Healthy Male Subjects Research Articles

Evaluation of drug-drug interactions of a novel potent FLT3 inhibitor SKLB1028 in healthy subjects.

SKLB1028 is a novel multi-target protein kinase inhibitor under investigation for the treatment of FLT3-ITD mutated acute myeloid leukemia. Based on the preclinical characterization of SKLB1028 metabolism, three drug-drug interaction clinical studies were performed to investigate the effects of itraconazole, rifampin (CYP3A4 inhibitor and inducer, respectively), and gemfibrozil (CYP2C8 inhibitor) on the metabolism of SKLB1028. Fourteen healthy Chinese male subjects were enrolled in each study. In Study 1, subjects were administered a single dose of SKLB1028 (100 mg on days 1 and 11) and multiple doses of itraconazole (200 mg twice daily on day 8 and 200 mg once daily from days 9 to 18). Itraconazole was given with a loading dose on Day 8 and the total administration of itraconazole was 11 days. In Study 2, subjects were administered a single dose of SKLB1028 (100 mg on days 1 and 12) and multiple doses of gemfibrozil (600 mg twice daily from days 8 to 19). In Study 3, subjects were administered a single dose of SKLB1028 (150 mg on days 1 and 15) and multiple doses of rifampin (600 mg once daily from day 8 to 22). Itraconazole increased the AUC and Cmax of SKLB1028 by approximately 28% and 41%, respectively. Compared to the single drug, co-administration with gemfibrozil increased the AUC of SKLB1028 by ~26% and the Cmax by ~21%. Co-administration with rifampin reduced the AUC of SKLB1028 by ~30%, while the Cmax did not change significantly. All treatments were well tolerated in all three studies.

A randomized, placebo-controlled first-in-human study of oral TQS-168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect.

TQS-168, a first-in-class small-molecule inducer of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study of TQS-168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach. Dosing in the SAD part was initiated with a crystalline methylcellulose (MC) suspension, and then spray-dried dispersion (SDD) and hot-melt extrusion (HME) suspensions were evaluated. The HME and SDD formulations showed two and fourfold higher exposure than the MC suspension, respectively, and the SDD formulation was selected for progression to subsequent SAD and MAD cohorts, in which there was further investigation of the food effect on exposure in addition to assessments of safety, tolerability, PK, and PD. Cmax and AUC plasma exposures of TQS-168 were supra-proportional at higher doses, irrespective of formulation. Median Tmax for TQS-168 occurred between 0.5 and 4.0 h post-dose and occurred later with higher doses. Geometric mean half-lives (T1/2) for TQS-168 were independent of formulation and food, ranging from 3.2 to 10.5 h following single doses and 4.1 to 7.3 h following multiple doses. Food blunted TQS-168 Cmax but had minimal impact on AUC. TQS-168 was considered to be safe and generally well tolerated following single and multiple oral doses. The SDD formulation was selected for future patient studies.

Analysis of the mean electrical axis of the heart from standard electrographic leads in normal adult males

Background: Electrocardiogram has been widely applied as a diagnostic tool for cardiovascular disease. The concept of the cardiac vector is crucial for the clinical application in ECG interpretation. Methods: A prospective cross-sectional study was conducted among 116 male subjects, aged 18-25 years, comprising students and staff of Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal, over the period from June to September 2023. Electrocardiograms (ECGs) were recorded using a standard ECG machine with conventional limb leads. The mean electrical axis of the heart for each individual was determined by plotting the net voltage of the QRS complex in Lead-I and Lead-III. The study aimed to analyze the correlation between the cardiac vector and physical measurements, such as height, weight, Body Surface Area (BSA), and Body Mass Index (BMI). Data analysis was performed using SPSS version 27.0. Results: The normal mean electrical axis of the healthy male subjects was observed as 57.88±24.55°. There was significant positive correlation of cardiac vector with height (p< 0.05), whereas negative correlation was observed with weight and BMI (p< 0.01). However, there was no significant correlation with BSA. In our study we observed the maximum left axis cardiac vector as -10° and right axis as 90° among 116 male subjects. Conclusion: We established a cardiac vector with values differing from those reported in other studies, using standard bipolar limb leads in normal, healthy male subjects. It is also examined that greater BMI has shifted the electrical activity of the ventricles to the left.

