Prevalence of methicillin resistant Staphylococcus aureus in a tertiary referral hospital in eastern Uttar Pradesh

We report the prevalence of methicillin resistant Staphylococcus aureus (MRSA) infections and their antibiotic susceptibility pattern in our hospital located in eastern Uttar Pradesh. Out of total 549 strains of Staphylococcus aureus isolated from different clinical specimens 301 (54.85%) were found to be methicillin resistant. More than 80% of MRSA were found to be resistant to penicillin, cotrimoxazole, ciprofloxacin, gentamicin, erythromycin, tetracycline, 60.5% to amikacin and 47.5% to netilmicin. However, no strains were resistant to vancomycin. Many MRSA strains (32.0%) were multi-drug resistant. To reduce the prevalence of MRSA, the regular surveillance of hospital associated infection, monitoring of antibiotic sensitivity pattern and formulation of definite antibiotic policy may be helpful.     

Induction of sister chromatid exchanges by cypermethrin and carbosulfan in bone marrow cells of mice in vivo

The public health effects of pesticides cannot be denied. However, the undesired effects of chemical pesticides have been recognized as a serious public health concern during the past decades. The present study describes the genotoxic effects of two pesticides, namely cypermethrin and carbosulfan, in a murine test system in vivo. The test parameter used was analysis of sister chromatid exchanges (SCE) in bone marrow cells. Both cypermethrin (5, 10 and 20 mg/kg) and carbosulfan (1.25, 2.5 and 5 mg/kg) induced significant increases in the frequency of SCEs (P < 0.001). However, no significant dose-response correlation could be found for either of the pesticides. Carbosulfan induced a cell cycle delay, as evidenced by an increase in average generation time accompanied by accumulation of cells in the first division cycle, but cypermethrin did not induce any such response. The present study indicates that carbosulfan has a higher potential to cause genetic alterations than cypermethrin in mice and may also pose a mutagenic risk to human beings.     

The cytoplasmic domain of tissue factor in macrophages augments cutaneous delayed-type hypersensitivity

In addition to its procoagulant role, tissue factor (TF) has important coagulation-independent roles, including in inflammation. The cytoplasmic domain of TF has been implicated in some of these coagulation-independent roles, particularly cell signaling. To assess the contribution of the cytoplasmic domain of TF to cell-mediated adaptive immunity, the development of cutaneous delayed-type hypersensitivity (DTH) was studied in mice lacking the cytoplasmic domain of TF (TF(deltaCT/deltaCT) mice). DTH responses in sensitized mice were significantly attenuated in TF(deltaCT/deltaCT) mice, and leukocyte-endothelial cell interactions, assessed by intravital microscopy, were impaired significantly. Studies in chimeric mice, created by bone marrow transplantation, showed that the absence of the cytoplasmic domain of TF in leukocytes rather than endothelial cells was responsible for reduced DTH and leukocyte recruitment. DTH responses to OVA could be induced in wild-type mice but not in TF(deltaCT/deltaCT) mice by transfer of activated CD4(+) OVA-specific TCR transgenic T cells, demonstrating that the defective DTH response in TF(deltaCT/deltaCT) mice was independent of any defect in T cell activation. Macrophage and neutrophil accumulation and expression of TNF-alpha mRNA and phospho-p38-MAPK were reduced significantly in TF(deltaCT/deltaCT) mice, and their macrophages had reduced P-selectin-binding capacity and reduced in vivo emigration in response to MCP-1. These results indicate that leukocyte expression of the cytoplasmic domain of TF contributes to antigen-specific cellular adaptive immune responses via effects on leukocyte recruitment and activation.     

Plasmodium falciparum signal peptidase is regulated by phosphorylation and required for intra-erythrocytic growth

The human malaria parasite Plasmodium falciparum exports a variety of its proteins through its endoplasmic reticulum (ER) based secretory pathway in order to survive in the host erythrocyte. Signal peptidases are membrane-bound endopeptidases and have an important role in the transport and maturation of these parasite proteins. Prokaryotic signal peptidases are indispensable enzymes required for the removal of N-terminal signal peptide from the secretory proteins. Eukaryotic signal peptidases exist as multimeric protein complex in the ER and the catalytic subunit of this complex catalyzes removal of the N-terminal signal peptide from preproteins. All the signal peptidases contain five regions of high-sequence similarity referred to as boxes A-E. Here we report characterization of the catalytic subunit of signal peptidase complex (SPC) from P. falciparum. This protein designated as PfSP21 shows homology with the similar subunit from other sources and contains all the conserved boxes A-E. PfSP21 is able to cleave the peptide substrate containing the signal peptidase cleavage site. PfSP21 is phosphorylated by protein kinase C and its enzyme activity was upregulated after this phosphorylation. Immunofluorescence assay studies revealed that PfSP21 is localized in the ER of P. falciparum. PfSP21 dsRNA specifically inhibits the growth of P. falciparum in culture and this inhibition is most likely due to the decrease in the amount of endogenous PfSP21 protein. These studies demonstrate the characterization of a functional subunit of SPC from P. falciparum and should make an important contribution in our better understanding of the complex process of protein translocation in the parasite.     

