Pathogenic Role of Proinflammatory Cytokines in the Development of Chronic Cerebral Ischemia

Aim: to evaluate the efficacy and safety of the L-lysine escinate venotropic drug in the treatment of cephalgic, atactic and asthenic syndromes in patients with chronic cerebral ischemia, mainly caused by venous disorders. Patients and Methods: the study involved 60 patients with a diagnosis of chronic cerebral ischemia with signs of chronic venous insufficiency. All patients were randomly divided into two groups consisting of 30 people. Patients in the main group received L-lysine escinate, and the control group received Vinpocetine. The drugs were administered by intravenous drip for 10 days. A dynamic assessment was performed using a modified subjective scale of asthenia evaluation (MFI-20), 100 mm long visual analogue scale (VAS) for headache, subjective neurological impairment scale (SNIS), and Tinetti test. An ophthalmic examination with an assessment of the fundus vessels and an ultrasound duplex scanning of head vessels (veins) were also conducted. Results: it was shown that L-lysine escinate therapy showed a statistically more significant reduction in the severity of headache (according to VAS) and an improved stability measured by Tinetti test versus during Vinpocetine treatment. There were no significant differences in the level of asthenia (MFI-20), the severity of emotional disorders, and the SNIS score. Also, the number of patients with dilated fundus veins significantly decreased during treatment in the main group (p<0.05), which was not the case in the control group. According to ultrasound duplex scanning data, the venous flow velocity through the veins of Rosenthal and angular veins during L-lysine escinate therapy was significantly higher (p<0.05) than in patients receiving Vinpocetine. Conclusion: the inclusion of vasotropic drugs (in particular, the L-lysine escinate venotonic drug) in the treatment regimen of patients with chronic brain ischemia seems appropriate, especially if there are signs of venous insufficiency. KEYWORDS: systemic venous insufficiency, chronic cerebrovascular disease, venous dyscirculation, glymphatic system, L-lysine escinate, Vinpocetine. FOR CITATION: Schukin I.A., Fidler M.S., Koltsov I.A. Chronic cerebrovascular disease: the role of venous disorders and the possibility of pathogenetic correction. Russian Medical Inquiry. 2020;4(9):544–551. DOI: 10.32364/2587-6821-2020-4-9-544-551.

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Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00209.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. G115-G122 ◽

Cited By ~ 7

Author(s):

Vatsalya Vatsalya ◽

Maiying Kong ◽

Leila Gobejishvili ◽

Wei-Yang Chen ◽

Sanjay Srivastava ◽

...

Keyword(s):

Cell Death ◽

Liver Disease ◽

Proinflammatory Cytokines ◽

Alcoholic Hepatitis ◽

Pathogenic Role ◽

Cytokeratin 18 ◽

Acute Alcoholic Hepatitis ◽

Noninvasive Biomarker ◽

Liver Cell Death

Alcohol-associated liver disease (ALD) remains a major health concern worldwide. Alcohol consumption gives rise to reactive/toxic acrolein, a pathogenic mediator of liver injury in experimental ALD. Elevated acrolein adducts and metabolites are detectable in blood and urine. This study evaluates the major urinary acrolein metabolite, 3-hydroxypropylmercapturic acid (HPMA), in patients with acute alcoholic hepatitis (AAH) and examines its association with disease severity and markers of hepatic inflammation and injury. Urine HPMA was significantly higher in patients with severe [model for end-stage liver disease (MELD) ≥ 20] AAH compared with nonsevere AAH (MELD ≤ 19) or non-alcohol-consuming controls, suggesting that urine HPMA is a novel noninvasive biomarker in severe AAH. The association between HPMA and MELD in patients with AAH was nonlinear. In patients with nonsevere AAH, there was a positive trend, although not significant, whereas in severe AAH the association was negative, indicative of extensive injury and glutathione depletion. Consistent with the multifactorial etiology of ALD, our data identified strong combined effects of HPMA and proinflammatory cytokines on hepatocyte cell death, thereby supporting the pathogenic role of acrolein in liver injury. HPMA, together with IL-1β, showed robust associations with cytokeratin 18 caspase-cleaved fragment (CK18-M30; adjusted R2 = 0.812, P = 0.016) and cytokeratin 18 full-length protein (CK18-M65; adjusted R2 = 0.670, P = 0.048); similarly, HPMA, with IL-8, correlated with CK18-M30 (adjusted R2 = 0.875, P = 0.007) and CK18-M65 (adjusted R2 = 0.831, P = 0.013). The apoptosis index (CK18-M30:CK18-M65 ratio) strongly correlated with HPMA, together with IL-1β (adjusted R2 = 0.777, P = 0.022) or tumor necrosis factor-α (TNFα; adjusted R2 = 0.677, P = 0.046). In patients with severe AAH, IL-1β, IL-8, and TNFα are the predominant proinflammatory cytokines that interact with HPMA and play important mediating roles in influencing the extent/pattern of liver cell death. NEW & NOTEWORTHY This is the first study to examine the urinary acrolein metabolite 3-hydroxypropylmercapturic acid (HPMA) in alcoholic liver disease. HPMA was higher in patients with severe acute alcoholic hepatitis (AAH) compared with controls or nonsevere AAH and may be a novel selective, noninvasive biomarker for severe AAH. Consistent with the multifactorial etiology of alcohol-associated liver disease, we identified strong combined effects of HPMA and proinflammatory cytokines (IL-1β, IL-8, and TNFα) on the extent/pattern of liver cell death, thereby supporting the pathogenic role of acrolein.

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The Role of Neurotrophic Protein S100 in the Pathogenesis of the Chronic Cerebral Ischemia Development

European Psychiatry ◽

10.1016/s0924-9338(15)31206-2 ◽

2015 ◽

Vol 30 ◽

pp. 1561

Author(s):

D. Usmanova

Keyword(s):

Cerebral Ischemia ◽

Chronic Cerebral Ischemia

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Use of brain slices in the study of pathogenic role of inducible nitric oxide synthase in cerebral ischemia-reperfusion

General Pharmacology The Vascular System ◽

10.1016/s0306-3623(98)00280-8 ◽

1999 ◽

Vol 32 (5) ◽

pp. 577-581 ◽

Cited By ~ 14

Author(s):

J De Alba ◽

A Cárdenas ◽

M.A Moro ◽

J.C Leza ◽

P Lorenzo ◽

...

Keyword(s):

Nitric Oxide ◽

Cerebral Ischemia ◽

Inducible Nitric Oxide Synthase ◽

Ischemia Reperfusion ◽

Brain Slices ◽

Pathogenic Role ◽

Cerebral Ischemia Reperfusion ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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The Role of Stress-Protective Therapy in the Course of Chronic Cerebral Ischemia

Sovremennye tehnologii v medicine ◽

10.17691/stm2015.7.3.14 ◽

2015 ◽

Vol 7 (3) ◽

pp. 95-102

Author(s):

E.A. Antipenko ◽

M.Y. Maksimova ◽

P.A. Soldatov

Keyword(s):

Cerebral Ischemia ◽

Chronic Cerebral Ischemia

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An Update on the Pathogenic Role of Macrophages in Adult-Onset Still’s Disease and Its Implication in Clinical Manifestations and Novel Therapeutics

Journal of Immunology Research ◽

10.1155/2021/8998358 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Po-Ku Chen ◽

Der-Yuan Chen

Keyword(s):

Proinflammatory Cytokines ◽

Macrophage Activation ◽

Clinical Manifestations ◽

Innate Immune ◽

Adult Onset Still’S Disease ◽

Pathogenic Role ◽

Novel Therapeutics ◽

Molecular Patterns ◽

Adult Onset Still's Disease

Increasing evidence indicates a pivotal role of macrophages in innate immunity, which contributes to the pathogenesis of adult-onset Still’s disease (AOSD). Despite the available reviews that summarized the pathogenic role of proinflammatory cytokines in AOSD, a systematic approach focusing on the crucial role of macrophages in this disease is still lacking. This review summarizes the updated functions of macrophages in AOSD and their implication in clinical manifestations and therapeutics. We searched the MEDLINE database using the PubMed interface and reviewed the English-language literature as of 31 March 2021, from 1971 to 2021. We focus on the existing evidence on the pathogenic role of macrophages in AOSD and its implication in clinical characteristics and novel therapeutics. AOSD is an autoinflammatory disease mainly driven by the innate immune response. Among the innate immune responses, macrophage activation is a hallmark of AOSD pathogenesis. The pattern recognition receptors (PRRs) on macrophages recognize pathogen-associated molecular patterns and damage-associated molecular patterns and subsequently cause overproduction of proinflammatory cytokines and recruit adaptive immunity. Some biomarkers, such as ferritin and gasdermin D, reflecting macrophage activation were elevated and correlated with AOSD activity. Given that macrophage activation with the overproduction of proinflammatory cytokines plays a pathogenic role in AOSD, these inflammatory mediators would be the therapeutic targets. Accordingly, the inhibitors to interleukin- (IL-) 1, IL-6, and IL-18 have been shown to be effective in AOSD treatment. Gaining insights into the pathogenic role of macrophages in AOSD can aid in identifying disease biomarkers and therapeutic agents for this disease.

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Function and role of system enzyme therapy in rehabilitation of patients with acute and chronic cerebral ischemia

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2008-5-1-135-140 ◽

2008 ◽

Vol 7 (5-1) ◽

pp. 135-140

Author(s):

V. V. Yefremov ◽

Yu. I. Sternin ◽

V. S. Sergienko

Keyword(s):

Cerebral Ischemia ◽

Serum Concentration ◽

Blood Serum ◽

Control Group ◽

Enzyme Therapy ◽

Chronic Cerebral Ischemia ◽

Tnf Α ◽

Complex Therapy ◽

Main Effects

Main effects of system enzyme therapy (SET) are antiinflammatory, fibrinolythic and immunomodulating. Combination of these effects proved to be important in the treatment of 30 patients with stroke and 30 patients with ischemic cerebrovascular diseas. The use of polyfermental preparation flogenzyme in complex therapy allowed to normalize the state of thrombocytic hemostasis and to improve the indexes of plasmatic hemostasis and rheology of blood, serum concentration of proinflamatory cytokines (TNF-α, IL-1β, IL-4) to a considerably greater degree than in control group (39 patients) and impaired velocity and reactivity parameters (33 control). Thus, SET medications are necessary and very important pathogenetically in the complex therapy of patients with acute and chronic cerebral ischemia.

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