Comparative characterization of two toxic phospholipases A2 from Indian cobra (Naja naja naja) venom.

Indian cobra venom contains many phospholipase A2 (PLA2) toxins. In the present study two toxic PLA2s have been purified from the Indian cobra (Naja naja naja) venom by column chromatography. The NN-XIa-and NN-XIb-PLA2s have mol. wts between 10,700 and 15,000. The NN-XIa-PLA2 induces myotoxic effects, oedema and neurotoxicity in mice and has an i.p. LD50 of 8.5 mg/kg body weight. The NN-XIa-PLA2 is also cytotoxic to Ehrlich ascites tumour cells. The other PLA2, NN-XIb, in contrast has an i.p. LD50 of 0.22 mg/kg body weight, and it induces acute neurotoxicity. The NN-XIb-PLA2 is devoid of the other biological activities which are exhibited by NN-XIa-PLA2.     

Dissociation of catalytic activity and neurotoxicity of a basic phospholipase A2 from Russell's viper (Vipera russelli) venom

A neurotoxic phospholipase A2, VRV PL-V was purified from Vipera russelli venom in a single step by CM-Sephadex C-25 column chromatography. VRV PL-V is a basic PLA2 with a mol. wt of approximately 10,000. The lethal potency of VRV PL-V was greater than that of the crude V. russelli venom. VRV PL-V showed anticoagulant activity and induced edema in the foot pad of the mouse. VRV PL-V undergoes aggregation at pH 4.8. The size of the aggregate increased as the temperature at which the enzyme was incubated was raised. A highly aggregated form with a mol. wt of 53,100 was formed at 96 degrees C. This aggregate showed a two-fold increase in its catalytic activity, while its neurotoxic activity disappeared. The aggregate also showed a significant increase in its anticoagulant activity when compared to the monomeric form. Edema-inducing activity decreased upon association to higher molecular form.     

Laboratory diagnosis of Japanese encephalitis using monoclonal antibodies and correlation of findings with the outcome

Detection of virus, viral antigen, and class-specific antibody was carried out in cerebrospinal fluid (CSF) and sera of 27 children with Japanese encephalitis. The diagnosis could be confirmed in 78.57% of cases (22/27) by demonstration of virus-specific IgM in CSF (15/22), viral antigen in CSF (5/22), or by virus isolation (2/22). Absence of virus specific IgM in CSF was associated with a fatal outcome (P = 0.05).     

Effects of chemical modification on enzymatic and toxicological properties of phospholipases A2 from Naja naja naja and Vipera russelli snake venoms.

The effects of chemical modification with 4-NN-dimethyl amino azo benzene-4'-isothiocyanate on various biological activities of phospholipases A2, NN-XIII-PLA2 from Naja naja naja and VRV-PL-VIIIa from Vipera russelli snake venoms were investigated. Modification of the enzymes resulted in significant reduction of lethal, hemolytic, anticoagulant and enzymatic activities. The Km value of the modified enzymes was increased. The modified enzymes failed to induce edema in the foot pads of mice and were non-lethal up to 16 mg/kg body weight. However, considerable myotoxicity was retained, suggesting that the toxins have multiple sites for biological activities. The aggregated form obtained from modified NN-XIII-PLA2 exhibited decreased enzymatic activity and increased toxicity compared to the modified monomer. This aggregated form did not show pyrophosphatase/phosphomonoesterase activity in contrast to the aggregated form obtained from the native NN-XIII-PLA2 molecule.     

Use of noninvasive ventilation in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Noninvasive positive pressure ventilation (NIPPV) is associated with improved survival in amyotrophic lateral sclerosis (ALS) and has been widely recommended. The extent of NIPPV use in ALS patients and the factors associated with its use have not been studied. METHODS: A cross-sectional study using the ALS Patient Care Database. Analyses were performed to assess the association of patient and care characteristics with use of ventilatory support. RESULTS: 1458 patients were studied. 15.6% used NIPPV and 2.1% used invasive mechanical ventilation. Patients who used NIPPV were significantly more likely to be male and have higher income than those who did not. They were also more likely to have a gastrostomy tube, lower vital capacity, more severe disease, bulbar involvement and poorer general health status as measured by the SF-12 and Sickness Impact Profile. Multivariate analysis revealed that lower FVC, higher income and use of gastrostomy tube were independently associated with use of NIPPV. CONCLUSIONS: NIPPV is used more than seven times as frequently as invasive ventilation in ALS patients. Patients who use NIPPV have more severe disease than those who do not use any respiratory intervention. Patients with lower income are less likely to use NIPPV, which raises concerns about disparities in the care of patients with ALS.     

Detection, using antibodies, of pharmacologically active sites, apart from the catalytic site, on venom phospholipase A2.

Polyclonal antibodies to a purified neurotoxic phospholipase A2 VRV PL-V from Vipera russelli venom were raised in rabbits. The gamma globulin fraction from the serum of the rabbits injected with VRV PL-V-toxoid (anti VRV PL-V antibodies) is termed anti PL-V Ig. Anti PL-V Ig neutralized the neurotoxic symptoms and lethal effects of neurotoxic PLA2s (VRV PL-V, VRV PL-VI and VRV PL-VIIIa) and neurotoxic symptoms of whole V. russelli venom, without affecting their phospholipase A2 activities. Their edema inducing activity was also unaffected. Anti VRV PL-V-antibodies inhibited the anticoagulant potencies of the neurotoxic PLA2s (VRV PL-V, VRV PL-VI and VRV PL-VIIIa) from V. russelli venom and VRV PL-V-toxoid. The myonecrotic activity of VRV PL-V, VRV PL-VIIIa and whole venom remain unaffected in presence of anti PL-V Ig. The hemoglobinuria induced in rabbits by injection of VRV PL-V-toxoid was inhibited by anti VRV PL-V antibodies. These results indicate the presence of multiple pharmacological sites apart from the catalytic site on V. russelli PLA2 molecules.     

A clinical study of benign tumours of nose and paranasal sinuses

In this prospective study, comprising of 30 cases, various benign tumours, both common and rare are compiled. The cases were selected in the OPD of Kempegowda institute of medical sciences, one of the tertiary referral centres in Bangalore. The sample consists of patients in the age group 9 months to 60 years. The study also compares sex differences,symptomatology and the relative incidence of various rumours. The commonest site was nasal cavity, followed by paranasal sinuses and external nose. They occur commonly in second and third decades with predominance in males. Epithelial tumours were less common when compared to non epithelial tumours. All masses should be subjected to histopathological examination for proper management All cases should be followed up for as long as two years for better assessment treatment and response.     

The value of local registry data for describing cervical cancer management and outcomes over three decades in Australia

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984‐2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease‐specific survival analyses using Kaplan‐Meier product‐limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five‐ and 10‐year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early‐stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in‐step with national trends. Little evidence of variation in risk‐adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk‐adjusted treatment and outcomes did not vary by socio‐economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources.