Sarika Arora

Role of neuropeptides in appetite regulation and obesity – A review

Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.

MCP-1: Chemoattractant with a role beyond immunity: A review

BACKGROUND Monocyte Chemoattractant Protein (MCP)-1, a potent monocyte attractant, is a member of the CC chemokine subfamily. MCP-1 exerts its effects through binding to G-protein-coupled receptors on the surface of leukocytes targeted for activation and migration. Role of MCP-1 and its receptor CCR2 in monocyte recruitment during infection or under other inflammatory conditions is well known. METHOD A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicines digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. RESULT Recent and ongoing research indicates the role of MCP-1 in various allergic conditions, immunodeficiency diseases, bone remodelling, and permeability of blood - brain barrier, atherosclerosis, nephropathies and tumors. CONCLUSION MCP-1 plays an important role in pathogenesis of various disease states and hence MCP-1 inhibition may have beneficial effects in such conditions.

Cytokines in recurrent pregnancy loss

BACKGROUND Recurrent pregnancy loss (RPL) is defined as the occurrence of three or more consecutive miscarriages prior to 20 weeks gestation. Exaggerated maternal immune response to fetal antigens has been proposed to be one of the mechanisms underlying recurrent pregnancy loss. METHOD A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicines digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. RESULT In normal pregnancy, tolerance of the genetically incompatible fetus by the maternal immune system depends on the interactions of an array of cytokines secreted by maternal and fetal cells at the site of implantation. Earlier research indicated that altered immunity in RPL is dominated by the Th1/Th2 hypothesis, which proposed that the fetus escapes maternal-derived T-cell responses through skewing the Th0 differentiation toward Th2 pathway which dampens pro-inflammatory Th1-type immunity. Recent studies indicate the role of proinflammatory Th17 cells and immunoregulatory Treg cells in RPL in addition to Th1/Th2 interactions. CONCLUSION Cytokines form a complex regulatory network which maintains homeostasis between the fetal unit and the maternal immune system. If this delicate balance is adversely affected, immunoregulatory mechanisms may be insufficient to restore homeostasis and this may lead to pregnancy failure.

Effect of integrated yoga practices on immune responses in examination stress - A preliminary study

Background: Stress is often associated with an increased occurrence of autonomic, cardiovascular, and immune system pathology. This study was done to evaluate the impact of stress on psychological, physiological parameters, and immune system during medical term -academic examination and the effect of yoga practices on the same. Materials and Methods: The study was carried out on sixty first-year MBBS students randomly assigned to yoga group and control group (30 each). The yoga group underwent integrated yoga practices for 35 minutes daily in the presence of trained yoga teacher for 12 weeks. Control group did not undergo any kind of yoga practice or stress management. Physiological parameters like heart rate, respiratory rate, and blood pressure were measured. Global Assessment of Recent Stress Scale and Spielbergers State Anxiety score were assessed at baseline and during the examination. Serum cortisol levels, IL-4, and IFN-γ levels were determined by enzyme-linked immunosorbent assay technique. Result: In the yoga group, no significant difference was observed in physiological parameters during the examination stress, whereas in the control group, a significant increase was observed. Likewise, the indicators of psychological stress showed highly significant difference in control group compared with significant difference in yoga group. During the examination, the increase in serum cortical and decrease in serum IFN-γ in yoga group was less significant (P<0.01) than in the control group (P<0.001). Both the groups demonstrated an increase in serum IL-4 levels, the changes being insignificant for the duration of the study. Conclusion: Yoga resists the autonomic changes and impairment of cellular immunity seen in examination stress.

Hepcidin: A novel peptide hormone regulating iron metabolism

BACKGROUND Hepcidin is a low-molecular weight hepatic peptide regulating iron homeostasis. Hepcidin inhibits the cellular efflux of iron by binding to, and inducing the internalization and degradation of, ferroportin, the exclusive iron exporter in iron-transporting cells. It has been recently recognized as a main hormone behind anemia of chronic disease. METHOD A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicines digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/) and the National Library of Medicine (http://www.ncbl.nlm.nih.gov). The data was also assessed from journals and books that published relevant articles in this field. RESULT Hepcidin regulates iron uptake constantly on a daily basis, to maintain sufficient iron stores for erythropoiesis. Hepcidin, by its iron regulatory action on iron metabolism may be expected to have an important role in immune regulation, inflammatory diseases and malignancies. Hepcidin is the underlying cause of anemia in these clinical settings. CONCLUSION Hepcidin analysis may prove to be a novel tool for differential diagnosis and monitoring of disorders of iron metabolism, and establishment of therapeutic measures in various disease conditions like hereditary hemochromatosis, anemia associated with chronic kidney disease, rheumatoid arthritis and cancers.

Modulation of immune responses in stress by Yoga

Stress is a constant factor in todays fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

Integrative role of neuropeptides and cytokines in cancer anorexia-cachexia syndrome.

