Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.     

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM To determine whether serum interleukin-18 (IL-18)levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC).METHODS Serum IL-18, IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls.RESULTS Serum IL-18, IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (＜ 105 pg/mL)(4 and 11 mo, respectively, P = 0.015). Multivariate analyses showed that serum IL-18 level, but not IL-6 and IL-12 levels, was a significant and independent prognostic factor of survival.CONCLUSION These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patien ts with HCC. Thus, the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.     

Relationships of body fat distribution,insulin sensitivity and cardiovascular risk factors in lean,healthy non-diabetic Thai men and women

In order to study the relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai men and women, 32 healthy, non-diabetic subjects, 16 men and 16 women, with respective mean age 28.4+/-6.6 (S.D.) and 32.8+/-8.9 years, mean BMI 21.0+/-2.8 and 21.2+/-3.7 kg/m(2), were measured for total body fat and abdominal fat by dual energy X-ray absorptiometry (DEXA), anthropometry and insulin sensitivity by euglycemic hyperinsulinemic clamp. Cardiovascular risk factors included fasting and post-glucose challenge plasma glucose and insulin, blood pressure, lipid profile, fibrinogen and uric acid. For similar age and BMI, men had a lower amount and percent of total body fat, but had a higher proportion of abdominal/total body fat than women. In men, insulin sensitivity, as determined by glucose infusion rate during euglycemic hyperinsulinemic clamp, was inversely correlated with total body fat, abdominal fat, BMI and waist circumference, whereas only total body fat, but not abdominal fat, BW and hip circumference were inversely correlated with insulin sensitivity in women. No cardiovascular risk factors, except area under the curve (AUC), of plasma insulin in women correlated with insulin sensitivity when adjusted for total body fat. After age adjustment, total body fat was better correlated with fasting and AUC of plasma glucose and insulin in men and with systolic blood pressure as well as triglyceride levels in women. Only HDL-C in men was better correlated with abdominal fat. In conclusion, there were sex-differences in body fat distribution and its relationship with insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai subjects. Total body fat was a major determinant of insulin sensitivity in both men and women, abdominal fat may play a role in men only. Body fat, not insulin sensitivity, was associated with cardiovascular risk factors in these lean subjects.     

Comparison study of combined DTPw-HB vaccines and separate administration of DTPw and HB vaccines in Thai children.

The safety, immunogenicity and tolerability of two different DTPw-HBV combination vaccines, containing 5 and 10 microg of HBsAg; were investigated in comparison with separate administration of DTPw and HBV (10 microg of HBsAg). A three dose primary vaccination course at 2, 4 and 6 months of age was followed by a booster dose at 18 months. All vaccines were safe and well tolerated. The DTPw-HBV combination vaccine containing 10 microg of HBsAg elicited significantly higher anti-HBs titres than the other two vaccines after the primary and booster vaccination course. All vaccines elicited a high response against the other components. Based on these results, DTPw-HBV (10 microg HBsAg) was the most effective vaccine at this schedule.     

Insufficient evidence of TT-viral etiology of post hepatitis aplastic anemia

Post-hepatitis aplastic anemia is a rather rare pathologic condition of as yet unclear etiology especially as hepatitis viruses A to G have been excluded as the potential agents responsible. The novel TT virus, a single-stranded DNA virus first isolated from the serum of a patient with post-transfusion hepatitis in Japan might cause this condition. Therefore, our group subjected the sera of two children with post-hepatitis aplastic anemia to semi-nested PCR using primers specific for detection of TTV DNA. Although TTV DNA was not detectable in either sample it might be speculated that, like hepatitis viruses A to G, TTV could be found associated with this condition whereas it certainly does not constitute its sole etiologic agent.     

Avian influenza H5N1 in naturally infected domestic cat

We report H5N1 virus infection in a domestic cat infected by eating a pigeon carcass. The virus isolated from the pigeon and the cat showed the same cluster as the viruses obtained during the outbreak in Thailand. Since cats are common house pets, concern regarding disease transmission to humans exists.     

Detection and differentiation of human herpesviruses 1-5 by consensus primer PCR and RFLP

Eight human viruses of the Herpesviridae family represent a significant public health problem world-wide. Detection and typing of five of the human herpesviruses (HSV-1, HSV-2, VZV, EBV, and CMV) was performed by applying a consensus primer polymerase chain reaction (PCR). The amplified PCR products from the five human herpesviruses were typed based on their restriction enzyme digestion polymorphism with Hinf I and Alu I. Fifteen clinically suspected specimens from herpesvirus-infected patients were also evaluated. A fragment of the DNA polymerase gene from each of the five human herpesviruses was successfully amplified by the set of consensus primers. Their amplicons obtained by PCR from the template DNAs were subjected to restriction endonuclease digestion and human herpesviruses 1-5 could be clearly differentiated and typed. This method can be used to detect and differentiate between the five human herpesviruses in clinical specimens. This study demonstrates the value of testing for five human herpesviruses by consensus PCR and restricted fragment length polymorphism (RFLP). These procedures are simple and straightforward techniques for the investigation of clinical specimens.