A study to evaluate the hepatoprotective effect of N- acetylcysteine on anti tuberculosis drug induced hepatotoxicity and quality of life.

BACKGROUND: Drug induced liver injury (DILI) is a serious adverse effect caused by first-line anti-TB (ATT) drugs, limiting the TB-treatment. The tissue inflammation induced by free radical burst and poor dietary intake in TB induces oxidative stress, which was proposed as one of the mechanisms responsible for ATT induced DILI. N-acetylcysteine (NAC) exerts a hepato-protective effect by enhancing the cellular antioxidant defense mechanism. There are few studies evaluating the effect of NAC on ATT induced DILI in Indian-population. METHODS: This is a prospective, randomized, double-blind, placebo-controlled, parallel-group study. Thirty-eight newly diagnosed TB patients on first-line ATT with normal liver function test (LFT) were recruited and randomized to receive either NAC 600 mg tablet or placebo twice daily for 4 weeks and followed-up for next 4 weeks. LFT [AST, ALT, ALP and Total bilirubin] was assessed at baseline, 2, 4 and 8 weeks. Oxidative-stress biomarkers [Malondialdehyde (MDA), Nitric Oxide (NO), Glutathione (GSH)] and quality of life (QOL) by SF-36 questionnaire were assessed at baseline, 4 and 8 weeks. Adverse Drug Reactions (ADRs) were monitored at every visit. Compliance was assessed by pill-count method. RESULTS: Baseline characteristics were homogenous among both the groups. In the NAC group, there was significant reduction in ALT (p < 0.01), ALP (p < 0.01), total bilirubin (p < 0.001) at 4 weeks compared to baseline. AST, MDA and NO showed a reduction of 19%, 21.6% and 5.5% respectively from baseline and GSH at showed an increase of 2.6% from baseline at 4 weeks in the NAC group, however these were not statistically significant. These effects in LFT and oxidative biomarkers persisted even at the end of 8 weeks. Significant improvement from baseline in QOL was observed in both the groups (p < 0.05). Between group analysis showed, significant reduction in ALT (p < 0.05) and AST (p < 0.05) in NAC group at 4 weeks, whereas bilirubin, MDA, NO and GSH showed improvement at 4 weeks compared to placebo in NAC group, however it was not statistically significant. This improvement in the LFT and oxidative biomarkers continued even at the end of 8 weeks. Itching and rashes were the most common ADRs, with similar incidence in both the groups. Compliance to treatment was good in both the groups. CONCLUSION: Significant improvement in liver function parameters is suggestive of hepatoprotective effect of NAC. This observed effect at 4 weeks was found to be persistent at 8 weeks, which signifies prolonged hepato-protective effect of NAC. Long duration studies with large sample size are required for further confirmation of hepato-protective action of NAC.

Human Skin Allograft: Is it a Viable Option in Management of Burn Patients?

Tangential excision and autologous split-thickness skin grafting is the standard management of the burn wound, but autograft has limitation of donor-site availability and morbidity. Human skin allograft is an alternate option of wound coverage when autograft is not available. Various synthetic skin substitute dressings are now available in the market, and thus use of human skin allograft has decreased. This case report explores the role of human skin allograft in burn wound management. Allograft facilitates excision of burn wounds during acute phase of burn injury in pediatric patients. It is cost-effective, reduces pain and risk of infection, and avoids frequent dressing changes. Availability of allograft and risk of infection are the two main constraints in its regular use.

Innovative Skin Hook.

Skin hook is an important instrument for skin surgeries. There are situations, such as operating in a health camp or operating at a peripheral health center with a limited number of instruments, where skin hook is not available in the operation theater. We present an innovative design of skin hook, which can be prepared by surgeons in the operation theater with the help of readily available materials. The innovative skin hook is a simple, safe, and effective solution for performing skin surgeries in a limited-resource setup.

Innovative Use of Abdominoplasty Specimen.

