Pharmacology

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    Evaluation of gastroprotective activities of aqueous and 80% methanol leaf extracts of Stephania abyssinica (Quart. -Dill. & A. Rich.) Walp. (Menispermaceae) in rats
    (Addis Ababa University, 2023-07) Firehun,Banchayehu; Nedi,Teshome(PhD)
    Peptic ulcer disease is the most common gastrointestinal tract disorder that mainly affects the stomach and proximal duodenum, and occurs when the protective and damaging factors are out of balance. Its therapy is challenging due to the rise of Helicobacter pylori resistance, adverse effects from current medications, and its complications. This calls for the development of effective and safe gastroprotective agents from alternative sources such as medicinal plants. Stephania abyssinica is a medicinal plant used for the treatment of gastritis in Ethiopia, but there is no scientific investigation. Thus, the aim of this study was to evaluate the gastroprotective activities of both aqueous and 80% methanol leaf extracts of Stephania abyssinica in experimental rats. Decoction and maceration techniques were used to prepare aqueous and 80% methanol leaf extracts, respectively. The extracts were evaluated against pyloric ligation, indomethacin, and ethanol-induced gastric ulcer models at doses of 100, 200, and 400 mg/kg. Negative control received 2% tween 80, while positive controls received 20 mg/kg of omeprazole and 100 μg/kg of misoprostol. In the pyloric ligation induced gastric ulcers, all doses of both extracts significantly reduced the ulcer index and gastric juice volume, while doses of 200 and 400 mg/kg exhibited a significant increase in mucus content and gastric juice pH as well as decrease in free and total acidity as compared to negative control. In indomethacin and ethanol induced gastric ulcers, pretreatment with both extracts significantly reduced the ulcer index and enhanced gastric mucin content in a dose dependent manner. Phytochemical screening of extracts showed the existence of flavonoids, phenols, tannins, saponins, alkaloids, and coumarins with high contents of alkaloids, phenols, and flavonoids in methanol extract. The findings indicated that the leaves of Stephania abyssinica possessed remarkable gastroprotective activities against experimentally induced gastric ulcers. This possibly justify the traditional use of Stephania abyssinica leaves to treat gastritis.
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    Pharmacogenetic study of 6-Mercaptopurine and L-Asparaginase based chemotherapy in pediatric Acute Lymphoblastic Leukemia patients in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia
    (Addis Ababa University, 2023-09) Ali,Awol Mekonnen(PhD); Abula,Tefera(Prof.); Howe,Raweligh(Dr.); Adam,Haileyesus(Dr.); Coenen,Marieke(Dr.)
    Background Acute lymphoblastic leukemia is the most common type of childhood cancer, necessitating a tailored combination of chemotherapy. However, dose-limiting hematotoxicity is a significant challenge. Genetic variations, in the thiopurine metabolic pathway gene, can predict toxicities related to 6-mercaptopurine. While L-asparaginase is crucial in treating childhood ALL, it can cause hypersensitivity reactions and hepatotoxicity. Reports have suggested that genetic variants in the CNOT3, GRIA1, and NFATC2 genes may contribute to hypersensitivity reactions, while PNPLA3 has been linked to hepatotoxicity. Objective The objective of this thesis was to examine the frequency of genetic variants of drug metabolizing enzyme and transporter polymorphisms and their association with the occurrence of adverse events during 6-MP and L-ASP based chemotherapy in pediatric acute lymphoblastic leukemia patients at TASH, Addis Ababa, Ethiopia. Methods A Cohort study was used and the clinical profile of the patients was collected for the first 6 months of the maintenance phase treatment. Genotyping of GRIA1 rs4958351, PNPLA3 rs738409, ITPA, and XDH was performed using KASP genotyping assay, while that of CNOT3 rs73062673, and NFATC2 rs6021191, TPMT, NUDT15, and ABCB1 with TaqMan® SNP genotyping assays. TPMT activity was measured in whole blood of theparticipant by HPLC. Results During the initial six months of the maintenance phase treatment, 52.8% of the patients experienced grade 4 neutropenia. The risk of developing neutropenia was found to be higher in children aged six years or less and those with low day 1 maintenance white blood cell counts. Furthermore, specific genetic variants in ITPA and XDH, were associated with 6-MP induced neutropenic fever and grade 4 neutropenia, respectively. Notably, patients with the CC genotype of XDH rs2281547 were found to have a nearly threefold increased risk of developing grade 4 neutropenia compared to individuals with the TT genotype (AHR 2.956, 95% CI=1.494-5.849, p = 0.002). Additionally, it was observed that 12.5% of the patients developed L-ASP hypersensitivity, but there were no significant differences between the frequency of hypersensitivity reactions and the risk alleles of the investigated genes. Conclusion In ALL patients, the genetic variant XDH rs2281547 was found to be a predictive factor for hematologic grade 4 toxicities caused by 6-MP. To detect hematotoxicity early, it is recommended to closely monitor the levels of white blood cells and neutrophils throughout the maintenance treatment. Furthermore, it is important to consider genetic variations apart from the TPMT gene that play a role in the metabolic pathway of 6- mercaptopurine in order to prevent hematological toxicity.
