Hypothalamic Centers Research Articles

Review of physiology, clinical manifestations, and management of hypothalamic obesity in humans

Hypothalamic injury from acquired structural damage due to infiltrative disease, tumor, or their treatment aftereffects frequently results in the development of an obesity syndrome characterized by a rapid, unrelenting weight gain that may be accompanied by severe hyperphagia. Weight gain occurs from the disruption of the normal homeostatic functioning of the hypothalamic centers responsible for controlling satiety and hunger and regulating energy balance with resulting hyperphagia, autonomic imbalance, reduction of energy expenditure, and hyperinsulinemia. Curtailment of weight increase has traditionally been refractory to usual dietary and lifestyle interventions. Pharmacotherapy targeting insulin secretion and augmenting sympathetic output have been attempted to promote weight loss or attenuate weight gain. In addition, case reports suggest that bariatric surgery may be an effective treatment option for these patients. Hormonal deficits are often present, and their management may also have consequences for weight control. Hypothalamic obesity confers significant morbidity and mortality, and there is a need for greater elucidation of its risk factors and pathogenesis so that more effective interventions can be developed.

Morphometric analysis of hypothalamic cells showing c-Fos proteins after movement restriction and EHF-irradiation

A morphometric analysis of hypothalamic cells containing c-Fos-like protein detected by an indirect immunoperoxidase method was carried out to clarify the responses to movement restriction and skin electromagnetic high frequency (EHF) irradiation (7.1 mm, 42.2 GHz, 20 mW output power) simultaneously to three acupuncture projection areas. The morphometry of c-Fos-protein positive neurons by their number and type was analyzed. Movement restriction (40 min) induced c-Fos protein expression primarily in cells with 10–50 μm 2 sizes (associative type neurons) only in anterior hypothalamic nucleus and lateral hypothalamic area; while additional EHF-irradiation of acupuncture projection areas (under movement restriction) induced c-Fos expression in all hypothalamic structures and mostly in cells with 70–150 μm 2 sizes (relay type neurons), i.e. changed the pattern of activated cell type distribution. In conclusion, the findings show that modest stress under which experimental animals often are exposed increase c-Fos protein expression in hypothalamic centers and skin EHF-irradiation of acupuncture projection areas seem to increase that.

Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone‐treated rats

Chronic low-dose dexamethasone (DEX) treatment in rats is associated to insulin resistance with compensatory hyperinsulinaemia and reduction in food intake. We tested the hypothesis that the elevation in circulating free fatty acids (FFAs) induced by DEX is the common mediator of both insulin resistance and insulin hyperproduction. For this purpose, an anti-lipolytic agent was administered during DEX treatment to lower lipacidaemia for several hours prior to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by Northern blot) and plasma leptin levels (by radioimmunoassay) were also investigated to verify whether a rise in circulating leptin could be responsible for the anorectic effect of DEX. Our data show that a transient pharmacological reduction of elevated plasma FFA levels abates the post-loading hyperinsulinaemia and counteracts the insulin resistance induced by DEX, supporting the hypothesis that the chronic elevation in FFAs is the common mediator of DEX-induced changes. Despite enhanced leptin expression in white adipose tissue, DEX-treated rats show no significant increase in plasma leptin levels. This suggests that the anorectic effect of DEX should be mediated, at least partially, by other factors, possibly related to the influence of concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers regulating feeding. Our results sustain the idea that a prolonged increase in plasma FFA levels plays an important role in the adaptive regulation of glucose and energy homeostasis, not only by potentiating insulin secretion but also by providing a signal of 'nutrient abundance' capable of restraining food intake.