Simulator training is important for understanding nipple-areolar complex reconstruction. Human tissue is the best tissue simulator for surgical training. Abdominoplasty specimen is a useful tissue simulator, which is suitable for practicing nipple-areolar complex reconstruction. It is similar to the natural mound created in breast reconstruction. Authors have shared their experience of using abdominoplasty specimen for simulator training of nipple-areolar complex reconstruction for plastic surgery residents. Abdominoplasty specimen is cost-effective, readily available, and an efficient tool for plastic surgery training for the residents.

In Staphylococcus aureus the regulation of pyruvate kinase activity by serine/threonine protein kinase favors biofilm formation.

Staphylococcus aureus, a natural inhabitant of nasopharyngeal tract, survives mainly as biofilms. Previously we have observed that S. aureus ATCC 12600 grown under anaerobic conditions exhibited high rate of biofilm formation and L-lactate dehydrogenase activity. Thus, the concentration of pyruvate plays a critical role in S. aureus, which is primarily catalyzed by pyruvate kinase (PK). Analyses of the PK gene sequence (JN645815) revealed presence of PknB site in PK gene indicating that phosphorylation may be influencing the functioning of PK. To establish this hypothesis the pure enzymes of S. aureus ATCC 12600 were obtained by expressing these genes in PK 1 and PV 1 (JN695616) clones and passing the cytosolic fractions through nickel metal chelate column. The molecular weights of pure recombinant PK and PknB are 63 and 73 kDa, respectively. The enzyme kinetics of pure PK showed K M of 0.69 ± 0.02 µM, while the K M of PknB for stpks (stpks = NLCNIPCSALLSSDITASVNCAK) substrate was 0.720 ± 0.08 mM and 0.380 ± 0.07 mM for autophosphorylation. The phosphorylated PK exhibited 40 % reduced activity (PK = 0.2 ± 0.015 µM NADH/min/ml to P-PK = 0.12 ± 0.01 µM NADH/min/ml). Elevated synthesis of pyruvate kinase was observed in S. aureus ATCC 12600 grown in anaerobic conditions suggesting that the formed pyruvate is more utilized in the synthesis phase, supporting increased rate of biofilm formation.

Vegetables' juice influences polyol pathway by multiple mechanisms in favour of reducing development of oxidative stress and resultant diabetic complications.

OBJECTIVE: Hyperglycemia induced generation of free radicals and consequent development of oxidative stress by polyol pathway is one of the crucial mechanisms stirring up development of diabetic complications. We evaluated influence of ten vegetables' juice on polyol pathway along with their antioxidant and antioxidative stress potentials. MATERIALS AND METHODS: Aldose reductase activity was determined utilising goat lens and human erythrocytes. In goat lens, utilization of nicotinamine adenine dinucleotide phosphate (NADPH) and aldose reductase inhibition was assayed. In human erythrocytes, sorbitol formation was measured as an index of aldose reductase activity under normoglycemic and hyperglycemic conditions. Ability of juices in inhibiting oxidative damage to deoxyribose sugar and calf thymus DNA and inhibitory activity against hydrogen peroxide induced hemolysis of erythrocytes was also analysed. Phytochemical contents like total polyphenol, total flavonoid and total protein were measured to find their influence on biological activities. RESULTS: Vegetables' juice displayed varying degrees of inhibitory potentials in mitigating NADPH dependent catalytic activity of aldose reductase in goat lens, accumulation of sorbitol in human erythrocytes under different glucose concentrations; Fenton-reaction induced oxidative damage to deoxyribose sugar, and calf thymus DNA. Substantial variations in vegetables phytochemicals content were also noticed in this study. CONCLUSIONS: Vegetables' juice possesses potent activities in influencing polyol pathway by various mechanisms in favour of reducing development of oxidative stress independent of their inherent antioxidative properties. Juice of ivy gourd followed by green cucumber and ridge gourd were among the most potent for they displayed strong activities on various parameters analysed in this study. These vegetables' juice may become part of mechanism-based complementary antioxidant therapy to prevent development of diabetic complications.

Membranous nephropathy superimposed on Churg-Strauss syndrome.

The association of membranous nephropathy with Churg-Strauss syndrome is not widely reported. We present a patient with myeloperioxidase-perinuclear antineutrophilic cytoplasmic antibody (MPO-pANCA)-positive necrotizing and crescentic glomerulonephritis who later developed membranous nephropathy.