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    Genetic analysis of resistance and PK/PD model-based study of Moxifloxacin and Levofloxacin in multi-drug resistant tuberculosis patients attending hospitals in Southern Ethiopia
    (Addis Ababa University, 2023-06) Sidamo,Temesgen; Engidawork,Ephrem(PhD, Professor); Aklillu,Eleni (PhD, Professor); Shibesh,Workineh (PhD, Assoc. Professor)
    Background: Multi-drug resistant tuberculosis (MDR-TB) has hindered the therapeutic success of TB. Patient, drug, and pathogen-related factors are critical to understanding, characterizing, and predicting drug resistance, which help to tailor drug dosing taking into account inter-individual differences and patient needs. The highly active World Health Organization (WHO) Group A fluoroquinolones, FQs (moxifloxacin, MXF, and levofloxacin, LFX), exhibit inter-individual pharmacokinetic variability (IIV) that may result in low drug exposure. The 24-hour area under the concentration-time curve over the minimum inhibitory concentration (AUC0-24/MIC) is a strong predictor of FQ exposure and positive treatment outcome. Ethiopia is one of the world nations with a high prevalence of MDR-TB. However, there is a lack of data on factors affecting MDR-TB treatment success and one-size-fits-all scenario is the single most common therapeutic strategy of TB in Ethiopia. Objective: This dissertation aimed to study treatment outcome and its predictors, characterize and predict MXF and LFX resistance in MDR-TB patient population using phenotypic and genotypic methods as well as a PK/PD model-based study. Methodology: A prospective observational study of 80 MDR-TB patients was carried out. Treatment outcomes in patients receiving MXF-and LFX-based regimens were compared at the end of treatment. We determined the plasma concentrations of MXF and LFX and their PK parameters. A PK/PD (AUC0- 24/MIC) analysis to predict the recommended probability of target attainment (PTA) was carried out for IV both drugs. The potential patient covariates which impact the model estimated PK profiles were also screened. Drug resistance was characterized by phenotypic and genotypic methods, and the association between patient and pathogen related variables, FQ-resistance and treatment outcome were evaluated. Result: The total treatment success in this study was lower than the report in previous local and international studies. The LFX-based MDR-TB regimen outperformed the MXF-based regimen. Unsuccessful treatment outcome was predicted by a delayed culture conversion rate, history of alcohol intake, lesion of lung cavities, serum levels of creatinine (Cr.). A one-compartment model with adjustments was fit to the LFX and MXF concentrations. Cr. and body mass index (BMI) were covariates identified to have impact on clearance and apparent volume distribution (Vd) of LFX and MXF, respectively. Exposures to LFX and MXF were lower in study participants than in other settings. However, LFX-treated groups experienced higher drug levels and exposure with dose. Nine clinical isolates (11.3%) were resistant overall, all of which were at least resistant to FQs, while 3 were resistant to both FQs and injectable drugs. Mutation in gyrA 94 was identified in 5 isolates. The MIC values were associated with patient treatment outcomes. Cavitary lesion and serum creatinine predict FQ-resistant tuberculosis. Conclusion: Exposure to either LFX or MXF may be inadequate, but LFX appears to provide better treatment outcomes. Patient clinical and behavioral variables can predict drug exposure, drug resistance and the overall treatment outcome. Even though the line probe assay (LPA) showed a moderate level of resistance in Ethiopian patients, genotypic test results do not always correlate well with phenotypic results. The actual drug resistance level could be higher than anticipated. Higher MIC values of clinical isolates correlate with a higher risk of treatment failure. In such scenarios, dosage optimization may improve outcome. GyrA mutation is associated with FQ-resistance in Ethiopian patients. Further controlled clinical studies are needed to establish optimal doses and exposure of FQs.
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    A comparative study of the leaf and root extracts of Stephania abyssinica (Dillon & A. Rich) Walp on wound healing activity in mice
    (Addis Ababa University, 2023-07) Girma,Minilu; Petros,Zelalem (PhD); Tamirat,Dagnachew(MD)
    The roots and leaves of Stephania abyssinica are traditionally used to treat wounds in several regions of Ethiopia. The pharmacological screening for wound-healing activity of the plant was done for the crude extract and solvent fractions of the root extract. But there have been no pharmacological studies done on the wound-healing effect of the leaf extract. In this study, the wound-healing effects of both the 80% methanol extract of the leaves and the roots of S. abyssinica were evaluated using the excision wound model, and the results were compared. Histopathological investigations were also carried out. The antioxidant activity of both the leaf and root extracts was also assessed. In addition, preliminary phytochemical screening tests and quantification of total phenolic, flavonoid, and alkaloid contents were done for both the leaf and root extracts. Both the root and the leaf extracts significantly increased the rate of wound contraction (p < 0.05) and shortened the re-epithelialization period (p < 0.01). The root extract significantly increased the skin‟s tensile strength (p ˂ 0.001). The quantity of secondary metabolites in the root extract, such as total phenolic, flavonoid, and alkaloid contents, was found to be higher than those of the leaf extract, and this concentration difference demonstrated a substantial difference in its wound healing activity.
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    Probiotic and Starter Culture Properties of Lactic Acid Bacteria Isolated from Selected Ethiopian Fermented Foods and Beverages
    (Addis Ababa University, 2023-10) Adall,Seyoum Gizachew(Phd); Engidawor,Ephrem(Prof.); Lebeer,Sarah(Prof.)
    Lactic acid bacteria (LAB) are a group of bacteria that form the majority of probiotics and are typically found in fermented products. Probiotics are currently accepted as reasonable alternative remedies in the control of infectious diseases and immuno-allergic disorders. Sub-Saharan African knowledge on cereal fermentations is largely unexplored and undocumented. Use of LAB as starter cultures is one of the key strategies to make most of these spontaneous African cereal fermentations of sufficient quality. The criteria for the selection of probiotic/probiotic starter strains include the functional characterization and safety assessments. This work aimed to isolate and assess in vitro probiotic and starter culture capacity of LAB strains from yoghurt, cheese, cottage cheese, Naaqe and Cheka. LAB were isolated by plating on MRS agar. Spot overlay, radial diffusion, and microdilution methods were used to assess antimicrobial activity against pathogens commonly causing foodborne diseases in Ethiopia. Species identification was done by 16S rRNA gene sequencing. Immunostimulatory activity was tested by measuring nuclear factor kappa B (NF-κB) and interferon regulatory factor (IRF) pathway activation in THP- 1 cell lines. In situ evaluation of starter culture performance of selected isolates from cereal beverages was conducted in a mock fermentation of Naaqe and Cheka. Genomes of three dairy isolates selected based on their potential probiotic properties were analyzed for the secondary metabolites biosynthetic gene clusters, resistome, virulome, and carbohydrate- active enzymes. 27 isolates from the dairy and 14 isolates from the cereal beverage samples were selected and identified to the species level. Limosilactobacillus fermentum was found to be the predominant species. Five strains from cottage cheese (L. plantarum 54B, 54C and 55A; L. pentosus 55B, and P. pentosaceus 95E) showed inhibitory activity against indicator pathogens tested. Six cereal beverages origin LAB strains also inhibited eight of the nine gastrointestinal indicator key pathogens tested. Strain-specific NF-κB and IRF iv activation was documented for dairy origin strains L. plantarum 54B, L. plantarum 55A and P. pentosaceus 95E. Three of the cereal beverages origin LAB isolates (L. fermentum 73B, 82C and 84C) significantly exhibited strain-specific NF-κB induction. During in situ primary fermentations, L. fermentum 73B, P. pentosaceus 74D, L. fermentum 44B, Weissella confusa 44D, L. fermentum 82C and Weissella cibaria 83E and their combinations demonstrated higher pH-lowering properties and colony-forming unit counts compared to the control spontaneous fermentation. The same pattern was also observed in the secondary mock fermentation by the Naaqe LAB isolates. Based on the whole genome sequence (WGS) analysis, Lactiplantibacillus plantarum 54B and 54C also showed to be closely related but different strains. The analysis also revealed that the three strains do not harbor resistome and virulome and have five classes of carbohydrate-active enzymes with several important functions. Cyclic lactone autoinducer, terpene, Type III polyketide synthases (T3PKS), ribosomally synthesized and post-translationally modified peptides (RiPP)-like gene clusters and complete riboflavin operon have been identified in the L. plantarum 55A genome. Overall, five isolates of dairy origin and six isolates of cereal beverages origin showed promising results in all assays and are novel probiotic and probiotic starter candidates of interest, respectively.
