Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

The process of harmonizing competency-based curricula for medicine and nursing degree programmes: A Multi-institutional and multi-professional experience from Tanzania.

In many low- and middle-income countries, there seems to be a mismatch between graduate skills and healthcare industry requirements due to variability in curricula. With the current increased global demand for competent health profession graduates, harmonizing competency-based curricula (CBC) is necessary to address this mismatch. This paper describes how three health professions training universities in Tanzania and their two long-standing United States partners embarked on developing harmonized CBC for undergraduate medicine and nursing degrees. The main goal of the activity was to develop templates to harmonize curricula that would support graduates to acquire mandatory national Graduate Minimum Essential Competencies (GMEC) irrespective of the institution of their training. The paper describes the processes of engaging multiple institutions, the professions of medicine and nursing and various stakeholders to develop mandatory curricula generic competencies, creating milestones for assessing competencies, training faculty at each of the three partnering institutions in curriculum delivery and assessments, resulting in the adoption of the curricula by the University leadership at each institution. Ultimately the Tanzania Commission for Universities (TCU) a regulatory body required all schools of medicine and nursing in the country to adopt the curricula, thus creating a harmonized national standard for teaching medicine and nursing beginning October 2022.

Anti-plasmodial activity of Norcaesalpin D and extracts of four medicinal plants used traditionally for treatment of malaria.

BACKGROUND: Malaria is an old life-threatening parasitic disease that is still affecting many people, mainly children living in sub-Saharan Africa. Availability of effective antimalarial drugs played a significant role in the treatment and control of malaria. However, recent information on the emergence of P. falciparum parasites resistant to one of the artemisinin-based combination therapies suggests the need for discovery of new drug molecules. Therefore, this study aimed to evaluate the antiplasmodial activity of extracts, fractions and isolated compound from medicinal plants traditionally used in the treatment of malaria in Tanzania. METHODS: Dry powdered plant materials were extracted by cold macerations using different solvents. Norcaesalpin D was isolated by column chromatography from dichloromethane root extract of Caesalpinia bonducella and its structure was assigned based on the spectral data. Crude extracts, fractions and isolated compound were evaluated for antiplasmodial activity against chloroquine-sensitive P. falciparum (3D7), chloroquine-resistant P. falciparum (Dd2, K1) and artemisinin-resistant P. falciparum (IPC 5202 Battambang, IPC 4912 Mondolkiri) strains using the parasite lactate dehydrogenase assay. RESULTS: The results indicated that extracts of Erythrina schliebenii, Holarrhena pubescens, Dissotis melleri and C. bonducella exhibited antiplasmodial activity against Dd2 parasites. Ethanolic root extract of E. schliebenii had an IC50 of 1.87 µg/mL while methanolic and ethanolic root extracts of H. pubescens exhibited an IC50 = 2.05 µg/mL and IC50 = 2.43 µg/mL, respectively. Fractions from H. pubescens and C. bonducella roots were found to be highly active against K1, Dd2 and artemisinin-resistant parasites. Norcaesalpin D from C. bonducella root extract was active with IC50 of 0.98, 1.85 and 2.13 µg/mL against 3D7, Dd2 and IPC 4912-Mondolkiri parasites, respectively. CONCLUSIONS: Antiplasmodial activity of norcaesalpin D and extracts of E. schliebenii, H. pubescens, D. melleri and C. bonducella reported in this study requires further attention for the discovery of antimalarial lead compounds for future drug development.

Preparing Institutions to Implement Harmonized Medicine and Nursing Curricula Through the Use of Cross-Institutional Faculty Developers.

Background: Effective implementation of new curricula requires faculty to be knowledgeable about curriculum goals and have the appropriate pedagogical skills to implement the curriculum, even more so if the new curriculum is being deployed at multiple institutions. In this paper, we describe the process of creating a common faculty development program to train cross-institutional faculty developers to support the implementation of national harmonized medicine and nursing curricula. Methods: A five-step approach was used, including a cross-institutional needs assessment survey for faculty development needs, the development of a generic faculty development program, the identification and training of cross-institutional faculty educators, and the implementation of cross-institutional faculty capacity-building workshops. Results: A list of common cross-cutting faculty development needs for teaching and learning was identified from the needs assessment survey and used to develop an accredited, cross-institutional faculty development program for competency-based learning and assessment. A total of 24 cross-institutional faculty developers were identified and trained in 8 core learning and assessment workshops. A total of 18 cross-institutional and 71 institutional workshops were conducted, of which 1292 faculty members and 412 residents were trained, and three cross-institutional educational research projects were implemented. Conclusion: The success attained in this study shows that the use of cross-institutional faculty developers is a viable model and sustainable resource that can be used to support the implementation of harmonized national curricula.

