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Abstract Tuberculous meningitis (TBM)—the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture—an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified—1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol—which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone (Haliotis midae) subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids) for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia. This article has an associated First Person interview with the first author of the paper.

Due to controversial evidence in the literature pertaining to the activity of plasminogen activator inhibitor-1 in platelets, we examined the effects of residual platelets present in plasma (a potential pre-analytical variable) on various plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays. Blood samples were collected from 151 individuals and centrifuged at 352 and 1500 g to obtain plasma with varying numbers of platelet. In a follow-up study, blood samples were collected from an additional 23 individuals, from whom platelet-poor (2000 g), platelet-containing (352 g) and platelet-rich plasma (200 g) were prepared and analysed as fresh-frozen and after five defrost-refreeze cycles (to determine the contribution of in vitro platelet degradation). Plasminogen activator inhibitor-1 activity, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasma clot lysis time, β-thromboglobulin and plasma platelet count were analysed. Platelet α-granule release (plasma β-thromboglobulin) showed a significant association with plasminogen activator inhibitor-1 antigen levels but weak associations with plasminogen activator inhibitor-1 activity and a functional marker of fibrinolysis, clot lysis time. Upon dividing the study population into quartiles based on β-thromboglobulin levels, plasminogen activator inhibitor-1 antigen increased significantly across the quartiles while plasminogen activator inhibitor-1 activity and clot lysis time tended to increase in the 4th quartile only. In the follow-up study, plasma plasminogen activator inhibitor-1 antigen was also significantly influenced by platelet count in a concentration-dependent manner. Plasma plasminogen activator inhibitor-1 antigen levels increased further after complete platelet degradation. Residual platelets in plasma significantly influence plasma plasminogen activator inhibitor-1 antigen levels mainly through release of latent plasminogen activator inhibitor-1 with limited effects on plasminogen activator inhibitor-1 activity, tissue plasminogen activator/plasminogen activator inhibitor-1 complex or plasma clot lysis time. Platelets may however also have functional effects on plasma fibrinolytic potential in the presence of high platelet counts, such as in platelet-rich plasma.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g - 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g - 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g - 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g - 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g - 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g - 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.

The medicinal use and commercialisation of the plants Aloe ferox and Aloe greatheadii are primarily based on research done on Aloe vera and Aloe arborescens. Consequently, in this study we investigated the possible antidiabetic effects of ethanol extracts of A. ferox and A. greatheadii var. davyana leaf gel in a streptozotocin (STZ)-induced type 2 diabetes rat model. Fifty male Wistar rats, weighing 200 g – 250 g, were randomly divided into five groups of n = 10: normal control rats, diabetic control rats, diabetic rats receiving A. ferox leaf gel extract (300 mg/kg), diabetic rats receiving A. greatheadii leaf gel extract (300 mg/kg), and diabetic rats receiving glibenclamide (600 μg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (40 mg/kg). Rats were sacrificed 5 weeks after injection, following a 12-hour fast, and blood and tissue samples were collected. Compared to the normal control group, STZ significantly increased relative liver and kidney weights, end-point plasma glucose, fructosamine, oxidative stress, liver enzymes, total cholesterol (TC), triglycerides, very low density lipoprotein-cholesterol and TC: high density lipoprotein-cholesterol (HDL-C) values and reduced serum insulin levels. Treatment with A. greatheadii moderately increased serum insulin and HDL-C levels and moderately reduced end-point plasma glucose and liver alkaline phosphatase (ALP) and significantly decreased TC:HDL-C ratios. A. ferox supplementation similarly resulted in moderately increased serum insulin, accompanied by slight corrections in ALP and HDL-C, without any change to end-point plasma glucose values. A. greatheadii and, to a lesser extent, A. ferox, resulted in a clinically relevant improved diabetic state (indicated by moderate to high effect sizes), suggesting that these Aloe species may show promise for treating diabetes.