Memory deficits associated with khat (Catha edulis) use in rodents.

Khat products and chewing practices are common in East Africa, Middle East for centuries with concomitant socio-economic and public health repercussions. We assessed memory deficits associated with khat use in rodents. Young male CBA mice, 5-7 weeks old (n = 20), weighing 25-35 g were used. Mice were treated with either 40, 120 or 360 mg/kg body weight (bw) methanolic khat extract, or 0.5 ml saline for 10 days. Spatial acquisition, reversal and reference memory were assessed using modified Morris Water maze (MMWM). Mice treated with 40 mg/kg khat extract had longer (t4 = 4.12 p = 0.015) and t4 = 2.28 p = 0.065) escape latency on first and second day during reversal relative to the baseline. Under 120 mg/kg khat dose, the escape latency was shorter (t4 = -2.49 p = 0.05) vs (t3 = -2.5 p = 0.05) on third and fourth day. Further, treatment with 360 mg/kg khat extract resulted in significantly longer time (49.13, 33.5, 40.2 and 35.75) vs. (23.5 s), compared to baseline. Mice treated with khat or control preferred the target quadrant post acquisition while differential pattern was seen during reversal phase. Mice treated with 40 or 120 mg/kg khat showed significant preference for target quadrant. Substantial time (19.9) was spent in the old target compared to the new (16.9 s) by animals treated with highest dose however, the difference was not significant. There is a biological plausibility that chronic khat use may induce memory deficits and impair cognitive flexibility. The differential patterns of memory deficits may reflect the differences in dose effect as well as time dependent impairment.

Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.

Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 µl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05) and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01) and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy.

BACKGROUND: Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target. METHODS: Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC). RESULTS: Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 mM) or lonidamine (300 µM) with 10 J cm(-2) 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA. CONCLUSION: As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PDT.

Implementing intensified tuberculosis case-finding among street-connected youth and young adults in Kenya.

BACKGROUND: Street-connected youth and young adults (SCY) suffer a myriad of health problems. In Kenya, SCY are at high risk for tuberculosis (TB) due to their congregate living situations. TB screening is not routinely implemented in SCY and there has been no published literature on the burden of TB in SCY in western Kenya. PROGRAM DESCRIPTION: In 2011, the AMPATH TB Program, an experienced TB screening program, partnered with the Tumaini Center, a trusted street youth organization, to conduct intensified case finding (ICF) for pulmonary TB among SCY. Our program aimed to investigate the numbers of SCY who reported symptoms and those diagnosed with smear-positive pulmonary TB, and link SCY with TB to treatment. RESULTS: Of 116 SCY who were screened, 114 (98%) had a positive questionnaire; 104 (90%) provided a spot sputum sample, 39 (34%) provided a morning sputum sample, and 111 (97%) reported cough of >2 weeks. One street youth tested smear-positive for TB and was treated through to cure. CONCLUSIONS: Implementing TB ICF is feasible in low-resource settings through unique collaborations between health care programs and community-based organizations. In addition to identifying smear-positive TB, our program uncovered a high burden of respiratory symptoms among SCY in Eldoret, Kenya.

Contexte : Les jeunes et les adultes vivant dans la rue (SCY) souffrent d'une myriade de problèmes de santé. Au Kenya, les SCY ont un risque élevé de tuberculose (TB) à cause de la promiscuité de leur habitat. Le dépistage de la TB n'est pas mis en œuvre en routine parmi les SCY et il n'y a eu aucune littérature publiée sur le poids de la TB chez les SCY de l'ouest du Kenya.Description du programme : En 2011, le programme TB AMPATH, un programme de dépistage de TB expérimenté, a établi un partenariat avec le Tumaini Center, une organisation fiable de jeunes de la rue, afin de réaliser une recherche de cas intensifiée (ICF) de la TB pulmonaire parmi les SCY. Notre programme a eu pour but de rechercher le nombre de SCY qui présentaient des symptômes et ceux qui ont eu un diagnostic de TB pulmonaire à frottis positif, et enfin de mettre en contact les SCY avec un site de traitement de la TB.Résultats : De 116 SCY qui ont été dépistés, 114 (98%) ont remis un questionnaire positif, 104 (90%) ont fourni un échantillon de crachats, 39 (34%) un échantillon matinal et 111 (97%) ont fait état d'une toux de >2 semaines. Un jeune de la rue a eu un frottis positif pour la TB et a été traité avec succès.Conclusions: La mise en œuvre de l'ICF de TB est faisable dans un contexte de faibles ressources à travers une unique collaboration entre les programmes de soins de santé et les organisations communautaires. En plus d'identifier la TB à frottis positif, notre programme a révélé un lourd fardeau de symptômes respiratoires parmi les SCY d'Eldoret, au Kenya.

Marco de referencia: Los jóvenes y los adultos jóvenes en situación de calle (SCY) sufren de una miríada de problemas de salud. En Kenia, los SCY tienen un alto riesgo de contraer la tuberculosis (TB), dada la situación de su convivencia. La detección de la TB no se practica de manera sistemática en esta población y no existen publicaciones científicas sobre la carga de morbilidad por TB en los SCY en el oeste de Kenia.Descripción del programa: En el 2011, el Programa TB AMPATH, un programa con experiencia en la detección sistemática de la TB, creó una alianza con el Tumaini Center, que es una organización reconocida que se ocupa de los SCY; su objetivo fue realizar una búsqueda intensiva de casos de TB pulmonar en esta población de jóvenes. El presente estudio tuvo por objeto investigar el número de SCY que refirieron síntomas y la cantidad de casos de TB pulmonar con baciloscopia positiva que se diagnosticaron, y vincular los SCY diagnosticados con los centros de tratamiento.Resultados: Se practicó la detección sistemática en 116 SCY, de los cuales 114 tuvieron un cuestionario positivo (98%), 104 aportaron una muestra inmediata de esputo (90%) y 39 una muestra de esputo matinal (34%). De los SCY, 111 refirieron tos de >2 semanas de duración (97%). Un joven tuvo una baciloscopia de esputo positiva y recibió tratamiento hasta su curación.Conclusión: La ejecución de una búsqueda intensiva de casos de TB es factible en los entornos de bajos recursos, por conducto de colaboraciones especiales entre los programas de atención de salud y las organizaciones comunitarias. Además de detectar los casos de TB bacilífera, el programa reveló una alta carga de morbilidad por síntomas respiratorios en los SCY en la ciudad de Eldoret, en Kenia.

Involvement of a community in schistosomiasis control: a Kenyan experience.

This paper illustrates how community participation was achieved in a study that was carried out between 1983-1988 whose general objective was to reduce the transmission of schistosomiasis in a rice irrigation scheme in Kenya. A community of 2,219 people was mobilized through health education, to effect changes in behaviour regarding water contact, water use and faecal disposal. Health education, alternative water sources, latrines and mass chemotherapy with praziquantel were the schistosomiasis control strategies utilized in this study. By the end of 2 years, the canals were cleared of their thick vegetation, water, sanitation, bathing and washing facilities were constructed, water contact with infective waters was reduced, faecal contamination of water was reduced, the people's knowledge on schistosomiasis increased and the rate and intensity of schistosomiasis infection was reduced. The study demonstrated that it is possible to fully involve the community in disease control efforts.

Pattern of Schistosoma mansoni infection after intervention in Mwea irrigation scheme in Kenya.

A longitudinal study of Schistosoma mansoni reinfection rate was carried out in an endemic area of Kenya, after intervention. Intervention measures applied involved chemotherapy, community mobilization to effect change in water contact habits and faecal disposal. This paper focuses on S. mansoni reinfection pattern over a two-year period. The age group 5-19 years showed an increasing trend of reinfection as compared to the 30-59 years age group. More than 50% in the 5-19 year age group had been reinfected by twelve months of follow-up. They were also responsible of 91% of all the egg-load and 83% of all the infections at the end of the study period. Since majority of the 5-19 year age group comprises school children, there is an urgent need of including issues related to schistosomiasis in the school curriculum especially in the endemic areas.

PIP: Schistosomiasis is a parasitic disease caused by blood flukes which live in the mesenteric and/or vesical veins of humans over a life span of several years. Cercariae are released by infected intermediate snail hosts into fresh water whose larvae then penetrate the skin of man when the individual contacts infected fresh water. Schistosomiasis is debilitating, setting in slowly and causing concern in its chronic stages. Chronic infection results in complications such as liver fibrosis and portal hypertension for Schistosoma mansoni and ureteric obstruction, bacterial infection, and cancer of the bladder for S. haematobium. In endemic areas, children have the highest prevalence and intensity of infection due to their more extensive contact with water relative to adults. Chemotherapy helps to control the disease, but population immigration, untreated pregnant women and very young children, and the selectiveness of control strategies make reinfection inevitable. This paper reports findings on the rate of reinfection with S. mansoni in Kirinyaga district, Kenya, between September 1983 and December 1988, after a prevention and control intervention. Schistosomiasis is endemic in that area of Kenya. Measures applied during the intervention included chemotherapy and community mobilization to effect change in water contact habits and faecal disposal. Individuals aged 5-19 years showed an increasing trend of reinfection compared to individuals aged 30-59 years, with more than 50% of subjects in the 5-19 year old age group being reinfected by twelve months of follow-up. The young age group also accounted for 91% of the egg-load and 83% of all infections at the end of the study period. The majority of the 5-19 year old age group comprises school children. An urgent need therefore exists to cover schistosomiasis-related issues in schools.

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one µmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC.