The role of Cdc42 Rho GTPase in the cystic fibrosis intestinal epithelial barrier

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. People with CF and CF mouse models experience increased intestinal permeability, but the molecular mechanisms linking CFTR dysfunction with intestinal barrier dysfunction are not well understood. Previously, we demonstrated that intracellular pH (pHi) is increased in Cftr KO mouse intestinal epithelium compared to wild-type (WT). Loss of Cftr-mediated Cl- and HCO3- conductance increased pHi and Dishevelled (Dvl)-mediated Wnt/β-catenin signaling and intestinal stem cell proliferation. Dvl also transduces the noncanonical Wnt/planar cell polarity (PCP) signaling pathway to activate the Rho GTPases RhoA, Rac1, and Cdc42 to regulate the cytoskeleton and tight junction remodeling during cell proliferation and migration. We hypothesized that Dvl-mediated transduction of the Wnt/PCP pathway in CF would lead to increased tight junction remodeling and paracellular permeability. In this study, we show that Cftr KO mouse enteroids have increased paracellular permeability in vitro, but not CFTR KO Caco-2 monolayers when compared to WT. Regardless, Cdc42 activity is increased in CF to maintain barrier function in the hyperproliferative CF intestinal epithelium.Includes bibliographical references

Anti-inflammatory and antioxidant properties of the root extract of Carissa edulis (forsk.) Vahl (apocynaceae)

Root extracts of Carissa edulis (Forsk.) Vahl (Apocynaceae) are used for the treatment several pathological states including inflammatory disorders. The present study was undertaken to evaluate the effect of an alcoholic extract of C. edulis (CEE) on carrageenan-induced foot oedema in chicks. Also since free radicals and reactive oxygen species are implicated in inflammatory diseases, the anti-oxidant potential of extract was investigated in in vitro experimental models. Oral administration of CEE (30- 300 mg kg-1 p.o.) significantly inhibited carrageenan-induced foot oedemas with a maximal inhibition of 53.8±8.2%. Similarly, the NSAID diclofenac (10-100 mg kg-1, i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3-3 mg kg-1, i.p ) reduced the total oedema with a maximal inhibition of 62.7±9.1% and 66.4±7.8% respectively. The extract also scavenged DPPH and prevented lipid peroxidation in rat brain homogenates. These results suggest that alcoholic extract of C. edulis exerts in vivo antiinflammatory activity after oral administration and also has antioxidant properties which may contribute to its activity.Journal of Science & Technology (Ghana) Vol. 27 (2) 2007: pp. 6-1

Adequacy of pain management in oncology patients at a tertiary hospital in Ghana

Background: Although cancer pain is well documented, efficient management is largely inadequate in most patients especially in developing countries. This study evaluated the adequacy of pain management as well as potential social factors that may be associated with inadequate pain management.Methods: 204 ambulatory oncology patients (82% female; mean age 53.5) attending clinic at the Oncology Directorate, of a tertiary hospital in Ghana from January to December, 2015 were recruited and their pain severity and functional interference assessed with the Brief Pain Inventory (BPI). The adequacy of pain management was computed as the pain management index (PMI) using the BPI.Results: Although 62% of respondents were prescribed high potency opioids, 56.9% of them exhibited significant pain while 34.9% required a stronger analgesic to manage their pain. Majority of patients (56%) were over-managed for their pain (had PMI score >0). Only 26.4% had optimal cancer pain management. Pain interfered mostly with patients’ sleep (46.2%) and general activity (42.5%). Patients with high pain intensity were more likely to have it affect their daily activity (P<0.0001). Men were more likely to have inadequate pain management than females.Conclusions: This study has shown that whereas pain management may be adequate, there is the tendency for opioid tolerance and abuse as over 50% of patients receive more analgesics than required. The tenets of the WHO 3-step analgesic ladder should be strictly adhered to achieve optimum cancer pain relief

Incidence of sexual dysfunction: a prospective survey in Ghanaian females

<p>Abstract</p> <p>Background</p> <p>Sexuality is a complex phenomenon that is being influenced by psychological as well as physiological factors. Its dysfunction includes desire, arousal, orgasmic and sex pain disorders. The present study aimed to assess the incidence of sexual dysfunction (SD) and related risk factors in a cohort of Ghanaian women.</p> <p>Method</p> <p>The Golombok Rust Inventory of Sexual Satisfaction (GRISS) was administered to 400 healthy women between 18 and 58 years old (mean +/- SD: 30.1 +/- 7.9) domiciled in the Kumasi metropolis.</p> <p>Results</p> <p>The response rate was 75.3% after 99 were excluded. Of the remaining 301 women, 50% were engaged in exercise, 26.7% indulge in alcoholic beverages and only 2% were smokers. A total of 62.1% of the women had attained high education, whilst, 28.9% were married. After logistic regression analysis, alcohol emerged (OR: 2.0; CI: 1.0 - 3.8; p = 0.04) as the main risk factor for SD. The overall prevalence of SD in these subjects was 72.8%. Severe difficulties with sexual function were identified in 3.3% of the studied population. The most prevalent areas of difficulty were anorgasmia (72.4%), sexual infrequency (71.4%), dissatisfaction (77.7%), vaginismus (68.1%), avoidance of sexual intercourse (62.5%), non-sensuality (61.5%) and non-communication (54.2%). Whereas 8% had severe difficulties with anorgasmia, only 6% had severe difficulties with vaginismus.</p> <p>Conclusion</p> <p>SD affects more than 70% of Ghanaian women who are sexually active. Alcohol significantly influences sexual activity.</p

