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Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro
(J. Appl. Physiol., 2000) Ojuka, Edward O.; Nolte, Lorraine A.; Holloszy, John O.
Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro. J. Appl. Physiol. 88: 1072–1075, 2000.—Exercise acutely stimulates muscle glucose transport and also brings about an adaptive increase in the capacity of muscle for glucose uptake by inducing increases in GLUT-4 and hexokinase.1 Recent studies have provided evidence that activation of AMP protein kinase (AMPK) is involved in the stimulation of glucose transport by exercise. The purpose of this study was to determine whether activation of AMPK is also involved in mediating the adaptive increases in GLUT-4 and hexokinase. To this end, we examined the effect of incubating rat epitrochlearis muscles in culture medium for 18 h in the presence or absence of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which enters cells and is converted to the AMP analog ZMP, thus activating AMPK. Exposure of muscles to 0.5 mMAICAR in vitro for 18 h resulted in an ,50% increase in GLUT-4 protein and an ,80% increase in hexokinase. This finding provides strong evidence in support of the hypothesis that the activation of AMPK that occurs in muscle during exercise is involved in mediating the adaptive increases in GLUT-4 and hexokinase. AMP kinase; exercise; gene expression; skeletal muscle; tissue culture; 5-aminoimidazole-4-carboxamide ribonucleoside
Intermittent increases in cytosolic Ca2 stimulate mitochondrial biogenesis in muscle cells
(Am J Physiol Endocrinol Metab 283, 2002) Ojuka, Edward O.; Jones, Terry E.; Han, Dong-Ho; Chen, May; Wamhoff, Brain R.; Sturek, Micheal; Holloszy, John O.
Intermittent increases in cytosolic Ca2 stimulate mitochondrial biogenesis in muscle cells. Am J Physiol Endocrinol Metab 283: E1040–E1045, 2002. First published July 24, 2002; 10.1152/ajpendo.00242.2002.—Muscle contractions cause numerous disturbances in intracellular homeostasis. This makes it impossible to use contracting muscle to identify which of the many signals generated by contractions are responsible for stimulating mitochondrial biogenesis. One purpose of this study was to evaluate the usefulness of L6 myotubes, which do not contract, for studying mitochondrial biogenesis. A second purpose was to evaluate further the possibility that increases in cytosolic Ca2 can stimulate mitochondrial biogenesis. Continuous exposure to 1 Mionomycin, a Ca2 ionophore, for 5 days induced an increase in mitochondrial enzymes but also caused a loss of myotubes, as reflected in an 40% decrease in protein per dish. However, intermittent (5 h/day) exposure to ionomycin, or to caffeine or W7, which release Ca2 from the sarcoplasmic reticulum, did not cause a decrease in protein per dish. Raising cytosolic Ca2 intermittently with these agents induced significant increases in mitochondrial enzymes. EGTA blocked most of this effect of ionomycin, whereas dantrolene, which blocks Ca2 release from the sarcoplasmic reticulum, largely prevented the increases in mitochondrial enzymes induced by W7 and caffeine. These findings provide evidence that intermittently raising cytosolic Ca2 stimulates mitochondrial biogenesis in muscle cells. caffeine; exercise; gene expression; ionomycin; L6 myotubes
Promoting Psychiatry in the medical school: "The case of Uganda"
(Psychiatry Bulletin, 2002) Ovuga, E; Buga, J; Oboke, Henry; Boardman, J
Uganda has a rich history of medical education Odonga, 1989) that was severely harmed by the rise of Idi Amin and the years of internal strife. It is only over recent years that the country has begun to rebuild itself Boardman & Ovuga, 1997). A central problem for psychiatry in Uganda …
Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2+
(Am J Physiol Endocrinol Metab 282, 2002) Ojuka, Edward O.; Jones, Terry E.; Nolte, Lorraine A.; Chen, May; Wamhoff, Brain R.; Sturek, Micheal; Holloszy, John O.
Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2 . Am J Physiol Endocrinol Metab 282: E1008–E1013, 2002; 10.1152/ ajpendo.00512.2001.—There is evidence suggesting that adaptive increases in GLUT4 and mitochondria in skeletal muscle occur in parallel. It has been reported that raising cytosolic Ca2 in myocytes induces increases in mitochondrial enzymes. In this study, we tested the hypothesis that an increase in cytosolic Ca2 induces an increase in GLUT4. We found that raising cytosolic Ca2 by exposing L6 myotubes to 5 mM caffeine for 3 h/day for 5 days induced increases in GLUT4 protein and in myocyte enhancer factor (MEF)2A and MEF2D, which are transcription factors involved in regulating GLUT4 expression. The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca2 release, and completely blocked by KN93, an inhibitor of Ca2 - calmodulin-dependent protein kinase (CAMK). Caffeine also induced increases in MEF2A, MEF2D, and GLUT4 in rat epitrochlearis muscles incubated with caffeine in culture medium. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), which activates AMP-activated protein kinase (AMPK), also induced approximately twofold increases in GLUT4, MEF2A, and MEF2D in L6 myocytes. Our results provide evidence that increases in cytosolic Ca2 and activation of AMPK, both of which occur in exercising muscle, increase GLUT4 protein in myocytes and skeletal muscle. The data suggest that this effect of Ca2 is mediated by activation of CAMK and indicate that MEF2A and MEF2D are involved in this adaptive response. 5 -adenosine monophosphate-activated protein kinase; gene expression; skeletal muscle; tissue culture; myocyte enhancer factor 2; Ca2 -calmodulin-dependent protein kinase
Acute toxicity effects of the methanolic extract of Fagara zanthoxyloides (Lam.) root-bark
(African Health Sciences, 2003) Ogwal-Okeng, Jasper; Obua, Celestino.; Anokbonggo, William W.
Background: Fagara zanthoxyloides is a well known medicinal plant in Uganda. It is used extensively in malaria and other infections. However nothing is known about its toxicity. Objective: The objective of the study was to evaluate the acute toxicity of the methanolic extract of the root-bark of F. zanthoxyloides, in mice. Methods: Methanolic extract of the root-bark of the plant was administered orally to mice at various dose levels to determine the acute toxic effects and the median lethal dose (LD50) in mice. Results: The LD50 of the methanolic extract was found to be 5.0 g/Kg body weight within 95 % confidence limits. The mice showed signs of cerebral irritation before dying. Histopathological examinations of the viscera showed congestion and focal necrosis of the liver and renal tubules. Conclusion: It was concluded that the extract of F. zanthoxyloides is safe, however the cerebral mechanism that lead to the death of the mice need to be investigated further.
Spontaneous rupture of bladder in puerperium
(African Health Sciences, 2004) Wandabwa, Julius; Kiondo, Paul; Otim, Tom Charles
Abstract Spontaneous rupture of bladder and extravasation of urine in the peritoneum without evidence of trauma is rare. This condition is an emergency. It presents in a unique way therefore, the diagnosis and treatment is usually delayed. This patient presented with an acute abdominal pain and oliguria. She had delivered normally eight days before re-admission. Investigations were done and an exploratory laparotomy was performed. There was a tear in the fundus of the bladder and the peritoneal cavity contained urine. Peritoneal lavage was done and the bladder was repaired in layers. She was put on continuous bladder drainage for three weeks followed by bladder training. The bladder resumed its normal function. Early diagnosis and appropriate management decreases the morbidity and mortality associated with this condition. African Health Sciences 2004; 4(2) 138-13
Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle
(Proceedings of the Nutrition Society, 2004) Ojuka, Edward O.
Contractile activity induces mitochondrial biogenesis and increases glucose transport capacity in muscle. There has been much research on the mechanisms responsible for these adaptations. The present paper reviews the evidence, which indicates that the decrease in the levels of highenergy phosphates, leading to activation of AMP kinase (AMPK), and the increase in cytosolic Ca2+, which activates Ca2+/calmodulin-dependent protein kinase (CAMK), are signals that initiate these adaptative responses. Although the events downstream of AMPK and CAMK have not been well characterized, these events lead to activation of various transcription factors, including: nuclear respiratory factors (NRF) 1 and 2, which cause increased expression of proteins of the respiratory chain; PPAR-a, which up regulates the levels of enzymes of b oxidation; mitochondrial transcription factor A, which activates expression of the mitochondrial genome; myocyte-enhancing factor 2A, the transcription factor that regulates GLUT4 expression. The well-orchestrated expression of the multitude of proteins involved in these adaptations is mediated by the rapid activation of PPARg co-activator (PGC) 1, a protein that binds to various transcription factors to maximize transcriptional activity. Activating AMPK using 5-aminoimidizole-4-carboxamide-1-b-D-riboside (AICAR) and increasing cytoplasmic Ca2+ using caffeine, W7 or ionomycin in L6 myotubes increases the concentration of mitochondrial enzymes and GLUT4 and enhances the binding of NRF-1 and NRF-2 to DNA. AICAR and Ca-releasing agents also increase the levels of PGC-1, mitochondrial transcription factor A and myocyte-enhancing factors 2A and 2D. These results are similar to the responses seen in muscle during the adaptation to endurance exercise and show that L6 myotubes are a suitable model for studying the mechanisms by which exercise causes the adaptive responses in muscle mitochondria and glucose transport.
Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo
(Am J Physiol Endocrinol Metab 292, 2006) Smith, James A. H.; Collins, Malcolm; Grobler, Liesl A.; Magee, Carrie J.; Ojuka, Edward O.
Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo. Am J Physiol Endocrinol Metab 292: E413–E420, 2007. First published September 19, 2006; doi:10.1152/ajpendo.00142.2006.—In vitro binding assays have indicated that the exercise-induced increase in muscle GLUT4 is preceded by increased binding of myocyte enhancer factor 2A (MEF2A) to its cis-element on the Glut4 promoter. Because in vivo binding conditions are often not adequately recreated in vitro, we measured the amount of MEF2A that was bound to the Glut4 promoter in rat triceps after an acute swimming exercise in vivo, using chromatin immunoprecipitation (ChIP) assays. Bound MEF2A was undetectable in nonexercised controls or at 24 h postexercise but was significantly elevated 6 h postexercise. Interestingly, the increase in bound MEF2A was preceded by an increase in autonomous activity of calcium/calmodulin-dependent protein kinase (CaMK) II in the same muscle. To determine if CaMK signaling mediates MEF2A/DNA associations in vivo, we performed ChIP assays on C2C12 myotubes expressing constitutively active (CA) or dominant negative (DN) CaMK IV proteins. We found that 75% more MEF2A was bound to the Glut4 promoter in CA compared with DN CaMK IV-expressing cells. GLUT4 protein increased 70% 24 h after exercise but was unchanged by overexpression of CA CaMK IV in myotubes. These results confirm that exercise increases the binding of MEF2A to the Glut4 promoter in vivo and provides evidence that CaMK signaling is involved in this interaction. rats; C2C12 myotubes; chromatin immunoprecipitation assay; autonomous calcium/calmodulin-dependent protein kinase activity; myocyte enhancer factor 2A; glucose transporter-4
Upper gastrointestinal endoscopic findings in adolescents at Lacor hospital, Uganda
(African Health Sciences, 2006) Okello, Tom Richard
Background and Objectives: Fiberoptic endoscopy is a highly efficient diagnostic tool, which is now being increasingly used, in the pediatric age group. This study has been carried out to demonstrate indications for and common findings of endoscopy in children. Materials and Methods: We retrospectively reviewed the medical records for endoscopy indication and result of children who had endoscopy between Jan 2000 to June 2005. Results: We analyzed 135 children who were referred for upper gastrointestinal endoscopy. There were 38 boys and 97 girls. The mean age was 16 years (SD+/-1.4293). The main indications comprised epigastric pain (67.4%), dyspepsia (11.9), hematemesis (8.9%), recurrent abdominal pain (3%) recurrent vomiting (3%), and miscellaneous (5.8%). Endoscopic diagnose included duodenal ulcer (14.8%) and gastritis (12.6%); duodenal scarring (5.2%), bile reflux (5.2%) duodenitis (4.4%) and miscellaneous 6.4%. Conclusion:In Upper gastrointestinal endoscopy is a diagnostic procedure in children with gastrointestinal disorder. Gastritis and duodenal disease are commonly seen in children, hence must be included in differential diagnosis of children with digestive complaints and its management.
