Browsing by Author "Mafuru, Magesa"
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Item Analysis of Combined Effect of CYP2C19 Genetic Polymorphism and Proton Pump Inhibitors Coadministration on through concentration of Voriconazole(Pharmacogenomics and Personalized Medicine, 2021) Mafuru, Magesa; Phillip, Amani; Mgone, Charles S.Purpose: To analyze the combined effect of CYP2C19 genetic polymorphism and PPIs coadministration on voriconazole trough concentration (VCZ-Ctrough) in Chinese patients with hematological disorders. Patients and Methods: A prospective observational study involved 250 plasma samples from 114 adult patients receiving voriconazole with or without PPIs were analyzed. Demographics and clinical characteristics were obtained from patient’s records. A validated LC-MS/MS was used to quantify the plasma VCZ-Ctrough. Genotyping for CYP2C19*2 and CYP2C19*3 variant alleles was performed by PCR-RFLP followed by DNA sequencing. The combined total score (from 2 to 5) was calculated for each patient. The higher the score, the lesser the metabolism of the patient. Findings: Fifty percent of patients administered with voriconazole were coadministered with PPIs, predominantly omeprazole or esomeprazole. Patients exhibiting CYP2C19 poor metabolizer phenotype showed a significantly higher median VCZ-Ctrough, (4.31µg/mL [IQR, 1.64µg/mL–7.36µg/mL]) than patients with normal metabolizer (1.38µg/mL, [IQR, 0.79µg/mL–2.14µg/mL], p < 0.0001). Similarly, patients co-administration with PPIs had higher median VCZ-Ctrough (2.86µg/mL [IQR 1.33µg/mL–4.66µg/mL]), than PPIs non-users (1.71µg/mL, [IQR, 0.86µg/mL–3.48µg/mL], p = 0.001). However, we noted that the median VCZ-Ctrough for each factor was ranging within the normal recommended therapeutic range in the Chinese population (0.5µg/mL–5µg/mL). But when the two factors were combined, the median VCZ-Ctrough was steadily increasing as the metabolic capacity (reflected by combined total score) was increasing. Importantly, the median VCZ-Ctrough in PM/PPIs user (total score 5) was significantly elevated to supra-therapeutic levels compared to NM/PPI non-user group (total score 2) (5.83µg/mL [IQR, 2.19µg/mL–9.51µg/mL] versus 1.13µg/mL [IQR, 0.67µg/mL–1.82µg/mL]), respectively, P < 0.0001. Furthermore, we observed that the elevation of median VCZ-Ctrough to supra-therapeutic levels was largely contributed by omeprazole or esomeprazole compared to lansoprazole or pantoprazole. Conclusion: Coadministration with PPIs significantly increased voriconazole trough concentrations and there was an additive effect in CYP2C19 PMs, who were most likely to have supra-therapeutic levels.Item The association of 18 F-FDG PET/CT and biomarkers in confirming coronary microvascular dysfunction(BMC research notes, 2018) Mafuru, MagesaObjective: The purpose of this study is to evaluate the association between PET/CT CFR and biomarkers combined in confirming the diagnosis of coronary microvascular dysfunction. Results: A total of 28 patients (21 males and 7 females) were included in this descriptive observational study (both qualitative and quantitative). The mean patient age was 55.50 ± 10.21 years (range 27–70 years) and the median was 56.5 years (range 49–63 years). All patients underwent Echo, CAG and PET/CT scan. Chest tightness was the most common symptom in our study. Most patients had normal blood pressure (n = 18, 64.3%) while only (n = 10, 37.5%) had hypertension, and (n = 1, 3.6%) had diabetes mellitus. The mean HDL in CMVD (n = 25) and non-CMVD (n = 3) were 1.30 ± 0.39 and 1.08 ± 0.95, respectively, indicating that the difference between the groups was statistically significant (p = 0.04). Similarly, the mean HBA1c- (glycated haemoglobin) in CMVD (n = 25) and non-CMVD (n = 3) were 5.6 ± 0.53 and 5.0 ± 0.26, respectively, with (p = 0.03). Our findings managed to show the association between biomarkers and PET/CT CFR in confirming the diagnosis of coronary microvascular dysfunction. Keywords: Coronary microvascular dysfunction (CMVD), Brain natriuretic peptide (BNP), Red cell distribution (RDW), Coronary flow reserve (CFR)Item Effects of nifedipine on doppler indices of fetal middle cerebral artery and umbilical artery in managing hypertensive disorders of pregnancy.(Authorea Preprints., 2020) Mafuru, MagesaBackground: Hypertensive disorders of pregnancy affects almost 6 percent of all pregnancies all over the world with recent statistical data showing an increase of incidence rates both in the developed and developing worlds. HDP affects uteroplacental and fetoplacental perfusion and may result into poor fetal conditions and increase morbidity and mortality. Calcium channel blockers (CCB) are the most commonly used antihypertensive oral medications in pregnancy due to effectiveness and less side effects. Aim: To study how effective CCB are in improving uteroplacental perfusion and as to study whether lowering of blood pressure by CCB may have positive or negative impact to Doppler indices of fetal middle cerebral artery (MCA) as well as umbilical artery (UA) S/D which were measure by Doppler indices variables which include MCA peak systolic velocity (PS), MCA pulsatility index (PI), MCA resistance index (RI) and UA systolic to diastolic ratio (S/D). Material and methodology: the study involved