Safety evaluation and bioassay-guided isolation of antimycobacterial compounds from Morella salicifolia root ethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Although the available medicines can cure almost all tuberculosis drug-susceptible patients some problems including the emergence of multi-drug resistant and extensively drug-resistant strains press for the need of new anti-TB medicines. Morella salicifolia is a common plant that is widely used in traditional medicine for managing HIV and AIDS-related conditions including tuberculosis but no studies have been done to evaluate its safety and efficacy. AIM OF THE STUDY: This study was designed to investigate the antimycobacterial activity and safety of M. salicifolia extract and its constituents. MATERIAL AND METHODS: Antimycobacterial activity of the crude extract was tested against non-pathogenic mycobacteria including Mycobacterium aurum (MA), Mycobacterium indicus pranii (MIP) and Mycobacterium madagascariense (MM) using the broth microdilution method. Bioassay-guided fractionation was employed to isolate the active compounds. Some of the isolated active compounds were tested for antimycobacterial activity against the standard and selected clinical isolates of M. tuberculosis. Safety of the crude extract was assessed using cytotoxicity assay and oral acute toxicity testing. RESULTS: The crude extract exhibited antimycobacterial activity against all the species used. The study led to isolation of six compounds; four pentacyclic triterpenoids; (3ß)-3-Hydroxyolean-12-en-28-oic acid (Oleanolic acid) (1), (2α,3ß)-2,3-Dihydroxyolean-12-en-28-oic acid (maslinic acid) (2), D-Friedoolean-14-ene-3ß,28-diol (taraxerol) (3), and D-Friedoolean-14-en-3ß-ol (myricadiol) (4), and two diarylheptanoids; (±)-myricanol (5) and myricanone (6). The six compounds exhibited activity against three nonpathogenic mycobacteria species. Compound 2, was the most active, with MICs of 17, 28 and 56 µg/ml against MM, standard a M. tuberculosis strain H37RV and rifampicin resistant M. tuberculosis clinical isolates, respectively. The crude extract did not show toxicity on peripheral blood mononuclear cells and it was safe in mice following acute oral toxicity test. CONCLUSION: The results from this study indicate that some isolated compounds in Morella salicifolia could form potential scaffolds for drug development efforts targeting M. tuberculosis. More studies are needed to further explore the potential of the plant extract and its secondary metabolites in the management of HIV and AIDS-related conditions using in-vivo models.

Larvicidal, antimicrobial and brine shrimp activities of extracts from Cissampelos mucronata and Tephrosia villosa from coast region, Tanzania.

BACKGROUND: The leaves and roots of Cissampelos mucronata A. Rich (Menispermaceae) are widely used in the tropics and subtropics to manage various ailments such as gastro-intestinal complaints, menstrual problems, venereal diseases and malaria. In the Coast region, Tanzania, roots are used to treat wounds due to extraction of jigger. Leaves of Tephrosia villosa (L) Pers (Leguminosae) are reported to be used in the treatment of diabetes mellitus in India. In this study, extracts from the roots and aerial parts of C. mucronata and extracts from leaves, fruits, twigs and roots of T. villosa were evaluated for larvicidal activity, brine shrimps toxicity and antimicrobial activity. METHODS: Powdered materials from C. mucronata were extracted sequentially by dichloromethane followed by ethanol while materials from T.villosa were extracted by ethanol only. The extracts obtained were evaluated for larvicidal activity using Culex quinquefasciatus Say larvae, cytotoxicity using brine shrimp larvae and antimicrobial activity using bacteria and fungi. RESULTS: Extracts from aerial parts of C. Mucronata exhibited antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Vibrio cholera, Bacillus anthracis, Streptococcus faecalis and antifungal activity against Candida albicans and Cryptococcus neoformans. They exhibited very low toxicity to brine shrimps and had no larvicidal activity. The root extracts exhibited good larvicidal activity but weak antimicrobial activity. The root dichloromethane extracts from C. mucronata was found to be more toxic with an LC50 value of 59.608 µg/mL while ethanolic extracts from root were not toxic with LC50>100 µg/mL). Ethanol extracts from fruits and roots of T. villosa were found to be very toxic with LC50 values of 9.690 µg/mL and 4.511 µg/mL, respectively, while, ethanol extracts from leaves and twigs of T. villosa were found to be non toxic (LC50>100 µg/mL). CONCLUSION: These results support the use of C. mucronata in traditional medicine for treatment of wounds. Extracts of C. mucronata have potential to yield active antimicrobial and larvicidal compounds. The high brine shrimp toxicity of T. villosa corroborates with literature reports that the plant is toxic to both livestock and fish. The results further suggest that T. villosa extracts have potential to yield larvicidal and possibly cytotoxic compounds. Further studies to investigate the bioactive compounds responsible for the observed biological effects are suggested.

Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, double-blind, double-dummy trial.

BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for treatment of moderate to severe oropharyngeal candidiasis. We conducted a prospective, randomized, double-blind, placebo-controlled trial to compare the clinical and mycological responses, relapse rates, and safety of a single 750-mg dose and a 14-day course of treatment with fluconazole. METHODS: A total of 220 HIV-infected patients with clinical and mycological evidence of oropharyngeal candidiasis were randomly assigned in a 1:1 ratio to receive either a 750-mg single dose of orally administered fluconazole (110 patients) or 150 mg of orally administered fluconazole once per day for 2 weeks (110 patients). The primary efficacy analysis was based on clinical and mycological responses at the end of treatment. Secondary parameters were safety and relapse rate. RESULTS: Single-dose fluconazole was equivalent to a 14-day course of fluconazole in achieving clinical and mycological cure, with clinical cure rates of 94.5% and 95.5%, respectively (odds ratio, 0.825; 95% confidence interval, 0.244-2.789; P= .99), and mycological cure rates of 84.5% and 75.5%, respectively (odds ratio, 1.780; 95% confidence interval, 0.906-3.496; P= .129). Drug-related adverse events were uncommon and were not different between the treatment groups. CONCLUSION: A single dose of 750 mg of fluconazole was safe, well tolerated, and as effective as the standard 14-day fluconazole therapy in patients with HIV infection and acquired immunodeficiency syndrome who had oropharyngeal candidiasis coinfection.

Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis.

BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2). RESULTS: Candida albicans was the most frequently isolated species from 250 (84.5%) patients followed by C. glabrata from 20 (6.8%) patients, and C. krusei from 10 (3.4%) patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients. CONCLUSION: C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

Mosquito larvicidal constituents from Lantana viburnoides sp viburnoides var kisi (A. rich) Verdc (Verbenaceae).

BACKGROUND & OBJECTIVES: Lantana viburnoides sp viburnoides var kisi is used in Tanzania ethnobotanically to repel mosquitoes as well as in traditional medicine for stomach ache relief. Bioassay-guided fractionation and subtraction bioassays of the dichloromethane extract of the root barks were carried out in order to identify the bioactive components for controlling Anopheles gambiae s.s. mosquito larvae. METHODS: Twenty late III or early IV instar larvae of An. gambiae s.s. were exposed to various concentrations of the plant extracts, fractions, blends and pure compounds, and were assayed in the laboratory by using the protocol of WHO 1996. Mean mortalities were compared using Dunnett's test (p < 0.05) and lethal concentration calculated by Lackfit Inversel of the SAS programme. RESULTS: The crude extract (LC50 = 7.70 ppm in 72 h) and fractions exhibited different level of mosquito larvicidal activity with subtraction of some fractions resulting in activity enhancement. The active fractions contained furanonaphthaquinones regio-isomers (LC50 = 5.48-5.70 ppm in 72 h) and the lantadene triterpenoid camaric acid (LC50 = 6.19 ppm in 72 h) as active principles while the lupane triterpenoid betulinic acid (LC50 < 10 ppm in 72 h) was obtained from the least active fraction. INTERPRETATION & CONCLUSION: Crude extracts and some fractions had higher or comparable larvicidal activity to the pure compounds. These results demonstrate that L. viburnoides sp viburnoides var kisi extracts may serve as larvicides for managing various mosquito habitats even in their semi-purified form. The isolated compounds can be used as distinct markers in the active extracts or plant materials belonging to the genus Lantana.

