According to the theory of inflammaging, aging of the body and the development of age-related diseases are a consequence of a chronic progressive generalized inflammatory process that develops and persists throughout life under the influence of negative factors of an infectious and non-infectious nature. Inflammaging has a number of features that distinguish it from acute inflammation: a chronic nature of inflammation, a low level of inflammation, blurry clinical state (in the early stages of clinical manifestations there may not be any at all). The key pathogenetic role in inflammation plays age-associated changes in the innate immune system, which are referred to in the English literature as “immunosenescence” and oxidative stress. The main source of reactive oxygen species and free radicals in the cells are mitochondria. With age, the concentration of intracellular glutathione, one of the main factors of the antioxidant protection of the cell, decreases and a pathological condition arises in which the rate of production of free radicals and reactive oxygen species significantly exceeds the antioxidant capabilities, which leads to the formation of oxidative stress and disruption of the structure and function of cells. Oxidative stress, inflammation and neuroinflammation are closely related to cognitive impairment, pathological state that is often observed in a group of elderly and senile patients. Further study of the pathogenesis of Inflammaging and the role of oxidative stress in it will potentially lead to development of methods to slow down aging and treat age-related cognitive impairments.
Drug-induced liver injury (DILI) is a fairly frequent adverse drug reaction, which accounts for about half (40–50 %) of cases of acute liver damage. The cholestatic variant of DILI is characterized by an increase in the activity of alkaline phosphatase (ALP) above the two upper limits of the norm (ULN) or the ratio of alanine aminotransferase (ALT) / ALP ≤ 2 in chronic course. A common cause of the cholestatic variant of DILI is a use of drugs for the treatment of infectious diseases, such as beta-lactam antibiotics, Aminoglycosides, Amphenicol, Lincosamides, macrolides, fluoroquinolones, antituberculosis drugs, etc. This problem has acquired particular urgency during the COVID-19 pandemic. The widespread use of azithromycin, hydroxychloroquine, interferons, lopinavir, and other drugs for the treatment of COVID-19 also contributed to an increase in the incidence of DILI. In accordance with clinical guidelines in case of suspicion of a drug-induced liver damage, one should stop use of suspected drug and, if necessary, prescribe hepatoprotectors, for example, ursodeoxycholic acid (UDCA). The effectiveness of the use of UDCA in patients with DILI, including those caused by the intake of antibacterial drugs, has been confirmed by randomized placebo-controlled clinical trials. The effectiveness of UDCA -drug Ursosan® has been confirmed in real life clinical practice. This drug can be used for long-term (up to several months), or lifelong treatment with hepatotoxic drugs like antituberculosis and antirheumatic drugs. The daily dose of Ursosan® is 12–15 mg/kg, if necessary – 20 mg / kg (with a weight of a patient about 75–100 kg, daily dose will be equal to two tablets of Ursosan Forte®, 500 mg).
Clinical practice and ongoing scientific research in recent years show the importance of the problem of multimorbidity in atrial fibrillation (AF). The prevalence of AF in the general population is 1–2%, while the frequency of its occurrence increases with age – from less than 0.5% at the age of 40–50 to 5–15% at the age of 80. Only 19.6% of patients with AF have no comorbidities, 69.3% of patients have 1 to 3 comorbidities, and 11.1% of patients with AF had 4 and more comorbidities. In patients with AF and with 4 and more comorbidities, the risk of death from all causes is almost seven times higher than in patients without comorbidities. As shown by the post hoc analysis of the ARISTOTLE study, apixaban was equally effective and safe in both patients without concomitant pathology and in muliborbid patients. The efficacy and safety of apixaban has been shown in AF and concomitant arterial hypertension, heart failure, coronary heart disease, including in patients with acute coronary syndrome, diabetes mellitus, chronic kidney disease and chronic obstructive pulmonary disease. The data of scientific research in recent years are reflected in the recommendations of the Ministry of Health of the Russian Federation on AF (2020), which presents a separate section on the management of patients with concomitant diseases. It is emphasized that apixaban has shown its superiority over warfarin and other direct oral anticoagulants in terms of efficacy and safety, both in isolated AF and in patients with concomitant diseases, which makes its choice preferable in the treatment of multimirbidity AF patients.
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