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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 Validation of Tablet Manufacturing Process in the Ethiopian Pharmaceuticals Manufacturing Factory (EPHARM)(Addis Ababa University, 2000-05) Mossisa, Lemu; Gebre-Mariam, Tsige (Prof.)Process validation may be defined as a systematic approach to identi fyi ng, measunng, evaluating, documenting and re-evaluating a series of critical steps III the manufacturing process that require control to ensure a reproducible final product. The approach is based on the principle that "quality is not tested into a product but rather is built into a product". It is with this principle in mind that this work has been designed and conducted. The validation study was limited to the tablet manufacturing process in the Ethiopian Pharmaceuticals Manufacturing Factory (EPHARM). Three tablet products were selected, namely, Chloroquine phosphate 250 mg, Paracetamol 500 mg and Frusemide 40 mg for the study. Chloroquine phosphate, is a highly water-soluble salt with little or no compressibility problems. Paracetamol is moderately soluble in water with a high tendency to capping. Frusemide is practically insoluble in water which may pose problems in drug release. In this study, the manufacturing facility and equipment, the raw material acquisition and testing procedures, the tablet manufacturing process, and the in-process control procedures were evaluated. Samples of the in-process materials and the fini shed products were taken and tested for compliance with quality specifications. The results of the study suggest that the proportion of fines in granulations of some of the products was excessive (chloroquine phosphate). Measurements of angle of repose indicate that the granulation bulk density, flow and surface characteristics were generally good. One-way analysis of variance (ANOY A) revealed that there was significant vari ation 111 the granulation moisture content of all of the products tested. Paracetamol tablets lacked the shiny smooth appearance expected of plain, compressed tablets. High hardness variation has been observed in some products (paracetamol, frusemide) but thickness was within the specification in all cases. Two batches of paracetamol capped and, hence, failed friability test specifications. The tablets complied with the official weight variation and content uniformity specifications, but the range need to be narrowed through the use of internal specifications. Tablets of all of the products tested disintegrated within the specified time. Dissolution rate was within the official requirements in all cases. Complete in vitro drug release (90% or more of label claim) was observed in all cases, but the optimum goal of achieving 90% drug release below 30 min was not attained particularly with frusemide and in some batches of paracetamol. Standard operating procedure (SOP) was not strictly followed during some of the unit operations. The document (batch manufacturing record) was lacking the necessary details required of such a document. For example, mixing time and mixing intensity in mixers, drying time and temperature in dryers, machine speed, compression force etc. in tablet presses were not clearly stated. No in-process control activity was observed at the granulation stage and there were no quality specifications available for the granules. Machine cleaning and maintenance procedure and documentation was lacking. Personnel training was inadequate. Generally the GMP requirements in the area of facility and equipment, personnel, process validation, documentation, etc. are not fulfilled.Item Standardisaltion and Tablet Formlulatilon of the Extracts of the Seeds of Glinus lotoides(Addis Ababa University, 2000-06) Endale, Abebe; Gebre-Mariam, Tsige (Prof.)Glinus lotoides Linne, locally known as "Mettere" is an ailliual herb, the seeds of which are traditionally used as anthelminthic for the prevalent tape worm infection. The taenicidal activity has been attributed to the saponins present in the seeds. This study reports on the development of suitable extraction and purification methods of the seeds of the plant; the development of analytical methods for quantification of the saponins in the crude extracts; the physico-chemical characterisation of the extracts; and tablet formulation thereof. Extraction and purification methods to obtain "total saponins" of G. lotoides were developed and the purified extract (i.e., total saponins) was used as a standard for quantitative determination. Sensitive colourimetric and UV -spectrophotometric methods were developed and ~-escin, a mixture of triterpenoidic saponins obtained from Aesculus hippocastanum, was used as a control