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.

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.

Environmental Pollutants and Oxidative Stress in Terrestrial and Aquatic Organisms: Examination of the Total Picture and Implications for Human Health.

There is current great international concern about the contribution of environmental pollution to the global burden of disease particularly in the developing, low- and medium-income countries. Industrial activities, urbanization, developmental projects as well as various increased anthropogenic activities involving the improper generation, management and disposal of pollutants have rendered today's environment highly polluted with various pollutants. These pollutants include toxic metals (lead, cadmium, mercury, arsenic), polycyclic aromatic hydrocarbons, polychlorinated biphenyls, pesticides and diesel exhaust particles most of which appear to be ubiquitous as well as have long-term environmental persistence with a wide range of toxicities such as oxidative stress among others. Oxidative stress, which may arise from increased production of damaging free radicals emanating from increased pollutant burden and depressed bioavailability of antioxidant defenses causes altered biochemical and physiological mechanisms and has been implicated in all known human pathologies most of which are chronic. Oxidative stress also affects both flora and fauna and plants are very important components of the terrestrial environment and significant contributors of nutrients for both man and animals. It is also remarkable that the aquatic environment in which sea animals and creatures are resident is also highly polluted, leading to aquatic stress that may affect the survival of the aquatic animals, sharing in the oxidative stress. These altered terrestrial and aquatic environments have an overarching effect on human health. Antioxidants neutralize the damaging free radicals thus, they play important protective roles in the onset, progression and severity of the unmitigated generation of pollutants that ultimately manifest as oxidative stress. Consequently, human health as well as that of aquatic and terrestrial organisms may be protected from environmental pollution by mitigating oxidative stress and employing the principles of nutritional medicine, essentially based on antioxidants derived mainly from plants, which serve as the panacea of the vicious state of environmental pollutants consequently, the health of the population. Understanding the total picture of oxidative stress and integrating the terrestrial and aquatic effects of environmental pollutants are central to sustainable health of the population and appear to require multi-sectoral collaborations from diverse disciplinary perspectives; basically the environmental, agricultural and health sectors.

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.

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.

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.

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.

Positive and inverse correlation of blood lead level with erythrocyte acetylcholinesterase and intelligence quotient in children: implications for neurotoxicity.

Blood lead level (BLL) is insufficiently sensitive for early detection of Lead-induced neurotoxicity (LIN). This study determined the possible role of the combination of BLL, intelligent quotient (IQ) and erythrocyte acetylcholinesterase (AChE) activity in the early detection of LIN in Children. Apparently healthy children (n=309) from eight public primary schools in Ibadan, Nigeria were recruited and classified into: children with Elevated BLL (EBLL) and children with Acceptable BLL (control) based on CDC cut-off for childhood lead exposure. Neurological indices (speech, memory, cranial nerves and cerebellar functions), IQ, BLL and erythrocyte AChE activity were assessed using standard methods, Standard Progressive Matrices, AAS and HPLC respectively. Statistical analysis involved Student's t-test, Pearson's correlation and multivariate regression. p<0.05 was considered significant. There were 169 (54.7%) children with EBLL while there were 140 (45.3%) control children. Both groups exhibited normal speech, memory, cranial nerves and cerebellar functions. However, IQ was lower in EBLL children (85.9±11.6) compared with control (91.5±14.0) while BLL and AChE activity were higher in EBLL children (0.4±0.1 µmol/l; 117.5±25.5 µkat/l) compared with control (0.2±0.0 µmol/l; 59.4±10.2 µkat/l). BLL showed inverse correlation with IQ (r=-0.134, p=0.019) but positive correlation with AChE (r=0.978, p≤0.001). 16.2% of the observed variation in BLL could be accounted for by AChE using the equation; [BLL=-0.007+0.003 AChE] p<0.05. Elevated blood lead level is prevalent among the school children and appears to have adverse effect on their IQ. Erythrocyte AChE could be a promising marker for early recognition of significant environmental lead exposure and lead-induced neurotoxicity in children.

Pituitary, Gonadal, Thyroid Hormones and Endocrine Disruptors in Pre and Postmenopausal Nigerian Women with ER-, PR- and HER-2-Positive and Negative Breast Cancers.

Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer. This study aimed to determine differences in the serum levels of sex hormones, gonadotropins, thyroid hormones, and endocrine disruptors (lead, cadmium, and arsenic) in Nigerian women with hormone responsive and non-hormone responsive breast cancers. Seventy-nine non-pregnant women aged 28⁻80 years with histologically confirmed breast cancer were recruited, pre-therapy, into this cross-sectional study. They comprised 52 premenopausal women and 27 postmenopausal women recruited from the Surgical Oncology Clinic of the Department of Surgery, University College Hospital, Ibadan. Comparison of biochemical parameters were based on the positivity (+) and negativity (-) of estrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor-2 (HER-2). Estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were determined using enzyme immunoassay (EIA). Serum lead, cadmium and arsenic were determined using atomic absorption spectrophotometry (AAS). Expression of ER, PR and HER2 were determined using immunohistochemistry. Data was analyzed using Mann-Whitney U-test and multiple regression, with p < 0.05 considered as being statistically significant. Estradiol and progesterone were significantly higher in breast cancer participants with ER- and PR- compared with those with ER⁺ and PR⁺ breast cancer (p < 0.05). Follicle stimulating hormone and LH levels were significantly higher in participants with ER⁺ and PR⁺ breast cancer compared with participants with ER- and PR- breast cancer (p < 0.05). Arsenic was inversely related with TSH in premenopausal participants with ER- and PR- (ß = -0.305; ß = -0.304, respectively). Sex hormones and gonadotropins appear to be involved in the pathogenesis of triple negative and luminal breast cancer, respectively.

