Decrease In Blood Pressure Research Articles

Predictors of liver fibrosis progression in cohort of type 2 diabetes mellitus patients with MASLD

AimTo investigate predictors of liver fibrosis progression in patients with T2DM over a minimum follow-up duration of three years. MethodsTwo hundred and thirty-three patients completed the follow-up period and their clinical, laboratory and liver FibroScan data are reported. Patients were categorized into progressors 42 (18.0 %) and non-progressors 191 (82.0 %) based on liver fibrosis progression. Factors influencing fibrosis progression were identified by comparing these groups. ResultsProgressors showed significantly increased aspartate aminotransferase (AST) (p = 0.010), increased alkaline phosphatase (ALP) (p = 0.001) and decreased platelet count (p = 0.002). Non-progressors exhibited significant decreases in diastolic blood pressure (DBP) (p = 0.050), body mass index (BMI) (p < 0.001), waist circumference (p < 0.001), gamma-glutamyl transferase (GGT) (p < 0.001), albumin (p < 0.001), alanine aminotransferase (ALT) (p = 0.022), glycosylated haemoglobin (HbA1c) (p = 0.002) and fasting blood sugar (FBS) (p = 0.030) with increase in HDL-cholesterol (p < 0.001), creatinine (p < 0.001), bilirubin (p < 0.001), and ALP (p = 0.007). Baseline parameters predictive of liver fibrosis progression included elevated AST and reduced platelet count. Delta changes from baseline to follow-up revealed that increases in ALP, BMI, waist circumference, and reduction in platelet count were correlated with fibrosis progression. Use of GLP-1 receptor agonist was associated with reduced progression. ConclusionIn conclusion, increase in ALP and waist circumference and reduction in platelet count are predictive of liver fibrosis progression in patients with T2DM. GLP-1 receptor agonists use seems to have a promising protective effect against liver fibrosis progression.ClinicalTrials.govID:NCT05697991

Klotho supplementation decreases blood pressure and albuminuria in mice with lupus nephritis.

Klotho deficiency is prevalent in various chronic kidney diseases. Although klotho is known to bind transforming growth factor β (TGFβ) receptor 1 to antagonize renal fibrosis, TGFβ also maintains regulatory T cells with inducing forkhead box protein P3 (FOXP3). Female New Zealand Black/White F1 (NZBWF1) mice were divided into two groups (n=10 for each): one group was treated with daily subcutaneous injection of klotho protein (30μg/kg/day) for 8 weeks, and the other only received vehicle. Klotho supplementation suppressed blood pressure, 8-epi-prostaglandin F2α excretion, albuminuria, and renal angiotensin II levels (p<0.05 for all) without affecting the glomerular filtration rate (GFR) in NZBWF1 mice. Klotho protein supplementation reduced the number of cluster of differentiation (CD)4+FOXP3+ T cells (p<0.05) without altering the anti-DNA antibody levels. Klotho supplementation augmented glomerular cellularity, but decreased glomerular crescent formation and interstitial fibrosis in NZBWF1 mice (p<0.05). Klotho protein supplementation inactivated renal renin-angiotensin system, ameliorating blood pressure and albuminuria in NZBWF1 mice. Klotho supplementation hampered regulatory T cells without altering autoantibodies, exerting dual effects on glomerular pathology in NZBWF1 mice without changes in GFR.

Pharmacokinetics and pharmacodynamics of ciprofol after continuous infusion in elderly patients

BackgroundCiprofol, a novel intravenous anesthetic, which has primarily been used for the induction and maintenance of general anesthesia in adults, is characterized by rapid onset, short duration of action, and quick and smooth recovery. However, the pharmacokinetic characteristics of continuous infusions and the correlation between the plasma concentration and the bispectral index (BIS) in elderly patients are still unknown.MethodIn this randomized, controlled study, thirty elderly patients (62–78 years old) undergoing elective gastrointestinal tumor resection were treated with propofol (N = 15) or ciprofol (N = 15) as sedatives during anesthesia. After induction, ciprofol/propofol was continuously infused intravenously until the end of the operation. Perioperative vital signs, injection pain, adverse events (AEs), BIS values, eyelid reflex disappearance times, and recovery times were recorded. The plasma concentrations of ciprofol and propofol were measured by liquid chromatography tandem mass spectrometry (LC‒MS/MS) and the pharmacokinetics were determined by noncompartmental analysis.ResultsBoth drugs caused a decrease in blood pressure and heart rate after induction. Eight cases (53. 3%) of hypotension and 3 cases (20%) of bradycardia occurred in the propofol group, while 8 cases (53. 3%) of hypotension and 5 cases (33. 3%) of bradycardia occurred in the ciprofol group. At intubation, the ciprofol group experienced fewer fluctuations in blood pressure than the propofol group. Ciprofol resulted in only one case (6.7%) of mild injection pain, less than that produced by propofol (10/15, 66.7%) (P < 0.05). Anesthesia induction was successfully completed with both drugs, and there were no significant differences in eyelash reflex disappearance or recovery time between the two groups. The plasma concentrations during maintenance were relatively stable in both groups (propofol 1.78 ± 0.67 μg/mL, ciprofol 0.71 ± 0.23 μg/mL), and a suitable depth of sedation was achieved with a BIS of 40–60. The pharmacokinetic (PK) parameters for ciprofol are listed as follows: Maximum Plasma Concentration (Cmax) 6.02 ± 2.13 μg/ml; Time to Maximum Concentration (Tmax) 0.18 ± 0.62 min; Apparent Volume of Distribution (Vz) 3.96 ± 0.84 L/kg; Total Clearance (CL) 0.83 ± 0.14 L/h/kg; Half-life (t½) 3.47 ± 1.85 h; Area Under the Curve (AUC) 5000 ± 900 L/h/kg; Terminal Elimination Rate Constant (λz) 0.23 ± 0.07 1/h. Similar to propofol, the plasma concentration of ciprofol was linearly correlated with the BIS.ConclusionCiprofol, a novel intravenous anesthetic, can be safely and effectively used in elderly patient continuous infusion with minimal injection pain. Plasma concentrations of ciprofol correlate well with BIS values, helping control sedation depth. For elderly patients undergoing gastrointestinal tumor surgery, an optimal maintenance dose of 0.8 mg/kg/h is recommended.Trial registrationThis clinical trial (registration No: ChiCTR2100047580, https://www.chictr.org.cn. The pre-registration date was June 20, 2021, and the review approval and official case solicitation began in December 2021; Retrospectively registered) was conducted in accordance with the World Medical Congress Declaration of Helsinki and Good Clinical Practice guidelines. All study subjects provided written informed consent.

Stretching, Isometrics, and Aerobic Exercise for Decreasing Blood Pressure Post-Exercise: A Randomized Cross-Over Study.

We compared stretching, isometrics, and aerobic exercise for effectiveness in decreasing blood pressure post-exercise. Using a randomized crossover design, 5 males and 4 females (21.3y; normotensive) participated in four 30-minute sessions on separate days: static stretching (30s stretches, major muscle groups), isometric exercise, aerobic cycling (75% VO2peak), and control (rest), with blood pressure and heart rate measured before exercise (or rest) and for 60 minutes post-exercise (or rest). Aerobic exercise and stretching decreased post-exercise systolic blood pressure (~10 mmHg each) (p<0.05) whereas isometric exercise and the control condition did not significantly decrease post-exercise blood pressure. Stretching is similar to aerobic exercise for reducing blood pressure post-exercise. ClinicalTrials.gov Identifier: NCT06628635.

Numerical and computational fluid dynamics experimental analysis of novel extended tetra-hybrid Tiwari and Das Sisko nanofluid passed a stenosed artery

The medical industry extensively uses nanoparticles for applications such as wound dressing, artificial organ components, drug delivery, tissue engineering, and cardiovascular disease treatment. The incorporation of nanoparticles into the base fluid enhances the rate of heat transmission and additionally decreases blood pressure. This study aims to examine the effects of a new tetra-hybrid nanofluid model, which includes nanoparticles, on the flow of blood through a stenosed artery with a circular shape. Model partial differential equations (PDEs) incorporate phenomena such as thermal radiation and viscous dissipation. Furthermore, we transform these modeled PDEs into dimensionless ordinary differential equations (ODEs) using self-similarity variables and numerically solve the proposed ODEs using the well-established Lobatto IIIa numerical technique. The impact of several dimensionless parameters on the heat transfer rate, skin friction, velocity, and temperature fields has been computed and analyzed using figures and tables. Moreover, we conducted a computational fluid dynamics (CFD) investigation on a tetra-hybrid nanofluid, using blood as the base fluid. The results indicate that heat transmission is higher in tetra-hybrid nanoparticles compared to tri-hybrid and di-hybrid nanofluids. The volume fraction of nanoparticles in the base fluid increases, resulting in a decrease in the surface drag coefficient and a decrease in the heat transport phenomenon. Amplification in the thermal radiation parameter improves heat transfer, helping to remove toxins and plaque from blood flowing through arteries. An increase in thermal radiation generates excess heat that dilates inflexible arteries, facilitating blood flow. From CFD analysis, it is observed that thermal conduction k and heat transfer coefficient h amplify by improving Reynolds number. Pressure at the outlet interface of the tube decreases from 3058 Pa to 2996 Pa for the case of a 10% volume fraction of nanoparticles. Velocity boundary layer thickness decreases from 1.46 to 1.37 with an increase in the volume fraction of nanoparticles from 1% to 10%. Heat deliverance rate amplifies in the case of tetrahybrid nanofluid 2.5394–2.6147 in contrast to trihybrid nanofluid 2.4008 to 2.4711 by amplifying Rd from 0.7 to 1.1. The surface drag coefficient amplifies by magnifying Re but the Nusselt number diminishes by improving the volume fraction of nanoparticles.