standard. For the colourimetric assay method, the official German Pharmacopoeia (DAB) method of determination of ~-escin was adopted with slight modification. In this, saponins were reacted with ferric chloride in acetic acid: sulphuric acid (1: 1) and the red-coloured complex formed was measured at 540 and 409 nm for ~-escin and saponins of G. lotoides respectively. Linear regression of the calibration curves yielded equation Y = 6.6314X - 0.0279 (r = 0.9983) for ~-escin and Y = 12.669X + 0.0456 (r = 0.9993) for saponins of G. lotoides at concentrations ranging from 0.02 to 0.12 mg/ml and 0.01 to 0.06 mg/ml, respectively. XIII Pre-derivatization of saponins with 10% acetic acid in 0.1 N HCI rendered them UVactive and absorption was measured at 238 nm. Linear regression of the calibration curve yielded an equation of Y = 7.9514X - 0.0536 (r = 0.9983) at concentrations ranging from 0.02 to 0.12 mg/ml. Both methods showed comparable and reproducible results on identical samples and were employed for standardisation of the extracts of the seeds of G. lata ides. Physico-chemical properties of the powdered extracts of the seeds such as particle size and distribution, morphology, water sorption pattern, densities, flow properties and compaction profiles were investigated. Based on the density results, properties, namely, porosity, consolidation index (Carr's index) and Hausner ratio were calculated. The effects of some extraction processes, such as extracting solvents and methods of extract drying, on the physical properties of the extracts were investigated and a suitable solvent system and drying method were determined. Based up on the results of the preformulation studies, the most suitable extract of the seeds of G. la/aides (570 mg of Extract A) was formulated and compressed into 1.15g oblong tablets (having long and short diameters of 20.1 and 8.2 mm respectively). The effects of types of filler/binder, disintegrants and compression force were investigated. Tablet properties such as hardness, disintegration time and friability were evaluated and suitable tablet formulation was developed.Item Evaluation of Local Gum of Acacia Polyacantha as a Binder in Tablet Formulations(Addis Ababa University, 2002-06) Aklilu, Tegegne; Gebre-Mariam, Tsige (Professor); Ibrahim, Sayed (Professor)Acacia gums are dried gummy exudates obtained from the stems and branches of acaica spp. (fam. Leguminosae). A. senegal is the source of most gum arabic of international trade and it finds wide applications in pharmaceutical, food and cosmetic industries. Other African acacia species of economic importance include A. seyal, A. drepanolobium and A. polyacantha. In this study, a local gum of A. polyacantha was evaluated as a tablet binder. Paracetamol and chloroquine phosphate were used as model drugs. The physico-chemical properties of the purified gum, and its rheological properties were investigated. The gum was found to have similar properties to Acacia BP (odourless, white to yellowish brown, glassy, no tannins, no starch or dextrin present and moisture content of 11.6%). It exhibited Newtonian flow up to 40% w/v solution but less viscosity than Acacia BP. Granules prepared with different concentrations (5 - 30% w/v for paracetamol and 5-20% w/v for chloroquine phosphate) of the gum mucilage were characterised for particle size distribution, bulk, tapped and true densities, friability and flow properties. The granules were mixed with Ac-Di-SolÒ (4%) and magnesium stearate (0.5%) and compressed into tablets at different compression forces. The optimum binder concentration (X1) and compression force (X2) (independent variables) of both substances (paracetamol and chloroquine phosphate) were investigated using 22 factorial design taking crushing strength (H), disintegration (DT) and friability (Fr) as response variables. Polynomial equations were generated for the responses (H = 84.175 + 26.825X1 + 33.375X2 + 5.625X1X2; DT = 9.24 + 8.38X1 + 4.59X2 + 4.45X1X2; Fr = 1.9725 – 0.7775X1 – 1.1225X2 + 0.6275X1X2 for paracetamol and, H = 118.8 + 12.35X1 + 48.05X2 – 1.7X1X2; DT = 8.375 + 1.125X1 + 3.875X2 – 0.375X1X2; Fr = 1.08 – 0.22X1 – 0.42X2 + 0.08X1X2 for chloroquine phosphate). Surface response curves and contour plots were constructed and the xi v optimum regions determined by superimposing the contour plots. The optimum values were re-transformed using the equation: Trans = [2A – (Max + Min)]/ Max – Min, where Trans is the transformed value, A is the actual value of the factor being transformed, and Max and Min are the maximum and the minimum values in the range of the factor being transformed, respectively. Granules of the optimum formulations (6.21% w/w of binder for paracetamol, and 1.386% w/w