alkaline conditions with the lactate production? LAB does lower gut pH. Is the risperidone lactation excess an attempt to lower abnormal tissue alkaline pH levels (including gut alkaline pH levels, or solely that area's pH lowering?). Alakaline levels that would also create the hyperglycemia seen in risperdal usage? In any case, gut flora could be affected by the AAP's and could be an area to research by possible adverse effects of the drugs. Espeically via the h1 receptor blockading.

[Harry Horton]

The psychking.net article is a very good article detailiong the gut region's nature, its flora content and the like and its relationship to the overall neurological functioning and general physiology of the human body. A soil tract, the gut region---probably sprung from, and the gut region's dynamics and operations, stem from such a soil tract operation prototype. With areas as sunlight, nutrient supply, soil and air temperature, oxygen and water amounts ect. as major stimuli for a soil tract's functions and micro organism evolvement. The gut region is very much like this soil tract functions in a lot of ways.
Additionally and along these lines is the small mountain of research studies on the TRPV1 nerve and its relationship to thermal (hot and cold) conditions, and substantial ATP production; TRPV1 is a heat shock protein oriented nerve. Toronto researchers injected capsaicin into this nerve, that surrounded pancreatic islets and dissipated diabetes 1 and substantially knocked out a good deal of the insulin resistance that creates diabetes II,(Cell, December 15, 2006 - the journal that is). Other substances (substance P, for example) and techniques were used to accomplish the same results from Sick Children's hospital in Toronto. In any case, risperidone blockades h1 receptor. The h1 receptor biologically interacts with the PLC-(PIP)2 pathway. And (PIP)2 normal metabolic functions are required for the proper sensitization and function of TRPV1. If risperidone blockades h1 receptor activity for an extended period of time, then sensistization abnormalities of TRPV 1 could develop. Particularly in psychiatric patients that have energy homeostasis vlunerabilities on a subclinical basis. Diabetes and metabolic syndrome features could develop from such blockading of the h1 receptor. The following articles on TRPV1 and affiliated nerve types are useful for further exploring the potential adverse situations in this area from h1 receptor blockading by risperidone and other AAP's. Clozaril and zyprexa and seroquel, the most notables along with abilify. Article 1. "Functional Recovery from Desensitization of Vanilloid Receptor TRPV1 Requires Resynthesis of Phosphatidylinositol 4,5,- Bi phopsphate" - A quote from the study: "These data suggest that depletion of (PIP)2 occurs concomitantly with activation of TRPV1 and its replenishnment in the membrane determines recovery of the channel from Desensitization" End quote. If risperidone blockades H1 receptor activity, then (PIP)2 activity becomes reduced and the replenishment of the above factors could be adversely affected by H1 R blockading. Article 2. "A Modular PIP2 Binding Site as Determinant of Capsaicin Receptor Sensitivity" Elizabeth D. Prescott and David Julius. A quote: "The capsaicin receptor (TRPV1), a heat activated ion channel of the pain pathway, is sensitized by phosphatidylinositol 4,5 biphosphate (PIP)2 hydrolysis and phospholipase C activation. Mutations that weaken PIP2 - TRPV1 interaction reduce thresholds for chemical and thermal stimuli..." Wikipedia entry- "histamine receptor 1" confirms h1 R's interaction with PLC-(PIP)2. Article 3. "Dual Regulation of TRPV1 by phosphoinositides" - Viktor Lukacs. Such are some further in depth studies on this potential AAP adverse area's effects on the h1R. And another region future research efforts should be aimed at to treat AAP adverse condtions and hyperglycemic developments.

[Harry Horton]

Risperidone's blockading of the histamine receptor 1 could affect the TRPV1 nerve as the previous commentary of mine asserts. TRPV1 could present a tricky and difficult scenario for understanding how diabetes develops, a scenario that may not be adequately appreciated for understanding how diabetes develops, a scenario that may not be adequately appreciated the neurology research community. The body's overall physiological functions, metabolism and the like, could be related to TRPV1. I call TRPV1 'the stealth nerve' because it could hold a lot of hidden principles on how basic human physiology and metabolism operates. TRPV1 holds a deceivingly simple authority over the body's metabolism perhaps, that I'll describe later. And thus there is a lot to learn from TRPV1's operations in the neurological system. The two simple paradigms could better illustrate this dilemma. Paradigm 1: is simply at first glance, how does the human body maintain energy functioning through all the seasons in order to keep its metabolism functioning normally. The ANswer would seem ridiculously simple. One eats the necessary amounts of vegetables, fruits, dairy products and meats that can be converted into energy. And one eats these foods winter, spring, summer, and fall. That is a major factor and all the millions of people that accomplish that are proof of this process of maintaining healthy energy balance. But that picture could be deceivingly too simple. Paradigm 2.--What happens if the majority of the body's metabolism functions along principles and processes like micro-organisms in a soil tract? And seasonal variations can determine the survival of the body like a soil tract micro organism. In the summer, night and day temperature are warm,-- well into the seventies and nineties, and the soil tracts of summer in some locales are teeming and flourishing with micro organisms. They grow, abound amongst each other, increasing and decreasing in variation to the environmental factors around them. But when the cold of air and soil develop with winter's onset---the summer scenario disappears totally. The micro organisms tend to recede from the landscape, that is disappear, or at least a sizeable amount of them.
And cold and hot conditions, of soil and air, play a major role in determining the disappearance of the micro organisms particularly at a point when winter begins. For example in July, a particular micro organism (we'll call micro organism a.) is at 100 in number over a square foot of soil tract. In October, that number could decrease to 60. By late December organism a. is at zero in number amount. The soil and environmental conditions do not support a wintertime existence for micro organism a. because of the onset of cold. Cold and hot temperatures of the air and soil play a major role in the decrease of organism a. from July to December.

[Harry Horton]

(The following is a continuance of ideas from previous Harry Horton entry above)
What is interesting about the TRPV1 nerve is that as a heat shock protein nerve, it communicates hot and cold conditions within the brain and thus communicates these conditions to other parts of the human physiology and metabolism processes. If its signalling is deficent, and hot and cold conditions are not read appropriately in the brain one may get micro- organismic decrease in certain functions of the body. Mitochondria for example,, in ancient times once was a soil tract micro organism, and it decreases in number, much like a soil tract organism in July heading to October perhaps. Would TRPV1 dysfunction communicate wrong information on hot and cold conditions to the body that in turn would create the conditions for once micro organismic mitochondria to start lessening its numbers along with functional irregularities from mal genetic expressions in response in part to abnormal hot and cold communication misinformation from TRPV1? And with such action bring on a reduced energy output. A reduced energy output that is the hallmark for diabetes? Particularly if there are deleterious mutations in the underlying genetic network for TRPV1? Shulman of Yale confirmed mitochondria number decrease and resultant energy reductions out put are central for the destructive functions of a typical diabetes case. At least in the elderly. A situation essentially of impaired tissue energetics. Risperidone blockades the histamine receptor 1 (h1R). h1R biologically interacts with the PLC-(PIP)2 pathway, and PLC -(PIP)2 could be adversely affected in its metabolic functions, particularly (PIP)2.(PIP)2 resynthesis is essential for the normal sensitization of TRPV1 and hence by this fact, normal healthy communication of hot and cold conditons, the successful communication of such conditions within the body via TRPV1 normalcy functions. And that by TRPV1.
Risperidone blockading of histamine receptor 1 could adversely affect TRPV1 neural functioning, weakening it perhaps, leading to inaccurate communication of hot and cold conditions.(PIP)2 activity is comprised in the manner which the three articles on TRPV1 detail.(The articles are listed in a previous commentary on this subject area: lactic acid bacteria, that is). Thus hot and cold TRPV1 communication could also mean, in principle, based on evolutionary history, a hot and cold air and soil temperatures would be a dominant all pervasive condition for determining micro organismic survival and existence, on a seasonal basis. I.E. Winter time is not conducive for some micro organisms existence because of the cold. This same dominant and all pervasive condition or manner of hot and cold conditions communicated by TRPV likewise could exist. No different in theory than the soil tract example, in similar effective influence like a soil tract, TRPV1 functions are. This could be. In regards to the Shulman info. previously mentioned. An article: The title goes as something as- "Mitochondria, problems in the furnace diabetes." Typing in that title should guide one to the info. Furthermore in regards to this article, if one arrives at the Howard Hughes edition of it, the right hand margin carries a further link to the fewer mitochondria number in elderly diabetes cases.This being a separate article, that is. That info. is interesting. Also.

[Harry Horton]

(FInally, continuance of earlier two commentaries of H. Horton, above that is) In reference to previous information, that is why the TRPV1 nerve is 'the stealth nerve' in my view. Like paradigm 1. in a previous commentary on this subject, eating the necessary food during all four seasons would seem only required for maintaining healthy energy homeostasis functions. But when TRPV1 misfunctions, the nerve reminds us that this body's metabolism basically functions like a soil tract and the body's healthy energy hpomeostais is much dependent on accurate cold and hot communications via TRPV1 in the body for maintaining energy homeostasis health.And hot and cold communication is overwhelmingly important, precedent, and dominant for the survival of the human body. The human body, is a soil tract micro organism, it may as well be, when it comes to TRPV1 hot and cold communication accuracy. And soil tract micro organisms die off when they do not get accurate hot and cold communications internally (environmental conditions that is being
communicated, internally that is.)
The atypicals can further injure this hot and cold communication of TRPV1 via h1R blockading and the resultant destructive effects on (PIP)2 metabolism. When mitochondria decreases in number, is like finding our micor organism a. in July,--- no longer in July, at least according to number amount. No longer a 100 in July maybe, the micro organism mitochondria is at 60, like October. And energy reduction occurs with this situation. So when diabetes onsets, one may as well think of mitochondria entering into October. And functioning as if it was in October, according to earlier paradigm 2. And risperidone, could help speed mitochondria to its October destination, by adversely affecting the (PIP)2 metabolism. Upsetting the hot and cold conditions communication of TRPV1. TRPV1, the stealth nerve, holds many secrets. And a major one is that the nerve reminds us that a good deal of the body's physiology and metabolism functions still operate along seasonal patterns of the soil tract. With hot and cold air and soil temperatures, holding significant power over the body's energy homeostasis functions ( a potential fact interwoven with glycolysis and mitochondrial energy producing processes). As opposed to the more popular, erring view, taught in medical schools, as metabolism housed and functioning as a sepearte sole entity within the confines of the body of an animal or human. Mistakenly, along paradigm 1 principles, in a sense. The above assertions in the three previous commentaries, though theoretical in air and nature, could hold validity to varying degrees.

