Diagnostic utility of selected faecal biochemical parameters in the determination of acute diarrhoea and associated defecation stooling characteristics in dogs: An observational study.

Diarrhoea, which is a clinical manifestation of various illnesses, is frequently observed in dogs. Regrettably, many dog owners find it difficult to provide comprehensive case histories, primarily because of limited interaction with their canine companions. This study aimed to evaluate the potential of faecal biochemical analytes in detecting and characterizing acute diarrhoea in dogs. Sixty-two domestic dogs were selected using the proportionate stratified sample technique. A structured questionnaire was used to collect demographic and clinical data. Faecal stool specimens from the dogs were obtained using the colon flush technique. The specimens were taken through biochemical analysis to determine urea, creatinine, total bilirubin, total cholesterol, triglycerides, gamma-glutamyl transferase and uric acid levels. Results showed a significant association between the diarrhoea status of the participants and their age, weight, breed, body size, source of last diet, period of inappetence, and other gastrointestinal signs (p < 0.050, respectively). Dogs that had not eaten in at least three days were five times more likely (p < 0.05) to have diarrhoea. Furthermore, miniature breeds were about six times more likely to develop diarrhoea (p < 0.05). Of the seven selected biochemical parameters, total faecal cholesterol was the most predictive index in diagnosing acute diarrhoea in dogs, with a likelihood ratio of 6.5, and it was the most accurate in predicting defecation stooling frequency and texture. In summary, in situations of inadequate case histories, measuring total faecal cholesterol could assist veterinarians in detecting diarrhoea and predicting its faecal stooling texture and frequency in dogs.

Blood C-peptide concentration as a proxy marker of cardiovascular disease: An observational cross-sectional study.

Background and Aims: Cardiovascular diseases (CVDs) are among the leading causes of disability and early death in sub-Saharan Africa. Most of the current blood tests for CVD diagnosis involve performing about three test profiles; often at additional cost to patients. C-peptide, a cleavage product of proinsulin, is a promising marker that has the potential to serve as a proxy marker for diagnosing CVDs in resource-poor settings. Methodology: The study was an observational cross-sectional one and involved 127 consenting persons diagnosed with CVD and 127 individuals without CVD. The socio-demographic and clinical characteristics of participants were obtained. Blood levels of C-peptide, fasting plasma glucose (FPG), total creatinine kinase (CK), creatine kinase myocardial bound (CKMB), lactate dehydrogenase (LDH), propeptide of brain natriuretic peptide (PBNP), Troponin T, lipids, and biomarkers of kidney and liver function were analyzed using ELISA and an automated analyzer. Insulin resistance was computed using the modified homeostatic model assessment (HOMA-IR). Results: The CVD Group had significantly higher levels of C-peptide, CK, CKMB, troponin T, PBNP, FPG, HOMA-IR, and several selected kidney, liver, and lipid parameters compared to the non-CVD Group (p < 0.05 for all). Troponin T recorded a positive correlation (r = 0.34, p < 0.001) with C-peptide among the CVD Group. The sensitivity and specificity of C-peptide in identifying CVD were 96.1% and 91.3% respectively (area under the curve = 0.938, p < 0.001). Conclusion: C-peptide levels were higher in the CVD Group and appeared to be a valuable (high sensitivity and specificity) biomarker in detecting CVD.

Effect of circulating ceramides on adiposity and insulin resistance in patients with type 2 diabetes: An observational cross-sectional study.

INTRODUCTION: Insulin resistance (IR) is one of the common chronic metabolic disorders in Africa and elsewhere. Accumulation of lipids in the body may be due to an imbalance in the metabolism of lipids, glucose and proteins. Ceramides are a sphingolipid class of lipids that are biologically active and vital in the production of more complex lipids. Circulating ceramides are thought to have a role in the development of obesity-related IR, although the precise involvement remains unclear. AIM: To investigate the impact of circulating ceramide on IR and body adiposity in people with and without type 2 diabetes mellitus (T2DM). METHODOLOGY: The study was observational and cross-sectional. There were a total of 84 volunteers with T2DM and 75 nondiabetics (control). The participants' ages, body mass indexes (BMI), waist circumferences, and blood pressure (BP) were among the clinical parameters assessed. Ceramide levels, fasting plasma glucose (FPG), lipids, basal insulin levels and glycated haemoglobin (HbA1c) were also measured. Additionally, the homeostatic model assessment for IR (HOMA-IR) and beta cell function (HOMA-ß) were computed. RESULTS: T2DM and control participants had different mean values for anthropometric parameters, BP, FPG, HbA1c, lipids, insulin, HOMA-IR, HOMA-ß and ceramide levels (p < .05 for all). HOMA-IR, HOMA-ß and cardiovascular risk were significant correlates with ceramide levels in the T2DM group (r = 0.24; -0.34; 0.24, p < .05, respectively). Further, FPG (OR = 1.83, p = .01) and ceramide (OR = 1.05, p = .01) levels were significant predictors of IR in the case group. CONCLUSION: Patients with T2DM exhibited high ceramide concentrations, which, when combined with high FPG, were associated with IR. The consequences of circulating ceramides in health and disease; however, merit further research.

