Reciprocal effects of IFN-beta and IL-12 on STAT4 activation and cytokine induction in T cells

IL-12 is an immunoregulatory cytokine, which promotes Th1 cell differentiation and is a major inducer of IFN-gamma. IFN-beta, a Type I IFN used in the treatment of multiple sclerosis, has been shown to significantly increase the expression of the anti-inflammatory cytokine IL-10, a major suppressor of Th1 cytokines. The beneficial immunomodulatory effects of IFN-beta may in part be a result of its ability to suppress IL-12. However, IL-12 and IFN-beta signal via the STAT4 pathway. Our aim was to investigate the relationship between IL-12 and IFN-beta by observing the effect of prior exposure to IL-12 or IFN-beta on the ability of T cells to subsequently respond to the other cytokine. We report that IFN-beta increases IL-12-induced STAT4 phosphorylation and up-regulates IL-12 receptor beta1 and beta2 expression. However, despite this up-regulation, IFN-beta suppressed IL-12-induced IFN-gamma expression. Our results suggest that this may be a result of the parallel induction of IL-10 by IFN-beta.     

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women

BACKGROUND: Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. OBJECTIVE: The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. DESIGN: Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. RESULTS: Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. CONCLUSIONS: Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.     

Biochemical studies of RT6 alloantigens in BB/Wor and normal rats. Evidence for intact unexpressed RT6a structural gene in diabetes-prone BB rats

Lymphocytes bearing the T-lymphocyte differentiation antigen RT6 play an important immunoregulatory role in the development of autoimmune diabetes in BB rats. Immunofluorescence studies suggest that diabetes-prone (DP)- but not diabetes-resistant (DR)-BB rat lymphocytes fail to express RT6 antigen during ontogeny. Two alloantigenic forms of the molecule exist, i.e., RT6.1 and RT6.2; both are linked to cell membranes by a phosphatidylinositol (PI) linkage. In these studies, PI-phospholipase C (PLC) treatment of lymphocytes from BB and normal rats followed by immunoabsorption and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of released proteins with anti-RT6 allotype-specific monoclonal antibodies was performed. RT6.1 in several nondiabetic rat strains was found to consist of a family of nonglycosylated and variably glycosylated molecules: an N-Glycanase-resistant 24,000- to 26,000-Mr peptide and four N-Glycanase-sensitive peptides of 29,000, 31,000, 33,000, and 34,000 Mr. In contrast, RT6.2 was found to be a 24,000- to 26,000-Mr nonglycosylated polypeptide. The electrophoretic pattern of RT6.1 was observed to be the same when the antigen was extracted from W3/25+ (CD4+) versus W3/25- T lymphocytes or from resting versus mitogen-activated cells. A pattern of bands characteristic of the RT6.1 antigen found in normal rat strains was detected after PLC treatment or detergent solubilization of lymphocytes obtained from DR rats. In contrast, no evidence of either RT6 species was found after PLC or detergent treatment of comparable numbers of T lymphocytes from DP-BB rats. Interestingly, T lymphocytes from Wistar-Furth (RT6.2+) x DP (RT6-) F1 crosses were observed to coexpress both RT6.2 and RT6.1 molecules, with the electrophoretic pattern of RT6.1 being similar to that obtained in DR and other rat strains. This study provides biochemical evidence that DP rats may have an intact RT6a structural gene.     

The effects of a ‘pets as therapy’ dog on persons with dementia in a psychiatric ward

A pets as therapy (PAT) programme was initiated in a closed ward of a major psychiatric hospital. The effect of regular contact with a dog on a selected group of chronic ward-bound patients suffering from dementia was assessed over a 12 week period using a number of measures. These included global measures of daily functioning, physiological measures (blood pressure and heart rate) and a measure of general ward noise levels. A matched group from a similar closed ward was used as a control. Results indicated significant experimental group changes in heart rate and a substantial drop in noise levels in the experimental ward during the presence of the dog.     

