Parameters In Healthy Volunteers Research Articles

Genetic variation in UGT1A1 is not associated with altered liver biochemical parameters in healthy volunteers participating in bioequivalence trials

Introduction: Bioequivalence clinical trials are conducted in healthy volunteers whose blood tests should be within normal limits; individuals with Gilbert syndrome (GS) are excluded from these studies on suspicion of any liver disease, even if the change is clinically insignificant. GS is a benign genetic disorder characterized by elevated bilirubin levels, the primary cause of which is the presence of polymorphisms in UGT1A1 gene. In this work, subjects with UGT1A1 intermediate (IM) or poor (PM) metabolizer genotype-informed phenotypes were investigated to determine whether they have a higher incidence of liver disease or other biochemical parameters.Methods: The study population comprised 773 healthy volunteers who underwent biochemical analysis at baseline and at the end of the study which were genotyped for UGT1A1*80 (rs887829), as an indicator of UGT1A1*80+*28 (rs887829 and rs3064744), and UGT1A1*6 (rs4148323).Results: Bilirubin levels were higher in subjects IMs and PMs compared to normal metabolizers (NMs). Decreased uric acid levels was observed in PMs compared to NMs. No associations were observed in liver enzyme levels according to UGT1A1 phenotype.Discussion: Considering that there is no hepatic toxicity in subjects with UGT1A1 IM or PM phenotype, who are more likely to develop GS, this study suggests that they could be included in bioequivalence clinical trials as their biochemical parameters are not affected outside normal ranges.

The effect of an anti-malarial herbal remedy, Maytenus senegalensis, on electrocardiograms of healthy Tanzanian volunteers

BackgroundThe emergence of resistance to artemisinin-based combination therapy necessitates the search for new, more potent antiplasmodial compounds, including herbal remedies. The whole extract of Maytenus senegalensis has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of M. senegalensis in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of M. senegalensis is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study's objective was to evaluate the electrocardiographic effects of M. senegalensis in healthy adult volunteers.MethodsThis study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56.ResultsNo QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800 mg) of M. senegalensis experienced a moderate transient change (△QTcF > 30 ms; specifically, the value was 37 ms) from baseline on day 28. There was no difference in maximum QTcF and maximum △QTcF between volunteers in all four study dose groups.ConclusionsA four-day regimen of 800 mg every 8 h of M. senegalensis did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that M. senegalensis could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of M. senegalensis. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of M. senegalensis in different demographic groups. This is especially important considering the potential use of M. senegalensis as a therapeutic agent and its widespread utilization as traditional medicine.Trial registration ClinicalTrials.gov, NCT04944966. Registered 30 June 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04944966?term=kamaka&draw=2&rank=1

Pancreatic stiffness and anthropometric parameters in healthy volunteers.

The aim of this study was to define the values of percutaneous ultrasound shear-wave and strain elastography of the pancreas in healthy volunteers. This is asingle-center prospective study conducted on volunteers who underwent examination of percutaneous point shear‑wave elastography and strain elastography. Both the shear-wave speed (Vs) and strain histogram were measured 3 times and median values were evaluated. Relevant recorded clinical data were age, sex, and height. From May 2020 to October 2021 atotal of 90 patients (21 male, 69 female) were included in the study. Their average age was 26 years (from 22 to 65). The average SWM in kPa was 6.07 (2.58-17.29). The average value of SE was 134.44 (78.51-184.35). Most of the patients had BMI in the range of normal weight with an average value of 22.75 (17.5-28). The average depth of the localization of the pancreas was 4.5 cm. The effect of BMI on the strain histogram was significant (p < 0.05). We found asignificant relationship between the strain histogram and the depth of localization of the pancreas (p < 0.01). We described normal values for pancreatic stiffness using ultrasound elastography by 2D-SWE and strain elastography. Our results indicate changes in values depending on BMI and depth of the pancreas. (Tab. 1, Fig. 5, Ref. 19).

Comparison of Bioelectrical Impedance Analysis (BIA)-Derived Parameters in Healthy Volunteers and Critically Ill Patients.

To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. Retrospective, observational data analysis. Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index.

Quantitative 4D flow MRI-derived thoracic aortic normal values of 2Dflow MRI parameters in healthy volunteers.

To utilize 4 D flow MRI to acquire normal values of "conventional 2 D flow MRI parameters" in healthy volunteers in order to replace multiple single 2 D flow measurements with a single 4 D flow acquisition. A kt-GRAPPA accelerated 4 D flow sequence was used. Flow volumes were assessed by forward (FFV), backward (BFV), and net flow volumes (NFV) [ml/heartbeat] and flow velocities by axial (VAX) and absolute velocity (VABS) [m/s] in 116 volunteers (58 females, 43 ± 13 years). The aortic regurgitant fraction (RF) was calculated. The sex-neutral mean FFV, BFV, NFV, and RF in the ascending aorta were 93.5 ± 14.8, 3.6 ± 2.8, 89.9 ± 0.6 ml/heartbeat, and 3.9 ± 2.9 %, respectively. Significantly higher values were seen in males regarding FFV, BFV, NFV and RF, but there was no sex dependency regarding VAX and VABS. The mean maximum VAX was lower (1.01 ± 0.31 m/s) than VABS (1.23 ± 0.35 m/s). We were able to determine normal ranges for all intended parameters. This study provides quantitative 4 D flow-derived thoracic aortic normal values of 2 D flow parameters in healthy volunteers. FFV, BFV, NFV, and VAX did not differ significantly from single 2 D flow acquisitions and could therefore replace time-consuming multiple single 2 D flow acquisitions. VABS should not be used interchangeably. · 4 D flow MRI can be used to replace 2 D flow MRI measurements.. · The parameter absolute velocities can be assessed by 4 Dflow MRI.. · There are sex-dependent differences regarding forward, backward, net aortic blood flow and the aortic valve regurgitant fraction..

The results of hemostasis assessment using thromboelastography in patients with COVID-19

All currently existing studies of the hemostasis system  in COVID-19 using thromboelastography (TEG) were performed on the delta strain of SARS-CoV-2, while there is no information in the literature on conducting such studies in patients infected with the current omicron strain.Research objective. To determine the state of the hemostasis system in hospitalized patients with COVID-19 (omicron strain) using TEG. To assess the relevance of existing guidelines on anticoagulant therapy.Materials and methods. TEG was performed in 93 hospitalized patients with COVID-19 aged 1 to 88 years, of which 66 patients (group 1) on the first day and 27 patients (group 2) – on the second day. For comparison with the parameters of healthy volunteers, a sample of 30 people was formed. Data analysis was performed using the Statistica, version  12 (StatSoft, USA). To compare the independent variable in more than two samples, a multivariate ANOVA analysis of variance was performed with the calculation of the Kruskal-Wallis test. To assess the relationships between continuous variables, the Spearman direct linear correlation coefficient (r) was determined.Results. 53% of patients had hypocoagulation, 31% had normocoagulation, and 16% had hypercoagulation. Elderly patients (61 [26–72]) more often have developed hypocoagulation. Young patients (24.5 [7–37]) more often have developed hypercoagulation. Routine methods for assessing hemostasis did not reflect its true state. Higher levels of fibrinogen (4.5 [5.8–4] g/l) and D-dimer (1.28 [0.5–2.77] µg/ ml) were observed in patients from the group with normocoagulation. Was revealed a statistical tendency towards an increase in the level of amylase when there was an increase in the coagulation properties of the blood.Conclusion. With the current course of COVID-19 and early admission of non-severe patients to the hospital, normocoagulation and hypocoagulation predominate. Elderly and senile patients are not recommended to prescribe anticoagulants without TEG. It is necessary to specify the recommendations for prescribing anticoagulants to hospitalized patients. For the diagnosis of hemostasis disorders expand application of TEG.

Effects Of Exercise With Blood Flow Restriction On Hemodynamic And Functional Parameters In Healthy Volunteers

Effects Of Exercise With Blood Flow Restriction On Hemodynamic And Functional Parameters In Healthy Volunteers

Spinal cord motion and CSF flow in the cervical spine of 70 healthy participants.