A novel site of adult doublecortin expression: neuropeptide neurons within the suprachiasmatic nucleus circadian clock

BackgroundThe mammalian suprachiasmatic nucleus (SCN) is composed of heterogeneous sub-groups of neurons that are organized into a neural system for the control of circadian physiology and behaviour. Molecular circadian 'clocks' are not an exclusive property of SCN neurons but the unique role of the SCN as a central integrative pacemaker is associated with specialized aspects of neuronal organization. Current studies are aimed at identifying the functional components of this hypothalamic integrative centre.ResultsIn the present study we have identified and characterized a quite novel aspect of SCN neurobiology, doublecortin (DCX) protein expression within a defined group of adult rat SCN neurons. Adult neuronal DCX expression is surprising because this microtubule-associated protein (MAP) is generally a developmentally restricted component of immature, migrating neurons. We have also demonstrated for the first time that the SCN as a whole exhibits low expression of the neuronal differentiation marker NeuN. However, DCX is co-localized with NeuN in the ventral SCN, and also with neuropeptides; DCX is extensively co-localized with GRP and partially co-localized with VIP.ConclusionThe highly selective expression of DCX in the adult SCN compared with other hypothalamic and thalamic nuclei shows that this MAP is somewhat uniquely required in certain SCN neurons, perhaps contributing to a specific functional property of the brain's circadian clock nucleus. DCX may maintain a capacity for dynamic cellular plasticity that subserves daily alterations in SCN neuronal signalling.

Impact of Resistant Starch on Body Fat Patterning and Central Appetite Regulation

BackgroundAdipose tissue patterning has a major influence on the risk of developing chronic disease. Environmental influences on both body fat patterning and appetite regulation are not fully understood. This study was performed to investigate the impact of resistant starch (RS) on adipose tissue deposition and central regulation of appetite in mice.Methodology and Principle FindingsForty mice were randomised to a diet supplemented with either the high resistant starch (HRS), or the readily digestible starch (LRS). Using 1H magnetic resonance (MR) methods, whole body adiposity, intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured. Manganese-enhanced MRI (MEMRI) was used to investigate neuronal activity in hypothalamic regions involved in appetite control when fed ad libitum. At the end of the interventional period, adipocytes were isolated from epididymal adipose tissue and fasting plasma collected for hormonal and adipokine measurement. Mice on the HRS and LRS diet had similar body weights although total body adiposity, subcutaneous and visceral fat, IHCL, plasma leptin, plasma adiponectin plasma insulin/glucose ratios was significantly greater in the latter group. Adipocytes isolated from the LRS group were significantly larger and had lower insulin-stimulated glucose uptake. MEMRI data obtained from the ventromedial and paraventricular hypothalamic nuclei suggests a satiating effect of the HRS diet despite a lower energy intake.Conclusion and SignificanceDietary RS significantly impacts on adipose tissue patterning, adipocyte morphology and metabolism, glucose and insulin metabolism, as well as affecting appetite regulation, supported by changes in neuronal activity in hypothalamic appetite regulation centres which are suggestive of satiation.

Do β-blockers combined with RAS inhibitors make sense after all to protect against renal injury?

In chronic kidney disease (CKD) sympathetic overactivity is stimulated by signals from the diseased kidney activating hypothalamic centers. In addition, breakdown of circulating catecholamines is decreased. Indications for beta-blockers are cardio- and renoprotection. Cardioprotection is important because cardiovascular (CV) death is two- to 20-fold more likely in CKD than end-stage kidney disease; consequently, beta-blockers, with their adverse effect on CV risk profile, should be avoided. Controlled prospective evidence for renoprotection by beta-blockers in nondiabetic CKD with hard end points is lacking, but renoprotection by antihypertensive agents was first documented by administering beta-blockers in patients with diabetic nephropathy. Renoprotection by beta-blockers was seen experimentally. Furthermore, controlled studies documented a beneficial effect on albuminuria as a surrogate marker for renoprotection in diabetic and nondiabetic patients. Renin-angiotensin system blockade is the undoubted first-line treatment in CKD. Several points argue for ancillary treatment with beta-blockers: in CKD often four or more different antihypertensive drugs are required and cardiac indications are frequent.

Role of neuronal nitric oxide in the regulation of vasopressin expression and release in response to inhibition of catecholamine synthesis and dehydration

We used neuronal nitric oxide synthase (nNOS) gene knockout mice to study the effects of catecholamines and neuronal nitric oxide on vasopressin expression in the hypothalamic neurosecretory centers. nNOS gene deletion did not change the level of vasopressin mRNA in the supraoptic or paraventricular nuclei. In contrast, vasopressin immunoreactivity was lower in nNOS deficient mice than in wild-type animals. Dehydration increased vasopressin mRNA levels and decreased vasopressin immunoreactivity in both wild-type and nNOS knockout mice, but these responses were more marked in the nNOS knockout mice. Treatment with alpha-mpt, a pharmacologic inhibitor of catecholamine synthesis, resulted in increased vasopressin mRNA levels in wild-type mice and in reduced vasopressin immunoreactivity in both wild-type and nNOS knockout mice. From these results, we conclude: (1) neuronal nitric oxide suppresses vasopressin expression under basal conditions and during activation of the vasopressinergic system by dehydration; (2) catecholamines limit vasopressin expression; (3) nNOS is required for the effects of catecholamines on vasopressin expression.

Low degree of anesthesia increases the risk of neurogenic pulmonary edema development

Neurogenic pulmonary edema is an acute life-threatening complication following central nervous system injury. The exact pathogenic mechanism leading to its development is still unclear. We introduce a new hypothesis that high levels of anesthesia might protect the organism against the development of neurogenic pulmonary edema due to a more pronounced inhibition of the hypothalamic, brainstem and spinal vasoactive sympathetic centers. On the basis of a more pronounced neuronal inhibition of the vasoactive centers, a severe sympathetic discharge does not occur and neurogenic pulmonary edema does not develop. In contrast, an insufficient anesthesia level is not able to inhibit the sympathetic nervous system during an injury of the central nervous system and thus neurogenic pulmonary edema develops. During experiments with central nervous system injury, low-anesthesia-induced neurogenic pulmonary edema might negatively influence the overall recovery of the animal. More importantly, during a neurosurgical intervention, insufficient anesthesia might similarly lead to neurogenic pulmonary edema development in operated patients. Our hypothesis indicates the necessity of precisely monitoring of the level anesthesia during experimental manipulations of the central nervous system in animals or neurosurgical interventions in humans.

The arcuate expression of NPY, POMC and CART responding to food deprivation was exaggerated by experience of maternal separation in female rats.

The hypothalamic feeding peptides expression responding to food deprivation was examined in female rats that experienced maternal separation early in life. Sprague-Dawley pups were separated from dam for 3 h daily during PND 1–14 (MS), or left undisturbed until weaning on PND 21 (NH). The mRNA expressions of NPY, POMC and CART in the arcuate nucleus of female pups were examined by in situ hybridization on PND 60 with or without 48 h food deprivation. Weight loss by food deprivation was bigger in MS rats than in NH rats. Interestingly, the arcuate NPY expression was increased, POMC decreased, by 48 h of food deprivation in MS females, but not in NH females; i.e. the changes were not statistically significant in NH. CART mRNA expression in the arcuate was decreased by food deprivation in NH female, and this decrease was more significant in MS females. It appeared that the basal expression levels of these peptides may not be affected by MS experience. Food deprivation decreased plasma leptin in both groups; however, the basal levels of plasma leptin appeared to be decreased by MS experience in female rats. The results suggest that the sensitivity of hypothalamic feeding center responding to fasting may be enhanced by MS experience in female rats, perhaps, in relation with decreased plasma leptin.

GH releasing peptide 2 test: the holy grail of testing GH deficiency?