Bioequivalence study of eltrombopag 75 mg film-coated tablets under fasting conditions during the Covid-19 pandemic in healthy Caucasian male subjects

This study aims to determine the bioequivalence of the reference preparation and the test preparation containing eltrombopag when both were given during the COVID-19 pandemic while fasting. Participants in the research were healthy male Caucasian subjects. One film-coated tablet of the test preparation or one film tablet of the reference preparation, equivalent to 75 mg of eltrombopag, was given to the participants in a randomized order throughout each treatment session. At pre determined blood sampling points, blood samples were taken to determine the pharmacokinetics of eltrombopag. Eltrombopag concentrations in the samples were determined using an LC-MS/MS technique verified using ESI(−). The study results were used to calculate the rate (the maximum plasma concentration, or Cmax) and extent (area under the concentration-time curve of plasma, or AUC(0−72) and AUC(0−t) of eltrombopag absorption from the test preparation and reference preparation. The 90% confidence intervals (CI) of the ln-transformed AUC(0−72), AUC(0−t), and Cmax of eltrombopag met the bioequivalence requirements of 80.00–125.00%. Both trial preparations had a similar and very satisfactory safety profile.

Deodorising Garlic Body Odour by Ingesting Natural Food Additives Containing Phenolic Compounds and Polyphenol Oxidase

Garlic consumption is a well-known cause of unpleasant breath and body odour, with volatile organosulfur compounds, such as diallyl disulfide (DADS) and allyl methyl sulfide (AMS) responsible for the characteristic odour. Certain foods that are rich in polyphenols (PPs) and polyphenol oxidase (PPO) are known to deodorise garlic breath. However, no study into garlic body odour has been reported owing to the very low amounts of emitted volatile organosulfur compounds. Herein, we aimed to demonstrate the effects of ingesting natural food additives rich in both PPs and PPO on the emissions of skin-derived DADS and AMS using a passive flux sampler in conjunction with gas chromatography–mass spectrometry. Three healthy male subjects were subjected to garlic-consumption testing, with all subjects commonly observed to exhibit remarkably higher dermal DADS- and AMS-emission fluxes after consuming 45 g of cooked garlic, which then gradually decreased toward their initial baseline levels. In comparison, remarkably lower emission fluxes of both organosulfur compounds were observed after consuming a natural food additive following garlic consumption in a dose-dependent manner. The optimal amount of ingested natural food additive required to reduce garlic body odour was found to be 1–2 g. Considering the metabolic pathway associated with garlic-derived sulfur compounds and elimination reactions involving PPs and PPO, allyl mercaptan is likely to be a key substance involved in reducing garlic body odour through the ingestion of natural food additives.

Single-dose and steady-state pharmacokinetics of clomipramine, yohimbine and clomipramine/yohimbine combination: A clinical drug-drug interaction study.

Clomipramine (CLOMI) has shown effectiveness in treating premature ejaculation but is linked to erectile dysfunction and reduced libido. Yohimbine (YOH), by contrast, is effective in treating erectile dysfunction and may improve libido. Combining CLOMI and YOH could potentially leverage the benefits of both drugs. This study aimed to investigate the interactions between these drugs and to evaluate their safety profile. A prospective, open-labelled, single-centre, pharmacokinetic (PK) drug-drug interaction study was performed in 15 healthy male subjects. Single-dose and steady-state PK were investigated using noncompartmental analysis after mono- and combination therapy of the 2 orally applied drugs. Plasma sampling was performed at baseline, 0.5 (YOH), 1, 1.5 (YOH), 2, 3, 4, 5, 6, 8, 12 and 24 h (CLOMI). Differences in the area under the curve after multiple dosing (MD) were determined using an equivalence boundary of 80-125%. The geometric mean ratio of the area under the curve up to 12 h for MD CLOMI (combination vs. monotherapy) was 112% (90% confidence interval: 104-120%), whereas for MD YOH this ratio was 137% (90% confidence interval: 112-168%). The study drugs were safe and well tolerated as mono- and combination therapy, with no major adverse events reported. A PK assessment of clomipramine and yohimbine indicated a clinically significant drug-drug interaction for MD YOH in combination with CLOMI. This might be explained by competitive, CLOMI-related inhibition of YOH metabolism, probably mediated by cytochrome P450 2D6. However, according to European Medicines Agency guidelines, the effect can be classified as interaction absent (<1,25 fold) or minor (>1.25-<2-fold). Given the complimentary mechanisms of action and the favourable safety profiles, the findings pave the way for future efficacy studies.