Antiplasmodial activity of extracts of selected medicinal plants used by local communities in western Uganda for treatment of malaria
(African Journal of Ecology, 2007) Katuura, Esther; Waako, Paul; Tabuti, John R. S.; Bukenya-Ziraba, Remigius; Ogwal-Okeng, Jasper
This study investigated the antiplasmodial activity of ten medicinal plants used to treat malaria in Southwestern Uganda. The study plants were Bothlioclines longpipes (Olive and Hiern), N.E.Br., Toddalia asiatica (L.) Lam., Maesa lanceolata Forssk., Indigofera emerginella steud. Ex A. Rich., Lantana trifolia L., Vernonia lasiopus O. Hoffm., Trimmeria bakeri Gilg., Rhus natalensis Bernh. ex. Krauss Erythrophleum pyrifolia and Conyza sp. Dry powdered plant material was extracted by sequential cold maceration using petroleum ether, chloroform and ethanol solvents respectively. Extracts were subjected to in vitro antiplasmodial screening against wild strains of Plasmodium falciparum using the nitro-tetrazolium blue-based lactate dehydrogenase assay. The chloroform extract of M. lanceolata (EC50 1.60 lg ml)1.), showed the highest antiplasmodial activity followed by R. natalensis (EC50 1.80 lg ml)1). Other extracts with significant activity were the chloroform leaf extract of Bothriocline longipes (EC50 3.66 lg ml)1) and the petroleum ether root extract of T. bakeri (EC50 3.955 lg ml)1).
CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene
(Am J Physiol Endocrinol Metab 295, 2007) Smith, James A. H.; Kohn, Tertius A.; Chetty, Ashley K.; Ojuka, Edward O.
CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene. Am J Physiol Endocrinol Metab 295: E698 –E704, 2008. First published July 22, 2008; doi:10.1152/ajpendo.00747.2007.—The role of CaMK II in regulating GLUT4 expression in response to intermittent exercise was investigated. Wistar rats completed 5 17-min bouts of swimming after receiving 5 mg/kg KN93 (a CaMK II inhibitor), KN92 (an analog of KN93 that does not inhibit CaMK II), or an equivalent volume of vehicle. Triceps muscles that were harvested at 0, 6, or 18 h postexercise were assayed for 1) CaMK II phosphorylation by Western blot, 2) acetylation of histone H3 at the Glut4 MEF2 site by chromatin immunoprecipitation (ChIP) assay, 3) bound MEF2A at the Glut4 MEF2 cis-element by ChIP, and 4) GLUT4 expression by RT-PCR and Western blot. Compared with controls, exercise caused a twofold increase in CaMK II phosphorylation. Immunohistochemical stains indicated increased CaMK II phosphorylation in nuclear and perinuclear regions of the muscle fiber. Acetylation of histone H3 in the region surrounding the MEF2 binding site on the Glut4 gene and the amount of MEF2A that bind to the site increased approximately twofold postexercise. GLUT4 mRNA and protein increased 2.2- and 1.8-fold, respectively, after exercise. The exercise-induced increases in CaMK II phosphorylation, histone H3 acetylation, MEF2A binding, and GLUT4 expression were attenuated or abolished when KN93 was administered to rats prior to exercise. KN92 did not affect the increases in pCaMK II and GLUT4. These data support the hypothesis that CaMK II activation by exercise increases GLUT4 expression via increased accessibility of MEF2A to its cis-element on the gene. myocyte enhancer factor; glucose transporter 4; chromatin immunoprecipitation assay; histone H3 acetylation; KN93; Ca2 /calmodulindependent kinase II phosphorylation
Access and use of medicines information sources by physicians in public hospitals in Uganda: a cross-sectional survey
(African Health Sciences, 2008) Tumwikirize, Winifred A.; Ogwal-Okeng, Jasper; Vernby, Åsa; Anokbonggo, Willy W.; Gustafsson, Lars L.; Lundborg, Cecilia S.