of binder for chloroquine phosphate) prepared had mean bulk densities of 0.41 and 0.508 g/ml, tapped densities 0.474 and 0.584 g/ml, Carr’s indexes of 13.58 and 13.01% and Hausner ratios of 1.16 and 1.15 for paracetamol and chloroquine phosphate, respectively. Tablets compressed at compression force of 14 KN (paracetamol) and 16 KN (chloroquine phosphate) were compared with predicted values (H: 122 and 119N, DT: 15 and 8.5 minutes and Fr: 0.6 and 0.9% for paracetamol and chloroquine phosphate, respectively). Tablets prepared with the gum showed H of 132 and 116N for paracetamol and chloroquine phosphate, respectively, and Fr of 0.9% for both substances. For comparison purposes, chloroquine phosphate tablets were prepared with 5% w/v PVP solution and H values of 122N and Fr of 0.9% were obtained. The DTs of the tablets made with the gum were 13 and 9.3 minutes for paracetamol and chloroquine phosphate, respectively. Dissolution profiles of the tablets were within the acceptable ranges (³ 80 and ³ 75% of drug release in 30 and 45 minutes for paracetamol and chloroquine phosphate, respectively). The respectiveT50s were 5 and 8 minutes. From the foregoing, it can be concluded that gum of A. polyacantha can be used as an alternative binder in tablet formulations.Item A Prospective Study on Self-Medication Practices and Consumers Drug Knowledge in Addis Ababa(Addis Ababa University, 2002-06) Andualem, Tenaw; Gebre-Mariam, Tsige (Professor)Background: Health and disease exist in a continuum. Self-care is as old as illness if not as humans. Self-care is a lay behavioural response of individuals to promote or restore their health. One form of self-care is self-medication. Drugs are central to self-medication. Although there are arguments for and against self-medication, its contribution to promote health, and prevent and treat diseases is beyond doubt. Self-medication is the selection and use of medicines by individuals to treat self-recognized illnesses or symptoms of illnesses. Socio-demographic and socio-economic variables affect self-medication. In this study, an attempt has been made to assess self-medication practices with modern drugs and consumers drug knowledge in Addis Ababa. Methods: A multi-stage stratified sampling of drug retail outlets and drug consumers (actual drug users and messengers) was designed and used. Structured questionnaires to assess prospective self-medication practices and consumers drug knowledge were employed. The data was analyzed using Epi Info Software. Results and Discussion: The respondents represented all socio-demographic characteristics such as age and gender (the proportion of males was twice that of females); education levels and occupation; religion (the majority being Orthodox Christians) as well as pregnant and breast-feeding women. The most frequently reported illnesses that prompted drug consumers for self-medication were found to be gastrointestinal (GI) diseases, headache/fever and respiratory tract infections (RTIs). More than 30% of illnesses/symptoms of illnesses were of less than 24 hours duration and more than 40% between one and seven days. The most common reasons for self-diagnosis and self-medication were non-seriousness of the diseases and prior experience about the drugs. More than 50% of the drug consumers requested drugs xi by specifically mentioning the names of the drugs and one-fifth of them by telling their illnesses/symptoms of illnesses. The most frequently requested category of drugs were analgesics/antipyretics (more than 30%), antimicrobials (more than 25%) and gastrointestinal drugs (more than 17%). Assessment of drug knowledge revealed that drug consumers know not only the names of OTC drugs but also other potent drugs, indicating widespread use of the latter. For example, among the top fifteen frequently recalled drugs five were antimicrobials. Drug consumers had also some dosage form preferences, the highest being injections and tablets for messengers and for actual drug users, respectively. Multivariate analysis showed that there is association between illness/symptoms of illness with the duration of illness and source of advice/information for self-medication (p value less than 0.05). Strong association (p value = 0.0000) was observed between the source of advice/information and the frequently requested category of drugs, some socio-demographic variables with sources of advice/information, knowledge of drugs, and the frequently requested category of drugs. Conclusion: Self-medication is widely practiced by all categories of respondents for a wide range of illnesses/symptoms of illnesses. More than 100 different types of drugs were used for self-medication. Although there is some apparent consumers