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Item Characterization of the Short-Term Effects of Prenatal Asphyxia and Screening of Some Ethiopian Medicinal Plants for the Probable Preventive Role in Rats.(Addis Ababa University, 1997-04) Engidawork, EpbremPerinatal asphyxia results from failure of normal respiratory gas exchange during or soon after labor and it remains an important cause of permanent neurological deficit in surviving infants. The most common features are hypoxia, hypercapnia, and metabolic acidosis. The present sf1ldy was undertaken to fUrther characterize the short-term effect of perinatal asphyxia and to investigate a possible preventive role of some Ethiopian medicinal plants and hypothermia in rats. The effect of perinatal asphyxia on survival pattern, brain and heart pH, levels of amino acids, monoamines, and glycolytic intermediates was studied using in vivo microdialysis and ex vivo biochemistry. Perinatal asphyxia was induced by immersing fef11S containing uterus horns, obtained by cesarean section from term pregnant rats, in a water bath at 370C for different periods (0-23 min), according to a non-invasive model that largely mimics the conditions resulting in asphyxia during human labor (Bjelke et al. , 1991; Andersson et aI., 1992; Herrera-Marschitz et al., 1993). Subcutaneous levels of pyruvate, lactate, glutamate, and aspartate were monitored with microdialysis 80 ~lin-8 days following delivery. In parallel experiments, pups were sacrificed 40 min after delivery and the brain and heart were removed to measure pH In addition, pups were also sacrificed 80 min-8 days after delivery and the brain was removed to measure striatal levels of pyruvate, lactate, glutamate, aspartate, and monoamines. At 37°C, a decrease in the rate of sU/vival was first observed following asphyxic period longer than 16 min and no survival was observed after 22 min. pH decreased with the length of asphyxia. In control pups (cesarean delivered), brain pH was (7.3±0.01;N=6) and heart pH was (7.35±0.01; N=6). A significant decrease in pH was observed following 10-11 min and 5-6 min, in brain and heart respectively. After 80 min of delivery, a significant increase in the levels of all the measured compounds, in subcutaneous and brain tissues, were observed follOWing exposure to mild asphyxia. However, the levels started to decline when asphyxia was prolonged With increasing age, the levels of the measured compounds in mild • asphyxic pups were almost similar as that of the control pups. Nonetheless, the time needed to recover depended upon how greatly the compound's metabolism was affected Lactate being the most severely affected, much time was needed to reduce its level. Thus, changes in systemiC pH, glycolytic intermediates, monoamines, and excitatory amino acids metabolism were observed following perinatal asphyxia. In particular, subcutaneous level of lactate preceded: (q) a decrease in brain pH, (b) an increase in brain lactate level, (c) a decrease in the rate of survival, and probably (d.) brain damage. The possible protective effect of some herbal medicines was evaluated by injecting the extract subcutaneously or using as a bathing fluid and subjecting the pups to asphyxia at 370 C. Asphyxia induction at 300C and I50C was also carried out to evaluate the protective effect of hypothermia and to use it for comparison purpose. Survival was prolonged when asphyxia was induced under hypothermic condition. No survival was observed after 50 min and 140 min when asphyxia was induced at 300C and I50C respectively. Survival pattern after treatment with plant extracts did not show any significant difference compared to saline injected control group. Thus, hypothermia seems the only intervention that can provide good protective effect amongst the interventions so far evaluated. However, with improvement in obstetric management, its role has been shown to be limited. As early as the 1930s, the cause of petlnatal brain damage was intimately tied up with attitudes towards the use of sedatives, analgesics, and anesthetics duriug labor and delivery (Eastman, 1936). It was demonstrated that the excessive use of these agents caused "apnea neonatomm" which was thought to be the principal cause of cerebral injwy (Sclueiber, 1938) and almost all Wliters of the time suppOlted this view and equated "asphyxia neonatorum" with "apnea neonatorwn". Although this view was later shown to be unlikely (Myers, 1977), the tendency to consider birth apnea as a causative factor for cerebral injmy dominated-the 1940s-and the 1950s-. - Hence, articles appeared in the I 940s strongly suggested a causal relationship between petlnatal asphyxia and cettain patterns of nemopathogenic changes in the brain. It was stated that the brain swelling and necrosis obsetved in newborns who died after cesarean delivety because of premature detachment of the placenta was due to asphyxia (Clifford, 1941). The injwies at buth were thought to be associated either to trawna to the head or to fetal systemic hypotension caused by asphyxia (Malamud, 1959,1963; Norman, 1969). It was believed that cerebral venous congestion causes the haemorrhagic infarction that often affects the brains ofbitth-injw·ed babies (Schwartz, 1961). The congestion was atttibuted to the rapid passage of the fetal head ii-om a wne of high pressure within the utems to one oflow pressw·e outside (Schwaltz, 1961). The infarction of the cerebrum associated with birth injwy was caused by fetal circulatOlY failure, generalized venous congestion, and cerebral venous stasis-thrombosis (Towbin, 1970). Thus, a nwnber of causes have been proposed for petlnatal brain damage of which petlnata1 asphyxia is one of the candidates. Asphyxia is defined as suffocation with anoxia and increased carbondioxide. It atises from impairment of normal respit·atOlY gas exchange with resulting hypoxia/ischemia, hypercapnia, and metabolic acidosis. The term perinatal asphyxia is often used to indicate an impainnent of gas exchange during or soon after labor (Nelson and Leviton, 1991; Martin and Nelson, 1993). The tenn hypoxic-ischemic or postasphyxial encephalopathy is often used to describe the illness thought to stem from such impaiIment. In most instances, during the peIinatal peIiod, hypoxemia and/or ischemia occm as a result of asphyxia (Hull and Dodd, 1991). When descIibing oxygen deptivation in hllJDan, the tenn asphyxia is used, because it is not known whether the insult is hypoxic, ischemic, or more probably a combination. Fmthennore, regarding the fetus, the telms hypoxia and ischemia have been used interchangeably, because, the most common cause of hypoxia in the fetus is hypoperfusion or ischemia. Hypoxia can also cause ischemia, as it is capable of producing hypotension and reduced cardiac output. Thus, in asphyxia, the major additional feature is hypercapnia, which results in a nllJDber of other metabolic disorders, such as acidosis and physiological effects including cerebral vasodilatation (Volpe, 1987). Hypoxia and partial regional ischemia commonly occm together, therefore, it appears that the regional distIibution of ischcmia in the face of hypoxia is a major determinant of the relatively selective nature of peIinatal asphyxial brain injury. Hence, this type of brain injmy is refelTed to as hypoxic-ischemia. PelIDatal asphyxia can occm in the human fetus or neonate as an acute total asphyxial episode resulting ii-om cord prolapse that leads to complete cessation of blood flow (Leech and Alvord, 1977), and as a prolonged partial asphyxial episode resulting from placental abruption that may occm during a long and complicated labor (Clifford, 1941). In order to understand the patterns of pelIDatal brain damage, two models in monkeys have been developed: acute total asphyxia (Ranck and Windle, 