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justashell

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  1. I was interested in reading about this, but can't get the pdf to download.
  2. Thanks---I've bookmarked it---I need to take it in little bites---lots of stuff there!
  3. Melissa B.---I've been reading up on porphyria---and other stuff too---but I think that somewhere, Porphyria was called the "royal" disease---due to lots of English royalty being afflicted with it. I have the same thoughts about Henry VIII being a cushie---he could have already been pre-disposed to the disease---and a head injury could have thrown things totally out of whack. I may be imagining things---but it seems like the documentary I saw on Henry VIII stated that he was a very nice fellow when he was younger---but turned into a royal tyrant later on. Of course being under tons of pressure doesn't help things either.
  4. I personally think that way too many people who are in jail or prison, are there due to health problems---that no one has ever picked up on. I'm not excusing the behavior---just saying that I think it's super important to have some serious screening for health problems.
  5. Link: http://74.125.155.132/search?q=cache:2yjXv...lient=firefox-a http://www.independent.org/pdf/tir/tir_08_2_whalen.pdf.
  6. I met a guy who was working on a local tv ad, and he had shoes with springs on them---very similar to what the dad is wearing. I wondered if they were therapeutic shoes---the guy said no---just comfortable. I looked to see if I could find the manufacturer---couldn't find that exact one---but there are others: http://z-coil-miami.com/catalog1.htm I kept thinking that if I tried walking in them, I'd end up the same way I do when I wear heels---tottering around and worried about falling down. After reading this: http://z-coil-miami.com/Testimonials.htm I wonder if this gal (from Corvallis) didn't get a case of Cushings via the anti-inflammatory drugs that were destroying his liver or if she had some sort of underlying endocrine problem that never got noticed? Apparently, Helena Bonham Carter is a big fan too. I wonder if it's THAT HBC? The way she talks, it sounds like it could be.
  7. I remember seeing Tanya on the Today show (I think)---another guest was the founder (I think) of the Pituitary Network. He mentioned that often times patient's like Tanya are told there is nothing that can be done---but there are doctors/specialists out there who may be able to help. It's sad when something so obvious is going on---and people still treat you like you're a freak. Ugh. It just goes to show how ignorant we all can be.
  8. Thanks for sharing this---I've been told that "drug store" brands are pretty good about maintaining good quality control---but I still wonder about things--- especially after the dog food/cat food melanin fiasco. A factory or plant might have good quality control---but they're taking the word of their suppliers, that they're being just as careful. Garbage in, garbage out. Don't know if anyone saw a recent Rachel Ray---she had Dr. G. Medical Examiner from Florida on---talking about how to be safe---shared a story about how a major pharmacy blunder caused the death of a young boy who had asthma. After taking his asthma pills, he started acting weird, eventually fell asleep and died. They did an autopsy and found that he had methadone in his system---the authorities first suspected the mother, but then they started looking at the medicine----the pills looked right---but they were wrong---somehow the pills were tainted with methadone---or were all methadone. Dr. G. said she couldn't imagine something like that happening---but it did. She went on to encourage everyone to: *double and triple check their medicines when they pick them up * to check them if they have any weird effects that they hadn't experienced before *and make sure that the pharmacy doesn't give them the someone else's meds or pills *realize that many medications have similar sounding names---and to make sure that you know which ones you are supposed to be taking *if you share a medicine cabinet with others---make sure that you mark your bottles with some sort of distinctive color---so you don't accidentally take someone else's when it's dark, you're tired, etc.
  9. My roid rages come and go---and they are nearly impossible for me to control---it's not a matter of choice---it's more like I'm in the fight of my life. I'm the same way---I'm usually very calm and don't get rattled---but talking to my pcp today, I told him that when I get bad, I'm a total, 100%, certified jerk. And I hate it. Check out your bp and your blood sugar when it happens---my bp and my blood sugar seem to be high when I'm raging. BP at doctor's office was high---they didn't say how high, but the machine took about four minutes to get a reading---and the cuff got so tight, I was about ready to cry. When I got home, my bp was 187/109 but my blood sugar (after eating) was just 72. I wasn't going into a rage today---although I was upset. Still trying to figure things out---but this seems to back up my theory that when my blood sugar is high, and my bp is high---I'm roid-raging.
  10. I keep refusing the drugs to "hide" things. I want to figure out what the heck is going on! Taking anti-depressants is like lying to my brain and my body.
