Neuroendocrine aspects of anorexia nervosa and bulimia nervosa.

Endocrine dysfunctions in eating disorders (anorexia nervosa, bulimia nervosa) result from disturbed regulation of hypothalamo-pituitary-gonadal, hypothalamo-pituitary-adrenal, hypothalamo-pituitary-thyroid and hypothalamo-pituitary-GH-IGF1 axes as well as of altered peripheral endocrine metabolism. Some peptides of hypothalamic origin, as well as those secreted by the adipose tissue and gastrointestinal tract including pancreatic hormones, are involved in the control of appetite and satiety. These peptides play also an important role in the mechanism of hormonal secretion. Altered activity of these biologically active substances may lead to the disturbances in the regulation of energy and hormonal homeostasis.

Assessment of plasma brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) concentrations in treatment-naïve humans with multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by coexisting processes of inflammation, demyelination, axonal neurodegeneration and gliosis. Autoimmune processes play a pivotal role in the disease. The immune system may be modulated by neurotrophins and neurotrophin factors. Aim of the study was to assess plasma levels of brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) in treatment-naïve humans with newly diagnosed multiple sclerosis. We also elucidated the potential influence of selected inflammatory agents on peripheral concentration of BDNF and ADNP. MATERIAL AND METHODS: The study population comprised of 31 untreated patients with MS and 36 controls from a single hospital centre. Assessment of BDNF and ADNP was performed with use of ELISA methods. VIP was measured with RIA. Selected cytokine levels (IL 6, IL 10, and TNF α) were evaluated with ELISA tests. Statistical analyses were performed. RESULTS: We failed to find any significant differences between ADNP, BDNF, VIP, CRP levels and concentration of cytokines between individuals with MS and the controls. No correlation was observed between ADNP, BDNF and VIP as the first parameter and CRP, IL 6, IL 10, TNFα levels and the Expanded Disability Status Scale score in MS. CONCLUSIONS: Newly diagnosed, treatment-naïve patients with MS have comparable levels of plasma BDNF, ADNP and VIP to those of healthy controls.

Plasma chemerin levels in patients with multiple sclerosis.

OBJECTIVES: Chemerin, a novel adipokine produced by adipose tissue and liver, is associated with markers of metabolic syndrome, and additionally, acting as chemoattractant for cells of immune system it may regulate immune cell properties. MATERIAL AND METHODS: In order to evaluate plasma chemerin concentration in multiple sclerosis (MS) individuals we investigated 39 MS patients (among them 23 subjects were lean and 16 were overweight or obese) and 42 controls with tension headaches (29 of them were lean and 13 were overweight or obese). All patients had a brain MRI scan with gadolinium contrast as well as an assessment of the presence of oligoclonal bands in cerebrospinal fluid (CSF) and estimation of the CSF IgG index. The neurologic status was evaluated with use of the Expanded Disability Status Scale. Chemerin levels in plasma were measured using ELISA kit. Lipid profile, glucose and insulin levels, CRP and selected cytokine concentrations were also determined. RESULTS: Plasma chemerin concentrations in overweight/obese MS subjects were higher when comparing to lean MS individuals and the controls, both from lean and overweight/obese subgroups. Significant difference was found between the results of overweight/obese MS and lean controls. CONCLUSIONS: An increase of chemerin levels in patients with multiple sclerosis is associated with overweight and obesity.

Plasma NPY concentrations in women with acute ischemic stroke.

OBJECTIVE: It has been reported that plasma NPY levels were increased in obesity, type 2 diabetes mellitus and hypertension. The symptoms of metabolic syndrome frequently appear in patients with acute ischemic stroke. The association between plasma NPY levels and metabolic markers in women with acute ischemic stroke was investigated in the current study. METHODS: Plasma NPY concentrations were determined using radioimmunoassay in 58 women aged 60-85 (mean age: 76.5±0.8) with acute ischemic stroke and in 24 women aged 63-67 (mean age: 65.6±0.6) of the control group. Stroke was defined according to the NIHSS (National Institute of Health Stroke Scale) and was confirmed using CT or MR scan. RESULTS: The prevalence of type 2 diabetes, hypertension and insulin resistance was higher in the group of patients with stroke. Plasma NPY levels measured during the 1st day and 10 days after the acute phase of stroke were significantly lower (p<0.001) compared to the control group. CONCLUSION: In women with acute ischemic stroke plasma NPY concentrations were decreased in spite of higher frequency of the occurrence of the symptoms of metabolic syndrome.

Do novel adipokines play a causative or only modulating role in the pathogenesis of obesity and metabolic disorders?

Adipose tissue is an endocrine and paracrine organ that releases a large number of bioactive mediators. Approximately 100 adipokines have been identified including cytokines, chemokines, growth factors and enzymes. The use of adipoproteomic analyses resulted in new findings and, in consequence, the number of new adipokines is rising rapidly. Novel adipokines such as visfatin, vaspin and omentin were discovered about five years ago. Visfatin and vaspin production and secretion take place in adipocytes, but omentin comes from the stromal cells of adipose tissue. Several differences are noticeable between these adipokines especially in correlation with obesity as visfatin and vaspin serum levels increase in obese subjects while omentin serum levels decrease. It has been suggested that these adipokines act as insulin-sensitizers/insulin-mimetics. Increasing number of publications reporting the role of new adipokines does not allow to assess clearly the influence of those adipokines on the pathogenesis of obesity.

Resistin levels in women with ischemic stroke.

OBJECTIVES: Resistin may be an independent inflammatory marker of atherosclerosis. Therefore, its circulating level might be important prognostic factor of cardiovascular disease in humans. We aimed in this study to assess plasma resistin concentration in Polish women with acute ischemic stroke, who additionally suffer from chronic diseases: diabetes, hypertension and/or obesity. The changes of resistin levels after 10 days from the onset of stroke and possible associations between resistin and pro-inflammatory cytokine TNFα were also evaluated. MATERIAL AND METHODS: Material consisted of 41 women with ischemic stroke (aged 60-85 years) and 64 controls (aged 60-85 years). Circulating resistin and TNFα concentrations were measured using ELISA. Blood was taken twice in the stroke group, in the first and tenth day from the onset of clinical symptoms, and only once in the controls. Clinical and biochemical data (blood pressure, weight, height, glucose, insulin, lipid profile) were collected. RESULTS: Higher concentrations of resistin and TNFα were observed in ischemic stroke patients at the first day comparing to the controls. Second evaluation after 10 days in comparison with the first measurement revealed significantly higher TNFα levels and non-significant lower values of resistin. Resistin positively correlated with TNFα and stroke severity. CONCLUSIONS: Changes in resistin and TNFα concentrations were observed in the course of stroke. Further investigations are required to assess the implication of these findings. Higher resistin concentration might be associated with worse neurological deficits.

The evaluation of estradiol and leptin action on the activity of the somatotropic and gonadotropic axes in peripubertal female rats.

OBJECTIVE: Available data suggest that estrogens and leptin play a role in the control of the pubertal process. In humans and some mammal species the increase of the activity of gonadotropic axis accompanies the decrease in the rate of growth at puberty. The effect of 17ß-estradiol and/or leptin administration on the somatotropic and gonadotropic axes was studied using prepubertal female rats as an animal model. MATERIAL AND METHODS: Prepubertal female rats received estradiol/saline, estradiol/leptin, oil/leptin or oil/saline (vehicles) respectively. The changes of growth rate, and serum 17ß-estradiol, leptin, GH, IGF-I and gonadotropins levels as well as LHRH and estrogen receptor (ER) concentrations in the medial basal hypothalamus (MBH) and the pituitary were determined. All hormones concentrations were measured by radioimmunoassay and ER by radioligand methods . RESULTS: In estradiol and/or leptin treated animals noticeable reduction of rate of growth was found. The decrease of growth in response to estradiol treatment accompanied the increase GH level and the decrease of IGF-I concentration in the circulation. Both hormones operating together activated reproductive axis, what was manifested by a significant increase of LHRH abundant in the hypothalamus as well as elevated LH and FSH levels in the circulation. In these rats a significant decrease of the estrogen receptor concentrations in the pituitary was observed. CONCLUSION: The role of estradiol and leptin in the control of growth and reproduction seems to overlap only partially. Estradiol plays a significant role in the activation of the reproductive axis, and leptin takes part as a permissive factor in pubertal process.

Evaluation of orexin A activity on LH and FSH release from primary culture pituitary cells in immature and mature female rats.

OBJECTIVES: Orexin A (OxA) is a regulatory neuropeptide which is involved in the control of various autonomic and neuroendocrine functions. It regulates sleep-wake cycle, food intake and modulates the hypothalamic and pituitary hormones secretion. Orexin A acts through two types of receptors, which proved to exist in the pituitary. This may indicate the possibility of direct action of OxA on the adenohypophysis level. The aim of this study was to evaluate the direct effect of orexin A on gonadotropin (LH and FSH) release from cultured pituitary cells of immature female rats as well as mature female rats (ovariectomized and ovariectomized and estradiol treated rats). MATERIAL AND METHODS: The effect of 0.1 nM and 100 nM orexin A on LH and FSH release from anterior pituitary cells after 1 h of incubation was examined in immature female rats (IM) as well as mature female (ovariectomized - M/OVX; and ovariectomized and estradiol treated - M/OVX+E2) rats. The concentration of LH and FSH in medium was determined by RIA method. RESULTS: Orexin A at a dose of 0.1 nM and 100 nM significantly stimulated LH secretion in IM group. In M/OVX group release of LH was inhibited by OxA only in higher dose (100 nM). No effect of orexin A on FSH secretion was found. CONCLUSIONS: OxA may directly modulate LH secretion from cultured pituitary cells and it has the contradictory effect on LH release in immature and ovariectomized mature female rats.

The influence of cocaine-amphetamine regulated transcript (CART) on pituitary hormones, corticosterone and leptin levels in starved rats.

OBJECTIVE: CART is involved in the control of food intake and hormonal secretion. We aimed to evaluate the effects of CART on hormonal profile in starved rats. METHODS: Study group included 100 male rats. Under conditions of food limitation CART (55-102) was given centrally (icv) or peripherally (iv). Non-starved animals underwent identical procedure. Vehicle (aCSF or saline)-injected rats served and as a controls. 60 minutes after CART or vehicle administration blood was collected to assess pituitary hormones (LH, FSH, PRL, GH, ACTH, TSH), corticosterone and leptin concentrations. RESULTS: Itracerebroventricular CART injection resulted in a significant increase in PRL, GH and corticosterone concentrations in non-starved rats compared with vehicle injected animals. However, in a group of starved animals only leptin levels were decreased in comparison with fasted controls. Peripheral CART administration caused a significant increase in PRL, GH and TSH levels in non-starved rats but no changes in investigated hormone levels were observed in starved animals when compared to saline injected controls. CONCLUSIONS: Our results indicate that CART is able to modulate hormonal profile in a non-starved rats. However, the modulatory effect depends on the CART administration method. Interestingly, CART administration, both icv and iv, does not have an impact on pituitary hormones and corticosterone levels in a course of food limitation.

Decreased total serum adiponectin and its isoforms in women with acute ischemic stroke.

OBJECTIVE: An association between cerebral infarct risk factors and serum adiponectin levels (both total and separate isoforms) has previously been identified. The aim of this study was to assess circulating levels of all forms of adiponectin in the course of an ischemic stroke. MATERIAL AND METHODS: Adiponectin and its isoforms (HMW, MMW and LMW) were measured in serum samples taken from 38 women in the first 24 hours of cerebral infarct and 38 controls matched for gender, body mass index (BMI) and age. In addition, biochemical parameters (glucose, insulin, lipid profile) and clinical data (blood pressure, weight, and height) were evaluated. RESULTS: A significant reduction in serum levels of adiponectin and all examined fractions of this adipokine was observed in women suffering from acute ischemic stroke, compared with the matched controls. CONCLUSIONS: Differences in the serum adiponectin array between stroke subjects and controls were identified and further studies are required to investigate the clinical implications of this finding.