[Harry Horton]

The importance of temperature regulation in the body could play a major role in the development of hyperglycemia and diabetes in people who use the AAP's (atypical antipsychotics). With the December 15 2006, Cell article of TRPV1 therapeutically treating diabetes 1 to the point of cure, and a strong possibility of near eradication of diabetes II, if not a total eradication---the results of these Toronto trials places temperature of tissues and body in a pre emminent position, as a powerful factor for diabetes development to occur. R.F. Green has noted that 'tissue energetics impairment' as a poikilothermic default mechanism as he noted in one of his writings appear to be valid. Consider the following wikipedia entry:"cold blooded"--a quote from this entry.---"Because their metabolism is so variable, poikilothermic animals do not easily support complex, high-energy organ systems such as brains or wings. Some of the most complex adaptions known invovle poikilotherms with such organ systems. One example is the swimming muscles of Tuna, which are warmed by a heat exchanger. In general, poikilothermic animals do not use their metabolism to heat or cool themselves. For the same body weight poikilotherms need 1/3 to 1/10 of the energy of homeotherms. They therefore eat only 1/3 to 1/10 of the food needed by homeothermic animals." End quote. The 1/3 to 1/10 food amounts of an average homethermic human diet, sounds like the reduced food amount a diabetic must eat in order to control blood sugar. And thus if this fact is true, poikilothermic is temerpature term, and relates that 'diabetic diet food amount reductions' are related to body temperature sensitivity to the cold and warm temperatures of the environment.(Diabetes Care carried an article in October 2007, of seasonal rise of A1c and blood pressure and a third measure of metabolic functioning with cold winter month temperature presence. Vitamin D (sunshine vitamin) amounts were reduced in the plasma during these months most likely furthering an adverse effect on intestinal calcium absorption. In any case, the above wikipedia entry-"cold blooded", and its centering on poikilothermia, relates a potential intimate relationship of body temperature with diabetes development, since poikilothermic status appears potnetially with the onsetting diabetic state. Also in a psychiatry TOpix entry - H. Horton - Risperidone histamine receptor 1 and temperature- the third commentary section that lists articles on TRPV1. Body temperature regulation is associated with TRPV1 via tonically activation processes in the body. And the above information, leaves the issue what could bring on this poikilothermia condition in AAP users to begin with. A question,-- is the poikilothermia condition emergence in the AAP user's body some sort of compensatory condition to lower body temperature in AAP usage states? Should this be a research angle, to approach AAP hyperglycemia conditions.

[Harry Horton]

Poikilothermic conditions seem to be a substantial feature for tissue energetics impairments in onsetting diabetic states and hyperglycemia. These diabetic states and hyperglycemia conditions appear with AAP usage. The following web site information goes as follows. "Seroquel Warnings and Precautions" - "Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents." End quote. Does the fact that AAP's create elevated core body temperature, mean that reduction of body temperature in a normal manner, can not take place with this AAP side effect, and a result the body has to develop a general overall poikilothermic condition for the body as a means or attempt to lower core body temperature? The development of 'poikilothermic core body temperature conditions' is some sort of compensatory regulatory mefchanism for core body temperature control, or more specifically in regards to the AAP side effect of Core body temperature elevation sustainment,a compensatory regulatory mechanism for lowering such elevated core body temperature elevations. AAP's adversely effect, blockade, the Histamine recptor 1 in the body. H1R biologically interacts with the PLC-(PIP)2 pathway.(PIP)2 metabolism is involved with accurate sensititization of the TRPV1 nerve. TRPV1 nerve is necessary for keeping body temperature in a healthy range. Thermoregulation is what it is called. A second web site - "Caterina MJ"- additional listing info- "lib.bioinfo.pl/.." A quote from this article: "However growing evidence suggests that TRPV1 also participates in thermoregulation" End quote. So the H1R blockading via AAP's could further influence, adversely, thermoregualtion status of the body temperature via TRPV1 senstization abnormalities that result from such blockading. With this in mind, note the following R.F Green quote from one of his articles: "The rise in temperature induced by the increased leak rate would be accompanied by a rise in glycolytic turnover increaing ATP yield from anaerobic glycolysis and the metabolic rate." The article by R.F. green in which this quote is derived from is called--"pH regulation of ATP synthase Activity: evolutionary biochemical bedrock". And additionally, increase leak rate is the proton leak rate of the electron transport chain of the mitochondria, that involves uncoupling protein processes in some situations. The increased glycolysis and anaerobic glycloysis activity is a hallmark of diabetes development and tissue energetics impairments. In any case, the above article quotes and articles in relation to the TRPV1 articles found in 'commentary section 3 'on the 'H1R and Temperature 'entry, of psychiatry topix- H. Horton, are all interesting to take together in context of altered core body temeprature variances with AAP usage. Elevated core body temperature is confirmed to occur with AAP usage, as the 'Seroquel warning' entry states as above. And as R.F. Green notes, high body temperature sustainment brings on the anaerobic glycolysis predominance, a predominance that is the hallmark and essence of diabetes and hyperglycemia. All of this could be from H1R dysfunctions on TRPV1 sensitizations, via AAP blockading of that receptor.

[Harry Horton]

Additional information, furthering the themes and ideas of the previous two commentaires. As well as other H. Horton entries on Psychiatry Topix and Diabetes Topix. for that matter.
The web article: "Sensitization and Trnaslocation of TRPV1 by insulin and IGF-1" Van Buren et al. Molecular Pain 2005, 1:17. A quote: "Insulin and insulin like growth factors (IGF's) maintain vital neuronal functions...Here we demonstrate that both insulin and IGF-1 enhance TRPV1 mediated membrane currents in heterologous expression systems and cultivated dorsal root ganglion neurons...These findings establish a link between the insulin family of trophic factors and vanilloid receptors."
If TRPV1, being a neuron of the CNS, is well associated with calcium mediated processes, the calcium metabolism and the like, as an early metabolic system that allows for evolutionary progress and diversity of cells, by calcium and alkaline environmental conditions- Kempe et al. from H. Horton Diabetes Topix - Soda Lakes and Diabetes, entry. In the above article, mitochondrial energy producing processes, implied with insulin and IGF-1 relationship to TRPV1 functions as later evolved energy production functions of the human being. TRPV1, well associated with temperature of the body and energy producing systems, mitochondrial and pyruvate production, is illustrated in the above article. Additional articles of interest from the footnote section of the above article goes as follows:
"An endogenous capsaicin - like substance with high potency of recombinant and native vanilloid VR1 receptors."
"Phosphatidylinositol 3- kinase activates ERK
in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization" (Note-AAP H1R blockading affects the PLC-(PIP)2 pathway, that is involved with appropriate sensitization of TRPV1. This idea kept in mind in regards to this article)
""Translocation of a calcium premeable cation channel induced by insulin - like growth factor - 1." (Note- calium metabolic processes involved with insulin functions, translocation of nutrient cation channels,calcium that is, like GLUT4 processes (that go down with AAP usage in diminshed fashion in some cell types, such as adipocytes)that are translocation processes.
"Rapid actions of insulin on sensory nerve functions"

[Harry Horton]

Temperature and heat play a central role in the development of diabetes evidently. R.F. Green in one of his writings stated that temperature measurements in patients along with pH measurements should be made a new God for treating 'tissue energetic impairments." The following article; "Serum IL-1 beta, IL-2 and Il-6 in Insulin Dependent Diabetic Children" a study that included tumour necrosis factor processes at least in implication, denotes how important cytokines are for diabetes development. Il-2 for example is a pyrogen. And along with the mediation of TRPV1, Il-2, are all involved in heat oriented processes. Pyrogen, the word itself, may as well be affiliated with bonfires and setting of fires. And as the above commentaries note, with hyperglycemia onset with AAP's, core body temperature elevations in the heated range, takes place, as a precondition for bringing on diabetes and hyperglycemia in these patients.
But what could be interesting in the years ahead, deals with these heat oriented situations, is the calcium processes of Kempe as detailed in the list of studies in H. Horton "Diabetes and Soda Lakes". In the earliest stretches of the earth's environment, "alkaline Soda Lakes" and calcium were present with the evolution of biodiversity of life forms. THese environments were most likely heated environments, well before oxygen's predominant inception in the atmosphere took place. Couple that fact with the definition of calx- where, it too, contains a susbtantial degree of heat, in order for its powdery production, to occur. So, these early environments involving hot earthly atmospheric conditions, as the background for life's biodiversity to occur, via calcium mediated processes. Calcium, too, has a role in its metabolic functions for producing diabetes. Possibly for contributing to a significant degree for increased membrane permeability of the mitochondria, that R.F. Green noted in his writings, on schizophrenia and diabetes developments. The early environments of Kempe's studies on alkaline oceans and calcium, could be fairly valuable for understanding a neglected, area of calcium dynamics that later, would carry features from these earlier ancient earth regions--carry into the workings of the eventual evolved human metabolisms, and within such metabolisms, particularly calcium, osteocalcim and osteopontin metabolic processes, for example,----
one can find the most basic earliest functions for diabetes developments springing from the most ancient earthly environmnets billions of years ago. The illustration of the Kempe studies would be most intersting in these above regards. Since Il-2 is a pyrogen, the inflammatory response is heat associated, TRPV1, a heat shock protein constituted nerve, where its processes are altered, delivers, diabetes cures as the Totonto studies has found. And R.F. Green's temperature emphasis for understanding tissue energetics impairments states these conditions are presnet as the core for metabolic syndrome conditions. Join calx along with these since it too is involved in a higher degree of heat for its creation. Join also Kempe's calcium processes in the hot, molten like ancient earthly environemts too, for understanding diabetes developments. How Kempe's processes could hook up with all the subsequent mitochondrial, leptin and glycolysis evolved processes for diabetes developments could be an interesting creation in future research studies.

[Harry Horton]

In regards along the themes presented in the previous three commentaries, the following can be additionally said. The August 2007, Columbia study on osteocalcin and its role in influencing energy homeostasis and insulin sensitivty with glucose level affections,---from this study, osteocalcin influences insulin sensitivity via adiponectin. This is another way of saying, the calcium metabolism process; Osteocalcin, works through adiponectin: the body composition entity that influences brown adipose tissue nature in the body, and thirdly through these processes, insulin sensitivity can be determined to operate on a healthy regular basis or dysfunctional if osteocalcin goes awry. The definition of calx, as H. Horton related in other commentaries on 'Psych. Topix' calx is constructed by calcium and brown adipose tissue. Two entities that also are present in osteocalcin. Calcium metabolism indigenous to the bones and brown adipose tissue presence created via adiponectin. But most importantly is how temperature and heat regulation can affect both the calx and brown adipose tissue nature of the human body metabolic processes. As one finds in the definition of calx, a substantial amount of heat must be present to create calx, the fine white powdery substance, that results from its conversion in heated, 'firey, at that most likely,' environments. Earthly environmnets much like Kempe's descriptions in his soda ocean studies. So if one considers the osteocalcin study, with its implications for calcium and brown adipose tissue for playing a role in determining the nature of diabetes onset, via whatever insulin sensitivity modulations, failures and the like occur with osteocalcin participation, then heated temperature, thermogensis, and body temperature regulation is also imbedded into these previous features aforementioned in the previous sentence. And themes further previous in this commentary. Next commentary picks up further on this commentary info and themes.

[Harry Horton]

The following article: "Nonthermal Activation of transient receptor potential vanilloid - 1 channels in abdominal viscera tonically inhibits autonomic cold defense effectors." Curr. Biol 2007 - Oct 23:17 (20): R885-7. A quote from the study: "We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on T(b)." T (b) is body temperature. AAP's raise body temperatures that the seroquel precaution and warnings article stated. And here in this study brown adipose tissue indigenous to visceral abodminal regions,(that undergo change, that is increase, in BAT with AAP dosings)is associated with modulation and chnages in body temperature regulation. AAP blockading of the H1R, could adversely affect (PIP)2 metabolism. That is also, resynthesis of (PIP)2 which in turn creates abnormalities in TRPV1 sensitization. Abnormal TRPV1 sensitization creates a loss in thermoregulation normalcy, since TRPV1 is associated with such thermoregulation. But in regards to the above study, note how 'TRPV1 - viscera fat of the abdominal region' too, could potentially relate to the osteocalcin processes since adiponectin changes occur with osteocalcin; that is viscera abdominal BAT changes (as an expression of body composition that adiponectin genes encode for)from osteocalcin and osteocalcin's interwoven affiliation with calcium metabolism in general. Furthermore note that calcium absorption is determined by vitamin D metabolism regularity. Sunshine, a heat entity also, determines vitamin D metabolism normalcy since skin receptors of the vitamin D metabolism determine its adequate functioning. Here a potential mechanism for suppressing body temperature occurs in the quote from this study. And raises the issue, is something going on in the viscera abdominal region when core body temperature elevations occur via AAP usage. And the development of hyperglycemia occurs as a symptom of the means of this abdominal region visera's role in trying to bring down body temperature when the normal regulatory means do not exist any more, because of AAP usage effects on thermoregulation. With this in mind, consider the wikipedia article entry; "Thermogenesis". A quote from this entry goes as follows: "Non-shivering thermogenesis usually occurs in brown adipose tissue (brown fat)...It is a process whereby substances such as free fatty acids (derived from triacylglycerols) remove puirne (ADP,GDP..) inhibition of thermogenin (uncoupling protein-1) which causes an influx into the matrix of the mitochondria and bypasses the ATP sunthase channel. This uncouples oxidative phosphorylation and the energy from the proton motive force is dissipated as heat rather than producing ATP from ADP." So problems in the furnace, mitochondrial dysfunctions can be related to TRPV1 dysfunctions, if TRPV1 has such an intimate participatroy function with abdominal viscera. And the (BAT) abdominal fat gain in AAP usage, too, could be a result of sensitization abnormalities of TRPV1 with thermoregulation loss via AAP H1R blcokading. The above artilce at the top of this commentary draws TRPV1 into more prominence for creating the original condtions that ripen for diabetes development since body temperature is determined by TRPV1 functions. And an invariable effect on tissue pH activity and levels, ensuant to these thermoregulrion modulations, too, subsequently could be affected.

