One-Week Elderberry Juice Treatment Increases Carbohydrate Oxidation after a Meal Tolerance Test and Is Well Tolerated in Adults: A Randomized Controlled Pilot Study.

Obesity in the United States continues to worsen. Anthocyanin-rich fruits and vegetables provide a pragmatic dietary approach to slow its metabolic complications. Given American diet patterns, foods with high anthocyanin content could address dose-response challenges. The study objective was to determine the effect of 100% elderberry juice on measures of indirect calorimetry (IC) and insulin sensitivity/glucose tolerance in a placebo-controlled, randomized, crossover pilot study. Overweight and obese adults were randomized to a 5-week study which included 2 1-week periods of twice-daily elderberry juice (EBJ) or sugar-matched placebo consumption separated by a 3-week washout period. Following each 1-week test period, IC and insulin sensitivity/glucose tolerance was measured with a 3 h meal tolerance test (MTT). Treatment differences were tested with linear mixed modeling. A total of 22 prospective study volunteers (18 F/4 M) attended recruitment meetings, and 9 were analyzed for treatment differences. EBJ was well tolerated and compliance was 99.6%. A total of 6 IC measures (intervals) were created, which coincided with 10-20 min gaseous samplings in-between MTT blood samplings. Average CHO oxidation was significantly higher during the MTT after 1-week EBJ consumption (3.38 vs. 2.88 g per interval, EBJ vs. placebo, p = 0.0113). Conversely, average fat oxidation was significantly higher during the MTT after 1-week placebo consumption (1.17 vs. 1.47 g per interval, EBJ vs. placebo, p = 0.0189). This was in-line with a significantly lower average respiratory quotient after placebo treatment (0.87 vs. 0.84, EBJ vs. placebo, p = 0.0114). Energy expenditure was not different. There was no difference in serum glucose or insulin response between treatments. This pilot study of free-living volunteers describes significant change in IC but not insulin sensitivity with an EBJ intervention. Controlled feeding and increased sample size will help determine the utility of EBJ on these outcomes.

Vascular Responses following Light Therapy: A Pilot Study with Healthy Volunteers.

(1) Background: Studies have reported the effectiveness of light therapy in various medical conditions. Our pilot study aimed to assess the effect of Maharishi light therapy (MLT) on physiological parameters, such as the heart rate (HR), HR variability (HRV), blood pressure (BP), BP variability (BPV), and the retinal microvasculature of healthy participants; (2) Methodology: Thirty (14 males and 16 females) healthy, non-smoking participants between 23 and 71 years old (46 ± 18 years) were included in this randomized crossover study. Each participant was tested with a placebo (using LED light) and gem lights, 24 h apart. Hemodynamic parameters were recorded during the session, and 24 h heart rate and BP levels were assessed via mobile devices. Retinal vascular responses were captured with fundus images and the subsequent analysis of retinal vessel widths. A linear model, using repeated measures ANOVA, was used to compare the responses across the sexes and to assess the effect of the MLT; (3) Results: Changes in the central retinal artery equivalent (CRAE) (p < 0.001) and central retinal vein equivalent (CRVE) (p = 0.002) parameters were observed. CRAE and CRVE decreased under MLT and increased under the placebo condition from before to after. However, the baseline values of the participants already differed significantly before the application of any therapy, and the variation in the retinal vessel diameters was already large in the baseline measurements. This suggests that the observed effect results may only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. Furthermore, no significant effects were observed in any other investigated parameters; (4) Conclusion: Our study with healthy participants finds significant changes in retinal parameters, but the biological variation in the baseline measurements was large to begin with. This suggests that the observed effect results only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. However, in the future, larger studies in which MLT is applied for longer periods and/or in patients with different diseases could discover the physiological impacts of this type of therapy.

Safety evaluation of an antimalarial herbal product from Andrographis paniculata (AS201-01) in healthy volunteers.

OBJECTIVES: Andrographis paniculata tablets (AS201-01) have previously been shown to have potent bioactivity as an antimalarial and to produce no unwanted side effects in animal models. Here, we present the phase 1 clinical trial conducted to evaluate the safety of AS201-01 tablets in healthy volunteers. METHODS: The study was a randomized, double-blind controlled cross-over, a placebo-controlled design consisting of a 4-day treatment of AS201-01 tablets. A total of 30 healthy human volunteers (16 males and 14 females) were divided into two groups, and each group was given 4 tablets, twice daily for 4 days. Group 1 received AS201-01, while group 2 received placebo tablets. Volunteers were given a physical examination before the treatment. The effects of AS201-01 on random blood glucose, biochemical, and hematological as well as urine profiles were investigated. RESULTS: There were no changes in observed parameters as a result of AS201-01 being administered. Statistical analysis showed no significant difference (p>0.05) between the test and control group regarding hematology profile, biochemical profile, and random blood glucose. Increased appetite and better sleep, which categorized as grade 1 adverse event was reported after treatment with AS201-01 tablet. CONCLUSIONS: The outcome supports our previous observation that the AS201-01 tablet, given twice a day for 4 days, is safe and nontoxic.

Effects of the combination of vitamins C and E supplementation on oxidative stress, inflammation, muscle soreness, and muscle strength following acute physical exercise: meta-analyses of randomized controlled trials.

Background:The combined supplementation of vitamins C and E potentially can mitigate oxidative stress (OS) and accelerate recovery following exercise. However, there is little evidence and a lack of consensus on the effects of these vitamins for this purpose. The objective of this systematic review was to summarize the evidence on the effects of the combined supplementation of vitamins C and E in OS, inflammatory markers, muscle damage, muscle soreness, and musculoskeletal functionality following acute exercise. Methods: The search was carried out from inception until March 2021, on MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and SPORT Discus. We included placebo-controlled randomized clinical trials (RCTs) that evaluated the effects of combined supplementation of vitamins C and E in OS, inflammatory markers, muscle damage, muscle soreness, and muscle strength following a single bout of exercise. Random-effect meta-analyses were used to compare pre to post-exercise mean changes in subjects who received supplementation with vitamins C and E or placebo versus controls. Data are presented as standard mean difference (SMD) and 95% confidence interval (95% CI). Results: Eighteen RCTs, accounting for data from 322 individuals, were included. The use of vitamins attenuated lipid peroxidation (SMD= -0.703; 95% CI= -1.035 to -0.372; p < 0.001), IL-6 (SMD= -0.576; 95%CI= -1.036 to -0.117; p = 0.014), and cortisol levels (SMD= -0.918; 95%CI= -1.475 to -0.361; p = 0.001) immediately, and creatine kinase levels 48 h following exercise (SMD= -0.991; 95%CI= -1.611 to -0.372; p = 0.002). Supplementing the combination of vitamins had no effects on protein carbonyls, reduced/oxidized glutathione ratio, catalase, interleukin-1Ra, C-reactive protein, lactate dehydrogenase, muscle soreness, and muscle strength. Conclusion: Prior supplementation of the combination of vitamins C and E attenuates OS (lipid peroxidation), the inflammatory response (interleukin-6), cortisol levels, and muscle damage (creatine kinase) following a session of exercise.

Nature and mechanism of immune boosting by Ayurvedic medicine: A systematic review of randomized controlled trials.

