The glutamic acid derivative thalidomide is a transcriptional inhibitor of TNF-alpha but is also known to affect human blood vessels, which may underlie its teratogenicity. Thalidomide has been used in the treatment of refractory Crohn's disease (CD), but the therapeutic mechanism is not defined. We examined the effect of thalidomide on primary cultures of human intestinal microvascular endothelial cells (HIMEC), the relevant endothelial cell population in inflammatory bowel disease (IBD), to determine its effect on endothelial activation, leukocyte interaction, and VEGF-induced angiogenesis. HIMEC cultures were pretreated with thalidomide before activation with either TNF-alpha/LPS or VEGF. A low-shear-stress flow adhesion assay with either U-937 or whole blood was used to assess HIMEC activation following TNF-alpha/LPS, and a Wright's stain identified adherent leukocytes. Expression of cell adhesion molecules (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) was assessed using radioimmunoassay. Effects of thalidomide on NF-kappaB activation, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression in TNF-alpha/LPS-activated HIMEC were determined by RT-PCR and Western blotting. Thalidomide blocked adhesion of both U-937 and whole blood leukocytes by 50% in HIMEC, inhibiting binding of all classes of leukocytes. Thalidomide also blocked NF-kappaB and cell adhesion molecule expression in HIMEC. In marked contrast, thalidomide did not affect either iNOS or COX-2 expression, two key molecules that play a role in the downregulation of HIMEC activation. VEGF-induced HIMEC transmigration, growth, proliferation, tube formation, and Akt phosphorylation were significantly inhibited by thalidomide. In summary, thalidomide exerted a potent effect on HIMEC growth and activation, suggesting that it may also function via an endothelial mechanism in the treatment of CD.

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This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B(12). Elevated concentrations of vitamin B(12) may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies.

Coffee consumption was associated with reduced circulating B-vitamin concentrations. The observed effect profiles indicated that coffee consumption preferentially affected the upper, but not the lower, part of the B-vitamin concentration distributions. We hypothesize that coffee consumption may increase the loss of surplus B-vitamins by excretion in urine.

This study suggests that agomelatine is effective in the treatment of GAD and is well tolerated. Additional trials, using an active comparator and extending over a longer period, are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for anxiety disorders.

Choline is involved in the synthesis of phospholipids, including blood lipids, and is the immediate precursor of betaine, which serves as a methyl group donor in a reaction converting homocysteine to methionine. Several cardiovascular risk factors are associated with plasma homocysteine, whereas little is known about their relationship to choline and betaine. We examined the relation of plasma choline and betaine to smoking, physical activity, BMI, percent body fat, waist circumference, blood pressure, serum lipids, and glucose in a population-based study of 7074 men and women aged 47–49 and 71–74 y. Overall plasma concentrations (means 6 SD) were 9.9 6 2.3 mmol/L for choline and 39.5 6 12.5 mmol/L for betaine. Choline and betaine were lower in women than in men and in younger subjects compared with older (P , 0.0001). Multivariate analyses showed that choline was positively associated with serum triglycerides, glucose, BMI, percent body fat, waist circumference (P , 0.0001 for all), and physical activity (P , 0.05) and inversely related to HDL cholesterol (P , 0.05) and smoking (P , 0.0001). Betaine was inversely associated with serum non-HDL cholesterol, triglycerides, BMI, percent body fat, waist circumference, systolic and diastolic blood pressure (P , 0.0001 for all), and smoking (P , 0.05) and positively associated with HDL cholesterol (P , 0.01) and physical activity (P , 0.0001). Thus, an unfavorable cardiovascular risk factor profile was associated with high choline and low betaine concentrations. Choline and betaine were associated in opposite directions with key components of metabolic syndrome, suggesting a disruption of mitochondrial choline dehydrogenase pathway. J. Nutr. 138: 914–920, 2008.

It has been suggested that an HIV diagnosis may increase the likelihood of mental disorders among infected individuals and that the progression of HIV may be hastened by mental disorders like anxiety and depression. Therefore, a brief screening measure, with good sensitivity/specificity for psychiatric diagnoses that could be given to HIV-infected individuals would be useful. We assessed the validity of the K-10, using the MINI International Neuropsychiatric Interview as the gold standard, in a sample of 429 HIV-infected adults enrolled in HIV care and treatment services near Cape Town, South Africa. There was significant agreement between the K-10 and the MINI-defined depressive and anxiety disorders. A receiver operating characteristic (ROC) curve analysis indicated that the K-10 showed agreeable sensitivity and specificity in detecting depression (area under the ROC curve, 0.77), generalized anxiety disorder (0.78), and posttraumatic stress disorder (PTSD) (0.77). The K-10 may be a useful screening measure for detecting mood and anxiety disorders, including PTSD, in patients with HIV/AIDS.

In both developed and developing countries, the clinical profile of GAD is similar regardless of duration. The DSM-IV 6-month duration criterion excludes a large number of individuals who present with shorter generalized anxiety episodes which may be recurrent, impairing and contributory to treatment-seeking. Future iterations of the DSM and ICD should consider modifying the 6-month duration criterion so as to better capture the diversity of clinically salient anxiety presentations.

While monoaminergic hypotheses of psychopathology remain popular, there has been growing interest in the role of neurotrophins in neuropsychiatric disorders. Basic laboratory work has documented the importance of neurotrophins in neuronal survival and synaptic plasticity, and a range of clinical studies has provided analogous evidence of their role in neuropathology. Work on gene variants in brain-derived neurotrophic factor, and associated changes in structural and function brain imaging, have further contributed to our understanding of this area. Much remains to be done to delineate fully the relevant mechanisms by which brain-derived neurotrophic factor and other neurotrophins contribute to psychopathology, and to develop targeted therapeutic interventions. Nevertheless, the neurotrophin hypothesis has already given impetus to a range of valuable research.

From 1952 to 2001, risk of death between 40 and 70 years was reduced by close to 50% in western Europe. Comparing mortality trends in the 12 countries for which complete cause-of-death data are available for the period, we see that the ranking of Spanish and Finnish women greatly improved with respect to women in other countries. A more moderate improvement was observed for men in the United Kingdom and Switzerland. By contrast, both women and men in Denmark, and women in the Netherlands dropped down the rankings and lost the advantageous position held at the start of the period.

The high co-morbidity of PD with axis I disorders in South Africa is consistent with previous reports elsewhere. However, more research is indicated to determine the reasons for the higher prevalence of cluster A disorders than of cluster B and C disorders in this population.

Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.

Overall, there does not appear to be a significant effect of gender on the efficacy of venlafaxine ER in the treatment of PTSD. Trauma type may affect treatment outcome but seems to affect domains such as disability and resilience more than core PTSD symptoms.