http://hdl.handle.net/123456789/55 Mon, 06 Apr 2026 14:32:56 GMT 2026-04-06T14:32:56Z http://hdl.handle.net/123456789/1965 TRACE METALS, NEUROTRANSMITTERS AND OXIDATIVE STRESS MARKERS IN THE PATHOGENESIS OF AUTISM SPECTRUM DISORDERS AND CEREBRAL PALSY IN CHILDREN AKINADE, Adekunbi Olufunke Autism Spectrum Disorders (ASD) and Cerebral Palsy (CP) are Neurodevelopmental Disorders (NDDs) with inconclusive genetic profiling. Currently, focus is on gene modulation in NDDs by environmental toxicants such as trace metals which induces oxidative stress. However, interrelationship between oxidative stress and neurotransmitters in the pathogenesis of NDDs is unclear. This study was conducted to assess in-utero placenta transfer of trace metals from occupationally-exposed pregnant mothers and effect on neurotransmitters in the pathophysiology of ASD and CP in children. Ethical approvals were obtained from UI/UCH Ethics Committee (UI/EC/15/0087) and Oyo State Ministry of Health. This case-control study had 180 participants; 50 pregnant women occupationally-exposed to metals (cases), 55 unexposed (controls), 25 each clinicallydiagnosed ASD, CP and Neuro-typical (NT) children, respectively. Maternal and cord blood obtained at parturition and blood samples from ASD, CP and NT were analysed for trace metals (selenium, zinc, copper, calcium, magnesium), lead, cadmium using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Samples from ASD, CP and NT were also assayed for neurotransmitters (glutamine, glutamate, GABA) using ELISA. Malondialdehyde (MDA), Total Antioxidant Capacity (TAC) and Total Plasma Peroxide (TPP) were spectrophotometrically determined, while Oxidative Stress Index (OSI) was calculated (TPP/TAC). Data were analysed using ANOVA and Pearsons’ correlation at α0.05. Maternal selenium, zinc, copper, lead, cadmium, calcium, magnesium levels in exposed (10.2±1.2, 370.8±193.0, 328.0±110.0, 11.0±1.4, 96.7±15.6 µg/dL; 8.6±0.9, 1.5±0.3 mg/dL) and unexposed (9.0±1.2, 416.8±277.0, 348.3±150.6, 10.0±1.9, 70.0±30.0 µg/dL; 8.6±0.9, 1.5±0.4 mg/dL) pregnant women were not significantly different. In the fetus cord-blood, selenium, zinc, copper and calcium levels were not significantly different, magnesium level (1.51±0.3 vs 1.6±0.1) was significantly reduced in exposed compared with unexposed, while lead and cadmium were not detectable. In ASD and CP, compared with NT, plasma calcium (7.9±1.4; 7.7±1.0 vs 9.8±1.3 mg/dL), magnesium (2.5±0.5; 2.8±0.6 vs 3.1±0.4 mg/dL), selenium (40.8±7.9; 27.6±6.8 vs 59.0±5.3 µg/dL), zinc (222.3±63.8; 233.8±105.3 vs 438.5±185.5 µg/dL) and copper (4.3±1.0; 4.0±0.8 vs 4.9±0.9 µg/dL) were significantly reduced, while lead level (9.5±4.0; 11.1±5.8 vs 5.4±2.05 µg/dL) was significantly elevated. The Zn/Cu ratio (55.3±22.0; 60.6±27.8 vs 92.3±44.6) was significantly reduced in ASD and CP compared with NT. Glutamine level (379.2±53.1; 296.3±59.6 vs 419.1±71.8 µmol/L) was decreased significantly in ASD and CP compared with NT. Glutamate (1.9±0.1; 1.8±0.3 vs 1.7±0.3 nmol/mL) and GABA (2.1±0.3; 1.8±0.4 vs 1.8±0.3 µmol/L) levels in CP and NT were comparable, and significantly elevated in ASD compared with NT. The OSI (0.6±0.2 vs 0.4±0.1; 0.4±0.1) and TPP (115.1±8.5 vs 105.9±2.3; 110.4±7.9) levels were significantly higher and TAC (209.8±57.9 vs 280.2±34.4; 303.8±33.1) was significantly reduced in CP compared with ASD and NT. The MDA (2.3±0.2; 2.1±0.2 vs 1.4±0.1) level was significantly elevated in ASD and CP compared with NT. Copper correlated positively with GABA and glutamine, while magnesium correlated negatively with GABA in ASD. Copper correlated positively with glutamate in CP. Transfer and imbalance of trace metals in-utero was established. Oxidative stress observed in autism spectrum disorders and cerebral palsy can be ascribed to imbalance in trace metals resulting in abnormal glutamatergic and GABAergic neuron activities in children