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.

Blood lead levels, calcium metabolism and bone-turnover among automobile technicians in Sagamu, Nigeria: Implications for elevated risk of susceptibility to bone diseases.

Lead is an occupational toxicant and a recognised health threat particularly in developing countries. Hence, this study explored the interaction of blood lead level (BLL), a conventional marker of lead exposure, with indices of calcium metabolism and biomarkers of bone-turnover in 120 adult male automobile technicians (AT) with ≥ 1 year duration in professional practice. The AT as well as the control group, which comprised 120 age, body-size and socio-economically matched male administrative workers, were recruited from Sagamu, South West Nigeria. Levels of blood lead, serum indices of calcium metabolism [total calcium (tCa), ionised calcium (iCa), phosphate, albumin, magnesium (Mg) and 25-Hydroxycholecalceferol (25-OHCC)], biomarkers of bone formation [bone alkaline phosphatase (BALP) and osteocalcin (OC)] and biomarkers of bone resorption [tartarate-resistant acid phosphatase-5b (TACRP-5b) and urinary hydroxyproline (UHYP)] were determined in all participants. The BLL, 25-OHCC, TRACP-5b and UHYP significantly increased while tCa and iCa significantly reduced in AT compared to control. However, no significant difference was observed in phosphate, albumin, Mg, BALP and OC in AT compared to control. Interestingly, BLL demonstrated a significant negative association with tCa and iCa but a significant positive association with 25-OHCC, TRACP-5b and UHYP. However, BLL did not show significant association with phosphate, albumin, Mg, BALP and OC. Increased lead exposure as well as altered calcium metabolism and bone-turnover demonstrated by the automobile technicians may be suggestive of lead-induced accelerated bone demineralisation. These workers may be predisposed to high risk of increased susceptibility to bone diseases if this sub-clinical picture is sustained.

Cadmium level in pregnancy, influence on neonatal birth weight and possible amelioration by some essential trace elements.

Cadmium (Cd) is currently of great concern in rapidly industrializing countries-India, China. Their products consumed especially due to increase demand in many developing countries like Nigeria can result in adverse effects. Cd is a ubiquitous environmental pollutant and toxicant and humans are continually exposed to the toxic effects of Cd primarily through food as well as from environmental pollution through industrial activities. Maternal exposure to Cd has been associated with the delivery of low-birth weight babies and an increase incidence of spontaneous abortion. Cd a toxic metal can displace zinc (Zn) an essential element necessary for normal fetal development and growth. With this consideration, 160 subjects comprising of 125 pregnant and 35 non-pregnant subjects as controls were recruited for this study. The pregnant subjects were classified according to the three trimesters of pregnancy as followed; 35, 35, and 55 from the first to the third trimesters respectively. The third trimester subjects were followed-up until after delivery where neonatal parameters (birth weight, head circumference, and length) of babies were measured. 32 (58%) of the women delivered babies with normal birth weight, 19 women (35%) delivered babies with low-birth weight while four women (7%) delivered babies with high- birth weight. Subject who delivered low-birth weight babies had significantly higher Cd concentration and lower Zn concentration and body mass index when compared with those with normal weight babies. These results suggest that Cd indeed has some toxic effects on neonatal birth weight.

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.

Haemoglobinuria among children with severe malaria attending tertiary care in Ibadan, Nigeria.

BACKGROUND: Haemoglobinuria is one of the manifestations of severe malaria and results from severe intravascular haemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been implicated in its aetiology. Haemoglobinuria may be associated with severe anaemia and, less frequently, acute renal failure. METHODS: A prospective case-control study was carried out to determine the incidence of haemoglobinuria as confirmed by dipstick urinalysis, microscopy and spectrophotometric measurement, among children with severe malaria. A total of 251 children presenting at the Children's Emergency Ward with severe malaria were recruited over a period of 21 months. The G6PD status and the outcomes of severe malaria in children with and without haemoglobinuria was studied with respect to renal failure, the recurrence of haemoglobinuria and blood pressure changes over a three-month follow-up period. RESULTS: It was found that the incidence of haemoglobinuria among children with severe malaria is 19.1%. Children <5 years constituted 76.8% of all the study patients. Patients with haemoglobinuria had median age of 52.5 months, which was significantly higher than 35 months in patients without haemoglobinuria (p=0.001). Although, haemaglobinuria was commoner among boys (54.2%) than girls (45.8%), the difference was not statistically significant. There were no significant differences between children with and without haemoglobinuria regarding their nutritional status or parasite densities. Among the clinical features of the study patients, only jaundice was significantly associated with haemoglobinuria (p=0.0001). Renal failure occurred in three out of 48 children with haemoglobinuria and in none of the 203 without. There was not recurrence of haemoglobinuria in the follow-up period. At discharge, blood pressure was elevated in six children (one previously haemoglobinuric), but all returned to normal within the follow-up period. CONCLUSIONS: Haemoglobinuria was a prominent feature of severe malaria and it was significantly associated with jaundice at presentation. Haemoglobinuria was commoner in older children than younger children but not related to sex. G6PD deficiency was not an independent predictor of the occurrence or outcome of haemoglobinuria. Blood pressure was not affected by haemoglobinuria on admission nor during follow-up.

