Development Of Arterial Hypertension Research Articles

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

Autologous Reconstruction of Anomalous Origin of a Right Pulmonary Artery From the Aorta.

Anomalous origin of a pulmonary artery branch from the aorta is a rare congenital anomaly in which one of the pulmonary arteries arises from the aorta. These patients require early surgery to prevent development of severe irreversible pulmonary arterial hypertension. Multiple techniques have been described for repair of this condition. In this report, we describe a different technique compared with previously described procedures and discuss its advantages.

Risk factors for the development of arterial hypertension in children and young people in present-day developments

In modern society, there is an intensive increase in the incidence of hypertension among young people, which is mainly due to lifestyle features and associated risk factors. Purpose. To analyze the results of Russian and foreign scientific research concerning the study of risk factors in the development of hypertension in children and young people. Material and methods. A qualitative analysis of the current data available in the literature on the risk factors of hypertension and its prevention has been carried out. Results. It has been established that the occurrence of arterial hypertension in childhood is influenced not only by hereditary factors, but also by a number of environmental risk factors. Conclusion. Further research is needed to study new and established risk factors that need to be considered when conducting primary prevention of the disease in children and young people from the high-risk group.

Leukotriene B4 levels in CHD-associated paediatric pulmonary hypertension.

The aim of this study is to evaluate the role of leukotriene B4, an inflammatory mediator, in the development of pulmonary hypertension in paediatric patients with CHD with left-right shunt. The study included forty patients with CHD with left-right shunts. Based on haemodynamic data obtained from cardiac diagnostic catheterisation, 25 patients who met the criteria for pulmonary arterial hypertension were included in the patient group. The control group comprised 15 patients who did not meet the criteria. The standard cardiac haemodynamic study was conducted. Leukotriene B4 levels were assessed in blood samples taken from both pulmonary arteries and peripheral veins. The median age of patients with pulmonary arterial hypertension was 10 months (range: 3-168), while the median age of the control group was 50 months (range: 3-194). In the pulmonary hypertension group, the median pulmonary artery systolic/diastolic/mean pressures were 38/18/24 mmHg, compared to 26/10/18 mmHg in the control group. Leukotriene B4 levels in pulmonary artery blood samples were significantly higher in the pulmonary arterial hypertension group compared to the controls (p < 0.05). Peripheral leukotriene B4 levels were also elevated in the pulmonary arterial hypertension group in comparison to the control group, though the difference was not statistically significant. The discovery of elevated leukotriene B4 levels in pulmonary artery samples from paediatric patients with pulmonary arterial hypertension secondary to CHD with left-to-right shunt suggests that local inflammation may have a pathological role in the development of pulmonary arterial hypertension.

Male Sex Is Associated With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort

BackgroundSex-based differences are important in the development and progression of pulmonary arterial hypertension (PAH). However, it is not established whether these differences are generalizable to all forms of pulmonary hypertension (PH). Research QuestionTo assess sex-based differences in right ventricular (RV) function and transplant-free survival in subjects with PH from the PVDOMICS cohort. Study Design and MethodsSubjects with PH enrolled in PVDOMICS cohort study underwent right heart catheterization, cardiac MRI, and echocardiogram. A multivariable linear regression model was used to investigate the interactive effect between sex and pulmonary vascular resistance (PVR) on RV ejection fraction (EF). Effects of sex, RVEF, and PVR on transplant-free survival were assessed using a Cox proportional hazards model. Results750 subjects with PH (62.8% female) were enrolled, including 397 subjects with Groups 2-5 PH. Group 1 was most predominantly female (73.4%). Men had multiple markers of worse RV function with significantly lower RVEF (Adjusted difference 5.5%, 95% CI: 3.2-7.8%, P<0.001) on cardiac MRI and lower RV fractional shortening (Adjusted difference 4.0%, 95% CI: 2.3 to 5.8%, P<0.001) and worse RV free wall longitudinal strain (Adjusted difference 2.4%, 95% CI: 1.2 to 3.6%, P<0.001) on echocardiogram. There was significant interaction between PVR and sex on RVEF with largest sex-based differences in RVEF noted at mild to moderate PVR elevation. Male sex was associated with decreased transplant-free survival (adjusted HR 1.46, 95% CI: 1.07 to 1.98, P=0.02), partially mediated by differences in RVEF (P=0.003). InterpretationIn subjects with PH in PVDOMICS, female sex is more common, while male sex is associated with worse RV function and decreased transplant-free survival, most notably at mild to moderate elevation of PVR.

Tumor biomarkers in evaluating the severity and prognosis of idiopathic pulmonary arterial hypertension: Acomprehensive analysis.

Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014-2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163-3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001-1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well-validated PH biomarkers, CA125 was still of prognostic value in the low-risk patients (HR: 1.014, 95% CI: 1.004-1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

Relationship between sleep quality and blood pressure level in nurses performing shift work

Abstract Objective The aim of the study was to evaluate the quality of sleep in nurses performing shift work in therapeutic and surgical departments and to establish possible relationships between level of blood pressure (BP) and quality of sleep. Methods A total of 20 nurses of the therapeutic departments and 20 nurses of the surgical departments were enrolled in the study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). BP was measured according to the standard protocol using the Korotkoff method; a sphygmomanometer was used for this twice with an interval of 2 min between 10:00 a.m. and 10:30 a.m. The average value for the 2 indicators was calculated. The diagnosis of essential arterial hypertension (AH) was established according to the recommendations of the European Association of Cardiology and the European Association of Hypertension (2018). Results The overall assessment of the sleep quality of the nurses involved in shift work indicates poor sleep quality; this was true in respondents of both the surgical and therapeutic profiles. However, it was observed that the quality of sleep was significantly lower in nurses of the therapeutic departments. Moreover, poor sleep quality was associated with AH, which was diagnosed in 65% of the nurses of the therapeutic departments and 45% of the nurses of the surgical departments, that is, in almost all of the subjects. Herewith, in the nurses of the therapeutic departments, the level of systolic BP exceeded that of the nurses of the surgical departments. Conclusions Poor sleep quality is a significant risk factor for AH development and is relevant to nurses performing shift work. Additional clinical studies should be conducted to better understand the mechanisms underlying such adverse cardiometabolic outcomes associated with sleep disorders in the health-sector shift workers.

Análisis de las variantes genéticas IL-6 – 174G/C y FNT-α -308 G/A en pacientes con diagnóstico de sepsis bacteriana

The objective of this study was to evaluate the IL-6 -174G/C and TNF-α -308G/A variants in patients diagnosed with bacterial sepsis in an Intensive Care Unit (ICU).&#x0D; Materials and methods. A prospective observational study was conducted that included one hundred patients with sepsis and thirty control subjects. Blood samples were collected to measure the concentrations of cytokines IL-6 and TNF-α and to detect the genetic variants IL-6-174G/C and TNF-α-308A/G. A multivariate analysis was performed with cytokine levels, sepsis progression, comorbidities and mortality as dependent variables and genetic variants analyzed as independent variables. Survival analysis was performed according to the Kaplan and Meyer model.&#x0D; Results. Multivariate analysis showed that the G allele of IL-6-174 G/C was a risk factor for developing sepsis due to infection by Gram-negative bacteria (62,3%; OR:2,619; IC95%1,095-6,259; p=0,030) and the GA genotype of TNF-α-308G/A was significantly associated with the development of septic shock (50%; OR:4,053; IC95%1,546- 10,623; p=0,004), arterial hypertension (53%; OR:3,359; IC 95% 1,253-9,008; p=0,016) and infection by Gram-positive bacteria (17,6%; OR:9,525; IC95%1,854-48,928; p=0,007). Conclusion. The GA genotype of TNF-α-308G/A was found to be a risk factor for the development of septic shock

Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension

AimsNuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH.Methods and resultsMice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca2+ influx and inducing phenotypic conversion of PASMCs.ConclusionsNupr1 activation could promote Ca2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy.Graphical 1. Chronic intermittent methamphetamine exposure can induce the development of pulmonary arterial hypertension.2. Nupr1 plays a key role in the development of methamphetamine-related pulmonary arterial hypertension.3. Nupr1 mediates PASMCs phenotypic transformation via STIM1signal axis, which results in the development of methamphetamine-related pulmonary arterial hypertension.

The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension.