  11. Thanks for setting me straight Monica. I have been looking at some other stuff about BPD---and I swear, I must be oozing cortisol right now---I'm so frigging mad!!! I was just complaining to our bishop from church who came by earlier this evening. His son just completed his first year of medical school, and we were talking about how he wished his son was here so he could look at the labs and reports that I have that cover the last 10 years. I've got what looks like hypokalemia, low DHEA-S's, polyuria, nocturia, polydipsia, etc., and more and more and more!!! It matches almost perfectly with Conn's syndrome or disease---where your adrenal glands are up to no good. The only thing I don't have is a headache---I don't get headaches very often. If they'd just open their eyes and think about it, they'd help people! What is their pathological personality disorder? Honestly, I've demonstrated over and over that I'm not helpless---but they seem to be stuck on some island of denial and delusion. Thanks for setting me straight Monica. I have been looking at some other stuff about BPD---and I swear, I must be oozing cortisol right now---I'm so frigging mad!!! I was just complaining to our bishop from church who came by earlier this evening. His son just completed his first year of medical school, and we were talking about how he wished his son was here so he could look at the labs and reports that I have that cover the last 10 years. I've got what looks like hypokalemia, low DHEA-S's, polyuria, nocturia, polydipsia, etc., and more and more and more!!! It matches almost perfectly with Conn's syndrome or disease---where your adrenal glands are up to no good. The only thing I don't have is a headache---I don't get headaches very often. OUr bishop, who has known me for more than 18 years, said that he doesn't know anyone who has had more physical problems and illnesses. Yeah, I know. I've been dealing with them for more than 50 years---but I keep getting blamed for them. I'm tired of it. Why would I want to do this to myself? If they'd just open their eyes and think about it, they'd help people! What is their pathological personality disorder? Honestly, I've demonstrated over and over that I'm not helpless---but they seem to be stuck on some island of denial and delusion.
  12. They didn't mention that these folks tended to be fat. Oh, I forgot. That's 'cause we're lazy and we eat too much. I don't know if it's the cortisol talking, but I find this all offensive. Personality??? Oh wait, now I remember---'cause I've seen the notes talk about suspected borderline personality disorder. What kind of borderline and non-border line personality disorder do doctors, lawyers, politicians, etc., have when they make misdx's, when they drink too much, lie, cheat and steal??? Oh, yeah, they have a DISEASE---not a personality disorder. I don't think it's the cortisol talking, I think that I'm just disgusted by the whole load of crap. BIG PS: Monica---this is in no way aimed at you---but at the friggin' idiots who come up with this crap. If you ask me, all diseases are physical. http://www.palace.net/~llama/psych/bpd.html Borderline Personality Disorder Borderline Personality Disorder (BPD) is one of the most controversial diagnoses in psychology today. Since it was first introduced in the DSM, psychologists and psychiatrists have been trying to give the somewhat amorphous concepts behind BPD a concrete form. Kernberg's explication of what he calls Borderline Personality Organization is the most general, while Gunderson, though a psychoanalyst, is considered by many to have taken the most scientific approach to defining BPD. The Diagnostic Interview for Borderlines and the DIB-Revised were developed from research done by Gunderson, Kolb, and Zanarini. Finally, there is the "official" DSM-IV definition. Some researchers, like Judith Herman, believe that BPD is a name given to a particular manifestation of post-traumatic stress disorder: in Trauma and Recovery, she theorizes that when PTSD takes a form that emphasizes heavily its elements of identity and relationship disturbance, it gets called BPD; when the somatic (body) elements are emphasized, it gets called hysteria, and when the dissociative/deformation of consciousness elements are the focus, it gets called DID/MPD. Others believe that the term "borderline personality" has been so misunderstood and misused that trying to refine it is pointless and suggest instead simply scrapping the term. What causes Borderline Personality Disorder? It would be remiss to discuss BPD without including a comment about Linehan's work. In contrast to the symptom list approaches detailed below, Linehan has developed a comprehensive sociobiological theory which appears to be borne out by the successes found in controlled studies of her Dialectical Behavioral Therapy. Linehan theorizes that borderlines are born with an innate biological tendency to react more intensely to lower levels of stress than others and to take longer to recover. They peak "higher" emotionally on less provocation and take longer coming down. In addition, they were raised in environments in which their beliefs about themselves and their environment were continually devalued and invalidated. These factors combine to create adults who are uncertain of the truth of their own feelings and who are confronted by three basic dialectics they have failed to master (and thus rush frantically from pole to pole of): * vulnerability vs invalidation * active