drug knowledge, it is suggested that the public has to be educated on the type of illnesses to be self-diagnosed and the type of drugs to be self-medicated. It is only then that responsible self-medication prevails to promote health and prevent/ treat illnesses.Item Phytopharmaceutical Studies of Some Selected Medicinal Plants Locally Used In the Treatment of Skin Disorders(Addis Ababa University, 2004-01) Tadeg, Hailu; Gebre- Mariam, Tsige (Professor); Asres, Kaleab (PhD)In this study, eight species of traditionally used medicinal plants namely Acokanthera schimperi (Apocynaceae), Calpurnia aurea (Fabaceae, Leguminosae), Kalanchoe petitiana (Crassulaceae), Lippia adoensis (Verbenaceae), Malva parviflora (Malvaceae) Olinia rochetiana (Oliniaceae), Phytolacca dodecandra (Phytolaccaceae) and Verbascum sinaiticum (Scrophulariaceae), were screened for antimicrobial activity against different strains of bacteria and fungi which are known to cause various types of skin infections. Among these plants, L. adoensis and O. rochetiana, which showed better antimicrobial activity in the initial screening test, were selected for further investigations. Fractionation and antimicrobial activity tests of the fractions, anti-inflammatory activity tests, phytochemical screening, evaluation of topical formulations, and preliminary standardization studies were carried out on the two species of plants. The results of the initial antimicrobial screening test indicated the potential of these herbal drugs in treating bacterial and fungal infections of the skin. Almost all species of plants were found to have activity on at least one strain of bacteria and/or fungi. This might justify their claimed uses in the treatment of various skin disorders the majority of which are of infectious origin. Among the different fractions (petroleum ether, chloroform, acetone and methanol) tested for antimicrobial activity, the non-polar fractions were found to be more active than the polar fractions. The phytochemical screening tests carried out on L. adoensis and O. rochetiana indicated the presence of tannins, flavonoids and saponins in both species of plants. The antiinflammatory activity test results however have indicated that the two species of plants do not have demonstrable anti-inflammatory activity. xii Performance evaluation of topical formulations of the crude extracts in different vehicles revealed that extracts incorporated into creams (especially the hydrophilic ones) are superior in performance than those incorporated in to ointments. In addition, crude extracts formulated into water soluble ointment (PEG ointment) demonstrated higher performance compared to lipophilic ointments. The most lipophilic formulation of the crude extracts, petrolatum ointment, was found to be devoid of any activity against all the tested strains of bacteria and fungi indicating that the active compound(s) could not be released from this vehicle. Although evaluation of the quality of the two herbal drugs was not possible due to absence of published data for comparison, the most commonly employed standardization/quality control parameters including ash values, solvent extractable matters, loss on drying and TLC fingerprints were determined for the two herbal drugs in an attempt to provide such base line data as an indication of their quality attributes.Item Ethnobotanical and Ethnopharmaceutical Studies on Medicinal Plants of Chifra District, Afar Region, North Eastern Ethiopia(Addis Ababa University, 2004-01) Seifu, Tesfaye; Gebre-Mariam, Tsige (Professor); Asres, Kaleab (PhD)Medicinal plants have not been well studied, tested or documented in Afar region, North Eastern Ethiopia. Most of the information is still in the hands of the traditional healers. A study was carried out during Nov.2002 – May 2003 to explore ethnobotanical information on the use of medicinal plants by Afar people in 13 rural communities of Chifra District, Afar Region, North Eastern Ethiopia. Based on the information found from ethnic leaders, 29 traditional medicine practitioners were interviewed by using pre-tested semi structured questionnaire. A total of 70 plant species were reported for their medicinal use in the district. Of these, 33 were fully identified by their botanical name, 10 at generic level and 27 couldn’t be identified and were recorded only by their vernacular names. 15% of the identified species belong to the family Fabaceae. Among 144 ethnoformulations reported, the majority were liquid preparations followed by unprocessed herbs and powder. The most widely used solvent to prepare the formulations was water. Size reduction, extraction and filtration were the most commonly employed unit processes in the formulation. Intranasal route of administration was frequently used next to oral route. Polyherbal preparations were common in order to have synergistic or summation effect. Although there is difficulty of determining accurate dose, the practitioners have an idea of dose and frequency of herbal preparations. Side effects are reported only for Aloe sp in therapeutic dose. Most of the oral herbal drugs are contraindicated for pregnant women. The practitioners have no idea of drug interactions and shelf life of the reported plant species. The data were analyzed using the concept of healer consent in order to identify culturally important medicinal plants. The medicinal uses of the plants were grouped into 9 disorder categories to have the factor of informant’s consensus (Fic) for each group. Accordingly, snakebite had the highest value (0.53) indicating the dependence of the practitioners on certain plants for the indication. The most frequently x i recorded medicinal plants of the Afar people were Aloe sp. used for the treatment of “Urribaqla”, malaria, abdominal cramp, TB and pasterlosis; Acalypha sp. for snakebite, blackleg, anthrax, “Barelitta”and impotence. The medicinal plants were assessed using published phytochemical and pharmacological data. Of the fully identified 33 medicinal plant species, the claimed medicinal uses of the six were in good agreement with other similar studies and pharmacological activity tests reported elsewhere. The medicinal uses of most of the reported plant species have not been documented in other parts of the country. This study underlines the need for further exploration of ethnobotanical information in the region and the results will be used as a basis for subsequent studies on pharmacology, phytochemistry and toxicology of medicinal plant.Item Studies on Extracts of Some Medicinal Plants Traditionally Used for Dermatological Disorders in Ethiopia(Addis Ababa University, 2004-02) Messele, Bruck; Gebre-Mariam, Tsige(Professor); Gamal, Mohammad (PhD)Key words: traditional medicine, medicinal plants, antimicrobial activities, anti-inflammatory test, skin sensitization test, topical formulations. The majority of the populations in the developing world rely on traditional medicine for their primary healthcare needs. Herbal therapy predominates in traditional medical practices as well as in complimentary/alternative medicine practiced in the developed world. Among the indications where traditional herbal medicines are used, skin and skin related disorders, which also happen to be common diseases in the communities, rank among the top. This study had the objective of evaluating the extracts of four medicinal plants traditionally used for skin diseases, namely Inula confertiflora, Clematis simensis, Zehneria scabra and Pycnostachys abyssinica, for some of their claimed activities by both in vitro and in vivo methods. The 80 % methanol extract of the dried, ground plant materials was prepared. The plant extracts were then tested for antimicrobial activity against common bacterial and fungal pathogens by the agar well diffusion method. Furthermore, the 80% methanol extract of I. confertiflora was subjected to minimum inhibitory concentration (MIC) determination, in vivo studies such as antiinflammatory and skin sensitization tests as well as in vitro tests such as preliminary screening for the presence of some plant constituents, TLC analysis, and evaluation of topical antimicrobial formulations of the plant extracts. The results of the study indicated all of the plant extracts to exhibit antimicrobial activities against one of the most common bacterial pathogens, namely Staphylococcus aureus (ATCC). x Although these activities were not impressive especially as compared to the positive control used, they lend some credibility to the traditional uses of the plants. Good antifungal activity was demonstrated by one of the plant extracts (I. confertiflora) against Trichophyton mentagrophytes, which was further corroborated by the agar dilution method. I. confertiflora (80% methanol) extract proved to exert a good anti-inflammatory activity at a dose of 1000 mg/kg but not at a lower dose (500 mg/ml) in the carrageenan-induced paw edema test. These activities support the traditional use of this plant. Furthermore, the 80% methanol extract of I. confertiflora, was not found to be a skin sensitizer in the mouse ear swelling test as opposed to its petroleum ether counterpart, which demonstrated a strong sensitizing property. Some secondary metabolites such as sesquiterpene lactones and flavonoids were detected, which may be responsible for some of the demonstrated pharmacological activities of this plant. Evaluation of topical formulations of the 80% methanol