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    The role of aflatoxin B1 in the etiology of liver cirrhosis in Eastern Ethiopia
    (Addis Ababa University, 2023-10) Mekuria,Abraham Nigussie(Phd); Abula,Tefera(Prof.); Engidawork,Ephrem(Prof.)
    Background: Liver cirrhosis is deemed to be a major cause of morbidity and mortality in Eastern Ethiopia; however, few studies have been conducted to identify its possible etiologies. For instance, in a hospital-based cross-sectional study, no definite etiologies were found in more than half of liver cirrhosis patients, suggesting a yet unidentified cause of this disease in this area. Meanwhile, as indicated in several studies, Eastern Ethiopia is a region with a diet particularly high in aflatoxin (AFB1). AFB1, a very toxic compound with sufficient evidence of carcinogenicity in humans, has been implicated as an emerging cause of liver cirrhosis. Objective: This study evaluated the role of AFB1 in the etiology of liver cirrhosis among patients attending Hiwot Fana Comprehensive Specialized University Hospital (HFCSUH), Eastern Ethiopia, in 2020-2021. Methods: A consecutive sample of 127 adult patients diagnosed with liver cirrhosis from internal medicine unit of HFCSUH were enrolled as cases, and 253 adults without any evidence of liver disease were enrolled from the same unit of the hospital as controls. Demographic, dietary, and lifestyle characteristics of the participants were collected using a structured questionnaire. Clinical data were abstracted on standardized reporting forms. Blood sample were collected and tested for hepatic enzymes, hepatitis C virus antibody, hepatitis B surface antigen, and AFB1-albumin adduct. Gluthatione S transferase M1 and T1 (GSTM1 and GSTT1) genes copy number variations were also determined by TaqManTM Assay. SPSS version 26.0 was used to compute the statistical analysis. V | P a g e Results: The etiology of liver cirrhosis was known in only 23% of patients. Sorghum consumption as a staple food was significantly associated with liver cirrhosis of unknown etiology. AFB1-albumin (AF-alb) detection rate was higher (p<0.05) in cases (75%) than in controls (64%) and with a median (interquartile range [IQR]) level of 11 pg/mg (5.5-25) and 7.0 pg/mg (4.3- 20.5), respectively (p<0.05). Exposure to high levels of AF-alb (adjusted odds ratio (AOR) = 2.0; 95% CI: 1.1–3.7) were significantly (p<0.05) associated with liver cirrhosis. The frequencies of null genotypes for GSTM1 and GSTT1 were 0.39 (95% CI: 0.32, 0.46) and 0.32 (95% CI: 0.26, 0.39), respectively. The risk of liver cirrhosis was shown to be reduced (p<0.05) in GSTT1 carriers compared to those with GSTT1 null genotypes (AOR = 0.47; 95% CI: 0.25, 0.86. Furthermore, the risk of liver cirrhosis was significantly lower in those with one copy of GSTT1 (AOR = 0.48; 95% CI: 0.25, 0.91) and a two or more combined copy of GSTT1 and GSTM1 genes (AOR = 0.38; 95% CI: 0.16, 0.91). Conclusions: Sorghum consumption was identified as a potential source of exposure in the current investigation, which implicated AFB1 exposure as a possible etiology of hepatic cirrhosis in Eastern Ethiopia with a high prevalence of cryptogenic cases. GSTT1 and GSTM1 genotypes also played a role in the risk of liver cirrhosis. To decrease the disease burden in this part of Ethiopia, plausible aflatoxin control strategies should be implemented.
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    Analgesic and anti-inflammatory activities of Albizia gummifera (J. F. Gmel) C.A. Sm. bark hydro-alcoholic extract and its fractions in rodents
    (Addis Ababa University, 2023-10) Tamirat,Mesfin; Petros,Zelalem(PhD); Shibeshi,Workineh(PhD)
    Background: The majority of illnesses present as pain and inflammation. Despite advancement in pain medicines, there is a need for safe, effective analgesic drugs. In folkloric medicine, A.gummifera has been used for pain and inflammation, but not scientifically evaluated. Objectives: This study aimed to investigate the analgesic and anti-inflammatory activities of A.gummifera bark crude extract and its fractions in rodents. Methods: The analgesic activity of the A.gummifera was evaluated using an acetic-acid- induced writhing test and hot plate test by using acetyl salicylic acid 150 mg/kg and morphine 10 mg/kg as standard, respectively. Carrageenan-induced paw edema and cotton pellet granuloma methods were used to investigate the anti-inflammatory effect with Indomethacin 10 mg/kg and dexamethasone 0.5 mg/kg as the reference drugs, respectively. Three doses are selected based on the acute toxicity test result: 100 mg/kg, 200 mg/kg, and 400 mg/kg. Results: The A.gummifera bark crude extract and its fractions did not show any sign of toxicity at 2000 mg/kg. The crude extract and its fractions showed statistically significant analgesic and anti-inflammatory activities as compared to the control group (p<0.05). The crude extract and methanol fractions reduced writhes by 66.68% and elongate latency period by 61.47% on 60 and 90 minute, respectively. The maximum edema inhibition was 62.15% in the aqueous fraction after 2 hours of administration. Aqueous fraction produces maximum exudate and granuloma inhibition (62.07% and 65.66%, respectively). Conclusion: This study found that, A.gummifera bark crude extract and its fractions possessed promising analgesic and anti-inflammatory property.
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    Antitrypanosomal Activity of Selected Medicinal Plants against Trypanosoma congolense Field Isolate
    (Addis Ababa University, 2023-11) Dereje,Beza; Abay,Solomon Mequanente(PhD)
    Trypanosomiasis is among the most common neglected tropical diseases (NTDs) of humans and animals. It mainly affects countries with poor health infrastructures and the actual disease burden is unknown. It is estimated that 10 to 14 million heads of cattle, goats and a million equines are at risk of contracting the disease in Ethiopia. Trypanocidal drugs are currently facing a number of problems like toxicity, resistance and availability issues. These limitations have prompted the search for new, safe and effective drugs. In Ethiopia, the seed of Brucea antidysentrica, the leaf of Clematis hirsuta and the root of Rumex nepalensis are used to treat animal trypanosome infection by traditional healers. The study aimed to investigate the in vitro activity of selected medicinal plants against Trypanosoma congolense and in vivo antitrypanosomal activity of the most active plant. The plants were extracted by 80% methanol maceration and tested for their in vitro activity using motility test (at concentration of 4, 2, 0.4 and 0.1 mg/ml) for cessation or reduction in motility of trypanosomes followed by monitoring for loss of infectivity of mice. After 12 days of T. congolense field isolate inoculation of mice and peak parasitaemia level (~108 trypanosomes/ml) was reached, 80% methanol extract of roots of Rumex nepalensis was administered at doses of 100, 200 and 400mg/kg orally once daily for 7 days. ii The packed cell volume, body weight, parasitaemia level and rectal temperature were used as parameters for monitoring in vivo activity by comparing with the positive control: 28 mg/kg dose of diminazene aceturate and negative control: 1% Dimethyl Sulfoxide (DMSO) treated groups. The statistical significance was determined by one-way ANOVA followed by Tukey post hoc test. The motility of T. congolense was ceased by R. nepalensis, B. antidysentrica, and C. hirsuta at concentration of 4mg/ml within 10, 25 and 35min, respectively. Mice treated with 4mg/ml of R. nepalensis and Diminazene aceturate caused loss of infectivity of trypanosomes in mice for 21 days after the inoculation of the in vitro mixtures. The 80% methanol extract of roots of Rumex nepalensis at dose of 2000 mg/kg did not show acute toxicity signs and symptoms. Highly significant (p<0.001) reduction in pre-treatment parasitaemia from (7.30±0.06) to (2.70±1.21) trypanosomes/ml on day 8 of treatment and increased PCV from (45.83±0.31) to (48.00±0.26) and body weight increased from (22.63±0.55) to (26.60±1.14) gram at day 14 was recorded in mice treated with 80% methanol extract of roots of R. nepalensis at the dose of 400 mg/kg. The results revealed that the selected medicinal plants showed antitrypanosomal activity that supports their traditional claim and prompted further studies on isolated active substances from these plants.
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    Anti-hyperglycemic activities of hydro-alcoholic, alkaloid and non-alkaloid extracts of Calpurnia aurea (aiton) benth (Fabacea) against streptozocin induced diabetic mice
    (Addis Ababa University, 2023-11) Beyene, Habtamu; Engidawork,Ephrem(Prof.); Shibeshi,Workineh(PhD)
    Background: Diabetes mellitus is a metabolic disease with several etiologies that is typified by persistently high blood sugar levels. Given the rising rates of diabetes-related morbidity and death in low- and middle-income countries, it is critical to evaluate the potential pharmacological effects of medicinal plants in order to complement current diabetes treatments. The experimental plant Calpurinaaurea(Aiton)Benth is among the Fabaceae species, which is used traditionally for diabetes and other health disorders. Objectives:The purpose of this study was to assess the effects of crude, alkaloid, and non- alkaloid leaf extractsof C.aurea on blood glucose control in streptozotocin-induced diabetic mice and normoglycemic mice. Methods: The crude, alkaloid, and non-alkaloid extracts were prepared using the proper solvents prior to the commencement of the in-vivo investigation. Swiss albino mice, weighing between 20 and 30 grams, were selected for the animal trials. In order to study the hypoglycemic/antihyperglycemic effect of the extract, nine groups of diabetic mice and eleven groups of normal mice were used. Streptozotocin was used to induce diabetes, and blood glucose levels were measured with a glucometer. Doses of the plant alkaloid and non-alkaloid extract (100, 200, and 400 mg/kg) were administered to the test groups in each model while the crude extract was administered at lower doses(50, 100, and 200 mg/kg). Glibenclamide(5 mg/kg) served as a standard drug. The negative control, and the normal control were given 1% of tween 80 (10 mg/kg). Results: The results demonstrated that crude, alkaloid, and non-alkaloid extracts of C.aurea leaves lowered the incidence of hypoglycemia. After the administration of2.5 mg/kg of glucose, the alkaloid extract demonstrated significant lowering of blood glucose levels: 200 mg/kg at 80 minutes (p<0.05) and 400 mg/kg at the first and second hour (p<0.01). All extract-treated groups of streptozotocin induced diabetic mice had decreased blood glucose levels, besides the mice iv administered the alkaloid extract showed a statistically significant drop in blood glucose levels. The alkaloid extract reduced blood glucose levels in the 200 (P<0.05) and 400 mg/kg doses (162±5.21, 142±3.51), respectively, were used in a single dose study. Furthermore, the alkaloid extract at the middle dose (p<0.05), higher dose (p<0.01), and all doses at the third week all significantly decreased the fasting blood glucose level. Furthermore, compared to the negative control group, the groups treated with crude, alkaloid and non-alkaloid extracts experienced a lesser drop in body weight following the onset of diabetes mellitus.Conclusion:it can be concluded that the alkaloid extracts of C.aurea leaves are effective in lowering blood glucose levels in diabetic mice and lack a hypoglycemic effect in normoglycemic mice. Additionally, the extracts were observed to exhibit no acute toxicity.
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    Assessment of Mobile-Based Vaccine Logistics Management Information System (vLMIS) Implementation in Public Health Facilities of Gambella Region, Southwest Ethiopia
    (Addis Ababa University, 2023-10) Abebaw Nigus; Zelalem Tilahun
    Ethiopia uses a combination of an integrated and interoperable information system to manage vaccines within Ethiopian Pharmaceuticals Supply Service’s (EPSS) supply chain system. Lack of access to reliable and timely data visibility for decision-making and poor vaccine management and efficiency are the challenges in Ethiopia. The mobile-based vaccine logistics management information system-(mBrana) implemented throughout Ethiopia for vaccine logistics information and inventory management.
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    In Vitro and in Vivo Antidiabetic Activity of 70 % Ethanolic Fruit Extract of Rosa Abyssinica R.Br. Ex Lindl (Rosaceae
    (Addis Ababa University, 2024-02-10) Mohammed Ahmed; Workineh Shibeshi
    Diabetes Mellitus (DM) is a metabolic disorder result from defects in insulin secretion, action or both. Given the high prevalence of disability and comorbidities associated with DM, it’s pivotal to bring forth sensible preventative and alternative treatment plans. Many plants in Rosacea family have been studied for their antidiabetic activity and Rosa abyssinica is one of the plant that widely used for its antidiabetic activity in traditional medicine in Ethiopia. The purpose of this study was to assess antihyperglycemic outcome of 70% ethanol extract of Rosa abyssinica. The in vitro antidiabetic effect was evaluated using assay for α-amylase inhibition of 70% ethanol fruit extract of R. abyssinica and positive standard, acarbose, at six different concentrations using 3,5-dinitrosalicylic acid (DNSA) technique. Conversely, normoglycemic, glucose-loaded, and streptozotocin (STZ)-induced diabetic mouse models were used to assess the in vivo antihyperglycemic activity. Five groups of mice—six mice in each group—were used in this investigation, consists of three experimental groups receiving 100, 200, and 400 mg/kg of the extract, positive control group receiving glibenclamide (GLC5 mg/kg), and negative control group receiving distilled water (10 ml/kg). In STZ-induced diabetes, a single intraperitoneal injection of 180 mg/kg body weight of STZ was used to cause diabetes. Anti-hyperglycemic effect of the extract in STZ -induced diabetic mice was evaluated using single dose and repeated dose study for three weeks. The in vitro test for α-amylase inhibition was analyzed using independent sample t test and the result showed there were no significant difference between the extract and the standard drug, acarbose, with triplicate measurement of IC50 of 26.72 ± 3.60 and 21.37 ± 4.25μg/ml respectively. The in vivo antihyperglycemic effect both in the oral glucose challenge and STZ induced diabetic mice showed similar result between the positive control and the two highest dose of the extract. In the normoglycemic experiment except with the highest dose of the extract, RA400, the other doses of the extract showed no hypoglycemic side effect and the extract showed positive for all tested qualitative secondary metabolite tests and quantitative test results showed alkaloids (83.37 mg ATP/g), phenols (892 mg GAE/g) and flavonoids (286.58 mg QCE/g) amounts.
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    Association of SLC2A2 rs8192675 and SLC22A1 rs72552763 polymorphisms to metformin treatment outcomes in Ethiopian patients with type 2 diabetes mellitus
    (Addis Ababa University, 2024-04) Abdi,Abraham Degaga; Shibeshi,Workineh (PhD); Engidawork,Ephrem(PhD); Huri, Hasniza Zaman(PhD); Sirgu,Sisay(MD)
    Metformin is recommended as the first-line oral glucose-lowering agent by most clinical guidelines for people with type 2 diabetes mellitus (T2DM), although there are extensive variations in the metformin treatment outcomes, related to the differences in individual genetic profiles. Thus, in this study the association of SLC2A2 rs8192675 and SLC22A1 rs72552763 polymorphisms with metformin treatment response and SLC22A1 rs72552763 with metformin gastrointestinal intolerance were investigated in Ethiopian patients with T2DM. Recently diagnosed patients with T2DM were enrolled at St Paul’s Hospital Millennium Medical College. In the metformin treatment response study, a prospective observational cohort was conducted on 86 patients receiving metformin treatment for < 1 year. The participants were classified into metformin responders and non-responders based on a cut-off value of 0.5% reduction in HbA1c levels. Genotyping of rs8192675 and rs72552763 was performed using TaqMan® Pre-Designed and Drug Metabolism Enzyme SNP Genotyping Assay, respectively. The association of each one of the polymorphisms with metformin response was assessed by measuring the change in HbA1c levels, while the association of rs8192675 polymorphism with metformin response in diabetic dyslipidemia was assessed by measuring the absolute change in lipid parameters as well as HbA1c levels. On the other hand, in the metformin gastrointestinal intolerance study, a retrospective study was conducted in 47 patients on metformin treatment for < 3 years. The association of rs72552763 polymorphism to metformin-induced gastrointestinal intolerance was assessed based on switching to a new class of glucose-lowering agents or failure to up-titrate metformin dose due to gastrointestinal intolerance. Dyslipidemia was defined in accordance with the adult treatment panel III. Chi-square, logistic regression, student’s t-test, Mann-Whitney and Kruskal-Wallis statistical tests were used as applicable. A p-value of less than 0.05 was taken as statistically significant. The minor allele frequency iv (MAF) of the C-allele in the T>C substitution SNP of SLC2A2 (rs8192675) was 66.2% while the MAF of the 3-base pair (GAT) deletion mutation at rs72552763 was 9.4% in our study population. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to wild-type GAT_GAT (G_G) genotypes 3.675 95% CI (1.005– 13.436) (p = 0.049). Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes 7% vs 8% (p=0.015). However, the association of rs72552763 with metformin response was not replicated at the allele level. Furthermore, the minor del_allele was significantly associated with good glycemic control compared to the G_allele 3.206 95% CI (1.165–8.823) (p = 0.016), though not replicated at del_G genotypes level. In contrast, the rs8192675 polymorphism showed no significant association with metformin treatment response, glycemic control and dyslipidemia. Likewise, no significant association was also observed between rs72552763 and metformin- induced gastrointestinal intolerance. The prevalence of dyslipidemia was 92.1 %. The prevalence of mixed atherogenic dyslipidemia, combined dyslipidemia and isolated dyslipidemia was 37 (29.1 %), 34 (26.8 %), and 27 (21.3%), respectively. The findings demonstrated that heterozygous carriers of the Met420del variants of SLC22A1 have an increased response to metformin. However, rs8192675 and rs72552763 genetic polymorphisms were not associated with metformin treatment response and metformin- induced gastrointestinal intolerance, respectively. The study also indicated a high prevalence of dyslipidemia in people with T2DM, with atherogenic mixed dyslipidemia being the commonest pattern.
