Pharmacology

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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
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.
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.
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.
Challenges of COVID-19 vaccine cold chain management practices and vaccine utilization selected governmental health facilities under Addis Ababa Regional Health Bureau
(Addis Ababa University, 2023) Endale, Betelhem; Mitiku,Shiferaw(PhD)
The COVID-19 pandemic is causing unprecedented or extraordinary human and economic costs in all countries and societies across the world. After the WHO declared COVID-19 to be an international public health emergency vaccines were manufactured within one year. The Purpose of the study was to assess COVID-19 vaccine cold chain practice, challenges of cold chain management practices and vaccine utilization in selected government health facilities under the Addis Ababa Health Bureau. Both quantitative and qualitative research approach were employed. The population of the study was EPI focal persons who work in health facilities under 47 which accounts (44 health centers and 3 hospitals) and questionnaires were used to collect data and secured 95% response rate. Challenges of cold chain practice and utilization were filled using the five point likert scale and questionnaire was coded and analyzed using SPSS-V-20.Descriptive statistics mean were under taken regarding on cold chain capacity, stock management and vaccine storage temperature practiced slightly but regarding to cold chain equipment highly practiced. Furthermore, cold chain management challenges are influential in insufficient cold chain capacity, lack of latest technology or standard vaccine fridge, inadequate temperature monitoring and maintenance system, knowledge gap of health workers on cold chain practice as dependent variable. For COVID-19 vaccines cold chain management practice: AACAHB, Sub city offices and other stakeholders should improve practice in storage capacity should be assessed and assign experienced cold chain equipment maintenance technicians at the facility level.COVID-19 vaccines require special storage temperature monitoring and stock management by using introduction of temperature monitoring and by identify and address logistical issues such as the distribution of adequate storage equipment and give training should be provided periodically to improve stock management and minimize wastage of vaccine.
Assessment of Availability, Affordability and Prices of Essential Medicines for Under-Five Children in Northwest Ethiopia
(Addis Ababa University, 2023) Sisay,Berihun; Habte,Bruck Messele(PhD)
Background: Maintaining the health of under-five children is a major indicator of a countries well- functioning health care system and socioeconomic development. To ensure this, essential medicines need to be available and affordable at all times. Thus, the objective of this study was to determine the availability, prices and affordability of essential medicines for under-five children in selected health facilities of North West Ethiopia. Methods: The availability and prices data of fifty essential medicines (EMs) for under-five children in 30 public and 30 private health facilities was collected by employing the WHO/HAI methodology using a cross sectional study design. Availability was calculated by dividing the number of health sectors which stocked the medicines at the time of data collection by the total number of facilities surveyed and expressed as percentage. Affordability was measured as the number of daily wages required for the lowest-paid government worker to purchase a full treatment course for an acute condition or a 30-day treatment for a chronic condition. Results: The mean availabilities of lowest priced generic (LPG) medicines were 52.1% in the public sector and 40.2% in the private sectors, whereas for highest priced medicines (HPMs) it was found to be 0% and 11.5% respectively. The median price ratios (MPRs) of LPG medicines were 0.98 and 2.3 times the international reference price (IRP) for public and private sectors respectively. In the private sector the patient prices of HPMs were 4 times the IRP. The percentages of unaffordable medicines for the assessed common conditions were 75% and 91% in the public and private sectors respectively. Conclusion: The overall availability of EMs for under-5 children was suboptimal. Prices of EMs in the private sector exceed the IRP and most EMs for under-5 children were found to be unaffordable in both public and private sectors. Thus, further analysis of reasons for low availability and regulations on price markups in the private sector are needed to promote health and prevent catastrophic expenses.
Interaction of Catha edulis (Vahl) Forssk. ex Endl. (Khat) and the Endocannabinoid system on spatial learning and memory in mice
(Addis Ababa University, 2023) Argaw,Hilina Melese; Engidawork,Ephrem(Prof.)
Numerous studies have looked into the neurocognitive impact of cannabinoid ligands. The effect of Catha edulis (Vahl) Forssk. ex Endl. (Khat) on learning and memory is also researched by few scholars, although the findings were inconsistent. Moreover, the interaction of cannabis with other drugs of abuse is well studied. Indeed, recently, it was reported that the neurobehavioral effects of khat, such as motor tasks, working memory and anxiety-like behaviors are modulated by the endocannabinoid system. However, it is not known whether such modulation is apparent in spatial learning and memory. To this effect, mice 6–8 weeks old (6 per group) and a single dose of either crude khat extract orally (300mg/kg) alone or the cannabinoids intraperitonially (WIN-55,212-2 (1 mg/kg), JWH133 (5 mg/kg), cannabidiol (5 mg/kg), AM251 (1 mg/kg) and AM630 (1 mg/kg)) alone and in combination with crude khat were administerd according to their respective groups. Controls were administered with 0.5 ml of 2% Tween 80 in water. Spatial learning and memory were assessed using a battery of tests, including the Radial arm maze, Multiple T maze and the Morris water maze. Parameters including latency, correct/incorrect decision, reference memory error, and working memory error were determined. The data were analyzed using the Statistical Package for the Social Sciences and considered statistically significant when the P value was ≤ 0.05. The study revealed that acute khat exposure does not have a substantial effect on spatial learning and memory. Except for JWH 133, lone administration of Cannabidiaol and WIN-55,212- 2 resulted in significant enhancement and impairment of cognition, respectively. Whlist, co- administration of khat with cannabinoid agonists attenuates the effect produced by the agonist regardless of the direction of change (enhanced or reduced cognition). Co-administration with antagonists, however, has a pro-cognitive effect. Especially the cannabinoid 1 receptor inveres agonist/antagonist AM251 augmented khat's effect on spatial learning and memory more precisely.