extract of I. confertiflora demonstrated that the hydrophilic formulations exhibited higher antimicrobial activities compared to the lipophilic formulations. The activity of the hydrophilic formulations against T. mentagrophytes was comparable to the commercially available antifungal products tested. These bases could thus be used as a starting point for further formulation studies.Item In-Vitro Comparative Evaluation of Different Co-Trimoxazole Tablet Products Obtained From Drug Retail Outlets in Addis Ababa(Addis Ababa University, 2004-02) Assefa, Haymanot; Gebre-Mariam, Tsige (Professor); Ibrahim, Seid(Professor)Evaluation studies provide a means of identifying quality differences between same products obtained from various manufacturers and quality evaluations are crucial in the era of increasing resistance to antibacterial agents The introduction of trimethoprim in combination with sulphamethoxazole constitutes an important advance in the development of clinically effective antimicrobial agents. In much of the world the combination of sulphamethoxazole with trimethoprim in the proportion of 5 to 1 is known as Co-trimoxazole. Co-trimoxazole has been used in a diverse range of infections due to sensitive bacteria and is widely prescribed for various indications. By virtue of sequential blockade of microbial folic acid synthesis the antimicrobial combination has excellent in vitro inhibitory activity against many common respiratory and urinary tract pathogens, as well as many nosocomial-infecting strains. In patients infected with the human immunodeficiency virus (HIV), trimethoprim-sulphamethoxazole provides prophylactic and therapeutic potency against Pneumocystis carinii but at the risk of side effects. Trimethoprim-sulphamethoxazole (TMPSMX) is also used for treatment of pulmonary and disseminated nocardiosis and some forms of Wagener’s granulomatosis, as well as for prophylaxis of spontaneous bacterial peritonitis. Bacterial resistance to trimethoprim-sulphamethoxazole is a rapidly increasing problem and is exacerbated by use of substandard products. In this work, it is aimed to evaluate the physical properties and the dissolution profiles of trimethoprim-sulphamethoxazole tablets produced by ten different manufacturers and are obtained from drug outlets in Addis Ababa. X I I Accordingly, the different tablets were evaluated for physical properties (Diameter, thickness, shape, hardness, friability and disintegration time) and their dissolution profiles were compared by the USP XXVI paddle method. The tablets investigated in this study could roughly be grouped as those, which exhibited, delayed drug release and those, which released the drug contained immediately. The tablets evaluated in this study differed in many of their physical properties. The average weights ranged from 502.41mg (Bactrim) to 709.98mg (Cotrimol), 480mg being the expected strength of the combination. The mean disintegration times ranged from 0.17 (±0) minutes (Cotrimoxazole) to 13.05 (±5.24) minutes (Lagatrim). Nine of the tested products gave an assay value above the lowest limit (93%-107%) specified in the pharmacopoeia. Assay values greater than the upper limit for sulphamethoxazole was obtained with four of the evaluated products. One product gave an assay value greater than the upper limit for both sulphamethoxazole and trimethoprim. Most of the tablets released the drug contained in an increasing fashion from the 5th minute to the 60th minute with varying proportion of increment. Products obtained from Europe released most of the drug within the first 5 to 10 minutes. More than 90 % of trimethoprim is released within 5 minutes from Bactrim and Septrin and with in 10 minutes from Lagatrim and Deprim. While Lagatrim and Septrin released more than 90 % of their Sulphamethoxazole within 10 minutes, Bactrim and Deprim released their Sulphamethoxazole within 20 minutes. However the European X I I I and the non-European products differed significantly in their sulphamethoxazole release. Both products showed a comparable trimethoprim release pattern. All of the tested products released more than 90% of the trimethoprim after one hour, ranging from 92.81%-Cotreich to 111.77%- Septrin. The very long t90% values of Cotreich and Cotrimol (60 & 45minutes respectively) for trimethoprim, the very long t50% & t90% values of Cotreich (38 and >60minutes respectively) for trimethoprim and sulphamethoxazole, and the very long t90% values of Cotreich, Cotrimol and Kanprim (>60 minutes) for sulphamethoxazole indicate that these products could result in lower rate and extent of bioavailability in the body. Similar problems could be encountered with the relatively long t90% values of Cotrimoxazole (45minutes) and Oriprim (40minutes) for Sulphamethoxazole. The smaller amount of sulphamethoxazole and trimethoprim released from products with delayed release could compromise the in vivo efficacy of these tablets.Item 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 Synthesis and Antimicrobial Activity of Triphenyltinbenzoate Aniline Complex(Addis Ababa University, 2008-04) Zewdie, Berhan; Choudhury, M.K.