Isolation and characterization of baculoviruses from three major lepidopteran pests in the semi-arid tropics of India.

Baculoviruses were isolated from three major lepidopteran pests, Helicoverpa armigera, Spodoptera litura and Amsacta albistriga in the semi-arid tropics during natural epizootic conditions at ICRISAT fields, Patancheru, Andhra Pradesh, India. Biological, morphological and biochemical analysis identified these isolates as Nucleopolyhedroviruses (NPVs). Scanning electron microscopy of the occlusion bodies (OBs) purified from diseased larvae revealed polyhedral particles of size approximately 0.5-2.5 µm [Helicoverpa armigera Nucleopolyhedrovirus (HearNPV)], 0.9-2.92 µm [Spodoptera litura Nucleopolyhedrovirus (SpltNPV)] and 1.0-2.0 µm [Amsacta albistriga Nucleopolyhedrovirus (AmalNPV)] in diameter. Transmission electron microscopy of thin sections of OBs of the three isolates revealed up to 5-8 multiple bacilliform shaped particles packaged within a single viral envelope. The dimensions of these particles were 277.7 × 41.6 nm for HearNPV, 285.7 × 34.2 nm for SpltNPV and 228.5 × 22.8 nm for AmalNPV. Each of HearNPV and AmalNPV contained up to 6 nucleocapsids and SpltNPV contained up to 7 nucleocapsids per envelope. The estimated molecular weights of the purified OB (polyhedrin) protein of the three NPVs were 31.29-31.67 kDa. Virus yield (OBs/larva) was 5.18 ± 0.45 × 10(9) for HearNPV, 5.73 ± 0.17 × 10(9) for SpltNPV and 7.90 ± 0.54 × 10(9) for AmalNPV. The LC50 values of various NPVs against 2nd and 3rd instar larvae indicated 2.30 × 10(4) and 1.5 × 10(5) OBs/ml for HearNPV, 3.5 × 10(4) and 2.4 × 10(5) OBs/ml for SpltNPV and 5.6 × 10(4) and 3.96 × 10(5) OBs/ml for AmalNPV. The lethal time required to cause 50% mortality (LT50) for these three species were also defined. This study has shown that the NPVs infecting three major lepidopteran pests in India are multiple NPVs, and they have good potential to use as biocontrol agents against these important pests.

A clinical trial of the efficacy and safety of montelukast as monotherapy in patients with chronic stable bronchial asthma.

This study is aimed to evaluate the efficacy and safety of montelukast, as monotherapy, in the treatment of chronic stable bronchial asthma in adults. This was a multicentre, open label, non-comparative, prospective, 4-week study. Eligible patients discontinued all anti-inflammatory medication (steroids, chromoglycate sodium) 2 weeks prior to starting therapy with montelukast (10 mg daily). The primary efficacy criteria were improvements in forced expiratory volume in one second (FEV1), peak exploratory flow rate (PEFR) after 4 weeks of therapy. Secondary efficacy criteria were improvement in the patients' symptoms (assessed on an ordinal scale), decrease in discomfort levels (scored on a scale of 0-100), change in peripheral eosinophil counts, decrease in total daily dose of inhaled beta2 agonist (salbutamol). A total of 148 patients, mean age (+/- SD) 40.21 +/- 13.70 years, were enrolled into the study. At the end of the study there were significant improvements in FEV1 and PEFR (29% and 28% increase respectively from baseline values, p<0.000001). The mean total daily dose of inhaled salbutamol decreased significantly from prestudy values of 461 +/- 332 microg/day to 161 +/- 207 microg/day (p<0.000001). The mean eosinophil counts fell from 5.80 +/- 4.90% (+/- SD) to 4.84 +/- 4.42% (+/- SD) (p=0.02). Symptom scores improved significantly as did subjective assessment of discomfort. A total of 29 (19.6%) adverse events were reported, all of which were of mild to moderate intensity. Monotherapy with montelukast significantly improved parameters of asthma control. It was well tolerated with no reports of serious or severe adverse events.