AACC Guidance Document on the Use of Point-of-Care Testing in Fertility and Reproduction.

BACKGROUND: The AACC Academy revised the reproductive testing section of the Laboratory Medicine Practice Guidelines: Evidence-Based Practice for Point-of-Care Testing (POCT) published in 2007. METHODS: A panel of Academy members with expertise in POCT and laboratory medicine was formed to develop guidance for the use of POCT in reproductive health, specifically ovulation, pregnancy, premature rupture of membranes (PROM), and high-risk deliveries. The committee was supplemented with clinicians having Emergency Medicine and Obstetrics/Gynecology training. RESULTS: Key recommendations include the following. First, urine luteinizing hormone (LH) tests are accurate and reliable predictors of ovulation. Studies have shown that the use of ovulation predicting kits may improve the likelihood of conception among healthy fertile women seeking pregnancy. Urinary LH point-of-care testing demonstrates a comparable performance among other ovulation monitoring methods for timing intrauterine insemination and confirming sufficient ovulation induction before oocyte retrieval during in vitro fertilization. Second, pregnancy POCT should be considered in clinical situations where rapid diagnosis of pregnancy is needed for treatment decisions, and laboratory analysis cannot meet the required turnaround time. Third, PROM testing using commercial kits alone is not recommended without clinical signs of rupture of membranes, such as leakage of amniotic fluid from the cervical opening. Finally, fetal scalp lactate is used more than fetal scalp pH for fetal acidosis due to higher success rate and low volume of sample required. CONCLUSIONS: This revision of the AACC Academy POCT guidelines provides recommendations for best practice use of POCT in fertility and reproduction.

A Proposed Concept Model for Cancer Risk in Nigerian Electronic Waste Exposure - A Brief Report.

Aim: This report aims to render a proposed concept model for cancer risk in Nigerian electronic waste exposure by making deductions from data on the assessment of Nigerians' exposure to toxic metals in e-waste, using biomarkers of exposure and genotoxicity to evaluate the risk of cancer development. Material and methods: In the cross-sectional study, 632 consenting participants, consisting of 381 e-waste workers (EW) and 120 environmental e-waste exposed participants (EEEP), age-matched with 131 unexposed participants (controls), were enrolled from Benin, Lagos and Ibadan, Southwestern Nigeria. Levels of selected toxic metals in blood and essential metals in serum were determined using inductively coupled plasma-mass spectrometry. Oxidative stress biomarkers, including malondialdehyde and uric acid (UA), and activities of enzymatic antioxidants [catalase, superoxide dismutase (SOD), γ-glutamyltransferase (GGT) and glutathione peroxidase (GPx)], were determined in serum using standard methods like spectrophotometry. Genotoxicity biomarkers - wild-type tumour suppressor protein (wt-p53), 8-oxoguanine-DNA glycosylase (OGG1), and 8-hydroxy-2'-deoxyguanosine (8-OHdG); glutathione (GSH); and tumour markers [prostate-specific antigen (PSA) and alpha-fetoprotein] - were determined in serum using ELISA. Micronucleus assay was carried out using microscopy. Data were analysed using ANOVA and Pearson's correlation coefficient at α0.05. Results: There was evidence indicating elevated levels of genotoxic toxic metals, decreased levels of genome protective metals, increased oxidative stress markers as well as reduced cellular antioxidants in both EW and EEEP compared to controls. Additionally, the levels of wt-p53 in EW and EEEP were lower than controls, while OGG1 activity in EEEP was higher. The PSA and alpha-fetoprotein in EW were more elevated than EEEP and controls, respectively. The MnPCE/1000PCE in EW was higher than EEEP and controls. Conclusion: The proposed schematic model could be adopted to illustrate cancer risk in Nigerian population exposed to electronic waste.