passivity (tendency to be passive when confronted with a problem and actively seek a rescuer) vs apparent competence (appearing to be capable when in reality internally things are falling apart) * unremitting crises vs inhibited grief. DBT tries to teach clients to balance these by giving them training in skills of mindfulness, interpersonal effectiveness, distress tolerance, and emotional regulation. Kernberg's Borderline Personality Organization Diagnoses of BPO are based on three categories of criteria. The first, and most important, category, comprises two signs: * the absence of psychosis (i.e., the ability to perceive reality accurately) * impaired ego integration - a diffuse and internally contradictory concept of self. Kernberg is quoted as saying, "Borderlines can describe themselves for five hours without your getting a realistic picture of what they're like." The second category is termed "nonspecific signs" and includes such things as low anxiety tolerance, poor impulse control, and an undeveloped or poor ability to enjoy work or hobbies in a meaningful way. Kernberg believes that borderlines are distinguished from neurotics by the presence of "primitive defenses." Chief among these is splitting, in which a person or thing is seen as all good or all bad. Note that something which is all good one day can be all bad the next, which is related to another symptom: borderlines have problems with object constancy in people -- they read each action of people in their lives as if there were no prior context; they don't have a sense of continuity and consistency about people and things in their lives. They have a hard time experiencing an absent loved one as a loving presence in their minds. They also have difficulty seeing all of the actions taken by a person over a period of time as part of an integrated whole, and tend instead to analyze individual actions in an attempt to divine their individual meanings. People are defined by how they lasted interacted with the borderline. Other primitive defenses cited include magical thinking (beliefs that thoughts can cause events), omnipotence, projection of unpleasant characteristics in the self onto others and projective identification, a process where the borderline tries to elicit in others the feelings s/he is having. Kernberg also includes as signs of BPO chaotic, extreme relationships with others; an inability to retain the soothing memory of a loved one; transient psychotic episodes; denial; and emotional amnesia. About the last, Linehan says, "Borderline individuals are so completely in each mood, they have great difficulty conceptualizing, remembering what it's like to be in another mood." Gunderson's conception of BPD Gunderson, a psychoanalyst, is respected by researchers in many diverse areas of psychology and psychiatry. His focus tends to be on the differential diagnosis of Borderline Personality Disorder, and Cauwels gives Gunderson's criteria in order of their importance: * Intense unstable relationships in which the borderline always ends up getting hurt. Gunderson admits that this symptom is somewhat general, but considers it so central to BPD that he says he would hesitate to diagnose a patient as BPD without its presence. * Repetitive self-destructive behavior, often designed to prompt rescue. * Chronic fear of abandonment and panic when forced to be alone. * Distorted thoughts/perceptions, particularly in terms of relationships and interactions with others. * Hypersensitivity, meaning an unusual sensitivity to nonverbal communication. Gunderson notes that this can be confused with distortion if practitioners are not careful (somewhat similar to Herman's statement that, while survivors of intense long-term trauma may have unrealistic notions of the power realities of the situation they were in, their notions are likely to be closer to reality than the therapist might think). * Impulsive behaviors that often embarrass the borderline later. * Poor social adaptation: in a way, borderlines tend not to know or understand the rules regarding performance in job and academic settings. The Diagnostic Interview for Borderlines, Revised Gunderson and his colleague, Jonathan Kolb, tried to make the diagnosis of BPD by constructing a clinical interview to assess borderline characteristics in patients. The DIB was revised in 1989 to sharpen its ability to differentiate between BPD and other personality disorders. It considers symptoms that fall under four main headings: 1. Affect * chronic/major depression * helplessness * hopelessness * worthlessness * guilt * anger (including frequent expressions of anger) * anxiety * loneliness * boredom * emptiness 2. Cognition * odd thinking * unusual perceptions * nondelusional paranoia * quasipsychosis 3. Impulse action patterns * substance abuse/dependence * sexual deviance * manipulative suicide gestures * other impulsive behaviors 4. Interpersonal relationships * intolerance of aloneness * abandonment, engulfment, annihilation fears * counterdependency * stormy relationships * manipulativeness * dependency * devaluation * masochism/sadism * demandingness * entitlement The DIB-R is the most influential and best-known "test" for diagnosing BPD. Use of it has led researchers to identify four behavior patterns they consider peculiar to BPD: abandonment, engulfment, annihilation fears; demandingness and entitlement; treatment regressions; and ability to arouse inappropriately close or hostile treatment relationships. DSM-IV criteria The DSM-IV gives these nine criteria; a diagnosis requires that the subject present with at least five of these. In I Hate You -- Don't Leave Me! Jerold Kriesman and Hal Straus refer to BPD as "emotional hemophilia; [a borderline] lacks the clotting mechanism needed to moderate his spurts of feeling. Stimulate a passion, and the borderline emotionally bleeds to death." Traits involving emotions: Quite frequently people with BPD have a very hard time controlling their emotions. They may feel ruled by them. One researcher (Marsha Linehan) said, "People with BPD are like people with third degree burns over 90% of their bodies. Lacking emotional skin, they feel agony at the slightest touch or movement." 