Background The rapid expansion of the cut flower industry in Africa has led to pervasive use and potential exposure of pesticides, raising concerns for local communities. Whether the risks associated with pesticide applications are localised or have broader implications remains unclear. Methods We measured biomarkers of real and perceived pesticide exposure in two Kenyan communities: Naivasha, where the cut flower industry is present, and Mogotio, where the cut flower industry is absent. We measured real exposure by the percentage of acetylcholinesterase (AChE) inhibition and perceived exposure by assessing hair cortisol levels, a biomarker of stress. Additionally, we conducted a demographic survey to evaluate the health and socioeconomic status of participants, as well as their perceptions of pesticide risks associated with the cut flower industry. Results Perceived pesticide exposure was more common in Naivasha (n = 36, 56%) compared to Mogotio (n = 0, 0%), according to community surveys. However, Mogotio residents had significantly higher mean hair cortisol levels (mean ((x) over bar) = 790 ng/g, standard deviation (SD) = 233) and percentage of AChE inhibition ((x) over bar = 28.5%, SD = 7.3) compared to Naivasha residents, who had lower mean hair cortisol levels ((x) over bar = 548 ng/g, SD = 187) and percentage of AChE inhibition ((x) over bar = 14.5%, SD = 10.1). Location (proximity to cut flower farms) and gender were significant factors influencing pesticide exposure, with individuals living outside the cut flower industrial complexes being at higher risk. Women in both communities were the most vulnerable demographic, showing significantly higher mean hair cortisol levels ((x) over bar= 646 ng/g, SD = 267.4) and percentage of AChE inhibition ((x) over bar = 22.5%, SD = 12.4) compared to men hair cortisol levels ((x) over bar = 558.2 ng/g, SD = 208.2) and percentage of AChE inhibition ((x) over bar = 10.4%, SD= 13.1). Conclusions A heightened awareness of the potential risks of pesticide exposure was widespread within cut flower industrial complexes. This may have led to a reduction in exposure of both workers and non-workers living within or close to these complexes. In contrast, communities living outside these complexes showed higher levels of exposure, possibly due to limited chemical awareness and a lack of precautionary measures. Despite this contrast between communities, women remained the most vulnerable members, likely due to their socioeconomic roles in African society. Monitoring women's pesticide exposure is crucial for providing an early warning system for community exposure.

Background:Several environmental factors are associated with the risk of acute lower respiratory infections (ALRIs) and upper respiratory infections (URIs) in children under 5 years of age (YOA). Evidence implicating chemical pesticides remains equivocal. There are also no data on this subject in these children in Ghana. This study investigated the association between urinary pesticide residual levels and the risk for ALRIs/URIs in children under 5 YOA. Methods:The participants for this study were from the Offinso North Farm Health Study, a population-based cross-sectional study. Two hundred and fifty four parents/guardians who had answered affirmatively to the question "Has your child ever accompanied you to the farm?" were interviewed on household socio-demographic and environmental factors, being breastfed, child education, age, gender, and respiratory infection. One hundred fifty children were randomly selected to provide the first void urine. Results:The proportion of children with ALRI was 22.1% and those with URI was 35.8%. We observed a statistically significant exposure-response relation of p,p '-DDE (tertile) with ALRI (1.7-3.2 mu g/L urine: prevalence ratio [PR] = 1.22 [1.05-1.70], > 3.2 mu g/L urine: 1.50 [1.07-3.53] [P-for trend = .0297]). This observation was in children older than two YOA (P-for trend = .0404). Delta-HCH and beta-HCH (2-levels) were significantly associated with ALRI but not URI. The risk of ALRI increased with deltamethrin levels in an exposure-response manner (2.5-9.5 mu g/L urine: 2.10 [1.37-3.24], > 9.5 mu g/L urine: 4.38 [1.87-10.32] [P-for trend = .0011]) and this was also observed in children older than two YOA. Similar observation was noted for URI. Bifenthrin (>0.5 mu g/L urine) was positively associated with ALRI and URI whereas permethrin (> 1.2 mu g/L urine) was not associated only with URI. Conclusions:The present study supports the hypothesis that exposure to chemical pesticides is associated with respiratory infections in children under 5 YOA.

The data presented here are from the Offinso North District Farm Health Study (ONFAHS), a population-based cross-sectional study among vegetable farmers in Ghana. The paper addresses knowledge, pesticide handling practices, and protective measures related to pesticide use by self-reported symptoms for 310 adult farmers who completed a comprehensive questionnaire on pesticide management practices and health. In addition, an inventory was prepared using information supplied by pesticide sellers/dealers in this district. We report that cough and wheezing (but not breathlessness) are positively associated with stirring pesticide preparations with bare hands/drinking water while mixing/applying pesticides, and stirring pesticide preparations with bare hands/drinking water/smoking cigarettes while mixing/applying pesticides. There is a significant exposure-response association between the number of precautionary measures practiced while handling pesticides and cough and wheezing but not with breathlessness. We also found unsafe practices to be associated with sexual dysfunction, nervousness, and lack of concentration. The results also suggest a negative association between practice of any precautionary measure when mixing/applying pesticides and sexual dysfunction, nervousness, and lack of concentration. We found that in spite of the fact that farmers have adequate knowledge about the environment and health effects of pesticides, several unhygienic practices are in widespread use, indicating that knowledge is not necessarily always translated in action. Further action is necessary to promote the safe use of pesticides and to replace existing poor management practices among these and other farmers in Ghana.

Background: Adverse drug reactions (ADRs) are a significant problem for HIV patients, with the risk of developing ADRs increasing as the infection progresses to AIDS. However, the pathophysiology underlying ADRs remains unknown. Sulphamethoxazole (SMX) via its active metabolite SMX-hydroxlyamine, when used prophylactically for pneumocystis pneumonia in HIV-positive individuals, is responsible for a high incidence of ADRs. We previously demonstrated that the HIV infection and, more specifically, that the HIV-1 Tat protein can exacerbate SMX-HA-mediated ADRs. In the current study, Jurkat T cell lines expressing Tat and its deletion mutants were used to determine the effect of Tat on the thiol proteome in the presence and absence of SMX-HA revealing drug-dependent changes in the disulfide proteome in HIV infected cells. Protein lysates from HIV infected Jurkat T cells and Jurkat T cells stably transfected with HIV Tat and Tat deletion mutants were subjected to quantitative slot blot analysis, western blot analysis and redox 2 dimensional (2D) gel electrophoresis to analyze the effects of SMX-HA on the thiol proteome. Results: Redox 2D gel electrophoresis demonstrated that untreated, Tat-expressing cells contain a number of proteins with oxidized thiols. The most prominent of these protein thiols was identified as peroxiredoxin. The untreated, Tat-expressing cell lines had lower levels of peroxiredoxin compared to the parental Jurkat E6.1 T cell line. Conversely, incubation with SMX-HA led to a 2- to 3-fold increase in thiol protein oxidation as well as a significant reduction in the level of peroxiredoxin in all the cell lines, particularly in the Tat-expressing cell lines. Conclusion: SMX-HA is an oxidant capable of inducing the oxidation of reactive protein cysteine thiols, the majority of which formed intermolecular protein bonds. The HIV Tat-expressing cell lines showed greater levels of oxidative stress than the Jurkat E6.1 cell line when treated with SMX-HA. Therefore, the combination of HIV Tat and SMX-HA appears to alter the activity of cellular proteins required for redox homeostasis and thereby accentuate the cytopathic effects associated with HIV infection of T cells that sets the stage for the initiation of an ADR.

Background: Indiscriminate use of pesticides is a common practice amongst farmers in Low and Middle Income Countries (LMIC) across the globe. However, there is little evidence defining whether pesticide use is associated with respiratory symptoms.Objectives: This cross-sectional study was conducted with 300 vegetable farmers in southern Ghana (Akumadan). Data on pesticide use was collected with an interviewed-administered questionnaire. The concentration of seven organochlorine pesticides and 3 pyrethroid pesticides was assayed in urine collected from a sub-population of 100 vegetable farmers by a gas chromatograph equipped with an electron capture detector (GC-BCD).Results: A statistically significant exposure-response relationship of years per day spent mixing/applying fumigant with wheezing [30-60 days/year: prevalence ratio (PR)=1.80 (95% CI 1.30, 2.50); > 60days/year: 3.25 (1.70-6.33), p for trend=0.003] and hours per day spent mixing/applying fumigant with wheezing [1-2 h/day: 1.20 (1.02-1.41), 3-5 h/day: 1.45 (1.05-1.99), > 5 h/day: 1.74 (1.07-2.81), p for trend=0.0225]; days per year spent mixing/applying fungicide with wheezing [30-60 days/year: 2.04 (1.31-3.17); > 60days/year: 4.16 (1.72-10.08), p for trend =0.00171 and h per day spent mixing/applying fungicide with phlegm production [1-2 h/day: 1.25 (1.05-1.47), 3-5 h/day: 1.55 (1.11-2.17), > 5 h/day: 1.93 (1.17-3.19), p for trend=0.00281 and with wheezing [1-2 h/day: 1.10 (1.00-1.50), 3-5 h/day: 1.20 (1.11-1.72), > 5 h/day: 1.32 (1.09-2.53), p for trend=0.0088]; h per day spent mixing/applying insecticide with phlegm production [1-2 h/day: 1.23 (1.09-1.62), 3-5 h/day: 1.51 (1.20-2.58), > 5 h/day: 1.85 (1.31-4.15), p for trend=0.03871 and wheezing [1-2 h/day: 1.22 (1.02-1.46), 3-5 h/day: 1.49 (1.04-2.12), > 5 h/day: 1.81 (1.07-3.08), p for trend =0.01851 were observed. Statistically significant exposure response association was also observed for a combination of activities that exposes farmers to pesticide with all 3 respiratory symptoms. Furthermore, significant exposure-response associations for 3 organochlorine insecticides: beta-HCH, heptachlor and endosulfan sulfate were noted.Conclusions: In conclusion, vegetable farmers in Ghana may be at increased risk for respiratory symptoms as a result of exposure to pesticides. (C) 2016 Elsevier Inc. All rights reserved.

PURPOSE: Our working hypothesis is that bioactive phytochemicals that are important constituents of Traditional Chinese Medicine and their defined mixtures have potential as complementary therapy for chemoprotection against adverse drug reactions whose toxicity is not related to the pharmacological action of the drug but where oxidative and nitrosative stress are causative factors. METHODS: In this investigation we measured cytotoxicity, lipid peroxidation, protein carbonylation and ROS/NOS-mediated changes in the disulfide proteome of Jurkat E6.1 cells resulting from exposure to sulfamethoxazole N-hydroxylamine with or without pre-treatment with low µM concentrations of baicalein, crocetin, resveratrol and schisanhenol alone and in defined mixtures to compare the ability of these treatment regimens to protect against ROS/RNS toxicity to Jurkat E6.1 cells in culture. RESULTS: Each of the Traditional Chinese Medicine constituents and defined mixtures tested had significant chemoprotective effects against the toxicity of ROS/RNS formed by exposure of Jurkat E6.1 cells to reactive metabolites of sulfamethoxazole implicated as the causative factors in adverse drug reactions to sulfa drugs used for therapy. At equimolar concentrations, the defined mixtures tended to be more effective chemoprotectants overall than any of the single constituents against ROS/RNs toxicity in this context. CONCLUSIONS: At low µM concentrations, defined mixtures of TCM constituents that contain ingredients with varied structures and multiple mechanisms for chemoprotection have excellent potential for complementary therapy with sulfa drugs to attenuate adverse effects caused by oxidative/nitrosative stress. Typically, such mixtures will have a combination of immediate activity due to short in vivo half-lives of some ingredients cleared rapidly following metabolism by phase 2 conjugation enzymes; and some ingredients with more prolonged half-lives and activity reliant on phase 1 oxidation enzymes for their metabolic clearance. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