Exogenous orexin-A downregulates luteinizing hormone secretory activity in prepubertal female rats.

INTRODUCTION: Orexin-A is a neuropeptide synthesized in the lateral hypothalamus. Orexin-A immunoreactive fibres overlap distribution with GnRH neurons. In adult rats, orexin A is known to affect LH secretion via GnRH release modulation. Because data concerning the impact of orexin-A on the hypothalamo-pituitary axis activity are limited, we focused on the involvement of orexin-A and receptors of NPY in the modulation of LH release and LH subunit b (Lhb) mRNA expression in prepubertal female rats. MATERIAL AND METHODS: Forty immature female Wistar rats were divided into 4 groups and received 2 intracerebroventricular (icv) microinjections of: 1 - artificial cerebrospinal fluid (CSF) (controls); 2 - CSF followed by orexin A; 3 - selective NPY receptor antagonist (BIBP) followed by CSF; 4 - BIBP followed by orexin A. One hour after the last microinjection, all rats were decapitated. Trunk blood was collected, and serum was stored at -20°C for the LH RIA examination. The adenohypophysis was immediately excised, flash-frozen, and kept at -80°C for RNA extraction. Real-time PCR amplification was carried out, and relative Lhb gene expression was calculated. RESULTS: In comparison to the CSF-treated controls with a mean LH serum concentration of 0.40 ± 0.02 ng/mL, the mean LH serum level was diminished both after orexin-A (0.27 ± 0.01 ng/mL) and after BIBP (0.30 ± 0.02 ng/mL) icv microinjections. In the presence of BIBP, orexin-A more effectively inhibited LH release (0.20 ± 0.01 ng/mL) when compared to the BIBP-treated group. Orexin-A and BIBP exerted a consistent inhibitory effect on Lhb mRNA expression levels in the anterior pituitary gland. In comparison to the CSF-treated controls, orexin-A, and BIBP-treated females responded with, respectively, 35% and 40% reduction of Lhb mRNA expression. Orexin-A and BIBP co-administration evoked a further reduction of Lhb gene transcriptional activity. CONCLUSIONS: Orexin-A exerts a down-regulatory effect on LH synthesis and release in immature female rats. Considering that Y1R-oriented down-regulation of endogenous NPY activity did not reverse the suppressive effect of exogenous orexin-A, it might be suggested that NPY and orexin A systems can operate independently to affect gonadotropin activity in the anterior pituitary of the immature female rats.

Adipokines and genetic factors in overweight or obese but metabolically healthy Polish women.

OBJECTIVE: Obesity may be accompanied by enhanced metabolic disturbances but not all obese patients suffer from metabolic syndrome. Since metabolic homeostasis is under control of genetic factors underlying expression of adipokines, we aimed to compare the serum concentrations of adiponectin and resistin, and polymorphism in their genes, in overweight or obese Polish women. MATERIAL AND METHODS: The study included 265 women with BMI above 25 kg/m2 (140 metabolically healthy and 125 with metabolic syndrome) and 104 non-obese women as a control group. Anthropometric parameters (BMI, BIA, WHR), blood pressure, lipid, glucose and HOMA-IR profiles as well as serum concentrations of adiponectin, HMW adiponectin and resistin were evaluated. Gene polymorphisms of adiponectin gene (276G/T; 11377C/G; 11391G/A) and resistin gene (420C/G; 62G/A; 537A/C) were analyzed using TaqMan SNP genotyping assays. RESULTS: Higher serum concentrations of total adiponectin and lower levels of resistin were found in metabolically healthy patients when compared to those diagnosed with metabolic syndrome. No differences of serum HMW and resistin concentrations were observed between overweight or obese but metabolically healthy subjects and normal weight controls. No associations of investigated polymorphisms and the presence of metabolic syndrome were noticed in overweight/obese women with metabolic syndrome. CONCLUSIONS: The assessment of total adiponectin in sera seems to be promising target in distinguishing subjects with obesity who undergo a diagnostic procedure for metabolic syndrome. Moreover, the evaluation of adipokine array may help to select patients with higher risk of metabolic disturbances that are associated with severe diseases.