Evaluation of the Fruit Mucilage of Cordia Africana as Table Binderin Paracetamol Table Formulation Optimization Using Response Surface Methodolgy
(2022-06) Ayalew, Tewodros; Mary, Nisha
Cordia africana Lam. (Amharic-wanza) (family: Boraginaceae) is a medium-sized evergreen tree that grows up to 4- 15 m with edible sticky fruits. It is native to Africa and is abundant in East Africa. The fruit mucilage of different species of cordia is found to be an excellent binder in tablet manufacturing. However, the binding ability of the cordiana african is not yet established. Therefore, this study aimed to evaluate the binding ability of Cordia africana fruit mucilage in tablet formulations using paracetamol as a model drug. The fruit mucilage of Cordia africana was extracted with maceration technique and characterized for different properties such as its compatibility with the model drug using the differential scanning calorimeter (DSC), the Fourier transform infrared spectroscopy (FTIR), surface morphology using scanning electron microscopy (SEM), and its crystallinity nature with X-ray Diffractometer (XRD). Furthermore, it was evaluated for loss on drying and moisture sorption studies. The mucilage was used to prepare granules using wet granulation method and finally compressed into tablet. The prepared tablets were evaluated for their hardness, disintegration time, friability, and drug release profile. Based on the preliminary study, concentration of disintegrant (starch -1500 (5-15%), mucilage concentration (3-10%), and compression force (50-100 N) were found to affect the response variables (Friability and Drug release) significantly (p value < 0.05). Therefore, the effect of these independent variables were further studied and optimized using the central composite design (CCD). The yield of extracted Cordia mucilage powder was found to be 29 %±0.9. The FTIR and DSC studies revealed that the mucilage is compatible with the model drug. The mucilage has shown no sharp peaks with noisy signal which was due to its amorphous nature. The loss on drying and moisture sorption studies were found to be 6%±0.02 and 1.3%-6.7%, respectively. The granules exhibited a good flowability and compressibility properties. All the prepared tablets have shown hardness value of less than 100 N and disintegration time in range from 0.55 to 10.27 minutes. The optimization study indicated that the quadratic model was the best fit model for both responses as per the model fitness summary. Furthermore, the ANOVA analysis for model adequacy testing confirmed the adequacy of the model for optimization.Accordingly, the model provided an optimum formulation at 5.32% of mucilage concentration, 5 % of disintegrant, and 76.71 N of compression force. Under this condition, the software predicted 83.3 % drug release at 30 minutes and 0.63% of friability. The validity of this optimum formulation was confirmed experimentally. The flowability of the granule of optimized tablet was found excellent as the angle of repose was found to be <30o while the Carr’s and Hausner ratios were determined as < 10 and < 1.11, respectively. Therefore, the results of this study suggest that the Cordia mucilage can be used as a tablet binder in tablet manufacturing.
Ex-Vivo Vasodilatory Activity and Possible Mechanisms of Action of Distillated Seed Extract From Lupinus Albus L. (“Gibto Arekei”) in Isolated Guinea Pig Thoracic Aorta
(Addis Abeba University, 2021-10) Likey, Yoseph; Shibeshi, Workineh
Hypertension is a major health problem globally necessitating exploration for new preventive and therapeutic tools. The community in North Western Ethiopia uses a local alcoholic beverage from Lupinus albus L. seed called “gebto arekei” for the treatment of hypertension. Although it has been extensively proven as an antihypertensive preparation, it lacks scientific evidence. Thus, the aim of this study was to investigate ex-vivo vasorelaxation activity and possible mechanisms of Lupinus albus L. distillated seed extract in isolated guinea pig thoracic aorta. Vasorelaxation effects of different concentrations of extract (4-32μg/ml) was investigated in isolated thoracic aorta strips of guinea pigs. Vasorelaxation response was evaluated by ex-vivo isometric tension recording method. The extract induced vasorelaxation response in both endothelium intact and endothelium denuded strips as well as strips pre-incubated with NG nitro-L-arginine methyl ester and methylene blue in concentration-dependent manner. The extract showed synergistic activity when combined with sodium nitroprusside. Determination of calcium concentration responses revealed significant inhibition of contraction. The concentration that caused maximal relaxation and 50% maximal relaxation was found to be 4.74μg/ml and 3.80μg/ml respectively in epinephrine pre-contracted endothelium intact strips where as it was 21μg/ml and 7.01μg/ml in similar strips pre-contracted by potassium chloride. Hence, popular usage of Lupinus albus L. seed preparation as a phytomedicine in the treatment of hypertension would be related to its effect through endothelial nitric oxide synthase-nitric oxide-cyclic guanosine monophosphate pathway and direct inhibitory effect on voltage dependent calcium channels. The findings shown that the preparation is endowed with vasorelaxation activity, providing evidence for its traditional use in the treatment of hypertension.
Anticonvulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.Ham ex D.Don (Lamiaceae) in Mice
(Addis Ababa University, 2021-11) Desalegn, Tesfaye; Prof. Engidawork, Ephrem
Epilepsy is one of the most common chronic neurological conditions that affect 70 million people in different parts of the world. The leaves of Ajuga integrifolia Buch.ham ex D Don have been used as anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting this claim is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant. To this effect successive Soxhlet extraction was performed using n-hexane, ethyl acetate, methanol and water. Anti-convulsant activity of the extracts was investigated in both acute (pentylenetetrazole, PTZ; and maximal electroshock, MES) and chronic (PTZ kindling) seizure models. For the acute model, various doses of the extract (100mg/kg, 200mg/kg and 400mg/kg) were administered. Positive controls received sodium valproate (200mg/kg) for PTZ and phenytoin (25mg/kg) for MES. Distilled water or 2% tween 80 was used for negative controls. Kindling was induced by repeated alternate day intra-peritoneal administration of sub-convulsive dose of PTZ (35 mg/kg) for 13 days and the most active extract (ethyl acetate) was tested in this model. Parameters including onset of clonus and duration of hind limb tonic extension were recorded. Moreover, total alkaloid, flavonoid and phenol contents of the most active extract were determined. Treatment of mice with ethyl acetate extract produced a superior effect among all solvent extracts in both PTZ and MES model. The mean latency to clonic seizure was significantly increased (p<0.01) with all doses of ethyl acetate extract in PTZ test compared to control and n.hexane extract ranked next to ethyl acetate extract in increasing onset of clonus. It significantly increased mean onset of clonus compared to controls, with a maximum increase (12.67min, p<0.001) displayed by HA400 mg/kg. Methanol extract at 200mg/kg and 400 mg/kg also significantly delayed onset of clonus (p<0.001) in PTZ model.Once again, all doses of ethyl acetate extract of the study plant significantly reduced (p<0.001) the mean duration of hind limb tonic extension in MES test compared to control. Hexane extract at 200 mg/kg and 400 mg/kg also significantly reduced (p<0.001) duration of hind limb tonic extension. Methanol extract at 200mg/kg and 400 mg/kg also significantly reduced (p<0.01) mean duration of hind limb tonic extension (HLTE) compared to control in MES test. Aqueous extract at all doses was devoid of any anti-convulsant effect in both models. A similar type of study done on the leaf crude extract and solvent fractions collected from different geographical location also reported anti-convulsant activity of the plant in acute seizure models. Treatment of mice with 200mg/kg and 400mg/kg of ethyl acetate extract along with alternate day PTZ injection significantly protected(p<0.01 for 200mg/kg and p<0.001 for 400 mg/kg) against PTZ induced kindling compared to controls in chronic model. Ethyl acetate extract of the plant was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045 ±0.8445 mg quercetin equivalent /g of dry weight extract of flavonoids and 21.928 ±1.118 mg gallic acid equivalent / g of dry weight of extract of phenols. This study indicated that the plant has anti-convulsant activity in both acute and chronic model and it could be a potential source to develop a new anti epileptic drug for pharmacoresistant epilepsy.
In Vitro Anti-leishmanial Activities of 80% Methanol Extract of Brucea Antidysenterica J.F. Mill Seeds and its Solvent Fractions
(Addis Ababa University, 2022-04) Ketema, Tasisa; Dr. Mequanente, Solomon; Prof.Makonnen, Eyasu; Prof.Hailu, Asrat
Leishmaniasis is a neglected tropical disease threatening lives of about 350 million people , globally. However, the currently available treatment options are limited and have drawbacks including variable efficacy, toxicity and unaffordability. Seeds of Brucea antidysenterica is used for the treatment of cutaneous leishmaniasis in traditional medicine. This study was aimed to evaluate its anti-leishmanial activity in vitro. Following preliminary anti-leishmanial activity studies, crude (80% methanol) extract of Brucea antidysenterica and its fractions were evaluated for their anti-leishmanial activities against promastigotes and intracellular amastigotes of Leishmania donovani and Leishmania aethiopica, and for their cytotoxic effects against mammalian cells. The quantitative estimations of total phenolic compounds (TPC), flavonoids (TFC) and alkaloids (TAC) were determined, spectrophotometrically. The crude extract and its hexane, ethyl acetate and butanol fractions showed anti-leishmanial activities with IC50 values of (4.14 ± 0.62 ≤ IC50 ≤ 60.12 ± 6.95 µg/ml) against promastigotes, and (6.16 ± 1.12 ≤ IC50 ≤ 40.12 ± 5.30 µg/ml) against amastigotes of both Leishmania species. They showed moderate cytotoxicity against Vero cell lines and peritoneal mice macrophages with CC50 values of 100 ≤ CC50 ≤ 500 µg/ml but > 1600 µg/ml against red blood cells. Having the selectivity index of (7.97 ≤ SI ≤ 30.97), the crude extract and its fractions showed selectivity toward Leishmania parasites. The crude extract, and its ethyl acetate and hexane fractions possessed (54.78 ± 1.39 ≤ TPC ≤ 127.72 ± 1.82 mg of gallic acid equivalent), (18.30 ± 0.07 ≤ TFC ≤ 79.21 ± 0.19 mg of quercetin equivalent) and (27.62 ± 0.27 ≤ TAC ≤ 97.22 ± 0.25 mg of atropine equivalent) per gram of extracts. The seeds of the plant possessed anti-leishmanial activities against L. aethiopica and L. donovani that might provide a scientific justification for its use in the treatment of leishmaniasis by traditional healers. Future works are recommended to isolate, purify and identify the possible secondary metabolites attributed to the anti-leishmanial activity of seeds of B. antidysenterica.