one hundred and twenty pregnant women with the gestation ages ranging from thirty-two weeks to forty weeks. Among them sixty were having hypertensive disorders of pregnancy including preeclampsia and sixty were normal pregnant women. In case groups blood pressure before and after at least one of medication were recorded, and Doppler ultrasound indices for fetal MCA and UA S/D after at least one week of medication was also recorded, follow up for calcium channel blocker dosage was recorded, delivery gestation age, mode of delivery and Apgar score, as well as neonate hospitalization was also recorded. In the control group, blood pressure, fetal MCA indices and UA S/D, delivery gestation age, mode and Apgar score were and related. Results: We analyzed the results by using statistical package for social sciences (SPSS) version 20, in which Doppler indices between the case and control groups were compared. MCA Peak systolic speed, UA S/D ratio, MCA Pulsatile index and MCA resistance index mean values differences between the two groups were not statistically significant i.e. p-value >0.05 (p- value=0.68,0.062,0.18,0.115 respectively). However, in comparing resistance index (RI) between case group nifedipine users of 30mg dose per day with control group p-value was statistically significant (p-value=0.026, 95% CI =-011 to-0.007). In correlation with p- value<0.05,and measured by (coefficient b±SE): PS was affected by gestation age (b±SE=1.63±0.42) , S/D ratio was affected by gestation age(b±SE=-01±0.02), systolic blood pressure (b±SE=0.013±0.004) and age of women (b±SE=0.007±0.013), PI on the other hand was impacted by gravidity(b±SE=0.07±0.03) and preeclampsia(b±SE=0.2±0.07). RI showed correlation with chronic hypertension (b±SE=-0.08±0.03). on outcomes of pregnancy there was a relationship between S/D and Apgar score, an increase of S/D was associated with decrease of Apgar score, b±SE=-0.16±0.06,95% CI=-0.27 to 0.05, p-value=0.06. Apgar score≥8 in the control group was 52(86.7%) compared to 60(100%) in the control group. Apgar score 6-7 was 7(11.7%) in case group compared to 0(0%) in control group. There was one case 1(1.6%) with Apgar score<6 in cases group comparing to 0(0%) in controls. Conclusion: Apart from having good effect in lowering blood pressure and having less teratogenic effects, oral use of nifedipine as an antihypertensive of choice in managing hypertensive disorders of pregnancy seem to improve uteroplacental perfusion in women with hypertensive disorders of pregnancy . Even with the use of CCB women with HDP had a high need for early termination of pregnancy compared to normotensive women . We also found out that low dose of nifedipine (30mg per day) in cases especially with preeclampsia was associated with a significantly high RI compared to those using high dose of nifedipine.Item Epifriedelanol is the key compound to antibacterial effects of extracts of Synadenium glaucescens (Pax) against medically important bacteria(Frontiers in Tropical Diseases, 2023-01-19) Mafuru, MagesaIntroduction: Synadenium glaucescens has been used for the treatment of bacterial infections in many parts of the world. We investigated the antibacterial and cytotoxicity activities of secondary metabolites of this plant. Methods: Hexane, dichloromethane, methanol, and water were used as extraction solvents. The extract of the root bark was fractionated with ethyl acetate and methanol. The isolation of compounds from root barks, leaves and stem wood extracts were carried out using column chromatography. Antibacterial activities were characterized based on growth curves, killing curves and MIC determinations. Haemolytic effect towards sheep red blood cells (RBCs) was analysed with spectrophotometer at the wavelength of 540nm. Results and Discussion: Extracts from whole root and root bark showed strong activity against Staphylococcus aureus, and Streptococci and Enterococci species, and moderate to weak activity against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella species, Shigella sonnei and Yersinia enterocolitica. Staphylococcus aureus was the most susceptible, and E. coli and Klebsiella pneumonia were the least susceptible ones. Likewise, extracts, fractions, sub-fractions and epifriedelanol demonstrated bacteriostatic activity against S. aureus. The haemolytic activity of the extracts, fractions, sub-fractions and epifriedelanol was significantly low compared to the positive control, hydrogen peroxide. But extract from leaves showed high haemolytic effects at the concentrations of 500 μg/mL and 1000 μg/mL. Thus, extracts of S. glaucescens have antibacterial activity against several Gram-positive bacteria including Methicillin Resistant S. aureus with low haemolytic activity. At high concentrations, the extracts from leaves have toxicity risk. More studies for the active compounds are required for biological testing.Item Feasibility study for the long-term management of refractory hyperkeratotic eczema with calcipotriol and betamethasone dipropionate (Daivobet ® ), viaminate and concomitant conventional therapies: a retrospective study(Cosmetic and Investigational Dermatology., 2020) Mafuru, MagesaBackground: The available treatments for refractory hyperkeratotic eczema are inadequate with frustrating results. We, therefore, incorporated