Recombinant YopJ induces apoptotic cell death in macrophages through TLR2

Bacterial species evolved evasive maneuvers to bypass their recognition by the receptors primarily TLRs of the innate immune cells. We have reported that 3 μg/ml of recombinant YopJ when provided extracellularly induced apoptosis in murine peritoneal macrophages in vitro. The present investigations demonstrate the role of TLR2 in apoptotic signals induced by rYopJ protein in murine peritoneal macrophages. The role of TLR2 in rYopJ induced macrophage apoptosis was shown by neutralization experiments and its co-immunoprecipitation with downstream molecule MyD88. The observed functional consequence of TLR2 neutralization were the inhibition of caspase-8 and caspase-3 activation, change in mitochondrial membrane potential (Δψm) and DNA fragmentation induced by rYopJ in macrophages. Further, rYopJ induced enhanced expression of IRAK-4, FADD, phosphorylation of IκB and p38 MAP kinase in macrophages. Pharmacological inhibitor of p38 MAP kinase and neutralization of TLR2 with neutralizing antibodies significantly inhibited the rYopJ induced caspases activation and DNA fragmentation, suggesting the possible involvement of TLR2 and p38 MAP kinase in rYopJ induced macrophages apoptosis.     

Clinicopathological Studies on Vitamin D(3) Toxicity and Therapeutic Evaluation of Aloe vera in Rats

A study was conducted to examine the clinical signs, hematological, biochemical and histopathological changes in vitamin D(3) toxicity at a dose rate 2 mg/kg b.wt. of vitamin D(3) and to assess the protective effect of Aloe vera in vitamin D(3) toxicity. The clinical signs observed were anorexia, progressive weight loss, difficulty in movement and respiration, diarrhea, epistaxis, subnormal body temperature and nervous signs before death. Mortality was observed in treated rats between day 10 and day 19 of treatment. The gross postmortem changes observed were severe emaciation, white chalky deposits on epicardial surface of heart, pin point white deposits on cortical surface of kidneys with pale yellow discoloration and diffused white deposits on serosal surface of stomach and intestine with bloody ingesta in lumen. The hematological changes included non-significant increase in hemoglobin and total leukocyte count and significant increase in relative neutrophil count. The biochemical changes observed were significant increase in plasma concentration of calcium, phosphorus and blood urea nitrogen, whereas a significant decrease in the concentration of albumin and total plasma protein was observed. The histopathological lesions included calcification of various organs, viz., tongue, stomach, intestines, kidney, heart, aorta, larynx, trachea, lungs, spleen, choroid plexus arteries of brain and vas deferens. The Aloe vera juice (2.5% in drinking water) has no protective effect on vitamin D(3) toxicity (2 mg/kg b.wt.).     

Diagnosis of optochiasmatic tuberculosis revealed by computed tomography and magnetic resonance imaging

A woman had a sudden painful decrease in vision in the left eye and then the right eye. Computed tomography and magnetic resonance imaging revealed a “ring” lesion in the right parietal lobe. Further testing and a past history of pulmonary tuberculosis led to a diagnosis of optochiasmatic tuberculosis. Antitubercular treatment led to dramatically improved vision and a radiologic resolution. Although rare, optochiasmatic tuberculosis should be considered in the differential diagnosis of nonspecific optic neuritis and optic nerve and chiasmal tumors.     

Utility of multidetector CT and virtual bronchoscopy in tracheobronchial obstruction in children

Purpose: The aim of this study was to evaluate the potential use of multidetector CT (MDCT) and virtual bronchoscopy (VB) in the evaluation of tracheobronchial patency in children with suspected bronchial obstruction and to compare its findings with fibreoptic/rigid bronchoscopy or surgery. Patients and methods: A total of 43 children (15 girls, 28 boys) with clinically suspected bronchial obstruction underwent contrast enhanced MDCT, using an age‐ and weight‐ adjusted low dose protocol. Post‐processing was performed and VB and multiplanar reformations (MPR) were obtained at the same sitting. Findings obtained at MDCT and VB were compared with fibreoptic/rigid bronchoscopy and surgery. Results: Obstructive pathology was found in 26 children, which included endoluminal foreign body, mucus plugs in 13 children, endobronchial tumour in three children and extrinsic compression (lymph node, aberrant Vessels, mediastinal cysts/tumours) of the tracheobronchial tree in 10 children. In 17 children, no obstructive lesion was identified. Excellent positive correlation was obtained, between MDCT‐VB and bronchoscopy/surgery, however, in one child with endobronchial obstruction caused by tracheitis, low dose MDCT‐VB was normal, but bronchoscopy revealed granularity and plaques. Conclusion: MDCT‐Virtual bronchoscopy is useful in evaluating bronchial stenosis and obstruction caused by both endoluminal pathology and external compression and has the advantage of looking beyond stenosis. Its main application lies in providing the exact location of suspected foreign body, prior to bronchoscopy. However, it fails to disclose exact nature of obstructing pathology.     