Background: Rational and cost-effective prescription of medicines requires up-to-date and readily accessible medicines information. There are several studies on availability and access to medicines information sources, but have been conducted only in high-income countries. Objective: To assess medicines information sources accessed by physicians in public hospitals in Uganda, and physicians’ opinion on establishment of a medicines information centre in the country. Methods: A cross-sectional survey including 369 physicians from six district, six regional and two university hospitals. Data was collected using a semi-structured self-administered questionnaire. Results Response rate was 91%. This included 31, 136 and 168 physicians from the district, regional and university hospitals, respectively. In the district hospitals the source of medicines information reported to be most available was colleagues (100%), while in the regional and university hospitals it was literature from pharmaceutical companies (98%) and hard copy of research publications (99%) respectively. The most frequently used source in the district and regional hospitals was National Standard Treatment Guideline (90% and 73% respectively), and colleagues in university hospitals (89%). Accessibility problems with reported available sources were commonest with research publications in medical journals, both hard copy and through the internet, MIMS, pharmacists and pharmacologists. Need for a medicines information centre was indicated by 80% of the respondents. Conclusion: Majority of the physicians in public hospitals in Uganda have limited access to unbiased drug information. Therefore, there is need to assess the feasibility of establishing a drug information centre, and then assess its use during a trial period. Key words: Medicines information, physicians, Uganda
Plasma levels of DDE/DDT and liver function in malaria control personnel 6 months after indoor residual spraying with DDT in northern Uganda, 2008
(South African Medical Journal, 2008) Bimenya, G S; Harabulema, M; Okot, J P; Olwa, Francis; Lugemwa, Myers; Okwi, A L
Objective. We investigated the relationship between plasma levels of dichlorodiphenyltrichloroethane (DDT) and liver function in malaria control personnel 6 months after one round of DDT indoor residual spraying (IRS). Method. This was a cross-sectional study in the districts of Apac and Oyam of Lango, northern Uganda. Volunteers were clinically examined, and 5 ml samples of venous blood were taken in heparinised tubes for a 6-month post-spray screening for DDT and plasma markers of liver function and internal organ disease. DDE/DDT was assayed using ELISA kits (Abraxis, USA); plasma enzyme activity concentrations of amylase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGT) were analysed using routine clinical chemistry automated methods (Konelab, Vantaa, Finland). Results. All 96 plasma samples analysed for xenobiotics contained DDE/DDT in the empirical range of 24.00 - 128.00 parts per billion (ppb) with a mean (SD) of 77.00 (±26.00) ppb. All 119 plasma samples studied for the markers exhibited enzyme activity concentration values within the population reference ranges, with empirical means (SD) of amylase 71.86 (34.07), AST 23.83 (12.71), ALT 7.84 (10.01) and GGT 58.37 (62.68) µg/l. Conclusion. Six months after IRS with DDT, the spray team had an average concentration of plasma DDE/DDT of 77 ppb. This had no deleterious effect on liver function. We recommend continued use of DDT for IRS disease control in Uganda until better practical alternatives are available.
Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination
(Malaria Journal, 2009) Ntale, Muhammad.; Obua, celestino; Mukonzo, Jackson; Mahindi, Margarita; Gustafsson, Lars L; Beck, Olof; Ogwal-Okeng, Jasper
Background: Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem® (artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper. Methods: Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood. Results: The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed. Conclusion: The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.
Sigmoid Volvulus and Ileosigmoid Knotting at St. Mary’s Hospital Lacor in Gulu, Uganda
(Eastand Central African Journal of Surgery, 2009) Okello, Tom Richard; Ogwang, David Martin; Kisa, P.; Komagum, P.
Background: Sigmoid volvulus is a common cause of intestinal obstruction in developing countries where it affects relatively young people. Little is known about this condition in our country and there is yet no literature from an environment like ours (northern Uganda) where civil war has devastated the economy with most of the populace displaced into internally displaced peoples’ camp. The main objective of this study was to determine the demographics, treatment and outcome of sigmoid Volvulus cases seen at Lacor Hospital. Methods: This was both a retrospective and prospective study of patients who presented with sigmoid volvulus at St. Mary’s Hospital Lacor over a period of 61/2 years from 1stJanuary 2002 to 31st July 2008. Medical records of patients who underwent sigmoid surgery was stratified for the following measures; demographic characteristics, presentation to hospital (emergency or elective), operative finding and operative procedure, complication, co-ominous factors and outcome. Similar data was gathered from patients who were prospectively followed up. Data was analyzed using SPSS. Results: A total of 44 patients were studied. Their age ranged from 16 to 80 years with a mean of 52.2years (SD +/- 15.98) and a mode of 60years. There was a preponderance of male (84%) with a male to female sex ratio of 5.3: 1. The disease significantly affected the older males compared with females P=0.032. Approximately 77% of the patients presented acutely and had to undergo emergency surgical intervention, the rest were subacute. About 75% of the patients were treated with primary resection and anastomosis, of which 52.2% were emergency cases. Colostomy was offered to 20.5% and sigmoidoscopic derotation to 4.5%. Overall mortality rate was 15.9% and of the patients who died, 18% had primary resection and anastomosis, while 11% were offered colostomy, (P>0.05). Most of those who died were either the older ones (median age 68years) and/or had co morbid illness such as diabetes mellitus, hypertension, intra-abdominal abscess and cancer. Conclusion: Sigmoid volvulus is relatively rare in our community. It commonly affect males particularly the old. Most of the patients presented acutely, requiring immediate resuscitation and surgical approach. In viable bowel, primary resection and anastomosis of the twisted sigmoid is feasible as it may not adversely affect outcome. Nevertheless colostomy should be considered if the bowel is gangrenous or perforated. Though the disease carries a high mortality, most of the patient who die are either older and/or have co-morbid conditions.