Pulsatile spinal cord and CSF velocities related to the cardiac cycle can be depicted by phase-contrast MRI. Among patients with spontaneous intracranial hypotension, we have recently described relevant differences compared with healthy controls in segment C2/C3. The method might be a promising tool to solve clinical and diagnostic ambiguities. Therefore, it is important to understand the physiological range and the effects of clinical and anatomical parameters in healthy volunteers. Within a prospective study, 3D T2 -weighted MRI for spinal canal anatomy and cardiac-gated phase-contrast MRI adapted to CSF flow and spinal cord motion for time-resolved velocity data and derivatives were performed in 70 participants (age 20-79 years) in segments C2/C3 and C5/C6. Correlations were analyzed by multiple linear regression models; p< 0.01 was required to assume a significant impact of clinical or anatomical data quantified by the regression coefficient B. Data showed that in C2/C3, the CSF and spinal cord craniocaudal velocity ranges were 4.5 ± 0.9 and 0.55 ± 0.15 cm/s; the total displacements were 1.1 ± 0.3 and 0.07 ± 0.02 cm, respectively. The craniocaudal range of the CSF flow rate was 8.6 ± 2.4 mL/s; the CSF stroke volume was 2.1 ± 0.7 mL. In C5/C5, physiological narrowing of the spinal canal caused higher CSF velocity ranges and lower stroke volume (C5/C6 B =+1.64 cm/s, p< 0.001; B =-0.4 mL, p =0.002, respectively). Aging correlated to lower spinal cord motion (e.g., B =-0.01 cm per 10 years of aging, p< 0.001). Increased diastolic blood pressure was associated with lower spinal cord motion and CSF flow parameters (e.g., C2/C3 CSF stroke volume B =-0.3 mL per 10 mmHg, p <0.001). Males showed higher CSF flow and spinal cord motion (e.g., CSF stroke volume B =+0.5 mL, p <0.001; total displacement spinal cord B =+0.016 cm, p =0.002). We therefore propose to stratify data for age and sex and to adjust for diastolic blood pressure and segmental narrowing in future clinical studies.

Intra-and inter-observer variability of point of care ultrasound measurements to evaluate hemodynamic parameters in healthy volunteers

BackgroundPoint-of-care ultrasound (POCUS) is a valuable tool for assessing the hemodynamic status of acute patients. Even though POCUS often uses a qualitative approach, quantitative measurements have potential advantages in evaluating hemodynamic status. Several quantitative ultrasound parameters can be used to assess the hemodynamic status and cardiac function. However, only limited data on the feasibility and reliability of the quantitative hemodynamic measurements in the point-of-care setting are available. This study investigated the intra- and inter-observer variability of PoCUS measurements of quantitative hemodynamic parameters in healthy volunteers.MethodsIn this prospective observational study, three sonographers performed three repeated measurements of eight different hemodynamic parameters in healthy subjects. An expert panel of two experienced sonographers evaluated the images’ quality. The repeatability (intra-observer variability) was determined by calculating the coefficient of variation (CV) between the separate measurements for each observer. The reproducibility (inter-observer variability) was assessed by determining the intra-class correlation coefficient (ICC).Results32 subjects were included in this study, on whom, in total, 1502 images were obtained for analysis. All parameters were in a normal physiological range. Stroke volume (SV), cardiac output (CO), and inferior vena cava diameter (IVC-D) showed high repeatability (CV under 10%) and substantial reproducibility (ICC 0.61–0.80). The other parameters had only moderate repeatability and reproducibility.ConclusionsWe demonstrated good inter-observer reproducibility and good intra-observer repeatability for CO, SV and IVC-D taken in healthy subjects by emergency care physicians.

The Effect of Device-Controlled Breathing on the Pulse Arrival Time and the Heart Rate Asymmetry Parameters in Healthy Volunteers