Electrophysiological Changes in Median Nerve among Young Male Cigarette Smokers

Background: Cigarette smoking has been associated with numerous cardiovascular and respiratory disorders. Chronic smoking may also disrupt neuronal function and damage neurons in the peripheral nervous system. Median nerve conduction study is an important electrodiagnostic test for the detection of peripheral nerve dysfunction. Objectives: To observe the impact of cigarette smoking on the electrophysiological status of median motor and sensory nerves in apparently healthy male cigarette smokers. Materials and Methods: This case-control study was carried out in the Department of Physiology, Sir Salimullah Medical College, Dhaka, from July 2017 to June 2018 on thirty male cigarette smokers aged 25 to 40 years. For comparison, thirty age and BMI matched non-smoker healthy male subjects were selected as controls. Motor and sensory nerve conduction parameters (latency, amplitude and nerve conduction velocity) of right median nerve were evaluated by standard methods, using standard nerve conduction study and electromyography machines in the Department of Neurology, Dhaka Medical College Hospital. For statistical analysis, unpaired t test was performed. Results: In this study, median sensory nerve latency was significantly prolonged (p ˂ 0.001) and sensory nerve conduction velocity was significantly slower (p ˂ 0.001) in cigarette smokers. The mean amplitude was also slightly reduced in smokers, but statistically, it was insignificant. However, the distal latency of median motor nerve was slightly prolonged whereas, the amplitude and motor nerve conduction velocity were slightly reduced in cigarette smokers in comparison to those of non-smokers. But the differences were not statistically significant. In addition, 10% of cigarette smokers had subclinical impairment in median sensory nerve function. Conclusion: Chronic cigarette smoking induces significant electrophysiological changes in median sensory nerve fibers and causes sensory nerve dysfunction, while it does not markedly affect median motor nerve fibers in young individuals. KYAMC Journal Volume: 15, No: 01, April 2024: 03-07.

Retinal Function in Young Adults Following Topical Application of Levodopa to the Eye.

Levodopa has been investigated as a therapeutic solution for ocular disorders involving dysregulation of the dopaminergic system, especially in the context of myopia. However, given the critical role dopamine plays in normal vision, this phase I trial examined whether levodopa/carbidopa eye drops induce any regional changes in retinal structure and function. Twenty-nine healthy male subjects 18 to 30 years of age were randomly assigned to receive either a low (1.4/0.34 µmoles/day, n = 14) or high (2.7/0.68 µmoles/day, n = 15) dose of levodopa/carbidopa eye drops in 1 eye for 28 consecutive days. A placebo solution was applied to all fellow eyes. Measures included visual acuity, regional frequency doubling perimetry, regional multifocal electroretinogram (mfERG) and optical coherence tomography (retinal thickness). Outcome measures were undertaken at baseline, end-of-treatment (4 weeks), and at a follow-up (4 months post-treatment). For low dose treated eyes, regional analysis showed a small, statistically significant change in mfERG recordings (increase in ring 5 amplitude in low dose treated eyes, P < 0.05) and the retinal thickness map (localized retinal thinning in low dose treated eyes, P < 0.05). These changes were not clinically significant. No significant changes were observed in high dose treated eyes. Pharmacokinetic analysis (rabbits) demonstrated that levodopa was not detectable within blood and peaked within the eye at 15 to 30 minutes (and eliminated within 4 hours). No clinically significant effects of levodopa/carbidopa eye drops were found with regard to normal retinal structure and function following short-term use. This study further demonstrates the safety of topical levodopa, which may support its use in the treatment of ocular disorders in which the dopamine system is dysregulated.

Comparative Impact of Organic Grass-Fed and Conventional Cattle-Feeding Systems on Beef and Human Postprandial Metabolomics-A Randomized Clinical Trial.

Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to measure whole beef metabolomics and postprandial metabolomic response of consumers between GRA and CON beef to elucidate potential health implications. This study followed a randomized double-blind crossover design with healthy male and female subjects (n = 10). Plasma samples were taken at fasting (0) and postprandially for four hours after consumption of a steak from each condition. Untargeted metabolomic analysis of whole beef and human plasma samples used LC/MS. Multivariate and pathway enrichment analysis in MetaboAnalyst was used to investigate metabolite and biochemical pathways that distinguished CON and GRA. Cattle-feeding systems impacted both postprandial and whole beef steak metabolomic profiles. Metabolites that contributed to this variation included carnitine species (Proionylcarnitine), fatty acids, amino acids (L-valine), and Calamendiol. These metabolites have been associated with oxidative stress, inflammation, and cardiovascular health. Functional pathway enrichment analysis revealed numerous amino acid degradation pathways, especially branched-chain amino acids, and fatty acid degradation that changed throughout the postprandial time course. These findings suggest that CON and GRA cattle-feeding systems differentially impact whole beef metabolomics, as well as consumer postprandial metabolic responses and the associated health implications.

Disposition of orally administered atuliflapon, a novel 5-lipoxygenase-activating protein inhibitor in healthy participants.

In this study, the mass balance, pharmacokinetics (PK) and metabolism of atuliflapon, a novel 5-lipoxygenase-activating protein inhibitor, were investigated in healthy male subjects. A single oral dose of 200 mg [14C]atuliflapon suspension was administered to six healthy male subjects. Mass balance, PK and metabolite profiles of atuliflapon were analyzed using radioactivity monitoring and liquid chromatography with mass spectrometry analysis. The safety of atuliflapon was assessed during the study. Atuliflapon was rapidly absorbed with a median tmax of 1.5 h, followed by a biphasic decline in plasma exposure rendering a terminal half-life of ~20 h. Unchanged atuliflapon was the predominant radioactive component in plasma, accounting for 40.1% of the total drug-related exposure (DRE), while a direct N-glucuronide was the only metabolite exceeding 10% of DRE, accounting for 20.9%. Renal excretion of intact atuliflapon accounted for <1% of the administered dose. In total 85.2% of administered radioactivity was recovered over 312 h with 79.3% and 5.9% in feces and urine, respectively. Parent atuliflapon contributed to approximately 40% of the recovered dose in excreta, while metabolites resulting from phase 1 oxidative pathways accounted for more than 30% of the excreted dose. Overall, a single oral dose of 200 mg [14C]atuliflapon suspension was well tolerated in healthy male subjects. The human metabolism and disposition data obtained will support future development and submissions of atuliflapon as a potential candidate drug for the treatment of cardiovascular, cardiorenal, and respiratory indications.

Mass balance and pharmacokinetic characterization ofzavegepant in healthy male subjects.

Zavegepant, a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist, is approved as a nasal spray for acute treatment of migraine in adults. This phase I, open-label, single-center, single-period, nonrandomized study in six healthy male subjects assessed mass balance recovery after a single 15-min intravenous (IV) infusion dose of carbon-14 ([14C])-zavegepant. Blood, urine, and fecal samples were collected over 192 h for analysis of zavegepant in plasma and urine; total radioactivity (TR) in plasma, whole blood, urine, and feces; and zavegepant metabolite profiling and structural identification in plasma, urine, and feces. An average of 96.6% of radioactivity administered was recovered in excreta. Most TR (mean 84.9%) was recovered in the feces, indicating that biliary/fecal elimination was the main route. Volume of distribution of zavegepant based on the terminal phase (129 L) was higher than total body water (42 L), indicating substantial distribution into tissue. Total plasma clearance of zavegepant (220 mL/min) is identical to whole blood clearance given the blood/plasma partition ratio of 1, lower than typical hepatic blood flow (1450 mL/min). The observed plasma terminal half-life of zavegepant was 6.8 h. Exposure to zavegepant accounted for ~90% of circulating plasma TR, suggesting that very low levels of uncharacterized circulating metabolites were present. Metabolite profiling did not identify any metabolites representing ≥10% of radioactivity in plasma, urine, or feces. A single IV infusion of 5 mg [14C]-zavegepant was well tolerated in healthy male subjects. Disposition findings of IV [14C]-zavegepant are applicable to the disposition of the approved zavegepant nasal spray.

