EP2 receptor mediated cAMP release is augmented by PGF2α activation of the FP receptor via the calcium-calmodulin pathway

Prostaglandins exert their effects on target cells by coupling to specific G protein-coupled receptors (GPCRs) that are often co-expressed in the same cells and use alternate and in some cases opposing intracellular signaling pathways. This study investigated the cross-talk that influences intracellular signaling and gene expression profiling in response to co-activation of the EP2 and FP prostanoid receptors in Ishikawa cells stably expressing both receptors (FPEP2 cells). In this study we show that in FPEP2 cells, PGF alone does not alter adenosine 3′,5′-cyclic monophosphate (cAMP) production, but in combination with Butaprost enhances EP2 receptor mediated cAMP release compared to treatment with Butaprost alone. PGF-mediated potentiation of cAMP release was abolished by antagonism of the FP receptor, inhibition of phospholipase C (PLC) and inositol phosphate receptor (IP3R) whereas inhibition of protein kinase C (PKC) had no effect. Moreover, inhibition of calcium effectors using calmodulin antagonist (W7) or Ca²⁺/calmodulin-dependent kinase II (CaMK-II) inhibitor (KN-93) abolished PGF potentiation of Butaprost-mediated cAMP release. Using siRNA molecules targeted against the adenylyl cyclase 3 (AC3) isoform, we show that AC3 is responsible for the cross-talk between the FP and EP2 receptors. Using gene array studies we have identified a candidate gene, Spermidine/N1-acetyltransferase (SAT1), which is regulated by this cAMP mediated cross-talk. In conclusion, this study demonstrates that co-activation of the FP and EP2 receptors results in enhanced release of cAMP via FP receptor-Gα_q-Ca²⁺-calmodulin pathway by activating calcium sensitive AC3 isoform.     

An ethnobotanical study of medicinal plants used in Kilte Awulaelo District,Tigray Region of Ethiopia

Background

The Ethiopian people have been dependent on traditional medicine, mainly medicinal plants, from time immemorial for control of human and animal health problems, and they still remain to be largely dependent on the practice. The purpose of the current study was to conduct ethnobotanical study to document medicinal plants used to treat diseases of human and domestic animals in Kilte Awulaelo District in the Tigray Region of Ethiopia.

Methods

Ethnobotanical data were collected between July and September 2011 through semi-structured interviews, ranking exercises and field observations. For the interviews, 72 knowledgeable informants were sampled using purposive sampling method. For the different ranking exercises, key informants were identified with the help of elders and local administrators from informants that were already involved in the interviews.

Results

The study revealed 114 medicinal plant species belonging to 100 genera and 53 families. The plants were used to treat 47 human and 19 livestock diseases. Of the species, the majority (74%) were obtained from the wild. Herbs were the most utilized plants, accounting for 44% of the species, followed by shrubs (29%). Leaf was the most commonly used plant part accounting for 42.98% of the plants, followed by roots (25.73%). Preference ranking exercise on selected plants used against abdominal pain indicated the highest preference of people for Solanum marginatum. Direct matrix ranking showed Cordia africana as the most preferred multipurpose plant in the community. Preference ranking of selected scarce medicinal plants indicated Myrica salicifolia as the most scarce species, followed by Boscia salicifolia and Acokanthera schimperi. According to priority ranking, drought was identified as the most destructive factor of medicinal plants, followed by overgrazing and firewood collection.

Conclusion

Medicinal plants are still playing significant role in the management of various human and livestock diseases in the study area with herbs taking the lead in the number of plants used in the preparation of remedies, which may be an indication of their relatively better abundance as compared to other life forms. Recurrent drought was reported to have seriously threatened medicinal plant resources in the District. Awareness is thus needed be raised among local people on sustainable utilization and management of plant resources. Ex situ and in situ conservation measures should be taken to protect the medicinal plants of the District from further destruction and special attention should be given to the medicinal plants that were indicated by preference ranking exercise as the most threatened ones.

     

Effect of mustard green manure and dried plant residue on chickpea wilt (Fusarium oxysporum f.sp. ciceris)

Pot experiments were carried out in the green house at Amhara Regional Agriculture Research Institute (ARARI) Bahirdar, Ethiopia, to evaluate the potential of Brassica carinata cultivars, namely Holleta-l, S-67 and Yellow Dodola in 2007 and 2008. The effect of B. carinata (Ethiopian mustard) cultivars Holleta-1, S-67 and Yellow Dodola as green manure and Holleta-1 as dried plant residue on chickpea fusarium wilt (Fusarium oxysporum f.sp. ciceris) was studied. Six rates of green manure and dried plant residue (0, 20, 40, 60, 80 and 100 g) each per kg of pathogen-infested soil were used in the experiments. Infested soil without B. carinata cultivars amendment as a control and susceptible check variety JG-62 without amendment was used in the experiments. In the experiments, the treatments were arranged in randomised complete block design in three replications and repeated twice. Data on seedling emergence, wilt incidence, fresh weight and dry weight were collected. The amendments of infested soil with B. carinata cultivars green manure and dried plant residue reduced the incidence of chickpea fusarium wilt. The incorporation of the green manure Holleta-1, S-67 and Yellow Dodola at 20–100 g/kg of infested soil was effective in reducing wilt incidences on chickpea. However, the incorporation of Yellow Dodola at 80 and 100 g green manure per kg of infested soil were the best combination in reducing significantly wilt incidence. The application of the dried plant residue at 20–100 g/kg of infested soil was effective in reducing wilt incidences on chickpea. However when applied dried plant residue at 60, 80 and 100 g green manure per kg of infested soil were better in reducing wilt incidence as compared to 20 and 40 g/kg of infested soil. The three cultivars green manure incorporated at different level of doses affected the influence of fusarium wilt on the fresh and dry weight respectively. The use of Holleta-1 green manure at 20–100 g/kg of infested soil significantly reduced disease incidence in the range of 20.0–33.3%. Green manure amendment S-67 significantly reduced disease incidence in the range of 20.0–46.6%. Yellow Dodola reduce disease incidence with 26.7–60%. The dried plant residue incorporated at different level influence fusarium wilt. The application of Holleta-1 dried plant residue at 20–100 g/kg of infested soil reduced disease incidence in the range 20.0–26.7%. The results imply the potential of using B. carinata green manure and dried plant residue as cultural management components in chickpea fusarium wilt disease management.     

High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease

IntroductionIntramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are key knowledge gaps for RHD control.MethodsTo evaluate BPG pharmacokinetics (PK) in patients receiving 4-weekly doses in Ethiopia, we conducted a prospective cohort study of ARF/RHD patients attending cardiology outpatient clinics. Serum samples were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time datasets for BPG were analyzed by nonlinear mixed effects modelling using NONMEM.ResultsA total of 190 penicillin concentration samples from 74 patients were included in the final PK model. The median age, weight, BMI was 21 years, 47 kg and 18 kg/m², respectively. When compared with estimates derived from Indigenous Australian patients, the estimate for median (95% confidence interval) volume of distribution (V/F) was lower (54.8 [43.9–66.3] l.70kg^-1) whilst the absorption half-life (t_1/2-abs2) was longer (12.0 [8.75–17.7] days). The median (IQR) percentage of time where the concentrations remained above 20 ng/mL and 10 ng/mL within the 28-day treatment cycle was 42.5% (27.5–60) and 73% (58.5–99), respectively.ConclusionsThe majority of Ethiopian patients receiving BPG as secondary prophylaxis to prevent RHD do not attain target concentrations for more than two weeks during each 4-weekly injection cycle, highlighting the limitations of current BPG strategies. Between-population variation, together with PK differences between different preparations may be important considerations for ARF/RHD control programs.     