Background: The development of wearables has facilitated the monitoring of biomedical parameters in everyday life. One of the most common sensors of these gadgets is the photoplethysmograph (PPG); hence, the proper processing and interpretation of the PPG signal are essential. Besides pulse rate detection, these devices—together with an ECG—compute the pulse arrival time (PAT), from which the actual beat-to-beat blood pressure can be estimated. The heart rate shows asymmetrical accelerations and decelerations, quantified by the parameters of heart rate asymmetry (HRA). In the present study, we investigated the influences of different breathing-patterns on the PATs and HRA parameters. Methods: The authors evaluated 5 min simultaneous respiratory-, ECG- and PPG-signal recordings of 35 healthy, young volunteers specifically expressing the following breathing patterns: metronome-controlled inspiration, and both inspiration and expiration controlled at 1:1 and 1:2 ratios, respectively. The records were analyzed by HRVScan_Merge v3.2 software. The PAT values were calculated at eight different reference points. The HRA parameters and the PAT values at different breathing patterns were compared using the Friedman test and post hoc Wilcoxon paired-sample test. Results: Porta- and Guzik-indices significantly increased at 1:1 breathing compared to 1:2 and single-paced breathing. PATs increased significantly in dual-paced series compared to single-paced series at each reference point. Conclusion: Based on our results, the increased PATs at dual-paced versus single-paced breathing may indicate the involvement of cognitive functions. The symmetrical respiration ratio increases the heart rate symmetry; however, this effect is not detectable in the periphery through the PATs.

Effect of Pomegranate Extract Consumption on Satiety Parameters in Healthy Volunteers: A Preliminary Randomized Study.

There has been an increasing interest in nutraceuticals and functional foods in reducing appetite and to lose weight. We assessed the effect of oral pomegranate extract (PE) and PE juice (PJ) intake vs. placebo on satiety parameters in healthy volunteers. Twenty-eight subjects (mean age 34.5 ± 13.7 years, body mass index [BMI] 25.05 ± 3.91 kg/m2) were randomized to 3-week priming supplementation with PE (Pomanox®) or placebo. On week 3, satiety parameters were determined on 1 testing day after participants ingested a breakfast and a lunch meal with PJ juice, using 100-mm visual acuity scales (VAS) for hunger, desire to eat, fullness and satisfaction. Meal quality and palatability were also tested. The desire to eat was less at all time points in the PJ juice with PE priming group and participants were also less hungry (p = 0.044) than those who consumed placebo. There was an overall significant difference between the groups (p < 0.001). Participants in the PJ juice with PE priming group experienced significantly greater satisfaction (p = 0.036) and feeling of fullness (p = 0.02) than those in the placebo group. These findings suggest that consumption of PE could have the potential to modulate satiety indicators.

