The influence of Losartanum and Amlodipinum fixed combination use on cardiovascular complications risk factors seasonal variability in patients with arterial hypertension

Rationale: The influence of drugs on adaptation to high temperatures and seasonal variability of cardiovascular disease factors is one of the most important issues of treatment raised during re-cent heat waves. The safety of calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) use during heat waves is quite controversial. Aim: To assess the seasonal variability of hemodynamic parameters, vessel wall stiffness, lipid, carbohydrate and electrolyte metabolism in patients with arterial hypertension (AH) and to as-sess safety and effectiveness of fixed combination of Losartanum and Amlodipinum (Lortenza® KRKA) use according to one-year follow-up results. Materials and methods. The study included 26 patients with stage 1 and 2 AH aged from 42 to 81 years. Office blood pressure measurement, electrocardiography, volumetric sphygmography (pulse-wave velocity, cardio-ankle vascular index), serum chemistry, blood osmolarity tests were performed. Visual Analog Scale (VAS), Heat Questionnaries and self-control diaries were also assessed. The baseline visit took place in spring of 2016, the first visit - in May-June 2016, the second - during the heat wave, the third - in September-October 2016, the fourth - in January-February 2017, and the fifth - in April-May 2017. Results. The treatment resulted in systolic and diastolic blood pressure decrease (р=0.000) to target value which persisted during the follow-up period. According to the self-control diaries 81% of patients did really control BP. During the heat wave only 58% of patients succeeded in BP control, in autumn - 63%, in winter and spring - 81% and 86%, respectively. By the third visit the heart rate decreased on -6.0 (-11.1; -2.8) beats per minute, p=0.007. The decrease in pulse-wave velocity from 15.2±3.4 m/s to 13.6±2.7 m/s, p=0.01 and CAVI on -2.1 (-2.9; -0.65), p=0.01 was observed on the third visit. Decrease in uric acid level (

Prognostic value of subclinical atherosclerosis in patients with a SCORE risk <5%: data from a 10-year follow-up

Aim. To evaluate the contribution of subclinical atherosclerosis to the stratification of patients with a SCORE risk of cardiovascular events (CVEs) &lt;5% based on a 10-year follow-up.Material and methods. The study included 379 patients with SCORE risk of CVEs &lt;5% (82 men, 297 women). In 2009, all patients underwent clinical examination, carotid artery (CA) ultrasound with the detection of plaques, total CA occlusion, intima-media thickness (IMT) of the common carotid artery (CCA). The plaque number was determined as the total number of all plaques in 6 following segments: both CCAs, both CCA bifurcations and both internal carotid arteries. The total stenosis was calculated as the sum of stenoses in 6 CA segments in %. In 2019, a telephone survey of patients was conducted with a questionnaire assessing the following CVEs: all-cause death, cardiovascular death, myocardial infarction (MI), stroke, myocardial revascularization, cardiovascular hospitalizations, and composite endpoint.Results. The initial patients’ age ranged from 35 to 67 years (51,1±7,5 years). Plaques from 20% to 50% were detected in 303 participants (79,94%). Over the past 10 years, there have been 5 cardiovascular deaths (1,3%), 7 MIs (1,8%), 5 cases of unstable angina (1,3%), 12 cases of myocardial revascularization (3,2%), 15 strokes (4,0%), 51 cardiovascular hospitalizations (13,5%). The proportion of patients with registered endpoints (CVE+) was 22,4% (n=85). The groups of patients with and without CVEs differed in the level of systolic blood pressure (BP) and blood triglycerides, and did not differ in the level of diastolic BP, lipid profile, glucose, heart rate, smoking status, sex, and age. In the CVE+ group, there were higher values of CCA IMT (0,65 (0,64; 0,70) mm vs 0,62 (0,62; 0,66) mm, p&lt;0,05), total CA stenosis (102,5 (88,1; 120,8)% vs 80 (72,5; 88,1)%, p=0,01), and the CA plaque amount (4,0 (2,8; 3,9) vs 3,0 (2,6; 3,1), p=0,01), respectively. Total CA stenosis was an independent predictor of CVEs when adjusted for sex, age, systolic and diastolic BP (β=0,149; p&lt;0,05), but not for lipid profile. A ROC-analysis revealed a cut-off point for total CA stenosis of 82,5% (AUC=0,598, 95% confidence interval 0,5243-0,673, p&lt;0,05).Conclusion. The total CA stenosis has shown itself to be an independent predictor of CVEs in patients with a SCORE risk &lt;5%

Stem cell‐derived enteroid cultures as a tool for dissecting host‐parasite interactions in the small intestinal epithelium.