Prognostic significance of micropapillary pattern in pure mucinous carcinoma of the breast

Breast carcinoma with micropapillary architecture is associated with aggressive behavior. Similar micropapillary pattern in pure mucinous carcinoma has been noticed and has been shown to convey poor prognosis. In this study 17 cases of pure mucinous carcinoma of the breast seen during a 10-year period have been reviewed, with special reference to micropapillary pattern. Diffuse micropapillary pattern was seen in 6 of 17 cases of mucinous carcinoma of the breast and demonstrated reverse polarity immunostaining pattern with "Epithelial Membrane Antigen." In all cases, the tumor cells showed grade I morphology, and no lymph node metastases were noticed. All the tumors except 1 expressed strong estrogen and progesterone receptor expression, however, all the cases were negative for Her-2/neu expression. In this present study, mucinous carcinomas with micropapillary pattern showed a low nuclear grade, higher incidence of hormone receptor positivity, and lower incidence of Her-2/neu similar to mucinous carcinomas without micropapillary pattern, thus explaining their indolent behavior.     

Comparable fMRI activity with differential behavioural performance on mental rotation and overt verbal fluency tasks in healthy men and women

To explicate the neural correlates of sex differences in visuospatial and verbal fluency tasks, we examined behavioural performance and blood-oxygenation-level-dependent (BOLD) regional brain activity, using functional magnetic resonance imaging, during a three-dimensional (3D) mental rotation task and a compressed sequence overt verbal fluency task in a group of healthy men (n=9) and women (n=10; tested during the low-oestrogen phase of the menstrual cycle). Men outperformed women on the mental rotation task, and women outperformed men on the verbal fluency task. For the mental rotation task, men and women activated areas in the right superior parietal lobe and the bilateral middle occipital gyrus in association with the rotation condition. In addition, men activated the left middle temporal gyrus and the right angular gyrus. For verbal fluency, men activated areas in the bilateral superior frontal gyrus, right cingulate gyrus, left precentral gyrus, left medial frontal gyrus, left inferior frontal gyrus, thalamus, left parahippocampal gyrus and bilateral lingual gyrus, and women activated areas in the bilateral inferior frontal gyrus and left caudate. Despite observing task related activation in the hypothesised areas in men and women, no areas significantly differentiated the two sexes. Our results demonstrate comparable brain activation in men and women in association with mental rotation and verbal fluency function with differential performance, and provide support for sex differences in brain–behaviour relationships.     

Structural evaluation of radially expandable cardiovascular stents encased in a polyurethane film

A method of encasing cardiovascular stents with an expandable polyurethane coating has been developed to provide a smooth homogeneous inner wall allowing for a confluent growth of endothelial cells. In this design, the metal wire stent structure is completely covered by the polyurethane film, minimizing biocorrosion of the metal (stainless steel or nitinol), and providing a homogeneous surface for surface treatment and incorporation of various eluting drugs to prevent platelet aggregation while supporting endothelialization. The polyurethane surface was treated with a helium plasma for sterilization and promotes growth of cells. The article details the performance of the coated film to expand with the metal stent up to 225% during deployment. Stress/strain behavior of polyurethane films, subsequent plasma treatment of the surface, and the adhesion of the coating to the stent structure upon expansion are presented. A film of less than 25 microm was found to be sufficient for corrosion resistance and flexibility without producing any excess stress on the stent structure. Straining the film to 225% and plasma modification did not affect the mechanical and surface properties, but allowed for improved biocompatibility as determined by the critical surface tension, surface chemistry, and roughness.     

Regulation of calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1): review

The response of living cells to change in cell environment depends on the action of second messenger molecules. The two second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interaction between cAMP and Ca2+ second messenger systems. Some PDE1 isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. Accumulating evidence suggests that the activity of PDE1 is selectively regulated by cross-talk between Ca2+ and cAMP signalling pathways. These isozymes are also further distinguished by various pharmacological agents. We have demonstrated a potentially novel regulation of PDE1 by calpain. This study suggests that limited proteolysis by calpain could be an alternative mechanism for the activation of PDE1. We have also shown PDE1 activity, expression and effect of calpain in the rat model in vitro of cardiac ischemia-reperfusion.