Changes in serum level of trace elements in pulmonary tuberculosis patients during anti-tuberculosis treatment.

INTRODUCTIONS: Tuberculosis is spreading throughout the globe, while it is a crucial cause of death in developing countries. In this study, trace elements concentrations and their alterations were determined in TB patients during anti-tuberculosis treatment period. MATERIALS AND METHODS: We have collected blood samples from a total of 180 TB patients with pulmonary Tuberculosis, and 180 healthy controls in Sistan, Iran. The serum iron, copper, lead, calcium, arsenic and selenium concentrations were detected at the beginning of anti-TB chemotherapy, at the end of 2nd, 4th and 6th month after treatment initiation. Data were then analyzed using SPSS version 20. RESULTS AND DISCUSSIONS: Although Ca, Pb, and As levels did not change during the treatment period, serum concentrations of Fe, Zn, Cu, and Se were diminished in TB patients significantly during treatment in comparison with controls (P < 0.001).We also found that there was a significant difference in the Cu/Se and Cu/Zn ratios in tuberculosis patients in comparison with healthy individuals (P < 0.001). CONCLUSIONS: Trace elements serum concentrations are affected by TB infection and anti-TB therapy. Their serum levels were strongly perturbed during infection as well as anti-TB treatment.

Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells.

The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP- and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB-231(breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.

Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application.

The mevalonate cascade is a key metabolic pathway that regulates a variety of cellular functions and is thereby implicated in the pathophysiology of most brain diseases, including neurodevelopmental and neurodegenerative disorders. Emerging lines of evidence suggest that statins and Rho GTPase inhibitors are efficacious and have advantageous properties in treatment of different pathologic conditions that are relevant to the central nervous system. Beyond the original role of statins in lowering cholesterol synthesis, they have anti-inflammatory, antioxidant and modulatory effects on signaling pathways. Additionally, Rho GTPase inhibitors and statins share the mevalonate pathway as a common target of their therapeutic actions. In this review, we discuss potential mechanisms through which these drugs, via their role in the mevalonate pathway, exert their neuroprotective effects in neurodegenerative and neurodevelopmental disorders.

Essential and toxic metals in serum of individuals with active pulmonary tuberculosis in an endemic region.

Trace elements play an important role in tuberculosis infection because their deficiencies can be associated with impaired immunity. Blood samples were collected from a total of 320 active pulmonary tuberculosis patients and healthy individuals. The serum concentrations of Zinc, Iron, Copper, Calcium, lead, Arsenic and Selenium were analyzed by atomic absorption spectrometry. The levels of trace elements were measured after 2, 4 and 6 months of anti-TB treatment initiation in TB infected groups. Compared to the control group, the concentrations of Zinc, Selenium, and Iron were significantly lower (P < 0.001) in tuberculosis patients; however, that of Arsenic, Lead, and copper was significantly higher (P < 0.001) in the serum of patients. Cu/Zn and Cu/Se ratios were also significantly higher (P < 0.001) in TB patients compared to the control group. In addition, serum concentration calcium was similar in both TB patients and healthy controls. Our results indicated that trace elements concentrations in tuberculosis patients are related to each element role in immune system. Wherever the element is essential for the pathogenesis of bacteria, its concentration will remain low; and contrariwise, when the element is toxic for the bacteria, its level will be regulated up to provide a perfect condition for bacterial growth.

Prevalence of Salmonella spp. in Packed and Unpacked Red Meat and Chicken in South of Tehran.

BACKGROUND: Despite of the advances in infectious diseases prevention and food technology, food-borne diseases are considered major problems in developed and developing countries. Meat plays a key role in transferring zoonotic diseases to human. OBJECTIVES: This study was conducted in south of Tehran, Iran, to investigate the prevalence rate of Salmonella spp. in packed and unpacked red meat and chicken. MATERIALS AND METHODS: A total of 379 packed and unpacked samples including 189 red meat and 190 chicken samples were collected randomly. From each sample, 25 g was separated and treated with 225 mL of buffered peptone water, homogenized and incubated at 37°C for 24 hours. Samples were enriched using Rappaport-Vassiliadis broth and then streaked onto Hektoen enteric agar. RESULTS: Totally, 86 out of 190 chicken and 38 out of 189 red meat samples were contaminated with Salmonella spp. The most isolated serotypes were Salmonella thompson (67.7%), S. heaardt (6.5%), S. enteritidis (4.8%), and S. veyle (4%), respectively. In general, the rate of chicken contamination was higher than meat, as 43.3% of packed and 46% of unpacked chicken samples were contaminated. CONCLUSIONS: These results confirmed the pervious findings, stating that proper packaging of meat products can effectively decreases the rate of microbial contaminations.

Construction of recombinant bacmid containing m2e-ctxb and producing the fusion protein in insect cell lines.

BACKGROUND: Sequence variations in glycoproteins of influenza virus surface impel us to design new candidate vaccines yearly. Ectodomain of influenza M2 protein is a surface and highly conserved protein. M2e in influenza vaccines may eliminate the need for changing vaccine formulation every year. OBJECTIVES: In this study, a recombinant baculovirus containing M2e and cholera toxin subunit B fusion gene was generated with transposition process to express in large amounts in insect cell lines. MATERIALS AND METHODS: M2e-ctxB fusion gene was created and cloned into pFastBac HT. The recombinant vector was transformed into DH10Bac cells to introduce the fusion gene into the bacmid DNA via a site-specific transposition process. The recombinant bacmid was then extracted from white colonies and further analyzed using PCR, DNA sequence analyzing, and indirect immunofluorescence assay. RESULTS: PCR and DNA sequence analyzing results showed that the fusion gene was constructed as a single open reading frame and was successfully inserted into bacmid DNA. Moreover, indirect immunofluorescence results showed that the fusion gene was successfully expressed. CONCLUSIONS: Baculovirus expression vector system is valuable to produce M2e based influenza vaccines due to its simple utilization and ease of target gene manipulation. The expressed protein in such systems can improve the evaluating process of new vaccination strategies.