Relationship between selected micronutrient deficiencies and oxidative stress biomarkers in diabetes mellitus patients with foot ulcers in Ibadan, Nigeria

Background/aim: Micronutrients are indispensable in the prevention of diseases and maintenance of good health. Their deficiencies have been implicated in several diseases associated with oxidative stress (OS). This study aimed at investigating the levels of some vitamins and minerals in association with OS markers in diabetic foot ulcer (DFU) patients in Ibadan, Oyo State, Nigeria. Materials and methods: Seventy DFU patients and 50 apparently healthy volunteers (controls) were recruited for the study. Blood samples of 10 mL were collected after a 10-h overnight fast from each participant after obtaining their consent. Levels of oxidative stress biomarkers such as lipid peroxide (LPO), 8-hydroxyl-2?-deoxyguanosine (8-OHdG), total antioxidant status (TAS), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and micronutrients such as vitamin C, vitamin E, copper, selenium, and zinc were determined. Results: Significant increases in the levels of LPO and 8-OHdG and GPx activity were found in DFU patients compared to controls (P < 0.001). Significant decreases in vitamin C (P = 0.003), selenium, vitamin E, and TAS concentrations were detected between DFU patients and controls (P < 0.001). However, nonsignificant decreases in SOD activity and copper and zinc levels were observed when DFU patients and controls were compared (P > 0.05). Vitamin C was significantly positively correlated with GPx and selenium was significantly negatively correlated with 8-OHdG in the DFU group. However, nonsignificant correlations were observed between other micronutrients and oxidative stress biomarkers of both the DFU and control groups. Conclusion: Diabetes mellitus patients with foot ulcers may require micronutrient supplementation for proper control and maintenance of oxidant/antioxidant homeostasis.

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.

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.

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.

Blood lead, calcium, and phosphorus in women with preeclampsia in Edo State, Nigeria.

The authors investigated the effect of blood lead (BPb) and its relationship with calcium and phosphorus in the development of preeclampsia in Nigeria. Blood samples were collected from 59 preclamptics, 150 normal pregnant, and 122 nonpregnant women. Blood lead and serum Ca and P were determined. Blood lead was significantly higher (p < .001), whereas serum Ca and P were significantly lower (p < .001) in preclamptics than in normal pregnant women (60.2 ± 12.8 vs 26.3 ± 8.0 µg/dL for Pb, 1.39 ± 0.33 vs 2.03 ± 0.22 mmol/L for Ca, and 0.76 ± 0.10 vs 0.99 ± 0.13 mmol/L for P, respectively). There was significant increase (p < .05) in BPb and decreases (p < .01) in serum Ca and P in pregnant women than in nonpregnant women (35.7 ± 18.0 vs 13.1 ± 6.4 µg/dL for Pb, 1.85 ± 0.33 vs 2.33 ± 0.20 mmol/L for Ca, and 0.93 ± 0.38 vs 1.24 ± 0.26 mmol/L for P). Also, BPb was negatively correlated with serum Ca and, P, and positively correlated with systolic and diastolic blood pressures in pregnancy (r = -.804 for Ca, r = -.728 for P, r = .908 for SBP, and r = .842 for DBP) and preeclampsia (p < .01). It appears that increase in blood lead, which parallels decreases in serum calcium and phosphorus, may be related to the development and progression of preeclampsia in this environment.

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.

Altered copper level and renal dysfunction in Nigerian women using skin-whitening agents.

The purpose of the study was to determine the concentration of trace elements in serum samples of women who are chronic users of skin-whitening agents as well as the hepatic and renal effects of these agents on these women. The study was conducted among 23 skin-whitening users while 25 women served as the controls. The serum concentrations of Zn, Mn, and Mg were not significantly changed in these women compared with controls (p > 0.05), but Cu was significantly increased in skin-whitening agent users compared with controls (p < 0.05). Serum urea and creatinine were significantly increased compared with the controls (p < 0.05). Moreover, ALT, AST, albumin, total protein, and bilirubin were not significantly changed (p > 0.05). The significant increase in the levels of renal indices shows that these agents might be nephrotoxic after prolonged usage while increase in copper level with accompanying renal dysfunction may be an indication that copper mediates in oxidative-induced renal dysfunction. However, further study is needed to identify the cause and source of high serum copper as many of the herbal extracts may be rich sources of copper. Moreover, a large population study may be necessary to examine the exact correlation between copper and renal indices.

Total antioxidants status and some hematological values in sickle cell disease patients in steady state.

Congenital hemoglobin mutations may alter the delicate balance of free-radical generation and antioxidant defense systems in the red cell. Oxidative stress may thus play a role in the pathophysiology of the clinical manifestations of the disease. We assessed the total antioxidant status in steady-state sickle cell anemia (SCA) patients and related it to certain hematological parameters and their recent clinical history. Forty (25 males/15 females) adult SCA patients and 30 age-matched controls were studied. All patients and control subjects had total antioxidant status (TAS), hematocrit, white blood cells, platelets and reticulocyte count done. The results showed that TAS levels were about 50% lower in the SCA patients compared with the controls. Among the SCA patients, 57.1% of those with TAS levels <1.00 mmol/L had bone pain crisis >3 times in the past year, compared with 16% in those with TAS levels >1.00 mmol/L. Total leukocyte count and platelets were also significantly higher in the SCA patients than controls. Our data support the growing evidence that oxidative stress has a role to play in the pathophysiology of SCA and intervention aimed at increasing the antioxidant capacity of these patients may be beneficial.

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.