19F qNMR based pharmacokinetics, metabolism and mass balance studies of SARS-CoV-2-3CL protease inhibitor simnotrelvir (SIM0417) in humans.

Simnotrelvir (SIM0417), an inhibitor of the 3CL protease of SARS-CoV-2, has been identified as a CYP3A sensitive substrate. This study investigated the pharmacokinetics, metabolism, and mass balance of simnotrelvir following a single oral dose of 750 mg in six healthy Chinese male subjects, co-administered with four doses of 100 mg ritonavir. Analysis using 19F qNMR combined with LC-MS/MS showed that the parent drug M0 constituted over 90% of the drug-related components in plasma. Of the administered dose, 55.4% (54.3% of M0) was recovered in urine, while 36.7% (4.57% of M0) was excreted in feces. UPLC/Q-TOF MS was used to identify metabolites in human plasma, urine and feces. Notably, oxidative metabolites catalyzed by CYP3A were scarcely detected in these matrixes. The amide hydrolyzed metabolite M9 and the cyano hydrolyzed metabolite M10 were recognized as the predominant metabolites, with the main excretion being through feces (19.0% and 12.7% of the administered dose, respectively). In vitro experiments indicated that M10 is primarily formed in the duodenum and jejunum, with further metabolism to M9 by microbiota in the large intestine. Overall, the co-administration of simnotrelvir with ritonavir led to predominant metabolism by intestinal enzymes or microbiota, resulting in hydrolyzed metabolites. These findings highlight the critical role of intestinal metabolism in the pharmacokinetics of simnotrelvir and emphasize the need to consider interactions with antibiotics and individual differences of intestinal microbiota.

The Clinical Efficacy of Lapachol in Facial Redness Reduction.

Facial erythema from acne, vascular rosacea, or photoaging is a common difficult-to-treat dermatologic challenge. The objective of this study was to examine the role of lapachol in alleviating facial erythema associated with a variety of common dermatologic conditions. Twenty-five healthy female and male subjects 35-65 years of age of Fitzpatrick skin types I-II with mild-to-moderate stable facial erythema from acne, rosacea or photoaging were enrolled in a single-site monadic study. Subjects received the study cream for twice daily application and were assessed at baseline, Week 4, and Week 8. The dermatologist investigator and subjects assessed efficacy and tolerability and facial photographic images were taken of all subjects at each visit. Noninvasive erythema assessments of the face were conducted using a colorimeter at baseline, Week 4, and Week 8 to document improvement in facial erythema. Twenty-five out of 25 subjects successfully completed the study without tolerability issues including 12 subjects with rosacea, 6 subjects with photoaging and 7 subjects with acne. After 8 weeks of use, the investigator rated a 44% decrease in facial erythema while the subjects rated a 40% decrease. Facial erythema was also noninvasively assessed with a colorimeter and dermaspectrophotometer (DSP). There was a 26% decrease in skin redness at Week 4 and a 31% decrease in skin redness at Week 8 on the colorimeter L*a*b* scale. This finding was collaborated by the DSP which registered a 29% decrease on the erythema scale at Week 8. Lapachol in a moisturizer formulation was found to be effective in reducing facial erythema from acne, rosacea, and photoaging.

Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.

Nivolumab (Opdivo®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab. This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed. A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC0-∞, and the secondary pharmacokinetic endpoints included AUC0-t and Cmax. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%. This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo® in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo® were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC0-∞, AUC0-t, and Cmax of LY01015 to Opdivo® were 94.49% (90.29-98.88%), 94.92% (88.73-101.54%), and 96.55% (93.32-99.90%), respectively, falling within the conventional bioequivalence criteria of 80.00-125.00%. The safety and immunogenicity were also comparable between the two groups. LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles. This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).

