Uridine diphosphate glucuronosyl transferase 1A (UGT1A1) promoter polymorphism in young patients with sickle cell anaemia: report of the first cohort study from Nigeria.

BACKGROUND: (TA) n repeat sequence (rs8175347) of UGT1A1 gene promoter polymorphism is associated with serum bilirubin levels and gallstones among different sickle cell anaemia (SCA) populations. There are no data on UGT1A1 polymorphisms and their impact on Nigerian SCA patients. In this study, we determined the distribution of the UGT1A1 (TA) n genotypes among a group of young Nigerian SCA patients and healthy controls. In addition, the influence of UGT1A1 (TA) n genotypes on the laboratory and clinical events among the patients was determined. METHODS: The distribution of the UGT1A1 (TA) n genotypes among 101 young Nigerian SCA patients and 64 normal appropriate controls were determined and studied. The UGT1A1 (TA) n genotypes were further classified into subgroups and used to differentiate the clinical events and laboratory parameters of the patients. RESULTS: Four (TA) n alleles:(TA)5, 6, 7, and 8 were found. These were associated with 10 genotypes: TA5/5, 5/6, 5/7, 5/8, 6/6, 6/7, 6/8, 7/7, 7/8, 8/8. The normal (wild-type)-(TA) 6/6), low- (TA) 7/7, 7/8, 8/8), intermediate- (TA) 5/7, 5/8, 6/7, 6/8), and high-activity (TA) 5/5, 5/6,) genotypes were found in 24.8, 24.8, 41.5, and 8.9% patients and 20.3, 15.6, 61, and 3.1% controls respectively. The general genotype distribution of the patients and control group were not significantly different. There were significant differences in serum bilirubin and lactate dehydrogenase (LDH) of the patients when differentiated by the UGT1A1 (TA) n genotypes (p<0.05). Asymptomatic gallstones were found in 5.9% of patients and were significantly of the low-activity genotypes sub-group 5 (20%) vs 1(1.3%) p = 0.0033. Although, bilirubin and fetal hemoglobin (HbF) of patients with gallstones were significantly different from those without gallstone, only the serum bilirubin was associated with UGT1A1 (TA) n genotypes on multivariate analysis (p < 0.0001). CONCLUSION: This study highlights the contribution of UGT1A1 polymorphisms, a non-globin genetic factor, to the laboratory and clinical manifestations of young Nigerian SCA patients for the first time. It also shows that children with co-inheritance of low UGT1A1 (TA) n affinity genotypes may be at risk of gallstone, hence the need to follow them up.

Nephroprotective Effect of Essential Oils from Ginger (Zingiber officinale) and Turmeric (Curcuma longa) Rhizomes against Cadmium-induced Nephrotoxicity in Rats.

Several studies have shown that cadmium (Cd) induces nephrotoxicity and many plant foods phytochemicals have been found useful but their possible mechanism of action still remains unexplored. Hence, this study aimed to investigate the nephroprotective effect of essential oils from Nigeria ginger and turmeric rhizomes in cadmium-treated rats by examining their effect on renal function biomarkers (creatinine, urea and BUN), inflammatory cytokines (IL-6, IL-10 and TNF-Alpha) and renal adenosine deaminase (ADA) activity. The result revealed that essential oils from ginger and turmeric rhizomes exert anti-inflammatory effect by preventing alterations of renal function markers and cytokines (IL-6, IL-10 and TNF-Alpha) levels in Cd-treated rats. In addition, the essential oils inhibited renal ADA activity in Cdtreated rats. In conclusion, inhibition of ADA activity and modulation of inflammatory cytokines could be suggested as the possible mechanism of action by which essential oils from ginger and turmeric rhizomes exert their nephroprotective activities.

Otological burdens of Nigerian children with sickle cell disease.

INTRODUCTION/OBJECTIVE: Sickle cell disease (SCD) is associated with episodic illnesses, multi-systemic affectations and end-organs damages. Otolaryngological related complications are not unexpected. Studies on the overall Otolaryngological pathologies in children with SCD relative to their non-SCD counterparts are scanty in Nigeria. We hypothesized that children with SCD are likely to have more otological burdens than their non-SCD counterparts. Thus, we embarked on this study to describe and compare the overall ear diseases burdens seen in children with sickle cell disease relative to their non-SCD counterparts. METHODOLOGY: A cross-sectional study of otologic diseases among children with SCD and their non-SCD counterparts attending the paediatrics and otolaryngological clinics of a Nigerian tertiary institution was conducted. RESULTS: Overall, 80 (47.62%) of the 168 ears of SCD patients compared to 37 (22.02%) of the 168 ears of their non-SCD counterparts were affected by diseases (p < 0.0001). The diseases were Wax, Otitis Media with Effusion, Suppurative Otitis Media, Otosclerosis and Sensorineural Hearing Loss (SNHL). There was a significant difference in the prevalence of SNHL and solitary otosclerosis between the SCD patients and their non-SCD counterparts (P < 0.05) respectively. Both the Haemoglobin concentration and HbF did not discriminate between the SCD participants with or without SNHL (P > 0.05). CONCLUSION: This study showed that otological burdens are more prevalent in children with SCD than the non-SCD population. The microbiological peculiarity of suppurative otitis media (SOM) among participants stresses the need for concerted efforts at preventing SOM in SCD children. There is need for special Otolaryngological care for SCD children.

Factors Influencing the Academic Performance of Children with Sickle Cell Anaemia in Ekiti, South West Nigeria.

Background: There is a paucity of information on factors that influence the school performance of children with sickle cell anaemia (SCA) in Nigeria, despite her huge burden of the disease. Methods: In total, 101 children with SCA were recruited at a paediatric clinic in Nigeria. Their socio-demographic-matched classmates were the controls. Academic performance and cognitive functioning were obtained from school reports and Ziler's Draw-a-Person Test, respectively. Factors influencing the academic performance were determined. Results: Children with SCA had higher rates of school absence and lower haemoglobin concentration (p < 0.05). There was no difference in overall school performance between children with SCA and controls (59.0 vs. 60.6%; p = 0.256). School absenteeism > 1 week independently predicts poor school performance among the study participants (odds ratio = 15.71; 95% confidence interval = 5.93-41.66; p =0.000). Most SCA children with poor performance were absent from school for > 1 week. Conclusion: There is need to address causes of school absenteeism among children with SCA.

Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney.

In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd) and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05). However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes) and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO). However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

Effect of Cadmium Stress on Non-enzymatic Antioxidant and Nitric Oxide Levels in Two Varieties of Maize (Zea mays).

Cadmium (Cd) is one of the most toxic heavy metals that inhibit physiological processes of plants. Hence, the present study sought to investigate the effect of cadmium-contaminated seeds from two varieties of maize (Zea mays) on non-enzymatic antioxidant and nitric oxide levels. Seeds of yellow and white maize were exposed to different concentrations of Cd (0, 1, 3 and 5 ppm) for two weeks. The results from this study revealed that both varieties of maize bio-accumulate Cd in leaves in a dose-dependent manner. In addition, Cd exposure caused a significant (p < 0.05) decrease in total phenolic, GSH and nitric oxide (NO) levels at the highest concentration tested when compared with control. Therefore, the observed decrease in NO and endogenous antioxidant status by Cd treatment in maize plants could suggest some possible mechanism of action for Cd-induced oxidative stress and counteracting effect of the plants against Cd toxicity.

Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model.

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage for 7 days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.