Treatment of growth hormone deficiency (GHD) with GH rests on the accurate biochemical diagnosis of the condition even though clinical symptoms, signs and the assessment of risk factors may aid the diagnosis. This is particularly true for the parallel occurrence of other pituitary dysfunctions, whichmay simplify the procedure according to national and international guidelines (1). Due to the pulsatile nature of GH secretion, simple measurement of basal GHconcentrations is not successful and only multiple sampling, clearly not practical, would help to define the GH status, especially as confounding factors such as age and sex hormone status, further influence GH levels. Insulin-like growth factor-I (IGF-1) or IGF-binding protein-3, as GH target hormones, are not pulsatile secreted but similarlymodulated byconfounding factors and are not diagnostic for GHD because normal levels of both factors may not preclude GHD. Diagnosis thus rests on provocative tests for GH (2, 3). None of the currently available procedures to stimulate GH is optimal and fulfils the requirements of an ideal test e.g. fast and easy to perform, safe, economical and most importantly accurately discriminates between the normal situation and full or partial GHD. The insulin tolerance test (ITT), still regarded as the ‘gold standard’, exemplifies these problems. Even though unwanted effects are very rare there are reports of serious side effects. The test is contraindicated in patients with a history of coronary, cerebrovascular or any convulsive disease, and requires particular attention in the elderly (3). Expensive close supervision by experienced personnel throughout the test is therefore mandatory. The mechanism of action includes hypothalamic centres, which allow evaluating and detecting both hypothalamic and pituitary causes of GHD. Generally, the discriminatory power is high but in patients with borderline tests the reproducibility of the ITT is not sufficient (4, 5). When different provocative tests were compared in patients with multiple pituitary hormone deficiencies, where GHD can be anticipated, the best discriminatory power was found with ITT and GHreleasing hormone (GHRH)-arginine test with a sensitivity of 96% (ITT) or 95% (GHRH-arginine) and a specificity of 92 or 91% respectively. Much poorer results were described with other stimulation procedures and the performance of all tests deteriorated when fewer pituitary axes were affected (6). The GHRH-arginine test recently gained wide acceptance because of its good

Leptin induces inflammation-related genes in RINm5F insulinoma cells

BackgroundLeptin acts not only on hypothalamic centers to control food intake but has additional functions in peripheral tissues, e.g. inhibition of insulin secretion from pancreatic islets. The leptin receptor (LEPRb) is a class I cytokine receptor that mediates activation of STAT transcription factors. In this study, we characterise the regulation of inflammation-related genes by leptin in insulinoma cells and compare the effect of transcriptional regulation by leptin with that of other cytokines.ResultsWe have used RINm5F insulinoma cells as a model system for a peripheral target cell of leptin. Six transcripts encoding inflammation-related proteins were found to be upregulated by activation of LEPRb, namely lipocalin-2, pancreatitis-associated protein, preprotachykinin-1, fibrinogen-β, tissue-type plasminogen activator (tPA) and manganese-dependent superoxide dismutase (MnSOD). Four of these transcripts (fibrinogen-β, lipocalin-2, tPA, MnSOD) were also induced by the proinflammatory cytokine interleukin-1β (IL-1β). Interferon-γ alone had no effect on the leptin-induced transcripts but enhanced the upregulation by IL-1β of lipocalin-2, tPA and MnSOD mRNA levels. Experiments with LEPRb point mutants revealed that the upregulation of the inflammation-related genes depended on the presence of tyrosine-1138 which mediates the activation of the transcription factors STAT1 and STAT3. Reporter gene assays showed that leptin induced the expression of preprotachykinin-1 and lipocalin-2 on the level of promoter regulation. Finally, leptin treatment increased caspase 3-like proteolytic activity in RINm5F cells.ConclusionThe present data show that leptin induces a cytokine-like transcriptional response in RINm5F cells, consistent with the proposed function of leptin as a modulator of immune and inflammatory responses.

Review: Drug treatments for obesity: where are we heading and how do we get there?

Obesity has reached epidemic proportions with an estimated 1.7 billion people worldwide classified as either overweight or obese. Obesity is associated with multiple co-morbidities (often clustered as the metabolic syndrome), and can result in decreased life expectancy, with enormous costs to society. Even modest weight loss has been demonstrated to exhibit beneficial effects on the co-morbidities of obesity. While reduced caloric intake and increased physical activity, combined with behavioural modification, appears to be the most rational approach to weight reduction, it only offers short-lived success. For severely obese individuals, bariatric surgery has become an increasingly preferred option resulting in dramatic and well-maintained weight reductions followed by significant changes in obesity-related diseases. Currently, few anti-obesity drugs are approved by regulatory authorities for long-term use (i.e. orlistat, sibutramine and rimonabant). Anti-obesity drug development is an active and dynamic field focusing on two major approaches: 1) inhibiting energy intake by addressing the input into the hypothalamic feeding centre or, 2) attempting to accelerate energy expenditure. Overcoming the hurdles of developing such medications is a daunting task, but it can be anticipated that several drugs in current development might become available within the next decade, and combination therapy of two or more agents could be the future of pharmacological prevention and treatment of obesity.

Getting to the bottom of feeding behaviour: who’s on top?

Traditionally there has been a tendency to focus on peripheral "bottom-up" feeding-related signals and their resulting downstream actions on hypothalamic centers when studying the feeding behaviour of animals. A problem with this hierarchal approach emerges especially with respect to acquiring a human model attempting to explain what is ultimately a distributed control of feeding and energy balance. This review focuses on illuminating the means by which we have come to understand the complexities of feeding, and takes the next step in an attempt to propose a distinctive top-down view of this composite behaviour. It is argued that in evolutionary terms humans demonstrate behaviours unique to all species as represented by an expanded forebrain and the resultant psychological "non-homeostatic" mediators of feeding. Emphasis is placed on a distributionist "two-tier" model, arguing that traditional short-term (cholescystokinin, ghrelin, peptide YY, glucagon-like peptide 1, etc.) and long-term (insulin and leptin) feeding signals may be actively suppressed by the nested nuclei and projections of cortical-limbic brain areas. It is the motivational state (dependent on depletion-repletion signals of hunger and satiety) that in turn has the capability to modulate how rewarding or how palatable a food item may be perceived; thus, both sides of the two-tiered model of feeding behaviour are complimentary and interdependent all at once. In the end, this paper is both commentary and critical review. This synthesis purports that as evolutionary processes spawned consciousness, the psychology of hunger and the present-day discordance of gene-environment interaction forever changed the feeding behaviour of Homo sapiens.

PACAP in the Glucose and Energy Homeostasis: Physiological Role and Therapeutic Potential

Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous neuropeptide in the central and peripheral nervous systems. PACAP is also produced by pancreatic islet cells. PACAP regulates the glucose and energy metabolism at multiple processes in several tissues. At postprandial states, PACAP potentiates both insulin release from pancreatic beta-cells and insulin action in adipocytes, contributing to energy storage. At fasting states, PACAP on the one hand promotes feeding behavior by activating neuropeptide Y neurons in the hypothalamic feeding center, arcuate nucleus, and on the other hand stimulates secretion of catecholamine and glucagon and thereby induces lipolysis in adipocytes and glucose output from liver. Thus, PACAP plays an integrative role in the glucose and energy homeostasis. Dysfunction of expression, secretion and/or action of PACAP might be involved in the type 2 diabetes and metabolic syndrome. PACAP receptor subtype-specific agonists and/or antagonists are hopeful therapeutic agents.

Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men

The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion. To verify whether FFA infusion modifies the ACTH/cortisol response to physical exercise, a well-known activator of the HPA axis at suprapituitary level. Exercise tests on a bicycle ergometer during infusion of a lipid-heparin emulsion (LHE) (experimental test) or normal saline (NaCl 0.9%) (control test). Department of Cardiology at the University-Hospital. Seven healthy male subjects aged 25-33 years. On two mornings, at weekly intervals, LHE or saline were infused for 60 min; infusion started 10 min before exercise test on a bicycle ergometer, which lasted about 15 min. Circulating ACTH/cortisol levels and physiological variables during physical exercise. FFA levels (0.4 +/- 0.1 mEq/l) remained constant during control test, whereas they progressively rose (peak at 60 min, 2.7 +/- 1.0 mEq/l) during LHE infusion. Neither basal nor exercise-induced changes in physiological variables were modified by LHE infusion. Both ACTH and cortisol increased during exercise, with peak levels at 20 min and 30 min (control test: 103% and 42%, P < 0.001; experimental test: 28.5% and 18.6%, P < 0.05 higher than baseline, respectively). Both ACTH and cortisol responses were significantly lower in the experimental than in the control test (at 20 min P < 0.002 and at 30 min P < 0.05 for ACTH; at 20 min P < 0.05 and at 30 min, 40 min and 50 min P < 0.001 for cortisol). These data represent the first demonstration of an inhibitory action of increased circulating FFA levels on the HPA axis under stimulatory conditions (i.e. physical exercise, a challenge acting at suprapituitary level). In contrast, previous studies did not show FFA effects on the CRH-induced ACTH/cortisol response. Therefore, our data suggest negative effects of FFAs on the HPA axis at hypothalamic or higher centres in the central nervous system.

