UWCScholar :: Browsing by Author "Mugabo, Pierre"

Browsing by Author "Mugabo, Pierre"

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Active Principles of Tetradenia riparia; II. Antispasmodic Activity of 8(14), 15-Sandaracopimaradiene-7α, 18-diol
(Georg Thieme Verlag, 1987) Van Puyvelde, Luc; Lefebvre, Romain; Mugabo, Pierre; De Kimpe, Norbert; Schamp, Niceas
Tetradenia riparia is one of the most popular medicinal plants in Rwanda. Previously, several new substances have been isolated from the leaves, including a new diterpenediol, i.e. 8(14),15-sandaracopimaradiene-7α,18-diol. This new diterpenediol exhibits a papaverine-like antispasmodic activity on the contractions of the guinea pig ileum provoked by methacholine, histamine, and barium chloride and on the noradrenaline-induced contractions of the rabbit aorta.
Acute pharmacokinetics of first line anti-tuberculosis drugs in patients with Pulmonary Tuberculosis and in patients with Pulmonary Tuberculosis co-infected with HIV
(David Publishing, 2011) Mugabo, Pierre; Hassan, Mogamat Shafick; Slaughter, R.
The aim of this study was to compare the pharmacokinetics of antituberculosis drugs in patients with pulmonary tuberculosis (PTB) and in patients with PTB and HIV during the first 24 h of treatment. Designed as a case-control study, it compares the pharmacokinetics of first line antituberculous drugs, in HIV-positive (cases) and HIV-negative (control) patients both presenting with pulmonary tuberculosis. Blood samples were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 8, 12 and 24 h after administration of drugs. Drugs plasma levels were tested using HPLC assays. Results: Fourteen HIV positive (7 males and 7 females) and 17 HIV negative (9 males and 8 females) enrolled. Rifafour, a combination tablet including rifampicin, isoniazid, pyrazinamide and ethambutol was used in HIV positive patients, CD4 counts were significantly lower, renal function mildly decreased in 85% patients and moderately decreased in 7% patients. Liver function was normal in both groups. None of these patients was on other drug therapy. In the HIV positive group isoniazid T1/2 and AUC were decreased and Cl increased whereas Tmax and Cmax were unchanged. Pyrazinamide Tmax and Cmax were significantly decreased in HIV positive patients and no significant changes were noticed in the T1/2, AUC and CL. Conclusion: The study suggest that ethambutol, pyrazinamide and rifampicin pharmacokinetics was not affected by HIV infection and that isoniazid disposition is affected by HIV.
Adverse effects experienced by patients on first line antiretroviral drugs used at Keetmanshoop Hospital (Namibia).
(University of the Western Cape, 2015) Mutenda, Nicholus Mbangu; Mugabo, Pierre
Adverse effects are a significant factor that determine how long patients will tolerate a given antiretroviral drug regimen. They also influence treatment options, and play an important role in the much needed adherence to treatment by patients on Highly Active Antiretroviral Therapy (HAART). This study is aimed at understanding adverse effects experienced by patients on the first line antiretroviral therapy at Keetmanshoop Hospital in Namibia. Methods : A retrospective quantitative method was used to review records of patients on first line antiretroviral treatment who started treatment between November 1st 2007 and December 1st, 2008 and followed up until they reached 36 – 48 months on treatment. Records of 94 patients were found eligible to be included in the study. Data was analysed using Stata 12 data analysis software. Results : The most reported adverse effect was musculoskeletal disorders (25%) whereas headache (16%) was the least reported. Low haemoglobin (78%) was the most common recorded hematologic adverse effect whereas low red cell distribution width and low mean platelet volume were the least recorded adverse effects (0%). A Male patient was more likely to experience a low haemoglobin levels compared to a female patient (adjusted OR: 3.29, 95% CI: 1.3 – 8.3). A male patient was found to be 64% times less likely to experience a higher mean cell haemoglobin compared to a female patient (adjusted OR. 0.31, 95% CI: 0.11 – 0.87). A patient on nevirapine was more likely to experience an elevated creatinine level compared to a patient on efavirenz (adjusted OR; 36.0, 95%CI: 2.02 – 62.5). At baseline, a patient who had prior exposure to ART had an 81 times (adjusted OR: 81.4, 95%CI: 5.3 – 119, p-value=0.00) increased odds of experiencing a high mean cell volume (MCV) compared to a patient with no ART exposure. A patient with a higher CD4 count was also less likely to experience a low hemoglobin compared to a patient with low CD4 count (adjusted OR; 0.31, 95% CI: 0.12 – 0.77). The author recommends further studies with higher sample size to confirm whether higher creatinine levels are more prevalent in patients on nevirapine compared to patients on efavirenz; this will have clinical implications especially in patients with impaired renal system. Antiretroviral treatment increases chances of developing macrocytosis anaemia; clinical implication of this condition may need to be investigated.
Adverse pregnancy outcomes among HIV-positive pregnant women treated with efavirenz-containing antiretroviral drugs: a retrospective cohort study in the Cape Flats
(University of the Western Cape, 2017) Mohammednur, Mohammedmekin Mohammedseid; Mugabo, Pierre
The use of efavirenz (EFV) in the first trimester of pregnancy remains controversial. In South Africa, the use of EFV-containing antiretroviral therapy (ART) as part of a Fixed Dose Combination (FDC) during the first trimester of pregnancy started in April, 2013. Literature to date has reported conflicting outcomes following the use of EFV-containing ART during the first trimester of pregnancy. The objectives of the study were to determine the prevalence of adverse pregnancy outcomes among HIV-positive pregnant women treated with EFV-containing ART and compare these results with those of pregnant women treated with NVP-containing ART and HIV-negative pregnant women in resource-limited settings. In addition, the study also aimed to determine the effect of the time of initiation of ART on the prevalence of adverse pregnancy outcomes.
Amount of cycloserine emanating from terizidone metabolism and relationship with hepatic function in patients with drug resistant tuberculosis
(Springer, 2019) Mulubwa, Mwila; Mugabo, Pierre
The dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not certain from the literature that these drugs are interchangeable. Therefore, the amount of cycloserine resulting from the metabolism of terizidone and the relationship with hepatic function were determined. This prospective clinical study involved 39 patients with drug-resistant tuberculosis admitted for an intensive phase of treatment. Cycloserine pharmacokinetic parameters for individual patients, like area under the curve (AUC), clearance (CLm/F), peak concentration (Cmax) and trough concentration (Cmin), were calculated from a previously validated joint population pharmacokinetic model of terizidone and cycloserine. Correlation and regression analyses were performed for pharmacokinetic parameters and unconjugated bilirubin (UB), conjugated bilirubin (CB), albumin, the ratio of aspartate transaminase to alanine aminotransferase (AST/ALT), or binding afnity of UB to albumin (Kaf), using R statistical software version 3.5.3.
Cardiovascular effects of (13S)-9_, 13_- epoxylabda-6_(19), 15(14)diol dilactone, a diterpenoid isolated from the organic extract of leonotis leonurus leaves, in anaesthetized normotensive rats
(2009) Chibuzo, Obikeze Kenechukwu; Mugabo, Pierre; Green, Ivan
Plants used in traditional medicines have served as sources of some of the drug compounds used in medicines today, and could still serve as leads for then development of new drugs to treat existing chronic diseases such as hypertension. This study was aimed at the isolation and identification of a cardio-active compound from L. leonurus, a plant commonly used in traditional medicines in South Africa for the treatment of hypertension and other cardiac problems. The possible mechanisms by which the isolated compound produced its effect on the cardiovascular system were explored using the anaesthetized normotensive rat model.Fractionation of the organic extracts of the leaves led to the isolation of a novel diterpene,(13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone (EDD) whose structure was elucidated using infra red (IR), nuclear magnetic resonance (NMR), mass spectroscopy(MS), and X-ray diffraction analysis. In anaesthetized normotensive male Wistar rats, EDD(0.5 mg/kg – 5.0 mg/kg; IV) produced slight non-significant decreases in systolic pressure(SP), diastolic pressure (DP), and mean arterial pressure (MAP) with the lower (0.5 mg/kg– 2.0 mg/kg) doses, while significant increases in SP, DP and MAP occurred with the higher (3.0 mg/kg – 5.0 mg/kg) doses. All doses of EDD administered also produced significant decreases in heart rate (HR).Prazosin and reserpine pre-treatment abolished the vasoconstrictive effect of EDD,suggesting an indirect vasoconstrictive effect for EDD via the release of catecholamines.Atenolol pre-treatment led to increases in the negative chronotropic effect of EDD, while the positive chronotropic effect of dobutamine was significantly decreased by EDD,suggesting the involvement of the 1 adrenoceptor in the negative chronotropic effect of EDD. In animals pre-treated with verapamil, a cardio-selective Ca2+ channel blocker, no significant changes in HR occurred with all EDD doses, but HR values were significantly lower than those obtained with EDD in non pre-treated animals.The results of this study indicate that (13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone, a novel dilactone diterpene isolated from the leaves of L. leonurus has an effect on the cardiovascular system. EDD exhibits a dual effect on the cardiovascular system by producing a vasoconstrictive effect accompanied by bradycardia. The vasoconstrictive effect of EDD is probably due to the release of catecholamines, while the negative chronotropic effect is probably due to 1 adrenoceptor antagonism. Further studies are however required to fully determine the mechanism by which EDD produces its cardiovascular effects.
