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Background: The outlook of chronic kidney disease (CKD) in low-and-medium-income-countries is poor. Modern farming practices in Nigeria are becoming increasingly associated with the use of herbicides and pesticides., Aim: The study aimed to evaluate agrochemical use in farming practices and risk factors for kidney disease among dwellers of rural farming communities in South-West Nigeria., Methods: This was a cross-sectional survey of adult dwellers of an agrarian rural farming community in South-West Nigeria. Participants provided information on demographics, lifestyles, knowledge, and awareness of risk factors for kidney disease, and the use of agrochemicals in farming practice. Anthropometric measurements and blood pressure values were obtained while blood and spot urine were collected for random blood glucose, serum creatinine, urinalysis, and albumin-creatinine ratio., Results: A total of 572 rural dwellers were enrolled in the study, with a mean age of 49.9 ± 17.5 years while 39.3% were male and 88.9% engaged in active farming. The prevalence of traditional risk factors for kidney disease was hypertension (24.3%), Diabetes mellitus (2.8%), cigarette smoking (7.5%), alcohol intake (20.8%) and herbal consumption (57.1%). The use of pesticides/herbicides was reported in 69.9%, while 25.3% did not use protective gear during its use. Proteinuria, hematuria, and reduced eGFR were observed in 29.8%, 6.1%, and 33.9% of participants, respectively., Conclusion: This study showed a high prevalence of herbicides and pesticide use and traditional risk factors for kidney disease, in addition to the high prevalence of markers of kidney damage among the dwellers of rural farming settlements in South-West Nigeria., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Abstract: Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) sham, 2) sepsis (cecal ligation and puncture) without subsequent resuscitation, and 3) sepsis with lactated Ringer plus norepinephrine resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output and glomerular filtration rate were measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary perfusion, and medullary tissue oxygen tension (mtPO 2 ) were determined for 12 h. Cecal ligation and puncture decreased mean arterial pressure and cardiac output by more than 50%, with a proportional increase in renal vascular resistance and a 60-80% reduction in renal blood flow, cortical perfusion, medullary perfusion, and mtPO 2 compared to sham. Cecal ligation and puncture also decreased glomerular filtration rate by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO 2 , changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to cecal ligation and puncture develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Chronic kidney disease (CKD) is a progressive and long-term condition marked by a gradual decline in kidney function. CKD is prevalent among those with conditions such as diabetes mellitus, hypertension, and glomerulonephritis. Affecting over 10% of the global population, CKD stands as a significant cause of morbidity and mortality. Despite substantial advances in understanding CKD pathophysiology and management, there is still a need to explore novel mechanisms and potential therapeutic targets. Urotensin II (UII), a potent vasoactive peptide, has garnered attention for its possible role in the development and progression of CKD. The UII system consists of endogenous ligands UII and UII-related peptide (URP) and their receptor, UT. URP pathophysiology is understudied, but alterations in tissue expression levels of UII and UT and blood or urinary UII concentrations have been linked to cardiovascular and kidney dysfunctions, including systemic hypertension, chronic heart failure, glomerulonephritis, and diabetes. UII gene polymorphisms are associated with increased risk of diabetes. Pharmacological inhibition or genetic ablation of UT mitigated kidney and cardiovascular disease in rodents, making the UII system a potential target for slowing CKD progression. However, a deeper understanding of the UII system's cellular mechanisms in renal and extrarenal organs is essential for comprehending its role in CKD pathophysiology. This review explores the evolving connections between the UII system and CKD, addressing potential mechanisms, therapeutic implications, controversies, and unexplored concepts., Competing Interests: The authors declared that they have no conflicts of interest in this work., (© 2024 The Authors.)

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., (© Association of Resident Doctors, UCH, Ibadan.)

Context and Aim: Given the challenges of microscopy, we compared its performance with SD-Bioline malaria rapid diagnostic test (MRDT) and polymerase chain reaction (PCR) and evaluated the time it took for positive results to become negative after treatment of children with acute uncomplicated malaria., Subjects and Methods: We present the report of 485 participants with complete MRDT, microscopy, and PCR data out of 511 febrile children aged 3-59 months who participated in a cohort study over a 12-month period in rural and urban areas of Ibadan, Nigeria. MRDT-positive children received antimalaria and tested at every visit over 28 days. Speciation was also carried out by PCR., Results: With microscopy as the gold standard, SD-Bioline™ had 95.2% sensitivity, 66.4% specificity, 67.5% positive predictive value (PPV), and 94.9 negative predictive value (NPV), while with PCR the findings were 84.3% sensitivity, 66.5% specificity, 72.7% PPV, and 80.1% NPV. PCR speciation of malaria parasites revealed 91.6% Plasmodium falciparum, 18.9% Plasmodium malariae, and 4.4% Plasmodium ovale. Among the 47 children with P. malariae infections, 66.0% were coinfected with P. falciparum, while 54.6% cases of P. ovale occurred as coinfections with P. falciparum. The median time to a negative MRDT was 23.2 days, while the median time to a negative malaria microscopy was 3.8 days. The two survival curves were significantly different., Conclusions: The SD-Bioline TM MRDT performed well, with remarkable persistence of rapid test-positive for an average of 23 days post treatment. The prevalence of P. malaria is somewhat greater than expected., Competing Interests: None