1. Shifts in mood lasting only a few hours. 2. Anger that is inappropriate, intense or uncontrollable. Traits involving behavior: 3. Self-destructive acts, such as self-mutilation or suicidal threats and gestures that happen more than once 4. Two potentially self-damaging impulsive behaviors. These could include alcohol and other drug abuse, compulsive spending, gambling, eating disorders, shoplifting, reckless driving, compulsive sexual behavior. Traits involving identity 5. Marked, persistent identity disturbance shown by uncertainty in at least two areas. These areas can include self-image, sexual orientation, career choice or other long-term goals, friendships, values. People with BPD may not feel like they know who they are, or what they think, or what their opinions are, or what religion they should be. Instead, they may try to be what they think other people want them to be. Someone with BPD said, "I have a hard time figuring out my personality. I tend to be whomever I'm with." 6. Chronic feelings of emptiness or boredom. Someone with BPD said, "I remember describing the feeling of having a deep hole in my stomach. An emptiness that I didn't know how to fill. My therapist told me that was from almost a "lack of a life". The more things you get into your life, the more relationships you get involved in, all of that fills that hole. As a borderline, I had no life. There were times when I couldn't stay in the same room with other people. It almost felt like what I think a panic attack would feel like." Traits involving relationships 7. Unstable, chaotic intense relationships characterized by splitting (see below). 8. Frantic efforts to avoid real or imagined abandonment * Splitting: the self and others are viewed as "all good" or "all bad." Someone with BPD said, "One day I would think my doctor was the best and I loved her, but if she challenged me in any way I hated her. There was no middle ground as in like. In my world, people were either the best or the worst. I couldn't understand the concept of middle ground." * Alternating clinging and distancing behaviors (I Hate You, Don't Leave Me). Sometimes you want to be close to someone. But when you get close it feels TOO close and you feel like you have to get some space. This happens often. * Great difficulty trusting people and themselves. Early trust may have been shattered by people who were close to you. * Sensitivity to criticism or rejection. * Feeling of "needing" someone else to survive * Heavy need for affection and reassurance * Some people with BPD may have an unusually high degree of interpersonal sensitivity, insight and empathy 9. Transient, stress-related paranoid ideation or severe dissociative symptoms This means feeling "out of it," or not being able to remember what you said or did. This mostly happens in times of severe stress. Miscellaneous attributes of people with BPD: * People with BPD are often bright, witty, funny, life of the party. * They may have problems with object constancy. When a person leaves (even temporarily), they may have a problem recreating or remembering feelings of love that were present between themselves and the other. Often, BPD patients want to keep something belonging to the loved one around during separations. * They frequently have difficulty tolerating aloneness, even for short periods of time. * Their lives may be a chaotic landscape of job losses, interrupted educational pursuits, broken engagements, hospitalizations. * Many have a background of childhood physical, sexual, or emotional abuse or physical/emotional neglect. )))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))) ))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))) )))))))))))))))))))))))))))))))))))))))))))) I think I hear someone barking up the wrong tree.
  13. Somehow it finally started... Great Job! Thanks!!!
  14. I don't know about anyone else---but I'm having trouble getting things to load up...
  15. What is the relationship between thyroid and cortisol? Why does diabetes get all the attention? Do you believe there is a chance that the ubiquitous artificial light we are exposed to causes some disruption of the pineal, pituitary or other glands? Do fictional shows like "House" and documentary shows like the one that featured you, "The Science of Obesity", help develop interest in endocrine research? How can we help further endocrine research? Why are so many doctors (other than you) so dismissive of patients symptoms? What can we do to help our doctors figure out complex medical issues? What changes would you like to see in the field of medicine? What would you as a doctor like the public to know? What changes would you like to see in the field of medicine? or: What have been the biggest changes you've seen in the field of medicine?