The horticultural sector has undergone tremendous growth in Kenya and is now the second largest foreign income earning sector in the country. Lake Naivasha is the hub of large scale horticultural farming in Kenya. This growth coupled with increased use of pesticides, may increase the possibility of pesticide exposure and its associated risks to workers and residents of the region. The purpose of this study was to assess the symptoms commonly experienced by residents of Naivasha town and their possible association to pesticide exposure. Purposive sampling of residents from Kamere, Kwa Muia, Kioto and Karagita was performed, as these residential areas have significant numbers of flower farm workers. By random selection, a total of 801 community members were recruited to participate in the study and data was collected by completing the prepared questionnaire and from clinical examinations. Results indicate that several residents exhibited respiratory; skin, joints and bones; and nervous system symptoms. We found a higher frequency of symptoms among planters, weeders, harvesters than in sprayers working in horticultural farms. We recommend training to planters, weeders, harvesters who are mainly women (61.6%) in this study concerning pesticide use as do sprayers; and second, longer reentry times between the last spraying of pesticide and entry of these workers is warranted, particularly in greenhouses. In this regard, reentry times for greenhouses and fields established for specific pesticides in Europe, North America, Japan or Australia should be adapted by Kenya, and these guidelines enforced by the Government of Kenya to reduce exposure to pesticides within this vulnerable work group. These workers should also use protective clothing including gloves and masks at all times while handling chemicals or recently sprayed plants or flowers. It would also be prudent for flower farm owners to introduce an integrated pest management regime to reduce pesticide use andworker exposures. Further research is required both to identify validated biomarkers that can reliably be used to identify pesticide exposure prior to the occurrence of acute toxicity; and to follow up individual cases of known exposures for chronic health effects.

PURPOSEOur working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer's. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells.METHODSEndpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status.RESULTSAt low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry.CONCLUSIONSWe conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Stress is known to contribute to overall health status. Many individuals in sub-Saharan Africa are believed to be stressed about their employment, income, and health. This study aimed to investigate hair cortisol as a biomarker of chronic stress in settlement communities in Kenya. Hair samples were collected from 108 volunteers from settlement communities in Kenya. An enzyme-linked immunosorbent assay technique was used to measure hair cortisol concentrations. In parallel, a health survey was completed. The mean ± SD for the cortisol concentration in the hair of volunteers from the settlement communities in Naivasha was 639 ± 300 ng/g, which was higher than found for a Caucasian reference group (299 ± 110 ng/g; one-way ANOVA, P = 0.0003). There were no differences in hair cortisol concentrations between members of slum settlements adjacent to large floriculture farms in Naivasha (Karagita, Kamere/Kwa Muhia/DCK, and Kasarani) compared with those well-removed from all floriculture in Mogotio (Mogotio and Westlands/Katorongot). However, hair cortisol concentrations were significantly higher in females, divorced volunteers, those who made below minimum wage, and those who reported feeling unsafe collecting water or using sanitation facilities within these 2 settlement groups. We found no evidence for increased chronic stress (measured by hair cortisol content) between members of slum settlements adjacent to versus distant to large floriculture farms. Cultural and socio-economic conditions that prevail in much of sub-Saharan Africa were found to be factors contributing to chronic stress.

