Adrenergic and muscarinic receptor subtypes functional regulation during diabetogenesis: Effect of curcumin and vitamin D3 pre-treatment

In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.

Clinical features and treatment response in social phobia : Axis II comorbidity and social phobia subtypes

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Cognitive-behavior therapy for compulsive checking in OCD

There is substantial evidence for the effectiveness of psychological treatments for OCD, and various approaches have been widely recommended. These approaches tend to be characterized by exposure and response prevention (ERP) and also tend to be applied equally to all forms of OCD. Patients/clients (and some therapists) often find ERP to be a difficult treatment, and both dropout and refusal rates are unacceptably high. Based on specific cognitive conceptualizations of different manifestations of OCD, new and refined cognitive treatment methods are now available. The present article describes a specific cognitively based approach to the treatment of compulsive checking.

Separating hoarding from OCD

There is confusion about the status of excessive hoarding. In particular, there is an unresolved question about whether or not it is a manifestation of obsessive-compulsive disorder (OCD). There are some definite similarities between 'compulsive' hoarding and OCD, but they are outweighed by the differences between them. It is proposed that the matter can be clarified by separating hoarding from OCD, and that this would advance clinical work and research. (c) 2009 Elsevier Ltd. All rights reserved.

Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential

The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the α-2,3 SA and human influenza viruses the α-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo, we show that many avian HA subtypes do not adhere to this canonical view of SA specificity. The propensity of avian viruses to adapt to human receptors may thus be more widespread than previously supposed.

Investigating subtypes of reward processing deficits as trait markers for depression

Background: Anhedonia, the loss of pleasure in usually enjoyable activities, is a central feature of major depressive disorder (MDD). The aim of the present study was to examine whether young people at a familial risk of depression display signs of anticipatory, motivational or consummatory anhedonia, which would indicate that these deficits may be trait markers for MDD. Methods: The study was completed by 22 participants with a family history of depression (FH+) and 21 controls (HC). Anticipatory anhedonia was assessed by asking participants to rate their anticipated liking of pleasant and unpleasant foods which they imagined tasting when cued with images of the foods. Motivational anhedonia was measured by requiring participants to perform key presses to obtain pleasant chocolate taste rewards or to avoid unpleasant apple tastes. Additionally, physical consummatory anhedonia was examined by instructing participants to rate the pleasantness of the acquired tastes. Moreover, social consummatory anhedonia was investigated by asking participants to make preference-based choices between neutral facial expressions, genuine smiles, and polite smiles. Results: It was found that the FH+ group’s anticipated liking of unpleasant foods was significantly lower than that of the control group. By contrast, no group differences in the pleasantness ratings of the actually experienced tastes or in the amount of performed key presses were observed. However, controls preferred genuine smiles over neutral expressions more often than they preferred polite smiles over neutral expressions, while this pattern was not seen in the FH+ group. Conclusion: These findings suggest that FH+ individuals demonstrate an altered anticipatory response to negative stimuli and show signs of social consummatory anhedonia, which may be trait markers for depression.

Quantitative Detection of Enterotoxigenic Bacteroides fragilis Subtypes Isolated from Children with and without Diarrhea

A rapid real-time PCR ( RT-PCR) approach was developed to detect the bft gene subtypes in Bacteroides fragilis isolated from fecal samples. DNA obtained from diarrhea (110) and nondiarrhea (150) samples was evaluated. Subtype 1 was observed in 9 (8.2%) diarrhea and 7 (4.7%) nondiarrhea samples. Subtype 2 was not detected in any DNA samples, and subtype 3 was observed in only 1 diarrhea sample. The presence of the bft-1 gene did not show any statistically significant differences between the groups of children. This technique could be used to evaluate a possible correlation between disease and the presence of B. fragilis enterotoxin.

Lifetime cost of stroke subtypes in Australia: findings from the North East Melbourne stroke incidence study (NEMESIS)

Background and Purpose-: Little is known about any variations in resource use and costs of care between stroke subtypes, especially nonhospital costs. The purpose of this study was to describe the patterns of resource use and to estimate the first-year and lifetime costs for stroke subtypes.

Methods-: A cost-of-illness model was used to estimate the total first-year costs and lifetime costs of stroke subtypes for all strokes (subarachnoid hemorrhages excluded) that occurred in Australia during 1997. For each subtype, average cost per case during the first year and the present value of average cost per case over a lifetime were calculated. Resource use data obtained in the North East Melbourne Stroke Incidence Study (NEMESIS) were used.

Results-: The present value of total lifetime costs for all strokes was Aus $1.3 billion (US $985 million). Total lifetime costs were greatest for ischemic stroke (72%; Aus $936.8 million; US $709.7 million), followed by intracerebral hemorrhage (26%; Aus $334.5 million; US $253.4 million) and unclassified stroke (2%; Aus $30 million; US $22.7 million). The average cost per case during the first year was greatest for total anterior circulation infarction (Aus $28 266). Over a lifetime, the present value of average costs was greatest for intracerebral hemorrhage (Aus $73 542), followed by total anterior circulation infarction (Aus $53 020), partial anterior circulation infarction (Aus $50 692), posterior circulation infarction (Aus $37 270), lacunar infarction (Aus $34 470), and unclassified stroke (Aus $12 031).

Conclusions-: First-year and lifetime costs vary considerably between stroke subtypes. Variation in average length of total hospital stay is the main explanation for differences in first-year costs.

Significance of histological subtypes of Kikuchi`s disease: comparative immunohistochemical and apoptotic studies

Kikuchi's disease (KD) is a self-limiting lymphadenitis mostly affecting the cervical lymph nodes of young individuals. It has been classified into three histological subtypes and postulated to progress from the proliferative type (PT) to the necrotizing type (NT) and finally resolve into the xanthomatous type (XT). Since KD has been shown to be an apoptotic disease, the apoptotic activity was studied by the TUNEL method on 6, 12, and 6 cases of PT, NT, and XT, respectively, to see if the apoptotic activity could be shown to decrease in the order of the postulated sequence of evoluation. Significant statistical difference among the three subtypes was found (P = 0.050). Further analysis revealed that PT versus NT was significant (P = 0.010), but NT versus XT (P = 0.385) or PT versus XT (P = 0.310) was not. Analysis of three stages of NT was also significant (P = 0.019). Immunohistochemical study showed that abundant CD8+ T cells and cytotoxic protein positive cells were present in PT and NT, but were relatively low in XT. Our results showed progression of PT to NT, but not from NT to XT. Xanthomatous type was not the resolving stage of KD, but seemed to be a distinctive histological variant of KD caused by either different etiology or an unusual host reaction.

Subtypes of psychopathy : proposed differences between narcissistic, borderline, sadistic and antisocial psychopaths

Atascadero State Hospital (ASH) is a maximum-security forensic hospital that houses male patients with a wide range of psychiatric diagnoses. Psychopaths at this institution appear to be a heterogeneous group of individuals who, while sharing core personality characteristics, manifest substantial variability in their behavior. Identifying subtypes within this clinical classification can have implications for patient treatment and management, as well as for the safety of the staff who work with them and for the communities to which they will eventually return. Several means of identifying subtypes have been proposed in the literature, and potential subgroups have been identified. Clinical observations at ASH have suggested 4 possible subtypes of psychopathy: narcissistic, borderline, sadistic, and antisocial. Issues related to the conceptualization of psychopathy are addressed, recognizing that additional data are needed to understand the observed variations in cases of psychopathy.