Toxoplasma gondii and Cryptosporidium spp. can cause devastating pathological effects in humans and livestock, and in particular to young or immunocompromised individuals. The current treatment plans for these enteric parasites are limited due to long drug courses, severe side effects, or simply a lack of efficacy. The study of the early interactions between the parasites and the site of infection in the small intestinal epithelium has been thwarted by the lack of accessible, physiologically relevant, and species-specific models. Increasingly, 3D stem cell-derived enteroid models are being refined and developed into sophisticated models of infectious disease. In this review we shall illustrate the use of enteroids to spearhead research into enteric parasitic infections, bridging the gap between cell line cultures and in vivo experiments

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease

Ordered sets and lattices

This book is another publication in the recent surveys of ordered sets and lattices. The papers, which might be characterized as "reviews of reviews," are based on articles reviewed in the Referativnyibreve Zhurnal: Matematika from 1978 to 1982. For the sake of completeness, the authors also attempted to integrate information from other relevant articles from that period. The bibliography of each paper provides references to the reviews in RZhMat and Mathematical Reviews where one can seek more detailed information. Specifically excluded from consideration in this volume were such topics as a

What “new” factors should be considered when assessing cardiovascular risk?

One of the causes of high mortality from cardiovascular diseases is the lack of effective measures for the primary and secondary prevention of cardiovascular complications (CCO), due to the difficulty of timely identification risk factors (RF) and individuals with a high individual risk of CCO. This is especially true for patients from low/mean risk. This group is heterogeneous. Often, clinical manifestations of atherosclerosis occur for the first time without “classical” RF. Possible factors that increase the risk of developing cardiovascular diseases and CCO, are: heart rate, increased formation of advanced glycation endproducts, disorders of bone mineral metabolism, thyroid function, low adherence to therapy, psychosocial factors and climatic features. This review is devoted to the analysis of the evidence base of the influence of these “new” CCO RF and the individual patient prognosis

Depressions with eating disorders: clinical manifestations and therapy

Depression is a common comorbid diagnosis in patients with eating disorders (EDs). The development of pathogenetic therapy for depression with EDs is far from being completed.The objective of the psychopharmacotherapeutic study was to evaluate the efficacy and tolerability of melatonergic monotherapy with the antidepressant agomelatine (25–50 mg/day at night) for depressions with two ED variants: hyperphagic (n=32) and hypo- and aphagic (n=31) EDs.Patients and methods. The investigation enrolled patients of both sexes, aged 18 to 65 years. The investigators performed clinical psychopathological and experimental psychological studies, as well as psychometric examination using the 21-item Hamilton Depression Rating Scale (HDRS-21), the Clinical Global Impression (CGI), the Supplemental Hospital Offset Payment Program (SHOPP), the Dutch Eating Behavior Questionnaire (DEBQ), and statistical data processing.Results and discussion. There was a significant pronounced antidepressant effect of 6-week agomelatine therapy for depressions occurring with different ED variants both in the pattern of the depressive symptom complex and in that of concurrent with and preceding the latter. At the same time, the efficacy of the drug did not depend on the clinical presentations of the leading hypothymic syndrome, the variants of EDs, and the duration of actual depression. However, by the end of the study period, a larger effect was achieved in the therapy for depressions with the hyperphagic variant of EDs, as well as in patients with EDs manifesting in the pattern of depressive symptom complex. Agomelatine has a favorable tolerance profile. BMI tends to become normal in patients with different variants of EDs during the therapy. The adverse events are transient and/or unclear; they do not require therapy discontinuation.Conclusion. Agomelatine is an effective and relatively safe drug that can be recommended to treat depressions concurrent with EDs in therapeutic dosages for at least 6 weeks