BACKGROUND:Cortisol level in hair is increasingly being used as a biomarker of chronic stress. Members of First Nation communities in Canada are experiencing stress related to a higher incidence of chronic diseases, socioeconomic factors, the state of their environment, and cultural oppression. This study aimed to investigate hair cortisol as a biomarker of stress in this population. MATERIALS AND METHODS:Hair samples were collected from the posterior vertex of 55 Walpole Island First Nation (WIFN) volunteers and compared with white volunteers living in and around London, ON, Canada. An enzyme-linked immunosorbent assay technique was used to measure cortisol content in 1 cm of hair, considered to represent 1 month of growth. In parallel, the Perceived Stress Scale (PSS), which measures short-term stress, was also completed. RESULTS:Median hair cortisol level (range) in WIFN volunteers was 177 (93-273) ng/g, significantly higher than the median hair cortisol in the healthy white controls of 116 (26-204) ng/g (P < 0.0001, Mann-Whitney U test). Hair cortisol correlated positively with gender, smoking status, and self-reported diabetes. Unlike hair cortisol, the Perceived Stress Scale did not differentiate between the First Nation and control population. CONCLUSIONS:The increased hair cortisol concentrations among WIFN volunteers compared with volunteers from a non-First Nation community suggests higher levels of chronic stress. The causes for this apparent increased stress are likely due to factors such as socioeconomic and poorer health and are worthy of further evaluation. The results highlight the difference between acute stress measured for short periods of time compared with chronic stress, measured by hair analysis.

While fish is rich in essential nutrients and women are encouraged to consume fish products, fish may contain methylmercury, which is an established neurotoxin to the fetus. Not surprisingly, there are high levels of anxiety among women of reproductive age regarding fish consumption. To be able to counsel women in this complex area, we have developed a two-step program: (1) probing women of reproductive age for their perceptions regarding the safety of consuming fish, and (2) piloting an intervention program with women of reproductive age to ensure mercury levels are below the recently proposed Lowest Observable Adverse Effect Level. This method may be used as a template to improve the understanding of clinicians, legal experts, and policy makers on the fetal risk-benefit ratio of environmental chemicals.

A systematic review was performed to evaluate the association between environmental exposures to polyhalogenated aromatic hydrocarbons (PHAHs) and organochlorine (OC) pesticides and the risk for type 2 diabetes (T2D). Searches of EMbase, Google Scholar, Medline, and Scopus were performed. Reports were included if they were original human studies whose design included a control group and if the sample size was larger than 10 participants per group. The articles were excluded if the type of diabetes was unknown or Type 1. Odds ratios (OR), 95% confidence intervals (CI), and modified Naranjo scores for the effects of environmental contaminants were determined for each study. Of the 35 eligible studies, six were included in the meta-analysis; these focused specifically on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Meta-analysis of these studies showed no significant increased OR for the development of T2D from exposure to TCDD. However, subgroup analysis showed significant elevated OR for the development of T2D if exposure is repeated and accompanied by exposure to other persistent pesticides (OR = 1.48; 1.10-1.90) but a decreased odds for T2D with exposure resulting from accidental exposure (OR = 0.46; 0.39-0.52). Our results suggest that there are significant risks of developing T2D in populations with recurring exposures to TCDD in concert with other persistent chlorinated pesticides. A mean Naranjo score of 2.0 was determined for all 35 articles; this score was 2.5 when examining only TCDD studies and 2.1 when examining studies that looked only at T2D. Each of these Naranjo scores suggests a possible association between the prevalence of T2D and exposure to PHAHs or OC pesticides.

The drug development process is a carefully regulated, very expensive, long and complex process designed to bring safe and effective drugs to the market. The process begins with preclinical studies that identify and evaluate promising compounds that are then studied in a series of carefully regulated steps to bring the products from the laboratory to the clinic. This process is closely regulated, even after approval is given for the drug to be marketed. The classical drug development process can be applied to drugs derived from plants, with the acknowledgement that there are both special opportunities and special challenges in using the drug regulatory process to bring drugs derived from plants to market. The drug development and regulatory process is facing a number of challenges, many of which are not unique to drugs derived from plants but rather reflect the changing nature of biomedical science and drug regulation. Some of these changes may in fact facilitate the development of plant-derived therapeutic agents, and recent successes in this area point to the considerable promise for development of drugs from plants.