The article presents a review of the literature on the role of hypertension in the mechanisms of atrial fibrillation, therelationshipbetweenwhichincreases the risk of cardiovascular disease and ...mortality. The importance of taking into account the increased variability of BP in the development of target organ damage and adverse cardiovascular events is shown. Approaches to the choice of antihypertensive therapy in patients with hypertension and atrial fibrillation have been identified. It has been found that reducing BP variability can be added as one of the most important strategies in the treatment of hypertension and atrial fibrillation.
Current guidelines do not suggest considering blood pressure variability in the management of hypertensive patients. At the same time, a sufficient evidence base has been accumulated on the ...relationship of blood pressure variability with damage to target organs, the development of stroke, myocardial infarction, cardiovascular mortality, and kidney disease. In general, assessing the effect of blood pressure variability on the course of arterial hypertension, it can be assumed that it is not as significant as the absolute values of blood pressure, but this effect has been proven, regardless of the degree of hypertension. And if a practitioner finds an increased variability in blood pressure in his patient, he should know what recommendations should be given to him. Not all traditional lifestyle modification factors that are suggested for hypertensive patients affect blood pressure variability in the same way as blood pressure readings. Thus, we were unable to find evidence of the influence of increased consumption of table salt, physical activity, «chronic psychological stress» on the variability of blood pressure in the general population. At the same time, dietary habits, alcohol abuse, smoking status affect the level of blood pressure, blood pressure variability in both healthy individuals and patients with arterial hypertension. The same effect is exerted by the relative intake of minerals with food, toxic agents (lead). If in individuals of the general population an increase in body weight leads to an increase in blood pressure, then in patients with arterial hypertension such an effect is nonlinear, depending on the type of obesity. It should be emphasized once again that the presence of psychoemotional disorders symptoms of anxiety, depression – in patients with arterial hypertension contributes both to an increase in the level of blood pressure, but also to its variability.
The article presents a review of the literature on the role of myocardial fibrosis in the development of myocardial remodeling in patients with arterial hypertension. Information about the state of ...the structure and function of the extracellular matrix in health and disease is generalized. The characteristics of myocardial fibrosis biomarkers detection in the circulating blood are reflected.
The emergence of direct-acting antivirals (DAAs) has become the basis for a new potential treatment for chronic hepatitis C (CHC) in patients with decompensated cirrhosis, who previously had no other ...alternative than liver transplantation (LT). However, optimal timing of antiviral therapy (AVT) remains an issue.
Objective
: to present a spectrum of clinical outcomes in LT waitlisted patients with HCV-related cirrhosis, who received and did not receive DAA therapy.
Materials and methods
. Enrolled for the study were 49 waitlisted patients with HCV-related end-stage liver diseases. The patients were divided into 2 groups: Group 1 included 40 patients who received DAA therapy before LT, while Group 2 consisted of 9 patients who did not receive antiviral treatment while on the LT waiting list.
Results
. The sample was represented in most cases by patients who had MELD/Na score <20. Only six had MELD/Na score >20, but <25. At the time of analysis, 38 patients had reached 12 weeks post AVT. Of these, 35 (92.1%) had sustained virologic response (SVR). Of these, 51.4% (n = 18) of cases showed decreased MELD/Na. There were no changes in 22.9% (n = 8). Increased MELD/Na was noted in 25.7% (n = 9). In 42.8% (n = 15) of cases, sustained elimination of HCV infection led to delisting. Among patients without SVR, increased MELD/Na was observed in all cases (n = 3). In the non-AVT group, one patient showed improved liver function (11.1%); in the rest, MELD/Na either remained stable or continued to increase - 44.5% (n = 4). A comparison of the frequency of deaths depending on AVT showed statistically significant differences (p < 0.001, V = 0.728). Among the non-AVT patients, the likelihood of waitlist death increased 66.5 times (95% CI: 7.99-554).
Conclusion
: DAA therapy carries significant advantages for waitlisted patients with MELD/Na score <25.
Introduction
. Liver transplantation restores patients' physical and social life, and its quality. The prevalence of low physical activity in liver recipients is unknown as well as the impact of late ...liver allograft dysfunction on it. Liver transplantation enhances patient's return to the usual physical and social activity and improves the quality of life. However, the prevalence of low physical activity among liver recipients and the impact of the late allograft dysfunction on it, which is a risk factor for obesity and cardiovascular diseases, require studying.
