Nitrosative stress and cytokines are linked with the severity of sepsis and organ dysfunction.

OBJECTIVE: An imbalance in oxidant-antioxidant status may impact the severity of sepsis. We hypothesised links between nitrosative stress and pro-inflammatory cytokines and their correlation with the severity of sepsis and associated organ dysfunction. METHODS: The hypothesis was tested in 110 patients with sepsis (in whom a disease severity score (APACHE II) and assessment of organ failure score (SOFA) were determined) and 55 healthy volunteers. Neutrophil inducible nitric oxide synthase (iNOS) expressions at mRNA and protein levels were estimated by real-time PCR and immuno-precipitation followed by Western blotting, respectively. Nitric oxide (NO) content was assessed in neutrophils by confocal microscopy, plasma nitrite by the Griess reaction and inflammatory cytokines (TNF-α, IFN-γ and IL-8) by ELISA (in plasma) and real-time PCR (in neutrophils). Serum bilirubin and creatinine were determined by routine methods and lung function by the PaO2/FiO2 ratio. RESULTS: Increased neutrophil iNOS expression and NO content, plasma total nitrite content and pro-inflammatory cytokines were present in sepsis patients (all P < 0.001). Plasma nitrite correlated with cytokines, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.63-0.85, P < 0.001). Cytokines correlated with nitrite, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.35-0.85, P < 0.001). CONCLUSION: Neutrophils iNOS expression, NO content, plasma nitrite and cytokines have a role in the assessment of the severity of sepsis and organ toxicity.

Land-use and land-cover change in Western Ghats of India.

The Western Ghats (WG) of India, one of the hottest biodiversity hotspots in the world, has witnessed major land-use and land-cover (LULC) change in recent times. The present research was aimed at studying the patterns of LULC change in WG during 1985-1995-2005, understanding the major drivers that caused such change, and projecting the future (2025) spatial distribution of forest using coupled logistic regression and Markov model. The International Geosphere Biosphere Program (IGBP) classification scheme was mainly followed in LULC characterization and change analysis. The single-step Markov model was used to project the forest demand. The spatial allocation of such forest demand was based on the predicted probabilities derived through logistic regression model. The R statistical package was used to set the allocation rules. The projection model was selected based on Akaike information criterion (AIC) and area under receiver operating characteristic (ROC) curve. The actual and projected areas of forest in 2005 were compared before making projection for 2025. It was observed that forest degradation has reduced from 1985-1995 to 1995-2005. The study obtained important insights about the drivers and their impacts on LULC simulations. To the best of our knowledge, this is the first attempt where projection of future state of forest in entire WG is made based on decadal LULC and socio-economic datasets at the Taluka (sub-district) level.

Anesthetic Management of a Patient with Myasthenia Gravis for Meningioma Surgery - A Case Report.

Myasthenia gravis is a disease of great challenge to the anesthesiologist, because it affects the neuromuscular junction. Anesthetic management involves either muscle relaxant or non-muscle relaxant techniques. This case report documents the safe use of fentanyl, propofol and sevoflurane combination guided by bispectral index, without the use of muscle relaxants in a patient with myasthenia gravis who presented for meningioma surgery.

Clinical evaluation of Deep Anterior Lamellar Keratoplasty (DALK) for stromal corneal opacities.

BACKGROUND: Corneal scars are commonly formed following many diseases of the eye like trauma, inflammation and infections. They lead to permanent diminution of vision which can be managed by Penetrating Keratoplasty (PK). PK is removing diseased as well as healthy tissues and is associated with many post-operative complications. Deep Anterior Lamellar Keratoplasty (DALK) is a relatively newer procedure which replaces only the diseased stroma, leaving the original corneal endothelium intact. This procedure is associated with lesser incidence of post-operative complications. METHODS: The study was conducted at a large tertiary care centre. 10 patients with stromal corneal scars were subjected to DALK and results were analysed after 06 months. Poor quality donor corneal tissue of B- and C grade was used in all cases. RESULTS: 7 out of 10 patients (70%) undergoing DALK had post-operative visual acuity of 6/24 or better. 03 patients who did not have adequate recovery of visual acuity were due to over-riding of the graft in 01 case (10%), fungal keratitis in 01 case (10%) and interface haze in 01 case (10%). CONCLUSION: DALK is a promising new technique for management of superficial corneal stromal scars using poor quality donor corneal tissue. Initial results are encouraging with minimal complications.

