Research Articles (School of Pharmacy)
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Raji, Ismaila; Mugabo, Pierre; Obikeze, Kenechukwu (BioMed Central, 2013)[more][less]
Abstract: Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect. Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30–120 mg/kg), muscarine (0.16 -10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS)) were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR) weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg) was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments, the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea (60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the chronic experiment. Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violaceatreated and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the captopril-treated group; while no difference in HR was observed among the groups. Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea. URI: http://hdl.handle.net/10566/600 Files in this item: 1
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Mugabo, Pierre; Els, Ilse; Smith, Johan; Rabie, Helena; Smith, Peter; Mirochnick, Mark; Steyn, Wilhelm; Hall, David; Madsen, Richard; Cotton, Mark F (Health & Medical Publishing Group, 2011)[more][less]
Abstract: Background. No pharmacokinetic data exist for premature infants receiving single-dose nevirapine (sd NVP) for prevention of mother-to-child transmission (MTCT) of HIV. Aim. To describe NVP decay pharmacokinetics in two groups of premature infants - those whose mothers either received or did not receive NVP during labour. Methods. Infants less than 37 weeks' gestation were prospectively enrolled. Mothers received sd NVP during labour if time allowed. Infants received sd NVP and zidovudine. Blood was collected on specified days after birth and NVP concentrations were determined by liquid chromatography-mass spectrometry. Results. Data were obtained from 81 infants, 58 born to mothers who received sd NVP during labour (group I) and 23 to mothers who did not receive NVP (group II). Of the infants 29.6% were small for gestational age (SGA). Median (range) maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the plasma concentration-time curve (AUC) and halflife (T) were 1 438 (350-3 832) ng/ml, 25h50 (9h40-83h45), 174 134 (22 308-546 408) ng×h/ml and 59.0 (15.4-532.6) hours for group I and 1 535 (635-4 218) ng/ml, 17h35 (7h40-29h), 168 576 (20 268-476 712) ng×h/ml and 69.0 (22.12-172.3) hours for group II. For group II, the median (range) volume of distribution (Vd) and body clearance (Cl) were 1 702.6 (623.7-6 189.8) ml and 34.9 (6.2-163.8) ml/h. The AUC was higher (p=0.006) and Cl lower (p<0.0001) in SGA infants. Plasma concentrations exceeding 100 ng/ml were achieved over 8 days in 78% infants in group I and 70.0% in group II. The MTCT rate was 4.8%. Conclusion. Women in preterm labour often deliver with little advance warning. Our study suggests that NVP dosing of preterm infants as soon as possible after birth without maternal intrapartum dosing may be as effective as combined maternal and infant dosing. URI: http://hdl.handle.net/10566/405 Files in this item: 1
MugaboPrematureMTCT.pdf (503.0Kb) -
Mugabo, Pierre; Obikeze, Kenechukwu; Njagi, Angela; Burger, Andries; Dietrich, Danielle; Green, Ivan (Open Access Science Research Publisher, 2012)[more][less]
Abstract: Crinum macowanii has been used extensively in traditional medicines for treatment of various illnesses such as oedema and ‘heart disease’. Previous studies of the crude bulb extracts on Langendorff perfused isolated rat hearts indicated a positive inotropic effect. The aim of this study was to isolate and characterize compound(s) from C. macowanii with cardiovascular effects similar to that observed with the crude extracts of the plant. The methanol extract of dried bulbs was extracted for alkaloids, and structural elucidation of the isolated alkaloid identified it as hippadine. The cardiovascular effects of hippadine was evaluated in vitro in isolated perfused rat hearts using the “double sided” working heart system. Perfusion with 0.5 μg/ml and 5.0 μg/ml hippadine in Krebs-Hanseleit buffer led to significant decreases in coronary flow, aortic output, cardiac output, systolic pressure, and heart rate, accompanied by increases in diastolic pressure. Hippadine exhibited a negative chronotropic and inotropic effect on the isolated rat heart and is responsible either partly or fully for the cardiovascular effects of C. macowanii. URI: http://hdl.handle.net/10566/401 Files in this item: 1
MugaboHippadine2012.pdf (63.78Kb) -
Mugabo, Pierre; Khan, Fatima; Burger, Andries (Open Access Science Research Publisher, 2012)[more][less]
Abstract: The use the aqueous decoction of Leonotis leonurus (L. leonurus) (Ll) R. Br. (Lamiaceae) in the treatment of hypertension (HPT) in traditional medicine is well documented. The effect of the aqueous extract of LI on the blood pressure (BP) and heart rate (HR) has been investigated in normotensive rats. The aim of this study was to investigate the effect of Ll aqueous extract on the in isolated perfused rat heart (IPRH). Hearts were excised from male Wistar albino rats weighing 250-350g, aged less than 6 months. They were perfused at constant flow using the modified Langendorff perfused model of the heart. Effects of adrenaline on the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), heart rate (HR), cardiac work (CW) and coronary perfusion pressure (CPP) were compared to that of Ll. Adrenaline (1µM) significantly (p<0.05) increased the LVSP by 40.6%, the LVDP by 43.9%, the HR by 22.5% and the CW by 89.4%. Ll (1.0 mg/ml and 2.0 mg/ml respectively and significantly (p<0.01) increased the LVSP by 25.36 and 14.91, the LVDP by 29.40 and 14.88. Ll (1.0 mg/ml and 2.0 mg/ml) significantly produced a negative chronotropic effect. Both adrenaline and Ll aqueous extract did not have any significant effect on the LVEDP. Adrenaline resulted in positive inotropic and chronotropic effects. At low concentrations Ll produced a positive inotropic and a negative chronotropic effect. At the concentration of 2.0mg/ml Ll decreased all parameters to zero. At higher concentrations higher than 2.0mg/ml, Ll seemed to have toxic effects on the heart. URI: http://hdl.handle.net/10566/400 Files in this item: 1
MugaboLeonotisLeonurus2012.pdf (362.4Kb)