Lipid profile and Atherogenic Indices in Nigerians Occupationally Exposed to e-waste: A Cardiovascular Risk Assessment Study.

Aim: This study investigated the effects of e-waste occupational exposure on lipid profile and atherogenic indices in Waste Electrical and Electronic Workers in South-South Nigeria. Matrials and methods: Whole blood levels of lead and cadmium were analyzed using ICPMS (Inductively Coupled Plasma Mass Spectrometry). Total serum cholesterol (TC), high density lipoprotein (HDL) cholesterol and triglycerides (TG) were determined using spectrophotometric method. Low density lipoprotein (LDL) cholesterol value was calculated by the Friedewald equation using analyzed values of TC, HDL cholesterol and TG. Atherogenic index of plasma (AIP) was calculated as log TG/HDLc, atherogenic coefficient (AC) as [(TC-HDLc)/HDLc], Castelli risk index (CRI-1) as (TC/HDLc) and CRI-II as (LDLc/HDLc). Results: Total cholesterol, LDL cholesterol, AC, CRI-1 and CRI-11 significantly increased in the e-waste exposed participants compared to the unexposed group. Significant positive correlations between lead and cadmium, cadmium and total cholesterol as well as between cadmium and LDL-cholesterol were observed Conclusion: Occupational exposure to e-waste borne chemicals may cause changes in lipid levels and increase risk of cardiovascular disease in the Nigerian e-waste workers included in the present study. The level of artisanal involvement in crude e-waste reprocessing should be considered critical in cardiovascular health risk assessment.

Arsenic exposure and its health effects and risk of cancer in developing countries: micronutrients as host defence.

Arsenic (As) is a ubiquitous metalloid found in several forms in food and the environment, such as the soil, air and water. The predominant form is inorganic arsenic in drinking water, which is both highly toxic and carcinogenic and rapidly bioavailable. As is currently one of the most important environmental global contaminants and toxicants, particularly in the developing countries. For decades, very large populations have been and are currently still exposed to inorganic As through geogenically contaminated drinking water. An increased incidence of disease mediated by this toxicant is the consequence of long-term exposure. In humans, chronic ingestion of inorganic arsenic (> 500 mg/L As) has been associated with cardiovascular, nervous, hepatic and renal diseases and diabetes mellitus as well as cancer of the skin, bladder, lung, liver and prostate. Contrary to the earlier view that methylated compounds are innocuous, the methylated metabolites are now recognized to be both toxic and carcinogenic, possibly due to genotoxicity, inhibition of antioxidative enzyme functions, or other mechanisms. As inhibits indirectly sulfhydryl containing enzymes and interferes with cellular metabolism. Effects involve such phenomena as cytotoxicity, genotoxicity and inhibition of enzymes with antioxidant function. These are all related to nutritional factors directly or indirectly. Nutritional studies both in experimental and epidemiological studies provide convincing evidence that nutritional intervention, including chemoprevention, offers a pragmatic approach to mitigate the health effects of arsenic exposure, particularly cancer, in the relatively resource-poor developing countries. Nutritional intervention, especially with micronutrients, many of which are antioxidants and share the same pathway with As, appears a host defence against the health effects of arsenic contamination in developing countries and should be embraced as it is pragmatic and inexpensive.

Cadmium toxicity: a possible cause of male infertility in Nigeria.

Serum and seminal plasma cadmium (Cd) concentrations were estimated by atomic absorption spectrophotometry in 60 infertile adult male Nigerians (40 oligozoospermics and 20 azoospermics). The results were compared with Cd level in 40 normozoospermic subjects (matched age, with proven evidence of fertility). The relationship between Cd levels and spermatograms or the hypothalamic-pituitary-gonadal (HPG) -axis was investigated by correlating serum and seminal plasma Cd levels with semen characteristics and hormone levels. The seminal plasma Cd level was significantly higher than those of serum in all studied groups (p<0.001). The serum and seminal plasma Cd levels were increased (p<0.001) in azoospermics in comparison to oligozoospermic and control subjects. A significant negative correlation was observed between serum Cd level and all examined biophysical semen characteristics except sperm volume. A positive correlation was also observed between seminal plasma Cd and FSH. Results of the study for the first time implicate cadmium as a cause of infertility in male Nigerians as well as extend and support previous findings concerning cadmium toxicity and male infertility. The strong deleterious effect of cadmium on spermatogenesis may be due to the systemic and cellular toxicity. A possible relationship between this element and the HPG axis is also suggested.