The aim
of the study was to identify whether the late liver allograft dysfunction influences the physical activity of recipients.
Material and methods
. The study included 87 liver recipients. We measured anthropometric parameters, physical performance (SPPB, LFI, 6-min walk test), mean step count per day. Late liver allograft dysfunction was determined if elevated transaminases and/or cholestatic enzymes or hepatic failure have been diagnosed later than 3 months posttransplant. Activity trackers were provided to assess physical activity.
Results
. Median age was 54 years 45;61, 33% were men. The median follow-up period was 36 months 16;64. The median of the average steps count was 5.9 4.1;8.7 thousand per day. 60.5% of recipients were sedentary and low active, 24.4% were somewhat active, 15.1% were active. In cases of liver allograft dysfunction, the mean step count was significantly lower than in patients with normal liver function: 4.1 thousand 2.6;5.3 versus 6.8 thousand 4.2;9.4, p=0.003, despite no differences in the physical activity test results.
Conclusion
. In case of a late liver allograft dysfunction, the physical activity can decrease; 60.5% of liver recipients, in the absence of pathological restriction of movement, have a sedentary and low active lifestyle. Activity trackers may allow identifying patients who need additional check-up or physical training.
The aim was to study the molecular mechanisms of the violation of the structural and functional integrity ofthe blood-brain barrier in chronic neurodegeneration of the Alzheimer’s type associated ...with the development of cerebral angiopathy.Materials and methods. The transgenic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon,PSEN1 * M146L * L286V) 6799Vas group which includes 9 months aged males. The control group included C57BL / 6 x SJL mice, males aged 9 months.Results. The total length of the vessels in the area of the dentate gyrus is 2.5 times greater in transgenic animal models of Alzheimer’s disease than in animals of the control group (p < 0.01). The average diameter of blood vessels in all areas of the hippocampus is smaller compared with the control (p < 0.05). Transgenic modeling of neurodegeneration in the CA2 zone of the hippocampus increases the relative area of tissue with increased permeability of blood-brain barrier (BBB) (17.80 9.15; 36.75) compared to control (1.38 0.04; 7.60) at p < 0.05. A similar difference (p < 0.05) is also observed in the hippocampal area CA1. A tendency (p > 0.05) to decrease the number of CD31+ endothelial cells in the dentate gyrus of the hippocampus (21.52 17.56; 24.50) in animals of the experimental group compared with the control group (23.0821.18; 29.84) was detected. A similar situation is observed in the CA2 and CA3 areas of the hippocampus.Conclusion. Neurodegenerative changes in the hippocampus of animals with a transgenic AD model are associated with impaired microcirculation in the brain tissue as a result of a reduction in the diameter and branching of blood vessels, and damage and increased permeability of BBB.
Aging is accompanied by the triggering of numerous pathophysiological events, which include inflammation, cellular senescence and the development of the
senescence-associated secretory phenotype
...(SASP), altered glucose tolerance, and insulin resistance (IR). Neuroinflammation significantly contributes to the development of brain IR due to the activation of the multiprotein oligomeric complex, NLRP3 inflammasome. The aim of the present study was to explore the impairment of the mechanisms underlying insulin signaling and metabolic inflammation in the brain of aging C57BL/6 mice. We found that aging in these mice is accompanied by an increase both in the number of senescent cells in brain slices, as well as neuron–astrocyte co-culture, and in the expression of phosphorylated protein kinases PKR and IKKβ, metaflammasome components. Another metaflammasome component, whose expression increased in the hippocampus during aging, was IKKβ. We demonstrated that constitutive IKKβ activation is related with cell senescence and aging, as well as overactivation of the NLRP3 inflammasome and increased lactate production in aging mice. Changes in NLRP3 expression in the brain are reflected in changes in complex behaviors. Here, we documented the impairment of contextual memory, but not the acquisition process and cued memory, in aging mice. Nevertheless, aging in mice did not led to a change in the expression of insulin receptors, insulin receptor substrate 1 (IRS1phospho-S312), suggesting that during physiological aging, without signs of neurodegeneration (e.g., reactive astrogliosis), insulin signaling is not yet impaired, but the manifestations of metabolic inflammation are already observed. Thus, modulation of the activity of PKR and IKKβ metaflammasome components may represent a new pathogenetically substantiated strategy for managing the mechanisms of metabolic inflammation and SASP development in the brain, aimed at improving age-related cognitive dysfunctions.