with these disorders. Mon, 01 May 2023 00:00:00 GMT http://hdl.handle.net/123456789/1965 2023-05-01T00:00:00Z http://hdl.handle.net/123456789/691 PHAGOCYTIC MECHANISM AND ITS PLASMA MODULATORS IN PULMONARY TUBERCULOSIS PATIENTS ON ANTI-TUBERCULOSIS CHEMOTHERAPY AND ZINC SUPPLEMENT B EDEM, VICTORY FABIAN The progression of tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) from latent to drug-sensitive TB (DS-TB) or multi-drug resistant TB (MDR-TB) depends on factors including host-pathogen interactions. The nature and course of these interactions are largely determined by host zinc levels, a function of host immune responses. Clear understanding of these interactions is crucial to identify protection mechanisms, which are not completely elucidated. This study was designed to assess phagocytic mechanism and its plasma modulators in TB patients before and during anti-TB chemotherapy with or without zinc supplementation. Ethical approval (UI/EC/13/0340) was obtained and 160 consenting participants (50 MDR-TB patients, 60 DS-TB patients and 50 controls) were enrolled. The MDR-TB and DS-TB patients were treated with anti-tuberculosis chemotherapy. Thirty DS-TB patients received zinc supplement. Blood sample was collected and plasma obtained from patients at baseline, 2, 4 and 6 months of anti-TB chemotherapy with or without zinc supplement. Phagocytic mechanism [percentage leucocyte migration (%LM) and intracellular killing (%NBT)] were determined by microscopy. Interleukin 6 (IL-6) and 8 (IL-8) were determined using ELISA; superoxide dismutase (SOD), myeloperoxidase (MPO), hydrogen peroxide (H2O2) and nitric oxide (NO) were determined by spectrophotometry. Iron (Fe), zinc (Zn) and copper (Cu) were determined using AAS while vitamins A, C, D and E were determined by HPLC. Data was analysed using Kruskal-Wallis, Mann-Whitney U, Friedman and Wilcoxon signed rank tests at α0.05. In MDR-TB patients, baseline levels of %LM (91.5±0.9 vs 55.0±2.2), IL-6, IL-8 (186.4±29.9 vs 3.7±0.8; 1116.4±198.3 vs 18.9±2.4 pg/mL) and vitamin C (4.80±0.2 vs 3.5±0.7 mg/dL) were significantly higher while MPO (7.5±0.3 vs 8.3±0.3 U/mL), NO (9.2±0.8 vs 14.8±1.3 µmol/L), Fe, Zn and Vitamin A (92.2±2.3 vs 123.3±1.2; 62.6±1.0 vs 118.3±3.1; 49.8±2.6 vs 80.8±6.4 µg/dL) were lower compared with controls. In DS-TB patients, baseline IL-8 (162.6±56.3 vs 18.9±2.4 pg/mL) and MPO (9.3±0.4 vs 8.3±0.3 U/mL) were significantly higher while SOD (0.2±0.0 vs 0.3±0.0 U/mL), H2O2 (269.1±8.3 vs 313.8±7.4 µmol/L), NO (10.3±1.6 vs 14.8±1.3 µmol/L), Zn (81.3±6.3 vs 118.3±3.1 µg/dL), vitamins C and E (0.7±0.0 vs 3.5±0.7; 1.1±0.1 vs 1.7±0.3 mg/dL) were lower compared with controls. At 2 months of anti-TB chemotherapy compared with baseline, MPO (11.1±0.3 vs 9.6±0.3 U/mL) was significantly increased in DS-TB patients on anti-TB chemotherapy alone while SOD (0.2±0.0 vs 0.1±0.0 U/mL), MPO (17.5±1.0 vs 9.0±0.7 U/mL) and NO (25.7±2.4 vs 20.7±1.8 µmol/L) were increased in DS-TB patients on chemotherapy and zinc supplement. At 4 months of anti-TB chemotherapy, MPO (18.7±1.2 vs 9.0±0.7 U/mL) and NO (26.8±2.2 vs 20.7±1.8 µmol/L) were significantly increased in DS-TB patients on anti-TB chemotherapy and zinc supplement compared with baseline. At 6 months of anti-TB chemotherapy in DS-TB patients compared with baseline, H2O2 and NO (372.9±6.1 vs 316.7±7.9; 14.7±1.4 vs 12.0±1.3 µmol/L) were 4 increased in patients on anti-TB chemotherapy alone while MPO (20.2±1.3 vs 9.0±0.7 U/mL) increased in patients on anti-TB chemotherapy and zinc supplement. Zinc supplementation with anti-tuberculosis chemotherapy improved phagocytic mechanism and its plasma modulators in TB patients from 2 months of treatment Mon, 01 Jul 2019 00:00:00 GMT http://hdl.handle.net/123456789/691 2019-07-01T00:00:00Z http://hdl.handle.net/123456789/689 INFLAMMATORY MARKERS IN MALE FARM WORKERS EXPOSED TO DICHLORVOS ORGANOPHOSPHATE PESTICIDE IN IBARAPA COMMUNITY, SOUTHWESTERN NIGERIA YAQUB, SURAJUDEEN ADEBAYO, The need for improved agricultural yield led to increased use of various pesticides, especially organophosphate chemicals because of non-persistence in the environment. Dichlorvos organophosphate pesticide (DOP) is indiscriminately used by farm workers in spite of its associated acute and chronic adverse effects on nervous system. Although, information on the adverse effects of DOP on nervous system of farm workers is well documented, information on its effects on their immune status which can be drawn from inflammatory markers is scarce. This study was designed to determine changes in inflammatory markers in DOP-exposed farm workers. Ethical approval (UI/EC/11/0107) and informed consent were obtained as appropriate. Knowledge, attitudes, practices of farm workers towards pesticide use and associated toxicity symptoms were obtained using structured questionnaire. Farm workers (FW) consisting of 60 pesticide applicators (PA) and 60 farmers exposed to DOP for ten to fifteen years were randomly selected into this case-control study. Sixty apparently healthy adults without occupational exposure to DOP served as controls. Blood sample was collected and serum obtained by centrifugation. Serum activity of acetylcholinesterase (AChE) was determined by HPLC, differential leucocyte count was determined using thin film microscopy, serum levels of immunoglobulin E (IgE), C-reactive protein (CRP), interferon gamma (IFN-γ), interleukins (IL) 4 and 10 were determined using ELISA. Activities of myeloperoxidase, NADPH oxidase (Nox) and catalase were determined by spectrophotometry. Type-1 hypersensitivity was carried out using skin prick test with environmental allergens and neutrophil-lymphocyte ratio (NLR) was calculated. Data were analysed using ANOVA, Student’s t-test and Pearson moment correlation coefficient (PMCC) at α 0.05 Lymphocyte counts (56.0±8.0; 56.0±8.0; 56.0±4.0 against 41.0±5.0), eosinophil (2.0±1.0; 3.0±1.0; 2.0±1.0 against 1.0±0.0), levels of IgE (327.4±169.3; 320.7±171.4; 334.2±168.4 against 229.3±178.4 IU/mL), CRP (10.1±8.8; 12.6±10.4; 7.6±5.7 against 7.2±6.6 mg/L), IFN-γ (104.8±9.5; 128.4±16.8; 81.2±7.9 vs 65.1±5.6 pg/mL), IL-4 (214.1±16.3; 249.7±27.8; 178.4±16.0 against 87.2±48.3 pg/mL), activities of myeloperoxidase (12.3±9.3; 10.5±7.3; 14.1±10.8 against 7.7±5.6 U/mL), Nox (7.9±5.4; 7.3±5.7; 8.6±5.1 against 4.8±3.9 U/mL), the diameter of skin reaction to grass (3.7±0.7; 3.6±0.9; 3.7±1.0 against 3.0±0.0 mm) and mold (3.6±0.7; 3.5±0.9; 3.6±0.9 against 3.0±0.0 mm) allergens were higher in FW, PA and farmers compared with control, respectively. Serum activities of AChE (7.3±0.9; 6.6±0.9; 7.9±0.6 against 9.4±1.0 IU/mL), neutrophil count (41.0±8.0; 40.0±7.0; 41.0±10.0 vs 57.0±6.0), catalase (2.9±1.4; 2.5±1.1; 3.3±1.6 against 4.2±2.1 U/mg protein) and NLR (0.8±0.0; 0.8±0.0; 0.8±0.0 against 1.4±0.0) were lower in FW, PA and farmers compared with control, respectively. However, significant decreases in serum activities of AChE (6.6±0.9 vs 7.9±0.6 IU/mL), myeloperoxidase (10.5±7.3 against 14.1±10.8 U/mL) and catalase (2.5±1.1 against 3.3±1.6 U/mg protein) but significantly raised counts of monocyte (2.0±1.0 against 1.0±0.0) and eosinophil (3.0±1.0 vs 2.0±1.0), serum levels of CRP (12.6±10.4 against 7.6±5.7 mg/L), IFN-γ (128.4±16.8 against 81.2±7.9 pg/mL), IL-4 (249.7±27.8 vs 178.4±16.0 pg/mL) and IL-10 (116.4±9.9 vs 91.1±11.1 pg/mL) were found in PA compared with farmers. Long term exposure to dichlorvos organophosphate pesticide increases most of the inflammatory markers in farm workers especially among pesticide applicators. Mon, 01 Jul 2019 00:00:00 GMT http://hdl.handle.net/123456789/689 2019-07-01T00:00:00Z http://hdl.handle.net/123456789/687 HUMORAL IMMUNE RESPONSES AND MICRONUTRIENT LEVELS OF Ascaris lumbricoides-INFECTED NIGERIAN CHILDREN ON ANTHELMINTHIC DRUG OR ORAL VACCINATIONS AKINWANDE, KAZEEM SANJO Intestinal helminth infection is associated with altered immune responses and micronutrient status in infected children. These alterations compromise vaccine efficacy of infected children. There is paucity of information on the interplay between humoral immunity, nutritional status and vaccine response, before and after anthelminthic (Albendazole) treatment or oral vaccination in Ascaris lumbricoides (Al)–infected Nigerian children. This study was designed to assess the micronutrient status and immune responses to vaccines in Al–infected Nigerian children before and after anthelminthic treatment or oral vaccination. After ethical approval (UI/EC/13/0331) and informed consent were obtained, a total of 349 children [149 preschool-aged (PSAC) and 200 school-aged children (SAC)] were enrolled into this case-control study. The stool samples were collected and examined for helminth ova using the concentration technique. Twenty three of the Al–infected children were Albendazole treated (AT) while twenty three received oral poliovirus vaccine (OPV) and nineteen received oral rotavirus vaccine (ORV). Age and sex-matched helminth free children were randomly selected as controls. Sera were collected before, one and two months after Albendazole treatment or three weeks after oral vaccinations. Serum concentrations of zinc and selenium were determined using Atomic Absorption Spectrophotometry. Vitamins A and C concentrations were determined using HPLC. Interferon–γ (IFN–γ), tumour necrosis factor–α, interleukins (IL)-4, 6, 8 and 10, transferrin, poliovirus-specific IgA and rotavirus specific IgA concentrations were determined using ELISA. Data were expressed as mean±SEM and analysed using Mann-Whitney U test, Wilcoxon Signed Ranks Test and Kruskal Wallis Test, with levels of significance set at α0.05. Eighty three (23.7%) of the children were infected with A. lumbricoides. In SAC, serum zinc (139.1±2.5 vs 152.7±2.4µg/dL) and vitamin A (119.3±1.7 vs 153.6±5.5µg/dL) levels were significantly lower while transferrin (178.9±4.1 vs 137.9±4.2mg/dL), selenium (62.1±5.8 vs 35.5±1.6ng/mL), IL-8 (995.2±49.3 vs 562.9±44.0pg/mL), IL-6 (16.6±1.8 vs 4.9±0.4pg/mL), IFN–γ (105.9±9.2 vs 62.9±11.6pg/mL), and IL-4 (210±18.3 vs 106.6±2.5pg/mL) levels were significantly higher in Al-infected group compared with controls. In AT group, serum vitamin A levels were significantly higher at one month (203.6±5.4 vs 118.5±2.0µg/dL) and two months (206.2±5.0 vs 118.5±2.0µg/dL) while IL-8 was significantly lower at one month (433.7±85.9vs 619.4±77.4pg/mL) compared with pre-treatment values. In OPV-vaccinated group, post-vaccination serum IL-8 (703.1±41.5 vs 1063.2±69.7pg/mL) and IL-6 (8.1±0.7 vs 7 14.7±2.5pg/mL) levels were significantly lower compared with pre-vaccination levels. Also, post-vaccination serum poliovirus-specific IgA level was lower in OPV-vaccinated group and higher in controls compared with pre-vaccination levels, but not significant. In ORV vaccinated group, post-vaccination serum IFN–γ (101.6±18.4 vs 181.1±37.3pg/mL), IL-4 (230.4±55.8 vs 507.1±130.2pg/mL), and IL-8 (545.3±78.9 vs 966.8±159.6pg/mL) levels were significantly lower while IL-10 (0.25±0.04 vs 0.13±0.02ng/mL) level was significantly higher compared with pre-vaccination levels. Also, serum rotavirus-specific IgA level was not significantly lower in ORV-vaccinated group, but was significantly higher (7.9±0.7 vs 6.9±0.4mg/dL) in controls compared with pre-vaccination levels. Inflammation, deficiencies of zinc, vitamin A and reduced vaccine-specific immunoglobulin A are associated with Ascaris lumbricoides infection in Nigerian children but were reversed with anthelminthic treatment. Anthelminthic treatment with micronutrient supplementation will benefit children during vaccination. Mon, 01 Jul 2019 00:00:00 GMT http://hdl.handle.net/123456789/687 2019-07-01T00:00:00Z