[harry Horton]

In a wider general analysis of diabetes and hyperglycemia, the following could be recapped. From the H. Horton entry 'Soda Lakes and diabetes' of Diabetes Topix, alklaine soda oceans and calcium appear early off in the history of the earth. And for hundreds of millions of years, scientists have had interest in these ancient phenomena, for understanding the developing dynmaics that would give way further for life's emergence. And central to the Kempe phenomena, is calcium within a hot firey earthly environment, for fueling this evolutionary destiny that would summate today with all of the plethora of species inudating the planet. So here is where the centrality of diabetes development can be found. In calcium and later the calcium metabolism. All of the early workings that Kempe details in his studies, will in process and principle, find their way into the human metabolism. Bones and the central nervous system being two prominent areas for the calcium metabolism to materialize itself. And as the Farlex definition for calx states--- Heat is an early process involved for the dynamics of calcium's presence and activity in the ancient spans of hundreds of millions of years of the globe. TRPV1 is involved in heat. Calcium's calx is involved in heat. Inflammatory cytokines as pyrogens are also involved in heat.And even as Toronto researchers found recently, the pancreatic islet progenitor cell is a 'central nervous system stem entity' that also produces neurons. Islets as such is the case with neurons thus become participants in substantial calcium metabolism processes in the body. Uncoupling protein phenomena that is replete in the four types of BAT tissue UCP1-4, that is, ---uncoupling protein predominance in the POMC and Islets, are hallmark developments found in diabetes emergence and all point to the following. UCP1-4's paricularly in BAT, especially in regards to hibernating animals all activate and proces along the lines of heat. And how thermoregulated heat is used. In the case of hibernation, dissipation out of the electron transport chain,heat occurs with UCP1-4 processes. Even heat plays a major role with calcium absorption. The vitamin D skin receptors are mandatory for adequate functioning to allow subsequent calcium absorption in the intestines. Sunlight and its heat stimulate such skin receptors. So as with TRPV1 oriented processes around heat and temperature, calcium metabolism shares also this same processes for its metabolism to transact appropriately also. The central nervous system, heat related phenomena, and the calcium metabolism, taken in its present day evolved status in relation to the metabolism's most ancient genesis of functions, back in the earth's earliest days--all are central features that could comprise diabetes developments in humans. And an area probably not considered even five or ten years ago, with any centrality, for having a significant role to any substanial magnitude for giving rise to tissue energetics impairment conditions.

[Harry Horton]

"Microbial Diversity of Soda Lakes" - Springerlink B.E. Jones et al.
"Biogenesis and Early Life on Earth and Europa: Favored by an Alkaline Ocean?"
"Origins of Skeletons" links.jstor"
The above studies are a sample of how calcium concentrations varied widely from saturation status to scarcity levels throughout the volatile heated ancient earth's environments. And how these environments fueled the developing bio diversity of different species over the previous hundreds of millions of years, such are conditions in which diabetes developments can be traced back to. Mollusk shells, that begin to appear as the wear and tear of alkaline soda ocenas that carry calcium within their essence, is an example, of how calcium processes and metabolisms start taking on their early roots. Bones would also eventually follow with these ancient terrains. And as August 2007 COlumbia Univeristy study on osteocalcin reveals, insulin sensitivity and glucose levels as well as energy homeostasis functions can be related to bone originated processes. And with it, calcium metabolism enters centrally into the mix. So the above Kempe studies illustrates this contrast between heat and calcium oriented processes, from these early environments to the present. So the above Kempe studies are good extensive illustrations of these emerging calcium oriented processes that eventually begin to appear in all sorts of life forms. All embedded in the alkaline environments of the soda oceans and other arid like land terrains of the early earth's environs. Compare the study of the above Kempe studies to previous H. Horton mentioned studies, of alkaline and lime usage from Utah State University studies on soil pH in the alkaline regions. And the David Larson 'Calcium is the King of Crop Nutrients' article. The findings in both these studies have some relevance to these early Kempe studies.

[Harry Horton]

More articles and further thoughts on the afore metnioned presented themes in previous commentaries.
"POMC melanocortin (adrenocorticotropin/beta - lipotropin / alpha - melanocyte -stimulating hormone / beta melanocyte stimulating hormone / beta endorphin"
"Weight management Biological and medical causes - weight..." 'health.nytimes.com/health/ ...' aquote: Researchers have also identified a mutation in a gene for a protein called propiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress horomones"
"ABnormalities of hypothalamo-pituary - thyroid axis in the proopiomelanocortin deficent mouse'--204.06.012 Science Direct. Martin et al.

The above three articles deal with the POMC genetic area of the hypothalamus where all the major metabolic systems are programmed from. And also, POMC is the grand central station for metabolic syndrome features, most likely.
Schizophrenia, schizo-affective disorder, the hibernating process like bi polar disorder. Diabetes, cardiovascular and possibly even Alzheimers and Parkinsons. Alcoholism too, shares attributes with this disorder. But one of the interesting features about the phenotypes listed in the above three articles is red hair. From a psychological point of view, red, has always been associated with fire. And with fire is heat. Dante's inferno, hell that is, the bible, all the myriad works of literature ranging from the west to the far east, have all depicted red with fire.
And what is fascinating about the above discoveries is along these lines, why not red hair be a further extended association of thermoregualted disorders that are heat related in essence. And particularly with that fact draws calcium metabolism into relation with the above three phenotypes, since calcium has had such an intimate geohistorical relevance with hot, molten earthly environments where the fires of the planet reach exceedingly roasted like dgrees. That is situations of heat, extreme in most cases, but present in some modulated form. More on this subsequently in following commnetaries.