  16. I'm 2 for 2 with Mystery Diagnosis. First the show on Cushings. Next up--- the show on Hypopituitarism. I'm waiting for the show on Growth Hormone Deficiency next. PS: I'm not counting the show where a woman spent something like 3 years, numerous doctors and thousands and thousands of dollars only to find out in the end that her thyroid was low.
  17. Forget about bonging the parents in the head----we need to bong the doctors in the heads---they're the ones who're really screwing us over. Let them try and live with a pit. that's on the fritz!
  18. I woke up in time to watch it. It's surprising to me that so many doctors STILL missed it, when her symptoms were so dramatic! A couple of things I wasn't too keen on: 1) They never mentioned that this can be caused by other things. 2) Apparently, two pills "cure" this condition. At the end of the second case, I turned to my husband and said: "Those have been mentioned on the message boards too." As they shared the second gal's story, I kept telling my husband that it was interesting that all of this started around the time this girl started experiencing her first period. I would have liked a bit more of an explanation as to whether this was related to endocrine changes.
  19. I can't wait to see this show!!! Shar McGraw's story on Mystery Diagnosis was the breakthrough for me. I've been dx'd with hypopituitarism---but I'm also testing for cyclical Cushings. Thanks for posting this for us! Mystery Diagnosis and this website, and all of you---have been my life-savers!!!
  20. Very interesting...I have had a couple of EKG's and one Echocardiogram in the last couple of years due to things doctors have noticed. One of the first symptoms of my thyroid/adrenal/pituitary problems was exercise intolerance---I would be ok one day/hour/minute----and near death the next. After seeing my second frowny heart on the exercise machine at the health club, I went to the doctor. He didn't see anything at the time---but apparently things are becoming more and more apparent as I go along. Thank goodness for GH!
  21. Media Moguls, MaryO and StaticNrg go where Oprah fears to tread... Way to GO!!! Way to GO!!! Way to Go Dr. Rob!!!
  22. Just chiming in here---I happened to see Mystery Diagnosis (Sharm's story) and realized that I may be suffering from Cushings. Later on, I saw Sam's story---and I realized that Cushings is not only not so rare---but that it could hit at any age. Thank goodness to all involved for sharing their experiences---and helping raise awareness and hope---for the rest of us.
  23. Thanks for sharing this Robin and Mertie...there are some things in this article that I don't really want to think too much about---I wonder if e-harmony or someone like that may incorporate some of these findings in their "compatibility" profile. I remember reading a book a long time ago when I was a kid---it was called something like "stress without destress". The whole premise of the book---is that STRESS is NATURAL---but it's the DIS-that we put into it that makes things hard for us. Of course this was a "self-help" book from the late 60's or early 70's---and some folks think of those days as the "dark ages". Maybe they weren't so dark after all. A couple of things to read if bored: http://www.nature.com/mp/journal/v8/n3/full/4001323a.html News and Commentary Molecular Psychiatry (2003) 8, 253–254. doi:10.1038/sj.mp.4001323 Stress without distress: homeostatic role for KATP channels L V Zingman1, D M Hodgson1, A E Alekseev1 and A Terzic1 1Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA Correspondence: Dr A Terzic, Guggenheim 7, Mayo Clinic, Rochester, MN 55905, USA. E-mail: terzic.andre@mayo.edu Stress is defined as a threat, real or implied, to the narrow range of physiological parameters necessary for survival, with the dynamic of existence comprising an ongoing sequence of stressful events and their consequences.1 Self-preservation is achieved through the general adaptation syndrome that is initiated by brain recognition of threat leading to modification of behavior and activation of the hypothalamic-pituitary–adrenal axis and autonomic nervous system.1 This ubiquitous response underlies the 'fight-or-flight' reaction by alteration of bodily functions to sustain a new performance level necessary for confrontation or evasion of threatening conditions.1 However, augmentation in performance is metabolically demanding, and requires a safety mechanism to prevent fatal exhaustion of resources. Recently, the ATP-sensitive potassium (KATP) channel, a cell membrane metabolic sensor, was identified as a critical component in maintaining the body's homeostasis during the adaptive reaction to stress, such that the reaction itself does not become deleterious to the organism.2 KATP channels, widely represented in metabolically active tissues, are formed through physical association of the pore-forming inwardly rectifying potassium channel, Kir6.x, with the