The combination of a high-fat diet and chronic stress aggravates insulin resistance in Wistar male rats.

We observed the effects of the combination of a high-fat diet and chronic stress on insulin resistance. Male Wistar rats were fed on either a control or a high-fat diet and given chronic stress with the electric foot shock or not for 10 weeks. After checking the glucose infusion rate (GIR) and the HOMA-IR index, the results showed that the three groups all revealed insulin resistance with increased free fatty acid (FFA), adrenocorticotropic hormone (ACTH) and corticosterone in the serum, in addition to increased tumour necrosis factor alpha (TNF-alpha) in the serum and adipose tissue, and decreased density of high affinity receptors (R1) and expression of peroxisome proliferator-activated receptor-alpha (PPARalpha) mRNA in the hepatocytes as compared with the control, but the highest alteration on aforementioned parameters revealed in the chronic stress fed with a high-fat diet. Significant interactions between high-fat diet and chronic stress were revealed on GIR, HOMA-IR index, FFA, ACTH, corticosterone, TNF-alpha (in adipose tissue) and R1. These observations strongly suggest that a combination of a high-fat diet and chronic stress can produce a synergic effect on aggravating insulin resistance associated with the abnormal hypothalamic-pituitary-adrenocortical axis, endocrine abnormality of the adipose tissue, and pathological changes of the liver.

The production of tumour necrosis factor-alpha is decreased in peripheral blood mononuclear cells from multidrug-resistant tuberculosis patients following stimulation with the 30-kDa antigen of Mycobacterium tuberculosis.

The clearance of intracellular bacteria requires the appropriate induction of proinflammatory cytokines and chemokines to recruit macrophages and T cells to the site of infection. In this study, we investigated the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-8 and interferon (IFN)-gamma by the peripheral blood mononuclear cells (PBMC) of patients with multidrug-resistant tuberculosis (MDR-TB) in response to in vitro stimulation with the 30-kDa antigen of Mycobacterium tuberculosis. The results were compared with those from cases of newly diagnosed TB (N-TB) and TB with treatment failure (TF-TB), and healthy tuberculin reactors (HTR). The most significantly depressed TNF-alpha levels were found in MDR-TB patients. IFN-gamma production was depressed significantly in all groups of TB patients compared with the HTR group. TNF-alpha secretion in response to the 30-kDa antigen was unchanged by coculturing with recombinant human interferon (rhIFN)-gamma, and was increased dramatically following IL-10 neutralization with an anti-human IL-10 antibody. The IL-8 levels were depressed significantly in MDR-TB patients compared with N-TB patients, but were similar to the IL-8 levels in TF-TB patients. Furthermore, rhTNF-alpha directly increased IL-8 secretion, and neutralizing antibody to TNF-alpha inhibited IL-8 production by the PBMC of MDR-TB patients that were stimulated with the 30-kDa antigen. Taken together, these data suggest that the PBMC of MDR-TB patients typically show TNF-alpha depression in response to the 30-kDa antigen, and this effect is modulated by IL-10. In addition, we highlight the role of TNF-alpha in IL-8 secretion in MDR-TB patients.

Profiles of IFN-gamma and its regulatory cytokines (IL-12, IL-18 and IL-10) in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis.

This study investigated the profiles of IFN-gamma and its regulatory cytokines (IL-12, IL-18 and IL-10) in response to a purified protein derivative (PPD) antigen in peripheral blood mononuclear cells (PBMC) from 18 HIV-negative patients with multidrug-resistant tuberculosis (MDRTB), and compared them with those from 19 healthy tuberculin reactors (HTR). ELISA results showed that following stimulation with PPD, IFN-gamma production was significantly reduced, whereas production of both IL-18 and IL-10 was significantly elevated in MDRTB patients compared with HTR. Three out of 18 patients with MDRTB of greater than 4 years duration showed significantly elevated IL-12 p70 production, induced by in vitro PPD stimulation of their PBMC, when compared with data from HTR. However, when taken as a group, MDRTB patients were similar to HTR in their IL-12 p70-producing capacity. IL-12 p70 protein paralleled IL-12 p40 protein expression. In addition, the production of IL-12 p40 was significantly correlated with IL-10 in all patients, but was not correlated with IFN-gamma. Neutralization of IL-10 increased IL-12 p40 about twofold, but did not significantly alter IFN-gamma induction in MDRTB. IFN-gamma in MDRTB was highly correlated with lymphoproliferation and CD4 counts, but was not correlated with IL-12, IL-18 or IL-10 production. Our findings suggest that patients with MDRTB have dysregulated IL-12, IL-18 and IL-10 production during Mycobacterium tuberculosis infection, and the cytokine profiles are similar to those in patients with drug-sensitive advanced TB previously reported in the literature. In addition, IL-10 may not have a dominant role in defective IFN-gamma production in patients with MDRTB.

Effect of surface properties on the antithrombogenicity of silk fibroin/S-carboxymethyl kerateine blend films.

Polymeric blends of silk fibroin (SF) and S-carboxymethyl kerateine (SCMK) were prepared by the solvent casting method to study the effect of surface properties on the antithrombogenicity. The films of SF/SCMK showed better antithrombogenic properties than SF or SCMK alone. Among them, the film containing 50 wt% SCMK showed the best antithrombogenicity. When the SF/SCMK films were treated with methanol, the antithrombogenicity of the films was scarcely affected except the SF-rich ones. The enhanced antithrombogenic properties were explained in terms of polarity of the surface. The blend films showed an enhancement of polar contribution to surface free energy (gamma(P)S and polar stabilization energy (I(SW)). SF-rich films showed high gamma(P)S and I(SW) values when treated with methanol. This change of surface properties was considered to be due to the fact that the conformational transition from random coil structure to beta-structure of proteins may have affected the surface properties, especially the polar properties.