Skeletal Muscle Microvascular Dysfunction in Obesity-Related Insulin Resistance: Pathophysiological Mechanisms and Therapeutic Perspectives

Obesity is a worrisomely escalating public health problem globally and one of the leading causes of morbidity and mortality from noncommunicable disease. The epidemiological link between obesity and a broad spectrum of cardiometabolic disorders has been well documented; however, the underlying pathophysiological mechanisms are only partially understood, and effective treatment options remain scarce. Given its critical role in glucose metabolism, skeletal muscle has increasingly become a focus of attention in understanding the mechanisms of impaired insulin function in obesity and the associated metabolic sequalae. We examined the current evidence on the relationship between microvascular dysfunction and insulin resistance in obesity. A growing body of evidence suggest an intimate and reciprocal relationship between skeletal muscle microvascular and glucometabolic physiology. The obesity phenotype is characterized by structural and functional changes in the skeletal muscle microcirculation which contribute to insulin dysfunction and disturbed glucose homeostasis. Several interconnected etiologic molecular mechanisms have been suggested, including endothelial dysfunction by several factors, extracellular matrix remodelling, and induction of oxidative stress and the immunoinflammatory phenotype. We further correlated currently available pharmacological agents that have deductive therapeutic relevance to the explored pathophysiological mechanisms, highlighting a potential clinical perspective in obesity treatment.

The optimal modeling method of specific tuberculosis peritonitis (experimental research)

The objective: to create a reproducible model of chronic tuberculosis peritonitis to study pathophysiological mechanisms of its progression and to develop pathogenetically based therapy.Subjects and Methods. The study was performed using 10 male rabbits of the Chinchilla breed. The animals were administered intraperitoneal culture of Mycobacterium tuberculosis, tuberculosis peritonitis modeling was performed according to the proposed method.Results. In the course of the experiment, it was proved that all animals developed tuberculous peritonitis with lesions of the large omentum and serous integuments of internal organs. Molecular genetic tests of fragments of the omentum and peritoneum detected DNA of Mycobacterium tuberculosis.

Long COVID (Medline OVID - text word).

Literature review on the epidemiology and pathophysiology of long COVID: How can long COVID be defined? How frequent is it? What are the most common symptoms? Which are the risk factors? What are the underlying pathophysiological mechanisms?

Anaphylactic shock in children and adolescents

Modern views about the various causes of the development of anaphylactic shock in children and adolescents, the classification of anaphylactic shock based on the pathophysiological mechanisms of the development are observed in the survey. The algorithm of the diagnosis of anaphylaxis and anaphylactic shock, the emergency assistance and further management of patients with anaphylactic shock, as well as the issues of its prevention are presented.

Pathophysiological Mechanisms of Hypertension Development Induced by Fructose Consumption

During the past several decades, there has been a dramatic increase in fructose consumption worldwide in parallel with epidemics of metabolic diseases. Accumulating evidence has suggested that excessive fructose consumption...

Impaired endogenous neurosteroid signaling contributes to behavioral deficits associated with chronic stress

Chronic stress is a major risk factor for psychiatric illnesses, including depression; however, the pathophysiological mechanisms whereby stress leads to mood disorders remain unclear. The recent FDA approval of antidepressants with novel mechanisms of action, like Zulresso®, a synthetic neuroactive steroid analog with molecular pharmacology similar to allopregnanolone, has spurred interest in new therapeutic targets and, potentially, novel pathophysiological mechanisms for depression. Allopregnanolone acts as a positive allosteric modulator of GABAA receptors (GABAARs), acting preferentially at δ subunit-containing receptors (δ-GABAARs). Accumulating clinical and preclinical evidence supports the antidepressant effects of exogenous administration of allopregnanolone and allopregnanolone analogs; however, the role of endogenous neurosteroids in the pathophysiology of depression remains unknown. Here, we examine whether altered neurosteroid signaling may contribute to behavioral deficits following chronic unpredictable stress (CUS) in mice. We first identified reductions in expression of δ-GABAARs, the predominant site of action of 5a-reduced neuroactive steroids, following CUS. Additionally, utilizing LC-MS/MS we discovered a decrease in levels of allopregnanolone in the BLA, but not plasma of mice following CUS, an indication of impaired neurosteroid synthesis. CRISPR knockdown the rate-limiting enzymes involved in allopregnanolone synthesis, 5α-reductase type 1 and 2, in the BLA mimicked the behavioral deficits associated with CUS in mice. Furthermore, overexpression expression of 5α-reductase type 1 and 2 in the BLA improved behavioral outcomes. Collectively, this suggests chronic stress impairs endogenous neurosteroid signaling in the BLA which is sufficient to induce behavioral deficits similar to those observed following CUS. Further, these studies suggest that the therapeutic efficacy of allopregnanolone-based treatments may be due to their ability to directly target the underlying pathophysiology of mood disorders. Therefore, targeting endogenous neurosteroidogenesis may offer a novel therapeutic strategy for the treatment of mood disorders.

Stasis Ulcers – The Unifying Concept

Chronic stasis dermatitis, usually confined to the lower legs, is a complication of longstanding interstitial edema and inflammation, due either to venous hypertension or disorders having in common excessive lymph overload. Heart failure, renal failure, liver cirrhosis, secondary and primary diseases of lymph vessels may complicate with stasis dermatitis. The same mechanisms causing stasis dermatitis can also generate skin ulcers superimposed on stasis dermatitis. In the appropriate context such skin ulcers are called "venous ulcers" or, in different situations, “stasis ulcers”. The distinction between venous and other stasis ulcers is usually possible at the bedside. Also, some general measures of therapy are similar for venous and other stasis ulcers: such are elastic compression, topical skin care and ulcer care. In having in common the pathophysiological mechanisms, in bearing clinical resemblance, and responding to similar therapies, a unifying concept may be opportune to comprise the spectrum of stasis dermatitis, venous and other stasis ulcers. The present work is an appeal to this aim.

Cytokine intoxication as a model of cell apoptosis and predict of schizophrenia - like affective disorders

For a long time there was no explanation of a study which had revealed that people with schizoaffective disorders and in particular suicidal attempts rarely get cancer. But now, we can assume that there are diseases that are “mirrored” because they occur with reverse/feedback pathophysiological mechanisms so that they are, in fact, antagonists.