Cardiovascular effects of aqueous leaf extract of Leonotis leonurus in Anesthetized rats
(University of the Western Cape, 2008) Tshambuluka, Noxolo; Mugabo, Pierre
The present study was designed to evaluate the hypotensive properties and the mechanisms of action of the aqueous leaf extract of Leonotis leonurus in anesthetized male Wistar rats, using computerized blood pressure recording system.
Cardiovascular effects of the alkaloid hippadine on the isolated perfused rat heart
(Open Access Science Research Publisher, 2012) Mugabo, Pierre; Obikeze, Kenechukwu; Njagi, Angela; Burger, Andries; Dietrich, Danielle; Green, Ivan
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.
Characterization and Cradiovascular Effects of (13S)-9α,13α-epoxylabda-6β(19),15(14)diol dilactone, a Diterpenoid Isolated from Leonotis leonurus
(South African Chemical Institute, 2008) Obikezea, Kene C.; McKenzieb, Jean M.; Green, Ivan; Mugabo, Pierre
A new diterpenoid, (13S)-9 ,13 -epoxylabda-6 (19),15(14)diol dilactone (1), was isolated from Leonotis leonurus and the structure determined via NMR analysis. The compound causes significant changes in blood pressure of anaesthetized normotensive rats and exhibits a negative chronotropic effect.
The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea
(BioMed Central, 2013) Raji, Ismaila A.; Mugabo, Pierre; Obikeze, Kenechukwu
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.
Determination of kanamycin plasma concentrations using LC/MS and pharmacokinetics of kanamycin in patients with multidrug-resistant tuberculosis and in patients with multidrug-resistant tuberculosis co-infected with HIV
(University of the Western Cape, 2012) Abaniwonda, Ibukunoluwa Mercy; Mugabo, Pierre
The aim of the study was to determine firstly, kanamycin plasma concentrations using liquid chromatography coupled with mass spectrometry (LC/MS); secondly, to investigate the PK parameters of kanamycin in patients infected with MDR-TB and in patients co-infected with MDR-TB and HIV; thirdly, to assess the influence of HIV infection and renal impairment on the PK of kanamycin and fourthly, to find out whether there is any interaction between antiretroviral drugs and kanamycin.
Determination of kanamycin plasma levels using LC-MS and its pharmacokinetics in patients with multidrug-resistant tuberculosis with and without HIV-infection
(OMICS, 2015) Mugabo, Pierre; Abaniwonda, Mercy, I.; Theron, Danie; Hassan, Shafick, M.; Stander, Marietjie; Van Zyl, Leonie; McIlleron, Helen; Madsen, Richard
The objectives of the study were: (1) to determine kanamycin plasma concentrations using liquid chromatography coupled with mass spectrometry (LC-MS), (2) to investigate kanamycin pharmacokinetics (PK) in patients with multi-drug resistant tuberculosis (MDR-TB), (3) to find out whether HIV infection, kidney dysfunction and antiretroviral drugs influence kanamycin PK. The study was designed as a non-randomized study involving male and female HIV- positive and HIVnegative patients admitted for MDR-TB treatment. Blood samples were collected before (baseline) and ½, 1, 2, 4, 8 and 24 hours after intramuscular injection of kanamycin. LC-MS was used to quantify kanamycin plasma concentrations. Thirty one patients including 13 HIV (+) participated in the study. The lower limit of detection and lower limit of quantification of kanamycin were 0.06 μg/ml and 0.15 μg/ml respectively. Kanamycin PK parameters were described and there was no significant difference between HIV-positive and HIV-negative patients. A statistical significant difference (p=0.0126) was found in the renal function in HIV - positive and HIV - negative patients. However, this difference did not affect kanamycin elimination. No interactions have been identified between antiretroviral drugs and kanamycin. Conclusion: LC-MS analysis method is highly specific and highly sensitive in the detection and quantification of kanamycin plasma concentrations. Kanamycin PK in patients with MDR-TB was described. Due to a limited number of patients, we cannot rule out any influence of HIV - infection, renal impairment and antiretroviral drugs on kanamycin pharmacokinetics. The relationship between the area under the curve of kanamycin free plasma concentrations (fAUC) and its minimum inhibitory concentrations (MIC) on M.tuberculosis isolated from the sputum of each patient should be assessed. Therefore, kanamycin free plasma concentrations and MIC should be determined.