Regulation of Corticolimbic Reactivity via the 5-HT 1A Autoreceptor in the Pathophysiology and Treatment of Depression

According to the National Institute of Mental Health, major depressive disorder (MDD) is among the leading causes of mortality and disability in the USA. In a given year, nearly 7% of Americans experience at least one clinically significant episode of MDD, manifested by a combination of symptoms that interfere with the ability to work, study, sleep, eat and enjoy once pleasurable activities. While an MDD episode may occur only once, they are typically recurring and result in lifetime disability. Although there are a number of widely applied pharmacological and psychological approaches to the treatment of MDD, the efficacy of these is poor, with less than 50% of individuals experiencing a therapeutic response [1]. Combination therapies may lead to higher rates of therapeutic response for a few individuals, but many others will experience severe side effects leading to treatment discontinuation [2]. In light of the immense personal and public health burden of MDD, the existing poor efficacy of available treatments has precipitated dedicated research efforts to better understand the pathophysiology of MDD with the aim of identifying predictive markers of disease liability and generating more effective intervention. Although the neurobiological mechanisms through which disturbances in emotional behavior, mood and temperament emerge and contribute to the development of MDD are not wholly understood, a myriad of converging evidence inextricably links these phenomena with functioning of the central serotonin (5-HT) system and its inter-related subsystems. Multiple mechanisms contribute to the regulation of 5-HT neurotransmission and variability in these regulatory mechanisms is associated with individual differences in temperament and risk for MDD. Key among these is the 5-HT type 1A (5-HT1A) somatodendritic autoreceptor, which is expressed on a population of serotonergic neurons projecting from the brainstem raphe nuclei to cortical and limbic target regions. The 5-HT1A autoreceptor mediates negative-feedback regulation of 5-HT neurons through G-protein coupled signaling cascades, resulting in diminished neuronal activity and subsequent 5-HT release at postsynaptic targets. These postsynaptic targets include the amygdala and prefrontal cortex, key nodes of a corticolimbic circuitry supporting emotional reactivity and control. In the context of emotional behavior, the subcortical amygdala mediates rapid physiological and behavioral arousal in response to salient, biological stimuli (e.g., threat-related facial expressions, such as anger and fear). In addition to regulating the activity of numerous hypothalamic and brainstem autonomic centers, the amygdala can stimulate the activity of the ventromedial and orbitofrontal cortices [3]. These prefrontal regions are critical for the integration of amygdala-mediated arousal in the service of complex, adaptive behavioral responses to environmental challenges [4,5]. The subsequent stimulation of dorsomedial, ventrolateral and dorsolateral prefrontal regions, resulting from such engagement of the ventromedial and orbitofrontal cortices, then precipitates top-down inhibition of the amygdala [6–8]. The coordinated activity within this distributed corticolimbic circuitry largely governs emotional arousal and regulation, and dysfunction of circuit components are pathological markers of MDD [9,10].

Challenged sodium balance and expression of angiotensin type 1A receptor mRNA in the hypothalamus of Wistar and Dahl rat strains

The present study investigates the influence of a chronic high Na + diet (8% Na +) on the expression of the angiotensin type 1A (AT 1A) receptor gene in the lamina terminalis and paraventricular nucleus of the hypothalamus (PVH) in normotensive Wistar (W) rats, as well as in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats. Three weeks of 8% Na + diet led to a higher blood pressure in DS rats compared to DR and W rats. Moreover, the high Na + diet was correlated with a decreased expression of AT 1A receptor mRNA in the median preoptic nucleus (MnPO) and in the PVH of DS rats, compared to DR and W rats. Contrastingly, the AT 1A receptor mRNA expression was not altered by the high Na + diet in the forebrain circumventricular organs of all the rat strains. Interestingly, a furosemide-induced Na + depletion was correlated with an increased expression of AT 1A receptor mRNA in the PVH, MnPO and SFO of both the DS and DR rats. It is concluded that chronic high Na + diet did differently regulate the expression of AT 1A receptor mRNA in two hypothalamic integrative centers for hydromineral and cardiovascular balance (the PVH and MnPO) in DS rats, compared to DR and W rats. However, the AT 1A receptor mRNA expression was similarly regulated in DS and DR rats in response to an acute Na + depletion, suggesting a distinct high Na +-induced regulation of the AT 1A receptor gene in the PVH and MnPO of DS rats.