1959) and prolonged partial asphyxia (Brann and Myers, 1975; Myers, 1972, 1977). The first model that replicated acute total asphyxia caused a lesion affecting spinal cord, brainstem and thalamus without brain swelling. TIle second model that replicated prolonged partial asphyxia, however, produced a different pattern of cerebral affecting mainly the COltiCal and subcortical stmctures with brain swelling (Myers, 1972). The reason for the different distribntion of the lesions depends upon the redistribution of regional cerebral blood flow and the degree of neuronal maturation dwing asphyxia. In most cases, tbe total pelinatal insnlt in hmnans most likely resnlts from prolonged partial asphyxial episode, and sometimes from partia~ combined with terminal acnte asphyxial episode (Scott, 1976; Braun, 1986). Heuce, fetal partial asphyxia of any cause, independent offetal circnlatOlY collapse and head compression, is believed to be the Priru31Y event that sets in motion a vicious cycle ofbraiu swelling, leading to stasis of blood flow and, fiually to cerebral necrosis (Br3lill and Myers, 1975). IufOlmatiou about the specific effect of birth asphyxia on the fetus or neouates has beeu possible only since the development of new techniques for detennining blood pH and blood gases. The introduction of risk scoring and assessment of fetal behavior has finther improved the identification of the fetus at risk for a.phyxia (Brallll, 1986; Lowet ai, 1992). Thus, Apgar (1953) developed a SCOling system to infer the occurrence of birth asphyxia and to quantifY its sevelity from several indicators, such as: (i) type of breatlling; (ii) healt rate; (iii) color of the skin; (iv) muscle tone; and (v) response to different sensory stimnli. UnfOltwlately none of these indicators is an accurate predictor of outcome, rather they are probably best used to indicate the need for active resuscitation (Hnll and Dodd, 1991). Biochemical data such as umbilical pH and gas levels obtained soon after birtb may be used to validate the judgement tbat the pathophysiological changes obselved during birth 31'e asphyxial in natme. But these putative markers of asphyxia do not always conelate well with one another. Because of the poor predictive value of the traditional indicators, alternativesand Sarnat, 1976). HIE develops in the first few hours and days of life and is characterized by abnonnalities of tone, feeding, level of consciousness, and in the more severe cases, seizures and finally coma with the need for ventilatOlY support. The postasphyxial encephalopathy is graded into mild (no seizure), moderate (seizures) and severe (coma). Those infants with mild encephalopathy have a unifonnly good outcome, those with moderate encephalopathy have a 20-30% chance of severe handicap, and the majOlity of infants with severe encephalopathy die (Hull and Dodd, 1991). Hence, HIE has been found to be a much more accurate predictor of outcome (Robertson and Finer, 1985), however, the recent identification of a group of infants with typical encephalopathies (Hull and Dodd, 1991), without previous evidence of asphyxia cast some doubt on the casual relation between the two phenomena. Thus, there is still no reliable clinical indicator of birth asphyxia. Nevertheless, with the development of magnetic resonance spectroscopy, a potential independent indicator of brain asphyxial states has emerged (Martin and Nelson, 1993). Several animal models have been developed to assess the role of asphyxia in mediating brain damage (see Raju, 1992). In the present thesis, the short-telm effect of perinatal asphyxia and its prevention was studied in rat using a novel non-invasive model that largely mimics the conditions resulting in asphyxia during human labor (Bjelke etaI., 1991; Anderson etal., 1992; Herrera-Marschitz etaI., 1993) sought. This effort led to the identification of the abnOlmal neurological signs known as hypoxic-ischemic encephalopathy (HIE), that was used as an assessment of asphyxia (SamatsinewyItem Anti Tuberculosis Drug Induced Hepatotoxicity in Hiv Positive and Negative Patients(Addis Ababa University, 2005-06) Yimer, Getnet; Aseffa, Abraham(PhD)Anti-tuberculosis drug induced hepatotoxicity (DIH) is a common problem in the management of tuberculosis. This study was intended to identify possible risk factors for development of DIH, including degree of immunosuppression. In this prospective 2-month cohort study, 103 HIV positive and 94 HIV negative newly diagnosed tuberculosis patients were followed after initiation of DOTS (direct observed treatment short course). CD4 count was measured for the HIV positive patients. All patients were also evaluated for different risk factors including HBsAg, Anti-HCV, alcohol intake, use of other drugs including traditional medicines, acetylation status and presence of chronic illness. Patients were monitored biochemically (by liver function tests) and clinically for development of DIH weekly in the first month and bi-weekly in the second month after start of therapy. Biochemical hepatotoxicity was seen in 17.3% of the patients. CD4 counts of these patients were 0-50 for 7 (35%), 51-100 for 8 (40%), 101-200 for 4 (20%), and > 200 for 1 (5%). Three patients were positive for HBsAg and none had anti-HCV. Five patients died of non-hepatic causes among the patients who developed DIH. Eight out of the 34 patients with biochemical hepatotoxicity (23.5%) developed clinical hepatotoxicity that necessitated discontinuation of their anti-TB drugs. Seven of the eight were HIV positive, seven were female, and 2 were positive for HBsAg. Biochemical hepatotoxicity was significantly associated with HIV co-infection (p=0.002), concomitant drug intake (p=0.008), decrease in CD4 count (p=0.001), high mortality (p=0.001), and having Wt/Wt allele for acetylation status (p=0.026). Clinical hepatotoxicity is also significantly associated with being female (p=0.027), HIV co-infection (p=0.043), concomitant drug intake (p=0.003), HBsAg (p=0.046), decrease in CD4 count (p=0.025), and high mortality (p=0.0001). No significant association was seen between hepatotoxicity with alcohol intake, age, body mass index, type of TB and anti HCV positivity. The findings would assist in selectively managing patients at risk. It is recommended to have a regular biochemical and clinical follow up for those patients who are at risk of developing DIH .These patients include HIV positive patients, with special emphasis to those with a lower CD4 count, and patients who take drugs other than their anti TB medication. We also recommend that further work should be done to explore the reason for the observed association between DIH and female sex, HBsAg positivity, and acetylation status. Key words: Tuberculosis, HIV, Hepatotoxicity, Acetylation status, NAT2 geneItem Drug Susceptibility Pattern of Mycobacterium Tuberculosis Isolates In Addis Ababa(Addis Ababa University, 2005-07) Asmamaw, Dawit; Aseffa, Abraham(PhD); Makonnen, Eyasu (Professor)Background:-Addis Ababa, the capital city of Ethiopia, has an estimated population of 3.5 - 4 million. Previous reports on anti-TB drug resistance suggested an increasing trend of anti-TB drug resistance despite differences in the methodology. A study in previously treated individuals also suggested an increased incidence of Rifampicin (RMP) and Isoniazid (INH) resistance in individuals treated with fixed dose combination (FDC) anti-TB drugs. Objectives:-To determine the prevalence of resistance to the four first line anti-TB drugs and to see whether there is association between HIV and drug resistance. Methods: - A cross-sectional survey on anti-TB drug resistance was done in 19 health centres (out of 21) and 3 hospitals in Addis Ababa. Sputum and serum was collected from each patient. Sputum was digested and decontaminated