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.

Biochemical observations in Blount's disease (infantile tibia vara).

Blount's disease or congenital tibia vara is a clinical entity characterized by tibia bowing, tibia torsion, and beaking of the medial tibia metaphysis on plain radiograph. In our environment, burnt-out rickets patients with biochemical and radiological diagnosis of rickets who after treatment still have residual bone changes despite normal bone biochemistry) can also present with similar clinical and radiological features as Blount's disease. However, certain biochemical variations, including antioxidants, may serve as a basis for differentiation between these two disorders. The serum levels of calcium, inorganic phosphate, zinc, copper, and alkaline phosphatase in 15 patients (10 females and five males) aged between two- and five years (mean 3.8 +/- 1.1 (SD)) with clinical and radiological features of Blount's disease were determined. The mean weight of the patients with Blount's disease was 14.0 +/- 2.4 kg (range: 11.5-16.3 kg). Fifteen subjects (nine females and six males) matched for age and sex without clinical features of any metabolic bone and/or nutritional diseases who were attending the surgical outpatient clinic served as control subjects. The serum concentrations of inorganic phosphate and calcium, though lower in patients with Blount's disease compared with controls, did not reach statistical significance. Alkaline phosphatase activity was increased in the serum of all patients with Blount's disease. In addition, there was an observed significant reduction in serum concentration of zinc (P < 0.03) compared to the control subjects. As for calcium level, the concentration of serum copper in Blount's patients was reduced, but this was not statistically significant. These biochemical observations, especially those of the antioxidant micronuent zinc, may serve as a basis for the differentiaion of the sometimes clinically inseparable disorders of Blount's and rckets and may aid in early differential diagnosis, appropriate treatment as well as prevention of complications.

Rising environmental cadmium levels in developing countries: threat to genome stability and health.

Cadmium (Cd) is a ubiquitous environmental pollutant of increasing worldwide concern. It is thought to be of greater concern to rapidly industrializing developing countries because of the increasing pace of industrial activities in these countries with increasing consumption and release into the environment. Traditionally, health concerns in exposed human populations have revolved around the association of Cd with bone disease, emphysema and possibly hypertension. Accumulating evidence suggest that Cd is involved in the disruption of many genomic processes, the mechanisms of which are being gradually understood. Changes in DNA Methylation may be induced by cadmium leading to epigenetic alterations. Additionally, though Cd is not thought to induce reactive oxygen species (ROS) directly because it is not capable of accepting or donating electrons under physiological conditions, 8-hydroxy deoxyguanosine (8-OHdG) (a marker of oxidative stress to DNA and a risk factor for cancer among others) has been shown to be elevated in the DNA of testes from rats treated with cadmium chloride, at least in part because Cd inhibits DNA repair mechanisms.  Cadmium is also a metabolic antagonist to Zinc (Zn), an important micronutrient involved in numerous molecular activities. This antagonism alters the physiological stoichiometric relationship between Cd and Zn leading to high Cd/Zn ratio, one consequence of which is high error rate and lack of efficient DNA repair systems leading to high mutation and genome instability culminating in many carcinogenic states, particularly prostate carcinogenesis. Cadmium has also been shown to replace Zn in the tumor suppressor protein, p53 thereby impairing p53's DNA binding activity and associated repair processes. The expression of the p53 protein is significantly depressed by cadmium. Although the rising level of Cd in the environment is widely acknowledged, the occult threat it poses to genome stability largely through inhibition of normal DNA damage repair, oxidative stress and apoptosis and health is poorly recognized. This paper examines the involvement of Cd in the molecular pathways of human disease, providing insight for the prevention of genome instability and associated disease susceptibility particularly cancer across populations through micronutrient intervention, aiding upregulation of the antioxidant defense and DNA repair systems.