Botulinum toxin therapy for palmar hyperhidrosis: experience in an Iranian population

There seems to be a genetic predisposition to primary (essential) hyperhidrosis and it often manifests itself in childhood or puberty. Essential or focal hyperhidrosis characteristically does not occur during sleep, but is made worse by heat and emotional situations, as it is considered that the hypothalamic sweat centers are more sensitive to emotional stimuli in nonhyperhidrotic subjects. 2 However, it is estimated that 0.6–1.0% of the population suffers from primary (essential) hyperhidrosis and in many it can become chronic and can lead to significant disruption in both social and professional life, leading to a marked impact on the patient's quality of life (QoL). 2 Patients find the symptoms embarrassing and often complain that the anticipation of sweating leads to avoidance of certain activities. 3 Sweat rates are highly variable between individuals and are thought to be a factor of acclimatization, sex, age, and possibly diet. 4 The aim of the present study was to evaluate the effectiveness, safety, and adverse reactions of botulinum toxin type A, Dysport® (Speywood Pharmaceuticals, Berkshire, UK) on the patients with recalcitrant palmar hyperhidrosis.

Attenuated pulse size, disorderly growth hormone and prolactin secretion with preserved nyctohemeral rhythm distinguish irradiated from surgically treated acromegaly patients

Radiation induces time-dependent loss of anterior pituitary function, attributed to damage of the pituitary gland and hypothalamic centres. The development of growth hormone deficiency (GHD) in irradiated acromegaly patients is not well defined. Detailed analysis of spontaneous 24-h GH and prolactin (PRL) secretion in relation to other pituitary functions and serum IGF-I concentrations in an attempt to find criteria for GHD in acromegalic patients with a GH response < 3 microg/l during the insulin tolerance test (ITT). Plasma hormone profiles obtained by 10 min sampling for 24 h in postoperatively irradiated acromegalic patients, compared with patients cured by surgery only and matched healthy controls. University setting. Fifteen subjects in each group. GH and PRL secretory parameters quantified by deconvolution, cluster, cosinor and approximate entropy (ApEn) analyses, IGF-I concentrations. Irradiation attenuated pulsatile secretion of GH and PRL, but total PRL secretion was unchanged. GH and PRL secretory regularity were diminished. Circadian timing remained intact. Pulsatile GH secretion and IGF-I were correlated (R = 0.30, P = 0.04). Criteria of pulsatile GH secretion = 12 microg/l/24 h and ApEn = 0.800 separated 12 of 15 irradiated patients from all others. Irradiated acromegaly patients with a subnormal GH response to ITT have very limited spontaneous GH secretion, with specific attenuation of the size of GH bursts and a highly irregular pattern, but with retained diurnal properties. These patients are thus likely GH-deficient and might benefit from GH replacement.

Hypertrichosis in a Horse with Alimentary T-Cell Lymphoma and Pituitary Involvement

A 13-year-old Quarterhorse mare had a 6-month history of diarrhea, progressive weight loss, and lethargy. At presentation the mare was hirsute, had hyperhidrosis, and abnormal fat distribution in addition to severe diarrhea. A presumptive clinical diagnosis of protein-losing enteropathy and pituitary pars intermedia dysfunction was made. T-cell lymphoma was diagnosed in a rectal biopsy specimen. The owner elected to euthanize the mare because of poor prognosis and the severity of the disease. At necropsy, the mare had hypertrichosis and the pituitary gland was diffusely enlarged. Histologically, neoplastic lymphocytes infiltrated the gastrointestinal mucosa, mesenteric lymph nodes, and the pituitary gland. In addition, there was hyperplasia of the pituitary gland pars intermedia. Pituitary adenoma was not present. Hypertrichosis in this case could have been triggered by a combination of adenomatous hyperplasia of pars intermedia and lymphoma resulting in disruption of the hypothalamic dopaminergic tone or disruption of the hypothalamic thermoregulatory center.