Impact of blood perilipin A levels on obesity and metabolic health.

OBJECTIVE: Perilipin A is a common protein that coats lipid surfaces preventing them from being exposed to oxidative damage. Researchers have found little consistency in the relationship between perilipin A levels in the blood and body fat. This study was a cross-sectional observational that looked at circulating perilipin A levels and how they relate to metabolic health. RESULTS: The participants in this study were 86 individuals with a mean age of 45.5 ± 1.2 years. Multiple clinical and metabolic indicators (age, weight, BMI, total body fat mass, triglyceride, and HOMA-IR) were shown to be inversely associated with perilipin A levels (rho = - 0.32, - 0.37, - 0.40, - 0.45, - 0.33 and - 0.29; p < 0.05 respectively). Obese persons were almost six times more likely than non-obese individuals to have lower perilipin A levels (odds ratio = 6.22, CI = 2.35-11.50, p < 0.001). Our findings underscore the important role of perilipin A proteins in metabolic health.

Extract of Mallotus oppositifolius (Geiseler) Müll. Arg. increased prefrontal cortex dendritic spine density and serotonin and attenuated para-chlorophenylalanine-aggravated aggressive and depressive behaviors in mice.

Background/Aim: Depression-related aggression is linked to serotonin (5-HT) and dendritic spine alterations. Although Mallotus oppositifolius extract (MOE) has potential for reducing this effect, its specific role remains uncertain. Herein, we evaluated this potential and associated alterations in the brain. Methods: A standard resident-intruder model of para-chlorophenylalanine (pCPA)-induced depression-associated aggression in male ICR mice was used. The resident mice received pCPA (300 mg/kg, i. p.) for 3 consecutive days while saline-treated mice served as negative control. The pCPA aggressive mice were subsequently treated orally with either MOE (30, 100, 300 mg/kg), fluoxetine (20 mg/kg), tryptophan (20 mg/kg) or saline (untreated pCPA group) for 28 days. Locomotor activity was assessed using open field test. Serotonin (5-HT) levels in mice brain and phytochemical fingerprint of MOE were determined by high performance liquid chromatography (HPLC) while gas chromatography-mass spectrometry (GC-MS) was used to identify constituents of MOE. Dendritic spine density and morphology were evaluated using Golgi-Cox staining technique and analyzed with ImageJ and Reconstruct software. Results: Administration of pCPA induced aggressive behavior in mice, evidenced by increased attack behaviors (increased number and duration of attacks), which positively correlated with squeaking and tail rattling. MOE treatment significantly reduced these characteristics of aggression in comparison with vehicle (non-aggressive) and untreated pCPA groups (p < 0.001), and also reduced social exploration behavior. Although the behavioral effects of MOE were comparable to those of fluoxetine and tryptophan, these effects were quicker compared to fluoxetine and tryptophan. Additionally, MOE also markedly increased 5-HT concentration and dendritic spine density in the prefrontal cortex relative to vehicle and untreated pCPA groups (p < 0.05). Interestingly, these behavioral effects were produced without compromising locomotor activity. GC-MS analysis of the MOE identified 17 known compounds from different chemical classes with anti-inflammatory, antioxidant, neuroprotective and antidepressant activities, which may have contributed to its anti-aggressive effect. Conclusion: MOE decreased depression-associated aggressive behavior in mice via increased 5-HT concentration and dendritic spine density in the prefrontal cortex. The MOE-mediated effects were faster than those of fluoxetine and tryptophan. Our finding suggests that MOE may have clinical promise in decreasing aggressive and depressive behaviors.