The metabolic, neuroprotective cardioprotective and antitumor effects of the Klotho protein.

Klotho is a transmembrane protein with a wide spectrum of activity. The human Klotho gene shows 86% amino acid identity with the mouse protein. Many important pleiotropic functions of the Klotho protein have been revealed. Amongst them, there is a regulation of nitric oxide production, suppression of oxidative stress and inflammation, influence on the insulin-like growth factors and fibroblast growth factors signaling, modulation of calcium and phosphate metabolism, synthesis of vitamin D and other. Two forms of the Klotho protein are known. The secreted form strongly inhibits the oxidative stress, and, in humans, is more dominant than the membrane form. Studies on a mouse model resulted in the finding of the anti-aging effect of the Klotho protein. This activity is mainly associated with the suppression of oxidative stress, as well as it could be related to neuroprotective, cardioprotective, and metabolic functions.It might be speculated that Klotho, regarded as a neuroprotective factor, may have therapeutical applications in the future in the treatment of demyelinating and neurodegenerative disorders, especially multiple sclerosis (MS) and Alzheimer's disease (AD). The Klotho through inhibition of oxidative stress possesses cardioprotective properties. Of note, one functional variant of Klotho is a risk factor for coronary disease as well as some nucleotide polymorphisms are associated with carotid arteriosclerosis. Moreover, the Klotho protein can inhibit Angiotensin II-induced cardiomyocyte hypertrophy. All those effects indicate that the Klotho protein may be useful in the therapy of heart failure and hypertension. Undoubtedly, metabolic disturbances play an important role in the pathogenesis of many neurodegenerative and cardiovascular diseases. The metabolic effects of the Klotho protein are strongly connected with its neuroprotective and cardioprotective activity. This protein affects adipogenesis, metabolism of glucose and lipids as well as calcium-phosphate system by influence on the activity of fibroblast growth factors (FGF19, FGF23, FGF21). Finally, it has been revealed that the Klotho protein has antitumor activity. Besides, the FGF-Klotho system may have a role in longevity and aging-related disorders.

Peripheral levels of selected adipokines in patients with newly diagnosed multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. The exact aetiology is unknown. However, genetic and environmental factors are suggested to be involved in the pathogenesis of MS. Improper diet, resulting in obesity and metabolic syndrome, can contribute to this disease. Adipokines, secreted by adipose tissue, link the metabolism and immune system. MATERIAL AND METHODS: We aimed to assess plasma levels of selected adipokines in newly diagnosed, treatment-naïve individuals with multiple sclerosis. Our group comprised 58 individuals (31 MS patients and 27 controls, matched for age and BMI) without diabetes, hypertension, or dyslipidaemia. Circulating adiponectin and all adiponectin fractions, visfatin, and omentin concentrations were measured. Metabolic parameters were also assessed. RESULTS: In MS individuals we observed the following results: higher concentrations of visfatin, lower levels of omentin, and no differences in adiponectin array. There were also correlations between some adipokines and metabolic parameters. After adjustment to BMI, a significant decrease in total adiponectin, high-molecular weight (HMW) adiponectin and omentin, and an increase in medium-molecular-weight (MMW) adiponectin were observed in the group of MS patients when compared to those of the controls. CONCLUSIONS: Our results indicate that adiponectin with its fractions, visfatin, and omentin cannot be considered as causative factors in the early phase of multiple sclerosis. However, the potential role of adipokines in MS is possible because they might be involved in the pathogenesis of MS, regarded as an autoimmune disorder.

Bombesin modulates the control of energy homeostasis and pituitary hormone release.

Bombesin and related peptides are widely distributed in gastrointestinal tract and central nervous system. It has been reported that they play an important role in the control of appetite, metabolism, sensory transmission and thermoregulation as well as in the regulation of pituitary hormone release. Central injection of these peptides leads to inhibition of feeding. There are controversial opinions about the effects of bombesin on pituitary hormone secretion both in vivo and in vitro experiments.

Adiponectin - a predictor of higher mortality in cardiovascular disease or a factor contributing to longer life?

Adiponectin, a protein secreted by adipocytes, has been recently found to be also secreted by cardiomyocytes. Adiponectin possesses several physiological functions including modulation of glucose metabolism and energy homeostasis. The interactions between adiponectin and metabolic parameters were found. Studies on aging humans revealed that enhanced adiponectin values are a distinctive feature of centenarians. Thus, this parameter may be considered as a prognostic factor of prolonged survival. However, it has also been demonstrated that high adiponectin levels may predict mortality in patients with cardiovascular disease (CVD). Several mechanisms of adiponectin elevation, both in the process of aging and in pathomechanism of CVD, are discussed in this paper.

Copeptin - a new diagnostic and prognostic biomarker in neurological and cardiovascular diseases.

Copeptin, arginine vasopressin (AVP)-associated 39 aminoacid glycopeptide, is a C-terminal part of pro-AVP. AVP acts through V1a, V1b, and V2 receptors. The effect on V1a receptors is connected with arterial vasoconstriction, on V2 with antidiuretic action, and on V1b with the secretion of ACTH, insulin, glucagon. Copeptin is found in the circulation in equimolar amounts with AVP. It is a very stable peptide and easy to estimate. Copeptin is a good diagnostic marker in many disorders in which vasopressinergic dysfunction plays a role in pathogenesis such as a polyuria-polydipsia syndrome, neurological disease (ischemic stroke, nontraumatic, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage and neurodegenerative disease (multiple sclerosis). Copeptin is a diagnostic and prognostic marker in cardiovascular diseases like heart failure (HF) and acute myocardial infarct (AMI). Copeptin is a sensitive diagnostic marker in the early stage of AMI especially in patients with non-ST segment elevation and post AMI complications. Copeptin is also an important diagnostic and prognostic marker in metabolic diseases (diabetes mellitus, metabolic syndrome, insulin resistance), connected with some neurological and cardiovascular diseases. In the future, these findings may have also therapeutic applications in conditions where the AVP receptor antagonist therapy is appropriate.

The role of leptin and orexins in the dysfunction of hypothalamo-pituitary-gonadal regulation and in the mechanism of hyperactivity in patients with anorexia nervosa.

Anorexia nervosa (AN) belongs to a group of eating disorders and is characterized by extreme body weight loss. AN patients show combination of physical, psychological and behavioral disturbances. Neuropeptides partly control energy homeostasis and modulate hormone release. Leptin, a peptide secreted by adipocytes, may influence the interactions between central and peripheral signals. Hypoleptinaemia found in AN is connected with disturbed control of appetite and hormonal dysfunction as well as has implications for the hypothalamo-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Low leptin levels are increased with refeeding. However, the prolonged hypoleptinaemia in weight recovered AN patients may result in persistent hypothalamic amenorrhoea. The hyperactivity has been observed in 31-80 % of AN cases. The mechanisms underlying the hyperactivity found in patients with anorexia nervosa seem to be more complicated as many factors including neuropeptides may be involved. Orexins may affect not only appetite but also behavior and psychophysical activity as they may regulate reproductive and stress hormone secretion, stimulate a variety of stereotypic behaviors including eating and stress reaction, and affect the hypothalamo-pituitary-adrenal (HPA) axis, alter glucocorticoid and catecholamine secretion and activate the sympathetic nervous system. Orexins influence the mechanism regulating arousal and sleep, cardiovascular function, temperature, metabolic rate and locomotive activity. It is worth considering how abnormal activity of hypothalamic neuropeptides or their receptors may play a role in the mechanisms of hyperactivity, disturbed control of appetite and hormonal dysfunction in patients with anorexia nervosa.

Involvement of the cocaine-amphetamine regulated transcript peptide (CART 55-102) in the modulation of rat immune cell activity.