Arterial hypertension represents a leading cause of cardiovascular morbidity and mortality worldwide, and the identification of effective solutions for treating the early stages of elevated blood pressure (BP) is still a relevant issue for cardiovascular risk prevention. The pathophysiological basis for the occurrence of elevated BP and the onset of arterial hypertension have been widely studied in recent years. In addition, consistent progress in the development of novel, powerful, antihypertensive drugs and their appropriate applications in controlling BP have increased our potential for successfully managing disease states characterized by abnormal blood pressure. However, the mechanisms responsible for the disruption of endogenous mechanisms contributing to the maintenance of BP within a normal range are yet to be fully clarified. Recently, evidence has shown that several natural antioxidants containing active ingredients originating from natural plant extracts, used alone or in combination, may represent a valid solution for counteracting the development of arterial hypertension. In particular, there is evidence to show that natural antioxidants may enhance the viability of endothelial cells undergoing oxidative damage, an effect that could play a crucial role in the pathophysiological events accompanying the early stages of arterial hypertension. The present review aims to reassess the role of oxidative stress on endothelial dysfunction in the onset and progression of arterial hypertension and that of natural antioxidants in covering several unmet needs in the treatment of such diseases.

Prediction of Cardiovascular Diseases in Women With Rheumatoid Arthritis.

To develop prognostic models for arterial hypertension (AH) and atherosclerosis based on studying the totality and significance of traditional and disease-mediated risk factors (RFs) in women with rheumatoid arthritis (RA). 223 female patients with RA aged 54.9±2.1 years were evaluated at the premises of the polyclinic of the Gulla Municipal Hospital #4 (Barnaul), the "Health Center", the City Rheumatology Department of the polyclinic, and the Hospital Department in 2016-2019. Statistical analysis was performed using Excel Microsoft Office 2007, Statistica 6.0 and 10.0, and SigmaPlot 12.5 software packages. Multivariate regression analysis was used for studying the attributes influencing the development of AH and atherosclerosis in RA and for constructing predictive models. ROC analysis was used to determine the quality of the developed models. Differences were considered statistically significant at p&lt;0.05. The following RFs predominating in the onset of disease were identified: traditional (hyperglycemia, obesity, increased diastolic BP (DBP), tachycardia, dyslipidemia); disease-mediated (ESR, fibrinogen, C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies, moderate and high DAS-28 activity), and psychosocial (stress, anxiety, depression, sleep disorders). The highest RF incidence and their combinations were determined with a RA duration of more than a year: traditional (obesity, hyperglycemia, increased systolic BP (SBP)), and decreased glomerular filtration rate; and disease-mediated (prednisolone treatment). A highly sensitive model for AH screening was developed that included a combination of RFs: disease-mediated (RA duration, CRP); traditional (improper diet, low physical activity, history of early cardiovascular diseases, increased SBP and DBP, preeclampsia and/or eclampsia, early menopause, older age, dyslipidemia); psychosocial (anxiety, depression), and a high salt-taste threshold. A highly sensitive model was developed for probable prediction of multifocal atherosclerosis in RA in women. The model includes a complex of risk factors: disease-mediated (RA activity by DAS-28, CRP, fibrinogen, ESR, dose-dependent prednisolone treatment); traditional (AH, SBP, waist circumference, heart rate, early menopause, preeclampsia and/or eclampsia, age 55 years and older, dyslipidemia); and psychosocial (sleep disorders, depression). Algorithms for early prevention of AH and atherosclerosis were developed with consideration of identified predictors and proposed prediction models for women with RA.

GRK2-YAP signaling is implicated in pulmonary arterial hypertension development.

Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown. GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2 -knockout mice ( Grk2ΔSM22 ), and littermate controls ( Grk2flox/flox ) were grouped into control and hypoxia mice ( n =8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP ) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2'-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2ΔSM22 mice compared with littermate controls. The amelioration of PH in Grk2ΔSM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2 . We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

The impact of war on the development and progression of arterial hypertension and cardiovascular disease: protocol of a prospective study among Ukrainian female refugees.