using Petroff’s method with 4% NaOH and inoculated on to Lowenstein Jensen media. Proportion method with Middlebrook 7H10 media & 10% OADC enrichment was used for drug sensitivity determination. HIV testing was also done for each patient with rapid assays (Determine®, Capillus® and Unigold®). Species identification was done with a combination of Thiophene-2- Carboxylic acid Hydrazide (TCH) test and species specific PCR amplification (pncA gene) Results & Discussion :-269 (242 new and 27 previously treated) patients were included in the study. Out of these, 75% were culture positive. Sensitivity result was available for 173 isolates from new cases and 19 isolates from previously treated patients. Among the isolates from new patients 78.6% were sensitive to all drugs tested and 21.4% were resistant to any one drug while these figures in previously treated patients were 47.4% and 52.6% respectively. Prevalence of MDR-TB among new cases was 0.6% (1 isolate). Resistance to RMP, INH, Streptomycin (STM) and Ethambutol (EMB) was 1.2%, 13.3%, 16.8 and 3.5% respectively. In previously treated patients RMP, INH, STM and EMB resistance was 5.3%, 36.9%, 52.6% and 11.1% respectively. The prevalence of resistance in a similar survey conducted in 1998 was lower and the increase in the current study was statistically significant for any type of resistance, any EMB resistance, any STM resistance and resistance to multiple drugs. However the prevalence of RMP resistance and multidrug-resistant (MDR) TB was not changed. There was also no association observed between drug resistance among new cases and HIV. Conclusion:- Multidrug-resistance did not show increase in the city particularly in the last six years, compared to the previous reports. However non-MDR type of drug resistance, precursor of MDR, is on the rise.Item In Vivo Anti-Malarial Activity of the Hydroalcoholic Extracts of Asparagus Africanus, Withania Somnifera and Laganaria Vulgaris in Mice(Addis Ababa University, 2005-07) Dikasso, Dawit; Mekonnen, Eyasu (Professor); Debella, Asfaw (PhD)Malaria is a major public health problem in the world in general and developing world in particular. It is known to cause 1-2 million deaths per year, with an annual incidence of 300- 500 million clinically manifested cases and with more than 2 billion people at risk of infection. It is becoming more difficult to prevent and to treat malaria due to the increasing resistance of the transmitting mosquito and of the malaria parasite to the insecticides and drugs that have been commonly used. The importance of malaria as a major public health and development problem has been reviewed on a number of occasions in Ethiopia. This study aims at investigating the in vivo antiplasmodial activity of the known traditionally used herbal drugs. A rodent malaria parasite, Plasmodium berghei, maintained in EHNRI laboratory, was inoculated into young male albino mice. Male mice were infected with 1x107 parasites intraperitonially. The extracts were administered by intra gastric tube daily for four consecutive days starting from the day of parasite inoculation. Control groups received the same amount of solvent (vehicle) used to suspend each dose of the herbal drug and Chloroquine was used as a standard drug given by the same route. The results showed that Asparagus africanus Lam. (Liliaceae) root and areal part and Withania somnifera (L) Dunal (Solanaceae) leaf and root bark are effective in P.bergei malaria, which is inconformity to the claim that they have therapeutic values in human malaria in traditional medicine. This study could partly confirm the claim, facilitate in initiating further in-depth investigation using different experient model. vii Key words: Asparagus africana Lam., Withania somnifera (L) Dunal, Plasomodium berghei, acute toxicity, in vivo, antimalarial activity,Item In Vitro and In Vivo Evaluation of Anthelmintic Activities of Crude Extracts of Selected Medicinal Plants Against Haemonchus Contortus(Addis Ababa University, 2005-12) Eguale, Tadesse; Mekonnen, Eyasu (Professor); Tilahun, Getachew(Associate Professor ); Debella, Asfaw (PhD)In the current study, in vitro experiments were conducted to determine the possible anthelmintic effects of crude aqueous and hydro-alcoholic extracts of the seeds of Croton macrostachyus, Ekebergia capensis, Coriandrum sativum, Acacia nilotica, Terminalia schimperiana, Jatropha curcas, leaves of Lawsonia inermis, Chenopodium ambrosioides, ripe berries of Hedera helix, and bark of Albizia gummifera on eggs and adult Haemonchus contortus. Aqueous extracts of C. sativum and H. helix were also investigated for toxicity (LD50 determination) in Albino mice and for in vivo anthelmintic activity in sheep infected with H. contortus. Both extract types of C. macrostachyus, E. capensis, C. sativum, J. curcas, A. gummifera and aqueous extract of A. nilotica inhibited hatching of eggs at concentration less than or equal to 2 mg/ml. Based on their ED50, the six most potent extracts were aqueous extract of E. capensis (0.06mg/ml), Hydro-alcoholic extract of C. ambrosioides (0.09mg/ml), aqueous extract of C. macrostachyus and J. curcas (0.1mg/ml) aqueous extract of C. sativum and H. helix (0.12mg/ml), in decreasing order of potency. Hydro-alcoholic extract of A. nilotica, both extracts of T. schimperiana and L. inermis did not inhibit hatching of eggs of H. contortus significantly and in dose dependent manner at all concentrations tested. Hydro-alcoholic extracts of most of the plants have shown better in vitro activity against adult parasites compared to the aqueous extract. Hydro-alcoholic extracts of C. macrostachyus, A. gummifera, C. sativum and H. helix produced mortality of adult H. contortus significantly to the level of 90, 86.67,85 and 66.67% at concentration of 8 mg/ml while aqueous extracts produced only 36.67, 33.33, 45,and 29.17% respectively at the same concentration. Like their activity on eggs, extracts of A. nilotica, T. schimperiana, J. curcas and L. inermis have shown no statistically significant effect on survival of the adult parasites at the concentrations tested, and a few mortality cases recorded were not dose dependent (p<0.05). Oral administration of aqueous extract of C. sativum didn’t produce mortality and no clinical sign of toxicity was detected in mice despite the high dose (15000 mg/kg) given, while intraperitonial (IP) administration caused mortality at lower doses. IP LD50 for C. sativum was 2177.5 mg/kg. Oral LD50 for H. helix was 3846.09 mg/kg. In vitro anthelmintic evaluation was conducted in total of 36 male sheep artificially infected with H. contortus. The sheep were randomly divided into six groups of six animals each. The first four groups were treated with crude aqueous extract of C. sativum (0.45g/kg), C. sativum (0.90g/kg), x H. helix (1.13g/kg), H. helix (2.25g/kg) respectively. The fifth group was treated with albendazole at 3.8mg/kg and the last group was left untreated. Efficacy was tested by faecal egg count reduction (FECR) and total worm count reduction (TWC). On day 2 post treatment, significant FECR was detected in group treated with higher dose of C. sativum, both doses of H. helix (p<0.05) and albendazole (p<0.001) compared to untreated control group. The maximum efficacy of the extracts observed on day 2 post treatment was 46.71% for higher dose of H. helix (2.25g/kg) and 24.79% for higher dose of C. sativum (0.9g/kg). On day 7 post treatment, significant reduction was detected only for higher dose of H. helix (p<0.05) and albendazole (p<0.001). The percentage reduction of FEC of sheep treated with both plant extracts decreased gradually on day 7 and day 14 post treatment, while that of albendazole increased from 97.8 on day 2 to 100% on day 14 post treatment. The percentage of larvae recovered