Existing capacity to manage pharmaceuticals and related commodities in East Africa
(BioMed Central : Human Resources for Health, 2009) Waako, Paul J; Odoi-adome, Richard; Obua, Celestino.; Owino, Erisa; Tumwikirize, Winnie; Ogwal-Okeng, Jasper; Anokbonggo, Willy W; Matowe, Lloyd; Aupont, Onesky
Background: East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities. Methods: Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building. Results: Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-thejob training and short courses were the preferred modes of training. Conclusion: There is inadequate capacity for managing medicines and related commodities in East Africa. There is an urgent need for training in aspects of pharmaceutical management to different categories of health workers. Skills building activities that do not take healthcare workers from their places of work are preferred.
A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.
(British Journal of Clinical Pharmacology, 2009) Mukonzo, Jackson K.; Röshammar, Daniel; Waako, Paul J; Andersson, Maria; Fukasawa, Takashi; Milani, Lili; Svensson, Jan Olof; Ogwal-Okeng, Jasper; Gustafsson, Lars L; Aklillu, Eleni
AIMS Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM. METHODS Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption. RESULTS Apparent oral clearance (95% confidence interval) was 4 l h l-1 (3.5, 4.5) in extensive metabolizers. In the final model, incorporating multiple covariates, statistical significance was found only for CYP2B6*6 and CYP2B6*11 on apparent oral clearance as well as ABCB1 (rs3842) on the relative bioavailability. Subjects homozygous for CYP2B6*6 (G516T, A785G) and *11 displayed 21 and 20% lower apparent oral clearance, respectively. Efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). The apparent peripheral volume of distribution was twofold higher in women compared with men. CONCLUSIONS The model identified the four factors CYP2B6*6, CYP2B6*11, a novel variant allele in ABCB1 (rs3842) and sex as major predictors of efavirenz plasma exposure in a healthy Ugandan population after single-dose administration. Use of mixed-effects modelling allowed the analysis and integration of multiple pharmacogenetic and demographic covariates in a pharmacokinetic population model.
War related sexual violence and it's medical and psychological consequences as seen in Kitgum, Northern Uganda: A cross-sectional study
(BMC International Health and Human Rights, 2009) Eugene, Kinyanda; Musisi, Seggane; Biryabarema, Christine; Ezati, Isaac; Oboke, Henry; Ojiambo-Ochieng, Ruth; Were-Oguttu, Juliet; Levin, Jonathan; Grosskurth, Heiner; Walugembe, James
Background: Despite the recent adoption of the UN resolution 1820 (2008) which calls for the cessation of war related sexual violence against civilians in conflict zones, Africa continues to see some of the worst cases of war related sexual violence including the mass sexual abuse of entire rural communities particularly in the Great Lakes region. In addition to calling for a complete halt to this abuse, there is a need for the systematic study of the reproductive, surgical and psychological effects of war related sexual violence in the African socio-cultural setting. This paper examines the specific long term health consequences of war related sexual violence among rural women living in two internally displaced person's camps in Kitgum district in war affected Northern Uganda who accessed the services of an Isis-Women's International Cross Cultural Exchange (Isis-WICCE) medical intervention. Methods: The study employed a purposive cross-sectional study design where 813 respondents were subjected to a structured interview as part of a screening procedure for an emergency medical intervention to identify respondents who required psychological, gynaecological and surgical treatment. Results: Over a quarter (28.6%) of the women (n= 573) reported having suffered at least one form of war related sexual violence. About three quarters of the respondents had 'at least one gynaecological complaint' (72.4%) and 'at least one surgical complaint' (75.6%), while 69.4% had significant psychological distress scores (scores greater than or equal to 6 on the WHO SRQ-20). The factors that were significantly associated with war related sexual violence were the age group of less than or equal to 44 years, being Catholic, having suffered other war related physical trauma, and having 'at least one gynaecological complaint'. The specific gynaecological complaints significantly associated with war related sexual violence were infertility, chronic lower abdominal pain, abnormal vaginal bleeding, and sexual dysfunction. In a multivariable analysis the age group of less than or equal to 44 years, being Catholic and having 'at least one gynaecological complaint' remained significantly associated with war related sexual violence. Conclusion: The results from this study demonstrate that war related sexual violence is independently associated with the later development of specific gynaecological complaints.
Lactose intolerance among severely malnourished children with diarrhoea admitted to the nutrition unit, Mulago hospital, Uganda
(BMC Pediatrics, 2010) Nyeko, Richard; Kalyesubula, Israel; Mworozi, Edison; Bachou, Hanifa
Background: Lactose intolerance is a common complication of diarrhoea in infants with malnutrition and a cause of treatment failure. A combination of nutritional injury and infectious insults in severe protein energy malnutrition reduces the capacity of the intestinal mucosa to produce lactase enzyme necessary for the digestion of lactose. The standard management of severe malnutrition involves nutritional rehabilitation with lactose-based high energy formula milk. However, some of these children may be lactose intolerant, possibly contributing to the high rate of unfavorable treatment outcomes. This study was therefore designed to establish the prevalence of lactose intolerance and associated factors in this population. Methods: A descriptive cross sectional study involving 196 severely malnourished children with diarrhoea aged 3-60 months was done in Mwanamugimu Nutrition Unit (MNU), Mulago hospital between October 2006 and February 2007. Results: During the study period, 196 severely malnourished children with diarrhoea were recruited, 50 (25.5%) of whom had evidence of lactose intolerance (stool reducing substance ≥ 1 + [0.5%] and stool pH < 5.5) and it occurred more commonly in children with kwashiorkor 27/75 (36.0%) than marasmic-kwashiorkor 6/25 (24.0%) and marasmus 17/96 (17.7%). Oedematous malnutrition (p = 0.032), perianal skin erosion (p = 0.044), high mean stool frequency (p = < 0.001) and having ≥2 diarrhoea episodes in the previous 3 months (p = 0.007) were the independent predictors of lactose intolerance. Other factors that were significantly associated with lactose intolerance on bi-variate analysis included: young age of 3- 12 months; lack of up to-date immunization; persistent diarrhoea; vomiting; dehydration, and abdominal distension. Exclusive breastfeeding for less than 4 months and worsening of diarrhoea on initiation of therapeutic milk were the other factors. Conclusions: The prevalence of lactose intolerance in this study setting of 25.5% is relatively high. Routine screening by stool pH and reducing substances should be performed especially in the severely malnourished children with diarrhoea presenting with oedematous malnutrition, perianal skin erosion, higher mean stool frequency and having had ≥2 diarrhoea episodes in the previous 3 months. Use of lactose-free diets such as yoghurt should be considered for children found to have evidence of lactose intolerance and whose response on standard therapeutic milk formula is poor.
Phytochemicals and uses of Moringa oleifera leaves in Ugandan rural communities
(Journal of Medicinal Plants Research, 2010) Kasolo, Josephine N; Bimenya, Gabriel S.; Ojok, Lonzy; Ochieng, Joseph; Ogwal-Okeng, Jasper
Moringa oleifera grown and used in many countries around the world is a multi-purpose tree with medicinal, nutritional and socio-economic values. In Senegal and Benin, M. oleifera leaves are dispensed as powder at health facilities to treat moderate malnutrition in children. It established the medicinal uses of M. oleifera leaves by local communities in Uganda and identified phytochemicals present in M. oleifera leaves extracts. It used quantitative and experimental methods that established the uses, and identified phytochemicals in M. oleifera leaves. Employed serial extractions, using ether, ethanol and water as solvents. The phytochemicals were qualitatively identified using standard chemicals and standard outcomes. Twenty-four medicinal uses of M. oleifera leaves were established. Phytochemicals present included: tannins, steroids and triterpenoids, flavonoids, saponins, anthraquinones, alkaloids and reducing sugars. The local communities in Uganda use M. oleifera leaves to treat common ailments. Presence of phytochemicals in the extracts, indicate possible preventive and curative property of M. oleifera leaves. There is need to standardize M. oleifera leaves use for nutrition and herbal medicine.

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