Risk Factors for MDR and XDR-TB in a Tertiary Referral Hospital in India

Background

India has a high burden of drug resistant TB, although there are few data on XDR-TB. Although XDR-TB has existed previously in India, the definition has not been widely applied, and surveillance using second line drug susceptibility testing has not been performed. Our objective was to analyze clinical and demographic risk factors associated with isolation of MDR and XDR TB as compared to susceptible controls, at a tertiary center.

Methodology/Findings

Retrospective chart review based on positive cultures isolated in a high volume mycobacteriology laboratory between 2002 and 2007. 47 XDR, 30 MDR and 117 susceptible controls were examined. Drug resistant cases were less likely to be extrapulmonary, and had received more previous treatment regimens. Significant risk factors for XDR-TB included residence outside the local state (OR 7.43, 3.07-18.0) and care costs subsidized (OR 0.23, 0.097-0.54) in bivariate analysis and previous use of a fluoroquinolone and injectable agent (other than streptomycin) (OR 7.00, 95% C.I. 1.14-43.03) and an initial treatment regimen which did not follow national guidelines (OR 5.68, 1.24-25.96) in multivariate analysis. Cavitation and HIV did not influence drug resistance.

Conclusions/Significance

There is significant selection bias in the sample available. Selection pressure from previous treatment and an inadequate initial regimen increases risk of drug resistance. Local patients and those requiring financial subsidies may be at lower risk of XDR-TB.     

Personal experience with obstetric care of diabetic pregnant women]

The authors, basing in the survey of literature and on own experience, discuss pregnancy in diabetic patients together with possible complications. Pregnancy exerts an unfavourable effect on diabetes mellitus with significant vascular disorders being in some cases even life-threatening. An of clinical status of the diabetes mellitus should be always carefully assessed in every diabetic woman to avoid serious complications, which may occur later-during possible pregnancy. Date of pregnancy termination in every pregnant diabetic with vascular disorders should depend on not only on status of fetus but also of the mother. A chance of getting pregnant in case of diabetic women depends on the advancement of the disease. Persisting vascular and systemic disorders seen in diabetic mellitus are contraindications for pregnancy.     

Surface antigenic profiling of stem cells from human omentum fat in comparison with subcutaneous fat and bone marrow

Omentum fat derived stem cells have emerged as an alternative and accessible therapeutic tool in recent years in contrast to the existing persuasive sources of stem cells, bone marrow and subcutaneous adipose tissue. However, there has been a scanty citation on human omentum fat derived stem cells. Furthermore, identification of specific cell surface markers among aforesaid sources is still controversial. In lieu of this existing perplexity, the current research work aims at signifying omentum fat as a ground-breaking source of stem cells by surface antigenic profiling of stem cell population. In this study, we examined and compared the profiling of cell surface antigenic expressions of hematopoietic stem cells, mesenchymal stem cells, cell adhesion molecules and other unique markers such as ABCG2, ALDH and CD 117 in whole cell population of human omentum fat, subcutaneous fat and bone marrow. The phenotypic characterization through flowcytometry revealed the positive expressions of CD 34, CD 45, CD 133, HLADR, CD 90, CD 105, CD 73, CD 29, CD 13, CD 44, CD 54, CD 31, ALDH and CD 117 in all sources. The similarities between the phenotypic expressions of omentum fat derived stem cells to that of subcutaneous fat and bone marrow substantiates that identification of ultimate source for curative therapeutics is arduous to assess. Nevertheless, these results support the potential therapeutic application of omentum fat derived stem cells.

Electronic supplementary material

The online version of this article (doi:10.1007/s10616-012-9427-4) contains supplementary material, which is available to authorized users.     

Modeling of phosphomethyl pyrimidine kinase from Leptospira interrogans serovar lai strain 56601

Many microorganisms, as well as plants and fungi, synthesize thiamin, but vertebrates do not produce it. Phosphomethyl pyrimidine kinase is an enzyme involved in an intermediary step of thiamin biosynthesis from purine molecules. This enzyme is absent in humans. Thus, it is a potential chemotherapeutic target for antileptospiral treatment. Structure of this enzyme from Leptospira interrogans serovar lai strain 56601 has not yet been elucidated. We used the structural template of phosphomethyl pyrimidine kinase from Thermus thermophilus HB8 for modeling the phosphomethyl pyrimidine kinase structure from Leptospira interrogans serovar lai strain 56601 . The model is deposited in Protein Data Bank (PDB ID: 2G53) at RCSB. Thus, we analyse and propose the usefulness of the modeled phosphomethyl pyrimidine kinase for the design of suitable inhibitors towards the treatment of leptospirosis.     