Growing evidence supports the impact of psychological factors such as traumatic experiences and Post Traumatic Stress Disorder (PTSD) on the incidence of arterial hypertension (HTN) and cardiovascular diseases (CVD). The war in Ukraine is exposing million inhabitants to traumatic experiences and severe stress. Part of Ukrainians (mostly women and children) left the country to escape war. We report the protocol of a prospective study aiming at the assessment of the impact of war-induced stress on HTN and CVD in women Ukrainian refugees who moved to Poland. The study will be conducted in 3 stages. Stage 1 will assess the prevalence of HTN and PTSD among Ukrainian refugees and will estimate the impact of war-related trauma exposure on these parameters. Data on office blood pressure (BP) will be compared to data already collected in STEPS data 2019 and May Measurement Month 2021 in Ukraine, matched for age and sex. Stage 2 will involve subjects diagnosed with HTN and/or PTSD referred for management and follow-up of these conditions. Psychologic targeted therapies will be offered to subjects with confirmed PTSD, with a periodical reassessment of the severity of PTSD-associated symptoms and of its impact on HTN and cardiovascular health. Clinical history and characteristics will be compared among three groups: subjects with HTN and PTSD, with HTN without PTSD, with PTSD but without HTN. Stage 3 will involve a subgroup among those screened in Stage 1, with the objective of investigating the biological mechanisms underlying the relation between HTN and trauma exposure, identifying early signs of subclinical target organ damage in subjects with HTN with/without PTSD. This study will test the hypothesis that trauma exposure and psychological stress contribute to BP elevation and progression of CVD in this population. It will provide new evidence on the effect of an integrated management, including psychological therapy, on BP and cardiovascular risk. Such approach may be further tested and extrapolated to other populations exposed to war and chronic violence, migrants and refugees around the world. number 2022/45/P/NZ5/02812.

The impact of dyslipidemia and hyperhomocysteinemia on the development of arterial hypertension

The impact of dyslipidemia and hyperhomocysteinemia on the development of arterial hypertension

ПРОГНОЗИРОВАНИЕ РАЗВИТИЯ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ У МОЛОДЫХ МУЖЧИН С ВЫСОКИМ НОРМАЛЬНЫМ АРТЕРИАЛЬНЫМ ДАВЛЕНИЕМ

High normal blood pressure (HNBP) is known to be associated with an increased risk of arterial hypertension (AH) development. The purpose of the study is to identify predictors of the development of AH in young men with HNBP, to assess their prognostic significance. Materials and methods. From a sample of 50 men aged 18-29 years with registered HNBP, groups were formed: group 1 – 18 patients with AH diagnosed within 10 years, group 2 – 32 patients in whom AH was not diagnosed. Cardiovascular risk factors, indicators of 24-hour blood pressure monitoring, bicycle ergometry, heart rate variability (HRV) during an active orthostatic test, echocardiography, and pulse wave velocity were analyzed. Results. Predictors of the development of AH in young men with HNBP are HRV indicators during active orthostatic test (ΔSDNN, ΔHF) and bicycle ergometry indicators (heart rate (HR) at the end of the physical load, diastolic BP (DBP) at the end of the recovery period). Conclusions. Predictors of the development of AH in young men with HNBP are ΔSDNN and ΔHF during active orthostatic test, HR in peak physical load and the level of DBP in the recovery period of bicycle ergometry (sensitivity – 88.89%, specificity – 93.75%, accuracy – 92.0%). The resulting prognostic model can be used as a method for determining the individual risk of AH development.

The significance of dynamic monitoring plasma TMAO level in pulmonary arterial hypertension - a cohort study.

Gut microbiota assumes an essential role in the development and progression of pulmonary arterial hypertension (PAH). Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, is correlated with the prognosis of patients with PAH. However, the correlation between changes in TMAO (ΔTMAO) and the prognosis of PAH remains elusive. To investigate the association between ΔTMAO and prognosis of PAH, and explore whether dynamic assessment of TMAO level was superior to measurement at a single time point in predicting prognosis. Single-center cohort study. Consecutive patients diagnosed with PAH and had at least two TMAO measurements taken from May 2019 to June 2020 were eligible. The outcome events of this study were defined as adverse clinical events. A total of 117 patients with PAH who had two TMAO measurements and follow-up were included in this study. Patients with ΔTMAO ⩾1.082 μmol/L had over four times increased risk of adverse clinical events than their counterparts after adjusting for confounders [hazard ratio (HR) 4.050, 95% confidence interval (CI): 1.468-11.174; p = 0.007]. Patients with constant high TMAO levels at both time points had the highest risk of adverse clinical events compared with patients with constant low TMAO levels (HR 3.717, 95% CI: 1.627-8.492; p = 0.002). ΔTMAO was also associated with changes in parameters reflecting PAH severity (p < 0.05). Changes in TMAO were independently correlated with prognosis in patients with PAH, irrespective of baseline level of TMAO. ΔTMAO also correlated with alteration in disease severity. Repeated assessment of TMAO level contributes to better identification of patients with increased risk of adverse clinical events.