Introduction. Impaired liver transplant function in the long term often leads to graft loss and the recipient death. There are many causes for the development of a late liver allograft dysfunction ...and different types of its clinical presentation, but there is no generally accepted definition. This hinders its timely diagnosis, analysis of its prevalence, and also makes it difficult to compare the performance of transplantation programs. Objective. To determine the clinical and prognostic value of late liver allograft dysfunction. Material and methods. The study included 103 cases of cadaveric liver transplantation from donors diagnosed with brain death to 100 recipients, of whom 36% were men, aged 48 years old (40;56) (18–68) at the time of transplant, having MELD score 17 (14;21) (7–41). The follow-up period was 52 months (20;77) (8–180). The cases where the graft loss occurred earlier than 3 months were excluded. The late liver allograft dysfunction was defined as a dysfunction of the transplanted liver, which was manifested by at least one of three following signs and occurred at more than 3 months after transplantation: 1) increased aspartate aminotransferase, alanine aminotransferase and/or gamma glutamyl transferase, alkaline phosphatase, bilirubin; 2) impaired synthetic function (increased international normalized ratio, decreased antithrombin III, cholinesterase); 3) liver cirrhosis complications (signs of portal hypertension, ascites, encephalopathy). The following limits were chosen as a diagnostic threshold for laboratory parameter abnormalities: more than 2 upper limits of normal for total bilirubin, more than 1.5 upper limits of normal for the levels of alanine or aspartic aminotransferases, more than 1.5 upper limits of normal for gamma-glutamyltransferase or alkaline phosphatase, more than 1.6 of normal for international normalized ratio. Results. Late liver allograft dysfunction was diagnosed at least once in 64% of recipients. Through the postoperative course, the proportion of patients with late dysfunction varied from 22% to 40%. The etiology of late liver allograft dysfunction was viral (38%), unknown (25%), biliary (19%), immune (17%), and vascular (1%). Late liver allograft dysfunction was reversible in 75% of cases, persistent in 17%, progressive in 8% of cases. Progressive late liver allograft dysfunction led to a graft loss in all cases observed. Recipients with late liver allograft dysfunction were found to have had a 33% higher incidence of early allograft dysfunction (OR 4.7, 95% CI 1.8–12.3); the incidence of biliary dysfunction was 3.1 times higher with distant choledochojejunostomy (OR 3.9, 95% CI 1.1–13.9); in patients with autoimmune and cholestatic disease, the incidence of immune dysfunction was 4.8 times higher (OR 5.8, 95% CI 1.7–20.3). Conclusion. The progressive nature of late liver allograft dysfunction negatively affects the results of transplantation and therefore should be considered as an indication for retransplantation. Reversible and persistent variants of late liver allograft dysfunction have favorable) prognosis. If the etiology of late dysfunction is not established, the regular surveillance with monitoring for fibrosis and repeated attempts to clarify the diagnosis should be continued.
The chemistry of naphthazarin derivatives Malinovskaya, G. V.; Chizhova, A. Ya; Anufriev, V. F.
Russian chemical bulletin,
05/1999, Letnik:
48, Številka:
5
Journal Article
It is known that mitochondrial dysfunction can be a trigger or a concomitant mechanism in the development of Alzheimer’s disease. It is also known that the restoration of intracellular mitochondrial ...activity of neurons and cerebral endotheliocytes is possible due to the transfer of intact mitochondria from other brain cells—in particular, astrocytes—and this transfer of mitochondria is mediated by the CD38 protein and functionally linked to it connexin 43 (Cx43). It follows that these molecules are promising for study both in relation to the mechanisms of development of neurodegeneration and in relation to the possible modulation of their activity for the correction of neurological deficits. The aim of this work was to study changes in the number of CD38- and Cx43-immunopositive cells in the neurovascular unit and the blood–brain barrier (BBB) of the brain in experimental Alzheimer’s disease. We have shown that the toxic effect of β-amyloid leads to a significant increase in the number of CD38- and Cx43-positive cells as in the hippocampus of animals in vivo, and as part of the BBB model in vitro. We have also shown that the cultivation of isolated astrocytes in the presence of β-amyloid leads to an increase in the content of Cx43 in cells and that the permeability of these half-channels significantly increases.
PDF