Capillary refill time paradoxically decreases in a blood loss shock model

BackgroundThis study aimed to investigate whether changes in capillary refill (CR) time precede macrovascular signs of deterioration in a human model of blood loss shock. The study was conducted at the Department of Emergency Medicine in Linköping, Sweden, and involved 42 healthy volunteers aged 18–45. Participants were randomized into two provocations of applied lower body negative pressure (LBNP): a stepwise escalation protocol and a direct application protocol, to simulate gradual and acute blood loss. The main outcome measure was CR time. Systolic, diastolic, and mean arterial pressures, heart rate, cardiac output, and systemic vascular resistance were measured continuously. CR time was assessed on the finger pulp using a standardized pressure and measured with a polarized reflectance imaging system.ResultsThe provocation elicited pre-syncope reactions and clear decrease in blood pressure for all participants, yet two-thirds of the participants in both protocols reacted with shorter CR times at maximum provocation, and the overall median CR time decreased by 0.2 s (Wilcoxon W = − 395.0, range: − 6.3 to 3.2, IQR − 1.3 to 0.1, P = 0.0070). Participants with shorter CR times exhibited comparatively greater increases in systemic vascular resistance and a more pronounced decrease in cardiac output.ConclusionsOur findings reveal that finger CR time paradoxically decreases in a majority of healthy volunteers in a lower body negative pressure model of blood loss, challenging traditional assumptions about the CR test’s reliability as a shock indicator in its present interpretation.

The eukaryotic elongation factor 2 kinase inhibitor, A484954, induces hypoglycaemic and hypotensive effects.

Eukaryotic elongation factor 2 kinase (eEF2K) belongs to the Ca2+/calmodulin-dependent protein kinase family. We previously revealed that A484954, a selective eEF2K inhibitor, caused hypotensive and diuretic effects via the production of nitric oxide (NO) in spontaneously hypertensive rats. Otsuka Long-Evans Tokushima Fatty (OLETF) rats are hypertensive because of obesity and type 2 diabetes. Because an NO synthase inhibitor was reported to increase the expression of sodium glucose co-transporter 2 (SGLT2), we hypothesised that A484954 causes not only hypotensive but also hypoglycaemic effects via NO production in OLETF rats. To test the hypothesis, we examined the effects of A484954 administration on hyperglycaemia and hypertension in OLETF rats. OLETF rats were given an intraperitoneal injection of A484954 (2.5 mg kg-1day-1) for 7 days. Then, we measured blood and urinary glucose level, urine output, systolic blood pressure and ventricular contractility. We also conducted Western blotting and isometric tension measurements. A484954 induced a decrease in blood glucose, an increase in urinary glucose excretion, and a decrease in protein expression of kidney SGLT2. In addition, A484954 induced a decrease in systolic blood pressure, an NO-dependent vasorelaxation, and a diuretic effect. Further, A484954 enhanced left ventricular contractility. We, for the first time, revealed that (1) A484954 caused hypoglycaemic effects through increasing urinary glucose excretion via decreasing SGLT2, (2) A484954 improved diabetic complication, including hypertension, through vasorelaxation and diuresis via NO production, and (3) A484954 had a positive inotropic effect.

