Increased cancer risk in HIV-infected individuals occupationally exposed to chemicals: Depression of p53 as the key driver.

The growing exposure to occupational chemicals and the spread of human immunodeficiency virus (HIV) infection are major global health issues. However, there is little data on the carcinogenic risk profile of HIV-infected individuals who have been occupationally exposed to chemical mixtures. This study therefore investigated the levels of cancer risk biomarkers in HIV-infected individuals exposed to occupational chemicals, exploring the relationship between apoptotic regulatory and oxidative response markers as a measure of cancer risk. Study participants (mean age 38.35±0.72 years) were divided into four groups according to their HIV status and occupational chemical exposure: 62 HIV-positive exposed (HPE), 66 HIV-positive unexposed (HPU), 60 HIV-negative exposed (HNE), and 60 HIV-negative unexposed (HNU). Serum p53, ß-cell lymphoma-2 (bcl2), 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured using standard methods. Clusters of differentiation 4 (CD4+) T-lymphocytes were enumerated using flow cytometry. Serum p53 and bcl2 levels in HPE (0.91±0.11ng/ml and 122.37±15.77ng/ml) were significantly lower than HNU (1.49±0.15ng/ml and 225.52±33.67ng/ml) (p < 0.05), respectively. Wildtype p53 and bcl2 were positively and significantly correlated with 8-OHdG (r = 0.35, p<0.001; r = 0.36, p<0.001) and SOD (r = 0.38, p<0.001; r = 0.39, p<0.001). After controlling for gender, age, BMI, and cigarette smoking, both HIV status and SOD activity were significantly associated with wildtype p53 and bcl2 (p < 0.05). Malondialdehyde was significantly higher in the HPE (0.72 ± 0.01 mg/ml) than in the HNE (0.68 ± 0.01 mg/ml) and HNU (0.67 ± 0.01 mg/ml) groups (p < 0.05). The HPE group showed significantly lower CD4 counts than the HNE and HNU groups. Individuals who are HIV-infected and occupationally exposed to chemicals have a constellation of depressed immunity, elevated oxidative stress, and loss of tumour suppressive functions, which together intensify cancer risk, providing valuable scientific and public health bases for preventive measures in this vulnerable population.

A pragmatic approach to the diagnosis of inborn errors of metabolism in developing countries.

Inborn errors of metabolism (IEM) are a group of genetically derived diseases that are individually rare but collectively common and can be very severe. While high-income countries usually employ modern scientific technologies like tandem mass spectrometry for IEM investigation, these disorders are, in contrast, only rarely screened for in developing countries due to misconceptions that the required facilities are beyond the reach of these countries. This paper attempts to educate scientists and clinicians in developing countries on low-technology IEM screening methods that only require moderate facilities. Although a definitive diagnosis of IEM may require specialised laboratory investigations and attendant interpretation, in most cases, the basic facilities available in the average clinical chemistry laboratory in developing countries can allow the early detection of IEM. This early detection would facilitate critical early decision making, thus leading to better management, optimised treatment, and reduced morbidity and or mortality of IEM in these resource-limited countries. With this approach, a few referral centres for confirmatory investigation, comparable to those existing in developed countries, could be established. This can be integrated into creative health education for healthcare professionals and families who have individuals with IEM. What this study adds: IEMs are important enough that every country, developed or developing, should have screening plans and basic laboratory facilities that are adequate for initial IEM diagnosis. No country should therefore give up on testing for IEMs on the excuse of a paucity of advanced facilities.

A Common Insecticide Induced-Oxidative Stress in Wistar Rats: Significance for Humans and Implications for Nutritional Modulation of Insecticide Toxicity.

OBJECTIVE: This study examined the levels of selected micronutrients and associated biochemical changes in rats exposed to Baygon® insecticide. Arsenic is a toxic metalloid commonly used in insecticides manufacture but unheralded. METHODS: Fifteen rats, divided into three equal groups: Group I (control); group II (administered 2.5 mg/kg sodium arsenite (SA) on alternate days for four weeks); group III (exposed to 14.0 mL Baygon® m-3 cage volume daily for four weeks). Serum levels of arsenic (As), selenium (Se) and zinc (Zn) were determined using flame atomic absorption spectrophotometry (FAAS). Reduced glutathione (GSH), glutathione peroxidase (GPx), and total protein (TP) were determined spectrophotometrically. RESULTS: Arsenic and Se levels were significantly raised in groups II and III compared with control (p < 0.05), unlike Zn levels that were significantly decreased in groups II and III (p < 0.05) in both. No significant change in the activity of GPx; though the activity increased in the group treated with SA, but decreased in the group treated with Baygon® compared to control (P < 0.05). Histology of the liver and lung was unaltered in control, but in contrast, the SA-treated group demonstrated moderate fibrous hyperplasia with prominent highly infiltrated portal area in the liver; while the lung revealed thickened alveolar walls from proliferated pneumocytes. In the Baygon®-treated group, there was mild hyperplasia of the fibrous connective tissue and congested prominent portal areas; while the lung exhibited severe thickened alveolar walls due to proliferated pneumocytes. CONCLUSION: Exposure of rats to Baygon® elicited alteration of key trace elements involved in the antioxidant system, culminating in oxidative stress with attendant deleterious effects. One significance of this for humans is that it has great potentials for possible nutritional modulation of insecticide toxicity with micronutrients, especially with zinc, holding great promise in tropical developing countries.