Comparison of CT-Determined Pulmonary Artery Diameter among Smokers and Non-smokers: A Cross-sectional Study

Introduction: Tobacco smoking is a common addiction in our society. The toxic chemical compounds present in tobacco smoke cause epithelial damage and inflammation of the airways. Chronic smoking results in the thickening of the pulmonary arterial wall and vasoconstriction, leading to the development of pulmonary arterial hypertension. Hence, measurement of pulmonary artery diameter using Contrast Enhanced Computed Tomography (CECT) may be helpful in the early detection of pulmonary arterial hypertension. Aim: To compare the diameters of the Main Pulmonary Artery (MPA), Right Pulmonary Artery (RPA), and Left Pulmonary Artery (LPA) using CECT thorax in smokers and non-smokers. Materials and Methods: A cross-sectional study was conducted from April 2021 to March 2022 in the department of radiodiagnosis, KS Hegde Hospital, Karnataka, India, consisting of 100 patients referred for CECT thorax in the age group of 18-85 years. They were divided into two groups: smokers and non-smokers, with 50 patients in each group. They were further categorised into three age groups: &lt; 50 years, 50-60 years, and &gt;60 years. The widest diameters of the MPA were measured at the level of bifurcation of the artery and perpendicular to the long axis of the artery. At this level, RPA and LPA diameters were measured at the widest portion on 1.25 mm axial images of the arterial phase. Variation in the pulmonary artery diameter was compared between smokers and non-smokers with respect to age and analysed by unpaired t-test and Pearson correlation. Results: Diameters of MPA, RPA, and LPA were statistically significant (p&lt;0.05) in smokers compared to non-smokers. In smokers, MPA and RPA diameters correlated with age, which was statistically significant (p&lt;0.05). No significant correlation (p&gt;0.05) was shown between age and MPA, RPA, and LPA diameter in non-smokers. The mean MPA diameter showed a significant difference (p&lt;0.05) in all three age groups. Conclusion: The diameter of the pulmonary artery is statistically significant in smokers compared to non-smokers. Hence, assessment of pulmonary artery diameters among smokers using CECT thorax will help to diagnose Pulmonary Hypertension (PH) at an early stage.

Low-Chloride Diet Prevents the Development of Arterial Hypertension and Protects Kidney Function in Angiotensin II-Infused Mice.

A comprehensive pathophysiological mechanism to explain the relationship between high-salt intake and hypertension remains undefined. Evidence suggests that chloride, as the accompanying anion of sodium in dietary salt, is necessary to develop hypertension. We evaluated whether reducing dietary Cl- while keeping a standard Na+ intake modified blood pressure, cardiac hypertrophy, renal function, and vascular contractility after angiotensin II (AngII) infusion. C56BL/6J mice fed with standard Cl- diet or a low-Cl- diet (equimolar substitution of Cl- by a mixture of Na+ salts, both diets with standard Na+ content) received AngII (infusion of 1.5 mg/kg/day) or vehicle for 14 days. We measured systolic blood pressure (SBP), glomerular filtration rate (GFR), natriuretic response to acute saline load, and contractility of aortic rings from mice infused with vehicle and AngII, in standard and low-Cl- diet. The mice fed the standard diet presented increased SBP and cardiac hypertrophy after AngII infusion. In contrast, low-Cl- diet prevented the increase of SBP and cardiac hypertrophy. AngII-infused mice fed a standard diet presented hampered natriuretic response to saline load, meanwhile the low-Cl- diet preserved natriuretic response in AngII-infused mice, without change in GFR. Aortic rings from mice fed with standard diet or low-Cl- diet and infused with AngII presented a similar contractile response. We conclude that the reduction in dietary Cl- as the accompanying anion of sodium in salt is protective from AngII pro-hypertensive actions due to a beneficial effect on kidney function and preserved natriuresis.