Studies on chemiluminescence and protein kinase-C activity of cisplatin treated mouse peritoneal exudate cells.

A single i.p. injection of cisplatin (10 mg/kg body weight) into mice results in a significant increase in chemiluminescence and ATP contents of the peritoneal exudate cells (PEC) than that of PEC from untreated mice. It is also observed that in vitro treatment of macrophages with cisplatin, rIFN-gamma and LPS show increased activity of the protein kinase-C (PK-C). The activation of PK-C could result in stimulation of NADPH-oxidase resulting in increased levels of chemiluminescence. Increased contents of ATP in PEC after cisplatin treatment also suggests that this activation is energy dependent.     

Heterogeneity of human serum high-density lipoprotein (HDL 2 )

A technique is described for the detection of free fatty acids, triglycerides, wax esters and cholesterol esters on thin-layer Chromatographic plates. The fatty acids present in each fraction can be recovered from the plates after detection and quantitatively measured by gas-liquid chiomatography. This procedure has been sucessfully applied to the analysis of skin surface lipids.     

Plasma cholesteryl esters turnover in man: comparison of in vivo and in vitro methods.

The rate of formation of plasma cholesteryl esters was determined by both in vivo and in vitro methods in 15 subjects. In vivo production of plasma cholesteryl esters was calculated from the specific activity slopes of plasma free and esterified cholesterol after an intravenous injection of [3H] mevalonic acid or [3H] cholesterol incorporated in plasma lipoproteins. In vitro production of cholesteryl esters was estimated by measuring lecithin:cholesterol acyltransferase activity in plasma. Lecithin:cholesterol acyltransferase was estimated by incubating the subjects' own plasma for 1 h at 37 degrees C. The plasma sample used for incubation was collected 2 h after the injection of radioactive precursor (when radioactivity of esterified cholesterol was very low relative to that in free cholesterol and the specific activity of free cholesterol in all of the major plasma lipoprotein classes was identical). The mean value for the production of plasma cholesteryl esters obtained by in vivo method was 126.2 +/- 41.9 mg/h, and it was not significantly different from the mean of 110.5 +/- 25.5 mg/h calculated from the results of in vitro method. The values obtained by the two methods in all 15 subjects had an excellent correlation (r = 0.93). It was found that in normotriglyceridemic subjects the values obtained by the two methods wwere essentially identical, but in hypertriglyceridemic subjects the values obtained by the in vitro method were consistently somewhat lower than the obtained by the in vivo method.     

Risk of hepatitis with various reintroduction regimens of anti-tubercular therapy: a systematic review and network meta-analysis

ABSTRACT

Objective: To compare risk of hepatotoxicity between various regimens for reintroduction of antitubercular therapy (ATT) in patients with previous episode of ATT hepatitis.

Methods: We searched various databases (PubMed, Embase, CENTRAL, Scopus, WoS and LILACS) for studies comparing ATT reintroduction regimens using terms ‘drug-induced liver injury’ and ‘antitubercular drugs’ AND ‘reintroduction’. The reintroduction regimens i.e concomitant (all drugs introduced together), sequential (reintroduction of one drug in full dose followed by another) or incremental (one drug in a low dose and then higher dose followed by next drug) were compared using Bayesian approach for network meta-analysis with random-effect model. Cochrane revised tool was used to assess risk of bias in included studies (RoB 2.0).

Results: Four randomized studies with 577 patients were eligible for analysis. Compared with concomitant regimen (baseline comparator), incremental regimen appeared to have lower risk of ATT hepatitis (odds ratio [OR] 0.24; 95% CrI 0.017, 1.2) as also the sequential regimen (OR 0.33; 95% CrI 0.033, 1.7). Rifampicin first and isoniazid first reintroduction regimens were similar via-a-vis recurrence of hepatotoxicity.

Conclusion: The sequential and incremental regimen may be better than concomitant regimen in reducing risk of ATT hepatitis although the odds did not achieve statistical significance.