Toxicant-nutrient interaction as a veritable host resistance against chemical toxicity in the rapidly industrializing developing nations

Growing evidence indicates that chemical utilization including toxic waste in the developing countries is on the increase. These nations have limited facilities for sound chemical management involving production, use and disposal of chemicals with minimal adverse effects on human and environmental health. Though concerns are important to all nations, they appear particularly salient to the industrializing countries under pressures to achieve development and eradicate poverty yet with limited capacity for sound chemical management. This increases the risk of chemical toxicity, with consequences such as genotoxicity, cancer and teratogenicity. The growing chemical burden implies the need for an efficient and effective means of xenobiotic metabolism and host resistance. Relevant literature on nutrients and toxicants interaction in various search engines were reviewed. The possible role of host resistance, essentially involving nutritional modulation has been ignored. Nutrient-toxicant response pathways could be affordable strategies against excessive chemical exposure. Zinc, a prime micronutrient is an antioxidant [Cu-Zn superoxide dismutase (SOD)], component of p53, guardian of the genome; active in the repair of DNA damage and apoptosis; protective against carcinogenesis. Zinc also plays an important role in vitamin A metabolism, in turn important in differentiation and central to retinoids involved in gene expression. Zinc is important in all the stages of the cell cycle, derangement of which may be a pathway to carcinogenesis. Use of this and other protective nutrients including folate and selenium, among others, appears a veritable approach to improving host resistance against chemical toxicity and should be considered promising in developing nations

Cadmium Level, Glycemic Control, and Indices of Renal Function in Treated Type II Diabetics: Implications for Polluted Environments.

Cadmium (Cd) has recently emerged as a major concern not only in environmental toxicology but also in metabolic diseases such as diabetes mellitus and its complications. Conflicting data aside, these studies have not been examined in a clinical population undergoing management as well as possible modulation by the prominent metabolic antagonist of Cd such as zinc (Zn). This study examined the relationship between cadmium levels, glycemic control, and renal pathology in established type II diabetic patients with focus on populations exposed to modern environmental health hazards (MEHHs). Sixty-five participants, consisting of 45 type-2 diabetics and 20 non-diabetics were enrolled for the study, mean age 61.51 ± 5.27 years. Glycated hemoglobin (HbA1c) was used to classify them into three sub-groups: (A) good glycemic control (44.4%), (B) fair glycemic control (24.4%), and (C) poor glycemic control (31.1%). Plasma levels of glucose, Cd, Zn, HbA1c, creatinine, urinary creatinine, microalbuminuria, and estimated glomerular filtration rate (eGFR) were determined in all participants using standard methods. Fasting plasma glucose was higher in diabetics than in non-diabetics (p = 0.000) as well as Zn level, though not significantly. Interestingly, Cd level, Cd/Zn ratio, and urinary creatinine were significantly lower in diabetics than in non-diabetics. The group with poor glycemic control (C) had significantly higher Cd level compared to the one with good glycemic control (group A). The renal function revealed that microalbuminuria and urinary albumin/creatinine ratio (UACR) was significantly higher in diabetics than in non-diabetics, while eGFR was found to be similar in both diabetics and non-diabetics. UACR inversely correlated with Cd level, while plasma creatinine level positively correlated with Cd but not significantly. Correlation between Cd and HbA1c revealed non-significant inverse correlation (r = -0.007; p > 0.05), while Zn showed a significant inverse correlation with Cd (r = -0.317; p < 0.014). The lower Cd level in diabetics compared to non-diabetics probably reflects the modulating effect of Zn in treated diabetics given nutritional education in addition to their regular regime, including good sources of Zn. The renal insufficiency with increasing Cd level may suggest that the progression of renal impairment may not be responsive to the putative modulating effect of Zn.

Waste dumps in local communities in developing countries and hidden danger to health.

AIM: The rapid industrialisation and urbanisation fuelled by a fast-growing population has led to the generation of a huge amount of waste in most communities in developing countries. The hidden disorders and health dangers in waste dumps are often ignored. The waste generated in local communities is usually of a mixed type consisting of domestic waste and waste from small-scale industrial activities. Among these wastes are toxic metals, lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), halogenated organic compounds, plastics, remnants of paints that are themselves mixtures of hazardous substances, hydrocarbons and petroleum product-contaminated devices. Therefore, there is the urgent need to create an awareness of the harmful health effect of toxic wastes in developing countries, especially Nigeria. METHOD: This is a review aimed at creating awareness on the hidden dangers of waste dumps to health in local communities in developing countries. Many publications in standard outlets use the following keywords: cancer, chemical toxicity, modern environmental health hazards, waste management and waste speciation in PubMed, ISI, Toxbase environmental digest, related base journals, and some standard textbooks, as well as the observation of the researcher between 1959 and 2014. RESULTS: Studies revealed the preponderance of toxic chemicals such as Pb, Cd, As and Hg in dump sites that have the risk of entering food chain and groundwater supplies, and these can give rise to endemic malnutrition and may also increase susceptibility to mutagenic substances, thereby increasing the incidence of cancer in developing countries. CONCLUSION: Industrialisation and urbanisation have brought about a change in the waste that is generated in contemporary communities in developing countries. Therefore, there is the need to embrace speciation and sound management of waste, probably including bioremediation. RECOMMENDATION: The populations in the local communities need regulatory agencies who are health educators as positive change agents.