The Effect of Acute and Subchronic Administration of Crude Khat Extract (Catha Edulis F.) on Weight in Mice

People widely chew khat, particularly in East Africa, for different purposes but there is no consistent data showing its effect on anorexia and weight. This study was made to add to the existing body of knowledge about khat and its effect on weight. A total of 50 albino mice, 6-8 weeks old, were administered orally with a single daily dose of khat extract for 30 days. The animals were divided into 4 groups. The first group served as controls and was administered with 0.5 ml 3% Tween 80 in water. Group two (K100), three (K200) and four (K300) were administered 100, 200 and 300 mg/kg khat extract, respectively.  The effect of crude khat extract on weight was measured and analyzed using One-way ANOVA. The result showed that acute administration of crude khat extract at doses used did have a significant effect on weight on all the three groups (khat administered) (p< 0.01) but there was no significant weight difference among the three groups. After the fourth days, this weight decrease, however, was followed by regaining the initial weight and then increasing till the end of the experiment.  Crude khat extract at acute and sub-chronic administration have anorexic effect but followed by development of tolerance which may be explained by a complex of Neuro-chemical processes

Investigations into the regulation of the desensitization of 5-HT4 receptors in the rat gastrointestinal tract

5-HT4 and 5-HT7 receptors contain introns that allow the formation of multiple splice variants which are potential targets for developing tissue selective drugs if they are expressed in specific parts of the gastrointestinal tract. 5-HT induces desensitization of 5-HT4 receptors which is facilitated by G-protein coupled receptor kinases (GRKs). This thesis describes investigations into the expression of 5-HT4, 5-HT7 receptors and GRKs (GRK2, GRK3, GRK5 and GRK6); identification of GRK(s) associated with the regulation of the desensitization of 5-HT4 receptors; and the effect of 5-HT4 receptor activation on the expression level of GRKs in the rat gastrointestinal tract. Reverse transcriptase polymerase chain reaction experiments revealed variations in the distribution of the 5-HT4 receptor splice variants in the rat gastrointestinal tract. Both the 5-HT4(a) and 5-HT4(b) receptor splice variants were consistently expressed in the rat oesophagus, ileum and colon. The 5-HT4(e) receptor splice variant was not detected in any tissue. There was no expression of any of the 5-HT4 receptor splice variants in the jejunum. Three 5-HT7 receptor splice variants (a, b and c) were found in the oesophagus, jejunum, ileum and colon. GRKs were also detected in all parts of the gut. Immunohistochemistry studies showed the expression of 5-HT4 receptors in the tunica muscularis mucosae of the oesophagus. These studies also identified 5-HT4 receptor immunoreactivity in the longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus and muscularis mucosae of both the proximal and distal colon. GRK2 was expressed in longitudinal muscle and occasionally in the myenteric plexus whilst GRK5 showed limited expression in the nerve endings of the myenteric and submucosal plexuses of the colon. GRK3 was expressed in the tunica muscularis mucosae of the oesophagus, circular muscle, submucosal plexus and muscularis mucosae of the colon. GRK6 was expressed in the tunica muscularis mucosae of the oesophagus, longitudinal muscle, circular muscle, and muscularis mucosae of the colon. Stimulation of the tunica muscularis mucosae of the oesophagus and distal colon using the 5-HT4 receptor agonist, tegaserod, followed by analysis of the 5-HT4 receptor antibody immunoprecipitate, revealed the coimmunoprecipitation of GRK6 with 5-HT4 receptors in the tunica muscularis mucosae of oesophagus. In the distal colon, GRK2 and GRK6 were coimmunoprecipitated with 5-HT4 receptors. This study indicates that GRK6 may be involved in the regulation of the desensitization of 5-HT4 receptors in the rat oesophagus whilst GRK2 and GRK6 may be involved in regulation of the desensitization of 5-HT4 receptors in the distal colon. The acute administration of the 5-HT4 receptor agonist tegaserod for 1, 2, 3, 4, 6, and 8 hr did not change significantly the immunodensity of GRK2 in the oesophagus and distal colon when compared with control animals. Also there was no significant change in the immunodensity of GRK6 in the oesophagus. This result shows that acute activation of 5-HT4 receptors using tegaserod did not alter the expression of GRK2 and GRK6. This may indicate that the basal level of GRK2 and GRK6 expression is sufficient to regulate the desensitization of 5-HT4 receptors in acute drug treatment

Evaluation of the antidiarrhoeal activity of 80% methanol extract and solvent fractions of the leaves of Lantana camara linn (Verbenaceae) in mice

Lantana camara L. is one of the medicinal plants traditionally used for the treatment of diarrhoea in Ethiopia. The aim of this study was to evaluate antidiarrhoeal activity of the 80% methanol extract and solvent fractions using mice model of diarrhoea. The 80% methanol extract was prepared by maceration and the fractions were obtained by successive soxhlet extraction with chloroform and methanol followed by maceration of the marc with water. The antidiarrhoeal activity of the extract and fractions were investigated using castor oil-induced diarrhoea (for 80% methanol extract), enteropooling and small intestine transit models (the three models for the fractions). The test groups received various doses (100, 200 and 400 mg/kg) of the extract or fractions, whereas positive controls received Loperamide (3 mg/kg) and negative controls received vehicle (10 ml/kg). The 80% methanol extract reduced the number and weight of feces at all tested doses significantly as compared to the negative control. The methanol and aqueous fractions showed a significant reduction on the number and weight of wet feces and weight and volume of intestinal content when compared with negative control. All the fractions produced a significant antimotility effect at all tested doses as compared to negative control. This study confirmed the antidiarrhoeal activity of the crude extract and further revealed all the three fractions possessed varying degree of antidiarrhoeal activity, with the methanol fraction being the most active fraction in all the three models.Keywords: Lantana camara, antidiarrhoeal activity, castor oil induced diarrhoea, gastrointestinal transit, antienteropoolin

Concordance between modification of diet in renal disease, chronic kidney disease epidemiology collaboration and Cockcroft-Gault equations in patients with chronic kidney disease at St. Paul’s hospital millennium medical college, Addis Ababa, Ethiopia

Abstract Background The most commonly used glomerular filtration rate estimating equations for drug dosing are Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. However there is still a concern about whether to use MDRD and CKD-EPI interchangeably with CG for drug dosage adjustment. Methods The study was initiated to determine the concordance between MDRD, CKD-EPI and CG equations and associated factors in patients with chronic kidney disease at Saint Paul’s Hospital Millennium Medical College (SPHMMC). This was a cross sectional study which involved patient chart review and physicians self-administered questionnaire. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The correctness of the drug dose prescribed for the level of renal function were compared to the drug database (Lexi-Comp) available through Up-to-date version 21.2. Results Among the total of 422 patients, 249 (59%) were males. Mean age of patients was 46.09 years. The use of MDRD equation for drug dose adjustment by physicians working in the renal clinic of SPHMMC was six out of nine physicians. The Pearson correlation coefficient between the CG with MDRD and CKD-EPI equations was r = 0.94, P  70 years was associated with discordance between CG and MDRD equations for drug dosing recommendation whereas serum creatinine 1.2–3.5 mg/dL, weight  70 years were associated with discordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories. However, none of the factors associated with discordance between CG and CKD-EPI for drug dosing. Conclusion MDRD equation can be used interchangeably with CG equation for drug dosing recommended in all adult patients between the age of 18 and 70 years. CKD-EPI can be used interchangeably with CG in all adult Ethiopian patients with CKD

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models

Background. Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method. The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test and p<0.05 was considered significant. Results. The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p<0.001). Conclusion. The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models

Hepatoprotective Effect of Croton macrostachyus Hochst. Ex Del Leaves Against CCl4-Induced Liver Damage

Croton macrostachyus Hochst is a medicinal plant widely used in Ethiopia for the treatment of dysentery, abdominal pain, hepatitis and jaundice. The aim of this study was to evaluate the hepatoprotective activity of aqueous extract of leaves of C. macrostachyus (AECM) in CCl4-induced hepatotoxicity in rats and mice. Seven groups of animals (n = 6) were used. Distilled water was given to group I; animals in group II were given distilled water along with CCl4 (1 mg/kg) every 72 h for 16 days, third group served as a positive control and received silymarin 100 mg/kg, and for the other groups 100, 200, 400 and 800 mg/kg AECM were given orally once daily for 16 days. Hepatotoxicity was induced by intra-peritoneal administration of 1 ml/kg of CCl4 every 72 h. At the 18th day blood samples were collected from the jugular vein. Serum concentrations of biochemical markers and histopathological analysis of the liver were conducted. Thiopentone-induced sleep time test was also conducted. The crude extract at all doses produced significant hepatoprotection by decreasing the level of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilurbin (IBIL). The extract at 100, 200 and 400 mg/kg also produced significant hepatoprotection by decreasing levels of alkaline phosphatase (ALP) as well as produced significant elevation of serum albumin (ALB) level. These results correlated well with the histopathological studies and thiopentone-induced sleeping time assessment. The study revealed that aqueous extract of the leaves of C. macrostachyus possesses hepatoprotective activity and could be used as a potential source of new hepatoprotective drugs.Keywords: Croton macrostachyus, hepatoprotective, carbon tetrachloride, biochemical markers, histopathological analysi

Evaluation of Hypoglycemia and Associated Factors among Patients with Type 1 Diabetes on Follow-Up Care at St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia

Background. Hypoglycemia is one of the most common acute complications of type 1 diabetes mellitus (T1DM). The knowledge of the factors associated with hypoglycemia will help in the prevention and management of the problem. Therefore, this study was conducted to assess hypoglycemia and its associated factors among T1DM patients who attended the diabetes outpatient clinic of St. Paul’s Hospital Millennium Medical College (SPHMMC). Methods. A cross-sectional study was conducted at the diabetes clinic of SPHMMC. Data on sociodemographic and clinical characteristics including duration of diabetes, type of insulin they have been taking, the factors associated with hypoglycemia, and the severity stage of hypoglycemia was obtained. Data was collected using a structured questionnaire and chart review. Multivariate logistic regression model was used to identify factors associated with hypoglycemia. Result. Out of the 247 participants who were recruited into the study, 233 (94.3%) of them experienced hypoglycemia. A total of 6.9 events of hypoglycemia per patient per year happened. Particularly, the events were categorized as 3.1 mild events, 2.3 moderate events, and 0.93 severe events of hypoglycemia. Shorter duration of diabetes history (<1 year) was significantly associated with less experience of hypoglycemia (AOR=0.09, 95% CI: 0.01-0.90). However, blood glucose monitoring at home was found to be significantly associated with more report of hypoglycemia (AOR=5.77, 95% CI: 1.16-28.66). Conclusion. The prevalence of hypoglycemia among T1DM patients was found as substantially high. Self/family blood glucose monitoring at home could not guarantee to minimize the occurrence of hypoglycemia events. Finger stick home blood glucose monitoring should be given a special attention. Therefore, the involvement of health care providers in diabetes care should be encouraged to address the occurrence of hypoglycemia in T1DM patients

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models

Abstract Background Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation. Methods Successive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80). Results In all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg. Conclusion This study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs