Characterization of three edema-inducing phospholipase A2 enzymes from habu (Trimeresurus flavoviridis) venom and their interaction with the alkaloid aristolochic acid

A basic phospholipase A2 (PLA2) enzyme, TFV PL-X (pI 9.2) and two acidic PLA2 enzymes, TFV PL-Ia (pI 4.9) and TFV PL-Ib (pI 4.5) were purified from Trimeresurus flavoviridis venom on CM-Sephadex C-25 and QAE-Sephadex A-25 columns, respectively. The basic enzyme exists as a monomer, whereas the acidic enzymes are dimers. These enzymes differ in properties such as molecular weight, Km, optimum pH and temperature and pharmacological properties. The basic enzyme hydrolysed purified phospholipids in the order of PC greater than PE greater than PS greater than PI = 0, while for TFV PL-Ia and TFV PL-Ib the order was PC greater than PE greater than PS = PI = 0. TFV PL-X was comparatively more toxic, with an LD50 value of 4.2 micrograms/g (i.p.), while the acidic PLA2 enzymes had LD50 values above 8 micrograms/g (i.p.). All three enzymes induced edema when injected into the mouse foot pad. Aristolochic acid, an alkaloid (8-methoxy-6-nitrophenanthro(3,4-d)-1,3-dioxole-5-carboxylic acid) from the medicinal plant Aristolochia radix, interacts with these PLA2 enzymes. It is a competitive inhibitor with varying affinity when PC is used as substrate. Aristolochic acid inhibits direct and indirect hemolytic activity, as well as edema-inducing activity, of TFV PL-X, but fails to neutralize the lethal potency of the enzyme. On the other hand, it inhibits direct and indirect lytic activity of TFV PL-Ia and TFV PL-Ib only at 10-fold higher concentrations and it enhances the edema-inducing activity of these enzymes. Such effects of aristolochic acid indicates that (1) different mechanisms may be involved in the edema-inducing activity of PLA2 enzymes and (2) catalytic and pharmacological sites are separate on the PLA2 molecule.     

Clinical profile and management of PDA in neonates

Patent ductus arteriosus (PDA) is recognised more often with increasing survival of preterm babies. The pharmacological closure of ductus by indomethacin has changed the man-agement of PDA¹. Twenty neonates admitted over a period of 21 months to Neonatal Intensive Care Unit (NICU) of M.S. Ramaiah Medical College hospital, Bangalore, who were diagnosed to have PDA, were analyzed. The objectives of this retrospective analysis were to study the clinical profile, the efficacy of oral indomethacin and the outcome of PDA. 2–D and Doppler echocardiaography were used to confirm the clinically suspected PDA. These neonates were treated with 3 doses of oral indomethacin (0.2–0.25 mg/kg/dose 12 hourly) along with fluid restriction and oxygen. Echocardiography was repeated to demonstrate the closure of PDA. The incidence of PDA was 2.3% of total NICU admissions. Seventy percent of this cohort were < 32 weeks of gestation, 55% had birth weight of < 1500 gms. Seventy percent (14) neonates had onset of PDA after 48 hrs of life. 81.25% of neonates responded to indomethacin and overall survival rate in treated group was 67%. Drug related complications were noted in 2 newboms. This study illustrates the utility of echocardiography in diagnosing and monitoring PDA in preterm and low birth weight babies with high index of suspicion of this common congenital heart disease. Pharmacological intervention with indomethacin is rewarding with acceptable results.     

A Narrative Review of Pharmacotherapy Treatment for Opioid Addiction and Application in a Community-Based Model in Victoria,Australia

International Journal of Mental Health and Addiction - To review the literature regarding the value and consumer focus of research on opioid replacement therapy (ORT) programs, relevant to the...     

Dietary associations with diabetic retinopathy—A cohort study

Purpose:To assess the role of dietary factors in the development of diabetic retinopathy (DR) in diabetics.Methods:This prospective study was carried out on patients attending the outpatient department of ophthalmology for a period of 1 year. An interview-based 24-hour diet recall was used to document average daily dietary nutrient intakes. Each patient was subjected to a comprehensive ocular examination to look for DR.Results:A total of 261 patients attending the outpatient department of ophthalmology were the participants for this study. The mean (±SD) age of the participants was 57.73 ± 11.29 years, and 67% were men. One hundred and six participants had DR. Univariate analysis revealed sex, duration, fish (times/week), egg (yes/no), rice lunch (yes/no), rice dinner, rice (boiled/white), and total calorie intake to be associated with DR (P < 0.05). Logistic regression multivariable analysis revealed males (OR: 3.20, 95% CI: 1.65–6.19), longer duration of diabetes (OR:1.05,95% CI:1.01-1.11), antioxidant intake (OR: 3.42, 95% CI: 1.65–7.05), and consumption of rice (OR: 3.19, 95% CI: 1.17–8.69) to have significant association with DR (P < 0.05), with the odds of developing DR increasing three times in these patients. The odds of developing DR were lesser with more frequent (>2 times/week) fish consumption (OR: 0.42, 95% CI: 0.18–0.94) and in patients on pharmacological treatment for diabetes mellitus (OR: 0.16, 95% CI: 0.04–0.58). Binary logistic regression revealed chapathi consumption (OR: 9.37, 95% CI: 1.64–53.68) to be associated with severe forms and fish consumption (OR: 0.06, 95% CI: 0.01–1.06) (P < 0.05) to be associated with less severe forms of DR.Conclusion:Males, longer duration of diabetes, antioxidant intake, fish consumption, and consumption of rice were associated with the occurrence of DR. Participants with diabetes who consumed fish more frequently and those who were on pharmacological treatment for diabetes mellitus had a significantly lower risk of DR and frequent fish consumption could reduce the risk of DR progression.     

Profile of inborn errors of metabolism in a tertiary care centre PICU

Objective  

To study the clinico-investigative profile and outcome of patients with inborn errors of metabolism (IEM) presenting to the pediatric intensive care unit (PICU).