Management of Psoriatic Erythroderma with Ayurvedic herbomineral preparations: A case report.

Psoriatic Erythroderma (PsE) is a presentation of Erythroderma due to a history of psoriasis showing inflammation and exfoliation of epidermal skin characterized by erythema and scaling. There is no definite treatment in contemporary medical science but the principle-based Ayurvedic approach has been proved to be effective. We present a case of PsE treated for 3 months with Ayurvedic herbomineral preparations and dietary restrictions for non-vegetarian and dairy items. As per the Ayurvedic diagnostic view, the presented case is correlated with Audumbara Kushtha and Ekakushtha due to their intricate features. Thus, Ayurvedic approaches were directed to eliminate vitiated doshas responsible for acute exacerbation of Kushtha (∼dermatitis) and to maintain equilibrium among them. The patient was initially considered as a case of Saam stage of Kushtha with Pitta-Rakta-Vata predominance. Thus, management was planned into different domains-treatment of Saam stage of Kushtha, Vyadhipratyanika chikitsa (∼disease antagonistic treatment), Rasayana intervention (∼Immunomodulation therapy) and Ayurvedic drugs were given accordingly. The assessment was done based on subjective parameters and PASI score. The patient was followed for about one and half year without any complication and relapse. This case study shows PsE can be managed with an Ayurvedic approach and proper diet planning.

Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis.

BACKGROUND: Recent reports from this lab have demonstrated a higher incidence of NETs, nitrosative, as well as oxidative stress, and have a direct correlation with the severity of sepsis and organ damage. However, the mechanistic perspective of NETs induced organ damage has not been understood at the cellular and molecular level. Interaction of inducible nitric oxide synthase (iNOS) with Rac2 in regulating reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and its implications in microbial killing has been reported. This study was, therefore, undertaken in neutrophils of sepsis patients to investigate the functional importance of iNOS-Rac2 interaction in ROS/ RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death. METHODS: The study was conducted on 100 patients with sepsis and 50 healthy volunteers. Interaction between iNOS and Rac2 was performed using co-immunoprecipitation and co-immunolabeling assay. Free radicals involving ROS and RNS were evaluated using cytochrome c reduction assay. NETs formation was evaluated by fluorescence microscopy. The cytotoxic effect of NETs was assessed on lung carcinoma cell line (A549) using colorimetric Alamar blue assay. RESULTS: Enhanced interaction between iNOS and Rac2 was found in sepsis neutrophils in comparison with control. This was accompanied by an increased level of superoxide (O2.-), nitric oxide (NO), and peroxynitrite (ONOO-) which were decreased in the presence of NAC, DPI, and 1400 W, signifying the role of iNOS-Rac2 interaction. Enhanced NETs release from activated sepsis neutrophils were abrogated in the presence of DPI. NETs from sepsis neutrophils exert a cytotoxic effect on lung epithelial cells (A549) in a concentration-dependent manner. CONCLUSION: Our findings exhibit the functional role of iNOS-Rac2 interaction in ROS/RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death.

A novel method to identify and correct asymmetry of dumbbells in a multi-cell elliptical superconducting cavity.