BACKGROUND: Many Ayurvedic preparations are claimed to have immune-boosting properties, as suggested in various published randomized clinical trials (RCTs). AIM: To compile evidence on the nature and mechanism of immune system enhancement by Ayurvedic preparations in healthy and sick individuals. METHODS: After prospectively registering study protocol with PROSPERO, we searched PubMed, DOAJ, Google Scholar, three dedicated Ayurveda research portals, two specialty Ayurveda journals, and reference lists for relevant records published until February 6, 2021 using appropriate search strategies. Baseline features and data pertaining to the nature and mechanism of immune system function were extracted from all eligible records. Methodological quality was assessed using the Cochrane RoB-2 tool. RESULTS: Of 12554 articles screened, 19 studies reporting 20 RCTs (17 parallel group design, three crossover design) with 1661 unique patients were included; 11/19 studies had Indian first authors. Healthy population was included in nine studies, of which one study included pregnant women and two included pediatric population; remaining studies included patients with different health conditions, including one study with coronavirus disease 2019 patients. A total of 21 Ayurvedic interventions were studied, out of which five were composite mixtures. The predominant route of administration was oral; dose and frequency of administration of the intervention varied across the studies. The results reported with five RCTs exploring five Ayurvedic interventions were incomplete, ambiguous, or confusing. Of the remaining 16 interventions, indirect evidence of immune enhancement was reported with four interventions, while lack of the same was reported with two interventions. Enhancement of T helper cells and natural killer cells was reported with three and four interventions, respectively, while the pooled results did not clearly point toward enhancement of other components of the immune system, including cytotoxic T cells, B lymphocytes, immunoglobulins, cytokines, complement components, leucocyte counts, and other components. Nine of the 20 RCTs had a high risk of bias, and the remaining 11 RCTs had some concerns according to RoB-2. CONCLUSION: Various Ayurvedic preparations appear to enhance the immune system, particularly via enhancements in natural killer cells and T helper cells.

Center of pressure position in the touches of the star excursion balance test in healthy individuals.

BACKGROUND: The Star Excursion Balance Test (SEBT) is a clinical test that aims to assess postural control. Its interpretation is related to the understanding of the motor specificities required. Adjustments must be made to the center of pressure (COP) to maintain balance during testing movements. Comprehend the specifics of these adjustments for each direction can allow the development of more suitable exercises for balance training. The aim was to compare the positions of the COP on the different directions of the SEBT and correlate the reachs obtained in the SEBT with the distances from the COP to the borders of the base of support (BOS). METHODS: Sixteen healthy subjects participated in the study. Measurements were made by performing the SEBT over the force platform. The Kruskal-Wallis test followed by Bonferroni's post hoc test was used to compare directions. The Pearson correlation test was used to check the correlation of parametric variables and Spearman correlation test for the nonparametric ones. RESULTS: The position of the COP at the touch differs from the anterior direction to the other directions of the SEBT and the performance in this direction is correlated with the proximity of the COP to the anterior limit of the support base. The performances in the other directions did not correlate with the COP position. CONCLUSION: The requirements of the compensation mechanisms for postural control are different between the directions of the SEBT.

Vitamin D in healthy Tunisian population: Preliminary results.

Background: Vitamin D deficiency is one of the most common medical conditions worldwide. In Tunisia, several studies evaluated Vitamin D status, but this was concerning specific populations (pregnant women, obese or diabetic patients and children with asthma). The only study that evaluated Vitamin D status in a healthy Tunisian population was conducted by Meddeb and associeties in 2002. The update of data available, based on the currently recommended limits, is necessary. This study aimed to estimate the prevalence of hypovitaminosis D in a healthy Tunisian population, and correlate the values with potential risk factors. Methods: It was conducted on 209 Tunisian healthy subjects. Data collected included clinical characteristics and dietary intakes. We measured 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), glycemia, creatinine, calcium, phosphorus, and alkaline phosphatase concentrations. Hypovitaminosis D was retained for 25(OH)D concentrations <75 nmol/L. Vitamin D deficiency was defined by 25(OH)D concentrations <25 nmol/L. Results: The prevalence of hypovitaminosis D and vitamin D deficiency were respectively 92.3% and 47.6%. The main factors that were significantly associated with low vitamin D levels in our multivariate analysis were veiling, living in rural areas and sunscreen use. However, sex, age, socioeconomic level, phototype, solar exposure score, smoking and bone mass index, were not statistically associated with hypovitaminosis D. The study of relationship between vitamin D status and serum PTH levels showed a significative and negative correlation (P < 0.005). Conclusions: Given the high prevalence of vitamin D, an adapted health policy is essential. A widespread vitamin D supplementation and food fortification seems to be necessary in Tunisia.

The Effect of Hyperbaric Oxygen Therapy on Markers of Oxidative Stress and the Immune Response in Healthy Volunteers.