Control of microvascular reactivity by 5-hydroxytryptamine (5-HT; serotonin) is complex and may depend on vascular bed type and 5-HT receptors. 5-HT receptors consist of seven families (5-HT 1 -5-HT 7 ), with 5-HT 2 predominantly mediating renal vasoconstriction. Cyclooxygenase (COX) and smooth muscle intracellular Ca 2+ levels ([Ca 2+ ] i ) have been implicated in 5-HT-induced vascular reactivity. Although 5-HT receptor expression and circulating 5-HT levels are known to be dependent on postnatal age, control of neonatal renal microvascular function by 5-HT is unclear. In the present study, we demonstrate that 5-HT stimulated human TRPV4 transiently expressed in Chinese hamster ovary cells. 5-HT 2A is the predominant 5-HT 2 receptor subtype in freshly isolated neonatal pig renal microvascular smooth muscle cells (SMCs). HC-067047 (HC), a selective TRPV4 blocker, attenuated cation currents induced by 5-HT in the SMCs. HC also inhibited the 5-HT-induced increase in renal microvascular [Ca 2+ ] i and constriction. Intrarenal artery infusion of 5-HT had minimal effects on systemic hemodynamics but reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in the pigs. Transdermal measurement of glomerular filtration rate (GFR) indicated that kidney infusion of 5-HT reduced GFR. HC and 5-HT 2 receptor antagonist ritanserin attenuated 5-HT effects on RBF, RVR, and GFR. Moreover, the serum and urinary COX-1 and COX-2 levels in 5-HT-treated piglets were unchanged compared with the control. These data suggest that activation of renal microvascular SMC TRPV4 channels by 5-HT impairs kidney function in neonatal pigs independently of COX production., Competing Interests: Declaration of competing interest The authors report no conflict of interest. The data underlying this article will be shared on reasonable request to the corresponding author., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Samuel Omokhodion was born to Pa Jacob Avblimen and Madam Victoria Edewede Omokhodion of Emuhi Ekpoma, Esan West Local Government of Edo State on 9 th 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., (© Association of Resident Doctors, UCH, Ibadan.)

Background: In Nigeria, declining responsiveness to artemether-lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine-artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared., Methods: In an open-labelled, randomized, controlled clinical trial, 172 children aged 3-144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation., Results: 165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise., Conclusion: PA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria., Retrospective Trial Registration: Clinicaltrials.gov: NCT05192265., (© 2023. The Author(s).)

Many drugs used in paediatric medicine are off-label. There is a rising call for the use of adaptive clinical trial designs (ADs) in responding to the need for safe and effective drugs given their potential to offer efficiency and cost-effective benefits compared with traditional clinical trials. ADs have a strong appeal in paediatric clinical trials given the small number of available participants, limited understanding of age-related variability and the desire to limit exposure to futile or unsafe interventions. Although the ethical value of adaptive trials has increasingly come under scrutiny, there is a paucity of literature on the ethical dilemmas that may be associated with paediatric adaptive designs (PADs). This paper highlights some of these ethical concerns around safety, scientific/social value and caregiver/guardian comprehension of the trial design. Against this background, the paper develops a non-static conceptual lens for understanding PADs. It shows that ADs are epistemically open and reduce some of the knowledge-associated uncertainties inherent in clinical trials as well as fast-track the time to draw conclusions about the value of evaluated drugs/treatments. On this note, the authors argue that PADs are ethically justifiable given they (1) have multiple layers of safety, exposing enrolled children to lesser potential risks, (2) create social/scientific value generally and for paediatric populations in particular, (3) specifically foster the flourishing of paediatric populations and (4) can significantly improve paediatric trial efficiency when properly designed and implemented. However, because PADs are relatively new and their regulatory, ethical and logistical characteristics are yet to be clarified in some jurisdictions, the cooperation of various public and private stakeholders is required to ensure that the interests of children, their caregivers and parents/guardians are best served while exposing paediatric research subjects to the most minimal of risks when they are enrolled in paediatric trials that use ADs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Studies have shown that cardiac triglyceride accumulation and impaired Na + -K + -ATPase activity are linked to diabetes- related cardiovascular disease, particularly in women. Objectives: We hypothesised that allopurinol (ALL) and valproic acid (VPA) treatment would improve cardiac triglyceride and Na + -K + -ATPase activity independent of circulating aldosterone in Combined Oral Contraceptive (COC)-induced dysglycemia Materials and methods: Rats received COC (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; po ) with or without ALL (1 mg; po ) and VPA (20 mg; po ) for 6 weeks. Results: COC-treatment led to impaired glucose tolerance, accumulated abdominal fat, dyslipidemia, elevated plasma MDA, PAI-1 and aldosterone levels and also reduced plasma nitric oxide bioavailability and cardiac Na + -K + -ATPase activity. However, either ALL or VPA treatment ameliorated these alterations comparably independent of elevated aldosterone level Discussion and conclusion: Our results suggest that either ALL or VPA would improve cardiac TG and Na + -K + -ATPase activity comparably in COC-treated rats, regardless of circulating aldosterone level.

Transdermal measurement of glomerular filtration rate (GFR) has been used to evaluate kidney function in conscious animals. This technique is well established in rodents to study acute kidney injury and chronic kidney disease. However, GFR measurement using the transdermal system has not been validated in pigs, a species with a similar renal system to humans. Hence, we investigated the effect of sepsis on transdermal GFR in anesthetized and mechanically ventilated neonatal pigs. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). The transdermal GFR measurement system consisting of a miniaturized fluorescence sensor was attached to the pig's shaved skin to determine the clearance of fluorescein-isothiocyanate (FITC) conjugated sinistrin, an intravenously injected GFR tracer. Our results show that at 12 h post-CLP, serum creatinine increased with a decrease in GFR. This study demonstrates, for the first time, the utility of the transdermal GFR approach in determining renal function in mechanically ventilated, neonatal pigs.

Background: Hypertension is the largest contributor to the global burden of disease. Emerging risk factors for cardiovascular disease include blood pressure variability (BPV), but evidence on BPV is lacking among older Nigerians. We reported BPV in a cohort of older persons at the University College Hospital (UCH), Ibadan., Methods: We conducted a retrospective cohort study of respondents aged >50 years within the Ibadan Ambulatory Blood Pressure Registry at the UCH, Ibadan, Nigeria. Socio-demographic characteristics, lifestyle habits and anthropometric measurements were obtained., Results: Among 639 respondents, 332 (52.0%) were female. The blood pressure (BP) variables were strongly associated with age. Compared with younger age groups, mean diastolic BP (DBP) was less at an older age, whereas mean pulse pressure was greater. During the wake-up and sleep periods, mean DBP and mean arterial BP were less with each increasing age category, whereas mean pulse pressure was larger with each increasing age category. BP dipping, systolic, diastolic and mean arterial BP decreased with age. Overall, timed BPV increased significantly with increasing age. The prevalence of white-coat hypertension was greater among older participants than younger participants. Most respondents in the 50-59 years' age group were non-dippers (55.8%), whereas 33.7% of older respondents were reverse-dippers., Conclusion: Older persons experienced a greater abnormal circadian blood variation and greater BPV than younger people. In Nigeria, follow-up data are needed to determine the prognostic significance of these data in this population., Competing Interests: None

Background: Although the global malaria burden is decreasing, there are still concerns about overdiagnosis of malaria and the danger of misdiagnosis of non-malaria causes of fever. Clinicians continue to face the challenge of differentiating between these causes despite the introduction of malaria rapid diagnostic tests (mRDTs)., Aim: To determine the prevalence and causes of non-malaria-caused fever in children in South-Western Nigeria., Methods: Secondary analysis of data obtained to evaluate the effect of restricting antimalarial treatment to positive mRDT children in rural and urban areas of southwest Nigeria. Clinical examinations, laboratory tests for malaria parasites (including thick blood film and mRDT) and bacterial identification were performed on children aged 3-59 months (n = 511). The non-malaria group comprised febrile children who had both negative mRDT and microscopy results, while the malaria group included those who were positive for either mRDT or microscopy. We compared the causes of fever among children with non-malaria fever and those with malaria., Results: The prevalence of non-malaria fever and bacteria-malaria co-infection was 37.2% and 2.0%, respectively. Non-malarial pathogens identified were viral (54.7%) and bacterial (32.1%) infections. The bacterial infections included bacteriaemia (2.7%), urinary tract infections (21.6%), skin infections (11.6%) and otitis media (2.6%). The leading bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae., Conclusion: The high prevalence and wide range of non-malarial infections reinforces the need for point-of-care tests to identify bacterial and viral infections to optimize the treatment of febrile illnesses in malaria-endemic areas., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© Association of Resident Doctors, UCH, Ibadan.)

Context: Suppressed glucose metabolism, elevated fatty acid metabolism and lipid deposition within myocardial cells are the key pathological features of diabetic cardiomyopathy. Studies have associated cadmium exposure with metabolic disturbances., Objective: To examine the effects of cadmium exposure on cardiac glucose homeostasis and lipid accumulation in male Wistar rats., Methods: Male Wistar rats were treated for 21   days as ( n   =   5): Control, cadmium chloride Cd5 (5   mg/kg, p.o. ), cadmium chloride Cd30 (30   mg/kg, p.o )., Results: The fasting serum insulin level in this study decreased significantly. Pyruvate and hexokinase activity reduced significantly in the Cd5 group while no significant change in lactate and glycogen levels. The activity of pyruvate dehydrogenase enzyme significantly increased with an increasing dosage of cadmium. The free fatty acid, total cholesterol and triglyceride levels in the heart increased significantly with increasing dosage of cadmium when compared with the control. Lipoprotein lipase activity in the heart showed no difference in the Cd5 group but a reduction in the activity in the Cd30 group was observed., Conclusion: This study indicates that cadmium exposure interferes with cardiac substrate handling resulting in impaired glucometabolic regulation and lipid accumulation which could reduce cardiac efficiency.

Lead acetate associated tissue injury has been linked to altered antioxidant defenses, hyperuricemia and inflammation. We hypothesized that watermelon rind extract, would ameliorate lead acetate-induced hepato-renal injury. Thirty Male Wistar rats received distilled water, lead acetate (Pb; 5 mg/kg) with or without watermelon rind extract (WM; 400 mg/kg; WM + Pb; 15 days of WM pretreatment); Pb + WM (15 days of WM post treatment) and simultaneous treatment (WM-Pb) for 30 days. Lead toxicity led to elevated serum malondialdehyde, creatinine, urea, uric acid, lactate dehydrogenase, liver injury enzymes, as well as decreased body weight. Decreased serum levels of reduced glutathione, nitric oxide, total protein and glutathione peroxidase activity was also observed. However, these alterations were ameliorated by watermelon rind extract in lead acetate-treated rats. Watermelon rind ethanol extract protects against lead acetate-induced hepato-renal injury through improved antioxidant defenses at least in part, via uric acid/nitric oxide-dependent pathway signifying the health benefits of this agricultural waste and a potential for waste recycling while limiting environmental pollution., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Aim: Environmental pollutants such as plastic-component substances (phthalates and bisphenol A) that coexist in natural ecosystems have been linked to an increase in the occurrence of human health hazards, particularly cardiovascular health. This study was designed to investigate single and combined cardio-toxic effects of dibutyl phthalate and bisphenol-A and the possible interventional role of rutin., Materials and Methods: Forty-two rats were randomized into 7 groups of 6 animals each and were treated as follows for 28 days: Control (0.1% DMSO), Bisphenol-A (BPA, 25 mg/kg, p.o), Dibutyl phthalate (DBP, 25 mg/kg, p.o), BPA + Rutin (25 mg/kg, Rt 50 mg/kg), DBP + Rt (25 mg/kg, Rt 50 mg/kg), BPA + DBP, BPA + DBP + Rt. Cardiac lipid peroxidation, antioxidants and inflammatory markers activities were measured., Key Findings: The result showed that BPA reduced the superoxide dismutase (SOD) activity, DBP and DBP+ BPA reduced the catalase (CAT) activity, DBP reduced glutathione (GSH) and nuclear factor erythroid 2-related factor 2 (Nrf2) while malondialdehyde (MDA) increased in DBP + BPA group. Also, DBP increased tissue C-reactive protein (CRP); DBP, DBP + BPA increased tissue nuclear factor kappa B (NF-κB); DBP + BPA increased plasma CRP; BPA increased plasma NF-κB. However, rutin efficiently reduced MDA level, CRP and NF-κB; increasing SOD, GSH and Nrf2 levels in DBP and BPA exposed rats., Significance: These results revealed that bisphenol and dibutyl phthalate exposure caused oxidative stress and inflammation in the heart through Nrf2/NF-κB signaling pathway while oral administration of rutin prevents these effects via upregulation of Nrf2 and suppression of NF-κB signaling pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent., Competing Interests: The authors report no declarations of interest., (Copyright © 2021 Javad Sharifi-Rad et al.)

Pregnancy is an insulin-resistant condition especially at near term predisposing maternal kidneys to hyperinsulinemia-induced oxidative stress. The impact of fructose on renal metabolic dysregulation and oxidative stress in pregnancy requires elucidation. Short-chain fatty acids (SCFAs) are known for protective roles in oxidative stress conditions. Therefore, the study aimed at investigating fructose-induced glucose dysregulation and renal oxidative stress in pregnant and non-pregnant rats and the possible preventive role of SCFA, acetate. Thirty female Wistar rats were grouped (n = 5/group). Three groups were made pregnant (P); the other three remained non-pregnant (NP). Both pregnant and non-pregnant rats received drinking water (control), 10% fructose (w/v) (NP+F or P+F), and 10% (w/v) fructose plus sodium acetate (200 mg/kg) (NP+F+A or P+F+A) for 3 weeks. Renal and plasma glutathione antioxidant index (GSH/GSSG), G6PDH, and adenosine were significantly lower in NP+F and P+F groups compared with control while renal and plasma adenosine deaminase (ADA), xanthine oxidase (XO), uric acid (UA), lactate dehydrogenase (LDH), and malonaldehyde (MDA) were significantly elevated in NP+F and P+F groups compared with controls. HOMA-IR showed marked impairment in both NP+F and P+F groups. The P+F group revealed greater suppression in plasma and renal G6PDH-dependent antioxidant index, adenosine, and aggravation of LDH, MDA compared with the NP+F group (p < 0.05). Sodium acetate reduces plasma and renal surrogate oxidative stress markers, improved G6PD-dependent antioxidant index, and HOMA-IR in NP+F and P+F groups. Pregnancy exacerbates fructose-induced insulin resistance and renal oxidative stress whereas acetate ameliorated fructose-induced redox and glucose dysregulation in pregnant and non-pregnant rats.

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., (© Association of Resident Doctors, UCH, Ibadan.)

Impaired renal function is a common complication of diabetes mellitus (DM) that often degenerates to cardiovascular disease, contributing to high morbidity and reduced survival worldwide. Short chain fatty acids (SCFAs), including acetate has shown potential benefits in glycemic or metabolic regulation but its effect on diabetes-associated renal toxicity/impairment is not clear. Herein, we investigated the hypothesis that acetate would ameliorate renal toxicity, accompanying DM, possibly by suppression of xanthine oxidase (XO) activity. Adult male Wistar rats (230-260 g) were allotted into groups (n = 6/group) namely: control (vehicle; po), sodium acetate (NaAc)-treated (200 mg/kg), diabetic with or without NaAc groups. DM was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide (110 mg/kg). Diabetic animals showed increased fasting glucose and insulin, renal triglyceride, total cholesterol, atherogenic lipid, malondialdehyde, XO, tissue necrosis factor-α, uric acid, interleukin-6, aspartate transaminase/alanine aminotransferase ratio, gamma-glutamyl transferase and decreased glutathione and nitric oxide concentration. The renal tissue was characterized with disrupted tissue architecture, enlarged Bowman's space, congested glomeruli and adherence of abnormal segments of tuft to Bowman's capsule with consequent elevated serum creatinine and urea concentration. However, these alterations were attenuated by NaAc. The study demonstrates that acetate ameliorates diabetes-induced nephrotoxicity, which is associated with suppressed XO and its accompanied pro-inflammatory mediators. Therefore, SCFAs, acetate would be a promising dietary-derived therapeutic agent for the prevention and management of diabetes-associated renal disturbances., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (© Association of Resident Doctors, UCH, Ibadan.)

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., Competing Interests: None

High fat diet (HFD) is a risk factor for metabolic syndrome which is characterized by overt glucose dysmetabolism and tissue derangement. The liver and pancreas are important metabolic tissues with anatomical proximity sharing splanchnic and mesenteric circulation but it is unclear whether, there is an associated metabolic status between the two organs in health and disease. Uric acid (UA) hypersecretion and ectopic lipid accumulation are characteristic pathophysiology of an array of non-communicable diseases. Sodium butyrate (BUT) is reputed for therapeutic roles in metabolic derangement. Therefore, the present study investigated synchrony in hepatic and pancreatic UA and lipid metabolic status in HFD-induced glucose dysregulation and probed the beneficial effects of BUT. Twenty-four female Wistar rats were treated with normal rat chow and distilled water (po) or sodium butyrate (200 mg/kg; po) or high fat diet and distilled water (po) or high fat diet and sodium butyrate. Results showed that HFD increased plasma, pancreatic and hepatic triglyceride, triglyceride-glucose index, malondialdehyde, uric acid (UA), lactate dehydrogenase but reduced glucose-6-phosphate dehydrogenase. Histological analysis revealed hepatic and pancreatic architectural derangement and cellular degeneration in HFD-fed animals. However, BUT reversed the HFD-induced systemic, pancreatic and hepatic synchronous dysmetabolism with evidence of improved histology. HFD-induced lipid and UA alterations were synchronous in the pancreas and liver. BUT elicits beneficial effects on systemic and tissue HFD-induced deleterious metabolic changes which were synchronized in pancreas and liver of rats., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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.

Background: Nature and size of rodent cages vary from one laboratory or country to another. Little is however known about the physiological implications of exposure to diverse cage sizes in animal-based experiments., Method: Here, two groups of male Swiss mice (Control group - Cage stationed, and Test group - Cage migrated) were used for this study. The cage-migrated mice were exposed daily to various cage sizes used across laboratories in Nigeria while the cage-stationed mice exposed daily to different but the same cage size and shape. At the end of the 30 days exposure, top-rated paradigms were used to profile changes in physiological behaviours, and this was followed by evaluation of histological and biochemical metrics., Results: The study showed a significant (p < 0.05) decrease in blood glucose levels (at 60 and 120 min of oral glucose tolerance test) in the cage-migrated mice compared to cage-stationed mice. Strikingly, peripheral oxidative stress (plasma malondialdehyde) and pain sensitivity (formalin test, hot-and-cold plate test, and von Frey test) decreased significantly in cage-migrated mice compared to cage-stationed animals. Also, the pro-inflammation mediators (IL-6 and NF-κB) increased significantly in cage-migrated mice compared to cage-stationed mice. However, emotion-linked behaviours, neurotransmitters (serotonin, noradrenaline and GABA), brain and plasma electrolytes were not significantly difference in cage-migrated animals compared to cage-stationed mice., Conclusion: Taken together, these results suggest that varied size cage-to-cage exposure of experimental mice could affect targeted behavioural and biomolecular parameters of pain and inflammation, thus diminishing research reproducibility, precipitating false negative/positive results and leading to poor translational outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Masson SAS.)

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 β-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.

Polycystic ovarian syndrome (PCOS) is a complex endocrine disease among women of reproductive age and is one of the main causes of infertility. Non-alcoholic fatty liver disease (NAFLD), the most prominent chronic liver disease in adults, is characterized by excess hepatic triglyceride (TG) accumulation. PCOS women have increased risk of NAFLD and uric acid has been documented to have a positive correlation with subclinical tissue damage and might be the link in the cystic. Spironolactone (SPL) is a mineralocorticoid receptor (MR) blocker that has been in wide clinical use for some decades. In this research, we investigated the effects of SPL on ovarian and hepatic tissue damage in experimental PCOS rats induced by letrozole (LET). A total of eighteen adult female Wistar rats were used for this study and the animals divided into 3 groups are treated with vehicle, LET (1 mg/kg), and LET+SPL (SPL; 0.25 mg/kg), p.o. once daily respectively for 21 uninterrupted days. Results showed that LET treatment induced features of PCOS characterized by increased plasma testosterone (T) and luteinizing hormone (LH) together with increased body weight. Abnormal ovarian and hepatic histomorphological changes were also observed with elevated uric acid (UA) and TG accumulation in both tissues respectively. Treatment with SPL however attenuated the elevated testosterone in the LET-induced PCOS model accompanied with a reversal in the observed ovarian and hepatic UA, TG accumulation, and altered histomorphological changes. Taken together, spironolactone reversed the PCOS-induced ovarian and hepatic tissue damage by suppressing tissue UA and TG accumulation.

Objectives: To investigate the consequence of restricting antimalarial treatment to febrile children that test positive to a malaria rapid diagnostic test (MRDT) only in an area of intense malaria transmission., Methods: Febrile children aged 3-59 months were screened with an MRDT at health facilities in south-west Nigeria. MRDT-positive children received artesunate-amodiaquine (ASAQ), while MRDT-negative children were treated based on the clinical diagnosis of non-malaria febrile illness. The primary endpoint was the risk of developing microscopy-positive malaria within 28 days post-treatment., Results: 309 (60.5%) of 511 children were MRDT-positive while 202 (39.5%) were MRDT-negative at enrolment. 18.5% (50/275) of MRDT-positive children and 7.6% (14/184) of MRDT-negative children developed microscopy-positive malaria by day 28 post-treatment (ρ = 0.001). The risk of developing clinical malaria by day 28 post-treatment was higher among the MRDT-positive group than the MRDT-negative group (adjusted OR 2.74; 95% CI, 1.4, 5.4). A higher proportion of children who were MRDT-positive at enrolment were anaemic on day 28 compared with the MRDT-negative group (12.6% vs. 3.1%; ρ = 0.001). Children in the MRDT-negative group made more unscheduled visits because of febrile illness than those in MRDT-positive group (23.2% vs. 12.0%; ρ = 0.001)., Conclusion: Restricting ACT treatment to MRDT-positive febrile children only did not result in significant adverse outcomes. However, the risk of re-infection within 28 days was significantly higher among MRDT-positive children despite ASAQ treatment. A longer-acting ACT may be needed as the first-line drug of choice for treating uncomplicated malaria in high-transmission settings to prevent frequent re-infections., (© 2019 John Wiley & Sons Ltd.)

Detection of acute HIV infection is a unique problem that fourth-generation HIV assays were expected to alleviate. In this commentary, we draw attention to the limitations and challenges with use of currently available rapid antigen-antibody (Ag/Ab) combination tests for detection of acute HIV infection in sub-Saharan Africa. Laboratory-based HIV-1 Ag/Ab immunoassays are complex, requiring specialized equipment and handling that are currently not affordable in many settings in Africa. The point-of-care Ag/Ab platform on the other hand is easier to deploy and potentially more accessible in resource-limited settings. However, available fourth-generation HIV-1 rapid diagnostic tests have demonstrated poor performance characteristics in field studies where non-B subtypes of HIV-1 dominate. The potential for point-of-care HIV-1 Ag/Ab diagnostics to significantly improve detection of acute HIV infection remains yet to be realized in sub-Saharan Africa. Assay platforms need to be optimized to identify local circulating subtypes, and optimal algorithms need to be determined.

Dipeptidyl peptidase-4 (DPP-4) inhibition has been shown to exert beneficial effects against insulin resistance (IR) and type 2 diabetes. Combined oral contraceptive (COC) treatment is associated with impaired glucose and lipid metabolism but the mechanisms are elusive. We therefore, hypothesized that DPP-4 inhibition ameliorates COC-induced glucose dysregulation and hepatic triglyceride (TG) accumulation through adenosine deaminase (ADA) /xanthine oxidase (XO) /uric acid-dependent pathway. Female Wistar rats received (po) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel; po) with or without DPP-4 inhibitor (sitagliptin; 100 mg/kg; po) for 8 weeks (n = 6/group). Glucose dysmetabolism was assessed by elevated fasting blood glucose, impaired oral glucose tolerance test and homeostatic model assessment of IR. Treatment with COC led to increased plasma fasting glucose, triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, IR and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic TG, TG/HDL-cholesterol ratio, malondialdehyde, uric acid (plasma; 25.2 ± 0.6 mg/dl; hepatic 128.9 ± 8.0 mg/100 mg tissue), lactate dehydrogenase, DPP-4, ADA and XO (plasma;10.5 ± 1.1 U/L; hepatic 21.2 ± 1.4 U/g protein) activities. Likewise, COC led to reduction in nitric oxide level. However, DPP-4 inhibition significantly ameliorated these alterations induced by COC treatment through suppression of uric acid (plasma; 15.1 ± 1.0 mg/dl, hepatic; 75.6 ± 5.0 mg/100 mg tissue), XO (plasma; 4.1 ± 0.9 U/L, hepatic; 8.7 ± 0.4 U/g protein), ADA and DPP-4 activities suggesting their involvement in glucose dysregulation and hepatic TG accumulation induced by COC treatment. Therefore, DPP-4 inhibition would impact positively on cardiometabolic disorders, at least in part, through XO, ADA and uric acid suppression., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogen-deprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-β, 1-hour postload glucose, glucose intolerance, platelet/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17β-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions.

Reduced liver glycogen synthesis might signify increased glucose flux towards fat synthesis and triggers hepatic triglyceride accumulation and dysmetabolism. Adenosine deaminase (ADA) reduces adenosine content which increases glycogenolysis. In the present study, we evaluate the effect of modulating glycogen synthesis and ADA by lithium chloride (LiCl) on nicotine-induced dysmetabolism. Twenty four male Wistar rats (n = 6/group) were allotted into four groups namely; vehicle-treated (po), nicotine-treated (1.0 mg/kg; po), LiCl-treated (5.0 mg/kg; po) and nicotine + LiCl-treated groups. The treatments lasted for 8 weeks. Nicotine exposure resulted in reduced body weight gain, liver weight, visceral adiposity, glycogen content and synthase. Along with increased insulin resistance (IR), fasting plasma glucose, lactate, plasma and hepatic ADA, XO, UA, and triglyceride (TG), total cholesterol (TC), free fatty acid, lipid peroxidation and liver injury markers. However, plasma and hepatic glucose-6-phosphate dehydrogenase-dependent antioxidant defenses were not affected by nicotine exposure. Concurrent treatment with LiCl normalizes all alterations with exception of hepatic TC. This result shows that enhancement of hepatic glycogen synthesis and suppression of ADA/XO/uric acid pathway by lithium can salvage the liver from nicotine-induced TG accumulation., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Combined oral contraceptive (COC) treatment has been shown to be associated with glucose deregulation and increased triglyceride levels, but the mechanisms are elusive. Soluble dipeptidyl peptidase-4 (sDPP-4) and adenosine deaminase (ADA) are involved in the initiation and/or progression of cardiometabolic disorders. We therefore, hypothesized that increased DPP-4 and ADA activities are involved in glucose deregulation and hepatic triglyceride accumulation induced by COC treatment. This study also investigated whether short-chain fatty acid, acetate, would protect against COC-induced dysmetabolic effects. Female Wistar rats received (p.o.) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel) with or without sodium acetate (ACE; 200 mg) for 8 weeks. Treatment with COC led to increased plasma triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, insulin resistance, and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic triglycerides (TG), TG/HDL-cholesterol ratio, malondialdehyde, uric acid, lactate dehydrogenase, DPP-4, ADA, and xanthine oxidase (XO) activities. On the other hand, COC led to reduction in nitric oxide level. However, ACE significantly ameliorated the alterations induced by COC treatment, but XO activity remains elevated during COC treatment. This result also demonstrates that increased DPP-4 and ADA activities are at least in part involved in glucose deregulation and hepatic TG accumulation induced by COC treatment. Therefore, sodium acetate would impact positively on cardiometabolic disorders, at least in part, by inhibition of DPP-4 and ADA activities.

Elevated circulating uric acid has been postulated to play an important pathophysiological role in estrogen-progestin combined oral contraceptive (COC)-induced hypertension and endothelial dysfunction. We hypothesized that disruption of glucoregulation and liver triglyceride (TG) accumulation induced by COC use would be abated by valproic acid (VPA) treatment through suppression of adenosine deaminase (ADA) and xanthine oxidase (XO) activities. Female Wistar rats aged 9-10 weeks were treated with a combination of estrogen-progestin COC steroids (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; p.o.) with or without VPA (100.0 mg/kg; p.o.) daily for 6 weeks. The result shows that the disrupted glucoregulation and associated elevated hepatic ADA activity, plasma and hepatic XO activity, uric acid (UA), TG/HDL-cholesterol, total cholesterol, and malondialdehyde induced by COC treatment were attenuated by VPA treatment. However, VPA did not have any effect on plasma aldosterone, corticosterone, ADA, circulating and hepatic free fatty acid. Our results demonstrate that suppression of plasma and hepatic XO activities, along with hepatic ADA activity and UA by VPA treatment, protects against disrupted glucoregulation and increased liver TG by COC independent of elevated corticosteroids. The findings imply that VPA would provide protection against the development of cardiometabolic disorder via inhibition of the ADA/XO/UA-mediated pathway.

Estrogen-progestin oral contraceptives (COC) or tobacco smoking has been associated with hypertension and endothelial dysfunction resulting in increased risk of cardiovascular diseases (CVD). Contrasting effects of nicotine exposure on endothelial function have been reported. The effect of non-smoking nicotine exposure on endothelial dysfunction during COC treatment remains to be fully elucidated. We therefore, sought to determine the effects of nicotine exposure during COC treatment on endothelial dysfunction mediators and circulating corticosteroids. Female Wistar rats aged 10 weeks were given (po) vehicle, nicotine (1.0 mg/kg) with or without COC steroids (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) daily for 6 weeks. Nicotine exposure caused 113.3% increase in insulinemia whereas COC treatment led to 76.9% increased insulinemia compared with control. Furthermore, COC treatment or nicotine exposure led to glucose deregulation, insulin resistance, reduced nitric oxide bioavailability, elevated plasminogen activator inhibitor-1, uric acid, oxidative stress, atherogenic dyslipidemia, and corticosteroids. However, COC + NIC treatment led to 41.2% decrease in insulemina compared with COC-treated rats. Furthermore, all other alterations were alleviated by nicotine exposure in COC-treated female rats with the exception of corticosteroids.

Gestational glucocorticoid (GC) treatment has been associated with cardiometabolic disorder (CMD) in offspring's in later life. Elevated dipeptidyl peptidase-4 (DPP-4) activity, endoglin and glycogen synthase kinase-3 (GSK-3) has also been implicated in the development of insulin resistance (IR) and/or vascular inflammation. We aimed to investigate the impact of GC exposure on glucose metabolism and the circulating levels of inflammatory biomarkers, DPP-4 activity and GSK-3 in pregnant rats. Pregnant Wistar rats received either vehicle or dexamethasone (DEX; 0.2 mg/kg; po) between gestational days 14 and 19. Gestational GC exposure resulted in impaired glucose homeostasis that is accompanied with elevated circulating levels of inflammatory biomarkers (endoglin, uric acid, and platelet/lymphocyte ratio), oxidative stress (malondialdehyde), blood viscosity, reduced NO level and increased DPP-4 activity. However, these effects were associated with atherogenic dyslipidemia and reduced GSK-3.We conclude that plasma endoglin, a marker of vascular inflammation, and plasma DPP-4 activity are increased in pregnant rats treated with GC during late gestation. Therefore, glucose deregulation associated with gestational GC exposure is through endoglin-/DPP-4-dependent but GSK-3-independent pathway., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Context: Cigarette smoking is considered to be a major risk factor for the development of diabetes and cardiovascular disease. Oestrogen-progestin combined oral contraceptive (COC) use has been associated with adverse cardiometabolic events., Objective: We hypothesized that nicotine would ameliorate insulin resistance (IR) that is accompanied by decreased cardiac glycogen synthase kinase-3 (GSK-3) and plasminogen activator inhibitor-1 (PAI-1)., Methods: Female Wistar rats received (po) low-(0.1 mg/kg) or high-nicotine (1.0 mg/kg) with or without COC containing 5.0 µg levonorgestrel plus 1.0 µg ethinylestradiol daily for 8 weeks., Results: Data showed that COC treatment or nicotine exposure led to IR, glucose deregulation, atherogenic dyslipidemia, increased corticosterone, aldosterone, cardiac and circulating GSK-3 values and PAI-1. However, these effects with the exception of corticosterone and aldosterone were ameliorated in COC + nicotine-exposed rats., Conclusion: Amelioration of IR induced by COC treatment is accompanied by decreased circulating PAI-1, cardiac PAI-1 and GSK-3 instead of circulating aldosterone and corticosterone.

