Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve.

BACKGROUND: Some components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler. RESULTS: In a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2 h (acute test) and 30 days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30 days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30 days, CFR improved with NUT A (p < 0.0001), because of the increase of hyperemic flow velocity (p = 0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30 days in NUT A (p < 0.02), with a higher CFR percent variation versus baseline (p = 0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p < 0.001 and p < 0.002, respectively) and B (both p < 0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A - but not NUT B - was independently associated with CFR changes (ß = 0.599, p = 0.003). CONCLUSIONS: LopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease. TRIAL REGISTRATION: (NUTRENDO)″(ClinicalTrials.gov, NCT02969070).

Capillary electrophoresis using triple layer modified capillary facilitating salivary ion analyses: Application to search for potential stress markers induced by cold pressure test.

In this study, we introduce a novel approach for the analysis of salivary ions using capillary electrophoresis (CE) with a triple-layer coated capillary. The capillary is sequentially coated with cationic silylating reagents, poly(vinylsulfonate), and polybrene to form a custom designed surface that effectively inhibits adsorption of protein matrix on the capillary inner wall and allows for reproducible ion analysis. For the CE with capacitively coupled contactless conductivity detection, we used suitable background electrolytes (BGEs) for salivary ion analysis. Anions were separated using a mixture of 2-(N-morpholino)ethanesulfonic acid and l-arginine, and cations were separated using that with 18-crown-6. This setup enabled rapid separation, within 4 min, together with sensitive detection. We quantified nine common anions and five cations typically found in saliva samples using this CE method, both before and after a cold pressure test (CPT, a standard stress test). The CE system demonstrated consistent ion separation across 30 consecutive measurements without requiring capillary replacement. Notably, the salivary ion balance remained predominantly anion-rich, regardless of the CPT. Cold water exposure induced greater variation in the total anion concentration than in the total cation concentration. Further analysis using multiple regression analysis revealed strong relationships between nitrate and nitrite, formate and phosphate, and potassium and nitrate, before and after the CPT. Notably, potassium and nitrate ions exhibited variations in response to stress. These results provided a method for assessing salivary ion composition and insights into the potential of salivary ions as biomarkers for stress.

The effect of preconditioning on the modalities of pain management.

OBJECTIVES: This study investigated the effect of positive preconditioning on the specific modality of verbal and touch interventions, in pain management. METHODS: We compared pain ratings in 51 participants who underwent a cold pressor test twice (T1, T2). The results from the first test were used as a reference. For the second test, the participants were divided into 5 groups. Four groups received verbal or touch intervention during the test, with or without preconditioning. The fifth group was a control group. We compared dVAS (pain ratings at T1 minus T2) between groups to assess the effect of the interventions and the preconditioning. We also explored the within-group association between dVAS and pain-related traits. RESULTS: We found a significant effect of preconditioning on dVAS. The post hoc test showed that the preconditioned verbal group reported higher dVAS than the non-preconditioned one. Participants' emotional awareness scores were negatively correlated with dVAS in the preconditioned touch group. CONCLUSION: These data suggested that preconditioning enhances pain management, regardless of intervention modalities. However, the preconditioning effect for the touch modality was negatively associated with the participants' emotional awareness. PRACTICE IMPLICATIONS: Communication must be adapted with caution, depending on the treatment and the patients' emotional status.

Response to experimental cold-induced pain discloses a resistant category among endurance athletes, with a distinct profile of pain-related behavior and GABAergic EEG markers: a case-control preliminary study.

Pain is a major public health problem worldwide, with a high rate of treatment failure. Among promising non-pharmacological therapies, physical exercise is an attractive, cheap, accessible and innocuous method; beyond other health benefits. However, its highly variable therapeutic effect and incompletely understood underlying mechanisms (plausibly involving the GABAergic neurotransmission) require further research. This case-control study aimed to investigate the impact of long-lasting intensive endurance sport practice (≥7 h/week for the last 6 months at the time of the experiment) on the response to experimental cold-induced pain (as a suitable chronic pain model), assuming that highly trained individual would better resist to pain, develop advantageous pain-copying strategies and enhance their GABAergic signaling. For this purpose, clinical pain-related data, response to a cold-pressor test and high-density EEG high (Hß) and low beta (Lß) oscillations were documented. Among 27 athletes and 27 age-adjusted non-trained controls (right-handed males), a category of highly pain-resistant participants (mostly athletes, 48.1%) was identified, displaying lower fear of pain, compared to non-resistant non-athletes. Furthermore, they tolerated longer cold-water immersion and perceived lower maximal sensory pain. However, while having similar Hß and Lß powers at baseline, they exhibited a reduction between cold and pain perceptions and between pain threshold and tolerance (respectively -60% and - 6.6%; -179.5% and - 5.9%; normalized differences), in contrast to the increase noticed in non-resistant non-athletes (+21% and + 14%; +23.3% and + 13.6% respectively). Our results suggest a beneficial effect of long-lasting physical exercise on resistance to pain and pain-related behaviors, and a modification in brain GABAergic signaling. In light of the current knowledge, we propose that the GABAergic neurotransmission could display multifaceted changes to be differently interpreted, depending on the training profile and on the homeostatic setting (e.g., in pain-free versus chronic pain conditions). Despite limitations related to the sample size and to absence of direct observations under acute physical exercise, this precursory study brings into light the unique profile of resistant individuals (probably favored by training) allowing highly informative observation on physical exercise-induced analgesia and paving the way for future clinical translation. Further characterizing pain-resistant individuals would open avenues for a targeted and physiologically informed pain management.

Recombinant Human Thyrotropin Improves Endothelial Coronary Flow Reserve in Thyroidectomized Patients with Differentiated Thyroid Cancer.

BACKGROUND: The role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone action or whether they are a consequence of a direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to TSH in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors. METHODS: The study population consisted of three men and seven women (Mage = 32.6 ± 8 years) who underwent total thyroidectomy for DTC. All were receiving therapy with L-thyroxine to maintain TSH within the reference range. No patient was obese, or had hypertension, diabetes, or dyslipidemia. Patients underwent standard echo-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second recombinant human TSH (rhTSH) injection. RESULTS: Left ventricular morphology and systolic and diastolic function were normal in all patients. Levels of thyroid hormones and thyroglobulin and antithyroglobulin antibodies did not differ significantly pre- versus post-rhTSH treatment, whereas TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest (22.3 ± 6 vs 23.2 ± 8.7; p = 0.66) did not differ between baseline and 24 h after rhTSH, while post-CPT velocity (29.3 ± 6.8 vs 34.4 ± 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 ± 0.2 vs. 1.53 ± 0.2; p < 0.01). CONCLUSIONS: rhTSH administration may improve the CFR after the non-pharmacological stressor CPT in DTC patients. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium.