Ethyl Gallate: Promising Cytoprotective against HIV-1-Induced Cytopathy and Antiretroviral-Induced Cytotoxicity.

Introduction: HIV-1 infection in cell culture is typically characterized by certain cytopathic effects such as vacuolization of cells and development of syncytia, which further lead to cell death. In addition, the majority of drugs during HIV treatment exhibit serious adverse effects in patients, apart from their beneficial role. During the screening of cytoprotective agents to protect the cells from HIV-1-associated cell death and also drug-associated toxicity, antioxidants from a natural source are assumed to be a choice. A well-known antioxidant, ethyl gallate (EG), was selected for cytoprotection studies which have already been proven as an anti-HIV agent. Objective: The main objective of the study was to explore the cytoprotective potential of EG against HIV-1-induced cytopathic effect and antiretroviral drug toxicity. Methods: DPPH free radical scavenging assay was performed with EG to find the effective concentration for antioxidant activity. HIV-1infection-associated cytopathic effects and further rescue by EG were studied in MT-2 lymphocytes by the microscopic method and XTT cytopathic assays. The cellular toxicity of different antiretroviral drugs in different cell lines and the consequent cytoprotective effectiveness of EG were investigated using an MTT cell viability assay. Results: Like ascorbic acid, EG exhibited promising antioxidant activity. HIV-1 infection of MT2 cells induces cell death often referred to as the cytopathic effect. In addition, the usage of antiretroviral drugs also causes severe adverse effects like cytotoxicity. In this context, EG was tested for its cytoprotective properties against HIV-1-induced cytopathic effect and drug-mediated cellular toxicity. EG reclaimed back the MT2 cells from HIV-1-induced cell death. Antiretroviral drugs, such as ritonavir, efavirinz, AZT, and nevirapine, were tested for their toxicity and induced more cell death at higher concentrations in different tissue models such as the liver (THLE-3), lung (AEpiCM), colorectal (HT-29), and brain (U87 MG). Pretreated cells with EG were rescued from the toxic doses of ART. Conclusion: EG was found to be exhibited cytoprotection not only from HIV-1-linked cell death but also from the chemotoxicity of antiretroviral drugs. Evidently, EG could be a cytoprotective supplement in the management of AIDS along with its enormous antioxidant benefits.

Reducing Vancomycin Use in a Level IV NICU.

BACKGROUND AND OBJECTIVES: Vancomycin remains one of the most commonly prescribed antibiotics in NICUs despite recommendations to limit its use for known resistant infections. Baseline data revealing substantially higher vancomycin use in our NICU compared to peer institutions informed our quality improvement initiative. Our aim was to reduce the vancomycin prescribing rate in neonates hospitalized in our NICU by 50% within 1 year and sustain for 1 year. METHODS: In the 60-bed level IV NICU of an academic referral center, we used a quality improvement framework to develop key drivers and interventions including (1) physician education with benchmarking antibiotic prescribing rates; (2) pharmacy-initiated 48-hour antibiotic time-outs on rounds; (3) development of clinical pathways to standardize empirical antibiotic choices for early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis; coupled with (4) daily prospective audit with feedback from the antimicrobial stewardship program. RESULTS: We used statistical process u-charts to show vancomycin use declined from 112 to 38 days of therapy per 1000 patient-days. After education, pharmacy-initiated 48-hour time-outs, and development of clinical pathways, vancomycin use declined by 29%, and by an additional 52% after implementation of prospective audit with feedback. Vancomycin-associated acute kidney injury also declined from 1.4 to 0.1 events per 1000 patient-days. CONCLUSIONS: Through a sequential implementation approach of education, standardization of care with clinical pathways, pharmacist-initiated 48-hour time-outs, and prospective audit with feedback, vancomycin days of therapy declined by 66% over a 1-year period and has been sustained for 1 year.

Anti-Ulcerative Effect of Curcumin-Galactomannoside Complex on Acetic Acid-Induced Experimental Model by Inhibiting Inflammation and Oxidative Stress.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.

"Because Even the Person Living With HIV/AIDS Might Need to Make Babies" - Perspectives on the Drivers of Feasibility and Acceptability of an Integrated Community Health Worker Model in Iringa, Tanzania.

BACKGROUND: Countries with health workforce shortages are increasingly turning to multipurpose community health workers (CHWs) to extend integrated services to the community-level. However, there may be tradeoffs with the number of tasks a CHW can effectively perform before quality and/or productivity decline. This qualitative study was conducted within an existing program in Iringa, Tanzania where HIV-focused CHWs working as volunteers received additional training on maternal, newborn, and child health (MNCH) promotion, thereby establishing a dual role CHW model. METHODS: To evaluate the feasibility and acceptability of the combined HIV/MNCH CHW model, qualitative in-depth interviews (IDIs) with 36 CHWs, 21 supervisors, and 10 program managers were conducted following integration of HIV and MNCH responsibilities (n=67). Thematic analysis explored perspectives on task planning, prioritization and integration, workload, and the feasibility and acceptability of the dual role model. Interview data and field observations were also used to describe implementation differences between HIV and MNCH roles as a basis for further contextualizing the qualitative findings. RESULTS: Perspectives from a diverse set of stakeholders suggested provision of both HIV and MNCH health promotion by CHWs was feasible. Most CHWs attempted to balance HIV/MNCH responsibilities, although some prioritized MNCH tasks. An increased workload from MNCH did not appear to interfere with HIV responsibilities but drew time away from other income-generating activities on which volunteer CHWs rely. Satisfaction with the dual role model hinged on increased community respect, gaining new knowledge/skills, and improving community health, while the remuneration-level caused dissatisfaction, a complaint that could challenge sustainability. Conclusions: Despite extensive literature on integration, little research at the community level exists. This study demonstrated CHWs can feasibly balance HIV and MNCH roles, but not without some challenges related to the heavier workload. Further research is necessary to determine the quality of health promotion in both HIV and MNCH domains, and whether the dual role model can be maintained over time among these volunteers.

Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and anti-arthritic activity in experimental arthritic model. CB as an anti-arthritic drug has beneficial effect for treating inflammation, tissue damage and pain associated with arthritis.

Orientation effect induced selective chelation of Fe2+ to a glutamic acid appended conjugated polymer for sensing and live cell imaging.

Intracellular detection and imaging of labile iron(ii) pools is very important in tracking physiological processes that demand new and rapid sensing probes. In this report, we present a water soluble polymer based probe for the fluorescence sensing and live cell imaging of labile Fe2+ ions with high selectivity for the first time. The polymer probe was based on conjugated polyfluorene which was appended with amino acid (l-glutamic acid). The biocompatibility of the polymer was confirmed from an MTT assay which demonstrated >90% cell viability even at 300 µg ml-1 loading of polymers. Simple glutamic acid did not show selectivity towards any of the divalent ions. However, glutamic acid appended polyfluorene exhibited selective chelation to Fe2+ ions resulting in immediate sensing activity for Fe2+ ions in water and living cells with fluorescence turn-off response. The limit of detection of the PF-Ph-GA polymer probe was 46 (±2) nM which indicated high sensitivity for Fe2+ over other ions reported in the literature. The polymer also exhibited improved sensing activity in the range of intracellular pH (5-9) which is advantageous in differentiating endogenous changes. The probe was successfully applied for the fluorescence imaging of intracellular and supplemented labile iron(ii) pools in living HeLa cells.

Supply-side dimensions and dynamics of integrating HIV testing and counselling into routine antenatal care: a facility assessment from Morogoro Region, Tanzania.

BACKGROUND: Integration of HIV into RMNCH (reproductive, maternal, newborn and child health) services is an important process addressing the disproportionate burden of HIV among mothers and children in sub-Saharan Africa. We assess the structural inputs and processes of care that support HIV testing and counselling in routine antenatal care to understand supply-side dynamics critical to scaling up further integration of HIV into RMNCH services prior to recent changes in HIV policy in Tanzania. METHODS: This study, as a part of a maternal and newborn health program evaluation in Morogoro Region, Tanzania, drew from an assessment of health centers with 18 facility checklists, 65 quantitative and 57 qualitative provider interviews, and 203 antenatal care observations. Descriptive analyses were performed with quantitative data using Stata 12.0, and qualitative data were analyzed thematically with data managed by Atlas.ti. RESULTS: Limitations in structural inputs, such as infrastructure, supplies, and staffing, constrain the potential for integration of HIV testing and counselling into routine antenatal care services. While assessment of infrastructure, including waiting areas, appeared adequate, long queues and small rooms made private and confidential HIV testing and counselling difficult for individual women. Unreliable stocks of HIV test kits, essential medicines, and infection prevention equipment also had implications for provider-patient relationships, with reported decreases in women's care seeking at health centers. In addition, low staffing levels were reported to increase workloads and lower motivation for health workers. Despite adequate knowledge of counselling messages, antenatal counselling sessions were brief with incomplete messages conveyed to pregnant women. In addition, coping mechanisms, such as scheduling of clinical activities on different days, limited service availability. CONCLUSION: Antenatal care is a strategic entry point for the delivery of critical tests and counselling messages and the framing of patient-provider relations, which together underpin care seeking for the remaining continuum of care. Supply-side deficiencies in structural inputs and processes of delivering HIV testing and counselling during antenatal care indicate critical shortcomings in the quality of care provided. These must be addressed if integrating HIV testing and counselling into antenatal care is to result in improved maternal and newborn health outcomes.

Program synergies and social relations: implications of integrating HIV testing and counselling into maternal health care on care seeking.

BACKGROUND: Women and children in sub-Saharan Africa bear a disproportionate burden of HIV/AIDS. Integration of HIV with maternal and child services aims to reduce the impact of HIV/AIDS. To assess the potential gains and risks of such integration, this paper considers pregnant women's and providers' perceptions about the effects of integrated HIV testing and counselling on care seeking by pregnant women during antenatal care in Tanzania. METHODS: From a larger evaluation of an integrated maternal and newborn health care program in Morogoro, Tanzania, this analysis included a subset of information from 203 observations of antenatal care and interviews with 57 providers and 190 pregnant women from 18 public health centers in rural and peri-urban settings. Qualitative data were analyzed manually and with Atlas.ti using a framework approach, and quantitative data of respondents' demographic information were analyzed with Stata 12.0. RESULTS: Perceptions of integrating HIV testing with routine antenatal care from women and health providers were generally positive. Respondents felt that integration increased coverage of HIV testing, particularly among difficult-to-reach populations, and improved convenience, efficiency, and confidentiality for women while reducing stigma. Pregnant women believed that early detection of HIV protected their own health and that of their children. Despite these positive views, challenges remained. Providers and women perceived opt out HIV testing and counselling during antenatal services to be compulsory. A sense of powerlessness and anxiety pervaded some women's responses, reflecting the unequal relations, lack of supportive communications and breaches in confidentiality between women and providers. Lastly, stigma surrounding HIV was reported to lead some women to discontinue services or seek care through other access points in the health system. CONCLUSION: While providers and pregnant women view program synergies from integrating HIV services into antenatal care positively, lack of supportive provider-patient relationships, lack of trust resulting from harsh treatment or breaches in confidentiality, and stigma still inhibit women's care seeking. As countries continue rollout of Option B+, social relations between patients and providers must be understood and addressed to ensure that integrated delivery of HIV counselling and services encourages women's care seeking in order to improve maternal and child health.

Dibenzazepin hydrochloride as a new spectrophotometric reagent for determination of hydrogen peroxide in plant extracts.

A rapid, simple, accurate, and sensitive visible spectrophotometric method for the determination of trace amounts of hydrogen peroxide in acidic buffer medium is reported. The proposed method is based on the oxidative coupling of Ampyrone with dibenzazepin hydrochloride by hydrogen peroxide in the buffer medium of pH 4.0 which is catalyzed by ferrous iron. The blue-colored product formed with maximum absorption at 620 nm was found to be stable for 2 h. Beer's law is obeyed for hydrogen peroxide concentration in the range of 0.03-0.42 µg ml(-1). The optimum reaction conditions and other important optical parameters are reported. The molar absorptive and Sandell's sensitivity are found to be 5.89 × 10(4) mol(-1) cm(-1) and 0.57 g/cm(2), respectively. The interference due to diverse ions and complexing agents was studied. The method is successfully applied to the determination of hydrogen peroxide in green plants satisfactorily.

Evidence-based reproductive health care in Cameroon: population-based study of awareness, use and barriers.

OBJECTIVE: To estimate the prevalence of awareness and use of evidence-based reproductive health interventions and to describe the barriers associated with the use of evidence-based interventions among health providers in north-west Cameroon. METHODS: In February 2004, a population-based descriptive study of the awareness and use of 13 evidence-based interventions targeted health workers providing reproductive health care. Their awareness and use of a composite of four vital interventions was also evaluated. These were peripartum use of antiretrovirals to prevent transmission of HIV, antenatal corticosteroid administration, magnesium sulfate prophylaxis and active management of placental delivery with uterotonics. In-depth interviews with key informants were conducted as part of a qualitative substudy to discover the barriers to the use of evidence-based interventions. FINDINGS: Overall, 91.4% (328/359) of reproductive health workers were surveyed. Their awareness of evidence-based interventions varied from 29% for the use of antenatal corticosteroids to 97% for the use of iron and folic acid supplementation during pregnancy. Their use of these interventions ranged from 10.2% for antenatal corticosteroids to 94.8% for iron and folic acid supplementation. Only 50/322 (15.5%; 95% confidence interval (CI)=11.8-20.0) of health workers were aware of all four vital interventions, and only 12/312 (3.8%; 95% CI=2.0- 6.6) reported using all of them regularly. A total of 26 key informants participated in the qualitative substudy. A deficiency in the education and training of health workers, especially a lack of continuing education, was commonly identified as the most important barrier to their awareness of evidence-based practices. A lack of awareness and a lack of supplies and materials were the main barriers to practice. CONCLUSION: The awareness and practice of important evidence-based reproductive health interventions were less than optimal. To improve maternal and perinatal outcomes both remedial programmes to enhance awareness, including continuing education for health workers, and the provision of necessary supplies are needed.

Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.