regulatory sulfonylurea receptor, SUR.3 In this way, Kir6.2 and SUR2A generate cardiac and skeletal muscle KATP channels.4 Metabolic sensing occurs through modulation of Kir6.2 ATP-sensitivity by the SUR2A subunit ATPase activity such that stabilization of SUR2A in a posthydrolytic state favors K+ efflux through Kir6.2 leading to membrane hyperpolarization.5 These intrinsic channel properties, along with tight integration of KATP channel proteins with cellular metabolic pathways, are responsible for the rapid and precise metabolic modulation of membrane potential-dependent cellular functions.5 Vascular smooth muscle channels combine Kir6.1 and SUR2B,6 and channels in pancreatic beta-cells comprise Kir6.2 and SUR1.3 In neurons, various permutations of Kir6.1 or Kir6.2 and SUR1 or SUR2 coexpression form KATP channels.7 Such structural diversity defines a wide spectrum of KATP channel involvement in tissue-specific functions, yet the underlying property of the metabolic mediator remains consistent. In the heart, while the role of KATP channels has been viewed as that of protection against the metabolic insult of ischemic injury, recent data support a broader interpretation of these channels as molecular mediators in the adaptive response to stress.2 Indeed, under exercise-stress, a natural trigger of the general adaptation syndrome,1 mice lacking KATP channels through genetic deletion of Kir6.2 perform at a significantly reduced level than age- and gender-matched normal controls.2 In stress situations, sympathetic stimulation augments cardiac output to support the body's immediate or anticipated requirement of enhanced performance. This augmented work imposes a significant demand on cardiac metabolic resources, mostly because of energy-consuming Ca2+ handling. To prevent cellular Ca2+ overload and associated energy depletion, increased Ca2+ influx is normally balanced by a compensatory increase in outward potassium ion currents. This protective feedback mechanism is absent in myocardium lacking KATP channels.2 Hearts from Kir6.2-knockout mice display less shortening of the action potential after adrenoreceptor stimulation than normal hearts. In fact, Kir6.2-knockout mice demonstrate a phenotype of increased vulnerability under stress manifested by aberrant regulation of cardiac membrane excitability, inadequate calcium handling, and fatal ventricular arrhythmia.2 This underscores the vital role of KATP channels in the coordination of cardiac function with changing metabolic conditions. Moreover, KATP channels regulate vascular tone, and thereby the delivery of metabolic resources to match demand.8 Furthermore, these channels are central in setting blood glucose levels by regulating insulin exocytosis in pancreatic beta-cells and insulin-dependent glucose uptake in skeletal muscle.3,9,10,11,12 Thus, KATP channels adjust the function of end-organ systems critical in the adaptive response to stress. Ultimately in the hierarchy of the general adaptation syndrome, KATP channels in the nervous system operate via changes in neuronal excitability as a feedback mechanism coupling the adaptive response to the metabolic state.7,13,14 In particular, KATP channel activity defines the firing rate of glucose-responsive neurons identified in a number of discrete brain areas including the ventromedial, arcuate and paraventricular nuclei of the hypothalamus, substantia nigra, as well as in the area postrema and the tractus solitarius nucleus.7,13,14,15 When extracellular glucose increases, glucose metabolism in neurons promotes KATP channel inhibition leading to membrane depolarization and increased neuronal activity. Conversely, with the decrease in extracellular glucose levels, ensuing changes in cellular metabolism favor KATP channel opening associated with a reduced rate of neuronal firing. KATP channels are gated not only in response to oscillations in extracellular glucose, but also respond to the direct action of stress-sensitive neuromediators, including endorphins, adenosine and leptin.15 Changes in neuronal activity translate into modification of the adaptive response through behavioral effects, and activation patterns of the hypothalamic-pituitary–adrenal axis. Kir6.2-knockout mice exhibit a severe defect in hypothalamic-pituitary–adrenal axis-dependent glucagon secretion and food intake in response to neuroglycopenia and hypoglycemia.14 Further, KATP channels have been implicated in the control of satiety and pain perception.7,15 Thus, the KATP channel/enzyme protein complex, integrated with cellular and systemic metabolism, acts at various levels to ensure energetic homeostasis under the augmented functional demands of the adaptation reaction (Figure 1). In this way, the KATP channel serves as a unifying molecular coordinator of metabolic well-being under stress. This homeostatic function identifies the role of KATP channels in the hierarchy of molecular events underlying propagation of the