Optimal conditions for ammonia leaching of copper/chalcocite-rimmed pyrite: Part 1

Oxidative ammoniacal leaching of copper/chalcocite-rimmed pyrite has been studied with the aim of searching for the optimal conditions for the separation of the pyrite that would preclude the formation of ammonium sulphate, the main drawback of the process. As the Redox Quotient (RQ) was varied, the resulting leached products were analyzed and the pH of the leached solution measured. At ambient temperature and a molar ratio of Cu:NH 3 = 1:4, it was observed that the amount of oxidant (H 2 O 2 ) supplied during the leaching process determines the maximum or minimum yield of copper. It has been found that the leaching process is most selective with respect to both copper and zinc when no external oxidant is supplied (RQ = 0). The optimum leaching of copper and zinc occurred at RQ = 2. It has been shown that at RQ = 8, no appreciable amounts of ammonium sulphate was formed and that the pH of the leached solutions, the yields of Cu and Zn, and the selectivity of the leaching process with respect to both Cu and Zn, are all periodic functions of the severity of the oxidation environment, as measured by RQ. It has also been demonstrated that even small deviations away from the maxima on the curves can significantly affect the process yield and selectivity negatively. This research showed that the more concentrated the leaching ammonia, the better the copper extraction and that it was more advantageous to do the extraction in multiple cycles in a single operation

Sintered alumina with low dielectric loss

Published versio

The need to address fragmentation and silos in mortality information systems: the case of Ghana and Peru

Objectives: We aimed to understand the information architecture and degree of integration of mortality surveillance systems in Ghana and Peru. Methods: We conducted a cross-sectional study using a combination of document review and unstructured interviews to describe and analyse the sub-systems collecting mortality data. Results: We identified 18 and 16 information subsystems with independent databases capturing death events in Peru and Ghana respectively. The mortality information architecture was highly fragmented with a multiplicity of unconnected data silos and with formal and informal data collection systems. Conclusion: Reliable and timely information about who dies where and from what underlying cause is essential to reporting progress on Sustainable Development Goals, ensuring policies are responding to population health dynamics, and understanding the impact of threats and events like the COVID-19 pandemic. Integrating systems hosted in different parts of government remains a challenge for countries and limits the ability of statistics systems to produce accurate and timely information. Our study exposes multiple opportunities to improve the design of mortality surveillance systems by integrating existing subsystems currently operating in silos

Varicella-zoster virus induces apoptosis in cell culture

peer reviewedaudience: researcherApoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis

A review of pharmacological effects of xylopic acid

Xylopic acid (15β-acetyloxy-kaur-16-en-19-oic acid) is a kaurene diterpene that can be obtained from various Xylopia spp. Xylopic acid has demonstrated several pharmacological activities in vitro and in vivo. The compound has shown promising effect as a potent analgesic, anti-inflammatory and anti-allergic agent. Xylopic acid is a CNS depressant and was able to ameliorate anxiety-like symptoms in mice in addition to its neuroprotective effects. Deleterious effects of xylopic acid on the reproductive system of mice have been well documented but extensive toxicity study detailing effect of the acid upon chronic exposure needs to be determined. Due to the heavy consumption of X. aethiopica fruits, it is recommended that the pharmacokinetics of xylopic acid be determined to ascertain the possible food-drug interaction that may occur when conventional drugs are taken together with foods containing xylopic acid

Understanding the barriers and facilitators to using self-sampling packs for sexually transmitted infections and blood-borne viruses : thematic analyses for intervention optimization

Purpose: Self-sampling packs for sexually transmitted infections (STIs) and blood-borne viruses (BBVs) are widely offered. There are ongoing problems with reach and sample return rates. The packs have arisen without formal intervention development. This paper illustrates initial steps of an intervention optimization process to improve the packs. Methods: Eleven focus groups and seven interviews were conducted with convenience samples of patients recruited from sexual health clinics and members of the public (n = 56). To enable intervention optimization, firstly, we conducted an inductive appraisal of the behavioural system of using the pack to understand meaningful constituent behavioural domains. Subsequently, we conducted a thematic analysis of barriers and facilitators to enacting each sequential behavioural domain in preparation for future behaviour change wheel analysis. Results: Overall, we found that self-sampling packs were acceptable. Participants understood their overall logic and value as a pragmatic intervention that simultaneously facilitated and reduced barriers to individuals being tested for STIs and BBVs. However, at the level of each behavioural domain (e.g., reading leaflets, returning samples) problems with the pack were identified, as well as a series of potential optimizations, which might widen the reach of self-sampling and increase the return of viable samples. Conclusions: This paper provides an example of a pragmatic approach to optimizing an intervention already widely offered globally. The paper demonstrates the added value health psychological approaches offer; conceptualizing interventions in behavioural terms, pinpointing granular behavioural problems amenable for systematic further improvement