Screening of Plants Used as Traditional Anticancer Remedies in Mkuranga and Same Districts, Tanzania, Using Brine Shrimp Toxicity Bioassay.

BACKGROUND: Inadequate specialized cancer hospitals and high costs are contributing factors that delay cancer patients from accessing health care services in Tanzania. Consequently, majority of patients are first seen by Traditional Health Practitioners (THPs) before they access specialized services. This study presents ethnomedical information and preliminary evaluation of 25 plant species claimed by THPs in Mkuranga and Same districts of Tanzania on use for treatment of cancer. Literature search and laboratory investigation results are presented to support evaluation. METHODS THIS STUDY WAS A SINGLE DISEASE ETHNOMEDICAL ENQUIRY FOCUSING ON PLANTS BEING USED FOR CANCER TREATMENT: Face-to-face interviews and questionnaires were administered to eight (8) THPs in Mkuranga and Same districts on the claimed plants and their use for management of cancer. Plants were selected based on being frequently mentioned and emphasis given by THPs. Literature search and brine shrimp toxicity (BST) of methanol : dichloromethane (1:1) extracts was used as surrogates to evaluate strength of the claims. RESULTS: This study reports 25 plant species used by the THPs in two districts of Tanzania. Eight plants (32%) have been reported in the literature to have activity against cancer cells. BST results revealed, 14 (56%) plants exhibited high toxicity against brine shrimps. The most active plants included Croton pseudopulchellus Pax (LC50 4.2 µg/ml), Dalbergia melanoxylon Guill. & Perr. (LC50 6.8 µg/ml), Loranthus micranthus Linn (LC50 4.0 µg/ml), Ochna mossambicensis Klotzsch (LC50 3.3 µg/ml), and Spirostachys africana Sond. (LC50 4.4 µg/ml); their toxicity was comparable to that of Catharanthus roseus (L) G. Don. (LC50 6.7 µg/ml), an established source of anticancer compounds. Nine other plants had LC50 values between (19.8 and 71.6) µg/ml, indicating also potential to yield anticancer. CONCLUSION: Literature search and BST results provide a strong support of the potential of the claimed plants to yield active anticancer compounds.

Antimicrobial activity and brine shrimp toxicity of extracts of Terminalia brownii roots and stem.

BACKGROUND: Ternimalia brownii Fresen (Combretaceae) is widely used in traditional medicine to treat bacterial, fungal and viral infections. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's wide application in traditional medicine system. METHODS: Extraction of stem bark, wood and whole roots of T. brownii using solvents of increasing polarity, namely, Pet ether, dichloromethane, dichloromethane: methanol (1:1), methanol and aqua, respectively, afforded dry extracts. The extracts were tested for antifungal and antibacterial activity and for brine shrimp toxicity test. RESULTS: Extracts of the stem bark, wood and whole roots of T. brownii exhibited antibacterial activity against standard strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, and Bacillus anthracis and the fungi, Candida albicans and Cryptococcus neoformans. Aqueous extracts exhibited the strongest activity against both bacteria and fungi. Extracts of the roots and stem bark exhibited relatively mild cytotoxic activity against brine shrimp larvae with LC50 values ranging from 113.75-4356.76 and 36.12-1458.81 microg/ml, respectively. The stem wood extracts exhibited the highest toxicity against the shrimps (LC50 values 2.58-14.88 microg/ml), while that of cyclophosphamide, a standard anticancer drug, was 16.33 (10.60-25.15) microg/ml. CONCLUSION: These test results support traditional medicinal use of, especially, aqueous extracts for the treatment of conditions such as diarrhea, and gonorrhea. The brine shrimp results depict the general trend among plants of the genus Terminalia, which are known to contain cytotoxic compounds such as hydrolysable tannins. These results warrant follow-up through bioassay-directed isolation of the active principles.

Antifungal activity of some Tanzanian plants used traditionally for the treatment of fungal infections.

Using the ethnobotanical approach, some Tanzanian plants reported to be used by traditional healers for the treatment of oral candidiasis and fungal infections of the skin were collected and screened for their antifungal activity against Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei and Cryptococcus neoformans. A total of 65 crude methanol extracts belonging to 56 plant species and 38 families were screened using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI) (formerly, National Committee for Clinical and Laboratory Standards) [National Committee for Clinical Laboratory Standards, 2002. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard-2nd Edition M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, USA]. Among the tested plant species, 45% (25 species) showed antifungal activity against one or more of the test fungi. The most susceptible yeasts were Cryptococcus neoformans, followed by Candida krusei, Candida tropicalis, and Candida parapsilosis. The least susceptible were Candida albicans and Candida glabrata. Strong antifungal activity was exhibited by extracts of Clausena anisata Oliv., Sclerocariya birrea Sond, Turraea holstii Gurk, Sterculia africana (Lour) Fiori, Acacia robusta subsp. Usambarensis (Taub) Brenan, Cyphosterma hildebrandti (Gilg), Desc, Elaeodendron buchannanii (Lows), Acacia nilotica (L.) Wild ex Del, Jatropha multifida L., and Pteridium aquilinum (L.) Kuhn.

Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania.

BACKGROUND: The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count. METHODS: Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2-17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells. RESULTS: A total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (chi2 = 4.31; df = 1; p = 0.03) and parotid enlargement (chi2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22-0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18-0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04-0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11-1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (chi2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (chi2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (chi2 = 8.17; df = 2; p = 0.04). CONCLUSION: Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children receiving HAART. The occurrence of oral lesions, in both HAART and non-HAART patients, correlated with WHO clinical staging and CD4+ less than 200 cells/mm3.

In vivo antimalarial activity of extracts of Tanzanian medicinal plants used for the treatment of malaria.

Plants used in traditional medicine have been the source of a number of currently used antimalarial medicines and continue to be a promising resource for the discovery of new classes of antimalarial compounds. The aim of this study was to evaluate in vivo antimalarial activity of four plants; Erythrina schliebenii Harms, Holarrhena pubescens Buch-Ham, Phyllanthus nummulariifolius Poir, and Caesalpinia bonducella (L.) Flem used for treatment of malaria in Tanzania. In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injection via tail vein with 2 × 10(7) erythrocytes infected with Plasmodium berghei ANKA. Extracts were administered orally, once daily, for a total of four daily doses from the day of infection. Chloroquine (10 mg/kg/day) and solvent (5 mL/kg/day) were used as positive and negative controls, respectively. The extracts of C. bonducella, E. schliebenii, H. pubescens, and P. nummulariifolius exhibited dose-dependent suppression of parasite growth in vivo in mice, with the highest suppression being by C. bonducella extract. While each of the plant extracts has potential to yield useful antimalarial compounds, the dichloromethane root extract of C. bonducella seems to be the most promising for isolation of active antimalarial compound(s). In vivo antimalarial activity presented in this study supports traditional uses of C. bonducella roots, E. schliebenii stem barks, H. pubescens roots, and P. nummulariifolius for treatment of malaria.

Plants used to treat epilepsy by Tanzanian traditional healers.

A cross-sectional study performed in Temeke District (Dar es Salaam, Tanzania) showed that 5.5% of the traditional healers have knowledge for the treatment of epilepsy. Of the 100 healers interviewed, 30 (30%) believed that epilepsy was caused by witchcraft, while 19 (19%) thought epilepsy has a genetic origin which can be inherited. Other healers thought epilepsy can be caused by head injury or malaria (24%), and the remaining 27% did not know the cause. Most of the healers (92%) could present an accurate account on the symptoms of the disease, including dizziness, loss of consciousness, abrupt falling down, frothing from the mouth, loss of memory, biting of the tongue, confusion, and restlessness. They showed competence in the treatment of the disease, whereby 60 plants that are commonly used were mentioned. Abrus precatorius L. (Leguminosae), Clausena anisata (Willd.) Oliv. (Rutaceae) and Hoslundia opposita Vahl (Lamiaceae), which are among the plants mentioned, have proven anticonvulsant activity, while a few other species on their list have been reported to be useful in the treatment of epilepsy. Biological testing of these plants, using different models of convulsions is, suggested.

Open Biomedical Engineering education in Africa.

Despite the virtual revolution, the mainstream academic community in most countries remains largely ignorant of the potential of web-based teaching resources and of the expansion of open source software, hardware and rapid prototyping. In the context of Biomedical Engineering (BME), where human safety and wellbeing is paramount, a high level of supervision and quality control is required before open source concepts can be embraced by universities and integrated into the curriculum. In the meantime, students, more than their teachers, have become attuned to continuous streams of digital information, and teaching methods need to adapt rapidly by giving them the skills to filter meaningful information and by supporting collaboration and co-construction of knowledge using open, cloud and crowd based technology. In this paper we present our experience in bringing these concepts to university education in Africa, as a way of enabling rapid development and self-sufficiency in health care. We describe the three summer schools held in sub-Saharan Africa where both students and teachers embraced the philosophy of open BME education with enthusiasm, and discuss the advantages and disadvantages of opening education in this way in the developing and developed world.

Antimicrobial activity, acute toxicity and cytoprotective effect of Crassocephalum vitellinum (Benth.) S. Moore extract in a rat ethanol-HCl gastric ulcer model.

BACKGROUND: A decoction of Crassocephallum vitellinum (Benth.) S. Moore (Asteraceae) is used in Kagera Region to treat peptic ulcers. This study seeks to evaluate an aqueous ethanol extract of aerial parts of the plant for safety and efficacy. METHODS: An 80% ethanolic extract of C. vitellinum at doses of 100, 200, 400 and 800 mg/kg body wt was evaluated for ability to protect Sprague Dawley rats from acidified ethanol gastric ulceration in comparison with 40 mg/kg body wt pantoprazole. The extract and its dichloromethane, ethyl acetate, and aqueous fractions were also evaluated for acute toxicity in mice, brine shrimp toxicity, and antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholera (clinical isolate), and Streptococcus faecalis (clinical isolate). The groups of phytochemicals present in the extract were also determined. RESULTS: The ethanolic extract of C. vitellinum dose-dependently protected rat gastric mucosa against ethanol/HCl insult to a maximum of 88.3% at 800 mg/kg body wt, affording the same level of protection as by 40 mg/kg body wt pantoprazole. The extract also exhibited weak antibacterial activity against S. typhi and E. coli, while its ethyl acetate, dichloromethane and aqueous fractions showed weak activity against K. pneumonia, S.typhi, E. coli and V. cholera. The extract was non-toxic to mice up to 5000 mg/kg body wt, and the total extract (LC50 = 37.49 µg/ml) and the aqueous (LC50 = 87.92 µg/ml), ethyl acetate (LC50 = 119.45 µg/ml) and dichloromethane fractions (88.79 µg/ml) showed low toxicity against brine shrimps. Phytochemical screening showed that the extract contains tannins, saponins, flavonoids, and terpenoids. CONCLUSION: The results support the claims by traditional healers that a decoction of C.vitellinum has antiulcer activity. The mechanism of cytoprotection is yet to be determined but the phenolic compounds present in the extract may contribute to its protective actions. However, the dose conferring gastro-protection in the rat is too big to be translated to clinical application; thus bioassay guided fractionation to identify active compound/s or fractions is needed, and use of more peptic ulcer models to determine the mechanism for the protective action.

Integration of Microfractionation, qNMR and zebrafish screening for the in vivo bioassay-guided isolation and quantitative bioactivity analysis of natural products.

Natural products (NPs) are an attractive source of chemical diversity for small-molecule drug discovery. Several challenges nevertheless persist with respect to NP discovery, including the time and effort required for bioassay-guided isolation of bioactive NPs, and the limited biomedical relevance to date of in vitro bioassays used in this context. With regard to bioassays, zebrafish have recently emerged as an effective model system for chemical biology, allowing in vivo high-content screens that are compatible with microgram amounts of compound. For the deconvolution of the complex extracts into their individual constituents, recent progress has been achieved on several fronts as analytical techniques now enable the rapid microfractionation of extracts, and microflow NMR methods have developed to the point of allowing the identification of microgram amounts of NPs. Here we combine advanced analytical methods with high-content screening in zebrafish to create an integrated platform for microgram-scale, in vivo NP discovery. We use this platform for the bioassay-guided fractionation of an East African medicinal plant, Rhynchosia viscosa, resulting in the identification of both known and novel isoflavone derivatives with anti-angiogenic and anti-inflammatory activity. Quantitative microflow NMR is used both to determine the structure of bioactive compounds and to quantify them for direct dose-response experiments at the microgram scale. The key advantages of this approach are (1) the microgram scale at which both biological and analytical experiments can be performed, (2) the speed and the rationality of the bioassay-guided fractionation - generic for NP extracts of diverse origin - that requires only limited sample-specific optimization and (3) the use of microflow NMR for quantification, enabling the identification and dose-response experiments with only tens of micrograms of each compound. This study demonstrates that a complete in vivo bioassay-guided fractionation can be performed with only 20 mg of NP extract within a few days.