from culturing faeces obtained from group of sheep treated with plant extracts was reduced in dose dependant manner compared to faeces obtained from untreated control group. Significant reduction (p<0.05) in TWC was detected for higher dose of C. sativum and both dose levels of H. helix compared to the untreated group. Reduction in male worm count was significant (p<0.05) in all treatment groups except for lower doses of C. sativum, while significant reduction of female worm count was detected only in the case of higher doses of H. helix. No worm was detected in the group treated with albendazole, indicating significant susceptibility of the strain of parasites employed in the current study. Treatment with both doses of H. helix helped the animals maintain their PCV while PCV of animals treated with C. sativum decreased significantly. Treatment with albendazole showed significant increase in PCV (p<0.05). The overall findings of the current study indicated that most of the plants have potential anthelmintic effect and further in vitro and in vivo evaluation is warranted to make use of these plants in the future.Item Antidiarrheal and Antispasmodic Activities of Stephania Abyssinica (Minspermaseae) Used In Ethiopian Traditional Medicine(Addis Ababa University, 2010-06) Deneke, Tatek; Engidawork, Ephrem(PhD)Diarrhea is a leading cause of morbidity and mortality in developing countries. Diarrhea may result from disturbance in bowel function in which case there is increased bowel transit, excessive intestinal secretion of water and electrolytes, decreased intestinal reabsorptions as well as more frequent defecations of loose, watery stool. Many plant preparations have claimed activities and traditional used as antidiarrhea and antispasmodic. S. abyssinica is traditionally used for treatment of diarrhea and stomachache in Ethiopia. The aim of this work was to evaluate the antidiarrheal and antispasmodic activities of the aqueous and methanol extract of the root and leaf of S. abyssinica. Antidiarrheal activities were studied in mice using castor oil-induced diarrhea at doses of 25, 50,100, and 200 mg/kg body weight. The extracts significantly prolonged the time of diarrheal induction, increased diarrhea free time, reduced the frequency of diarrhea episodes, decreased the weight of stool, and decreased general diarrheal score in a dose dependent way. With dose of 200 mg/kg the extracts produced higher in-vivo antidiarrheal index (ADI) than the reference loperamide. ADI of loperamide, SALM, SALA, SARM and SARA was 77.33, 88.79, 89.21, 91.08 and 82.23, respectively. In Entropooling test in mice the extract significantly (p < 0.01) inhibited intestinal fluid accumulations of mice in a dose dependent fashion; with dose of 100 mg/kg from1.03±0.093 ml of the control to 0.403±0.019ml, 0.210±0.018 ml, 0.494±0.012ml and 0.288±0.026ml by SALM, SARM, SALA and SARA respectively. The antispasmodic activity studies were performed as in vitro and in vivo models. The in-vitro antispasmodic activity studies were performed on isolated GPI. The methanol and aqueous extracts of the leaf showed significant and concentration dependent inhibition of acetylcholine induced contraction of isolated GPI. The extracts depressed Emax of Ach, and decreased PD2 value of the Ach. The Emax of Ach at conc of 10-3M is decreased (from100 for the control group) i viii by SALM with concentration of 200 and 100 ug/ml to 45.6±2.13 and 73.2±3.04 respectively, whereas by SALA with 200 and 100 ug/ml to 62.0±2.98 and 74.8±2.46 respectively. In the in vivo antispasmodic activity test, the extract significantly decreased the peristaltic index (PI). In normal transit test, the PI of SALM, SALA, SARM and SARA with dose of 200 mg/kg was all 0.00 (100% suppression of normal peristalsis). However in castor oil induced transit with dose of 200 mg/kg the peristaltic index (PI) of SALM, SALA, SARM and SARA was 26.67, 36.85, 22.00 and 40.65 respectively. The result of this study indicated that the plant extract possesses antidiarrheal and antispasmodic activities and proves the fact that this plant is used in traditional medicine for treatment of diarrhea, stomachache and abdominal cramp. Key words: S. abyssinica, antidiarrheal, antispasmodic, antienteropooling, aqueous and methanol extract, animal (mice or guinea pig)Item Gastrointestinal Effects of Crude Khat (Catha Edulis F) Extract Following Acute and Sub-Chronic Administration in Rodents(Addis Ababa University, 2011-08) Tadesse, Wintana; Engidawork, Ephrem(PhD)Khat (Catha edulis F) belongs to the Celastraceae family and is a dicotyledonous evergreen shrub/tree used for recreation and alleviation of fatigue in several countries of East Africa and South Arabia. Recently, this habit has spread considerably, raising concern in view of medical and socio-economic consequences of khat consumption. Even though khat has several medicinal, social, and economical values, there are numerous reports regarding its gastrointestinal tract (GIT) adverse effects. As the effects of khat chewing on digestive system mentioned in earlier studies were based on clinical observations, the present study was designed to evaluate the GIT activity of the crude khat extract after acute and sub-chronic administration using different rodent models and parameters used for ulcer and motility measurement were quantified. For acute study, animals were randomly assigned into different groups. Negative control received Tween 80 2% in distilled water, whereas positive controls were given ranitidine (pylorus ligation and cysteamine HCl models), misoprostol (indomethacin induced gastric ulcer), and loperamide (castor oil induced diarrhea and enteropooling assay). The other group received different doses of crude khat extract: 100 mg/kg, 200 mg/kg and 300 mg/kg. For sub-chronic study, one group was administered vehicle and served as control, whilst the other three were administered three doses of khat extract (100, 200, and 300 mg/kg) for 45 days. Acute khat administration in pylorus ligation model was shown to aggravate ulcer compared to controls in the highest dose used, as evidenced by increased volume of gastric acid secretion (p<0.05), total acidity (p<0.05) and ulcer index (p<0.01). Similar results were obtained in indomethacin induced gastric ulcer model where 300 mg/kg khat extract increased mucosal damage as demonstrated by a significant reduction in mucin content compared with misoprostol (p<0.001) and vehicle (p<0.05) treated animals. Khat at 300 mg/kg was also shown to accentuate duodenal ulcer induced by cysteamine HCl by significantly increasing (p<0.01) ulcer area as compared to vehicle-treated rats. Whilst ranitidine was shown to offer antiulcer activity in the models tested, khat at 100 mg/kg was devoid of any significant ameliorating or accentuating effect. Surprisingly, sub- viii chronic administration of khat at all doses failed to produce neither gastric nor duodenal ulcer. In castor oil induced diarrhea, 300 mg/kg (p<0.001) and 100 mg/kg (p<0.01) khat extracts significantly decreased the number of watery fecal discharge against vehicle treated rats. In addition, 300 mg/kg dose decreased (p<0.05) weight and volume of intestinal content in castor oil induced enteropooling model. In sub-chronic studies, 300 mg/kg and 200 mg/kg khat extracts significantly inhibited intestinal motility in in-vivo gastrointestinal motility model by 53.2% and 48.6%, respectively. On the other hand, weight change on sub-chronic khat extract administration was observed and the change became significant at the 3rd (p<0.05), 4th and 5th week (p<0.01), and 6th week (p<0.001) with 300 mg/kg dose. While in 200 mg/kg decline of weight at 4th week (p<0.05) and for following weeks (p<0.01) was obtained. In conclusion, acute use of khat at higher dose in the presence of ulcerogenic agents could aggravate gastric and duodenal ulcer, while sub-chronic khat administration alone did not produce ulcer. Furthermore, acute and sub-chronic administration of khat extract at higher dose produced a significant constipating activity. And sub-chronic administration of khat extract at higher dose markedly decreased body weight. These effects collectively indicate that khat consumption in large amount and for a longer period of time is associated with adverse GIT outcomes. Key words: Catha edulis, Pylorus ligation, Cysteamine HCl, Indomethacin, Castor oil, and Mucin.Item Evaluation of the diuretic activity of the aqueous and 80% methanolic extracts of the leaves of Ajuga remota B. in mice(Addis Ababa University, 2011-09) Hailu, Wubshet; Engidawork, Ephrem(PhD)In the Ethiopian traditional medicine the leaves of Ajuga remota (Local name ‘Armagusa’) is used as diuretic agent. Since the diuretic activity of this plant had not been investigated in scientifically controlled studies, the aim of the present study was to evaluate the diuretic potential of the aqueous and hydroalcoholic extracts of the leaves of A. remota in mice after acute oral administration. Adult mice were administered orally either aqueous (250 mg/kg, AA250; 500 mg/kg, AA500 and 1000 mg/kg, AA1000) or 80% methanolic (250 mg/kg, AM250; 500 mg/kg, AM500 and 750 mg/kg, AM750) extract and urine output and electrolyte contents were quantitated up to 5 h and compared with those administered with furosemide 10 mg.kg (F10) and distilled water (CON). The hydroalcoholic extract increased diuresis significantly (p<0.01) only at the maximum dose, while the aqueous extract increased diuresis at moderate (AA500, p<0.01) and higher (AA1000, p<0.01) doses by the end of the fifth hour compared to CON. Results on electrolyte excretion showed both the aqueous and hydroalcholic extracts had an increased natriuresis at the maximum doses (p<0.001 for AA1000 and p<0.01 for AM1000), while the kaliuresis effects were smaller at those doses when compared with standard, thus the plant had a beneficial potassium saving effect at these doses. Phytochemical screening of both extracts revealed the presence of secondary metabolites like phenolic compounds, tannins, saponins, flavonoids, terpenoids, steroids, and cardiac glycosides which might account for the diuretic activity. The plant was also found to be safer at a maximum dose of 5000 mg/kg for both extracts. In conclusion the results indicated significant diuretic activity at different doses and thus provide evidence for its folkloric use. And the different components like flavonoids are thought to be responsible for the evidenced diuretic activity. Key Words: Furosemide, Diuretics, A. remota, Natriuresis, Kaliuresis.Item Wound Healing Activity Guided Isolation Of Active Constituent (S) From The Leaves Of Allophylus Abyssinicus (Hochst.) Radlk(Addis Ababa University, 2011-10) Yesuf, Adem; Asres, Kaleab (PhD)Item Synthesis and Biological Screening of Some Pyrazole Derivatives as Antimalarial and Antileishmanial Agents(Addis Ababa University, 2012-06) Tuha, Abdu; A. Bekhit, Adnan(PhD)Malaria and leishmania are very common parasitic diseases of the developing world and drug resistance has hindered their efficient control. Pyrazole derivatives were synthesized using aldol condensation and subsequent cyclization reactions. The compounds were synthesized in a good yield (71.39%-95.23%). The compounds were purified by recrystallization and their chemical structure was characterized by elemental microanalysis, IR, and 1HNMR spectroscopy. In vivo antimalarial and in vitro antileishmanial activity was conducted using four day suppression test and Alamar blue reduction method, respectively. The results for antimalarial activity conducted using P. berghei infected mice at a dose level of 48.46μmol/kg/day showed that all the synthesized compounds have lower activity than the standard drug chloroquine phosphate. Compound IIc, 1-phenyl-4-(3-(thiophen-2-yl)-4,5- dihydro-1H-pyrazol-5-yl)-3-p-tolyl-1H-pyrazole, showed relatively the highest % suppression, 63.40%. The result for antileishmanial activity test revealed that all the synthesized compounds except compound IIb had better antileishmanial activity than the standard drug miltefosine (IC50= 3.1911 μg/ml). All of the synthesized compounds except compounds III and IIIb exhibited lower antileishmanial activity compared to the standard drug amphotericin B deoxycholate (IC50=0.0460 μg/ml). Compound IIIb, phenyl pyrazoline with propanoyl side chain, 1-(3-phenyl-5-(1-phenyl-3-p-tolyl-1H-pyrazol-4-yl)-4,5- dihydropyrazol-1-yl)propan-1-one, was found to be the most active (IC50= 0.0112) and two hundred eighty five and four fold more active than the standards miltefosine and amphotericin B deoxycholate, respectively. Keywords: pyrazole, in vivo antimalarial activity, in vitro antileishmanial activity.Item Ethnopharmacological Survey of Medicinal Plants among the Hamer Ethnic Group, Hamer Woreda, South Omo Zone, SNNPR, Ethiopia and Evaluation of a Selected Plant for its Antimalarial Activity(Addis Ababa University, 2012-07) Paulos, Biniam; Asres, Kaleab (PhD); Gedif, Teferi (PhD)Health seeking behaviour of people around the globe will be affected by different socio-cultural and economical factors. People in Ethiopia, particularly tribal people have long history of using medicinal plants as a major component of their traditional medical practices over many centuries to satisfy their health care needs. The transfer of this sort of knowledge from generation to generation is mainly effected by words of mouth. Cross-sectional survey was conducted to document ethnopharmacological information of the Hamer semi pastoralists by using semi structured questionnaires administered to eight traditional healers/key informants and one thousand six hundred household (HH) respondents supplemented by eight focus group discussions (FGDs). The majority (84%) of HH respondents were males, 94.4% of whom suffered illnesses in the last two weeks recall period and had taken action. The prevalence of the use of traditional medicine among the Hamer community was found to be very common as indicated by FGD participants, key informants and HH respondents. HH respondents reported that traditional medical practices are their first choice when family members get sick. Females’ preference of traditional medical practices was higher than males. The main reasons for the preference of the community members to traditional medical practices include its effectiveness, low cost and ease of availability. A total of sixty medicinal plants were reported and collected along with their local names, indication(s), parts used and method of preparations. The health seeking behavior of the Hamer ethnic group is affected by different socioeconomic and cultural factors. There is also a strong indication for traditional medical practices and use of plant materials to treat various ailments and health problems among the study population. Therefore, due attention should be given to these traditional medical practices. The ethnopharmacological survey part of this study revealed that Aloe otallensis Baker., an indigenous Ethiopian plant, was among the most widely used medicinal plants by the members of the Hamer Ethnic Group. The plant is used for the treatment of malaria and wound healing. Malaria, a diseases caused by protozoan parasites is a major obstacle to the socioeconomic xii development of several developing countries including Ethiopia. The phytoconstituents of A. otallensis studied by thin layer chromatography (TLC) and its antimalarial and antioxidant activities were assessed by in vivo four day Plasmodium berghei suppressive test and 1,1- diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. The study revealed the presence of picataloside (2,8-O,O-di (β-D-glucopyranosyl)-1,2,8-trihydroxy-3-methylnaphtalene) in the exudate of A. otallensis, which was isolated from the plant for the first time. The study further showed that the leaf exudate of the plant possesses maximum antimalarial activity (60.7% suppression) at a dose of 300 mg/kg. Similarly, at a dose of 100 mg/kg the isolated compound suppressed P. berghei parasites by 47.9%. Both the exudate and the isolated compound displayed comparable radical scavenging activity possessing IC50 value of 26.9 and 26.2 μg/ml, respectively in DPPH assay. The results of the present study do seem to justify the traditional use of A. ottalensis for the treatment of malaria.Item Studies on Antimalarial Activity of the Leaf Constituent of Otostegia Integrifolia Benth. (Lamiacea) Against Plasmodium Berghei in Mice(Addis Ababa University, 2012-08) Endale, Abyot; Asres, Kaleab (PhD); Bisrat, Daniel(PhD)Medicinal plants play an important role in the treatment of malaria especially in developing countries where resources are limited. A continued search for other effective, safe and cheap plant-based antimalarial agents thus becomes imperative in the face of these difficulties. The leaves of Otostegia integrifolia Benth. are used traditionally as malarial remedy in Northern Ethiopia. This study was aimed to investigate the antimalarial potentials of the crude leaf extract, solvent fractions as well as isolated compound(s) in vivo in Plasmodium berghei infected mice to give scientific proof to the ethnobotanical claims. Leaves of O. integrifolia were collected and dried under the shade. The dried plant material was pulverized and extracted with 80% methanol. The dried crude extract was then further fractionated with different solvents. Both the crude extract and fractions were evaluated for their antimalarial activity in vivo, in 4-day suppressive assays against P. berghei in mice. Column chromatography was used to isolate compound/s from the most active fraction. The isolated compound was evaluated for its antimalarial activity in vivo, in 4-day suppressive assay against P. berghei and its structure elucidated using spectroscopic methods (MS and NMR). Preliminary phytochemical screening was performed using standard procedure. Acute and sub-acute toxicity studies of the crude extract were carried out in Swiss albino mice prior to antimalarial activity tests. No sign of toxicity was observed up on administration of the 80% methanol extract of the plant up to the highest dose (5000 mg/kg) given. Preliminary phytochemical screening showed the presence of saponins, flavonoids and other phenolic compounds in the hydroalcoholic leaf extract. The hydroalcoholic leaf extract (200, 400 and 600 mg/kg/day) and solvent fractions (200, 400 and 600 mg/kg/day) exhibited significant (P<0.01) antimalarial activity compared to the negative control group in four day suppression test with a considerable mean survival time. The highest parasite suppression (80.52%) was observed at 600 mg/kg /day for the crude extract, while the ethyl acetate fraction was found to be the most active among the solvent fractions and showed highest suppression (60.15%) at 600 mg/kg/day. The isolated compound also showed significant antimalarial (P<0.001) activity at the tested doses (25, 50 and 100 mg/kg/day) with chemosuppression of 50.13, 65.58, and 73.16%, respectively. Structural elucidation revealed that the isolated compound is a labdane type diterpenoid, 15,16-epoxy-3α,9α-dihydroxy-labda-13(16),14-diene. The crude extract, solvent fractions and the isolated compound possess considerable antiplasmodial activities which justify the use in ethnomedicine and can be exploited in the control of malaria.Item In vitro antimicrobial and in vivo antimalarial evaluation of latex and compounds isolated from the leaves of Aloe sinana(Addis Ababa University, 2013-04) Minale, Genet; Bisrat, Daniel(PhD); Asres, Kalaeb(PhD)Aloe sinana Reynolds is endemic to Ethiopia where its leaf exudate is traditionally used in Debre Sina and in other central highlands of the country for the treatment of various illnesses, including malaria, wound and snake bite. Phytochemical investigation of the exudate led to the isolation of three anthrones identified as microdontin, aloin and aloinoside by means of spectroscopic techniques including 1H and 13C-NMR. The latex and isolated compounds were assessed for their antimicrobial activities against 20 bacterial and 4 fungal strains using disk diffusion method, and their antimalarial activities were evaluated by a 4-day suppressive test against mice infected with Plasmodium berghei. When administered up to a dose of 5,000 mg/kg, neither the latex nor the isolated compounds were found to be acutely toxic to Swiss albino mice. Both the latex and isolated compounds showed potent antibacterial activity, whilst their effect against the tested fungal strains was rather moderate. In addition the latex and all the isolated compounds showed significant chemosuppression in mice infected with P. berghei. At a dose of 400 mg/kg, the latex suppressed parasite growth by 68.2% compared to the negative control group and improved survival time considerably. Among the isolated compounds, aloinoside showed the most potent antiplasmodial activity inhibiting parasite growth by 85.2% at a dose of 100 mg/kg. From the results obtained in the present study, it can be concluded that the leaf exudate of A. sinana and its isolated compounds could serve as potential candidates for the treatment of microbial infections and malaria supporting the traditional uses of the plant. Key words: Aloe sinana; Aloaceaae; antimalarial; antibacterial; anthraquinones; microdontin; aloin; aloinoside.Item Screening for antimicrobial and anti inflammatory activities and, formulation studies on the extracts of selected medicinal plants topically applied in Ethiopia(Addis Ababa University, 2014-02) Taddese, Samuel; Gebre-Mariam, Tsige (Professor); Asres, Kaleab (PhD)In an attempt to integrate traditionally used herbal products into modern topical formulation, extracts of the leaves of Maesa lanceolata (Myrsinaceae), Osyris quadripartita Decn. (Santalaceae), Steganotaenia araliacea Hochst ExA. Rich (Apiaceae), Cadaba farinosa (Capparidaceae) and; the aerial parts of Plantago lanceolata (Plantagonaceae) and Alachemilla pedata A. Rich (Rasaceae) have been screened for their antibacterial and antifungal activities. All hydroalcoholic extracts, except C. farinosa and S. araliacea were active against E. coli. And, all extracts had activities against S. aureus and P. aeroginosa. Similarly, screeneing of the total extracts against Candida albicans and Trichophyton mentagrophytes indicated that all extracts, except P. lanceolata on both strains and C. farinosa on T. mentagrophytes, were active. But none of the extracts tested displayed activity against Aspergillus niger. The antimicrobial activities of A. pedata and M. lanceolata were higher than those plants tested and hence, further works have been undertaken on these plants. In an attempt to localize the active ingredients, successive fractionation with petroleum ether, chloroform, acetone and methanol have been carried out. The antimicrobial activity study of the various fractions revealed that the antimicrobial effect of A. pedata was because of the non-polar components (petroleum ether fraction) and that of M. lanceolata, the activities were distributed among the various fractions. The action against T. mentagrophytes of the latter was entirely because of the polar compounds present in the methanol extract. To assess the clinical utility of these plants, MICs were determined. Accordingly, the results for A. pedata were 5 mg/ml against S. aureus and E. coli and, 10 mg/ml for C. albicans using agarwell diffusion technique. The MIC of this plant extract using agar dilution technique on the same bacteria was 0.125 mg/ml. Similarly; the MIC of M. lanceolata was 1.25 mg/ml against the abovementioned bacteria and, 0.625 mg/ml against fungi using agar-well diffusion technique. And, using dilution technique, the result was 1.25 mg/ml for bacteria and 0.0625 mg/ml for fungi. Anti-inflammatory activities and semi-quantitative standardization works were also conducted and it was found that M. lanceolata has significant anti-inflammatory activity at 100 mg/kg and 750mg/kg with better activity at 100 mg/kg. Similarly, A. pedata has also displayed antiinflammatory activity, even though the effect was less than M. lanceolata. The water extractive values were 4.66 and 5.24% (W/W) for A. pedata and M. lanceolata, respectively. Successive extractive values using petroleum ether, chloroform, acetone, methanol and water were (3.20, 4.56), (3.38, 4.36), 1.28, 0.56), (5.38, 6.52), (4.60, 6.64) for A. pedata and M. lanceolata, respectively. Ash value determination and TLC-fingerprinting were also conducted as part of the standardization work. Ointments and creams were formulated using the hadroalcoholic extracts of A. pedata and M. lanceolata. Study on the in vitro performances of the proposed formulations indicated that releases from hydrophilic bases were better and polyethylene glycol-based preparations were superior in activity than formulations prepared with hydrophobic bases. Furthermore, the in vitro performances of the formulated topical dosage forms were comparable to the activity of locally available marketed antimicrobial products.Item Appropriateness of Type 2 diabetes mellitus drug therapy: A case of Tikur Anbessa Specialized Hospital Diabetes Clinic(Addis Ababa University, 2014-03) Ayele, Alemseged; Engidawork, Epherm(PhD); Yifter, Helen(PhD)Background: Diabetes mellitus (DM) is a metabolic problem involving chronically high blood glucose levels or hyperglycemia, which is thought to arise from insulin deficiency. This insulin deficiency can be decrease in amount or a complete absence in body. In the long run high blood glucose level could lead to various complications. Beside altered glucose metabolism carbohydrate, protein, and lipids metabolisms are also affected in diabetes mellitus. Objective: To assess appropriateness of Type 2 diabetes mellitus drug therapy (T2DM) and investigate association between fasting blood glucose (FBG) and the patients’ clinical and demographic characteristics at the diabetes clinic of Tikur Anbessa specialized hospital (TASH). Methods: The study was a cross sectional hospital based survey and used both quantitative and qualitative methods. T2DM patients who came for their follow up treatment at the diabetes clinic of TASH over a one month period (April 2013) were used as research participants. Plus key informant interview with the help of semi-structured open ended questioner was used focusing on the experience and practice physicians within the diabetes clinic regarding medication choice and guidelines they use. Results: A total of 103 patients enrolled in the survey and the proportion of females (59.2%) was higher than males (40.8%). The mean age was 52.2 years and most of them live in Addis Ababa. When it comes to clinical characteristics mean FBG was 155.99 ± 44.32 mg/dl, the difference in FBG between male and female was insignificant (P=0.325). Body mass index (BMI) had a mean value of 26.4± 3.05 kg/m2 and 51.45% of the patients were overweight. Medication wise NPH (56.3%), metformin plus glibenclamide (19.4%) and metformin (10.7%) were the most prescribed drug therapies. And 3.88% of patients were only on glibenclamide. The association of gender, age, BMI and medication used with the FBG levels of patients was not significant with a p value of 0.6, 0.803, 0.97 and 0.081 respectively. The key informants point out that patient load, physician rotation, lack of guide-line and devices as a reason for inadequacy of treatment. Conclusions: The treatment of T2DM is appropriate with existing problems. Metformin was the first choice oral medication, while most patients were on NPH. And no single factor was associated with influencing the FBG of patients. Key Words: Type 2 diabetes mellitus, Drug therapy AcknowledgmentsItem Evaluation of ceftriaxone utilization in medical and emergency wards of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia(Addis Ababa University, 2015-01) Sileshi, Alemayehu; Shibeshi, Workineh(PhD); Tenna, Admasu(PhD)Evaluation of ceftriaxone utilization in medical and emergency wards of Tikur Anbessa Specialized hospital By: Alemayehu Sileshi Addis Ababa University, 2015 Background: Ceftriaxone is one of the most commonly used antibiotics due to its high antibacterial potency, wide spectrum of activity and low potential for toxicity. The global trend shows misuse of this drug. Objective: This study was conducted to evaluate the appropriateness of ceftriaxone use in medical and emergency wards of Tikur Anbessa Specialized Hospital (TASH). Methods: A prospective cross-sectional study was conducted by reviewing medication records of 314 patients who received ceftriaxone during hospitalization at TASH between February 1 and June 30, 2014. Drug use evaluation (DUE) was conducted to determine whether ceftriaxone was being used appropriately based on six criteria namely indication for use, dose, frequency of administration, duration of treatment, drug-drug interaction (DDI) and culture and sensitivity (C&S) test. The evaluation was made as per the protocol currently developed. Additionally, areas which need intervention were identified and interventions were implemented. Results: The prescribing rate of ceftriaxone was found to be very high (58% point prevalence). Ceftriaxone use was empiric in 274 cases (87.3%) and specific in 5 cases (1.6%). The most common indication for ceftriaxone use was pneumonia; observed in 110 cases (35.0%). The most common daily dosage, frequency of administration and duration of treatment with ceftriaxone were 2g (88.9%), twice-daily (98.4%) and 8-14 days (46.2%), respectively. Inappropriate use of ceftriaxone was observed in most cases iv (87.9%), the greatest proportion of which was attributed to inappropriate frequency of administration (80.3%), followed by absence of C&S test (53.2%). Conclusions: This study revealed that the inappropriate use of ceftriaxone was very high in the medical and emergency wards of TASH. This may lead to emergence of resistant pathogens which in turn lead to treatment failure and increased cost of therapy. Therefore, adherence to current evidence-based guidelines is recommended. Key words: Ceftriaxone, drug use evaluation, antibiotic, rational use.Item Antihypertensive Activity of Aerial Parts of Satureja Punctata (Benth.) Briq. (Lamiaceae)(Addis Ababa University, 2015-02) Hika, Debabe; Hymete, Ariaya(PhD); Yonathan, Mariamawit(PhD); Mammo, Wendemagegn(Professor)Satureja punctata Benth. Briq. (Lamiaceae) locally known as ‘‘Lomishet’’ is among the plants used in Ethiopian traditional medicine for the treatment of various diseases including hypertension. The current study aimed at evaluating the antihypertensive activity of the decoction of the aerial parts of this medicinal plant in guinea model of hypertension and its vasorelaxant effect on isolated aorta. Acute hypertension was induced by surgical procedures involving clamping of the left renal artery and blood pressure was recorded invasively by direct cannulation method from the right common carotid artery. Intravenous administration of the decoction at doses of 10, 20 and 30 mg/kg caused 13.66 ± 0.27, 34.35 ± 0.33, 45.78 ± 0.23% (n=6) fall in (p < 0.01) MABP, respectively, in normotensive guinea pig and a respective fall of 16.02 ± 0.28, 38.52 ± 