OBJECTIVE: Cocaine-amphetamine regulated transcript peptides (CART) belong to a neuropeptide family expressed in the central nervous system, especially in the hypothalamus, and also in peripheral tissues. The physiological functions of CART include modulation of pituitary hormone release, regulation of body weight, and the control of feeding behavior and metabolic activity. The reciprocal relationships between CART and immune system function have to be established. Therefore, in the present study we aimed to investigate the influence of CART, administered intracerebroventricularly (icv), on selected immune parameters and pituitary-adrenal axis hormone secretion in the rat. RESEARCH METHODS: In rats submitted to icv infusion of CART or artificial cerebrospinal fluid (aCSF, control) selected immune parameters: splenocyte proliferation (spontaneous and mitogen-stimulated) and peritoneal leukocyte (PTL) activity (spontaneous and phorbol myristate acetate (PMA)-stimulated) were examined 60 and 120 min after treatment. The direct effect of CART on splenocytes in culture in vitro was also examined. Concentration of adrenocorticotrophic hormone (ACTH) and corticosterone was also measured in serum of control and CART infused rats. RESULTS: Splenocytes isolated 60 min after CART infusion exhibited a decreased, albeit non-significant, ability to proliferate spontaneously and were unable to answering to the mitogenic stimulation. This effect was not seen 120 min after CART treatment, which restored splenocyte proliferation decreased by aCSF infusion. CART addition in vitro did not influence proliferation of splenocytes from control rats. Spontaneous activity of peritoneal leukocytes was not modified by CART infusion. PMA-stimulated PTL activity was significantly decreased in aCSF-infused rats 120 min after treatment and CART infusion antagonized this effect. Non-significant increase in serum cortisol after 60 min followed by a significant decrease after 120 min with no change in ACTH concentration was found. CONCLUSION: The immunomodulatory activity of icv-infused CART appears to consist in the creation of a short-lasting immunosuppressive internal milieu, followed by the immunostimulatory one. This first effect was most probably due to the activation of the HPA axis and/or other immunosuppressive peptides, but not through the direct action of CART on immune cells. Thus, CART appears to be short-lasting and indirect modulator of immunity.

Plasma beta amyloid and cytokine profile in women with Alzheimer's disease.

Alzheimer's disease (AD) belongs to a group of neurodegenerative disorders. It is characterized by irreversible and progressive memory loss accompanied with decline in other cognitive functions. At a microscopic level, the typical neuropathologic features, senile plaques and neurofibrillary lesions are found. The pathological processes lead to neuronal loss, synaptic dysfunction and inappropriate activity of neurotransmitters. The major constituent of senile plaques is abnormally aggregated beta amyloid protein. Beta amyloid (Abeta) is a short (40-42 amino acid) product of proteolysis of the transmembrane amyloid precursor protein (APP). Extracellular depositions of Abeta 1-42 may initiate a wide range of pathological processes including glia activation, neuroinflammation and neuronal apoptosis. There is convincing evidence that inflammatory response to accumulation of beta amyloid plays a pivotal role in the progression of neuropathological changes found in AD. Current research was directed at assessing beta amyloid, cytokines (IL-6, IL-10 and TNF alpha) plasma levels in women with AD. Hundred and twenty four women, aged between 59 to 86 years, were enrolled in the study. Amongst them 57 were diagnosed with AD (29 subjects in early stage and 28 subjects with moderate to severe stadium of disease) and 67 women without dementia were investigated as a control group. The lowest values of Abeta 1-42 were found in AD subjects in moderate to severe stage of disease as compared with the early stage of AD (p< 0.05) and the control group (p<0.01). Change in IL-6 values was significantly different between groups with the lowest values found in women without dementia. Both subset of AD patients demonstrated statistically enhanced IL-6 levels when compared with the control group (p<0.001, p<0.01 respectively for early and moderate/severe stage of AD). Moreover, our study revealed a trend to increase in TNF alfa and IL-10 values in AD. However, those differences were not statistically significant. In addition, we did not detect any correlations between plasma beta amyloid and investigated cytokines.