(Professor)Triphenyltinbenzoate and triphenyltinbenzoate aniline complex had been synthesized and characterized on the basis of infrared, mass and nuclear magnetic resonance (1H and 13C) spectral studies. The synthesized compounds had sharp melting point which indicated the purity of the compounds. The antimicrobial activities of the synthesized compounds were tested against six different pathogenic microorganisms; Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Aspergillus niger and Candida ablicans in vitro. The results indicated that the synthesized compounds exhibit a higher activity against Escherichia coli, Streptococcus pyogenes, Pseudomonas aeruginosa and Candida ablicans than the starting compound. The results also indicated that the compounds did not exhibit any activity against Aspergillus niger at concentration as high as 200 μgml-1.Item Evaluation of the Diuretic and Analgesic Activities of the Rhizomes of Rumex Abyssinicus Jacqinmice(Addis Ababa University, 2008-10) Mekonnen, Teshale; Engidawork, Ephrem (PhD)Rumex abyssinicus Jacq (Polygonaceae) is a widely spread medicinal plant used traditionally for treatment of several ailments, including hypertension, inflammatory and painful conditions. The present study aimed to examine the diuretic and analgesic activities of aqueous and 80% methanol extracts of the rhizomes of the plant at different doses in mice. To this effect, negative controls were orally treated with distilled water (DW) or Tween 80(4%) (TW80), solvents used for reconstitution of the extracts. Positive controls were treated with furosemide (10 mglkg) (FrIO) for diuretic test or aspirin (100 mg/kg) (ASA100) and morphine (10 mg/kg) (MIO) for acetic acid-induced writhing and hot-plate analgesic studies, respectively. For the diuretic study, treatment groups received an oral dose of SOO mgikg (RASOO), 7S0 mglkg (RA7S0) or 1000 mg/kg (RA1000) of the aqueous extract or 2S0 mglkg (RM2S0), SOO mg/kg (RMSOO) or 7S0 mglkg (RM7S0) of 80% methanolic extract. Urine volume was then measured at different time (1,2, 3, 4, and S h) and the urinary Na+, K+ and cr also measured at S h. For both analgesic tests, 2S0 mglkg (RM2S0), SOO mg/kg (RMSOO) or 1000 mglkg (RM1000) of 80% methanolic extract doses were used. Whereas the number of writhes was counted for 20 min just S min after intraperitonial injection of 0.6% acetic acid (O.lS mLilOg) for the writhing test, the reaction time of each mouse was evaluated at 30, 4S, 60, and 90 min after treatment for the hot-plate test. For the acute toxicity study, SOOO mglkg of aqueous or 80% methanolic extract was administered orally and observed for the following IS days. Both extracts displayed a clear dose-dependent diuretic and analgesic effect as compared to controls. RA1000 and RM7S0 were able to increase diuresis significantly (PItem Evalva Tion of the Diuretic and Analgesic Activities of the Rizomes of Rumex Abyssinicus Jacq in Mice(Addis Ababa University, 2008-10) Mekonnen, Teshale; Fngidawork, Ephrem (PhD)Rumex abyssinicus Jacq (Polygonaceae) is a widely spread medicinal plant used traditionally for treatment of several ailments, including hypertension, inflammatory and painful conditions. The present study aimed to examine the diuretic and analgesic activities of aqueous and 80% methanol extracts of the rhizomes of the plant at different doses in mice. To this effect, negative controls were orally treated with distilled water (DW) or Tween 80(4%) (TW80), solvents used for reconstitution of the extracts. Positive controls were treated with furosemide (10 mglkg) (FrIO) for diuretic test or aspirin (100 mg/kg) (ASA100) and morphine (10 mg/kg) (MIO) for acetic acid-induced writhing and hot-plate analgesic studies, respectively. For the diuretic study, treatment groups received an oral dose of SOO mgikg (RASOO), 7S0 mglkg (RA7S0) or 1000 mg/kg (RA1000) of the aqueous extract or 2S0 mglkg (RM2S0), SOO mg/kg (RMSOO) or 7S0 mglkg (RM7S0) of 80% methanolic extract. Urine volume was then measured at different time (1,2, 3, 4, and S h) and the urinary Na+, K+ and cr also measured at S h. For both analgesic tests, 2S0 mglkg (RM2S0), SOO mg/kg (RMSOO) or 1000 mglkg (RM1000) of 80% methanolic extract doses were used. Whereas the number of writhes was counted for 20 min just S min after intraperitonial injection of 