Eradication of Helicobacter Pylori with Standard Triple Therapy and its Clinical Implications
(Addis Ababa University, 2021-09) Gebeyehu, Endalew; Engidaworku, Ephrem
Background: Helicobacter pylori eradication based on standard triple therapy (STT) has been accepted to curb risks associated with H. pylori infection, commonly chronic gastritis and peptic ulcer disease. However, rate of eradication of H. pylori with triple therapy has been claimed to be below the recommended level due to several factors such as adverse drug effects (ADEs) and its determinants. ADEs during triple therapy may initiate poor medication adherence, which in turn reduces rate of eradication and associated patient outcomes. Evaluation of symptom resolution after H. pylori eradication therapy is the most common clinical practice in Ethiopia. As a result, studies that aimed at assessment of the rate of H. pylori eradication with STT, incidence of ADEs, status of symptom resolution after therapy and predictors for each of these consequences can have paramount importance in improving eradication therapy based on triple therapy regimen. Methods: STT based on a proton pump inhibitor, amoxicillin and clarithromycin was given to consented H. pylori positive adult outpatients in this facility based follow up study from May 2016 to April 2018 at Bahir Dar city in Ethiopia. Pre-developed structured questionnaire as used to collect anthropometric, sociodemographic and clinical data before and after eradication therapy. Eradication was confirmed with H. pylori monoclonal stool antigen test conducted after the end of 4–6 weeks of standard triple therapy. Data was analyzed by using descriptive statistics, chi-square test, bivariate and backward LR multivariate logistic regression. Significance was considered when p-value is less than 0.05 at 95%CI.Results: A total of 421 patients who completed follow up were involved in this study. The overall H. pylori eradication rate was 90.02% (379/421). Self-reported ADE was the only factor associated with H. pylori eradication rate with adjusted odds ratio of 2.92 (95%CI; 1.52-5.59, p < 0.001). Nearly a quarter (26.1%) of the patients reported ADEs and of all the reported ADEs, more than 85% were revealed as gastrointestinal symptoms, including gastrointestinal discomfort (39.1%), nausea (13.6%), diarrhea (12.9%), constipation (12.7%), and anorexia (10%). Predictors of self-reported ADEs were failure of eradication therapy (AOR: 12.64; 95% CI [3.29 - 48.53], p=0.001), body mass index above 25 (AOR: 2.82; 95%CI [1.26 - 6.31], p = 0.011), pain feeling during long interval between meals (AOR: 2.18; 95%CI [1.20 - 3.98], p = 0.011), failure to achieve complete symptom resolution (AOR: 5-19; 95%CI [1.46 - 18.50], p =0.011) and duration of acid-pepsin disorder more than 3weeks (AOR: 3.67; 95%CI [1.62 - 8.29], p = 0.002). Patients who achieved complete symptom resolution were 84.3%, which was lower than the overall H. pylori eradication rate of 90.02%. Positive predictive value and negative predictive value of complete symptom resolution after H. pylori eradication therapy was 98.9% (351/355) and 57.6%(38/66), respectively. Being non-user of traditional homemade supplements prepared from Fenugreek and/or Flaxseed (AOR: 2.14 95%CI [1.25 - 3.65], p = 0.005) was the only factor associated with complete symptom resolution. Conclusions: Modification or replacement of the STT observed in different healthcare institutions are not evidence-based since eradication of H. pylori with STT is still within the recommended level for clinical practice. Self-reported ADEs manifested with gastrointestinal symptoms are common during STT. Self-reported ADEs affect H. pylori eradication therapy. Body mass index, time duration of acid-pepsin disorder, pain feeling period in a day, eradication status and symptom resolution are determinants of self-reported ADEs. Success of H. pylori eradication is predictable with complete symptom resolution. Use of traditional food supplements prepared from Fenugreek and/or Flaxseed during eradication therapy affects status of symptom resolution. Key words: H. pylori eradication rate, Adverse drug effects, Predictive values, Complete symptom resolution, Associated factors
Antidepressant-like Activity of Solvent Fractions of the Root Bark of Carissa spinarum Linn. (Apocynaceae) in Rodents
(Addis Ababa University, 2022-03) Saif, Hana; Prof. Engidawork, Ephrem
Depression is a chronic and recurrent psychiatric disorder affecting mental and physical health. Traditional medicines have been used for decades in the treatment of depression due to resistance development, side effects, inadequate accessibility and affordability of modern antidepressant drugs. The root bark of Carissa spinarum Linn. (Apocynaceae), which is used traditionally for depression is reported to possess antidepressant- like activit y in rodent models of depression. In the current study, different fractions of the root bark obtained using solvents of different polarities were investigated using a host of models, including tail suspension test (TST), forced swim test (FST), muricidal behavioral test, and open field test (OFT). Moreover, markers for depression and phytoconstituents were determined, and preliminary mechanistic studies using different drugs were also conducted. Five groups of animals of either sex each having 6 animals per group were randomly assigned for every model and each solvent fraction (Ethyl acetate, n-butanol, and aqueous). Group I, served as a negative control group and received a vehicle (2% Tween 