Bioanalysis of aminoglycosides using high-performance liquid chromatography.

Aminoglycosides are broad-spectrum antibiotics used in the treatment of gram-negative bacterial infections. Due to their nephrotoxic and ototoxic potential (narrow therapeutic index), the use of aminoglycoside for clinical indications requires monitoring. The objective of this review was to identify relevant literature reporting liquid chromatographic methods for the bioanalysis of aminoglycosides in both preclinical and clinical settings/experiments. Data on liquid chromatographic methods were collected from articles in an online academic database (PubMed, Science Direct, Scopus, and Google Scholar). All 71 articles published from 1977 to 2020 were included in the review. Reversed-phase liquid chromatography was the most used method for the bioanalysis of aminoglycosides. Fluorescence or ultraviolet detection methods were mostly used from 1977 to 2002 (51 articles), while mass spectrometry was predominantly used as a detector from 2003 to 2020 (15 articles). Sixty-seven articles reported calibration ranges, which varied significantly for the various drugs assayed: some in the range of 0.1-0.5 ng/mL and others 1250-200000 ng/mL. Also, 61 articles reported R2 values (0.964-1.0) for almost all analytes under consideration. Sixty-three articles reported percent recoveries mostly between 61.0 % to 114.0 %, with only two articles reporting recoveries of 4.9 % and 36 %. Out of the 71 reviewed articles, 56 reported intermediate precision values ranging between 0.331 % to 19.76 %, which is within the acceptable limit of 20 %. This review will serve as a guide for research and/or routine clinical monitoring of aminoglycosides in biological matrices.

Preliminary Investigation into Plasmodium-like Piroplasms (Babesia/Theileria) among Cattle, Dogs and Humans in A Malaria-Endemic, Resource-Limited Sub-Saharan African City.

Babesia and Theileria are protozoan parasites belonging to the order piroplasmida, transmitted by hard ticks, and can cause diseases known as piroplasmosis. Human infections are usually asymptomatic, except in immuno-compromised persons who present malaria-like symptoms. Moreover, microscopically, the morphologies of Babesia and Theileria can resemble that of the malaria parasite, Plasmodium. In malaria-endemic areas with limited resources, these similarities can increase the possibility of misdiagnosing a patient as having malaria instead of piroplasmosis, which may further lead to inappropriate choice of disease management. This preliminary investigation aimed at detecting Babesia/Theileria in cattle, dogs and humans in some parts of Accra. Whole blood samples were taken from febrile cattle (n = 30) and dogs (n = 33), as well as humans diagnosed with malaria (n = 150). Blood samples of all study subjects were microscopically screened for possible presence of haemoparasites. Samples whose smears had features suggestive of possible piroplasmic infection were all given the label "suspected Babesia/Theileria-infected" samples. Nested polymerase chain reaction (PCR) was performed on extracted deoxyribonucelic acid (DNA) from all the "suspected" samples of cattle, dogs and humans, with primer sets that can detect 18S rRNA genes of Babesia/Theileria spp. In addition to this, amplification was performed on the "suspected" dog samples using the BcW-A/BcW-B primer set which detects the 18S rRNA genes of B. canis, while the BoF/BoR primer set which targets the rap-1 region of B. bovis and another primer set which detects the 18S rRNA genes of most bovine Babesia spp. (including B. divergens) were used on the suspected cattle samples. For the human samples, however, additional amplification was done on the extracted DNA using primers for the three other Babesia targeted (B. divergens, B. bovis and B. canis). Microscopy showed possible Babesia/Theileria infection suspected in all three groups of subjects in the following proportions: cattle (10/30; 33%), dogs (3/33; 9%) and humans (6/150; 4%). DNA from one-third of the "suspected" dog samples yielded amplification with Babesia canis primers. Moreover, a broad-detecting set of primers (that can amplify some Babesia and Theileria species) amplified DNA from nine (9/30; 30%) of the "suspected" cattle samples, but none from those of the humans. Although for this study conducted in the city, the Babesia/Theileria primers used did not amplify DNA from the six "suspected" human samples; the possibility of Babesia/Theileria infection in humans in other parts of the country cannot be overruled. There is therefore a need for further studies on possible emergence of human babesiosis/theileriosis in other parts of Ghana and sequencing for specific identification of any circulating strain.

High performance liquid chromatography: A versatile tool for assaying antiepileptic drugs in biological matrices.

Epilepsy is a recurrent long-term illness occurring in approximately 1.0% of the world's population. There are currently about 29 approved antiepileptic drugs for the management of epilepsy. Due to narrow therapeutic indices of most antiepileptic drugs, clinical pharmacokinetic characteristics and therapeutic drug monitoring of these drugs are imperative. The objectives of this review were to identify common chromatographic principles, requirements and/or conditions for high-performance liquid chromatography as applied to assay of antiepileptic drugs in biological matrices. The review was conducted using 66 peer reviewed articles (1990 to 2020) from 29 journals that were sought via PubMed, Science Direct and Google Scholar. In all, 29 antiepileptic drugs were assayed from 6 different biological matrices. Forty-three of the reviewed articles estimated the concentration of only one antiepileptic drug, whilst 23 articles focused on simultaneous determination of two or more antiepileptic drugs. Thirty-four, 20, and 14 articles reported using liquid-liquid extraction, protein precipitation, or solid phase extraction for sample clean up, respectively. The ratio of reversed-phase to normal phase, LC-UV to LC-MS and isocratic elution to gradient elution were 61:3, 43:7 and 55:11, respectively. With the exception of one article the reported recoveries ranged from 60.3% to 109.6%. It is noteworthy, that, the performance metrics of high-performance liquid chromatography are better compared to other assays of antiepileptic drugs in biological matrices. This review describes the relevant liquid chromatographic method conditions over the past 30 years for the analysis of this class of drugs, which provides a basis for further method development and optimization.

Unravelling the Perspectives of Day and Night Traders in Selected Markets within a Sub-Saharan African City with a Malaria Knowledge, Attitude and Practice Survey.

BACKGROUND: Malaria is still endemic in sub-Saharan Africa, with a high disease burden. Misconceptions about malaria contribute to poor attitudes and practices, further increasing the burden in endemic countries. Studies have examined the knowledge, attitudes, and practices (KAP) of malaria among different populations. However, there seems to be no available literature reporting on the perspectives of day and night market traders. To the best of our knowledge, this is the first report on malaria KAP with a focus on day and night market traders. METHODS: A descriptive cross-sectional study involving day and night market traders in 10 selected markets within the Greater Accra Region of Ghana was carried out. Data were collected from consenting respondents using a structured questionnaire. RESULTS: Of the 760 respondents (33.3% (n = 253) night and 66.7% (n = 507) day traders) interviewed, there was no significant difference between the day and night market traders in terms of malaria KAP. Although the market traders had an overall moderate knowledge (54.0% of the day traders and 56.5% of the night traders), misconceptions about malaria (especially that it could be caused by exposure to the sun) still existed among the traders. Moreover, the majority of the traders who demonstrated high knowledge (43.98%, n = 250) did not always take laboratory tests to confirm their suspicion, indicating poor attitude. Furthermore, the market traders' choice of drug for malaria treatment (p = 0.001) and preferred malaria treatment type (orthodox or herbal) (p = 0.005) were significantly associated with their knowledge level. CONCLUSIONS: Despite the observation that no significant difference in KAP exists between day and night market traders, appropriate health education programs and interventions still need to be directed at misconceptions, poor attitudes, and poor practices revealed by this study. This will ultimately help in the prevention and control of malaria in Ghana, and globally.

Plasma Folate Levels in Acutely Ill and Steady State Pediatric Sickle Cell Disease Patients in Ghana.

BACKGROUND: Individuals with sickle cell disease (SCD) are susceptible to infective conditions that predispose them to hemolysis and anemia. Folic acid is recommended as a preventative measure against anemia in SCD patients; however, there is scarce literature on the implications of this practice. PATIENTS AND METHODS: Plasma concentrations of folate were measured in acutely ill pediatric SCD patients presenting with malaria or bacteremia and compared with those of SCD patients in steady state, or acutely ill non-SCD patients with confirmed malaria. RESULTS: The proportion of individuals with high (>45.3 nmol/L) folate concentrations was 29.5% (13/44), 18.2% (8/44), 33.3% (6/18), and 0% in the SCD-malaria, SCD steady state, SCD bacteremia, and the non-SCD malaria groups, respectively. The proportion of SCD patients with high folate levels did not vary significantly at steady state and during confirmed malaria (p = 0.216), and during acute bacteremia (p = 0.20). The median (interquartile range) plasma folate levels were 34.50 (24.40-52.00 nmol/L), 33.40 (15.83-60.85 nmol/L), 30.85 (24.68-39.65 nmol/L), and 13.30 (10.03-17.18 nmol/L), respectively, in the SCD malaria, SCD bacteremia, SCD steady state, and the non-SCD malaria sub-groups. The median folate levels of SCD steady state, SCD malaria, and SCD bacteremia sub-groups differed significantly (p < 0.0001) when compared with non-SCD patients, but the levels in the SCD bacteremia and malaria groups were not significantly different from the SCD steady state group. CONCLUSION: Elevated levels of plasma folate were found in a high proportion of pediatric SCD patients. The implications of such elevated folate levels in pediatric SCD patients are unknown but may suggest a need for review of current recommendations for prophylactic doses of folic acid in SCD patients.

Persistent Urogenital Schistosomiasis and Its Associated Morbidity in Endemic Communities within Southern Ghana: Suspected Praziquantel Resistance or Reinfection?

BACKGROUND: schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. The disease has a worldwide distribution, with more cases occurring in Africa. Urogenital schistosomiasis caused by S. haematobium with its associated morbidity is prevalent in many areas of Ghana. Praziquantel is still the recommended drug of choice for schistosomiasis treatment, although a number of studies have reported sub-therapeutic effects and associated treatment failure. The current study, therefore, assessed whether persistent schistosomiasis, with its associated morbidity among children living in endemic areas within the Greater Accra Region of Ghana, is as a result of reinfection or suspected praziquantel resistance. METHODOLOGY: this was a longitudinal study involving a baseline and follow-up sampling after praziquantel treatment. Urine samples were collected from school children (whose parents had also consented) for the detection of S. haematobium ova using a sedimentation technique. The morbidity parameters were examined with urine chemistry strips, as well as microscopy. Viability was assessed using a modified hatchability technique, vital staining (0.4% trypan blue and 1% neutral red) and fluorescent (Hoechst 33258) microscopy. Infected individuals were treated with a single dose of praziquantel (40mg/kg). Resampling to determine reinfection was done sixth months post-treatment, after evidence of total egg clearance. For possible resistance assessment, egg counts and viability testing were conducted on the positive samples at the baseline, as well as weekly post-treatment follow-ups for 12 weeks. RESULTS: out of the 420 school children sampled, 77 were initially positive but, after the sixth month sampling for reinfection assessment, eight out of the initial positives were infected again, giving a reinfection percentage of 10.4%. No suspected praziquantel resistance was recorded in the 21 positives detected out of the 360 sampled for suspected resistance assessment. The egg reduction rate increased weekly in the follow-up samples with a gradual reduction in the egg count. The study also recorded a gradual decrease in the percentage of live eggs after the first week; with all viability testing methods used complimenting each other. The morbidity parameters (proteinuria, haematuria and pyuria) changed between the baseline and post-treatment samples, eventually reducing to zero. CONCLUSIONS: the outcome of this study suggests that the persistent schistosomiasis, with its associated morbidity observed in these endemic communities, is not likely to be as a result of praziquantel resistance, but reinfection. Even though there was no suspected resistance observed in the study, there remains the need to continuously intensify the monitoring of praziquantel in other endemic communities.

Population Pharmacokinetic Estimates Suggest Elevated Clearance and Distribution Volume of Desethylamodiaquine in Pediatric Patients with Sickle Cell Disease Treated with Artesunate-Amodiaquine.

BACKGROUND: There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. OBJECTIVES: This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). METHODS: Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. RESULTS: The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). CONCLUSIONS: The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population.

In Vitro Antioxidant Potential and Effect of a Glutathione-Enhancer Dietary Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity.

BACKGROUND: There is considerable evidence that many people take dietary supplements including those of herbal origin as an alternative therapy to improve their health. One such supplement, with an amalgam of constituents, is CellGevity®. However, the effect of this dietary supplement on drug-metabolizing enzymes is poorly understood, as it has not been studied extensively. Therefore, we investigated the effect of CellGevity dietary supplement on selected rat liver microsomal cytochrome P450 (CYP) enzymes, the most common drug-metabolizing enzymes. We also determined the total antioxidant potential of this dietary supplement in vitro. METHODS: To determine the antioxidant potential of CellGevity dietary supplement, 2,2-diphenyl-2-picryl-hydrazyl (DPPH), total phenolic, and flavonoid assays were used after initial preparation of a solution form of the supplement (low dose, LD; 4 mg/kg and high dose, HD; 8 mg/kg). Rats received oral administration of these doses of the supplement for 7 days, after which the effect of the supplement on selected liver CYP enzymes was assessed using probe substrates and spectroscopic and high-performance liquid chromatographic methods. Rats which received daily administration of 80 mg/kg of phenobarbitone and distilled water served as positive and negative controls, respectively. RESULTS: The IC50 value of the supplement 0.34 ± 0.07 mg/ml compared to 0.076 ± 0.03 mg/ml of the BHT (positive control). The total phenolic content of the supplement at a concentration of 2.5 mg/ml was 34.97 g gallic acid equivalent (GAE)/100 g while its total flavonoid content at a concentration of 2.5 mg/ml was 6 g quercetin equivalent (QE)/100 g. The supplement significantly inhibited rat CYP2B1/2B2 (LDT 92.4%; HDT 100%), CYP3A4 (LDT 81.2%; HDT 71.7%), and CYP2C9 (LDT 21.7%; HDT 28.5%) while it had no significant inhibitory effect on CYPs 1A1/1A2, CYP1A2, and CYP2D6. CONCLUSION: CellGevity dietary supplement possesses moderate antioxidant activity in vitro and has an inhibitory effect on selected rat liver CYP enzymes, suggesting its potential interaction with drugs metabolized by CYP enzymes.

Population Pharmacokinetic Characteristics of Amikacin in Suspected Cases of Neonatal Sepsis in a Low-Resource African Setting: A Prospective Nonrandomized Single-Site Study.

BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings. OBJECTIVES: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin. METHODS: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12 hours), were recruited. Serum amikacin concentration was measured at specified times after treatment initiation and analyzed using a population PK modeling approach. RESULTS: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n = 25), and preterm (<37 weeks' gestation n = 36) neonates were 6.2 (3.4) and 9.2 (5.7) µg/mL, respectively (P = 0.02). A 1-compartment model best fitted amikacin disposition, and birth weight was the most important predictor of amikacin clearance (CL) and distribution (V). The population CL and V of amikacin were related as CL (L/h) = 0.153 (birth weight/2.5)1.31, V (L) = 2.94 (birth weight/2.5)1.18. There was a high between-subject variability (58.9% and 50.7%) in CL and V, respectively. CL and V were 0.058 L/h/kg and 1.15 L/kg, respectively, for a mean birth weight of 2.1 kg, and the mean half-life (based on 1-compartment model), was 13.7 hours. CONCLUSIONS: The V and half-life of amikacin in this cohort varied from that reported in non-African populations, and the high trough and low peak amikacin concentrations in both term and preterm neonates suggest strategies to optimize amikacin dosing are required in this population.

In vitro activity of extract and fractions of natural cocoa powder on Plasmodium falciparum.

Several flavonoids isolated from certain plants have demonstrated antiplasmodial activity, after their initial indigenous use in malaria treatment. Cocoa has been found to be a rich food source of flavonoids in comparison with many common foods and beverages. The aim of this work was to investigate the in vitro activity of natural cocoa powder on the growth of Plasmodium falciparum. Prepared crude methanol extract was partitioned successively with petroleum ether, ethyl acetate, chloroform, and butanol. Total flavonoid concentration in the crude methanol extract and fractions was measured by the AlCl(3) colorimetric assay. Direct inhibitory activity of the natural cocoa powder was assessed by culturing extract and fractions with P. falciparum in vitro. Greater antiplasmodial activity was observed in nonpolar solvent fractions (chloroform, ethyl acetate, and petroleum ether) compared with polar solvents. The chloroform fraction was most active, with mean±SEM 50% and 90% inhibition concentrations of 48.3±0.9 and 417±7.8 µg/mL, respectively. The study showed a weak association between total flavonoid concentration and antiplasmodial activity. Early trophozoite (ring-stage) synchronized cultures treated with the chloroform fraction of natural cocoa powder showed a decline in growth. Further reduction in parasitemia was also observed for other erythrocytic stages. These results suggest that natural cocoa powder has measurable direct in vitro inhibitory effect on P. falciparum and support the anecdotal reports of its ability to prevent malaria as a result of regular intake as a beverage.