0.50, 52.07 ± 0.42 % (n=6) (p < 0.01) MABP in renovascular hypertensive guinea pig. The decoction also caused a dose-dependent relaxation of aorta precontracted with KCl at a concentration of 2.5- 40 mg/ml, with a maximum relaxation of 98.19 % achieved at 40 mg/ml. Preparative reversed-phase HPLC analyses of the aerial part decoction of S. punctata resulted in isolation of two phenolic compounds, rosmarinic acid and linarin. The structures of these compounds were elucidated by utilization of spectroscopic techniques, i.e., MS, UV, IR, 1D, and 2D NMR. Further, rosmarinic acid showed significant (p<0.01) reduction of MABP by 8.14 ± 0.27, 15.79 ± 0.33 and 31.78 ± 0.64 % (n = 6) at doses of 0.75, 1.5 and 3 mg/kg, respectively, in normotensive guinea pig. The findings of this study suggest that the aerial parts of S. punctata have genuine antihypertensive activity.Item Assessment of Knowledge, Attitude and Practices on Adverse Drug Reaction Reporting among Pharmacy Personnel Working at Community Pharmacy, Addis Ababa, Ethiopia(Addis Ababa University, 2015-05) Goshime, Alaynesh; Gedif, Teferi (PhD)Assessment of Knowledge, Attitude and Practice on Adverse Drug Reaction Reporting among Pharmacy Personnel Working at Community Pharmacy, Addis Ababa, Ethiopia Alaynesh Goshime Addis Ababa University, 2015 Modern medicines have changed the way in which diseases are managed and controlled. However, despite all their benefits, evidence continues to mount that adverse drug reactions (ADRs) are common cause of illness, disability and even death. Knowledge, attitude and practices of health professionals towards ADR reporting are known to have crucial contribution in the detection and reporting of the reactions. A cross sectional study was conducted on a sample of 379 pharmacy personnel working at randomly selected community pharmacies of Addis Ababa to assess their knowledge, attitude and practice towards ADR reporting. Data was collected using self administered questionnaire. Majority of the respondents were male (57.5%) and in the age group 26-30 (55.1%). Over half (70.7%) of the respondents had poor knowledge. One hundred seventy three (45.6%) participants encountered ADRs in the past 12 months but none of them reported to the relevant authority. The majority of respondents (82.8%) had a positive attitude towards ADRs reporting. The study revealed that majority of pharmacy personnel at community pharmacy in Addis Ababa had poor knowledge, positive attitudes and very limited practices towards ADR reporting. The Ethiopian Food, Medicine and Health Care Administration and Control Authority should create awareness iv on the existence of ADR monitoring system and the purpose and importance of ADR reporting and should also conduct continuous trainings and seminars about ADR reporting with community pharmacies dispensers and finally ADR reporting forms should be made available at community pharmacies. Keywords: Pharmacovigilance , ADR reporting, Community Pharmacy Personnel, Knowledge, Attitude, PracticeItem Antiprolif-erative Constituents of Roots of Podocarpus falcatus (Thunb.) R.Br. ex Mirb(Addis Ababa University, 2015-06) Mekuria, Ermias; Hymete, Ariaya(PhD); Yonathan, Mariamawit(PhD)Once thought of as the disease of the developed, cancer nowadays is becoming the prob-lem of every nation across the globe claiming millions of lives every year. Incidence, and thus prevalence, is increasing every year due to adoption of lifestyle factors that are known to be major cancer risk factors. Making things worse is the development of MDR to the known effective anticancer drugs. Moreover, the currently available drugs are cost-ly and are associated with severe side effects. Thus, discovering new anticancer drugs with new and safe modes of action is urgently needed. Natural products derived from medicinal plants are well-known contributors of clinically useful anticancer drugs; suffice to mention taxol, the Vinca alkaloids, podophyllotoxin and camptothecin and their de-rivatives. Relying on traditional medicines for most of their health needs, Ethiopians use various plants for prevention and treatment of cancer. For example, the roots of Podocar-pus falcatus are used as “anticancer” remedies in some parts of Ethiopia, which formed the basis of the present study to isolate the “responsible” “bioactive” compounds. Bioassay guided fractionation using the human colorectal adenocarcinoma (HT-29) cell line of the methanol extract of dried roots of P. falcatus (Podocarpaceae) led to the isola-tion of two new type C nagilactones, 16-hydroxy nagilactone F (PF-1) and 2β,16-dihydroxy nagilactone F (PF-3) and a new totarane-type bisditerpenoid 7β-hydroxy mac-rophyllic acid (PF-2), along with the seven known compounds: inumakinol D (28), mac- rophyllic acid (37), nagilactone D (41), ponasterone A (94), 2β-hydroxy nagilactone F (108), nagilactone I (109), and 15-hydroxy-nagilactone D (110). The structures of the new compounds were determined by 1D and 2D-NMR, HRESIMS and by comparison with the reported spectroscopic data of their congeners. The orientation of the hydroxyl group at C-2 of 108 and 109 was revised to be β based on evidence from detailed analysis of 1D and 2D-NMR data and single crystal X-ray diffraction studies. Among the isolated compounds the nagilactones, including the new dilactones 16-hydroxy nagilactone F (PF-1) and 2β,16-dihydroxy nagilactone F (PF-3), were the most active (ED50 0.3–5.13 μM range) against the HT-29 cell line, whereas the bisditerpenoids (PF-2 and 37) and the other known compounds 28 and 94 were inactive. The presence of bioactive nagilactones in P. falcatus supports its traditional use.Item Hypoglycemic and antihyperglycemic effect of leaves extracts of Psidium guajava in normoglycemic and streptozotocin-induced diabetic mice(Addis Ababa University, 2015-06) Godebo, Amanuel; Mekonnen, Negussu(PhD); Makonnen, Eyasu (PhD)Background: Diabetes mellitus is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia. As the morbidity and mortality rate from diabetes is increasing in low- and middle-income countries, it is necessary to evaluate medicinal plants for their pharmacological effects to support existing drugs in treating diabetes. The present study was undertaken to evaluate the hypoglycemic and antihyperglycemic activity of leaf extracts of Psidium guajava in normoglycemic and streptozotocin-induced diabetic mice. Methods: The aqueous and ethanol extracts of Psidium guajava leaves were prepared. Swiss albino mice of either sex weighing 20-30 grams were selected for the experiments. Normal mice were grouped into eight groups to carry out hypoglycemic effect of the extracts, whereas mice that were made diabetic were grouped into nine groups to study the antihyperglycemic effect of the extracts. Diabetes was induced by Streprozotocin (STZ). Blood glucose levels were measured using glucose oxidase method. Results: The aqueous and ethanol extracts of Psidium guajava leaves lack hypoglycemic effect on normoglycemic mice. However, a significant decrease in blood glucose levels (P<0.05) was observed after administering for 21 days treatment of the aqueous and ethanolic extracts of Psidium guajava leaf to Streptozotocin-induced diabetic mice. Guava leaf extracts contain alkaloids, phenols, flavonoids, tannins and saponins that could be responsible for the observed antihyperglycemic effect. It was also observed that the extracts have shown no acute toxicity. Conclusion: The aqueous and ethanol extracts of Psidium guajava leaves are effective in lowering blood glucose level in diabetic mice, but lack hypoglycemic effect in normoglycemic mice. Further studies are warranted to elucidate possible mechanism(s) of action of the plant material. Key words: Hypoglycemic, Antihyperglycemic, Psidium guajava, Strepotozotocin, Mice.