0.6% acetic acid (O.lS mLilOg) for the writhing test, the reaction time of each mouse was evaluated at 30, 4S, 60, and 90 min after treatment for the hot-plate test. For the acute toxicity study, SOOO mglkg of aqueous or 80% methanolic extract was administered orally and observed for the following IS days. Both extracts displayed a clear dose-dependent diuretic and analgesic effect as compared to controls. RA1000 and RM7S0 were able to increase diuresis significantly (PItem Anti-Malarial Drug and Mosquito Net Use Pattern in Pawe Special Woreda: A Community Based Survey(Addis Ababa University, 2009-06) Mussa, Seid; Gedif, Teferi (PhD)Item Cost as a Barrier to Access: Availability, Affordability and Identifying Component Cost of Essential Medicines(Addis Ababa University, 2009-06) Nuru, Mohammedsied; Gedif, Teferi (PhD)Item Cost as a Abrrier to Access: Availabilty, Affordability and Identifying Component Cost of Essential Medicines(2009-06) Nuru, Mohammedsied; Gedif, Teferi (PhD)Item Assessment of Dot Implementation in Tigray, Northern Ethiopia(Addis Ababa University, 2009-07) Alisani, Seid; Gedif, Teferi (PhD); Tadesse, Zerihun (PhD)Mycobacterium tuberculosis infects one third of the world's population. Ethiopia ranks seventh in the world & third in Africa with TB prevalence. TB is the leading cause of morbidity, the third cause of hospital admission and the second cause of hospital death in Ethiopia. TB patients take drugs for very long period of time. Hence, adherence is a major problem. To resolve this issue, the World Health Organization recommends the strategy of Directly Observed Therapy-Short Course (DOTS) which includes Directly Observed Treatment (DOT) to ensure a better patient adherence. The observer may be a health worker or a trained and supervised community member. Studies elsewhere show varying results on the effectiveness of Community Based DOT (CBDOT) compared to Health Facility Based DOT (HBDOT) option. In Ethiopia, although attempts have been made to assess quality of DOT implementation, comparative effectiveness of CBDOT versus HBDOT programs has not yet been assessed. This study was conducted to assess effectiveness of DOT implementation in CBDOT and HBDOT program areas in Tigray region. The study also aimed to compare implementation practice between the two DOT options and identify the factors affecting DOT implementation. The study was a comparative cross sectional study conducted between October and December, 2008. Both quantitative and qualitative methods were used for data collection. The quantitative methods used were retrospective review of Unit TB Registers avai lable in the health faci lities, prospective observation of DOT observers' practice, exit interview of TB patients and selfadministered questionnaire for health profess ionals. The qualitative method used was Focus Group Discussions (FGD) for both groups. A total of 378 patients, 118 from Hintalo Wajirat (CBDOT) and 266 from Enderta (HBDOT) Woredas, registered from September 2005 to February 2008 treatment outcomes were reviewed retrospectively from Unit TB Registers. Effectiveness was measured by success rate. Treatment was successful for 101 (88.6%) and 181 (87.4%) new TB patients in CBDOT and HBDOT program areas, respectively. For new sputum smear positive pulmonary TB cases treatment was successful for 19 (90.5%) patients in CBDOT and 28 (84.8%) patients in HBDOT options. CBDOT option was as effective as HBDOT in treating TB patients and can achieve good treatment outcomes. CBDOT option also reduced transfer out of TB patients.This study found out that DOT implementation as indicated by observation of DOT provider practice was comparable for CBDOT and HBDOT program areas. This indicated that CBDOT observers can practice DOT like HBDOT providers. Hence, CBDOT can complement HBDOT and could be a viable alternative in areas where people live faraway from health facilities. The study also identified access, acceptability of DOT option and DOT providers, awareness of patients and providers, support to the patient, incentive to CBDOT providers, health improvement, documentation and supervision as factors that could affect DOT implementation. Voluntary Community Health Workers are available in each and every village and are willing to render service to their villagers. National/regional policy should be adopted to equip them with proper training and provide supportive supervision so that they tremendously increase both access and quality of DOT. Mechanisms should be devised to ensure that health workers develop supportive attitude and facilitate wide scale deployment of voluntary Community Health Workers. Key words: TB, DOT, CBDOT, HBDOT, Effectiveness, Treatment success and Tigray