The use of continuous remimazolam and propofol for procedural sedation and analgesia during colonoscopy: A case series

Rationale and patient concerns: Propofol is the most frequently used sedative for procedural sedation and analgesia (PSA). However, side effects are cardiovascular and respiratory depression and pain on injection. Remimazolam is equally effective as propofol with improved hemodynamic stability and less respiratory depression and not painful on injection. However, propofol achieves a deeper level of sedation, suggesting that the addition of propofol to remimazolam may combine the best of both worlds. Continuous administration of remimazolam for PSA during colonoscopy has never been described. Here, we evaluate 11 cases in which the combination of continuous remimazolam and propofol with alfentanil is used for PSA during colonoscopy. Diagnoses and interventions: Eleven patients received intravenous remimazolam to induce sedation, followed by continuous infusion at varying rates to maintain sedation. A low dose of propofol was also administered, along with boluses of alfentanil for analgesia during the procedure. Outcomes: The combination of remimazolam, propofol, and alfentanil resulted in adequate sedation depth, quick emergence from sedation, and 100% amnesia for the procedure. Patients and physicians expressed high satisfaction with the approach. Vital signs were stable during the procedure, with minimal instances of decreased blood pressure and no significant oxygen desaturations. The combination of sedatives showed potential benefits, but further investigation through randomized controlled trials is necessary to confirm its advantages. Lessons: Continuous administration of remimazolam, propofol, and alfentanil during colonoscopy appears to be a promising option for PSA, offering effective sedation with relatively low risk of adverse effects.

Case report: Management of acute progressive hemothorax in pregnancy complicated by maternal pulmonary sequestration.

Pulmonary sequestration is a rare pulmonary malformation, typically characterized by asymptomatic presentation or recurrent pulmonary infections, with chest pain and hemothorax being exceedingly rare occurrences. The rupture and hemorrhage of maternal pulmonary sequestration during pregnancy pose a life-threatening condition that is challenging to diagnose. We present a case of a 37-year-old pregnant woman in her third trimester who presented with acute progressive hemothorax, a complication arising from maternal pulmonary sequestration. The patient experienced chest pain, which was followed by a decrease in blood pressure, albeit without a concomitant drop in blood oxygen saturation. Within a critical 24-h window, an emergency cesarean section was performed, promptly followed by a right inferior lobectomy. Intraoperative diagnosis confirmed pulmonary sequestration. Fortunately, both the patient and the newborn had a favorable prognosis post-surgery. The diagnosis of pulmonary sequestration in pregnancy is challenging and can present with non-specific symptoms. Clinicians should maintain a high index of suspicion for pulmonary sequestration, especially in cases of unexplained chest pain or hemothorax during pregnancy. Timely surgical intervention can be life-saving and is crucial for maternal and fetal well-being.

ВЛИЯНИЕ АРТЕРИАЛЬНОГО ДАВЛЕНИЯ НА СНИЖЕНИЕ ГИПЕРТЕНЗИИ ПОСЛЕ БЕРЕМЕННОСТИ: КЛИНИЧЕСКИЙ АСПЕКТ

The study aims to evaluate the effectiveness of self-monitoring of blood pressure using digital technologies in women with hypertension after pregnancy, in order to reduce the risk of long-term cardiovascular complications. Materials and methods. A clinical trial involving 20 women was conducted, divided into two groups randomly. The study was conducted at the Republican Clinical Hospital in Makhachkala. The participants of the experimental group had their blood pressure measured daily and transmitted the data via a mobile application to adjust the dosage of medications. The control group received standard medical support. Results. The average diastolic blood pressure in the intervention group was significantly lower (-5.70 mmHg, P &lt; 0.001), as was the systolic blood pressure (-6.41 mmHg, P &lt; 0.001), compared with the control group. The difference in pressure levels was evident already in the first week and was maintained until the ninth month. Conclusions. Self-monitoring of blood pressure and remote adjustment of antihypertensive drugs lead to a significant decrease in both systolic and diastolic blood pressure in women after childbirth. These methods can be put into practice to improve women's long-term health.

Importance of early use of tolvaptan in hyponatremic acutely decompensated heart failure patients, a retrospective study

BackgroundHyponatremia is one of the complicating findings in acute decompensated heart failure. Decrease in cardiac output and systemic blood pressure triggers activation of renin–angiotensin–aldosterone system, antidiuretic hormone, and norepinephrine due to the perceived hypovolemia. Fluid-overloaded heart failure patients are commonly treated with loop diuretics, acutely decompensated heart failure patients tend to be less responsive to conventional oral doses of a loop diuretic, while other different diuretics could work in different part of nephron circulation system. In this study, we aim to further examine the role of tolvaptan, a vasopressin receptor antagonist, in the treatment of hyponatremia secondary to acutely decompensated heart failure.ResultsA total of 71 patients with hyponatremia secondary to ADHF were included, and all patients were given tolvaptan. 37 patients were administered tolvaptan early (up until 5 th day of admission). 34 patients received tolvaptan after 5 th day of admission mean administration as 6.86 th day, and median administration was 5 th day. Analysis showed lower length of stay in patients receiving early administration of tolvaptan compared to late administration (8.86 ± 5.06 vs 18.5 ± 9.05 p0.001, respectively). Patients with early initiation of tolvaptan also achieved a larger net increase in sodium levels at discharge compared to admission (6.46 ± 6.69 vs 3.68 ± 4.70 p0.048, respectively).ConclusionsEarly administration of tolvaptan in treating hyponatremia in acutely decompensated heart failure patients is associated with a lower length of hospitalization and a higher increase in serum sodium of patients in hyponatremic ADHF patients.

Comparative study on blood pressure and metabolic improvements in hypertensive patients using copper bianstone scraping.

To evaluate the effectiveness and feasibility of the copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy program by comparing and analyzing the improvement of blood pressure, blood lipids and blood glucose in hypertensive patients who received copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy intervention. We selected 160 cases of hypertensive patients from July 2022 to March 2024 for the study. They were divided into 80 cases in the comparison group and 80 cases in the observation group according to whether or not they underwent copper bianstone scraping combined with Chinese modified dietary therapy for termination of hypertension. In the comparison group, conventional Chinese dietary therapy with improved termination of hypertension was used, and in the observation group, copper bianstone scraping combined with Chinese dietary therapy with improved termination of hypertension (DASH) was used on the basis of the comparison group. Differences in vitamin D, Homocysteine and serum calcium levels, blood pressure, blood glucose and lipid levels were compared between the 2 groups. The decreases of glycosylated hemoglobin, fasting blood glucose and 2-hour postprandial blood glucose in the observation group were greater than those in the comparison group; the decreases of blood pressure and BMI in the observation group were greater than those in the comparison group. The difference in comparison was statistically significant (P-value < 0.05). After the intervention, the improvement of homocysteine, vitamin D, serum calcium, albumin, hemoglobin and transferrin in the observation group was greater than that in the comparison group, and the difference was statistically significant (P-value < 0.05). Copper bianstone scraping combined with Chinese modified termination of hypertension dietary therapy in hypertensive patients has a better effect, can effectively improve the patient's blood glucose and lipid levels, improve the nutritional status of the patient, can be promoted in the rehabilitation management of hypertension.

Smaller decrease in late second trimester blood pressure is associated with gestational hypertensive disease development.

We investigated whether a smaller reduction in 2nd trimester blood pressure (BP) is associated with the development of gestational hypertensive disease. We conducted a retrospective cohort study utilizing a clinical database at an urban safety-net hospital. Individuals ages 18-40 with a singleton gestation and 1st trimester prenatal care were included. Those with chronic hypertension were excluded. Systolic BP (SBP), diastolic BP (DBP), & mean arterial pressure (MAP) decrease were calculated. The outcome variable, gestational hypertensive disease (GHDP) included gestational hypertension and preeclampsia with and without severe features. Of N=3,355 individuals that met inclusion criteria, 18% had GHDP. The mean gestational age of 1st trimester and 2nd trimester BP values were 9.8±2.1 and 23.5±2.3weeks. Those with GHDP compared to those without GHDP had a significantly higher mean 1st trimester SBP (p<0.01), DBP (p<0.01), and MAP (p<0.01). Those with GHDP compared to those without GHDP had a significantly smaller decrease between 1st and 2nd trimester SBP (-1.7±12.3 vs -2.9±11.8, p<0.001) and MAP (-2.1±8.4 vs -2.7±7.9, p=0.01). Those with GHDP compared to those without GHDP had a smaller DBP decrease but it was not statistically significant (-2.3±8.7 vs -2.7±8.2, p=0.19). Pregnant individuals who experienced a smaller decrease in SBP and MAP were more likely to develop GHDP. A reduced physiologic drop in 2nd trimester BP may suggest underlying vascular dysregulation. Future studies investigating biological mechanisms driving diminished 2nd trimester BP decline, utilizing non-invasive hemodynamic monitoring, are necessary.

Enhancing the Practicality along with Greenness Sustainability of a High Throughput HPLC-MS/MS Bioanalytical Method for the Simultaneous Determination of Amlodipine, Perindopril, and Its Active Metabolite Perindoprilat in Human Plasma: Application to a Pharmacokinetic Study

Numerous studies have demonstrated the benefits of amlodipine and perindopril combination therapy in decreasing blood pressure and improving outcomes for high-risk patients. In order to assess the pharmacokinetics of the 2 drugs along with perindoprilat; the active metabolite of perindopril, a simultaneous LC-MS/MS quantification method of amlodipine (AML), perindopril (PER) and perindoprilat (LAT) in human plasma has been developed and validated using amlodipine D4, perindopril D4 and perindoprilat D4 as internal standards (ISs), respectively. A simple and fast protein precipitation method was used to analyze the three analytes from K3EDTA human plasma. The chromatographic separation included the use of a mixture of methanol and acetonitrile (80:20, v/v) and 0.2% aqueous formic acid (60:40, v/v) as a mobile phase pumped onto a Zorbax® SB-AQ C18 column. Detection was carried out using a tandem mass spectrometer (MS/MS) in multiple reactions monitoring (MRM) mode. This method exhibited great sensitivity (LLOQ of 0.2 ng/mL for AML and PER and 0.4 ng/mL for LAT), linearity, accuracy (ranging from 97.64% to 110.28%), precision (ranging from 2.54% to 7.60%), and stability. The method showed good linearity over the range of (0.2-10 ng/mL) for AML, (0.2-160 ng/mL) for PER and (0.4-80 ng/mL) for LAT. The average extraction recoveries of AML, PER and LAT samples were between 81.92 % and 85.07%. Total elution time was as low as 3 min only. In addition, to ensure the practicality of the developed method, BAGI tool was applied, and the current method has achieved the highest score among the compared methods. Moreover, the sustainability of the proposed method was evaluated using AGREE tool and RGB 12 paradigm showing remarkable sustainability. The developed method is fast, accurate, sensitive, reproducible, ecofriendly, sustainable and suitable for the determination of the concentration of the cited analytes in human plasma. Moreover, it was applied for the bioequivalence study of a generic product to the innovator.

Decreased blood pressure with acute administration of quercetin in L-NAME-induced hypertensive rats.

Quercetin is known to reduce blood pressure (BP); however, its acute effects are unclear. We investigated the acute effects of quercetin on BP, aortic mechanical properties and vascular reactivity in female Sprague-Dawley (SD) rats. Hypertension was induced using L-NAME (40 mg/kg/day). Quercetin (4.5mg/kg) was administered intravenously. Mechanical properties of the aortae were measured by echo-tracking in normotensive and hypertensive rats. L-NAME and quercetin quantities in the aorta were determined using AP-MALDI-MSI. Vascular reactivity was performed in mesenteric and renal arteries. L-NAME increased BP and PWVβ while decreasing strain. Quercetin decreased BP and ameliorated PWVβ in L-NAME-induced hypertensive rats. Ex vivo, the acetylcholine (ACh)-induced increase in tension at 100 μM was reduced in renal arteries when exposed to quercetin while phenylephrine (Phe)-induced contractile response was augmented. In quiescent rings of renal arteries incubated with L-NAME (10μM) and TRAM-34 (1μM), the ACh-induced vasoconstrictions were inhibited by quercetin. Quercetin resulted in concentration-dependent vasodilation in mesenteric arteries and increased its sensitivity to ACh-induced relaxations. Quercetin lowered BP in L-NAME-induced hypertensive rats, likely due to changes in aortic mechanical properties and relaxation of resistance arteries. Further research is warranted to clarify the acute effects of quercetin on renal arteries in this hypertensive model.

TGR5 attenuates DOCA-salt hypertension through regulating histone H3K4 methylation of ENaC in the kidney.

Epithelial sodium channel (ENaC), located in the collecting duct principal cells of the kidney, is responsible for the reabsorption of sodium and plays a critical role in the regulation of extracellular fluid volume and consequently blood pressure. The G protein-coupled bile acid receptor (TGR5) is a membrane receptor mediating effects of bile acid and is implicated in kidney diseases. The current study aims to investigate whether TGR5 activation in the kidney regulated ENaC expression and potential mechanism. Lithocholic acid (LCA), a TGR5 agonist, markedly decreased systolic blood pressure induced by DOCA-salt in mice, which was associated with decreased ENaC expression in the kidney. DOCA-salt treatment increased renal expression of histone H3 lysine 4 trimethylation (H3K4me3) and decreased expression of lysine-specific demethylase 5A (KDM5A), a lysine demethylase, which was markedly reversed by LCA. TGR5 knockout caused further increased systolic blood pressure and ENaC expression in mice with DOCA-salt in association with increased H3K4me3 and decreased KDM5A. In immortalized mouse cortical collecting duct (mpkCCD) cells LCA markedly inhibited aldosterone-induced ENaC-mediated current. LCA treatment or TGR5 overexpression markedly inhibited ENaC and H3K4me3 protein expression in association with decreased KDM5A in mpkCCD cells treated with either aldosterone or angiotensin II. Inhibition or knockdown of KDM5A in mpkCCD cells prevented LCA-induced downregulation of ENaC expression by promoting H3K4me3 on the ENaC transcription start site. LCA upregulated KDM5A expression was likely through JNK/c-Jun signal pathway. In conclusion, LCA decreased blood pressure and ENaC protein expression in the kidney of mice with DOCA-salt, likely through activating TGR5 and upregulating KDM5A-induced H3K4me3 demethylation in ENaC promoter region.

Differentiation between Hypovolemic Shock and Septic Shock in Patients with Unstable Vital Signs after Cesarean Section: A Case Report

Hypovolemic shock and septic shock present similar symptoms, such as increased heart rate and decreased blood pressure. However, the two conditions have different causes, mechanisms, and treatment approaches. Early differentiation between the two conditions can have a positive impact on patient prognosis. In this case, the patient underwent a right ovarian cystectomy due to a teratoma torsion during a previous pregnancy, followed by treatment for a postoperative infection. While recovering, the patient underwent an emergency cesarean section due to sudden severe abdominal pain. After the surgery, unstable vital signs were suggestive of hypovolemia due to massive bleeding from the cesarean section. Therefore, fluid infusion and blood transfusion were initiated. The vital signs did not improve. So, the patient was reassessed. Body temperature and the previously elevated C-reactive protein levels were remeasured. The results of the reassessment indicated a septic condition due to previous infection. The patient was prescribed additional vasopressors and antibiotics for the following week. Subsequently, the patient’s vital signs stabilized, and the treatment was discontinued.

A Clinical Validation of Safety and Effectiveness of Pain Relief and Joint Mobility Tablet

Abstract: Introduction: Millions of people worldwide are dealing with joint discomfort and issues with mobility, which are mostly caused by diseases like rheumatoid arthritis and osteoarthritis. These illnesses not only hurt physically but also seriously limit mobility, which diminishes activity levels and impairs quality of life. Materials and Methods: An open-label, single-arm, safety study was conducted on 32 individuals. One tablet of Pain Relief and Joint Mobility twice daily after a meal for 30 days was given. The research objectives were to evaluate changes in compliance, clinical, vital parameter assessment, and tolerability of the investigational product from baseline to the end of the study. Changes in complete blood count (CBC), liver function test(LFT), and renal function test (RFT)parameters on screening and day 30. Results: The analysis of the vital sign parameters revealed a statistically significant decrease in diastolic blood pressure (p=0.0075) and body temperature (p=0.0133) from the screening to day 30 time points. Hematological and biochemical investigations demonstrated no clinically significant changes from baseline to endpoint, indicating the safety of the intervention. After a 30-day treatment regimen, significant reductions were observed across all Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales: a 32.42%, 34.12%, and 34.76% decrease in pain, stiffness, and physical function scores respectively, indicating substantial alleviation of pain, improvement in stiffness, and enhanced physical function. Conclusion: The study indicates that the Pain Relief and Joint Mobility Tablet is found to be safe and effective in managing joint pain and mobility issues, proving beneficial for patients ranging from those newly diagnosed to those with chronic conditions.

Effects of Exergaming on Morphological Variables, Biochemical Parameters, and Blood Pressure in Children and Adolescents with Overweight/Obesity: A Systematic Review with Meta-Analysis of Randomized Controlled Trials.

This systematic review with meta-analysis aimed to evaluate the available body of published peer-reviewed studies on the effects of exergaming (EXG) compared to the control group (CG) on morphological variables, biochemical parameters, and blood pressure in children and adolescents with overweight/obesity. A systematic literature search was conducted until September 2024 using five databases: PubMed, Medline, CINAHL Complete, Scopus, and Web of Science. PRISMA, TESTEX, RoB 2, and GRADE tools assessed the methodological quality and certainty of evidence. Hedge's g effect sizes (ES) for morphological, biochemical, and blood pressure variables were calculated for meta-analyses. Using a random effects model, potential sources of heterogeneity were selected, including subgroup analyses (age) and single training factor analysis (program duration, training frequency). The protocol was registered in PROSPERO (code: CRD42024626992). Out of 72 records, 6 randomized controlled trials with 191 children and adolescents with overweight/obesity were included. Nine meta-analyses were performed, showing significant decreases in body mass index (p = 0.04), waist circumference (p = 0.03), and systolic blood pressure (p = 0.007). However, no significant improvements were observed in diastolic blood pressure, body fat percentage, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and glucose. Subgroup analyses showed significant decreases in total cholesterol (<15 years, ES = 0.56; p = 0.006), HDL-cholesterol (<15 years, ES = 0.51; p = 0.01), LDL-cholesterol (<15 years, ES = 0.63; p = 0.01), and triglycerides (<15 years, ES = 0.82; p = 0.000). In training duration, only significant decreases in total cholesterol (ES = 0.69; p = 0.02) were presented in favor of <12 weeks vs. ≥12 weeks. While in training frequency only significant decreases in triglycerides (ES = 0.70; p = 0.03) were reported in favor of ≥3 sessions per week vs. <3 sessions per week. EXG significantly decreases body mass index, waist circumference, and systolic blood pressure in children and adolescents with overweight/obesity.

The Role of Metabolic Therapy in the Treatment of Chronic Coronary Syndrome. Results of Own Research

Ischemic heart disease (IHD) and stroke are the main causes of mortality and disability worldwide. One of the most controversial issues in modern cardiology is the feasibility of using metabolic drugs for the treatment of patients with angina. The main directions in metabolic therapy are optimization of energy production and expenditure and normalization of the balance between the intensity of free radical oxidation and antioxidant processes. The objective: to determine the clinical effectiveness of combined metabolic therapy with domestic drugs meldonium, ethylmethylhydroxypyridine succinate and armadin in the complex treatment of military personnel with IHD. Materials and methods. The study included 36 military personnel with coronary artery disease with stable angina pectoris of functional class II–III. Patients were treated in the cardiology department of the Military Medical Clinical Treatment and Rehabilitation Center (Irpin). All examined patients were male, the average age was 43.7 ± 2.7 years, the duration of the disease was 4.2 ± 2.3 years, the onset of angina attacks was 39.6 ± 2.8 years. All patients received standard therapy in accordance with the ESC recommendation. Additionally intravenous drip infusions of meldonium (100 mg/ml, 5 ml per 100.0 saline), ethylmethylhydroxypyridine succinate (50 mg/ml, 2 ml intravenously in a 1:2 dilution in saline, slowly in a jet) and armadin (300 mg, 1 tablet in the evening for 2 weeks, then 1 tablet solution twice a day for 4 weeks) were prescribed. The effectiveness of the prescribed complex was monitored based on the dynamics of clinical status, bicycle ergometry indicators, and Holter ECG monitoring before the start of treatment and after 14–16 days. Results. The use of metabolic therapy significantly improved the general condition of patients, reduced the number of angina attacks, and reduced the need for nitroglycerin tablets. Analysis of the sample with dosed physical activity before the start of therapy revealed a significant percentage of patients with ST segment depression of 2 mm at the height of physical activity, and the total relative number of patients with ST segment depression of 1.5–2 mm was 72.2%. During the repeated examination ST segment depression was not determined in 94.4% of patients. Before treatment, rhythm disturbances in the form of supraventricular and ventricular extrasystoles were recorded on the background of maximum exercise, and after treatment, no rhythm disturbances were detected. In the dynamics of the therapy, it was possible to achieve a decrease in blood pressure (BP) indicators during exercise, the level of systolic BP decreased by 16.4%, and diastolic BP – by 9.4% (p &lt; 0.05). Recovery time significantly decreased by 35.2%, but oxygen consumption and tolerance index significantly increased. Conclusions. The results of the study demonstrated that combination therapy with domestically produced metabolic drugs (meldonium, ethylmethylhydroxypyridine succinate and armadine) with a combination of injectable and tablet forms showed high effectiveness in the treatment of military personnel with coronary artery disease. The combination of drugs that patients received during the study demonstrated good tolerability and the absence of adverse reactions.