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    Investigation of Non-Communicable Diseases Prevalence, Patterns and Outcomes Among Hospitalized patients: A Prospective Observational Study in Three Tertiary Hospitals
    (Addis Ababa University, 2024-07) Belayneh,Alemu; Chelkeba,Legese(PhD, Ass.Prof.); Amare,Firehiwot(Ass.Prof.); Guteta,Senbeta(MD, Prof.); Fisseha,Henok(MD)
    Background: Non-communicable diseases (NCDs) pose a significant global health challenge, constituting over 71% of overall mortality and morbidity. Cardiovascular diseases, cancer, diabetes mellitus, and chronic respiratory disease are the major classes of NCDs and the leading cause of death globally. Recently, the burden of these NCDs have become more pronounced in low- and middle-income countries, including Ethiopia. Objective: To determine the prevalence, patterns, patient outcome, and pattern of medication use of major NCD among hospitalized population. Methods: A prospective follow-up study was conducted across three tertiary hospitals from October 2022 to January 2023 among hospitalized population. Socio- demographic and clinical data were collected through medical records review and interviews. Descriptive statistics, multinomial logistic regression, survival analysis and negative binomial regression were conducted to summarize, and determine the independent predictor of clinical outcomes, P-value < 0.05 was considered statistically significant. Results: The overall prevalence of NCDs among hospitalized patients was 1302 (58.2%). However, after the exclusion of patients who did not fulfill the inclusion criteria for follow- up, the proportion of NCD among hospitalized patients in our sample became 523 (23.4%), of which 80 (15.3%) faced in-hospital mortality and 90 (17.2%) were discharged with unsatisfactory clinical outcomes. Cardiovascular diseases and cancer were the dominant NCDs among these patients, with a rate of 53% and 30% hospitalization and 13% and 22.7% in- hospital mortality, respectively. Participants diagnosed with cancer showed significantly higher odds of mortality and prolonged hospital stays. Medication non-adherence (AOR: 4.679, 95% CI: 2.48–8.80), the presence of other co-morbid conditions (AOR: 3.81, 95% CI: 2.024–7.19), and the presence of complications (AOR: 10.24, 95% CI: 5.35–19.63) were significant predictor of in-hospital mortality. Conclusion: Our study reveals a substantial prevalence of NCDs among hospitalized patients, primarily with CVDs and cancer. Alarmingly, a significant mortality rate and prolonged hospitalization were observed among patients diagnosed with cancer.
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    Pharmacokinetics and Pharmacogenetics Studies of Rifampicin and Isoniazid in Ethiopian Tuberculosis Patients
    (Addis Ababa University, 2024-04) Sileshi,Tesemma; Makonnen,Eyasu(PhD); Aklillu, Eleni (PhD)
    Introduction: Tuberculosis (TB) is an ancient disease of mankind and remains a major public health problem despite tremendous efforts made to combat it. Globally, 10.6 million people fell ill and 1.13 million died from TB in 2022. Short-course regimens of first-line anti-TB drugs can cure about 90% of cases. However, the success of treatment appears to be on a declining trend over time. Unfavorable TB treatment outcomes might result from altered plasma exposure to antitubercular drugs. Rifampicin and isoniazid display wide between-patient pharmacokinetics variability. Ethiopia is among the 20 high TB and TB-HIV burdens countries. Ethiopians display significant genetic variation from other black African populations. Despite these facts, data on the extent of exposure to rifampicin and isoniazid, as well as inter-patient variability in plasma concentration, remains scarce among Ethiopian TB patients. Objective: The study aimed to determine the plasma levels of rifampicin and isoniazid and investigate the effect of genetic polymorphism and socio-demographic characteristics on the pharmacokinetics of rifampicin and isoniazid in Ethiopian tuberculosis patients. Methods: The study was conducted at the primary healthcare centers in Addis Ababa, Ethiopia. A total of one hundred forty-six adult patients with newly diagnosed TB who had received 2 weeks of first-line anti-TB therapy were enrolled. Venous blood samples were drawn at three- time points from the majority of the patients ranging from 1 to 7 h post-drug intake. Genotyping of NAT2, SLCO1B1 (c.388A>G, c.521T>C), ABCB1 (c.3435C>T, c.4036A>G), AADACc.841G>A, and CES-2 (c.269-965A>G) was done using TaqMan drug metabolism assay. Rifampicin, isoniazid, and its metabolite concentration were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Population pharmacokinetic (POPPK) modeling of rifampicin was done using NONMEM. Results: The overall median isoniazid maximum plasma concentration (Cmax) was 4.73 μg/mL and the area under the curve (AUC0-7h) was 11.21μg.h/mL. The majority of patients 94(64.4%) had isoniazid Cmax within the recommended therapeutic range (3-6 μg/mL), while only 19 (13%) had an isoniazid Cmax of below 3 μg/mL. The median rifampicin Cmax was 6.79μg/mL. Only 42 IV | P a g e (29%) patients achieved the therapeutic efficacy threshold (> 8μg/mL). The median rifampicin AUC0-7h was 17.055μg.h/mL. The frequency of slow, intermediate, and fast NAT2 acetylators genotypes was 74.2%, 22.4%, and 3.3%, respectively. The overall concordance between NAT2 genotype and phenotype was 85%. The minor allele frequency for SLCO1B1*1B (c.388A>G), SLCO1B1*5 (c.521T>C), ABCB1 c.3435C>T, ABCB1 c.4036A>G, AADAC c.841G>A and CES-2 c.269-965A>G were 2.2%, 20.2%, 24.4%, 14.6%, 86.1% and 30.6%, respectively. NAT2 acetylator genotypes alone accounted for 26.1% and 40.6% of the variability in isoniazid Cmax and AUC0-7h, respectively. ABCB1 c.4036A>G genotypes independently accounted for 7.4%, and 6.1 % of the variability in rifampicin Cmax and AUC0-7h, respectively. A two-compartment model coupled with a transit absorption model adequately fitted the rifampicin data. Subjects with ABCB1 c.4036A>G GG genotype were estimated to have 41% lower intrinsic clearance of rifampicin compared to subjects with ABCB1 c.4036A>G AA or AG genotypes. Similarly, subjects with ABCB13435C TT genotype were estimated to have a 100% higher absorption rate constant than those with ABCB1 3435C>T CC or CT genotypes. Conclusion: There is high inter-patient variability in isoniazid and rifampicin exposure in Ethiopian TB patients. The majority of the patients attained therapeutic plasma concentration of isoniazid but not that of rifampicin. NAT2 acetylation genotypes, dose, and sex are strong predictors of isoniazid exposure. Rifampicin exposure varied with sex, dose, ABCB1 c.4036A>G, and ADAC c.841G>A genotypes. The clinical significance of higher isoniazid and lower rifampicin exposure in Ethiopian TB patients needs further investigation.
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    Forecasting Accuracy of Anti Retroviral Medicines and its Contributing Factors: the Case of Ethiopian Pharmaceutical Supply Service
    (Addis Ababa University, 2022-07) Mahlet Tibebu; Tariku Jebena
    Quantification is one of the core process of supply chain management. Its performance needs to be measured to check whether the set targets are met or not. Performance of quantification is measured by forecasting accuracy. Forecasting accuracy is a measure of how close the actual demand is to the forecast quantity. Accuracy of forecasts heavily relies on data availability, quality of data, quantification procedures and tools, assumptions made, skill and experience of forecasting experts. EPSS have not analysed forecasting accuracy of both RDF and program pharmaceuticals for the previous five years (2014-2018 G.C.).This study was carried out to assess forecasting accuracy of ART medicines and explore reasons for deviation.