general adaptation syndrome. KATP channels maintain balance between the adaptive response to stress and metabolic resources to ensure survival. KATP channels, comprised of the pore-forming Kir6.x and regulatory SUR subunits, are represented in metabolically active tissues where they support execution of the general adaptation syndrome under stress and allocation of resources to balance the need for escape or confrontation with prevention of metabolic exhaustion. In this way the KATP channel, with a broad range of tissue-specific properties, acts as a unifying molecular coordinator of the body's response to stress. Is this why my sodium levels rise and fall? http://www.vetscite.org/publish/items/000843/index.html 14 October 2002 How the heart copes with stress without distress Mayo Clinic researchers today identified a genetic basis for the heart's ability to withstand fight-or-flight responses: a protein called Kir6.2 enables the heart to react to stress without distress. Mice lacking this key protein had reduced cardiac tolerance for both exercise- and adrenaline-like stress. Nearly three-quarters (73 percent) of the Kir6.2-deficient mice died within 14 minutes after a stressor challenged their cardiac response -- yet all the mice that possessed Kir6.2 survived the stress tests. As reported in the 1 October edition of Proceedings of the National Academy of Sciences (PNAS), the research provides provocative leads to understanding and treating stress-related disorders of the heart. These may range from sudden death of highly conditioned athletes to the cumulative effects of psychological stress at work, school or in family life. "We have identified in the heart a protective mechanism against stress that is roughly analogous to an automatic sprinkler system that douses a fire in an emergency," says Andre Terzic, M.D., Ph.D, lead researcher. "The Kir6.2 protein senses stress and prevents damage to the heart by helping the cells maintain equilibrium even under peak workloads. Lack of Kir6.2 protein function causes sudden, irreversible damage to heart cells, which could lead to heart failure." In the study, the Mayo Clinic team led by Dr. Terzic compared mice in which the gene that produces the Kir6.2 protein had been eliminated to a control group of mice that possessed the Kir6.2 protein. Their goal was to determine whether Kir6.2 enables heart cells to maintain high levels of activity without suffering damage, and to discover how it works. Study Findings In treadmill testing, the normal mice tolerated more than three times the workload that the Kir6.2-deficient mice could. Both groups of mice were also tested under stress induced by a compound similar in effect to adrenaline, the body's natural fight-or-flight hormone. In mice lacking Kir6.2, hearts did not contract as completely under stress – and 73 percent developed severe heart rhythm disturbances called arrhythmias, then died suddenly. By contrast, none of the normal mice experienced a fatal arrhythmia. Study Significance Kir6.2, a protein common to all animals, is at the core of the KATP channel complex that choreographs an intricate chemical dance between potassium and calcium flow in the heart. By conducting potassium, the KATP channel enables the cells to more quickly restore electrical balance following each heartbeat, thus limiting the entrance of calcium into the cells. "The system needs to be fully orchestrated," says Dr. Terzic. "It must have perfect harmonization to bring sufficient calcium for contraction without overdoing it." When the orchestra is "off tempo," the chemical dancers are out of step. The result: cardiac distress under stress. The Mayo Clinic study found that heart cells in the mice lacking Kir6.2 overloaded with calcium – and this damaged cell structure. Administering calcium-channel blockers, a common heart medication, to those Kir6.2-deficient mice prevented the fatal arrhythmias in five out of six. Thus, the Mayo Clinic study shows that Kir6.2 is crucial to survival under the sudden rush of cardiac output required by the flight-or-fight response of the sympathetic nervous system to threats – be they from a saber tooth cat or a bear market. "Because of the selective advantage it confers, Kir6.2 has been maintained through evolution in the gene package of many organisms," explains Dr. Terzic. The next steps for the Mayo Clinic researchers will be developing the diagnostic and therapeutic potential of these findings. A blood test could identify individuals who are deficient in KATP channel proteins, or whose supporting protein-signaling system isn't working, and drug or gene therapies could compensate for those deficiencies. "Understanding that this protein is so important, we can now work on ways to repair it when defective within the cells, or to boost its ability to respond," Dr. Terzic concludes. Original source: Mayo Clinic Bio.com 30 September 2002
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