Calcipotriol and Betamethasone Dipropionate (Daivobet®), and Viaminate into the mainstay treatment to improve the clinical symptoms. The study aimed to evaluate the efficacy of Daivobet® and Viaminate as a potential treatment alternative for refractory hyperkeratotic eczema. Patients and Methods: Between 2013 and 2015, 61 patients diagnosed with refractory hyperkeratotic eczema (RHE) who had shown inadequate response to conventional therapies were pooled from a single center. Besides, they were all treated with Daivobet®, Viaminate, and an occlusive dressing mixture containing 5% salicylic acid ointment and 25% zinc oxide paste following inadequate response to conventional therapies (corticosteroids plus 25% zinc oxide paste and 5% salicylic acid ointment). Investigators Global Assessment (IGA) and Patient-Oriented Eczema Measure (POEM) assessed baseline and outcome measures for the degree of hyperkeratinization (0-clear; 3-moderate; 4-severe). Results: Of the 61 patients, 49 (80.3%) patients presented with moderate RHE and 12 (19.7%) with severe RHE. After 24 weeks of treatment, the period for loss of keratinization was significantly lower in patients with moderate RHE (3.9±1.9 weeks) than those with severe RHE (10.8±1.0 weeks) with a P-value <0.01. Furthermore, they required a significantly shorter total treatment duration (10.6 ± 4.3 weeks) than those with severe RHE (20.3±3.6 weeks) with a P-value of <0.01. However, there were no significant differences in post hoc analysis at week 36 with P-values of 0.46 and 1.00 for IGA and POEM, respectively. Conclusion Our results showed that the incorporation of Viaminate and Daivobet® into mainstay treatment was effective and safe for the long-term management of RHE.Item The influence of Proinflammatory Cytokines on voriconazole trough concentration in patients with different forms of hematologic disorders(The Journal of Clinical Pharmacology, 2019) Mafuru, MagesaEven though multiple factors are involved in the high fluctuation of voriconazole (VCZ) plasma concentration, little is known regarding the influence of proinflammatory cytokines on VCZ concentration. The aim of this study was to investigate the influence of proinflammatory cytokines, namely, interleukin (IL)-1β, IL-6, IL-18, interferon-γ, tumor necrosis factor-α, and transforming growth factor (TGF)-β1 on VCZ trough concentration (VCZ-Cmin) in Chinese patients with different forms of hematologic disorders. A total of 250 plasma samples from 113 patients were analyzed for VCZ-Cmin and proinflammatory cytokines using a validated liquid chromatography–tandem mass spectrometry and enzyme-linked immunosorbent assay methods, respectively. Patient demographics and clinical characteristics were obtained from hospital records. VCZ-Cmin was significantly correlated with IL-18 in acute myeloid leukemia (r = 0.456; P ˂ .0001), acute lymphoblastic leukemia (r = 0.317; P = .019), and chronic myeloid leukemia (r = 0.737; P = .004) while VCZ-Cmin and TGF-β1 were correlated (r = 0.436; P ˂ .001) in acute myeloid leukemia patients only. VCZ-Cmin at different concentration range showed significant inhibitory effect of IL-6. A backward multiple linear regression model revealed patient age (coefficient [β] = 0.025; P = .04), gamma-glutamyl transferase (β = 0.003; P = .023), IL-6 (β = –0.001; P = .024), proton pump inhibitor coadministration (β = 1.518; P = .002), and cytochrome P450 (CYP) 2C19 polymorphism as predictors of VCZ-Cmin; however, these factors explained only 29% of VCZ-Cmin variation. In conclusion, IL-18 and TGF-β1 have correlation with VCZ-Cmin in Chinese patients with leukemia. Apparently, VCZ may have an inhibitory effect on IL-6 levels. Furthermore, patient age, gamma-glutamyl transferase, IL-6, PPI coadministration, and cytochrome P450 2C19 polymormorphism partially predicted the VCZ-Cmin. Therapeutic drug monitoring of VCZ in Chinese patients is highlyItem The variation of superior semicircular canal bone thickness in relation to age and gender(Acta oto-laryngologica, 2019) Mafuru, MagesaBackground: Superior semicircular canal dehiscence syndrome (SSCD) is a current diagnosis that is due to a loss of bone covering the superior semicircular canal (SSC). This results in pressure-/sound- induced vertigo and oscillopsia. Objective: To find the variation of the thickness of the bone that covers the Superior Semicircular Canal with relation to age and gender among the Chinese descents. Materials and methods: Three hundred and eleven temporal bone Cone Beam Computed Tomography (CBCT) images of patients who attended Otology clinic at Second Hospital of Shandong University from January, 2017 to April, 2018 were retrospectively studied. The images were reconstructed in the line of Poschl and the thinnest area of the bone covering the SSC was taken. Results: We included 172 (55.31%) females and 139 (44.69%) males. Mean age was 41 years. Overall mean difference in thickness was found to be –0.0210. There was no significant difference between the female and male bone thickness (p = .7113). With age the mean difference was 0.0801 (p = .1557) which was not statistically significant. Conclusion and significance: There was no significant change in bone thickness with advancing age. CBCT is the best method of assessing SSCD.