POS1268 PHASE II TRIAL OF ENPATORAN IN PATIENTS HOSPITALIZED WITH COVID-19 PNEUMONIA

BackgroundEnpatoran is a selective and potent dual toll-like receptor (TLR) 7/8 inhibitor in development for the treatment of cutaneous and systemic lupus erythematosus (CLE/SLE). Enpatoran inhibits TLR7/8 activation in vitro and suppresses disease activity in lupus mouse models.1 Enpatoran was well tolerated and had linear pharmacokinetic (PK) parameters in healthy volunteers.2 As TLR7/8 mediate immune responses to single-stranded RNA viruses, including SARS-CoV-2, it was postulated that enpatoran may prevent hyperinflammation and cytokine storm in COVID-19.ObjectivesIn response to the COVID-19 pandemic, we conducted an exploratory Phase II trial to assess safety and determine whether enpatoran prevents clinical deterioration in patients (pts) hospitalized with COVID-19 pneumonia. PK and pharmacodynamics (PD) of enpatoran were also evaluated.MethodsANEMONE was a randomized, double-blind, placebo (PBO)-controlled study conducted in Brazil, the Philippines, and the USA (NCT04448756). Pts aged 18–75 years, hospitalized with COVID-19 pneumonia (WHO 9-point scale score =4) but not mechanically ventilated, with SpO2 &lt;94% and PaO2/FiO2 ≥150 (FiO2 maximum 0.4) were eligible. Those with a history of uncontrolled illness, active/unstable cardiovascular disease and SARS-CoV-2 vaccination were excluded. Pts received PBO or enpatoran (50 or 100 mg twice daily [BID]) for 14 days, with monitoring to Day 28 and safety follow-up to Day 60. Primary outcomes were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (time to clinical status &gt;4, WHO 9-point scale) was a secondary outcome. Exploratory endpoints were enpatoran and biomarker concentrations (cytokines, C-reactive protein [CRP], D-dimer and interferon gene signature [IFN-GS] scores) assessed over time.Results149 pts received either PBO (n=49), or enpatoran 50 mg (n=54) or 100 mg (n=46) BID; 88% completed treatment and 86% received concomitant steroids. Median age was 50 years (77% &lt;60 years old), 66% were male, and 50% had ≥1 comorbidity (40% hypertension, 24% diabetes). Overall, 59% pts reported a treatment-emergent adverse event (TEAE) with three non-treatment-related deaths; 11% reported a treatment-related TEAE. The proportion of pts in the enpatoran group reporting serious TEAEs was low (50 mg BID 9%; 100 mg BID 2%) vs PBO (18%). Gastrointestinal disorders were most common (PBO 8%; 50 mg BID 28%; 100 mg BID 9%). The primary outcome of time to recovery with enpatoran vs PBO was not met; medians were 3.4–3.9 days. A positive signal in time to clinical deterioration from Day 1 through Day 28 was observed; hazard ratios [95% CI] for enpatoran vs PBO were 0.39 [0.13, 1.15] (50 mg BID) and 0.30 [0.08, 1.08] (100 mg BID). Mean enpatoran exposure was dose-proportional, and PK properties were within expectations. The median (quartile [Q]1– Q3) interleukin 6 (IL-6), CRP and D-dimer baseline concentration across the groups were 5.7 (4.0–13.5) pg/mL, 30.04 (11.40–98.02) and 0.62 (0.39–1.01) mg/L, respectively. Baseline IFN-GS scores were similar across groups.ConclusionThe ANEMONE trial was the first to evaluate the safety and efficacy of a TLR7/8 inhibitor in an infectious disease for preventing cytokine storm. Enpatoran up to 100 mg BID for 14 days was well tolerated by patients acutely ill with COVID-19 pneumonia. Time to recovery was not improved with enpatoran, perhaps due to the younger age of patients who had fewer comorbidities compared to those in similar COVID-19 trials. However, there was less likelihood for clinical deterioration with enpatoran than placebo. This trial provides important safety, tolerability, PK and PD data supporting continued development of enpatoran in SLE and CLE (NCT04647708, NCT05162586).

Fasting-Mimicking Diet Reduces Trimethylamine N-Oxide Levels and Improves Serum Biochemical Parameters in Healthy Volunteers.

Elevated plasma levels of trimethylamine N-oxide (TMAO) have been proposed as a diet-derived biomarker of cardiometabolic disease risk. Caloric restriction is the most common dietary intervention used to improve cardiometabolic health; however, novel trends suggest a fasting-mimicking diet (FMD) as a more feasible alternative. FMD is a variation of intermittent fasting, based on caloric restriction and limitation of protein sources of animal origin, applied in daily cycles during a 5-day period. As TMAO is intensively produced by gut microbiota after the consumption of animal-derived products, we aim to investigate whether a 5-day FMD affects plasma TMAO levels and markers of metabolic health. To investigate whether an increase in vegetable intake possesses similar effects on TMAO levels and metabolic parameters, healthy volunteers (n = 24) were subjected to a 5-day FMD and 19 volunteers served as a reference group (VEG). This group of volunteers consumed an additional four servings of vegetables per day, but otherwise stayed on their usual diet. FMD resulted in a twofold decrease in plasma TMAO levels, which was not evident in the volunteers from the VEG group. Moreover, FMD led to a weight loss of 2.8 ± 0.2 kg and a subsequent reduction in BMI compared to baseline. The FMD group exhibited a significant elevation in plasma ketone bodies (14-fold compared to baseline) and a decrease in IGF-1 levels by 37 ± 8 ng/mL. Since fasting glucose and C-peptide levels decreased, all volunteers in the FMD group showed improved insulin sensitivity and a decreased HOMA-IR index. In contrast, in the VEG group, only a slight reduction in plasma levels of fasting glucose and triglycerides was noted. In conclusion, we show that FMD is a viable strategy to reduce plasma levels of TMAO by limiting caloric intake and animal-derived protein consumption. The reduction in the level of TMAO could be an additional benefit of FMD, leading to a reduced risk of cardiometabolic diseases.