80), group II served as a positive control and received the standard drug Imipramine (30 mg/kg), group III-V received increasing doses of the solvent fractions 50, 100 and 200 mg/kg, respectively. Ethyl acetate (CSE) and n-butanol (CSB) fractions significantly (p<0.001) reduced the duration of immobility in TST and FST, while the aqueous fraction (CSA) failed to show any appreciable antidepressant- like activity. No change in the locomotor activity using OFT was observed at all doses. From the two active fractions, the ethyl acetate fraction was the most effective and contributed to reducing the muricidal behavior in rats. Serum corticosterone level was reduced by both fractions and once again the ethyl acetate fraction was the most effective. Mechanistic studies revealed the involvement of multiple neurotransmission systems, including adrenergic, dopaminergic and choline r gic as well as the L-Arginine-NO-cGMP pathway in the antidepressant- like effect of the plant, hence only both the dopaminergic and the L-Arginine-NO-cGMP pathway were the predominant by which the ethyl acetate fraction might mediate its action. Phytochemica l analysis showed the presence of high content of alkaloids (0.17 mgATE/g and 0.07 mgATE/g), flavonoids (12.43 mgQE/g and 2.07 mgQE/g), and phenols (42.42 mgGAE/g and 29.8 mgGAE/g) for CSE and CSB, respectively. The findings collectively indicate that CSE and CSB are endowed with antidepressant- like activity due to the presence of phenols, flavonoids, and alkaloids, which are medium polar in nature.
Anticonvulsant Effect of Pterlobium stellatum (Leaves), Moringa stenopetala (Root) And Clutia abyssinica (Leaves) Traditionally Used for Treatment of Epilepsy in Ethiopia Using Mice Model
(Addis Ababa University, 2021-06) Sahile Salile, Samson (PhD); Prof. Abula, Teferra
Background :Epilepsy is the third leading contributor to the global burden of disease for neurological disorders and affects 65 million people worldwide. Although the current antiepileptic drugs achieve symptomatic seizure relief they do not prevent or reverse the pathological process that underlies human epilepsy. Drug resistant epilepsy is also one of the most important unmet needs in the daily management of epilepsy. These currently unmet needs provide a roadmap for the development of more effective antiseizure drugs, as well as for disease modifying and antiepileptogenic drugs especially from plants. This study was conducted to investigate the anticonvulsant activity of the crude hydroalcoholic extracts of 3selected plants Pterlobium stellatum ( leaves), Moringa stenopetala (root) and Clutia abyssinica (leaves). These all are used for treatment of epilepsy by traditional healers in different parts of Ethiopia. Additionally the solvent fractions of the Pterlobium stellatum were tested for anticonvulsant activity as the crude extract showed positive response in all the models used. Methods :.The dry residues of the plant extracts were used for test in different doses. Male balb c mice were used for in vivo study and for in vitro study P14-P21 of C57BL16 mice were used. In vitro mice model of hippocampal slice with 0Mg 2+ was used and the extracts were tested at the 0.7mg/kg concentration. Diazepam 3µM was positive control and DMSO as negative control. In in vivo PTZ and MES mice models 400mg/kg and 800mg/kg of each test extract were used for efficacy test in as positive control Diazepam 5mg/kg and phenytoin 10mg/kg were used respectively. The negative control was 2% tween 80 .Fisher's exact test was used to analyze proportions and ANOVA with post hoc LSD to test means. The tests were conducted after the ethical clearance was obtained from the ethical committee of Addis Ababa University and university of Cape Town. Qualitative test and quantitative tests were used to determine the secondary metabolites in the plants. And ultraperformance liquid chromatography-mass spectrometer (UPLCMS) tests were used to characterize plant constituents in Pterlobium stellatum crude extract and its fractions. Results :In the in vitro study the hydroalcoholic extract of P.stellatumand M. stenopetalaat 0.7mg/ml had a statistically significant anticonvulsant activity compared to negative control(P<0.05). The hydroalcoholic extract of C.abyssinicaat 0.7mg/ml didn't show statistically significant effect compared to negative control (P>0.05). A positive control, diazepam(3µM), showed statistically significant anticonvulsant activity compared with negative control (P<0.05).When we compare the in vitro activity of different solvent fractions of P. stellatum,the chloroform and water fractions at 0.7mg/ml were also shown to have significant anticonvulsant activity as compared to negative control (P<0.05). The petether and butanol fractions activities were not statistically significant compared to negative control (P>0.05). Pterolobium stellatum hydroalcoholic extract shown that dose dependent and statistically significant anticonvulsant activity with PTZ model(P<0.05).Whereas the activity of M. stenopetala and C. abyssinica hydroalcoholic extracts were not statistically significant (P>0.05) in in vivo PTZ model. The in vivo PTZ test has also revealed the chloroform fraction and the water fraction of Pterolobium stellatum to have anticonvulsant effect(P<0.05) compared with the negative control. Whereas the pet ether and butanol fractions shown activity which was not statistically significant with negative control(P>0.05).The effect of the diazepam was statistically significant with the negative control and all test extracts (P<0.05). Pterolobium stellatum and M. stenopetala hydroalcoholic extracts shown statistically significant anticonvulsant activity with MES model in both lower and higher doses(P<0.05). The C. abyssinica hydroalcoholic extracts activity at the given doses were not statistically significant (P>0.05).The in vivo MES test has also revealed the chloroform fraction to have anticonvulsant effect at both doses (P<0.05). The water fraction at 400mg/kg dose shown anticonvulsant effect compared with the negative control(P<0.05). The pet ether and butanol fractions shown activity which was not statistically significant at the given doses (P>0.05).The effect of the phenytoin was statistically significant with the negative control as well as compared with other tested extract doses(P<0.05). The qualitative and quantitative analysis indicated the presence of different plant secondary metabolites in hydromethanolic extracts of the three plants. In Pterolobium stellatum the UPLCMS analysis indicated also the presence of gallic acid, ellagic acid, kaempferol, myricitrin, isoquercitrin and quercitirin in the crude extract. Of these gallic acid and ellagic acid were found in chloroform fraction. In the water fraction ellagic acid, kaempferol, myricitrin and isoquercitrin were found. Conclusion: The results demonstrated that Pterolobium stellatum has anticonvulsant effect. The hydroalcoholic and chloroform and water fraction of Pterolobium stellatum demonstrated effect in both in vitro and in vivo MES and PTZ models of epilepsy. The crude extract of Moringa stenopetala has also shown to have anticonvulsant effect both in the in vitro and in vivo MES models. But was negative on PTZ model. The traditional use of both herbs for treatment of epilepsy can be supported by the finding of this study. However ,C. abyssinica didn't show anticonvulsant activity at the tested doses in the models used in this study and its traditional use for treatment of epilepsy is not supported according to the findings of this study.
Treatment Outcome of Neonatal Sepsis and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: A Retrospective Cohort Study.
(Addis Ababa University, 2022-02) Lemma, Bethlehem; Abebe, Workeabeba(MD, MPH Associate Professor of Pediatrics); Ayalew, Eskinder (BPharm, MPharm, Assistant professor)
Globally, neonatal sepsis is a major cause of neonatal death. A definitive early diagnosis and appropriate antimicrobial therapy which significantly reduce mortality are challenging in resource limited settings like Ethiopia. This study aimed to assess the treatment outcome and factors associated with neonatal sepsis mortality among those treated at the neonatal intensive care unit of Tikur Anbessa referral hospital (TASH), Addis Ababa, Ethiopia. A retrospective cohort study was conducted from September, 2018 to September, 2020.Neonates diagnosed with sepsis by the attending physician either clinically or laboratory-confirmation was included in the study. Data such as patient’s age, sex, and address, type of antimicrobial administered, date of treatment started and completed, microbiological results and other clinical characteristics were collected retrospectively from medical chart. Data were entered and analyzed using the Statistical Package for Social Sciences version 25. Survival analysis was performed using Kaplan Meier Method. Log-rank test was used to determine survival period differences and cox hazard regression was used to identify associated factors of neonatal mortality. Systematic random sampling technique was employed to recruit the study participants. Binary logistic regression was used to predict determinants of length of hospital stay. Statistical significance was declared at p-value <0.05.The total number of neonates in this study was 206. One hundred ninety three (93.7%) neonates have survived from neonatal sepsis and 77 (37.4%) of the neonates stayed in the hospital for more than seven days. Multivariable analysis showed that risk hazard of neonatal mortality was 5.486 higher among pregnant women with history of vaginal discharge compared to pregnant women’s without discharge (AHR, 5.486, 95% CI: 1.308-26.134).Conversely, absence of Premature rupture of membranes (PROM) (0.503 CI: 0.326-0.776) and those neonates delivered through SVD (AHR 0.265, CI: 0.091-0.767), were associated with decreased risk of mortality. Kaplan-Meier survival analysis using log-rank test shows there was a statistically significant decrease in survival period among neonates delivered through spontaneous vaginal delivery (SVD) than neonates delivered by caesarian section (CS) (p = 0.014). Low-birth weight (AOR=11.87, 95%CI: 2.344-60.15) and being on Ampicillin (AOR=16.09, CI: 4.484-57.74) were associated with prolonged hospitalization. On the other hand, being female (AOR= 0.090, 95%CI: 0.018-0.458); absence of GI symptoms (AOR= 0.214, 95%CI: 0.19-0.350); and antibiotics dose change from initial treatment (AOR= 0.081, 95% CI: 0.001-0.703) were associated with a decreased rate of hospitalization. The Obstetrics and gynecology department should promote delivery though SVD, and to increase Antenatal care and aggressively manage of pregnant women with vaginal discharge as it significantly affects the outcome of their newborns with neonatal sepsis. Emphasis should be given on meticulous management of neonatal sepsis and early change of antibiotics is imperative when needed as it reduces length of hospital stay thereby decreasing mortality.
Evaluation of the Antidepressant-like Activity of Sennasingueana (Del.) Lock, (Fabaceae) in Rodents.
(Addis Abeba University, 2021-03) Bogale, Mikyas; Prof. Engidawork, Ephrem
Depression is a multifactorial, chronic, and life-threatening disease with high prevalence, disability, and societal cost. Currently, 20%–30% of patients treated with commonly used antidepressants do not achieve complete recovery and develop treatment-resistant depression. Drug resistance in addition to side effects and drug interactions are the major restrictions in the treatment of depression. Thus, there is an urgent need to identify new treatment options including herbal drugs. In this study, the essential oil extract of Senna singueana (Del.) (Fabaceae) was assessed for its antidepressant property using the tail suspension test (TST) and the forced swimming test (FST) models. To rule out the false-positive antidepressant-like activity of the oil, open field test (OFT) was used. The composition of essential oil was determined using gas chromatography–mass spectrometry (GC/MS) analysis. All animals were randomly assigned to six different groups for each model. Group I received the vehicle (2% Tween 80) and served as a negative control. Group II received the standard drug imipramine (30 mg/kg) and served as a positive control. The test groups were from group III-VI and received increasing doses of the extract at 100 mg/kg, 200 mg/kg, 400 mg/kg, and 600mg/kg, respectively. In TST, 600 mg/kg showed a significant immobility time reduction (56.6%) as compared to 100 mg/kg, 200 mg/kg (p<0.05) and 2% Tween 80 (p<0.01) treated groups. In FST, on the other hand, 400 mg/kg (50.6%) and 600 mg/kg (61.8%) test doses exhibited a statistically significantly reduction in immobility time (p< 0.01) as compared to 2% Tween 80, 100 mg/kg and 200 mg/kg treated groups. It was also demonstrated that the essential oil extract of Senna Singueana didn’t significantly alter the spontaneous locomotor activity of mice during the OFT test. From GC-MS analysis a total of 33 compounds were identified and compounds like eugenol, linalool, n-hexadecanoic acid, octadecanoic acid and heneicosane, which previously reported to have antidepressant activity were found. In conclusion, this study indicated the essential oil extract of Senna Singueana may have potential therapeutic value for the management of depression.
Assessment of vaccine provider’s knowledge, and attitude, and private healthfacilities compliance with World Health Organization requirement of vaccinemanagement practice, Addis Ababa, Ethiopia.
(Addis Abeba University, 2021-06) Alemayehu, Lake; Dr. Messele, Bruck(B. Pharm, MSc, Ph.D); Dr.Berhanu, Tariku(BSc,MPH, Ph.D)
Introduction: Vaccines are exceedingly efficient biological substances and the first lines of public health strategies against infectious diseases. Due to the sensitive nature of vaccines, appropriate measures need to be put in place to ensure that vaccines remain potent from point of manufacture to administration. Objective: To assess vaccine provider‟s knowledge, and attitude, and private health facilities compliance with World Health Organization requirement of vaccine management practice, Addis Ababa, Ethiopia. Methods: Cross-sectional study design was employed to collect data using a structured questionnaire and observation tools in the private health facilities offering immunization services in Addis Ababa. The study was conducted from March to July 2020. Data were analyzed by SPSS and the result was presented by frequency and percentage in the form of tables and graphs. Result: Thirty private health facilities were included in the assessment and, only 3(10%) had WHO prequalified functional refrigerators, while 90% of the facilities had domestic types of refrigerators. Of the 34 study participants who participated in the study, 7(20.6%) respondents had poor knowledge of vaccine cold chain management while 26 (76.5%) had a positive attitude toward vaccine cold chain management. Determinants of knowledge on vaccine cold chain management training were (P = 0.042), and supportive supervision (P = 0.026). The knowledge of healthcare workers towards the vaccine cold chain management was significantly associated with the health workers‟ training and supportive supervision in health facilities. Determinants of attitude on vaccine cold chain management training were (P= 0.019) and supportive supervision was (P= 0.043). The attitude of healthcare workers towards the vaccine cold chain management was significantly associated with the health workers‟ training and supportive supervision in health facilities. Conclusion: This study indicates that WHO standard refrigerators are available only in some health facilities for vaccine storage. There was also a gap, in training, knowledge, and attitude of vaccine providers toward vaccine management, and inappropriate vaccine management practice. Therefore, there is a need to improve cold chain management.
Anti-ulcer activity of aqueous root extract of Ensete ventricosum (Welw.) Cheesman (Musaceae) in experimental rats
(Addis Abeba University, 2021-07) Hailu, Dejene; Shibeshi, Workineh (PhD); Umer, Shemsu (PhD); Arayaselassie, Mahlet (MD)
Peptic ulcer is a chronic disease of gastrointestinal system caused by an imbalance between damaging factors and protective factors. Even though many antiulcer drugs used to treat this disease are available, most of these drugs produced undesirable side effects, microbial resistance and danger of drug interactions during therapy. An ethnobotanical study showed that Ensete ventricosum is used for treatment of peptic ulcer but the efficacy and safety are not established. Thus, this study was aimed to evaluate the anti-ulcer activity of aqueous root extract of Ensete ventricosum (E. ventricosum) in experimental rats. The effect of the extract on gastric ulcer was evaluated against indomethacin, ethanol and pyloric ligation-induced ulcer models at doses of 100, 200 and 400mg/kg. Dose levels were selected based on outcome of acute toxicity study. Pantoprazole at a dose of 40mg/kg was used as a standard drug while distilled water was used as negative control. In indomethacin and ethanol-induced ulcer, pretreatment with aqueous root extract of E. ventricosum significantly reduced level of gastric mucosal ulceration and improved ulcer protection. Furthermore, histopathological findings of rats pretreated with aqueous root extract of E. ventricosum also revealed gastroprotective activity. In pyloric ligation-induced ulcer, administration of E. ventricosum at a dose of 200 and 400mg/kg significantly (p<0.05) reduced both ulcers number and severity scores and histopathological findings also revealed gastroprotective activity of the extract. The extract at a dose of 400mg/kg exerted best ulcer protection (98.53%) which was comparable to standard drug in pyloric ligation-induced ulcer as compared to other models studied. The extract at a dose of 200 and 400mg/kg also displayed antisecretory activity as revealed by significant (p<0.05, p<0.001) reduction in volume, free and total acidity of gastric juice with significant (p<0.05, p<0.001) increment in pH of the gastric juice in both ethanol and pyloric ligation-induced ulcer in dose dependent manner. In conclusion, the aqueous root extract of E. ventricosum showed significant antiulcer activity.
Antitrypanosomal Activity Of Hydromethanol Extract Of Leaves Of Cymbopogon Citratus And Seeds Of Lepidium Sativum In-Vivo Mice Model
(Addis Abeba University, 2021-07) Yetayeh, Ayechew; Prof.Mekonnen, Eyasu(PhD, Professor of Pharmacology); Beyene, Takele(Associate Professor of Pharmacology)
Trypanosomiasis is one of the neglected tropical diseases of both humans and animals caused by the protozoa Trypanosomes mainly endemic in Africa. Unavailability of vaccine, difficulty of vector controls, low therapeutic index of the available trypanocidal drugs, and development of resistance lead to the need for research focused on developing alternative safer, more effective and more accessible treatment options especialy from medicinal plants. In Ethiopia, many medicinal plants such as Cymbopogon citratus and Lepidium sativum are used for treatment of trypanosomiasis as traditional remedies. The objective of the present study was, therefore, to investigate antitrypanosomal activities of leaves of C. citratus and seeds of L. sativum in in vivo mice model. The acute toxicity result showed that the extracts were safe at the dose of 2000mg/kg, and the test doses were adjusted to 100, 200 and 400mg/kg based on the toxicity profile. The Plants extracts were administered to the respective groups of mice after the 12 th days of T. congolense inoculation where the peak parasitemia were achieved. The treatment continues consecutively up to seven days and the parameters were recorded every other day up to the 14 th day of treatment commenced. The in vivo test results revealed that both plant extracts had dose dependent antitrypanosomal activity. Both crude extracts showed a significant reduction in parasite load (P<0.05), ameliorated anaemia (increased or prevent the fall of PCV value) (P<0.05), decreased lymphocytosis and increased neutrophil counts (p<0.05) and improved body weight but significant body weight increment (P<0.05) was observed only in C. citratus treated mice compared to the negative and positive controls. Comparative results from all tested parameters showed that the best activities were observed with C. citratus treated groups of mice (73.2% reduction).
Assessment of Drug Therapy Problems and Contributing Factors among Ambulatory Patient with Type 2 Diabetes mellitus in Dagmawi Menelik Hospital, Addis Ababa, Ethiopia
(Addis Abeba University, 2021-07) Yenesew, Asmamaw; Prof.Makonnen, Eyasu(PhD, Professor of Pharmacology); Alemkere, Getachew(BPharm, MSc, Assistant Professor of clinical pharmacy)
Patients with diabetes are at high risk of drug therapy-associated problems (DTPs), as they are exposed to multiple medications. Studies conducted on DTPs in diabetic patients in Ethiopia are, however, limited. This study was, therefore, aimed to assess the magnitude, pattern, and factors associated with DTPs among patients with type 2 diabetes at Dagimawi Menelik Hospital (DMH). A cross-sectional study was conducted among 294 patients who fulfilled the inclusion criteria. Patients were interviewed using a structured data collection format, involving retrospective medical chart review. DTPs were assessed using Cipolle‘s classification system. Descriptive data were reported using tables and figures. A multivariate logistic regression analysis was performed to identify factors associated with DTPs. A total of 448 DTPs in 193 (65.6%) patients were identified. Most commonly identified DTPs were non-compliance, 118(26.3%), need additional drug, 110(24.6%), and dosage too low 89 (19.9%). On multivariate analysis, history of hospitalization (AOR= 4.34, 95% CI: 1.21, 15.54), poor glycaemic control (AOR= 59.5 95% CI: 18.9, 188.0), presence of co-morbidity (AOR= 6.7, 95% CI: 2.4, 19.0) and diabetes complication (AOR= 4.1, 95% CI: 1.1, 15.2) were positively associated with occurrence of DTP On the other hand, physical activity (AOR= 0.2, 95% CI: 0.0, 0.7), absence of polypharmacy (≤3 drugs) (AOR= 0.1, 95% CI: 0.0, 0.6) were protective for the development of DTP. In conclusion, there was high prevalence of DTP particularly among patients with poor glycemic control, history of hospitalization, comorbidities, complications, inactivity and polypharmacy.. Further studies on the prevention and management of DTPs, therefore, need to be conducted.

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