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(1) Good initial weight loss with moderate late regain, anemia, and multiple nutrient deficits was the common pattern. (2) Massive weight loss, frequent vomiting, dumping syndrome, and women in reproductive age were risk factors for hemoglobin or vitamin deficits, whereas superobesity, diabetes, and use of multiple drugs were associated with EWL result. (3) Most laboratory tests became stable by 2 years and along with BMI correlated with late EWL. (4) Two-year nutritional investigation is especially recommended because of its long-term predictive value.

We investigated the effects of dietary trans fatty acids, PUFA, and SFA on body and liver fat content, liver histology, and mRNA of enzymes involved in fatty acid metabolism. LDL receptor knockout weaning male mice were fed for 16 wk with diets containing 40% energy as either trans fatty acids (TRANS), PUFA, or SFA. Afterwards, subcutaneous and epididymal fat were weighed and histological markers of nonalcoholic fatty liver disease (NAFLD) were assessed according to the Histological Scoring System for NAFLD. PPARalpha, PPARgamma, microsomal triglyceride transfer protein (MTP), carnitine palmitoyl transferase 1 (CPT-1), and sterol regulatory element binding protein-1c (SREBP-1c) mRNA were measured by quantitative RT-PCR. Food intake was similar in the 3 groups, although mice fed the TRANS diet gained less weight than those receiving the PUFA diet. Compared with the PUFA- and SFA-fed mice, TRANS-fed mice had greater plasma total cholesterol (TC) and triglyceride (TG) concentrations, less epididymal and subcutaneous fat, larger livers with nonalcoholic steatohepatitis (NASH)-like lesions, and greater liver TC and TG concentrations. Macrosteatosis in TRANS-fed mice was associated with a higher homeostasis model assessment of insulin resistance (HOMA(IR)) index and upregulated mRNA related to hepatic fatty acid synthesis (SREBP-1c and PPARgamma) and to downregulated MTP mRNA. Diet consumption did not alter hepatic mRNA related to fatty acid oxidation (PPARalpha and CPT-1). In conclusion, compared with PUFA- and SFA-fed mice, TRANS-fed mice had less adiposity, impaired glucose tolerance characterized by greater HOMA(IR) index, and NASH-like lesions due to greater hepatic lipogenesis. These results demonstrate the role of trans fatty acid intake on the development of key features of metabolic syndrome.

Immunization by intramuscular injection of plasmid DNA expressing mycobacterial 65-kDa heat shock protein (hsp65) protects mice against challenge with virulent Mycobacterium tuberculosis H37Rv. During infection or after immunization, CD4 ؉ /CD8 ؊ and CD8 ؉ /CD4 ؊ hsp65-reactive T cells increased equally in spleens. During infection, the majority of these cells were weakly CD44 positive (CD44 lo ) and produced interleukin 4 (IL-4) whereas after immunization the majority were highly CD44 positive (CD44 hi ) and produced gamma interferon (IFN-␥). In adoptive transfer of protection to naive mice, the total CD8 ؉ /CD4 ؊ cell population purified from spleens of immunized mice was more protective than that from infected mice. When the cells were separated into CD4 ؉ /CD8 ؊ and CD8 ؉ /CD4 ؊ types and then into CD44 hi and CD44 lo types, CD44 lo cells were essentially unable to transfer protection, the most protective CD44 hi cells were CD8 ؉ /CD4 ؊ , and those from immunized mice were much more protective than those from infected mice. Thus, whereas the CD44 lo IL-4-producing phenotype prevailed during infection, protection was associated with the CD8 ؉ /CD44 hi IFN-␥-producing phenotype that predominated after immunization. This conclusion was confirmed and extended by analysis of 16 hsp65-reactive T-cell clones from infected mice and 16 from immunized mice; the most protective clones, in addition, displayed antigen-specific cytotoxicity.

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The high incidence of tuberculosis around the world and the inability of BCG to protect certain populations clearly indicate that an improved vaccine against tuberculosis is needed. A single antigen, the mycobacterial heat shock protein hsp65, is sufficient to protect BALB/c mice against challenge infection when administered as DNA vaccine in a threedose-based schedule. In order to simplify the vaccination schedule, we coencapsulated hsp65-DNA and trehalose dimicolate (TDM) into biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres. BALB/c mice immunized with a single dose of DNA-hsp65/TDM-loaded microspheres produced high levels of IgG2a subtype antibody and high amounts of IFN-g in the supernatant of spleen cell cultures. DNA-hsp65/TDM-loaded microspheres were also able to induce high IFN-g production in bulk lung cells from challenged mice and confer protection as effective as that attained after three doses of naked DNA administration. This new formulation also allowed a ten-fold reduction in the DNA dose when compared to naked DNA. Thus, this combination of DNA vaccine and adjuvants with immunomodulatory and carrier properties holds the potential for an improved vaccine against tuberculosis. Gene Therapy (2003) 10, 678-685.

Based on the biochemical and histological evidence in this pilot study, NAC in combination with MTF appears to ameliorate several aspects of NASH, including fibrosis. Further studies of this form of combination therapy are warranted to assess its potential efficacy.