Objectives: To determine the metabolic abnormalities among Hepatitis C Virus (HCV) co infected HAART naïve HIV infected persons within the adult ARV clinic of the University College Hospital/University of Ibadan, Ibadan, Nigeria Methods: This was a retrospective study involving the review of clinical records of newly recruited HIV-infected persons in the adult antiretroviral (ARV) clinic over a 12 month period (January - December 2006). Baseline results for fasting plasma glucose (FPG) and fasting lipid profile were retrieved., Results: Out of the 1,260 HIV infected persons seen during the study period, HCV co-infection was found in 75 (6%) persons. The median values for total cholesterol, LDL-cholesterol and HDL-cholesterol were lower in the HCV co-infected persons. HIV-HCV co-infection was associated with a 0.31 mmol/L depression in Total Cholesterol (TC). The median FPG concentration was significantly higher in HIV-HCV co-infected than HIV only infected persons (5.33mmol/L vs. 5.00mmol/L, p = 0.047). However, regression analysis showed there was no relationship between the HIV-HCV co infected state and fasting glucose levels., Conclusion: HIV-HCV co-infection may be associated with a predictable decline in plasma cholesterol, but FPG may not be sufficient to demonstrate insulin resistance in these persons.

Background: Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent., Methods: Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks., Results: COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment., Conclusions: Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent., (Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.)

The book appraised in this edition of Chronicles of Medical History, History of Dentistry in Nigeria, is a product of many years of painstaking research. The Author, Professor Eyitope Ogunbodede, has put together an excellent book that is a great work of art. Dentistry is one of the first specialties in medicine with a very long history; evidence of periodontal disease has been traced back to at least 100, 000 years in human remains. However, the book by Professor Ogunbodede is the first comprehensive record of the History of dentistry in Nigeria. It is a must-read for every medical professional practicing in Nigeria and a worthy addition to every library.

Background: The combination and use of multiple drugs in the treatment of tuberculosis (TB) predispose to adverse drug events and reactions. This study evaluated the incidence, frequency, and severity of adverse events to first line anti-tuberculosis (anti-TB) drugs in patients with TB and co-infections with Human Immunodeficiency Virus (HIV)., Objective: The objective of this study was to determine the effects of HIV status on the risk of developing adverse events to first line anti-TB therapy., Method: The study was carried out between 2006 and 2007 when TB therapy was administered without concomitant anti-retroviral therapy. Patients with TB presenting at the chest clinic of a tertiary hospital were sequentially enrolled. Those with TB alone were allocated to the first group while those with TB-HIV infection were allocated to a second group. A checklist of adverse events to the drugs was used to screen for adverse drug events and reactions during the period of anti-TB therapy. Adverse drug events were graded as serious and others (mild-moderate)., Results: One hundred and three patients completed the study. Thirty one (30.1%) of the patients had TB-HIV co-infection. Majority (70.4%) of the events were detected during the first week of therapy, 92% of these events were mild-moderate. Eight (25.5%) of those with TB-HIV co-infection had serious adverse events. All the serious events occurred in the TB-HIV group. Independent factors for occurrence of ADEs include HIV status, increasing age, and female gender., Conclusion: The rate of adverse drug events among patients on first line antituberculosis treatment was higher in HIV co-infected patients.

The German Friedrich Hartmut Dost (1910-1985) introduced the word Pharmacokinetics. Clinical pharmacokinetics is the direct application of knowledge regarding a drug's pharmacokinetics to a therapeutic situation in an individual or a population. It is the basis of therapeutic drug monitoring with the ultimate goal of keeping drugs safe. This branch of pharmacology has become the most relevant to the sub-specialty of clinical pharmacology. First reports of Clinical Pharmacokinetics in Nigeria can be credited to two gifted Nigerians, Prof Ayodele O. Iyun and Prof Lateef A. Salako, both of whom were affiliated to the great institutions- University of Ibadan (UI) and the Teaching Hospital, University College Hospital (UCH). Prof A.O Iyun was Nigeria's first home-trained Clinical Pharmacologist, while Prof L.A. Salako played a most significant role in the creation of the Department of Clinical Pharmacology, UCH. This edition of the Chronicles highlights a few of the first reports of this exciting branch of pharmacology in Nigeria. This historical review is based on publications listed on the United States National Library of Medicine database (PUBMED).

The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.

Women are exposed to sex steroids in several formulations such as oral contraceptives (OCs) and hormone replacement therapies. Estrogen is believed to have cardiometabolic protection effect; but its beneficial effects have recently been queried. The aim of the present study was to clarify whether or not the altered glucose tolerance and plasma lipid profile was associated with OC and due to the estrogenic or progestogenic-component and if that was dose-dependent in 7-8 weeks old female rats. Rats were divided into vehicle-treated (control), high dose combined OC-treated (HCOC; receiving 1.5μg ethinyl estradiol/15.0μg norgestrel), low dose combined OC-treated (LCOC; receiving 0.15μg ethinyl estradiol/1.5μg norgestrel), high dose progestogen OC-treated (HOC; receiving 35.0μg levonorgestrel) and low dose progestogen OC-treated (LOC; receiving 3.5μg levonorgestrel) groups. Rats were given (p.o.) vehicle (distilled water), HCOC, LCOC, HOC and LOC daily for 6 weeks. When compared with the controls, HCOC treatment led to significant decreases in glucose tolerance and plasma high-density lipoprotein-cholesterol. However, HCOC-treated and LCOC-treated groups had significantly higher plasma triglyceride levels when compared with the control group. Fasting blood glucose, plasma total cholesterol, and low-density lipoprotein-cholesterol were comparable among groups. Body weight gain appeared to be attenuated by OC treatments, particularly in LOC-treated rats. In conclusion, our findings demonstrate that combined estrogen-progestogen but not progestogen-only OC use resulted in impaired glucose tolerance that was associated with increased triglyceride and decreased high-density lipoprotein-cholesterol. The effects on glucose tolerance and high-density lipoprotein-cholesterol were dose-dependent while that on triglyceride was not., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)