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    Evaluation of Analgesic and Anti-Inflammatory Activities of 80% Methanol Extract of Vernonia Filigera Leaves in Rodents.
    (Addis Ababa University, 2024-06-24) Asfaw Abenezer
    Evaluation of analgesic and anti-inflammatory activities of 80% methanol extract of Vernonia filigera leaves in rodents
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    Glucose Metabolism Disorders among People Living with HIV/AIDS on Efavirenz and Atazanavir/Ritonavir-Based Combination Antiretroviral Therapy: A Pharmacogenetic and Pharmacokinetic Evaluation
    (Addis Ababa University, 2023) Tadesse, Wondmagegn Tamiru(PhD); Engidawork, Ephrem(Prof.); Aklillu, Eleni(Prof.); Amogne, Wondwessen(PhD)
    This dissertation reports the results of cross-sectional and case-control studies investigating the prevalence and the link between pharmacogenetic and pharmacokinetic factors with glucose metabolism disorders (GMDs) among patients on efavirenz (EFV) and ritonavir (RTV)- boosted atazanavir (ATV/r)-based combination. GMD status was identified based on fasting glucose, fasting insulin, and HOMA-IR values. Cases were defined as the presence of any impaired fasting glucose, insulin resistance (IR), or diabetes mellitus (DM) while controls were those without GMDs. The cross-sectional prevalence study was conducted on EFV- (n=240) and ATV/r -based (n=111) combination antiretroviral therapy (cART). The prevalence and predictors of GMDs were determined by association and regression analysis. Samples from patients on long-term EFV (75 cases and 165 controls) and ATV/r-based cART (22 cases and 89 controls) were then genotyped for CYP3A4*1B, CYP3A5 (*3 and *6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). The mid-dose (CP12) of EFV, ATV, and RTV plasma concentrations (CP12) was determined using LC-MS/MS. The association of genotypes and CP12 of EFV and ATV/r with the incidence of GMDs were then investigated. vii The prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0-32.6%], with 31.1% (75/240) [95% CI 25.4-37.5%] for EFV-based and 19.8% (22/111) [95% CI 12.9- 28.5%)] for ATV/r-based cART group. All genotype frequencies followed the Hardy- Weinberg Equilibrium (p>0.05) between cases and controls. In the EFV group, the CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Similarly, multivariate analysis indicated CYP3A haplotype as a significant predictor of GMDs (p = 0.02) and IFG (p = 0.004), while CYP2B6*6 significantly predicted DM (p = 0.03) in EFV-based cART group. Furthermore, EFV Log CP12 ≥ 3.7 (5000) ng/ml was an independent predictor of GMDs. In ATV-based cART-receiving participants, the C allele carriers of SLCO1B1*5 c.521 T>C demonstrated a 2.9 times higher risk of GMDs [AOR=2.9; 95% CI 1.03-8.1, p=0.04] than the wildtype allele carriers. Haplotypes containing any *6 and only *3 of CYP3A conferred 80.0% (p=0.03) and 90.0% (p=0.01) protection, respectively, from GMDs than the wildtype combination haplotypes. In contrast, a 90% protection from IR was recorded for both haplotype combinations containing any *6 (p=0.03) and only *3 (p=0.01) types than the wild-type haplotype combinations. According to the plasma concentration analysis, the mean (SEM) logCP12 of ATV was 3.24 ng/ml (0.04) in controls and 3.52 ng/ml (0.06) in cases. But, the logCP12 of both ATV and RTV failed to show significant association with the GMDs. In conclusion, GMDs are highly prevalent among adults on EFV- than ATV/r-based cARTs. CYP3A haplotype and CYP2B6*6 genotype positively predicted GMDs and DM, respectively, among patients on long-term EFV-based cART. On the other hand, the CYP3A haplotypes decreased and the SLCO1B*5 allele increased the risk of GMDs among PLWH on ATV/r- based regimens. Higher EFV plasma concentration level independently predicted GMDs while viii the ATV plasma concentration did not. Our findings warrant further research with a larger sample size
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    Glucose Metabolism Disorders among People Living with HIV/AIDS on Efavirenz and Atazanavir/Ritonavir-Based Combination Antiretroviral Therapy: A Pharmacogenetic and Pharmacokinetic Evaluation
    (Addis Ababa University, 2023) Tadesse,Wondmagegn Tamiru(PhD); Engidawork,Ephrem(Prof.); Aklillu,Eleni(Prof.); Amogne,Wondwessen(PhD)
    This dissertation reports the results of cross-sectional and case-control studies investigating the prevalence and the link between pharmacogenetic and pharmacokinetic factors with glucose metabolism disorders (GMDs) among patients on efavirenz (EFV) and ritonavir (RTV)- boosted atazanavir (ATV/r)-based combination. GMD status was identified based on fasting glucose, fasting insulin, and HOMA-IR values. Cases were defined as the presence of any impaired fasting glucose, insulin resistance (IR), or diabetes mellitus (DM) while controls were those without GMDs. The cross-sectional prevalence study was conducted on EFV- (n=240) and ATV/r -based (n=111) combination antiretroviral therapy (cART). The prevalence and predictors of GMDs were determined by association and regression analysis. Samples from patients on long-term EFV (75 cases and 165 controls) and ATV/r-based cART (22 cases and 89 controls) were then genotyped for CYP3A4*1B, CYP3A5 (*3 and *6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). The mid-dose (CP12) of EFV, ATV, and RTV plasma concentrations (CP12) was determined using LC-MS/MS. The association of genotypes and CP12 of EFV and ATV/r with the incidence of GMDs were then investigated. vii The prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0-32.6%], with 31.1% (75/240) [95% CI 25.4-37.5%] for EFV-based and 19.8% (22/111) [95% CI 12.9- 28.5%)] for ATV/r-based cART group. All genotype frequencies followed the Hardy- Weinberg Equilibrium (p>0.05) between cases and controls. In the EFV group, the CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Similarly, multivariate analysis indicated CYP3A haplotype as a significant predictor of GMDs (p = 0.02) and IFG (p = 0.004), while CYP2B6*6 significantly predicted DM (p = 0.03) in EFV-based cART group. Furthermore, EFV Log CP12 ≥ 3.7 (5000) ng/ml was an independent predictor of GMDs. In ATV-based cART-receiving participants, the C allele carriers of SLCO1B1*5 c.521 T>C demonstrated a 2.9 times higher risk of GMDs [AOR=2.9; 95% CI 1.03-8.1, p=0.04] than the wildtype allele carriers. Haplotypes containing any *6 and only *3 of CYP3A conferred 80.0% (p=0.03) and 90.0% (p=0.01) protection, respectively, from GMDs than the wildtype combination haplotypes. In contrast, a 90% protection from IR was recorded for both haplotype combinations containing any *6 (p=0.03) and only *3 (p=0.01) types than the wild-type haplotype combinations. According to the plasma concentration analysis, the mean (SEM) logCP12 of ATV was 3.24 ng/ml (0.04) in controls and 3.52 ng/ml (0.06) in cases. But, the logCP12 of both ATV and RTV failed to show significant association with the GMDs. In conclusion, GMDs are highly prevalent among adults on EFV- than ATV/r-based cARTs. CYP3A haplotype and CYP2B6*6 genotype positively predicted GMDs and DM, respectively, among patients on long-term EFV-based cART. On the other hand, the CYP3A haplotypes decreased and the SLCO1B*5 allele increased the risk of GMDs among PLWH on ATV/r- based regimens. Higher EFV plasma concentration level independently predicted GMDs while the ATV plasma concentration did not. Our findings warrant further research with a larger sample size.