Predicting developmental outcomes in very preterm infants: validity of a neonatal neurobehavioral assessment

Aim: This study explored inter‐rater reliability, discriminative, construct and predictive validity of the Neurobehavioral Assessment of the Preterm Infant (NAPI) in a gestational‐age‐based cohort. Methods: The NAPI was conducted at 35 weeks post‐menstrual age for 170 infants born <32 weeks. Cognitive and motor development was assessed at 2 years using the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of Bayley Scales of Infant Development‐II for 159 infants. Results: Only NAPI motor and irritability scores were significantly different between very (29–3 w) and extremely preterm (<28 w) infants. Results regarding construct validity were variable: there were weak correlations between NAPI motor scores and gestational age (r = ?0.23; p = 0.003), days in NICU (r = ?0.24; p = 0.001); NAPI alertness scores and days in NICU (r = ?0.16; p = 0.037); and NAPI irritability scores and gestational age (r = 0.21; p = 0.006). There were no significant associations with other markers of adverse outcome. Only NAPI irritability scores were correlated with MDI scores (r = ?0.16; p = 0.040) but accounted for little additional variance after adjustment for neonatal factors (ΔR² = 0.035; p = 0.012). Conclusion: We found little evidence of the utility of the NAPI as a measure of short‐term neurobehavioural function or for predicting neurodevelopmental outcomes in very preterm infants. It may have greater predictive power when used serially to detect delayed neurobehavioural maturation.     

Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT)

Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk factors; however, to our knowledge, no randomized clinical studies have addressed whether resistance training (RT) improves the MS when performed alone or combined with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years completed a 4-month inactive run-in period and were randomized to 1 of 3 eight-month exercise programs (n = 196). The exercise programs were (1) RT (3 days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting all major muscle groups); (2) AT (～120 minutes/week at 75% of the maximum oxygen uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86 participants with complete data for all 5 MS criteria were used in the present analysis, and a continuous MS z score was calculated. Eight months of RT did not change the MS score. AT improved the MS score (p <0.07) and showed a trend toward significance compared to RT (p <0.10). AT/RT significantly decreased the MS score and was significantly different from RT alone. In conclusion, RT was not effective at improving the MS score; however, AT was effective. Combined AT and RT was similarly effective but not different from AT alone. When weighing the time commitment versus health benefit, the data suggest that AT alone was the most efficient mode of exercise for improving cardiometabolic health.     

Oxidative Stress in Follicular Units During Hair Transplantation Surgery

Background  

Hair transplantation surgery currently is a well-established procedure in plastic surgery. It consists of harvesting a strip of scalp from the back of the head, then obtaining grafts called follicular units (FUs) from this strip and implanting them in the bald area. The FUs undergo oxidative stress during cold ischemia and after their implantation.     

Exercise-induced changes in metabolic intermediates, hormones, and inflammatory markers associated with improvements in insulin sensitivity

OBJECTIVE

To understand relationships between exercise training-mediated improvements in insulin sensitivity (S_I) and changes in circulating concentrations of metabolic intermediates, hormones, and inflammatory mediators.

RESEARCH DESIGN AND METHODS

Targeted mass spectrometry and enzyme-linked immunosorbent assays were used to quantify metabolic intermediates, hormones, and inflammatory markers at baseline, after 6 months of exercise training, and 2 weeks after exercise training cessation (n = 53). A principal components analysis (PCA) strategy was used to relate changes in these intermediates to changes in S_I.

RESULTS

PCA reduced the number of intermediates from 90 to 24 factors composed of biologically related components. With exercise training, improvements in S_I were associated with reductions in by-products of fatty acid oxidation and increases in glycine and proline (P < 0.05, R² = 0.59); these relationships were retained 15 days after cessation of exercise training (P < 0.05, R² = 0.34).

CONCLUSIONS

These observations support prior observations in animal models that exercise training promotes more efficient mitochondrial β-oxidation and challenges current hypotheses regarding exercise training and glycine metabolism.Targeted mass spectrometry-based measurements of small molecule metabolic intermediates have provided insight into the pathogenesis of chronic metabolic diseases including obesity, type 2 diabetes, and cardiovascular disease (1–5). Our objective was to elucidate mechanisms by which exercise training improves S_I in a group of middle-aged, sedentary, overweight to obese men and women, at risk for but without overt type 2 diabetes. In particular, we sought to elucidate relationships between changes in whole-body S_I and plasma metabolic and inflammatory biomarkers after 6 months of aerobic exercise training.