Stunting Is Associated with Food Diversity while Wasting with Food Insecurity among Underfive Children in East and West Gojjam Zones of Amhara Region,Ethiopia

Background

Food insecurity has detrimental effects in protecting child undernutrition.This study sought to determine the level of child undernutrition and its association with food insecurity.

Methods

A community based comparative cross-sectional study design involving multistage sampling technique was implemented from 24^th of May to 20^th of July 2013. Using two population proportion formula, a total of 4110 randomly selected households were included in the study. Availability of the productive safety net programme was used for grouping the study areas. A multiple linear regression model was used to assess the association between food insecurity and child malnutrition. Clustering effects of localities were controlled during analysis.

Results

Stunting (37.5%), underweight (22.0%) and wasting (17.1%) were observed in East Gojjam zone, while 38.3% stunting, 22.5% underweight, and 18.6% wasting for the West Gojjam zone. Food insecurity was significantly associated with wasting (β = - 0.108, P < 0.05).Food diversity and number of meals the child ate per day significantly associated with stunting (β = 0.039, P < 0.01) and underweight (β = 0.035, P < 0.05) respectively. Residential area was the significant predictor of all indices.

Conclusion

The magnitude of child undernutrition was found to be very high in the study areas. Food insecurity was the significant determinant of wasting. Food diversity and number of meals the child ate per day were the significant determinants of stunting and underweight respectively. Child nutrition intervention strategies should take into account food security, dietary diversity, and carefully specified with regard to residential locations. Addressing food insecurity is of paramount importance.     

Childhood Diarrhea Exhibits Spatiotemporal Variation in Northwest Ethiopia: A SaTScan Spatial Statistical Analysis

Background

Childhood diarrhea continues to be a public health problem in developing countries, including Ethiopia. Detecting clusters and trends of childhood diarrhea is important to designing effective interventions. Therefore, this study aimed to investigate spatiotemporal clustering and seasonal variability of childhood diarrhea in northwest Ethiopia.

Methods

Retrospective record review of childhood diarrhea was conducted using quarterly reported data to the district health office for the seven years period beginning July 1, 2007. Thirty three districts were included and geo-coded in this study. Spatial, temporal and space-time scan spatial statistics were employed to identify clusters of childhood diarrhea. Smoothing using a moving average was applied to visualize the trends and seasonal pattern of childhood diarrhea. Statistical analyses were performed using Excel^® and SaTScan programs. The maps were plotted using ArcGIS 10.0.

Results

Childhood diarrhea in northwest Ethiopia exhibits statistical evidence of spatial, temporal, and spatiotemporal clustering, with seasonal patterns and decreasing temporal trends observed in the study area. A most likely purely spatial cluster was found in the East Gojjam administrative zone of Gozamin district (LLR = 7123.89, p <0.001). The most likely spatiotemporal cluster was detected in all districts of East Gojjam zone and a few districts of the West Gojjam zone (LLR = 24929.90, p<0.001), appearing from July 1, 2009 to June 30, 2011. One high risk period from July 1, 2008 to June 30, 2010 (LLR = 9655.86, p = 0.001) was observed in all districts. Peak childhood diarrhea cases showed a seasonal trend, occurring more frequently from January to March and April to June.

Conclusion

Childhood diarrhea did not occur at random. It has spatiotemporal variation and seasonal patterns with a decreasing temporal trend. Accounting for the spatiotemporal variation identified in the study areas is advised for the prevention and control of diarrhea.     

