Involvement of CB2 Receptors in the Neurobehavioral Effects of Catha Edulis (Vahl) Endl. (Khat) in Mice.

There is behavioral evidence for the interaction between crude khat extract and the endocannabinoid system, whereby the endocannabinoid system alters khat extract-mediated behavioral effects through modulation of the monoaminergic system. The objective of this study was to investigate the role of the endocannabinoid system on the neurobehavioral effect of khat extract in mice following concomitant administration of khat extract and the CB2R agonist, JWH133. Locomotor activity test, immunohistochemistry, and reverse transcriptase polymerase chain reaction technique were utilized to assess locomotor activity, tyrosine hydroxylase immunoreactivity, and expression of dopamine transporter mRNA gene. The results show sub-acute administration of khat extract alone increased locomotor activity in mice and co-administration of the CB2R agonist, JWH133, reduced khat extract induced hyperlocomotor activity. The data revealed that cell type specific deletion of CB2Rs on dopaminergic neurons increased the hyperlocomotor behavior of khat extract. Furthermore, the results revealed that khat extract attenuated MPTP induced motor deficits, which is enhanced by JWH133. Khat extract also increased expression of tyrosine hydroxylase positive cells and expression of dopamine transporter mRNA gene in wild type mice. Nevertheless, JWH133 did not alter the effect of khat extract on tyrosine hydroxylase immunoreactivity and dopamine transporter mRNA expression when given together with khat extract. Taken together, the results suggest that the CB2Rs selectively interact with khat extract-mediated locomotor effects and could be utilized as therapeutic target in central nervous system movement disorders associated with dopamine dysregulation.

Mortality among tuberculosis patients under DOTS programme: a historical cohort study.

BACKGROUND: In high human immunodeficiency virus (HIV) prevalence population, tuberculosis (TB) is the leading cause of morbidity and mortality. HIV is driving the TB epidemic in many countries, especially those in sub-Saharan Africa. We assessed the survival time and predictors of mortality among tuberculosis patients under directly observed treatment, short course (DOTS) strategy in Dessie Referral Hospital tuberculosis clinic, Northeast Ethiopia. METHOD: A historical cohort design was utilized to assess survival time and determinants of mortality. A total of 1260 records of patients who started ant-tuberculosis treatment from January 2006 up to December 2010 were analyzed. Survival curves were estimated using Kaplan-Meier and were compared using the Log-rank test. The Cox proportional hazard model was used to assess the relationship between baseline variables and mortality. RESULTS: Out of the 1260 registered patients, 117 (9.3 %) died over the entire follow-up period. Among those died, 113 (18 %) were HIV positive and 4 (0.6 %) were HIV negative. The 1260 patients contributed a cumulative total of 634.25 person­years observation. CONCLUSION: The mortality of HIV positive tuberculosis patients was higher than those of HIV negative patients and the use of cotrimoxazole preventive therapy increased the survival time of patients.

Behavioral evidence for the interaction between cannabinoids and Catha edulis F. (Khat) in mice.

Several studies have shown the existence of an interaction between the endocannabinoid system and some drugs of abuse, such as opioids, nicotine, alcohol, and cocaine. For instance, the endocannabinoid system has long been known to play a role in the underlying mechanisms of drug reward and dependence. The aim of this study was to evaluate the possible existence of an interaction between the endocannabinoid system and khat after acute administration. Behavioral interactions of khat extract with cannabinoids were assessed. To this effect, mice were randomly divided into different groups (vehicle, khat extract, khat and WIN55,212-2, a cannabinoid agonist, khat extract and cannabinoid antagonists, AM251 & AM630) and their behavioral responses were evaluated in activity monitor, elevated plus maze and Y-maze tests. These tests were used to determine changes in locomotor activity, anxiety-like behavior, and working memory. Khat and WIN55,212-2 demonstrated differential responses in these tests, but co-administration of these agents invariably increased the measured parameters, which were reversed by the cannabinoid receptor antagonists used. The data collectively indicate that there is an interaction between khat and the endocannabinoid system, which most likely involves the cannabinoid receptors or a common mechanism separately activated by the two agents.

Khat (Catha edulis F.) and cannabinoids: Parallel and contrasting behavioral effects in preclinical and clinical studies.

After a brief outline of Catha edulis F. (khat) and the cannabinoid systems, the interactions between the pharmacological effects of khat and cannabinoids will be reviewed. Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. Experimental studies conducted to investigate khat's central and peripheral effects have revealed an amphetamine-like mechanism of action mediated through the dopaminergic system. The endocannabinoid system comprises the receptors, the endogenous agonists and the related biochemical machinery responsible for synthesizing these substances and terminating their actions. Endocannabinoids are synthesized "on demand" from membrane phospholipids and then rapidly cleared by cellular uptake and enzymatic degradation. Khat and cannabinoids produce a body of parallel and contrasting behavioral effects. Concurrent consumption of khat and cannabinoids may increase the risk of getting or precipitating psychosis, has rewarding and motivational effect, increases the threshold of pain perception and impairs learning and memory. On the other hand, the action of cannabis to enhance food intake is likely to reduce khat's appetite suppressant effects.

Retrospective evaluation of cotrimoxazole use as preventive therapy in people living with HIV/AIDS in Boru Meda Hospital.

BACKGROUND: Drug use evaluation is a performance improvement method that focuses on evaluating and improving drug use process to achieve optimal patient outcomes. Drug use evaluation helps in identifying, preventing or resolving actual and potential drug related problems. The objective of the study was to evaluate the use of cotrimoxazole as preventive therapy in people living with HIV/AIDS in Boru Meda Hospital, Northeast Ethiopia. METHODS: A retrospective drug use evaluation was conducted on patients' medical history records based on a validated drug use evaluation criteria according to the national guideline. Medical history records of 248 patients were selected using systematic sampling method. RESULTS: The result showed that 49.6% of the patients were at WHO clinical stage III at the start of cotrimoxazole preventive therapy. In this study, the use of cotrimoxazole preventive therapy was consistent with the guideline in the rationale for indication (97.98%), dose (96.77%), and its use despite the presence of contraindications (91.93%). Problems regarding drug-drug interaction were identified in 49.59% of cases, and 20.97% of patients discontinued cotrimoxazole preventive therapy due to different reasons. CONCLUSIONS: In most patients cotrimoxazole preventive therapy was consistent with the national guideline regarding the rationale for indication, dose, discontinuation and its use in the presence of contraindications.