Hyperbaric oxygen therapy (HBOT) consists of breathing 100% oxygen under increased ambient pressure. There are indications that HBOT induces oxidative stress and activates immune pathways. However, previous research on immunological effects of HBOT has mainly been established in in vitro experiments and selected patient populations, limiting generalizability and increasing the chances of confounding by comorbidities and specific patient-related factors. More insight into the immunological effects of HBOT would aid investigation and comprehension of potentially novel treatment applications. Therefore, in this study, we investigated the effects of three 110-min HBOT-sessions with 24-h intervals on immunological parameters in healthy, young, male volunteers. Blood samples were obtained before and after the first and third HBOT sessions. We assessed neutrophilic reactive oxygen species (ROS) production, systemic oxidative stress [plasma malondialdehyde (MDA) concentrations] as well as neutrophil phagocytic activity, plasma concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and IL-10, and production of TNF, IL-6, and IL-10 by leukocytes ex vivo stimulated with the Toll-like receptor (TLR) ligands lipopolysaccharide (TLR4) and Pam3Cys (TLR2). We observed decreased neutrophilic ROS production and phagocytosis following the second HBOT session, which persisted after the third session, but no alterations in MDA concentrations. Furthermore, plasma concentrations of the investigated cytokines were unaltered at all-time points, and ex vivo cytokine production was largely unaltered over time as well. These results indicate no induction of systemic oxidative stress or a systemic inflammatory response after repeated HBOT in healthy volunteers but may suggest exhaustion of ROS generation capacity and phagocytosis.

A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma.

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2-50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

Effectiveness of Mindfulness-Based Cognitive Therapy for Improving Subjective and Eudaimonic Well-Being in Healthy Individuals: A Randomized Controlled Trial.

Objectives: Better subjective and eudaimonic well-being fosters better health conditions. Several studies have confirmed that mindfulness-based interventions are effective for improving well-being; however, the samples examined in these studies have been limited to specific populations, and the studies only measured certain aspects of well-being rather than the entire construct. Additionally, few studies have examined the effect of mindfulness-based cognitive therapy on well-being. The present study examines the feasibility of mindfulness-based cognitive therapy and its effectiveness for improving subjective and eudaimonic well-being among community residents. Methods: The study design featured an 8-week randomized, waiting-list controlled, parallel-group study. 8 weekly mindfulness classes, followed by 2 monthly classes, were provided for healthy individuals aged 20-65 years who had a Satisfaction with Life Scale score of ≤ 24 indicating average to low cognitive aspect of subjective well-being. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000031885, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036376). Results: The results showed that cognitive aspect of subjective well-being and mindfulness skills were significantly improved at 8 weeks, and this effect was enhanced up to the end of the follow-up period. Positive affective aspect of subjective and eudaimonic well-being were significantly improved at 16 weeks. Conclusions: Eight weeks of mindfulness-based cognitive therapy with a 2-month follow-up period improves cognitive and affective aspects of subjective and eudaimonic well-being in healthy individuals. The order of improvement was cognitive, positive affective, and eudaimonic well-being. To verify these findings, multi-center randomized controlled trials with active control groups and longer follow-up periods are warranted.

Effects of Bee Propolis on FBG, HbA1c, and Insulin Resistance in Healthy Volunteers

Objectives: Bee propolis is a natural substance that is used in traditional medicine due to its versatile pharmacological actions. This study evaluates whether short term use of bee propolis supplementation could have an impact on glycemic control in healthy individuals. Materials and Methods: A single daily dose of 1000 mg of bee propolis was administered orally to a total of 34 healthy individuals for 60 days. Body weight, body mass index (BMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and insulin resistance were measured in all participants before and after the use of bee propolis. Results: The results of this study showed that bee propolis was associated with a significant increase in body weight and BMI of healthy volunteers. Bee propolis supplementation decreased FBG and HbA1c, but did not affect insulin resistance. Conclusion: Based on these results, bee propolis supplementation has a potential effect on glycemic control in healthy individuals and this should be considered when using this supplement in medical conditions.

Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) turn out to be a promising source of cell-free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose-derived MSC-EVs (haMSC-EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC-EVs in healthy volunteers. DiR-labelled haMSC-EVs were used to explore the distribution of nebulized haMSC-EVs in the murine model. Pseudomonas aeruginosa-induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL-6, TNF-α and IL-10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC-EVs through the nebulized route. Twenty-four healthy volunteers were involved and received the haMSC-EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC-EVs improved survival rate to 80% at 96 h in P. aeruginosa-induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC-EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC-EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC-EVs in lung injury diseases.

Jet or conventional local anaesthesia? A randomized controlled split mouth study.

OBJECTIVES: To compare the efficacy, acceptance and preference of conventional infiltration technique with a needleless jet anaesthetic device (Comfort-In). MATERIALS AND METHODS: Non-fearful healthy adult volunteers, aged 19-40 years, were recruited in the Dental School of Aristotle University of Thessaloniki, Greece. Intact maxillary premolars were selected for local anaesthesia. Both techniques were applied sequentially with 35 min time gap on either buccal side on the same day by the same operator. The quadrant and the order of administration were randomly assigned using an online randomization generator. Immediately after administration, at 1, 3, 5, 10, 15, 20, 25 and 30 min, pulp vitality and soft tissue pain reaction tests were performed. Each participant was asked 6 questions in order to assess acceptance. At the end of the session, at 24 h and 7 days, all participants were asked to report any adverse events and their preference. RESULTS: In 63 volunteers who were successfully followed, 63 teeth received conventional local infiltration and 63 the Comfort-In. Both techniques presented with similar anaesthetic efficacy at 1, 3, 5, 10 and 15 min, whereas the conventional technique was more efficacious at 20 min (p < 0.005). Both presented similar acceptance apart from higher pain/discomfort during administration of Comfort-In (p = 0.002). Significantly higher preference was reported for the conventional technique immediately after the session, at 24 h and at 7 days (p < 0.0005); 19 (30.2%) reported the presence of ecchymosis or lacerations at the Comfort-In site as opposed to 5 (7.9%) with the conventional method (p < 0.0001). CONCLUSION: Both techniques showed similar effectiveness. Conventional infiltration was preferred to needleless anaesthesia by non-fearful adult volunteers and was associated with less adverse events. CLINICAL RELEVANCE: This study enhances the advantages of conventional local anaesthesia. TRIAL REGISTRATION: ISRCTN17400733.

Grape Seed Extract Positively Modulates Blood Pressure and Perceived Stress: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers.

It is well established that maintaining healthy blood pressure is fundamental in order to avoid disorders to the heart and blood vessels. In prevention, and alongside pharmacological therapy, the use of natural substances has been proven to be extremely helpful for pre- and mild hypertensive subjects. Our study was therefore focused on the effects, both in vitro and in humans, of a grape seed extract, Enovita (GSEe), a highly standardized extract in polyphenols of Vitis vinifera L. The in vitro human umbilical vein endothelial cells (HUVEC) model was chosen to explore the extract properties related to vascular inflammation/vasodilation. A significant reduction of both soluble Inter-Cellular Adhesion Molecule-1 (sICAM) and endothelin-1 secretion/release was induced by GSEe in HUVEC cells. A randomized, double-blind, placebo-controlled clinical study in healthy volunteers was further performed to investigate GSEe benefits. In healthy volunteers, both supplementations significantly modulated blood pressure, with a pronounced effect after GSEe tablets (300 mg/day for 16 weeks) in respect to placebo. In the male gender subgroup, no placebo effect was observed as it was for the female group. As an additional outcome, an overall GSEe positive modulation emerged on mood related to stress perception. Thus, GSEe resulted in a benefit of modulating endothelial functionality and blood pressure. It was noteworthy that GSEe relieved the perceived stress, promising new future perspectives on mood comfort.

Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration.

Realgar, an arsenic-containing traditional Chinese medicine of As2S2, has significant therapeutic effects for hundreds of years. NiuHuangJieDu tablets (NHJDT) is one of the most commonly prescribed realgar-containing preparations for the treatment of sore throat, swelling, and aching of gums. However, realgar-containing TCMs raise great safety concerns due to the adverse effects reported by arsenic poisoning. In this study, the arsenic-related health risk assessment of NHJDT was conducted in healthy volunteers after single and multiple doses oral administration. Blood, plasma, and urine samples were collected after dosing at predetermined time points or periods. Simple, rapid, and sensitive methods were established for the quantification of total arsenic and arsenic speciation in biological samples. The total arsenic and arsenic speciation were determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) and high-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS), respectively. No significant fluctuation of total arsenic was observed in human blood, and no traces of arsenic speciation were found in human plasma. Dimethylarsenic acid was detected as the predominated arsenic species in human urine after dosing. Therapeutic dose administration of NHJDT was relatively safe in single dose for the limited blood arsenic exposure, but long-term medication may still pose health risks due to the accumulation of arsenics in blood and its extremely slow excretion rate. Therefore, arsenic exposure should be carefully monitored during realgar-containing TCM medication, especially for long-term regimen. The results obtained in this study will provide scientific references for the clinical application of realgar and its-containing TCMs.

Assessment of Herb-drug Interactions Based on the Pharmacokinetic Changes of Probe Drug, Midazolam.

BACKGROUND: In healthy volunteers, the probe drug method is widely practised to assess the pharmacokinetic mediated herb-drug interactions (HDI). We analyzed the clinical evidence of CYP3 A4 probe drug, Midazolam. METHODS: Literatures, where Midazolam was used as a probe drug for prediction of herb-drug interaction, were surveyed through an online database such as google scholar, Scopus, Cochrane, PubMed and clinicaltrials.gov. RESULTS: Midazolam was considered a sensitive probe for CYP3A4 substrates due to its bioavailability. We observed that not all the herbs are causing drug interaction. However, significant changes of the Midazolam pharmacokinetics were found after high-dose and long-term intake of some herbs and food supplements, suggesting the induction and/or inhibition of CYP activities. CONCLUSION: Probe drug technique is one of the easiest ways for predicting CYP enzyme-mediated herb-drug interactions. Midazolam shows a good response in clinical studies because of short halflife and low harmfulness compared with other probe drugs.

Disposition of cannabinoids and their metabolites in serum, oral fluid, sweat patch and urine from healthy individuals treated with pharmaceutical preparations of medical cannabis.

Recently, several countries authorized the use of cannabis flowering tops (dried inflorescences) with a standardized amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and their acidic precursors [Δ-9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA)] to treat neurogenic pain. We studied the acute pharmacological effects and disposition of cannabinoids and their metabolites in serum, oral fluid, sweat patch and urine of 13 healthy individuals treated with medical cannabis decoction and oil. Cannabinoids and their metabolites were quantified by ultrahigh performance tandem mass spectrometry. Even if the oil contained a significantly higher amount of THC, the absorption of THC and its metabolites were similar in both herbal preparations. Conversely, whereas oil contained a significantly higher amount of CBD and a lower amount of CBDA, absorption was significantly higher after decoction intake. Only cannabinoids present in both herbal preparations (THC, CBD, THCA-A and CBDA) were found in oral fluid, due to the higher acidity compared with that of serum. THC metabolites urinary excretion was always higher after decoction administration. Decoction induced greater feeling of hunger and drowsiness than oil preparation. Pharmacokinetics of cannabinoids, their precursors and their metabolites in biological fluids of individuals treated with cannabis decoction and oil showed a high interindividual variability. The aqueous preparation was generally better absorbed than the oil, even if it contained a minor amount of THC, THCA-A and CBD.

Quantifying Lumbar Mobilization With Inertial Measurement Unit.

OBJECTIVE: Lumbar mobilization is a standard intervention for the management of low back pain, yet ways to quantify lumbar mobilization are limited. An inertial measurement unit (IMU) is a small and inexpensive device that can be used to quantify lumbar mobilization. The objective of this study was to determine the validity and reliability of an IMU in measuring the amplitude of displacement of a clinician's hand movement during oscillatory lumbar mobilization. METHODS: An IMU was secured on a clinician's hand during application of mobilization forces at the L4 segment of 16 healthy participants. The validity of the IMU was tested against common laboratory methods of measurements (force plate and motion capture system). The reliability of the IMU measurements was determined between 2 clinicians (inter-rater reliability) and between 2 sessions (intra-rater reliability) by calculating percent error of measurement (%e) and limits of agreement (LOA). The reliability was considered high when |%e| ≤ 10% and |LOA| ≤ 20%; moderate when |%e| 10% to 20% and |LOA| 21% to 40%; and non-acceptable when |%e| > 20% and |LOA| > 40%. RESULTS: The IMU measurements had high correlation with the force plate measurements (rs = 0.94) and high agreement with the motion capture system measurements (%e = 4%, LOA = -11% and 20%). Both the inter-rater reliability (%e = 6%, LOA = -25% and 37%) and the intrarater reliability (%e = -1%, LOA = -29% and 27%) of IMU measurements were moderate. CONCLUSION: The IMU seems to be a valid device to measure the amplitude of a clinician's hand movement. The moderate reliability found in this study may not reflect poor reliability of the IMU as much as inconsistency in reapplication of lumbar mobilization.

A Pharmacologic "Stress Test" for Assessing Select Antioxidant Defenses in Patients with CKD.

BACKGROUND AND OBJECTIVES: Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic "stress test" for gauging gene responsiveness and antioxidant reserves. DESIGN: , setting, participants, & measurementsA total of 18 healthy volunteers and 24 participants with stage 3 CKD (n=12; eGFR 30-59 ml/min per 1.73 m2) or stage 4 CKD (n=12; eGFR 15-29 ml/min per 1.73 m2) were injected once with SnPP (9, 27, or 90 mg). Plasma and/or urinary antioxidant proteins were measured at baseline and for up to 4 days post-SnPP dosing. Kidney safety was gauged by serial measurements of BUN, creatinine, eGFR, albuminuria, and four urinary AKI biomarkers (kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, cystatin C, and N-acetyl glucosaminidase). RESULTS: Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (r=-0.85 to -0.95). All four proteins manifested statistically significant dose- and time-dependent elevations after SnPP injection. However, marked intersubject differences were observed. p21 responses to high-dose SnPP and HO-1 responses to low-dose SnPP were significantly suppressed in participants with CKD versus healthy volunteers. SnPP was well tolerated by all participants, and no evidence of nephrotoxicity was observed. CONCLUSIONS: SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.

Effects of vitamin C on oxidative stress, inflammation, muscle soreness, and strength following acute exercise: meta-analyses of randomized clinical trials.

BACKGROUND: Vitamin C (ascorbic acid) seems to attenuate the overproduction of reactive species during and after exercises. Yet, no meta-analysis has summarized the magnitude of this effect. The objective of this study was to systematically review the effects of vitamin C supplementation on oxidative stress, inflammatory markers, damage, soreness, and the musculoskeletal functionality after a single bout of exercise. METHODS: Major electronic databases were searched, from inception to September 2019, for placebo-controlled randomized clinical trials (RCTs) that evaluated the effects of vitamin C supplementation on oxidative stress parameters, inflammation markers, muscle damage, muscle soreness, and muscle functionality after a single bout of exercise in healthy volunteers. Random-effects modelling was used to compare mean changes from pre- to postexercise in participants that were supplemented with vitamin C versus placebo. Data were reported as standard mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 18 RCTs, accounting for 313 participants (62% males, median age = 24 years) were included. Vitamin C supplementation reduced lipid peroxidation immediately (SMD = - 0.488; 95% CI = - 0.888 to - 0.088), 1 h (SMD = - 0.521; 95% CI = - 0.911 to - 0.131) and between 1 and 2 h (SMD = - 0.449; 95% CI = - 0.772 to - 0.126) following exercise. Exercise induced interleukin-6 (IL-6) response was attenuated 2 h (SMD = - 0.764; 95% CI = - 1.279 to - 0.248) and between 1 and 2 h (SMD = - 0.447; 95% CI = - 0.828 to - 0.065) after exercise. No effects of vitamin C supplementation were found on creatine kinase (CK), C-reactive protein (CRP), cortisol levels, muscle soreness, and muscle strength. CONCLUSION: Vitamin C supplementation attenuates the oxidative stress (lipid peroxidation) and inflammatory response (IL-6) to a single bout of exercise. REGISTRATION: PROSPERO (CRD42018094222).