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Objectives: Fetuin-A is a circulating glycoprotein, formed in the liver. It regulates bone remodelling and calcium metabolism. Fetuin-A has adipogenic properties, so fat accumulation in the liver may be associated with higher levels of fetuin-A. Fetuin-A is an inhibitor of the phosphorylation of the insulin receptor tyrosine kinase., Key Findings: High concentrations of fetuin-A in humans causes insulin resistance. Insulin sensitivity is also found to be increased in fetuin-A knockout mice. Fetuin-A has been shown to cause insulin resistivity in type-2 diabetes mellitus and worsens the pro-atherogenic milieu., Summary: Fetuin-A should be considered as a hepatic bio-marker. Vascular diseases like atherosclerosis are major causes of disability in patients with diabetes mellitus., (© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.)

Objectives: Adipose tissue is the key regulator of energy balance, playing an active role in lipid storage and metabolism and may be a dynamic buffer to control fatty acid flux. Peroxisome proliferator-activated receptor gamma isoform-2 (PPARg2), an isoform of the nuclear hormone receptor superfamily, has been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance, type-2 diabetes and dyslipidaemia. The PPARg2 isoform is highly present in adipose tissue where it functions as a thrifty phenotype, which promotes adipocyte differentiation and triglyceride storage. Thiazolidinediones, antidiabetic drugs, induce insulin sensitivity by controlling adipokines. The thiazolidinediones bind with PPARg2 in adipocytes and exert an agonist effect by enhancing adipogenesis and fatty acid uptake. Thiazolidinediones stimulate PPARg2, by which they down-regulate tumour necrosis factor-α, leptin, interleukin-6 and plasminogen and also enhance insulin sensitivity. The aim of this work is to define role of PPARg2 transcription factor in thiazolidinedione-induced insulin sensitization., Key Findings: The PPARg2 alters the transcription of the target gene. This altered gene transcription results in the up-regulation of insulin-sensitizing factors and down-regulation of insulin-resistant factors. The variant Pro12Ala of the PPARg2 gene is an important modulator in metabolic control in the body. Thiazolidinediones stimulate PPARg2 transcription factor by which PPARg2 binds to responsive elements located in the promoter regions of many genes and modulates their transcriptive activity. There is a strong mutual relationship between receptor binding and agonism, which is evidence of the insulin-sensitizing target of thiazolidinediones in PPARg2. This evidently increases the biological potency of the glucose-lowering effect of thiazolidinediones in vivo as well as their antidiabetic activity., Conclusions: PPARg2 transcription factor plays an important role in treatment of type-2 diabetes with thiazolidindiones. The variant Pro12Ala of the PPARg2 gene promotes the activity of thiazolidinediones in minimizing insulin resistance. Transcriptional activity of Pro12Ala variant improves the activity of insulin. Thus thiazolidinediones promote the phosphorylation of PPARg2 to induce insulin sensitivity., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Background: Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background., Methods: We investigated the association of 51 single-nucelotide polymorphisms (SNPs) in anti-inflammatory cytokines (IL-10, TGFB1, IL-6, IL-4, and IL-13) and receptors (IL-10RA, IL-10RB, TGFBR1, TGFBR2, IL-6R, IL-4R, IL-5RA, IL-5RB, and IL-13RA1) with susceptibility to leprosy in a case-control study from New Delhi in northern India. This was followed by replication testing of associated SNPs in a geographically distinct and unrelated population from Orissa in eastern India. The functional potential of SNPs was established with in vitro reporter assays., Results: Significant associations (P < .05) were observed for 8 polymorphisms (rs1800871, rs1800872, and rs1554286 of IL-10; rs3171425 and rs7281762 of IL-10RB; rs2228048 and rs744751 of TGFBR2; and rs1800797 of IL-6) with leprosy. This association was replicated for 4 SNPs (rs1554286 of IL-10, rs7281762 of IL-10RB, rs2228048 of TGFBR2, and rs1800797 of IL-6). The interaction study revealed a significantly greater association with leprosy risk than was obtained for any SNP individually., Conclusions: This study provides an interesting insight on the cumulative polygenic host component that regulates leprosy pathogenesis.

Objective: To survey a cross section of patients presenting to three urban primary care clinics to understand online health information search behaviors., Design and Analysis: At three urban primary care clinics affiliated with University at Buffalo, School of Medicine, 315 patients were interviewed. Interview questions included items on education, demographic information, employment, number of current prescriptions, insurance, online access, and specifics of health-searching behaviors. Chart review determined patient body mass index and number of chronic illnesses. Logistic regression and chi2 statistics were used to investigate the relationship between patient characteristics and the proportion of patients who use the Web for seeking health information., Results: Approximately 53% of respondents reported using Web or e-mail in the past year and 68% (33% of total sample) of those who accessed the Web used it to search for health information. The two most commonly cited search areas included information about a physical illness and nutrition/fitness. Education and race significantly predicted online health-seeking behavior when considering all factors in the study. Many patients (22%) relied on friends and family to navigate the Web, and 45% of patients reported that the information that they sought was unrelated to their clinical visit., Conclusion: Current use of the Internet for health information was limited among more disadvantaged patient groups. More research is needed to examine the relationship between health-seeking behavior and patients' management of their health and well-being.

Bromocriptine (CB-154, Parlodel, Sandoz) was given to 35 acromegalic patients for a period of 6-36 months. Basal and post-therapy endocrine functions including estimation of serum growth hormone (GH) profile; and GH kinetics during oral glucose tolerance test, augmented insulin tolerance test and thyrotrophin releasing hormone test were determined. The pituitary tumour size was delineated by a pneumoencephalogram. The mean GH levels ranged from 14 micrograms/l to 316 micrograms/l. Bromocriptine suppressed GH values to 5 micrograms/l or less in 16 patients and less than 10 micrograms/l in a further 6 patients. In 33 patients GH values fell to 50% of the basal value or less. There was no significant GH reduction in 2 'nonresponders'. Bromocriptine did not block the stress-induced GH secretion. It did not disturb pituitary functions other than prolactin which was suppressed much earlier and was maintained with smaller doses. GH suppression on the other hand was shortlived and rebounded when the drug was omitted. It had no adverse effect on tumour size in 2 patients having suprasellar extension of the tumour. Bromocriptine improved carbohydrate tolerance and sexual function although it did not affect insulin and gonadotrophin values. It seems reasonable to offer a trial of bromocriptine in all patients with acromegaly where therapy is deemed necessary as it is well tolerated, has insignificant side effects and no adverse drug interactions. Its high cost and prolonged course are obvious disadvantages. Caution should be exercised in cases with suprasellar extension and visual field involvement.

Pituitary apoplexy or spontaneous pituitary necrosis is an ill-understood clinical syndrome. It may occur as a neurological emergency requiring urgent interference in a patient with a known pituitary dysfunction or it may be responsible for drawing attention to an as yet unrecognized pituitary pathology. It has a bizarre clinical profile and an unpredictable neurological and endocrine course. Patients may die at once or may recover with or without endocrine/neurological deficit. Six cases of pituitary apoplexy with varied clinical presentation are cited.