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    In-vivo and In-vitro Mechanistic Study in The Antidiarrheal Activity of Hydro-alcoholic Extract of Ocimum lamiifolium HOCHST. EX BENTH Leaves.
    (Addis Ababa University, 2023) Beyene,Dinberu; Shibeshi,Workineh(PhD); Umer,Shemsu(PhD)
    Ocimum lamiifolium is used in the management of various diseases such as fever, malaria, headache, cough, and gastrointestinal disease (diarrhea). This study was undertaken to evaluate the in-vivo and in-vitro mechanistic studies in the antidiarrheal activity of hydro-alcoholic extracts of the leaves of O. lamiifolium. The anti-diarrheal activity was assessed using a castor- oil-induced diarrhea model, charcoal meal test, and entero-pooling test in mice. The standard drug loperamide 3 mg/kg was given to the positive control. Different doses of the hydro- alcoholic extract of O. lamiifolium (100, 200, and 400 mg/kg were given to the test groups, and distilled water (10 ml/kg) was given to negative controls. The ex-vivo spasmolytic activity was evaluated using organ bath perfusion in isolated guinea pig ileum. The mechanistic study was also explored using a castor-oil-induced diarrheal model in the presence of naloxone (opioid antagonist). In the mechanistic study, the test group received 400 mg/kg extract with naloxone 2 mg/kg, the positive control received loperamide 3 mg/kg with naloxone 2 mg/kg, and the negative control received distilled water 10 ml/kg with naloxone 2mg/kg. In the castor oil-induced diarrhea model, all the tested ingredients significantly prolonged the onset of diarrhea and reduced the number of defecation (p<0.05). However, the mean weight of wet and total feces was significantly reduced by only the higher doses (200 and 400 mg/kg) (p<0.05). All doses also produced a significant (p<0.01) reduction in mean weight and mean volume of intestinal contents in the entero-pooling study. Similarly, in the charcoal meal test, all the study doses of the substance also produced significant (p<0.001) antimotility effects. In the mechanistic studies, the percentage inhibition of diarrhea by 400 mg/kg of the extract in the presence of naloxone (2 mg/kg) is 64.69%. In this case, charcoal meal traverse is significantly reduced by the extract compared to the control p<0.001. However, in the presence of naloxone (2mg/kg), the percentage inhibition by loperamide 3mg/kg is 6.89%. In the ex-vivo studies, the percentage of response or relaxation produced by the extract was 20%, 65%, and 75% at the doses of 0.1, 0.2, and 0.4 ml respectively. The doses that produced 50% maximal relaxation (EC50) by the extract were 0.18 ml or 1.8 mg of hydro-alcoholic extracts of O. lamiifolium. In conclusion, this study revealed that the hydro-alcoholic leaf extract of O. lamiifolium exhibits considerable anti- diarrheal activity because of its inhibitory effect on gastrointestinal motility and secretion. This is partly mediated through blockage of muscarinic acetylcholine receptors but not opioid receptors.
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    Warehouse Performance Assessment: The Case of Ethiopian Pharmaceutical Supply Service Head Office
    (Addis Ababa University, 2023) Kinde,Dagim Ayalew; Issa,rebu(Asst. Prof.)
    Introduction: Warehouse plays an essential part in the supply chain management, as it is an important hub for receiving and holding stocks until they distributed to the end consumers. In today's competitive landscape, the success of organizations depends on the productivity and effectiveness of their warehouse. Understanding warehouse efficiency is crucial for organizations to identify where inefficiency is and to improving warehouse performance. Therefore, assessing warehouse performance provides a valuable measure of how well these expectations being met and to help the decision maker to identify where the inefficiency is exist to set the policy to improve the warehouse performance. Objective: This study aims to evaluate the warehouse performance of the Ethiopian Pharmaceutical Supply Service head office with frequently used warehouse key performance indicator, which proposed by Frazzle (2002), namely quality, response time, productivity and cost/financial indicators. Methods: A descriptive cross-sectional study design employed and followed by quantitative data collection approaches. Primary data collected through a questionnaire adapted from prior literature and employing a five-point Likert scale. Since the total population less the researcher took all population using census method and the collected data analyzed descriptively. Results: The mean average score value of quality 3.1, response time 3.2, productivity 3.0 and cost indicator was 2.9, all indicators rated under the moderate performance level. The lower rating received for the Cost/Financial indicator, as reported by the respondents and EPSS should focus on this aspect to enhance warehouse performance. The overall mean average score value of the EPSS central warehouse performance of Head office measured across the four KPIs on a five-point Likert scale found to be 3.1, the level indicating an average level of agreement, which categorized under Moderate. This includes implementing cost-saving measures, reducing the overall cost of warehouse operations, and optimizing financial resources. Conclusions: The findings concluded that warehouse performance of Ethiopian Pharmaceutical Supply Service head office is at a moderate level. Further efforts should make to enhance the quality, response time, productivity, and cost efficiency to optimize warehouse performance and meet customer expectations effectively. Special attention should have given to the cost indicator since it rated least among the four KPIs.