Metabolomic biomarkers in a model of asthma exacerbation: urine nuclear magnetic resonance.

RATIONALE: Airway obstruction in patients with asthma is associated with airway dysfunction and inflammation. Objective measurements including sputum analysis can guide therapy, but this is often not possible in typical clinical settings. Metabolomics is the study of molecules generated by metabolic pathways. We hypothesize that airway dysfunction and inflammation in an animal model of asthma would produce unique patterns of urine metabolites measured by multivariate statistical analysis of high-resolution proton nuclear magnetic resonance ((1)H NMR) spectroscopy data. OBJECTIVES: To develop a noninvasive means of monitoring asthma status by metabolomics and urine sampling. METHODS: Five groups of guinea pigs were studied: control, control treated with dexamethasone, sensitized (ovalbumin, administered intraperitoneally), sensitized and challenged (ovalbumin, administered intraperitoneally, plus ovalbumin aerosol), and sensitized-challenged with dexamethasone. Airway hyperreactivity (AHR) to histamine (administered intravenously) and inflammation were measured. Multivariate statistical analysis of NMR spectra based on a library of known urine metabolites was performed by partial least-squares discriminant analysis. In addition, the raw NMR spectra exported as xy-trace data underwent linear discriminant analysis. MEASUREMENTS AND MAIN RESULTS: Challenged guinea pigs developed AHR and increased inflammation compared with sensitized or control animals. Dexamethasone significantly improved AHR. Using concentration differences in metabolites, partial least-squares discriminant analysis could discriminate challenged animals with 90% accuracy. Using only three or four regions of the NMR spectra, linear discriminant analysis-based classification demonstrated 80-90% separation of the animal groups. CONCLUSIONS: Urine metabolites correlate with airway dysfunction in an asthma model. Urine NMR analysis is a promising, noninvasive technique for monitoring asthma in humans.

Antibacterial effects of Carica papaya on common wound organisms [abstract]

OBJECTIVE: The objective was to investigate the antibacterial activity of the crude Carica papaya preparations as used by nurses, on gram negative and gram positive organisms; to determine which part and stage of maturity of the fruit yielded the best antibacterial activity, and determine the effects of storage conditions on the observed activity. METHODS: The pathogens commonly found in human wounds were obtained from the Microbiology Department, University of the West Indies, Biochemistry Section, The University of the West Indies and the Jamaican Bureau of Standards. Cultures were routinely maintained in nutrient agar slants at 4§c. Extracts were obtained by separately grinding fractions of the epicarp, endocarp and seeds of the immature, mature and ripe Carica papaya fruit and filtering them through guaze. Sensitivity tests were conducted by adding 0.06 ml. of agar wells (6 mm diameter) prepared from 20 ml agar seeded with 10 cells/ml suspension of one of the eight organisms per plate. The inoculated plates were allowed to equilibrate at 4§c for one hour then incubated at 37§c for 24 hours, after which zones of inhibition were measured in millimeters. Antibacterial activity was expressed in terms of the radius of the zone of inhibition calculated as the difference in radius of the observed zones and the edge of the agar wells. Daily sensitivity tests were carried out on extracts stored at 5§c, 25§c and 35§c for 7 days. RESULTS: The seed extracts from all three stages of the fruit showed an average order of inhibition in the following order: B cereus> E coli> S faecalis> S aureus> P vulgaris> and X flexneri. There was no significant difference in bacterial sensitivity between the immature, mature and ripe fruits tested. The epicarp and endocarp did not produce any inhibition zone in any of the three stages of the fruit tested. There was a gradual reduction in antibiotic activity with increasing storage item. Also, a fall-off of activity was found to be more drastic at higher temperatures. CONCLUSION: The findings show that crude extracts of Carica papaya seed have antibacterial activity that inhibits the growth of both gram positive (B cereus, S aureus and S faecalis) and gram negative (E coli, P vulgaris and S flexneri) organisms. Observed activity was dependent on stage of maturity but tended to decrease with duration and conditions of storage. No antibacterial activity was observed from the epicarp and the endocarp of the fruit. (AU)

Effect of aqueos neem leaf extract on blood pressure in conscious Wistar rats (a preliminary report)[abstract]

OBJECTIVE: This work investigates the effects of aqeous neem leaf extract on blood pressure (systolic, diastolic, and mean arterial pressure), heart rate and body weight in conscious Wistar rats. METHODS: The rats were divided into three groups of six. The first group received a daily intra-oesophageal bolus of 0.5 ml water. The 2nd and 3rd were given 20 mg/kg and 40 mg/kg body weight, respectively, of aqeous neem leef extract. Blood pressures and heart rate were measured using the LE 5002 Stroage Pressure meter (Letica Scientific Instruments). Body weight was also measured weekly for eight weeks. Statistical analysis was carried out using SPSS. RESULTS: Blood pressure, heart rate and body rate were not statistically different between the three groups on day 1. By week 8, the diastolic and mean arterial pressures wre significantly lower (p<0.0001) in the two neem-treated groups than in the controls. There was also no significant difference in weight between the groups. CONCLUSION: The results show that administration of o 20 mg/kg-body weight of aqeuous neem leaf extract reduces diastoloc and mena arterial blood pressures in conscious rats (AU)

Salt-Induced hypertension in rats alters the response of isolated aortic rings to cromakalim

The effect of cromakalim, an opener of ATP-sensitive potassium (K atp) channel, on precontracted aortic rings from control and salt-loaded rats was studied in spague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride(NaCl)per kilogram(kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/a-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphstase (Na-KATPase) pump activity was measured by potassium(K)-induced relaxation (with or without ouabain) following precontraction with 10-7 M noradrenaline.The KATP channel was studied by measuring the relaxation response to cromakalim,precontracted with either 10-7M noradrenalineor 60mM potassiumchloride(KCl). The Na- k ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K - induced contraction. Cromakalim produced relaxation of noradrenaline precontracted rings frem the control rats; rings from salt-loaded rats showed significantly less relaxtion than control(p<0.05) under similar conditions. During K-induced precontraction, cromakalim produced a weak biphasic response in the control rings-an initial relaxation and then a reversal. Cromakalim produced further contraction of K-induced precontraction in salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.(AU)