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

Unsweetened Natural Cocoa Powder: A Potent Nutraceutical in Perspective

Unsweetened natural cocoa powder is a pulverized high-grade powder of compressed solid blocks which remains after extraction and removal of the cocoa butter. The authors determined the elementary composition of UNCP, investigated its effect on nitric oxide levels, toxicity, and its protective effect on the heart, kidney, and liver during simultaneous administration with high dose (HD) artemether/lumefantrine (A/L). Macro- and microelements in UNCP were analyzed with energy dispersive x-ray fluorescence spectroscopy (EDXRF). Adult male guinea pigs were administered various doses of UNCP alone and also simultaneously with A/L. Phytochemical analysis of UNCP showed the presence of saponins, flavonoids, tannins, cardiac glycosides, and 38 macro- and microelements. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Administration of various doses of UNCP increased white blood cell counts and lymphocyte count (p > 0.05) compared with the controls. Additionally, UNCP and A/L combination caused an increase in nitric oxide levels when compared with the control group and restores some hematological disorders induced by the 3-day HD A/L administration. Even though UNCP appears to be relatively safe, care should be taken due to the high content of copper element to avoid the possibility of intestinal lining erosion

Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria

IntroductionLimited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM).MethodsA prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR).ResultsAmong SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (−5.38 to 58.57) vs. no-HU −0.34 (−3.19 to 4.44), p = 0.024]; bilirubin [HU+, −4.44 (−16.36 to 20.74) vs. no-HU −18.37 (−108.79 to −7.16)]; and alanine aminotransferase, [HU+, −4.00 (−48.55 to 6.00) vs. no-HU, 7.00 (−22.00 to 22.00)] were observed during follow up.ConclusionParasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies

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

Abstract 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‐β) were computed. Results T2DM and control participants had different mean values for anthropometric parameters, BP, FPG, HbA1c, lipids, insulin, HOMA‐IR, HOMA‐β and ceramide levels (p < .05 for all). HOMA‐IR, HOMA‐β 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

Comparative Determination of Mitochondrial Biomarkers and Their Relationship With Insulin Resistance in Type 2 Diabetic Patients: An Observational Cross‐Sectional Study

ABSTRACT Introduction Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c (CC), acylcarnitine (AC) and citrate synthase (CS) are essential components of the mitochondria machinery and can be used as reliable biomarkers of mitochondrial dysfunction. This study aimed to determine whether mitochondrial biomarkers (AC, CS and CC) are altered in individuals with type 2 diabetes mellitus (T2DM) and to examine the association between these biomarkers and insulin resistance. Methodology A cross‐sectional observational study that recruited 170 participants (88 with T2DM and 82 without DM) was conducted. Blood samples were collected from the recruits and analysed for levels of fasting glucose (FBG), AC, CS, CC, insulin, total cholesterol, triglycerides (TG), glycated haemoglobin (HbA1c) and magnesium. Blood pressure (BP) and anthropometric characteristics of participants were also taken. Appropriate formulas were used to determine %body fat, body mass index (BMI), waist‐to‐hip ratio (WHR), the homeostatic model assessment for insulin resistance (HOMA‐IR) and insulin sensitivity (HOMA‐β). Results Patients with T2DM had higher levels of CC, %body fat, FBG, TG, HbA1c, BMI and HOMA‐IR than controls (p < 0.05, respectively). Results showed a significant relationship between circulating CC levels versus HOMA‐β (r = −0.40, p = 0.001), CS (r = −0.70, p = 0.001) and AC (r = −0.72, p = 0.001) levels in patients with T2DM. The adjusted odds increased in the T2DM patients for VLDL (OR = 6.66, p = 0.002), HbA1c (OR = 6.50, p = 0.001), FPG (OR = 3.17, p = 0.001), TG (OR = 2.36, p = 0.010), being female (OR = 2.09, p = 0.020) and CC (OR = 1.14, p = 0.016). Conclusion Overall, alterations in mitochondrial biomarkers, measured by AC, CC and CS, were observed in people with T2DM and showed a direct relationship with insulin resistance. These findings are potentially significant in Africa, although additional confirmation from a larger cohort is necessary

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