[Harry Horton]

Red heads have more fun. An old saying goes. SOme popular psychological studies and literature, have reported women that have sexual relationships that are falling apart, maritial or otherwise, start dying their hair red, when they think of ending the relationship and go looking for other partners. What is fascinating about these above phenomena, is that it draws POMC into the picture, since the gene programs hair color. And possibly red hair is an expression of all the dysregulated metabolic processes that occur when POMC is genetically abberant in some form. Alcohol drinking is dysregulated, blood sugar is dysregulated, body composisiton features are dysregulated,-- in psychiatric disorders, emotional and thought processes are dysregulated also. Sexual urges become dysregulated. And also interestingly, inflammation, the metabolic feature for, insulin resistance to emerge from, it too is dysregulated also. Inflammation is already associated with heat since its functions are intimately interwoven with TRPV1 nerve processes, the heat shock protein nerve that mediates pain and heat, related phenomena. So the red hair, also is another feature of heat. And thus could be another feature for bringing calcium metabolism further into more relevant positioning along with POMC related abberancies for understanding the the basics for metabolic syndrome conditions and their arisings. Red hair, additionally, has a more salient symbolic essence, particularly since redness of any sort is associated with the fiery domminions of hell--John Milton, Cervantes and the large amounts of religious literature that attest to. So the red hair phenotype bridges both the literary symbolism and the scientific biologically based regions of research, that details dysregulated features of metabolic syndrome. Perhaps the hellish thinkings and despair indigenous to schizophrenia and schizoaffective disorders along with the other maladies, such as diabetes and cardiovascular condtions. The aforementioned Kempe studies in earlier commentaires describe calcium with heat endowed environments. And thus heat related calcium functions, of his, in relationship to POMC is another future area for research to determine in more accurate fashion--with such developments delivering more understanding of metabolic syndrome diseases.

[Harry Horton]

"The Phlogiston Theory - Wikipedia" is an entry worth reading and has relevance to the points included in the previous three to four commentaries on the lactic acid risperidone section, above. The word phlogiston- in Greek, means burnt up. THe root of the word is from 'phlox - fire', fire being the definition of the word. The theory was an attempt to explain oxidation processes, such as combustion and the rusting of metals. Between 1703 and 1731 Georg Ernst Stahl, a German Chemist, analyzed the role of phlogiston in combustion and calcination, which ironically, was the seventeenth century term for oxidation. Today, biochemistry refers to oxidation mainly in terms of mitochondrial ATP production utilizing respiratory functions for running the energy needs of the cell. But here, in this definition, that may be more deceivingly accurate in a lot of ways than current understandings of oxidation of energy producing processes, calcium is drawn into centrality. And now in diabetes research, calcium metabolism is moving more to the forefront as a major metabolic process in determining metabolic syndrome characteristics and the essence of the disorder itself. When one looks at the Farflex and wikipedia definition for calx, extreme heat, roasted and phlogiston, are all terms indigenous to these entries. So what this means, calcium metabolism and thermoregulation processes in the body move towards more significance for understanding the development of diabetes and hyperglycemia. And additionally, calcium and heat related thermoregualted phenoemna also play a role in psychiatric disorders also, potentially.
The adipokine leptin, for example participates with bone remodelling as well as being a member of the cytokine family, roughly,---, that is, since cytokines are related to inflammatory responses.And leptin is homolgous to a very substantial extent to the cytokines. This means that heat related phenomena of the inflammatory cytokine family is one in the same with the calcium processes' bone remodelling, of osteocalcin, in the body. Heat, the inflammatory response (along with TRPV1, the CNS heat shock protein, since leptin is structurally similar to cytokines). Simply as that. And leptin is structurally similar to cytokines , for that matter. Leptin comes from fat tissue, BAT is a type of fat tissue, thus recalcitrant's definition might as well include leptin along with calcium and BAT. Seemingly. But all this means that heat and thermoregulation and calcium affiliated processes are central to understanding the development of diabetes. And thus another avenue, as listed in this commentary, could be taken into consideration for further illumination for calcium and heat related phenomena's participation in creating diabetes.

[Harry Horton]

Along the themes presented in the previous commentaries above, one could consider the artisitic world, of sculptors, painters, musicians and the like. Beethoven for example may have had a form of paranoid schizophrenia, with mania comprised features of his emotional state.
But what is interesting are other historical areas of artistic enterprise, particularly the sculptures of ancient Greece, ROme and the Renaissance. For example the Elgin marbles, the statues of David and other statues and rock representations of artisitc endeavors indigenous to these cultures and times. Secondly couple these artisitc areas with geological phenomena of Kempe of ancient geo historical times dealing with the hot, red firey domminions of the earth's nature along with caclination and calcium processes in general. THirdly consider the age old religious dichotomoy of red fires of hell. The red fires of hell in contrast to the gauzy white ethereal realms of heaven. Angelic in nature, these higher spiritual regions are. When one considers all three together one gets these interesting results. The statues of the artists of the Renaissance, Greece and Rome and the like are marble, limestone, comprised works. They are artisitic results of the world's calcium entities.
And if artisitc endeavors are the result of the battle between the firey dominions of hell and heaven as such writers as Rollo May have indicated. Here in these statues one has the calcium based results of Kempe's firey dominions of the earth's past that have given humanity calx, that is limestone, marble--the results of calcination processes of ancient geohistorical climes. Marble and limestone are generally,are calcium. In some form. And they are also white. Heaven is white. Hell is red. And maybe calcium metabolism deals with a substance calcium that is generally white. But calcium, white in its essesnce, results from red. The Firey realms of the erath's ancient molten environment with its red savagery firelike nature that comprised extreme degrees of heat. All three above examples are very similar in these regards. The Kempe geo historical studies on calcium and heat related earth phenomena for one. The marble white statues of Greece, Rome and the Renaisaance, secondly, that is. And thirdly and finally the red fires of hell in relation to the white gauzy angelic comprisement of heaven as depicted in literature. Two features of literature and religion, that have always been communicated in abundance down through the years of civilization--in various cultures, additionally. Its intersting how all the above three seemingly disparate phenomen have strikingly similar features.

[Harry Horton]

More loopy thinking of mine perhaps, having suffered a schizo affective disorder, that I feel at times gives me more creative insights on a lot of topics at the risk of going way out over the edge sometimes. The following is a continuation of the philogiston theory. Combined, secondly, with Kempe's studies on the hundreds of millions of years calcium and its amounts, that traveled through time in the firey ravages of the ancient earth's environments, taking up in alkaline soda oceans and dry land mass terrains for that matter. In eastern religions, the bible, and various literary works of western literature, the red firey realms of hell co exist with the gauzy white ethereal heights of heavens, the latter that contains their angelic beings. And yet the firey realms of the earth give rise to the white solid phenomena of calcium, from calx. It seems the described heaven and hell and co joined with Kempe's 'calcium from firey earthly environments' are one in the same. Each is an expression of the other, and thus both are one in the same, especially if earth is a spiritual plane as religions like Eckankar assert. So what would seperate earthly matter and energy as spiritual essence entities, extending say into the astral plane, without any real delineation, distinction, borders if one will,----if earth and the surrounding universe is a spiritual plane, the same as the other plances of consciousness. So phlogiston, as this hard to define, abstract spiritual feature, the Greeks developed could hold some validity in this regards. And all of this is headed to the fact that calcium and thermoregualtion, are truly fundamental, primordial and basic in their existence. And could be the metabolic areas that hold the most therapeutic power for eliminating tissue energetic impairment maladies, if such metabolic areas are centered on. Since thermoregulation and calcium could hold additional spiritual power and significance. As the poet Rilke stated: "If my devils are to leave me, my angels will take flight as well." The devilish situation of thermoregulation dysregulation and dysfunction, that originated from acnient earth's molten firey domains, probably will affect our white heavenly like resultant calcium metabolism functions, bringing on diabetes in its wake. Angels and cherubs, and bibical figures cast in the calcium based marble and limestone of the renaisasance, such ethereal beings probably have found their rightful home. Especially if one applies Kempe's principles to their coming into being via the sculptor's hand and craft. And these created angelic creatures grace the marble and limestone, as to say this substance of white rock, is really the same stuff as us. Possibly in terms of a phlogiston like approach to their presence in these rocks born of calcium that was present since the beginning ot time perhaps.

[Harry Horton]

The spiritual and phiolosophical essence of the phlogiston theory is something to contemplate, especially in regards the theory has to psychiatirc disorders and diabetes. The term"quintessence" is used in the definition of the phlogiston theory. From the web site "Dictionary.com Unabridged" the definition of 'quintessence' goes as follows. 1. the pure and concentrated essence of a substance. 2. the most perfect embodiment of something. 3.(in ancient and medieval philosophy) the fifth essence or element, ether, supposed to be constituent matter of the heavenly bodies, the others being air, fire, earth, and water. In the "American Heritage Dicitionary - Cite This Source -Share. Their 3. definition,(which for relevance sake to the earlier enumerated definitions above, I'll call 3.b.) 3.b. goes as follows: "In ancient and medieval philosophy, the fifth and highest essence after the four elements of earth, air, fire, and water, thought to be the substance of the heavenly bodies and latent in all things." When in regards to the phlogiston theory, quintessence's substance of heavenly bodies,relates a spiritual, heavenly attribute, essence, character if you will to the phlogiston theory. And when the phlogiston theory deals with calx biochemical reactions, these reactions have this heavenly, spiritual existence to it, because calx development through combustible means occurs via spiritual means and processes according to the 'quintessence part' of the phlogiston theory. While seemingly such combustible reactions are also of the physical world. Furthermore, the religous philosophy Eckankar- denotes its first plane of God to be called soul plane, which is the fifth plane. A character of being fifth, in regards to its spiritual ranking of sorts amidst other planes of consciousness, seemingly similar to quintessence's depiction of 'fifth' element amongst the earthly ones, while the fifth one bridges both the physical world and the spiritual domains, according to the phlogiston theory. The Four earthly planes of consciousness, so easily manifested in the earth among the human mind, lower four planes fall beneath the fifth- soul plane. No negative essence or currents are found on the fifth soul plane. In Eckankar's terms. And thus this fifth plane- soul plane- is quintessent for that reason.