The role of insulin resistance and oxidative stress in the mechanisms of arterial hypertension development

Hypertension is a pathophysiological process associated with morphological and functional disorders in cellular structures that lead to progressive imbalance of the cardiovascular system of the organism. The purpose of the study was to study the role of insulin resistance and oxidative stress in the mechanisms of development of arterial hypertension. The study included 55 patients with controlled arterial hypertension aged 57.3 ± 4.5 years. The content of glucose, insulin, products of free radical oxidation of lipids and proteins, and the activity of antioxidant protection enzymes were determined in the patients' blood. According to the results of determining the content of glucose, insulin and calculating the HOMA index, patients were divided into two groups - patients with controlled arterial hypertension without and with insulin resistance. An increase (p ≤ 0.05) in the content of primary (diene conjugates) and secondary (TBA-positive products) lipid oxidation products, protein oxidation products in the blood serum of patients with arterial hypertension without and with insulin resistance was demonstrated. Higher levels of lipid and protein oxidation products (p ≤ 0.05) were observed in patients with hypertension and insulin resistance compared to patients with hypertension without insulin resistance. A decrease (p ≤ 0.05) in the activity of antioxidant protection enzymes - superoxide dismutase and catalase in patients with arterial hypertension without and with insulin resistance was also shown. In patients with arterial hypertension and insulin resistance, the decrease in the activity of these enzymes was significantly greater (p ≤ 0.05) compared to patients with arterial hypertension without insulin resistance. Taking into account the obtained results, it is necessary to distinguish between patients diagnosed with hypertension, depending on the presence or absence of insulin resistance. Patients with hypertension and insulin resistance require a complex approach to treatment, as they have more profound changes in metabolic processes, in particular, oxidative metabolism. Insulin resistance and arterial hypertension are mutually reinforcing, therefore, for effective treatment and prevention of further complications, it is necessary to combine means and approaches to influence each of these links to more effectively prevent the development of metabolic disorders in the orgsnism.

Нові підходи до лікування отруєнь синтетичними опіоїдами: застосування великих доз Налоксону та перспективи створення альтернативних антидотів

Introduction. In the conditions of the spread of powerful synthetic opioids, the traditionally recommended doses of Naloxone may be insufficient; instead, a significant increase in the dose of Naloxone leads to side effects, which in turn creates a threat to life. Aim. Analysis of the results of own research and scientific information regarding the use of Naloxone in the treatment of synthetic opioids poisoning and the development of alternative antidotes. Materials and Methods. The medical data of 174 patients treated with the diagnosis: "Acute narcotic poisoning" (ICD-10:Т40.0-Т40.3) were studied. Laboratory studies were carried out by the method of immunochromatographic analysis and chromatographymass spectrometry. Statistical data processing was performed using the IBM SPSS Statistics 29.0.0.0 program, using Spearman's rank correlation analysis (r), with p ≤ 0.05. Results. Among patients who received Naloxone, the best dynamics according to the Glasgow coma scale at the 4th and 6th hours of observation were those who received 2-6 mg of Naloxone. A significant part of patients (76 cases, 43.68 %) required repeated administration of Naloxone due to the renarcotization, in such cases a direct correlation was established with the occurrence of undesirable clinical effects (r = 0.864, p = 0.05). A direct relationship between an increase in the dose of Naloxone and the development of arterial hypertension (r = 0.945, p = 0.01), convulsions (r = 0.887, p = 0.01), withdrawal and pain syndrome (r = 0.881, p = 0.01). In general, the occurrence of clinical effects was correlated with an increase in the dose of Naloxone (R2 = 0.92), however, the rank correlation analysis did not confirm the relationship between the dose of Naloxone and the development of pulmonary edema (r = 0.938, p &gt; 0.05), cardiac arrhythmia (r= 0.598, p &gt; 0.05), cardiac arrest (r= -0.146, p &gt; 0.05). Conclusions. The use of high doses of Naloxone does not solve the problem of prevention of opioid overdoses and their effective treatment. The development of new models of antidotes to opioids using сovalent Naloxone nanoparticles, serotonin 5-HT1A agonists, Fentanyl-binding Cyclodextrin scaffolds, specific vaccines, etc. is considered promising. Keywords: opioids, antidotes, Naloxone, Fentanyl.