Evaluation of Intravenous Phenobarbital Pharmacokinetics in Critically Ill Patients With Brain Injury

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.

Preload Dependency of 2D Right Ventricle Speckle Tracking Echocardiography Parameters in Healthy Volunteers: A Prospective Pilot Study.

(1) Background: Right ventricular (RV) strain parameters derived from the analysis of the tricuspid annular displacement (TAD) are emergent two-dimensional speckle tracking echocardiography (2D-STE) parameter used for the quantitative assessment of RV systolic function. Few data are available regarding 2D-STE parameters and their dependency on RV preload. Our aim was to evaluate the effect of an acute change in RV preload on 2D-STE parameters in healthy volunteers. (2) Methods: Acute modification of RV preload was performed by a fluid challenge (FC): an infusion of 500 mL of 0.9% sodium chloride was given over 5 min in supine position. Preload dependency (responder group) was confirmed by a stroke volume increase of at least 10% measured by echocardiography. (3) Results: Among 32 healthy volunteers, 19 (59%) subjects were classified as non-responders and 13 (41%) as responders. In the responder group, the tricuspid annular plane systolic excursion (TAPSE) significantly increased (20 (20–23.5) mm to 24 (20.5–26.5) mm; p = 0.018), while RV strain parameters significantly decreased after FC: −23.5 ((−22.3)–(−27.3))% to −25 ((−24)–(29.6))%; p = 0.03) for RV free wall longitudinal strain and −22.8 ((−20.4)–(−30.7))% to −23.7 ((−21.2)–(−27))%; p = 0.02) for RV four-chamber longitudinal strain. 2D-STE parameters derived from the TAD analysis were not influenced by the FC (all p > 0.05). (4) Conclusions: In young, healthy volunteers, RV strain parameters and TAPSE are preload dependent, while TAD parameters were not. The loading conditions must be accounted for when evaluating RV systolic function by 2D-STE parameters.

Influence of Classical Massage on Biochemical Markers of Oxidative Stress in Humans: Pilot Study.

Classical massage is one of the most popular forms of conservative treatment in various diseases. Despite the wide scope of research, the mechanisms of massage are not fully known and understood. Apart from the well-described effects on individual body systems, there are few scientific reports on the effects of massage on the human body at the subcellular level. The study was designed to assess changes in oxidative stress parameters in healthy volunteers after a single session of classical massage. 29 healthy volunteers aged 22.24 ± 3.64 participated in the study. Before and 30 minutes after the massage procedures, blood samples were taken by experienced personnel. Biochemical markers of oxidative homeostasis were assessed with highly specific methods for each parameter: oxidase ceruloplasmin, glutathione, malondialdehyde, glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. The study demonstrates that massage therapy caused statistically significant decrease in the concentration of glutathione peroxidase (red blood cells) and increase in the level of glutathione peroxidase (plasma), superoxide dismutase, and malondialdehyde. In contrast, statistically significant changes in the hematocrit, glutathione, NO2-/NO3-, and oxidase ceruloplasmin were not observed. The results show that complex influence of classical massage therapy on human organism may be reflected in parameters of the oxidative stress. To understand this mechanism clearly, further research is needed.

Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers.

Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.

Effects of Heavy Isotopes (2H1 and 18O16) Depleted Water Con-Sumption on Physical Recovery and Metabolic and Immunological Parameters of Healthy Volunteers under Regular Fitness Load.

Water depleted of heavy isotopes, such as 2H1 and 18O16 (HIDW), has shown numerous biological/health effects in vitro, in vivo, and in epidemiological studies. Major observations were related to cell growth/differentiation, immune/nervous system responses, endurance/adaptation, mitochondrial electron transfer, energy production, glucose metabolism, etc. No human studies to confirm physiological, metabolic, and immune responses to the consumption of HIDW have been performed. A placebo-controlled study on healthy volunteers (n = 50) under fitness load who consumed 1.5 L HIDW (58 ppm 2H and 1780 ppm 18O) or normal water for 60 days was carried out. Plasma content of 2H1 and 18O16, markers of energy, lipid, and glucose metabolism, anthropometric, cardio-vascular, oxidant/antioxidant, and immunological parameters were determined. Significant decrease in plasma heavy isotopes in the group consuming HIDW was observed in concomitance with an increase in ATP, insulin, and LDH, and diminished plasma lactate. Several anthropometric and cardio-vascular parameters were improved as compared to placebo group. Lipid markers demonstrated antiatherogenic effects, while oxidant/antioxidant parameters revealed HIDW-induced hormesis. Antibacterial/antiviral immunity was remarkably higher in HIDW versus placebo group. Conclusions: HIDW consumption by humans under fitness load could be a valid approach to improve their adaptation/recovery through several mechanisms.