Impaired overload-induced hypertrophy is associated with diminished mTOR signaling in insulin-resistant skeletal muscle of the obese Zucker rat

Recent data have suggested that insulin resistance may be associated with a diminished ability of skeletal muscle to undergo hypertrophy (Paturi S, Gutta AK, Kakarla SK, Katta A, Arnold EC, Wu M, Rice KM, Blough ER. J Appl Physiol 108: 7-13, 2010). Here we examine the effects of insulin resistance using the obese Zucker (OZ) rat with increased muscle loading on the regulation of the mammalian target of rapamycin (mTOR) and its downstream signaling intermediates 70-kDa ribosomal protein S6 kinase (p70S6k), ribosomal protein S6 (rpS6), eukaryotic elongation factor 2 (eEF2), and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Compared with that observed in lean Zucker (LZ) rats, the degree of soleus muscle hypertrophy as assessed by changes in muscle wet weight (LZ: 35% vs. OZ: 16%) was significantly less in the OZ rats after 3 wk of muscle overload (P < 0.05). This diminished growth in the OZ rats was accompanied by significant impairments in the ability of the soleus to undergo phosphorylation of mTOR (Ser(2448)), p70S6k (Thr(389)), rpS6 (Ser(235/236)), and protein kinase B (Akt) (Ser(473) and Thr(308)) (P < 0.05). Taken together, these data suggest that impaired overload-induced hypertrophy in insulin-resistant skeletal muscle may be related to decreases in the ability of the muscle to undergo mTOR-related signaling.     

Evolution of protein kinase signaling from yeast to man

Protein phosphorylation controls many cellular processes, especially those involved in intercellular communication and coordination of complex functions. To explore the evolution of protein phosphorylation, we compared the protein kinase complements ('kinomes') of budding yeast, worm and fly, with known human kinases. We classify kinases into putative orthologous groups with conserved functions and discuss kinase families and pathways that are unique, expanded or lost in each lineage. Fly and human share several kinase families involved in immunity, neurobiology, cell cycle and morphogenesis that are absent from worm, suggesting that these functions might have evolved after the divergence of nematodes from the main metazoan lineage.     

Structural diversity of sequentially identical subsequences of proteins: Identical octapeptides can have different conformations

One of the most important questions in the protein folding problem is whether secondary structures are formed entirely by local interactions. One way to answer this question is to compare identical subsequences of proteins to see if they have identical structures. Such an exercise would also reveal a lower limit on the number of amino acids needed to form unique secondary structures. In this context, we have searched the April 1996 release of the Protein Data Bank for sequentially identical subsequences of proteins and compared their structures. We find that identical octamers can have different conformations. In addition, there are several examples of identical heptamers with different conformations, and the number of identical hexamers with different conformations has increased since the previous PDB releases. These observations imply that secondary structure can be formed entirely by non-local interactions and that an identical match of up to eight amino acids may not imply structural similarity. In addition to the larger context of the protein folding problem, these observations have implications for protein structure prediction methods. Proteins 30:228–231, 1998. © 1998 Wiley-Liss, Inc.     

Informatics issues in large‐scale sequence analysis: Elucidating the protein kinases of C. elegans

With the availability of the nearly complete genomic sequence of C. elegans, the first multicellular organism to be sequenced, molecular biology has definitely entered the postgenomic era. Annotation of the genomic sequence, which refers to identifying the genes and other biologically relevant sections of the genome, is an important and nontrivial next step. A first‐pass annotation will be necessarily incomplete but will drive further biological experiments, which in turn will help to annotate the genome better. Given the scale of the genome sequence analysis, it is clear that the annotation should be automated as much as possible without sacrificing the quality of analysis. In this work, we outline our approach to identifying the protein kinases of C. elegans from the genomic sequence. We describe new tools we have developed for analysis, management and visualization of genomic data. By developing modular and scalable solutions, this study has provided a framework for future analysis of the Drosophila and human genomes. J. Cell. Biochem. 80:181–186, 2000. © 2000 Wiley‐Liss, Inc.