Do HIV infection and antiretroviral therapy influence multidrug-resistant tuberculosis treatment outcomes?
(Academic Journals, 2015) Mugabo, Pierre; Adewumi, A.O.; Theron, Danie; Burger, Andries; Van, Zyl L.
The aim of this study was to find out whether human immunodeficiency virus (HIV)-infection and antiretroviral drugs influence multidrug-resistant (MDR)-tuberculosis (TB) treatment outcomes. The study compares MDR-TB treatment outcomes between HIV-positive and HIV-negative patients. It involved patients admitted for treatment of MDR-TB between 1 January 2004 and 31 December 2006. From 363 patients selected, 268 (177 males and 91 females) had MDR-TB and 95 patients (59 males and 36 females) were co-infected with HIV. Children in the HIV-negative group were 41 and 7 in the HIV-positive group. The HIV-infection was treated with Stavudine, Lamivudine and Efavirenz in 54 patients. Kanamycin, Ethionamide, Ofloxacin, Terizidone, Pyrazinamide and Ethambutol were used for MDR-TB treatment. In HIV-negative and HIV-positive patients MDR-TB treatment outcomes were, respectively as follows: 37 and 35% cure, 9 and 5% treatment failure, 20 and 25% lost to follow up, 11 and 17% mortality, 19 and 13% treatment completed, 6 and 5% transfer-out. The cure rate was 100% in children. In HIV-positive patients, MDR-TB cure rate was 35% in patients on ARVs and 34% in patients not receiving ARVs. The difference between these cure rates is not statistically significant (p-value = 0.79). The median (range) duration of ART before the start of MDR-TB treatment was 10.5 (1 to 60) months and did not influence MDR-TB treatment outcomes. In children, the full treatment was supervised in hospital. This could explain the 100% cure rate. Adults' treatment was supervised in hospital only during the intensive phase then followed up as out patients over 18 months. According to the results of this study, HIV-infection and antiretroviral therapy did not influence MDR-TB treatment outcomes.
Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive wistar rats
(University of the Western Cape, 2011) Raji, Ismaila; Mugabo, Pierre; School of Pharmacy
Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family, Alliaceae, most commonly associated with onions and garlic. In South Africa (SA), this herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension (HTN) and stomach problems. The aim of this study was to evaluate the effect of methanol leaf extracts (MLE) of T. violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats and to find out the mechanism(s) by which it acts. The MLE of T. violacea (5 - 150 mg/kg), angiotensin I (ang I, 3.1 - 100 mg/kg), captopril (10 mg/kg), angiotensin II (ang II, 3.1 - 50 g/kg), losartan (30 mg/kg), phenylephrine (0.01 ; 0.16 mg/kg), prazosin (1 mg/kg), dobutamine (0.2 ; 10.0mg/kg), propranolol (0.1 - 12.8 mg/kg), muscarine (0.16 -10 mg/kg), and atropine (0.02 - 20.48 mg/kg) were administered intravenously into male spontaneously hypertensive rats (SHR) weighing between 300 g and 350 g and aged less than 5; months. The MLE of T. violacea and/or the standard drugs were infused alone, simultaneously, or separately into each animal. The BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab. The vehicle (0.2 mls of a mixture of dimethylsulfoxide and normal saline), T. violacea (60 mg/kg) and captopril (10 mg/kg) were injected intraperitoneally into some SHR for 21 days to investigate the chronic effect of these agents on plasma levels of aldosterone. The mean change, the mean of the individual percentage changes and the percentage difference (in mean) observed with each intervention was calculated and statistically analyzed using the Student t test for significant difference (p < 0.05). The Microsoft Excel software was used for statistical analysis. T. violacea significantly (p < 0.05) reduced the systolic, diastolic, and mean arterial BP; and HR dose-dependently. In a dose-dependent manner, ang I, ang II, phenylephrine significantly (p < 0.05) increased the BP, while propranolol, muscarine and atropine reduced the BP. The increases in BP due to dobutamine were not dose-dependent. In a dose dependent manner, phenylephrine and propranolol reduced the HR, while dobutamine increased the HR. The effect of ang I, ang II, muscarine and atropine on HR were not