Ethnomedicine of the Kagera Region, north western Tanzania. Part 3: plants used in traditional medicine in Kikuku village, Muleba District.

BACKGROUND: The Kagera region of north western Tanzania has a rich culture of traditional medicine use and practice. Traditional medicines are the mainstay of healthcare in this region and are known to support the management of many illnesses such as malaria, bacterial infections, epilepsy, gynecological problems and others. However, most of the plants being used have either not been documented or evaluated for safety and efficacy or both. This study, the sixth of an ongoing series, reports on the medicinal plants that are used at Kikuku village, Muleba District. METHODOLOGY: A semi-structured questionnaire was used to collect information on the common/local names of the plants, parts of the plants used, diseases treated, methods of preparing the herbal remedies, dosage of the remedies administered, frequency and duration of treatment and toxicity of the medicines. A literature review was carried out for information on the ethnomedical uses of the reported plants. RESULTS: A total of 49 plant species belonging to 47 genera and 24 plant families were documented. The family Euphorbiaceae and Asteraceae had the highest representation. The plants are used for the treatment of skin conditions (10 plants; 20%), bacterial infections and wounds (14 plants; 28.6%), malaria (14 plants; 28.6%), gastrointestinal disorders (11 plants; 22.4%), gynecological problems including infertility (8 plants; 16.3%), hypertension (5 plants; 10.2%), viral infections (7 plants; 14.3%), chest problems (5 plants; 10.2%), diabetes (3 plants; 6.1%), cancer (2 plants; 4.1%), inflammatory conditions (arthritis, rheumatism), HIV and AIDS, and hernia each treated by 1 plant (3 plants in total; 6.1%). Information obtained from the literature indicate that 25 (51.0%) of the therapeutic claims are supported by laboratory results or have similar claims of ethnomedical use from other countries. CONCLUSION: Herbal remedies comprise an important and effective component of the healthcare system in Kikuku village with plants in the families Euphorbiaceae and Asteraceae comprising an important part of plants used in the indigenous healthcare management in the village. Malaria and bacterial infections dominate the list of diseases that are managed using traditional medicines.

A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model.

BACKGROUND: The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. METHODS: A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. RESULTS: The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual plant extracts and the mixed extracts of 5 plants exhibited weak to moderate antibacterial activity against four G-ve bacteria. Despite Ozoroa insignis being toxic to mice at doses above 1000 mg/kg body wt, the other plant extracts and the combined extract of the 5 plants were tolerated by mice up to 5000 mg/kg body wt. The brine shrimp test results showed the same pattern of toxicity with Ozoroa insignis being the most toxic (LC50 = 10.63 µg/ml). Phytochemical tests showed that the combined extract of the five plants contained tannins, saponins, steroids, cardiac glycosides, flavonoids and terpenoids. Flavonoids, tannins and terpenoids are known to have antioxidant activity. CONCLUSION: The combined extract of the five plants exhibited a dose-dependent protective activity in the rat ethanol-HCl gastric ulcer model. The extracts also exhibited weak antibacterial activity against four Gram negative bacteria and low acute toxicity in mice and brine shrimps. Although the results support claims by traditional healers who use a decoction of the five plants for treatment of peptic ulcers, more models of gastric ulceration and proper animal toxicity studies are needed to validate possible clinical use of the polyherbal extract. It is also evident that the doses of the crude extracts showing protection of the gastric mucosa are too large for realistic translation to direct clinical application, but further studies using bioassay guided fractionation are important to either identify more practical fractions or active compound/s.