Raja Ramanna Centre for Advanced Technology (RRCAT) has an ongoing program to develop 650 MHz, 5-cell elliptical superconducting RF (SCRF) cavities under the Indian Institutes and Fermilab Collaboration. The elliptical multi-cell SCRF cavity fabrication process involves forming of half-cells and their precise machining and joining by electron beam welding to form end groups and dumbbells, which are then joined to make the final cavity. To ensure that the final welded cavity achieves physical lengths and resonant frequencies within design tolerance and has good field flatness, the measurement and correction of resonant frequency are carried out for dumbbells and end groups. A novel method to identify the frequency of individual half-cells in a dumbbell cavity and a dedicated tuning fixture to correct them had been developed. The paper details the RF characterization and correction procedure employed during fabrication of the first six 650 MHz cavities at RRCAT.

Synthesis and anticonvulsant activity of some potential thiazolidinonyl 2-oxo/thiobarbituric acids.

A series of 5-[(N-substituted benzylidenylimino)amino]-2-oxo/thiobarbituric acids (3a-3h) have been synthesized by the condensation of 5-hydrazino-2-oxo/thiobarbituric acids (2a-2b) with various aromatic aldehydes. Cycloaddition of thioglycolic acid to 3a-3h, yielded 5-[(2'-substituted phenyl-4'-oxothiazolidin-3'-yl)amino]-2-oxo/thiobarbituric acids (4a-4h). All these compounds were screened, in vivo, for their anticonvulsant activity and acute toxicity studies. Compounds 4f and 4g were found to be most potent compounds of this series and were compared with the reference drugs, phenytoin sodium, lamotrigine and sodium valproate. The structures of these compounds have been established by IR, 1H NMR and mass spectroscopic data.

Hepatoprotective activity of Beta vulgaris against CCl4-induced hepatic injury in rats.

Ethanolic extract of Beta vulgaris roots given orally at doses of 1000, 2000 and 4000 mg/kg exhibited significant dose-dependent hepatoprotective activity against carbontetrachloride (CCl(4))-induced hepatotoxicity in rats. Hepatotoxicity and its prevention were assessed by serum markers viz. cholesterol, triglyceride, alanine amino transferase and alkaline phosphatase.

Serodiagnosis of dengue during an outbreak at a tertiary care hospital in Delhi.

Dengue, an important human arboviral infection, is endemic in many parts of India. Outbreaks are now reported quite frequently from different parts of the country. We report here findings of serological investigation of serum samples received during a recent outbreak of dengue infection in Delhi from September to November 2003. Acute phase serum samples from suspected cases of dengue infection (including dengue fever, dengue haemorrhagic fever and dengue shock syndrome) of duration 5 days, were tested for dengue specific IgM antibodies by enzyme linked immuno sorbant assay (ELISA). Of the 874 serum samples tested, 456 (52.3% ) were positive for dengue specific IgM antibodies. The maximum number of positive cases was reported in October, peaking in second and third week. Patients in the age group of 21-30 yr accounted for 34.2 per cent of positive cases. This outbreak was less severe as compared to the previous 1996 outbreak and showed a shift towards an older age group.

Synthesis and anti-inflammatory activity of some heterocyclic derivatives of phenothiazine.

Some new 10-{[5'-amino-(1"-ace tyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-thiadiazol-2'-yl] methyl}-phenothiazines (11-16) and 10-{[5'-amino-(1"-acetyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazines (26-31) have been synthesized from 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-thiadiazol-2'-yl)]methyl}phenothiazines (5-10) and 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-oxadiazol-2'-yl)]methyl}phenothiazines (20-25), respectively. All these compounds of the present series have been screened in vivo for their anti-inflammatory and acute toxicity. Compounds 16 and 31 were found to be potent members of the present series, which showed 46.2% and 48.0% anti-inflammatory activity, respectively, at a dose of 50 mg/kg p.o., while standard drug, phenylbutazone, exhibited 44.52% anti-inflammatory activity at same dose. However, 10-{[5'-amino-(1"-acetyl-5"-(o-methoxyphenyl)-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazine (31) was found to be most active and less ulcerogenic compound of this series. The structure of these compounds have been elucidated by IR, 1H NMR, mass spectroscopy and elemental analysis.