dose-dependent; with both increases as well as decreases observed with ang I, and II and atropine, while decreases were seen with muscarine. Captopril produced significant (p < 0.05) reduction in BP which were not associated with any change in HR. The co-infusion of ang I with the MLE produced significant (p < 0.05) reduction in BP, which were not associated with significant changes in HR. The co-infusion of ang II with the MLE did not produce any significant changes in BP or HR when compared to the infusion of the standard drug alone. The co-infusion of phenylephrine with the MLE did not produce any significant change in BP or HR when compared to the values obtained with the infusion of the standard drug alone, in both the absence and presence of prazosin. The co-infusion of dobutamine with T. violacea produced siginificant (p < 0.05) increases in DBP which were associated with significant (p < 0.05) reductions in HR, when compared to the values obtained with the infusion of the standard drug alone. Theco-infusion of atropine with the MLE did not produce any significant change in BP or HR when compared to the values obtained with the infusion of atropine alone. However, the infusion of T. violacea, 20 minutes after pre-treating animals with atropine (5.12 mg/kg) lead to dose dependent significant (p< 0.05) increases in BP, which were associated with dose-dependent increases in HR. The chronic treatment of animals with T. violacea or captropril produced (a) signicant (p < 0.05) reductions in the plasma levels of aldosterone when compared to the values obtained in the vehicle-treated group, (b) produced signifiant (p< 0.05) reduction in BP in the captopril treated group when compared to the vehicle-treated, (c) did not produce any signficant change in BP in the T. violacea-treated group when compared to the vehicle-treated group and (d) did not produce any signifiant change in HR or body weight in any of the groups. The result obtained in this study suggests that T. violacea reduced BP and HR in the SHR. Secondly, the BP and HR reducing effect of the MLE may involve a) the inhibition of the ACE, b) the inhibition of the beta; adrenoceptors, c) the stimulation of the muscarinic receptors and d) the reduction of the levels of aldosternone in plasma. The results also suggest that the MLE may not act through the angiotensin II receptors or the alpha adrenergic receptors.
Effects of aqueous leaf extract of Asystasia gangetica on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats
(BioMed Central Ltd, 2013) Mugabo, Pierre; Raji, Ismaila A.
Background: Asystasia gangentica (A. gangetica) belongs to the family Acanthaceae. It is used to treat hypertension, rheumatism, asthma, diabetes mellitus, and as an anthelmintic in South Africa, India, Cameroun, Nigeria, and Kenya respectively. It has also been reported to inhibit the angiotensin I converting enzyme (ACE) in-vitro. Therefore, the aim of this study is to investigate the in-vivo effect of aqueous leaf extract (ALE) of A. gangetica on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats (SHR); and to elucidate possible mechanism(s) by which it acts. Methods: The ALE of A. gangetica (10–400 mg/kg), angiotensin I human acetate salt hydrate (ANG I, 3.1–100 μg/kg) and angiotensin II human (ANG II, 3.1–50 μg/kg) were administered intravenously. The BP and HR were measured via a pressure transducer connecting the femoral artery to a Powerlab and a computer for recording. Results: A. gangetica significantly (p<0.05), and dose-dependently reduced the systolic, diastolic, and mean arterial BP. The significant (p<0.05) reductions in HR were not dose-dependent. Both ANG I and ANG II increased the BP dose-dependently. Co-infusion of A. gangetica (200 mg/kg) with either ANG I or ANG II significantly (p<0.05) suppressed the hypertensive effect of both ANG I and ANG II respectively, and was associated with reductions in HR. Conclusions: A. gangetica ALE reduced BP and HR in the SHR. The reduction in BP may be a result of actions of the ALE on the ACE, the ANG II receptors and the heart rate.
Effects of Leonotis leonurus aqueous extract on the isolated perfused rat heart
(Open Access Science Research Publisher, 2012) Mugabo, Pierre; Khan, Fatima; Burger, Andries
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.
Effects of the alkaloid present in the ethyl acetate: hexane (1 :4) fraction of Crinum macowanii on the isolated perfused rat heart
(University of the Western Cape, 2004) Njagi, Angela Gakii; Mugabo, Pierre
Crinum macowanii (CM) is used in traditional medicine in the treatment of various diseases including ischemic heart disease, rheumatic fever, cancer and skin diseases. The aqueous extract of CM bulbs was found have a positive inotropic effect similar to the one of adrenaline in normotensive rats. After the extraction of CM bulbs four fractions were collected, (1:4), (2:3), (3:2) and (4:1), from ethyl actetate: hexane as an eluent. The (1:4) further using PLC and the major band used for the experiments. Structure elucidation was further carried out on the major band isolated and a new alkaloid was identified from the bulbs of CM. The major aim of the study was to test the alkaloid isolated on the "double sided" working heart system. The parameters to be assessed were coronary flow (Qe), aortic output (Qa), cardiac output (CO), systolic and diastolic pressure (SP/DP), pulse pressure and heart rate (Hr). Wistar rats weighing between 250-350g were used. The hearts were isolated and perfused using Krebs Henseleit solution on the "double sided" working heart system. The parameters were monitored through a pressure transducer connected to a power lab and a computer. The Qe, Qa, CO, SP/DP, Pulse pressure and Hr reduced significantly when lycorinone (the proposed name given to the new alkaloid extracted from Crinium macowanii) was used at the concentrations of 0.005μg and 0.05μg. Further studies are recommended for the verification of the mechanism of action of lycorinone (negative chronotropic and negative inotropic effects).
Ethionamide pharmacokinetics in multidrugresistant tuberculosis patients with and without HIVinfection
(University of the Western Cape, 2017) Ezeukwu, Ifeoma Patricia; Mugabo, Pierre
Many studies have investigated the pharmacokinetics (PK) of anti-tuberculosis drugs in tuberculosis patients. However, currently in South Africa, no studies have been done on ethionamide (ETH) PK in adult MDR-TB patients that are infected with HIV and those without HIV infection. Therefore, the objective of this current study was firstly, to find out ethionamide plasma concentration using the LC-MS method; secondly, to evaluate and compare the pharmacokinetics of ethionamide in MDR-TB patients infected with and without HIV infection; thirdly, to examine the effects of ARVs and kidney impairment on the PK of ethionamide and fourthly, to find out the consequence of sex and age on ETH PK parameters.
Expanding presumptive male partner management of sexually transmitted infections (STIs) to Western Cape, South African community retail pharmacies
(University of the Western Cape, 2007) Ward, Kim Lana; Butler, Nadine; Mugabo, Pierre; School of Pharmacy; Faculty of Science
The effect of industrialisation has thrust the pharmaceutical profession into a clinical paradigm where the approcah to pharmaceutical decisions is more disease and patient orientated. Consequently, South African community pharmacies are inundated with requests from the public for advice and treatment on a wide range of medical conditions, including sexually transmitted infections (STI's). Although community pharmacies are often the first port of call for undiagnosed STI, limited diagnostic skills and legally-imposed prescribing restrictions preclude pharmacists from providing the necessary clinical management. The overarching goal of this dissertation was to present objective arguments and evidences (new and existing) around an expanded role for pharmacists in STI partner management.
Factors affecting the pharmacokinetics of vancomycin in children admitted to the intensive care unit (icu) of the Red Cross War Memorial Children's Hospital (RCWMCH).
(University of the Western Cape, 2023) Akunne, Onyinye Onyeka; Mugabo, Pierre
Vancomycin is a glycopeptide antibiotic that inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminal end of cell wall precursor units preventing the elongation and cross-linkage of the peptidoglycan. Vancomycin is used to treat infections with gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (S. aureus), coagulase-negative staphylococci and penicillin-resistant Streptococcus pneumoniae (S. pneumoniae). It is a time-dependent drug, and its efficacy depends on the duration of pathogen exposure to vancomycin. Low plasma concentration may lead to treatment failure and the re-emergence of bacterial resistance. Vancomycin is known to cause adverse effects at high concentrations. Therefore, it is necessary to monitor plasma concentrations to maintain vancomycin concentration within the therapeutic window. Vancomycin is mainly administered as an intravenous (IV) infusion as it is poorly absorbed from the gastrointestinal system.

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