A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects

AimsBronchiectasis patients face an unmet need for treatment options that reduce inflammation. Cathepsin C inhibition is expected to achieve this by reducing the activation of neutrophil‐derived serine proteases. Here, we present safety and pharmacokinetic (PK) data from a Phase I trial evaluating the novel cathepsin C inhibitor BI 1291583 in healthy Japanese male subjects.MethodsThis randomized, double‐blind, placebo‐controlled, parallel‐group study investigated BI 1291583 in healthy Japanese male subjects (jRCT2071210111) and consisted of a single‐rising‐dose (SRD) part and a multiple‐dose (MD) part. The primary endpoint was the percentage of subjects with drug‐related treatment‐emergent adverse events (AEs). Secondary PK endpoints (SRD: AUC0‐∞ and Cmax; MD: AUCτ,1 and Cmax,1 after first dose and AUCτ,ss and Cmax,ss after last dose), as well as further safety and PK endpoints, were also assessed.ResultsOverall, 36 subjects (n = 24 for SRD part; n = 12 for MD part) entered this Phase I trial. BI 1291583 was safe and well tolerated across the doses tested. All AEs were of mild intensity, with no drug‐related treatment‐emergent AEs, deaths, serious AEs or AEs of special interest reported in either part of the trial. Following both SRD and MD administration, BI 1291583 was readily absorbed, and PK was supraproportional over the doses assessed.ConclusionThe results show that BI 1291583 has an appropriate benefit–risk ratio for Japanese patients, with no safety or exposure concerns at the doses studied. Japanese patients with bronchiectasis can be safely integrated into future global clinical trials of BI 1291583, with no dose adjustment required.

Analytical Performance of the FreeStyle Libre 2 Glucose Sensor in Healthy Male Adults.

Continuous Glucose Monitoring (CGM) not only can be used for glycemic control in chronic diseases (e.g., diabetes), but is increasingly being utilized by individuals and athletes to monitor fluctuations in training and everyday life. However, it is not clear how accurately CGM reflects plasma glucose concentration in a healthy population in the absence of chronic diseases. In an oral glucose tolerance test (OGTT) with forty-four healthy male subjects (25.5 ± 4.5 years), the interstitial fluid glucose (ISFG) concentration obtained by a CGM sensor was compared against finger-prick capillary plasma glucose (CPG) concentration at fasting baseline (T0) and 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min post OGTT to investigate differences in measurement accuracy. The overall mean absolute relative difference (MARD) was 12.9% (95%-CI: 11.8-14.0%). Approximately 100% of the ISFG values were within zones A and B in the Consensus Error Grid, indicating clinical accuracy. A paired t-test revealed statistically significant differences between CPG and ISFG at all time points (T0: 97.3 mg/dL vs. 89.7 mg/dL, T30: 159.9 mg/dL vs. 144.3 mg/dL, T60: 134.8 mg/dL vs. 126.2 mg/dL, T90: 113.7 mg/dL vs. 99.3 mg/dL, and T120: 91.8 mg/dL vs. 82.6 mg/dL; p < 0.001) with medium to large effect sizes (d = 0.57-1.02) and with ISFG systematically under-reporting the reference system CPG. CGM sensors provide a convenient and reliable method for monitoring blood glucose in the everyday lives of healthy adults. Nonetheless, their use in clinical settings wherein implications are drawn from CGM readings should be handled carefully.

Real-time estimation of blood oxygenation parameters from human foot sole during leg elevation: A preliminary study with diffuse reflectance spectroscopy

This study investigated the applicability of diffuse reflectance spectroscopy (DRS) for real-time and non-invasive measurement of blood oxygenation parameters (BOPs) such as reduced hemoglobin (RHb), oxyhemoglobin (HbO2), and oxygen saturation (SO2) from human foot sole during leg elevation. Seventeen (17) healthy male subjects aged between 21 to 39 years were included in this study. Diffuse reflectance spectra were recorded from measurement sites namely the 5th metatarsal, ball of great joint, calcaneum, and great toe of the human foot sole w.r.t. leg elevation angles such as 00, 150, 300, 450, and 600, respectively. The localized BOPs were derived from the recorded spectra. In addition, blood hemodynamic parameters (BHPs) such as heart rate (HR), SO2, perfusion index (PI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were also measured for each elevating angle. To study and assess the changes in BOPs and BHPs w.r.t. leg elevation, a One-way ANOVA test followed by a Tukey HSD post-hoc test was performed. We observed a statistically significant increase in RHb (p < 0.001) and a decrease in HbO2 (p < 0.001) after 45° of leg elevation, however, there was no statistically significant difference in SO2 (p = 0.74) and HR (p = 0.84) for each measurement site w.r.t. leg elevation, respectively. Furthermore, PI (p < 0.01), ankle SBP (p < 0.001) and DBP (p < 0.001) were decreased w.r.t. leg elevation. The obtained results are in agreement with the literature. The preliminary results suggest that DRS has the potential for real-time estimation of BOPs from the local sites of healthy human foot soles during leg elevation. Thus, it opens the possibility of DRS to monitor and evaluate the diagnosis and treatment of ischemia and edema during leg elevation of patients through BOPs measurement.

A Compound Containing Aldehyde Dehydrogenase Relieves the Effects of Alcohol Consumption and Hangover Symptoms in Healthy Men: An Open-Labeled Comparative Study.

This open-labeled and comparative study aimed to test the efficacy and safety of a fermented rice extract-based substance containing yeast-fermented powder having aldehyde dehydrogenase (KisLip®, Pico Entech, Republic of Korea) in healthy male individuals. Healthy male subjects (n = 20) consumed 90 g of alcohol at their first visit. At the second visit, participants consumed 90 g of alcohol or alcohol with a low dose of KISLip® (2000 mg, KL-L) and then 90 g of alcohol or alcohol with a high dose of KISLip® (3000 mg, KL-H) at the third visit. The efficacy of KISLip® depends on the mutational status of important genes related to alcohol metabolism, including alcohol dehydrogenase (ADH1B), cytochrome P4502E1 (CYP2E1 (5B) and CYP2E1 (6)), and aldehyde dehydrogenase (ALDH2). KISLip® significantly reduced the highest level (Cmax) of alcohol and overall levels of acetaldehyde compared to the alcohol-only group in a dose-dependent manner. These significant effects of KISLip® on alcohol metabolism were observed independent of mutations in the four genes. In addition, hangover symptoms were significantly decreased in the KISLip® treated groups. During the study, the participants did not show any adverse events after KISLip® intake. This clinical study suggested that supplementation of KISLip® had beneficial effects on alcohol metabolism and might ameliorate the severity of hangovers without any adverse events.

Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects.

Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20mg/100µCi of [14C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.

Advanced myocardial deformation echocardiography for evaluation of the athlete's heart: Functional and mechanistic analysis

BackgroundAssessment of the athlete's heart is challenging because of a phenotypic overlap between reactive physiological adaptation and pathological remodelling. The potential value of myocardial deformation remains controversial in identifying early cardiomyopathy. AimTo identify the echocardiographic phenotype of athletes using advanced two-dimensional speckle tracking imaging, and to define predictive factors of subtle left ventricular systolic dysfunction. MethodsIn total, 191 healthy male athletes who underwent a preparticipation medical evaluation at Nancy University Hospital between 2013 and 2020 were included. Clinical and echocardiographic data were compared with 161 healthy male subjects from the STANISLAS cohort. Borderline global longitudinal strain value was defined as<17.5%. ResultsAthletes demonstrated lower left ventricular ejection fraction (57.9±5.3% vs. 62.6±6.4%; P<0.01) and lower global longitudinal strain (17.5±2.2% vs. 21.1±2.1%; P<0.01). No significant differences were found between athletes with and without a borderline global longitudinal strain value regarding clinical characteristics, structural echocardiographic features and exercise capacity. A borderline global longitudinal strain value was associated with a lower endocardial global longitudinal strain (18.8±1.2% vs. 22.7±1.9%; P=0.02), a lower epicardial global longitudinal strain (14.0±1.1% vs. 16.6±1.2%; P<0.01) and a higher endocardial/epicardial global longitudinal strain ratio (1.36±0.07 vs. 1.32±0.06; P<0.01). No significant difference was found regarding mechanical dispersion (P=0.46). ConclusionsBorderline global longitudinal strain value in athletes does not appear to be related to structural remodelling, mechanical dispersion or exercise capacity. The athlete's heart is characterized by a specific myocardial deformation pattern with a more pronounced epicardial layer strain impairment.