IntroductionDespite the development and wide implementation of Directly Observed Therapy Strategies (DOTS), multidrug-resistant tuberculosis (MDR-TB) remains a serious global health threat. In this study, the role of host immune response in patients with MDR-TB is investigated and compared with that of patients with smear-positive drug-sensitive tuberculosis (SP-TB).Material and methods27 patients with SP-TB, 20 patients with MDR-TB, and 20 healthy controls were included in the study. Immune parameters were determined by flow cytometry using monoclonal antibodies in order to compare the percentage values of these markers in the two study groups and the control group.ResultsThe levels of lymphocyte subgroups in the gate of CD45(+)/CD14(–) lymphocyte: CD45(+), CD3(+), CD4(+), NK, CD3/HLA-DR, CD 95(+) cells were significantly lower; by contrast CD23(+), CD25(+), CD19(+), CD4(+)/CD8(+), HLA-DR cells were found to be lower, but not significantly so in patients with MDR-TB, compared to levels in patients in the SP-TB and control groups. Besides these findings, the levels of NKT cells and γδ TCR(+) cells were significantly higher in the MDR-TB than in the healthy control and SP-TB group.ConclusionsThe lower levels of CD3/ HLA-DR, CD4 (+), Fas (+), and NK, and the higher level of NKT together with γδ T cells in patients with MDR-TB compared to those in SP-TB may indicate a profound immune suppression in MDR-TB patients and thereby may denote an accumulation in the bacterial load. Our findings may shed light on the pathogenesis and prognosis of MDR tuberculosis, and may point towards the use of flow cytometry findings as an aid to early diagnosis in MDR-TB patients.

Morinda elliptica L. (Rubiaceae) is a phytomedicinal herb, used to treat gastrointestinal complications in Peninsular Malaysia. The study evaluates the in vivo hepatoprotective activity of ethanolic extract of M. elliptica stem in thioacetamide (TAA) induced liver fibrosis in male Sprague Drawly rats. Thirty adult rats were divided into five groups of six rats each. Rats of the normal control group received intraperitoneal injections (i. p.) of vehicle 10% Tween-20, 5 ml/kg, and hepatotoxic group 200 mg/kg TAA three times per week respectively. Three supplementary groups were treated with TAA plus daily oral silymarin (50 mg/kg) or M. elliptica (250 or 500 mg/kg). After 8 weeks of treatment, all rats were sacrificed. Liver fibrosis was assessed by gross macroscopic and microscopic tissue analysis, histopathological, and biochemical analysis. The livers of the TAA treated group showed uniform coarse granules, hepatocytic necrosis with lymphocytes infiltration. Contrary, the livers of M. elliptica treated groups (250 and 500 mg/kg) were much smoother and the cell damage was much lesser. The livers of M. elliptica treated groups rats showed elevated activity of SOD and CAT with a significant decrease in MDA level at p < .0001. The level of liver damage parameters, that is, ALP, ALT, and AST, bilirubin, total protein, and albumin were restored to the normal comparable to silymarin. M. elliptica stem extract significantly promoted normal rat liver architecture with significant perfections in biochemical parameters. The molecular contents of M. elliptica with hepatoprotective influence could be discovered, is the future prospective of this study.

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In the context of searching for anticancer compounds in natural products, snake venom is one of the important sources for peptide/ protein based bioactive molecules. Proteins and peptides with anticancer activity were purified and identified from snake venoms. The aim of the present study was to determine the in vitro cytotoxicity of Macrovipera lebetina obtusa (Blunt-Nosed Viper) crude venom from southeastern Anatolia against K562 human chronic myelogenous leukemia (CML) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Adenosine tripohsphate (ATP) assays. Additionally, the apoptosis induction was assessed by morphological evaluation and immunohistochemical analysis for activated caspase-3. For histopahtological evaluation, haematoxylineosin, giemsa and papanicolau stains were used in combination. M. l. obtusa venom showed dose-dependent toxicity against K562 cells after 72 h treatment with different concentrations of crude venom. IC50 values were 0.45 and 0.37 µg/mL for MTT and ATP assays, respectively. Nuclear fragmentation and condensation, apoptotic bodies and activation of caspase-3, as an induction of apoptosis were also observed in K562 cells. Since apoptosis-inducing compounds are important for the treatment of cancer, further studies on Anatolian M. l. obtusa venom could result in the purification and identification of new proteins and peptides, which might have therapeutic value for the treatment of CML. Keywords: Anticancer, Apoptosis, Blunt-nosed viper, Macrovipera lebetina obtusa, Snake venom ÖZET Anadolu'da Yayılış Gösteren Macrovipera lebetina obtusa (Dwigubski, 1832) Zehrinin K562 İnsan Kronik Myeloid Lösemi Hücreleri Üzerinde in vitro Sitotoksik ve Apoptotik Aktiviteleri Doğal ürünlerde antikanser bileşiklerin araştırılması kapsamındaki çalışmalarda kullanılan önemli biyoaktif peptit/protein kaynaklarından biri de yılan zehridir. Yılan zehirlerinden antikanser etkili protein ve peptitler saflaştırılmış ve tanımlanmıştır. Bu çalışmanın amacı, güneydoğu Anadolu bölgesinde bulunan Macrovipera lebetina obtusa (Koca Engerek) ham zehrinin K562 insan kronik myeloid lösemi (KML) hücreleri üzerinde in vitro sitotokik etkisinin 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) ve Adenosine tripohsphate (ATP) testleri ile belirlenmesidir. Ek olarak, morfolojik değerlendirme ve aktif kaspaz-3 immünohistokimyasal analizi ile zehrin apoptotik etkisi de değerlendirilmiştir. Histopatolojik değerlendirme için hematoksilen-eozin, gimza ve papanikolau boyaları kullanılmıştır. M. l. obtusa zehrinin farklı konsantrasyonlarıyla 72 saatlik inkübasyon sonucunda K562 hücrelerine karşı doza bağlı toksisite görülmüştür. IC50 değerleri MTT ve ATP testleriyle sırasıyla 0.45 and 0.37 µg/mL olarak hesaplanmıştır. Ayrıca apoptoz uyarımının göstergeleri olarak nükleer fragmentasyon ve yoğunlaşma, apoptotik veziküller ve kaspaz-3 aktivasyonu gözlenmiştir. Apoptoza neden olan bileşiklerin kanser tedavisinde önemli bir yeri olması göz önünde bulundurulduğunda, Anadolu'da bulu...

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