A fluorescence study of differently substituted 3‐styrylindoles and their interaction with bovine serum albumin

Interaction of 3‐styrylindoles 1–8 viz. 3‐(2‐phenylethenyl‐E)‐NH‐indole (1), 3‐[2‐(4‐nitrophenyl)ethenyl‐E]‐NH‐indole (2), 5‐bromo‐3‐[2‐(4‐nitrophenyl)ethenyl‐E]‐NH‐indole (3), 5‐methoxy‐3‐[2‐(4‐nitrophenyl)ethenyl‐E]‐NH‐indole (4), 3‐[2‐(4‐cyanophenyl)ethenyl‐E]‐NH‐indole (5), 3‐[2‐(4‐cyanophenyl)ethenyl‐E]‐N‐ethylindole (6), 5‐bromo‐3‐[2‐(4‐chlorophenyl)ethenyl‐E]‐NH‐indole (7) and 5‐methoxy‐3‐[2‐(4‐chlorophenyl)ethenyl‐E]‐NH‐indole (8) with bovine serum albumin (BSA) was examined by UV–vis and steady‐state fluorescence spectroscopy. The fluorescence intensity of 1–8 increases with the increasing BSA concentration. Upon binding with BSA, while 1 and 5–8 show a blue shift in their λ_{f max}, 2–4 do not exhibit such behavior. Compounds 1–8 also quench the 345 nm fluorescence of BSA in phosphate buffer (λ_ex, 280 nm). These compounds intercalate in the hydrophobic regions of BSA, as evidenced by the determination of BSA binding site micropolarity using compounds 2–8. As evidenced by the estimation of energy transfer efficiency and distance between the donor (BSA‐Trp‐212) and the acceptor (3‐styrylindoles), the halo‐substituted compounds 3 and 7 interact with BSA more effectively than the other 3‐strylindoles. These compounds have potential for use as neutral and hydrophobic fluorescence probes for examining the microenvironments in proteins, polymers, micelles, etc. Copyright © 2008 John Wiley & Sons, Ltd.     

Film mulch with irrigation and rainfed cultivations improves maize production and water use efficiency in Ethiopia

Improving productivity of maize (Zea mays L.) and water use efficiency is of great significance for agriculture in Ethiopia. In this study, the effects of ridge‐furrow with film mulch cultivation were tested on maize yields in Melkassa, Ethiopia. Three field experiments (drip irrigation, furrow irrigation and rainfed) were conducted each with randomised complete block design with three replicates. The drip irrigation experiment was conducted in the dry season and constituted three film mulch methods (non‐mulch, transparent film mulch and black film mulch) with three irrigation levels (357, 435 and 515 mm). The furrow irrigation experiment was also conducted in the dry season and constituted two film mulches (non‐mulch and transparent film mulch) with three irrigation levels (484, 674 and 865 mm). The rainfed experiment was conducted in the rainy season and constituted three mulches (non‐mulch, transparent film mulch and black film mulch) with two farming methods (ridge‐furrow farming and flat farming). In the drip irrigation experiment, the highest maize yields (5.9 ± 0.6 t ha^?1) and irrigation water use efficiency (9.6 ± 1 kg ha^?1 mm^?1) were recorded in the treatment using black film mulch with high irrigation, with increases of 68% and 68.4% compared to using non‐mulch treatment at that irrigation level. In the furrow irrigation experiment, maize yields and irrigation water use efficiency reached 7 (± 0.8) t ha^?1 and 9.1 (± 1.9) kg ha^?1 mm^?1 in the treatment using transparent film mulch with medium irrigation (674 mm), with increases of 46% and 46.8% compared to that with non‐mulch treatment. In the rainfed experiment, the film mulch rather than farming method had positive effects on the maize yields and rainwater use efficiency. The average maize yield reached 8.5 (± 0.7) t ha^?1 in the film mulch treatments, with an increase of 39% than using the non‐mulch treatment. Compared with that of non‐mulch treatment, the net income in the film mulch treatments increased by 94% in the furrow experiment and 31% in the rainfed experiment. Our results indicate that the ridge‐furrow with film mulch system can be recommended for water‐saving irrigation with low cost in dry seasons, and film mulch with flat farming can be recommended in rainy seasons for maize production in Ethiopia. This study provides strong evidence that maize productivity can be effectively improved in Ethiopia and other similar areas of the world using this simple and cost‐effective technology.