Evaluation of safety of Arohi Snehapana (Incremental Oleation Therapy) Over Physical, Hematological and Biochemical Parameters in Healthy Volunteers

Background: Ayurveda strongly recommends the Panchakarma (Purification or detoxification therapies), e.g., Vamana (Therapeutic emesis) &amp; Virechana (Therapeutic purgation) etc., in healthy persons for the prevention of the diseases &amp; maintenance of the health. Vamana &amp; Virechana are preceded by the Arohi Snehapana (Incremental oleation) compromising of intake of specific lipid in a large quantity. As it facilitates the smooth conduction of these procedures &amp; brings bio-toxins in the systemic circulation for their easy elimination through these procedures;therefore it is the mandatory criteria before these procedures. However, there is apprehension about its lipid elevating effect; therefore, there is quite a restriction in its acceptability in the current cholesterol-sensitive era. Ultimately, people hesitate to undergo Shodhana measures &amp; they get deprived of their miraculous results.&#x0D; Aim and Objective: Considering these hurdles, the current study was planned to evaluate and assess the safety effects of Arohi Snehapana over physical, hematological, and biochemical parameters in healthy volunteers.&#x0D; Materials and Methods: This is a single-centric, open-labeled clinical trial in which a total of 50 healthy volunteers (both male &amp; female) were recruited. All volunteers were selected by purposive sample method &amp; were prescribed Incremental oleation with cow ghee before Shodhana therapy for a maximum of 7 days or till achievement of proper oleation features, whichever is earlier. All volunteers were assessed for physical (weight, B.M.I.), hematological &amp; biochemical parameters before &amp; just after the intervention.&#x0D; Result and Observations: In this study, Bodyweight declined significantly by 3-4 kg (1.47%. ) for (P&lt;0.001) within 1-7 days of an intervention despite using a good amount of fat (Go-Ghrita). Blood urea was significantly decreased by 12.63 % (for p-Value &lt;0.001), but this decrease was absolutely within the normal range. Significant reduction in blood urea after invention proves the role of Snehapana to reduce overload over the kidney and perform the protective role. No significant elevation in lipid profile due to this intervention.&#x0D; Conclusion: The current study evaluates the efficacy of Incremental oleation with respect to various proper oleation features and its safety over physical, hematological, and biochemical parameters in healthy volunteers.

Immediate effects of the practise of Sheethali pranayama on heart rate and blood pressure parameters in healthy volunteers.

Sheetali pranayama, a cooling pranayama is best known for its calming and relaxing nature, widely used for many conditions like depression, anxiety and hypertension. The aim of the study was to evaluate the immediate effect of the practice of Sheetali pranayama on heart rate and blood pressure parameters in healthy volunteers. Apparently, 60 healthy volunteers were involved, from both sexes. They were split into pranayama (n=30) and control (n=30) groups at random. Sheetali pranayama was performed for 5min (5 cycles) in the pranayama group and normal breathing (12-16 breaths/min) was permitted in the control group. Heart rate (HR) and blood pressure (BP) were recorded with RMS polyrite in the supine position after 5min of rest. The HR in the pranayama group significantly decreased (p=0.04). Systolic (SBP) and diastolic blood (DBP) pressure, pulse pressure (PP) and mean arterial pressure (MAP) decreased significantly (p<0.05) relative to control after pranayama practice. Pre-Post inter-group results has also shown that the pranayama group has substantially decreased HR and BP indices. Present study shows that the practice of Sheetlai pranayama creates a relaxed state, and parasympathetic activity overrides sympathetic activity in this state. It indicates that in healthy volunteers, pranayama strengthens the resting cardiovascular parameters.