BACKGROUND The cachexia anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, weight loss, anorexia, early satiety, fatigue, weakness due to shifts in metabolism caused by tumour by-products and cytokines. Various neuropeptides like Leptin, neuropeptide Y, melanocortin, agouti-related peptides have been known to regulate appetite and body weight. METHOD A comprehensive literature search was carried out on the websites of Pubmed Central (http://www.pubmedcentral.nih.gov/), National Library of Medicine (http://www.ncbl.nlm.nih.gov) and various other net resources. RESULT Data from observational studies shows that various cytokines (TNF-α, IL-6 and IL-1) are associated with metabolic changes resulting in cachexia in cancer patients. These cytokines may mimic the action of various neuropeptides resulting in anorexia, various metabolic effects resulting from enhanced catabolic state and weight loss. CONCLUSION There is a need to understand and explore the role of various neuropeptides and cytokines in the pathophysiology of cancer-anorexia syndrome so that therapeutic measures may be designed for effective palliative care.

Homocysteine and lipoprotein (a) correlation in ischemic stroke patients.

BACKGROUND Homocysteine and Lipoprotein (a) have been recognized as risk factors for coronary heart disease. However, their role in ischemic stroke is still not defined. Therefore the present study was undertaken to evaluate their levels and relationship in patients of ischemic stroke. METHODS The study was conducted in consecutive patients admitted with a diagnosis of acute ischaemic stroke and age and sex matched healthy controls. Plasma homocysteine and serum l lipoprotein (a) levels were determined in the fasting venous blood samples using ELISA and immunoturbidimetric assay respectively. RESULTS 66 patients with ischaemic stroke (30 males, 36 females) of mean age 54.43+/-1.97 years and 72 controls (39 males, 33 females) of mean age 53.86+/-1.88 years were studied. Mean plasma homocysteine levels in the stroke patients and control groups were 28.40+/-2.08 micromol/L and 11.16+/-1.09 micromol/L respectively (p<0.001). Odds ratio for raised homocysteine levels in stroke cases was 15.7. Plasma homocysteine levels showed a positive correlation with smoking (Pearsons correlation coefficient=0.324 and p-value of 0.008), (Odds ratio=5.71). Serum Lipoprotein (a) levels in stroke cases and control group were 57.33+/-4.40 mg/dl and 23.46+/-1.09 mg/dl respectively, (p<0.001), (Odds Ratio=8.62). A positive correlation was also observed between Homocysteine and Lipoprotein (a) levels with Pearsons correlation coefficient of 0.75 and p-value<0.001. CONCLUSIONS Raised homocysteine and serum lipoprotein (a) levels were found to be independently associated with ischemic stroke with a significant positive correlation between the two parameters. Elevated homocysteine levels may modulate the toxicity of lipoprotein (a) in ischemic stroke.

NAD(P)H oxidases in coronary artery disease.

Reactive oxygen species (ROS), especially superoxide anion and hydrogen peroxide, are important signaling molecules in cardiovascular cells. ROS participate in growth, apoptosis, and migration of vascular smooth muscle cells, in the modulation of endothelial function, including endothelium-dependent relaxation and expression of proinflammatory phenotype, and in the modification of the extracellular matrix. They have also been linked to hypertension and to pathological states associated with uncontrolled growth and inflammation leading to coronary artery disease (CAD). The NAD(P)H oxidase is a multisubunit enzyme that catalyzes the reduction of molecular oxygen to form superoxide (O2*-). Although first described in phagocytes, NAD(P)H oxidases have also been demonstrated as major sources of superoxide in vascular cells and myocytes. Enhanced superoxide production increases nitric oxide inactivation and leads to an accumulation of peroxynitrites and hydrogen peroxide. An entire new family of NAD(P) H oxidase (Nox) homologs has emerged, which vary widely in cell and tissue distribution as well as in function and regulation. Recent and ongoing research tends to highlight the biochemical characters, activation paradigms, structure, and function of this enzyme. In this review, we provide a brief overview of structural features of NAD(P)H oxidases and then discuss their role in pathophysiology of CAD.

Influence of menopause on biochemical markers of endothelial dysfunction—A case-control pilot study in North Indian population

OBJECTIVE Menopause, an estrogen deficient state, is known to increase the cardiovascular risk. Lipid changes accompanying menopause account for only few cases of coronary artery disease (CAD). Endothelium-dependent nitric oxide-mediated vasodilatory mechanisms are also known to play a role in development of coronary artery disease, but studies in menopausal women are very few. This study was hence undertaken to see if nitric oxide (NO)-cyclic guanidine monophosphate (c-GMP) pathway is influenced by menopause. DESIGN This study was a hospital-based case-control study involving 100 women in age group 40-55 years. Of these, 50 women were postmenopausal and 50 were premenopausal. Women with known risk factors for CAD were excluded. Fasting blood samples from these women were collected and analyzed for estradiol levels, lipid profile, apolipoprotein B, plasma nitric oxide, c-GMP and platelet nitric oxide using standard kits and reagents. Statistical analysis was done on SPSS and two-tailed p-value <0.05 was considered significant. RESULT Postmenopausal women had significantly lower estradiol, plasma NO, and c-GMP levels as compared to premenopausal women (p<0.05). Cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) levels were higher and HDL levels were lower in postmenopausal as compared to premenopausal women (p<0.05). Plasma NO showed a significant positive correlation with estradiol, HDL levels and negative correlation with apo-B levels. CONCLUSION Menopause tends to downregulate NO-c-GMP pathway resulting in endothelial dysfunction. The mechanism may be directly through estrogen receptors or indirectly through potentiation of dyslipidemia.