PROFESSOR SAMUEL OMOKHODION: NIGERIA'S ICON OF PAEDIATRIC CARDIOLOGY.

Samuel Omokhodion was born to Pa Jacob Avblimen and Madam Victoria Edewede Omokhodion of Emuhi Ekpoma, Esan West Local Government of Edo State on 9th March 1953, in Ondo state while his father was working in the Civil Service of the old Western Region of Nigeria. Samuael Omohodion attained the illustrious age of 70 years in December 2022. This edition of chronicles examines his biography - early life, career in paediatric cardiology, number of publications, professional affiliations, and priestly calling.

PRELIMINARY REPORT ON THE USE OF NUTRACEUTICALS IN THE MANAGEMENT OF SICKLE CELL ANEMIA: A CASE SERIES.

Background: There is growing recognition of the benefits of nutraceuticals in the management of sickle cell disease but a scarcity of reports on their use. Nutraceuticals are food or parts of food that provide medical or health benefits. They include botanicals, functional foods and medicinal foods. This is a preliminary report on the use of nutraceuticals in the management of a small cohort of children with sickle cell disease in Nigeria. Patients and Methods: The retrospective audit of clinical outcomes was carried out at a brain center located within the Federal Capital Territory, Abuja, Nigeria. Children, aged 1 to 12 years, presenting with sickle cell anaemia were evaluated at baseline and at six months after the commencement of a cocktail of nutraceuticals using an objective grading tool. Changes in weight, haematocrit and frequency of sickle cell crises were determined. On account of the small sample size, Wilcoxon sign test was used to determine the similarity / difference between the average values of weight, PCV, and crises obtained at enro7lment and six months. Results: Ten children with sickle cell anaemia were placed on nutraceuticals therapy. The average age of the children was 8.5 (range 1 - 12) years. Aroga immune support was the commonest component of the nutraceutical cocktail given to the children. There was a rise in average weight (from 21.8 to 23.0 Kg, p-value 0.236) and average haematocrit (22.8 to 27.2, p-value 0.011) at six months compared to values obtained at baseline. There was also a fall in the average frequency of sickle cell crises at six months compared to values obtained at baseline (from 7.4 to 3.2, p-value 0.011). Overall, eight out of the ten children showed moderate to good clinical improvement. There was no documentation of any adverse reaction to the medications in any of the children. Conclusion: The results suggest that the use of nutraceuticals may be beneficial in the management of sickle cell anaemia in children. However, the results are preliminary and will require stronger evidence. There is a need for controlled clinical trials for using larger sample sizes. Such clinical trials of unconventional therapies should be conducted with great care and concern for the safety of the participants.

BIBLIOMETRIC ANALYSIS AND IMPACT FACTOR OF ANNALS OF IBADAN POSTGRADUATE MEDICINE JOURNAL BETWEEN 2003-2023: THE PIVOTAL ROLES OF THE FRONTIERSMAN.

Background: Bibliometric appraisal of a research publication outfit of this nature serves as a tool to evaluate the direction of research activities of Annals of Ibadan Postgraduate Medicine Journal as it pertains to article publication between 2003 and 2023, and to determine the research impacts on the body of knowledge. The essence of this review is to determine the quantum volume of research output, nature of publication, regional distribution, and citations. Methodology: Information was transcribed on the cataloguing cards for the generation of data bank. Subject analysis was carried out using Medical Subject Headings of 2023 edition. Excel spreadsheet was used to analyze the data. Univariate analysis was done and presented in frequency and proportions. Descriptive statistics were presented in charts, line graphs, and tables. Results: Five hundred and fifty-two research articles were submitted during this period (2003 - 2023) while 21 out of this are still in the peer review cycle and has been carried forward to year 2024. Of the 531 reviewed, 441 was published with a manuscript acceptance rate of 83%. The highest number of articles, 45 (8.2%) was published in 2023, followed by 2021 with 39 articles (7.1%) and the least published year was 2003 with eight. AIPM has contributed significantly to the body of knowledge with a total of 441 research output over this period, out of which we had 309 publications between 2008 - 2021 with 2,869 citations. Oyo State recorded the maximum number of publications in terms of geographical distribution with most of the authorship from Ibadan. Conclusion: AIPM has contributed significantly to the body of knowledge with a total of 441 research output, and manuscript acceptance rate of 83%. Also, a 2,869 citations were recorded over a 13-year period. There was a gradual increase in research output during the period.

DAY OF TRIBUTES: PROFESSOR ISAAC ADETAYO GRILLO.

Professor Isaac Adetayo Grillo was born on January 15, 1931, in Lagos. He had both his elementary and secondary school education at Baptist Academy, Lagos. His autobiography recorded that he excelled brilliantly at the school. He earned the Doctor of Medicine at the University of Kansas in 1960. He completed his residency training in General Surgery and Cardiothoracic Surgery, passing the American Board of General Surgery and the American Board of Thoracic Surgery examinations in 1966 and 1967 respectively. He returned to Nigeria in 1968. Of particular note, Professor Grillo led a team that performed the first open heart Surgery in Nigeria by a group of all Nigerian Doctors and Nurses in 1978. He lived an illustrious life. Always wanting to excel and do his very best, he became Nigeria's most famous Cardiothoracic Surgeon during his time. Professor Grillo passed on after a brief illness on the 4th of April, 2022.

Comparative evaluation of three histidine-rich Protein-2 based rapid diagnostic tests, microscopy and PCR for guiding malaria treatment in Ibadan, Southwest Nigeria.

BACKGROUND: Malaria rapid diagnostic tests (mRDTs) are the preferred option for programmatic deployment. AIMS: There are numerous mRDTs on the Nigerian market and there is a need to guide practitioners on the relative performance of the commonly used brands of mRDT in Nigeria. SUBJECTS AND METHODS: The performance of three commonly used Histidine-Rich-Protein-2-based mRDTs (SD-Bioline™, Carestart™ and Paracheck-Pf™) against microscopy of Giemsa stained blood and polymerase chain reaction (PCR) was evaluated among 190 febrile under-5 children in Ibadan, Nigeria. We calculated the sensitivity, specificity, predictive values, accuracy, and agreements. RESULTS: There were 53.2% males. The prevalence of malaria parasite by microscopy was 46.8% and 57.9% by PCR. Malaria parasite detection by SD-Bioline™ was 60.5%, Carestart™: 60.0% and Paracheck-Pf™ 60.0%. Using microscopy as the gold standard, the sensitivities of SD-Bioline™, Carestart™ and Paracheck-Pf™ mRDT were 97.8%, 96.7% and 97.8% respectively while the specificities were 73.0%, 72.0% and 74.0% respectively. Using PCR as the gold standard, the sensitivity for both SD-Bioline™ and Paracheck-Pf™ was 85.5% and for CareStart was 84.6% while the specificity of SD-Bioline™, Carestart™, and Paracheck-Pf™ was 73.8%, 72.4%, and 75.0% respectively. The test accuracy was 81.0% for both SD-Bioline™ and Paracheck-Pf™ and 80.0% for Caresatrt™. The kappa coefficient of agreement between PCR and each of SD-Bioline™, Carestart, ParaCheck™ and microscopy was 0.597, 0.578, 0.609 and 0.739 respectively. CONCLUSION: The performance of the three mRDTs is a proof that any of the three is suitable for use in the diagnosis of malaria in the southwest of Nigeria.

Exposure to Agrochemicals and Markers of Kidney Damage among Farmers in Rural Communities in Southwestern Nigeria.

BACKGROUND: Chronic kidney disease of unknown origin (CKDu) is assuming an epidemic proportion, especially in farming communities worldwide. We explored the relationship between CKD markers and agrochemical exposure among rural farmers in South Western Nigeria. METHODS: We studied selected farming communities in Southwestern Nigeria where the use of agrochemicals was widespread. A pre-tested questionnaire was administered to participants. Anthropometric data, information on use of agro-chemicals; urine and blood samples were obtained. Informed consent was obtained from participants. The study was approved by the Institutional Ethics committee and complied with 1975 Helsinki declaration, as revised in 2000. RESULTS: A total of 438 farmers made up of 202 males (46.1%) and 236 females (53.9%) were studied. The mean microalbuminuria was 30.2 ±11.7 mg/dl. Majority of the farmers had CKD stage 2(42.0%) and CKD stage 3 (37.7%). The type of farming engaged in had a positive, but not significant, correlation with eGFR (r=0.012, p=0.832). There was positive correlation between type of farming and GFR category (r=0.24, p=0.000). Frequency of use of hexachlorocyclohexane had a positive and significant correlation with eGFR (r=0.111, p=0.045). Annual crop farming had a correlation with UACR (r=0.149, p=0.024). CONCLUSION: Annual crop farming had a positive correlation with UACR, eGFR and GFR category. The prolonged use of agrochemicals on an annual basis can cause kidney damage.

PERSISTENCE OF PLASMODIUM FALCIPARUM HRP2 ANTIGEN AFTER EFFECTIVE ANTIMALARIAL THERAPY.

Introduction: Histidine Rich Protein 2 based (HRP2-based) malaria rapid diagnostic tests (mRDTs) have been shown to perform as well as routine light microscopy, however, they are limited by some factors including persistence of HRP2 antigenemia. In this paper we report the evaluation of an HRP2-based mRDT in a prospective study that enrolled children and followed them up for 28 days. Methods: Children aged below five years, with acute episode of fever/pyrexia, were enrolled. The enrolled participants had expert malaria microscopy and RDT done at enrolment (Day 0), and on days 1, 2, 3, 7, 14, 21, and 28. The malaria RDT test was considered positive when the antigen and control lines were visible in their respective windows, negative when only the control band was visible and invalid when the control band was not visible. Faint test lines were considered positive. The RDT results were compared to those of expert microscopy. Results: Two hundred and twenty-six children aged 29.2 ± 15.5 months were enrolled. The proportion of children positive by expert malaria microscopy and RDT was 100% and 95.6% respectively. During the 28 day follow up of the children the proportions positive by microscopy and RDT on days 3, 7, 14, and 28 were 1% and 94.6%, 0% and 93.5%, 0% and 91%, and 16.5% and 80.6% respectively. Gender and age dependent analysis of proportion of positive children were similar. Proportion of children with persistence of HRP2 antigen appeared to be lower in those with parasite density below 200/µL, however, this observation requires further evaluation in larger studies. Conclusion: the study revealed a high proportion of persistence of HRP2 antigen in the children 28 days after effective antimalarial therapy. Histidine rich protein 2 based malaria rapid diagnostic tests are not recommended for monitoring of antimalarial therapies.

PERSPECTIVE: SUSTAINING EFFECTIVE MALARIA CONTROL DURING THE COVID-19 PANDEMIC.

The COVID-19 pandemic has spread to many malaria endemic countries in sub Saharan Africa. There is little or no experience on how the impact of policies put in place to curtail further spread of the pandemic will affect the epidemiology of malaria during the malaria season. The objective of this write-up is to put in perspective, the need to ensure effective malaria control in the midst of the COVID-19 crises. Proper integration of the COVID-19 safety and treatment guidelines with malaria control policies and effective diagnosis in malaria endemic countries in sub Saharan Africa are important in mitigating morbidity and mortality rates which may rise if malaria cases are neglected due to the current burden of the COVID-19 pandemic.

Sodium acetate prevents nicotine-induced cardiorenal dysmetabolism through uric acid/creatine kinase-dependent pathway.

BACKGROUND: Cigarette smoking or nicotine replacement therapy has been associated with cardiometabolic disorders (CMD). Hyperuricemia has been implicated in the pathogenesis of CMD and cardiorenal dysfunction. Gut microbiota-derived short chain fatty acids (SCFAs) have been reported to have beneficial glucoregulatory and cardiorenal protective effects. This study aimed at investigating the effect of acetate, a gut-derived SCFA, on nicotine-induced CMD and associated cardiorenal dysmetabolism. MATERIALS AND METHOD: Twenty-four male Wistar rats (n = 6/group) were grouped as: vehicle (p.o.), nicotine-exposed (1.0 mg/kg; p.o.), and sodium acetate-treated (200 mg/kg; p.o.) with or without nicotine exposure daily for 6 weeks. Glucose regulation was evaluated by oral glucose tolerance test and homeostatic model assessment of insulin resistance. Cardiac and renal triacylglycerol (TG), lactate, nitric oxide (NO), uric acid (UA) levels, lactate dehydrogenase (LDH), creatine kinase (CK), adenosine deaminase (ADA), and xanthine oxidase (XO) activities were measured. RESULTS: The CMD were confirmed in the nicotine-exposed rats that exhibited lower body weight, insulin resistance, endothelial dysfunction, glucose intolerance, increased cardiac and renal TG, TG/HDL-cholesterol, UA, lactate, lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, LDH, CK, ADA and XO activities. Concurrent treatment with acetate prevented nicotine-induced glucometabolic and cardiorenal alterations. CONCLUSION: In summary, these results implied that nicotine exposure caused glucometabolic dysregulation and surplus lipid deposit in the heart and kidney through increased UA production and CK activity. Therefore, oral acetate administration prevents cardiorenal lipotoxicity and glucometabolic dysregulation via suppression of UA production and CK activity in nicotine-exposed rats.

Estrogen-progestin oral contraceptive and nicotine exposure synergistically confers cardio-renoprotection in female Wistar rats.

Approximately fifty percent of premenopausal women who smoke cigarettes or on nicotine replacement therapy are also on hormonal contraceptives, especially oral estrogen-progestin. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR) which causes lipid influx into non-adipose tissue and impairs Na+/K+ -ATPase activity, especially in the heart and kidney. However, the effects of nicotine on excess lipid and altered Na+/K+ -ATPase activity associated with the use of estrogen-progestin therapy have not been fully elucidated. This study therefore aimed at investigating the effect of nicotine on cardiac and renal lipid influx and Na+/K+ -ATPase activity during estrogen-progestin therapy. Twenty-four female Wistar rats grouped into 4 (n = 6/group) received (p.o.) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 µg ethinyl estradiol and 5.0 µg levonorgestrel) and estrogen-progestin only daily for 6 weeks. Data showed that estrogen-progestin treatment or nicotine exposure caused IR, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, reduced bilirubin and circulating estradiol. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase activity while nicotine did not alter Na+/K+-ATPase activity but increased plasma and tissue cotinine. Renal Na+/K+-ATPase activity was not altered by the treatments. However, all these alterations were reversed following combined administration of oral estrogen-progestin therapy and nicotine. The present study therefore demonstrates that oral estrogen-progestin therapy and nicotine exposure synergistically prevents IR-linked cardio-renotoxicity with corresponding improvement in cardiac and renal lipid accumulation, oxidative stress, inflammation and Na+/K+-ATPase activity.

Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid.

Context: Estrogen-progestin combined oral contraceptive (COC) has been connected to mineralocorticoid receptor (MR) activation and adverse cardiometabolic events. We consequently hypothesised that insulin resistance (IR), hyperuricemia, and elevated circulating GSK-3 induced by COC is through activation of MR via mineralocorticoid and glucocorticoid pathways.Methods: Female Wistar rats aged 12 weeks received (po) vehicle and COC (1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel) with or without MR blocker (0.25 mg/kg spironolactone; Spl), daily for eight weeks.Results: Data showed that COC treatment led to increased IR, 1-hour postload glucose level, insulinemia, triglyceride/HDL-cholesterol ratio, total cholesterol/HDL-cholesterol ratio, uric acid, GSK-3, aldosterone, corticosterone values, impaired glucose tolerance and pancreatic ß-cell function. However, MR blockade by Spl ameliorated all these alterations except that of aldosterone.Conclusion: The results demonstrate that COC induces IR, hyperuricemia and high GSK-3 levels through activation of MR via glucocorticoid dependent pathway.