Activation of Cardiac δ2-Opioid Receptors Increases Heart Tolerance to Reperfusion.

Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia.

The Role of δ2-Opioid Receptors in the Regulation of Tolerance of Isolated Cardiomyocytes to Hypoxia and Reoxygenation.

Hypoxia (20 min) and reoxygenation (30 min) were simulated on isolated rat cardiomyocytes to evaluate the cytoprotective effect of selective δ2-opioid receptor agonist deltorphin II, opioid receptor antagonist naloxone methiodide, µ-opioid receptor antagonist CTAP, κ-opioid receptor antagonist nor-binaltorphimine, ε1-opioid receptor antagonist BNTX, and δ2-opioid receptors naltriben. Deltorphin II was administered 5 min before reoxygenation, antagonists were administered 10 min before reoxygenation. The cytoprotective effect of deltorphin II was assessed by the number of cardiomyocytes survived after hypoxia/reoxygenation, as well as by the lactate dehydrogenase content in the incubation medium. It has been established that the cytoprotective effect of deltorphin II occurs at a concentration of 64 nmol/liter and is associated with activation of δ2-opioid receptors.

Comparative Analysis of Infarct-Limiting Activity of Peptide and Non-Peptide δ- and κ-Opioid Receptor Agonists during Heart Reperfusion In Vivo.

A comparative analysis of the infarct-limiting activity of δ- and κ-opioid receptors (OR) agonists was carried out on a model of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used selective δ2-OR agonist deltorphin II (0.12 mg/kg), δ-OR agonists BW373U86 and p-Cl-Phe DPDPE (0.1 and 1 mg/kg), selective agonists of δ1-OR DPDPE (0.1 and 0.969 mg/kg), κ1-OR U-50,488 (0.1 and 1 mg/kg), κ2-OR GR-89696 (0.1 mg/kg), and κ-OR ICI-199,441 (0.1 mg/kg). All drugs were administered intravenously 5 min before reperfusion. Deltorphin II, BW373U86 (1 mg/kg), p-Cl-Phe DPDPE (1 mg/kg), U-50,488 (1 mg/kg), and ICI-199,441 had a cardioprotective effect. The most promising compounds for drug development are ICI-199,441 and deltorphin II.

[Predicting the presence of MEN1 gene mutation based on the clinical phenotype of patients with primary hyperparathyroidism].

BACKGROUND: Timely referral of patients for genetic testing to rule out MEN1-associated primary PHPT is important factor in determining treatment strategy and prognosis. In the context of the limited availability of genetic testing, the search for clinical markers indicative of MEN1 gene mutations remains an extremely relevant task. AIM: To determine the diagnostic value of clinical features of primary PHPT in young patients for predicting the presence of MEN1 gene mutations. MATERIALS AND METHODS: A single-center, prospective study was conducted at the Endocrinology Research Centre, involving 273 patients with PHPT in the period 2015-2022. Based on the results of genetic and laboratory tests, patients were divided into three groups: those with MEN1 gene mutations (MEN+ group, n=71), those without MEN1 gene mutations - isolated sporadic PHPT (MEN- group, n=158), and patients with PHPT and associated endocrine gland disorders - MEN-1 syndrome phenocopies (PHEN group, n=32). Subgroups of patients younger than 40 years of age were also identified. Comparative analysis was performed among the independent groups and subgroups, and logistic regression analysis was used to develop a mathematical model for predicting the probability of the presence of MEN1 gene mutation. RESULTS: Patients in the MEN+ and MEN- groups were comparable by gender and age at manifestation, as well as calcium-phosphorus metabolism parameters and PHPT complications. In the PHEN group, PHPT manifested at older age compared to the other groups (p<0.001 for all), with lower total calcium levels and a trend toward lower iPTH concentrations. The MEN+ group had a significantly higher frequency of multiglandular parathyroid (PG) involvement, PHPT recurrence, and positive family history compared to the MEN- and PHEN groups. Histologically, adenomas predominated in the PHEN and MEN- groups (92% and 94%, respectively), whereas hyperplasia of PGs were more common in the MEN+ group (49%). None of the PHEN patients had all three «classic¼ components of the MEN-1 syndrome, and the clinical course of PHPT was similar to that of the MEN- group. These differences were also observed in the subgroups of patients younger than 40 years, which formed the basis for the development of a mathematical model. The logistic regression equation for predicting the probability of the presence of the MEN1 gene mutation included eight predictors, with a diagnostic sensitivity of 96% and specificity of 98%. CONCLUSION: Based on the analysis performed, eight hereditary predictors of PHPT within the MEN-1 syndrome were identified. A mathematical model was developed to predict the presence of the MEN1 gene mutation in patients, which demonstrated high classification performance on the training dataset. Further refinement of the model will help improve the quality of medical care for patients with PHPT.

[Non-ischemic priapism (post-traumatic arteriovenous fistula of the right cavernous body) in the background of Landusy-Dejerine myopathy].

Landouzy-Dejerine myopathy (Facial-shoulder-shoulder myodystrophy) is a disease which causes weakness of the muscles of the shoulder girdle, back and hip muscles, which predisposes patients to an increased risk of injury and disability. The article presents a clinical observation of non-ischemic priapism, which developed as a result of perineal trauma with the formation of a fistula of the right cavernous body in a patient against the background of facial shoulder-shoulder myodystrophy. Methods for the differential diagnosis of this condition are also discussed.

[Modern aspects of diagnostics and treatment of renal infarction].

One of the causes of acute kidney injury is the renal artery thrombosis. Clinical manifestations depend on the level of thrombus. This pathology is characterized by non-specific clinical manifestations in the early period, the complexity of differential diagnosis, often delayed verification of the diagnosis and unfavorable prognosis in case of prolonged (5-7 days) anuria. There is no generally accepted protocol for the diagnosis and treatment of renal artery thrombosis. To clarify the diagnosis, intravenous urography, radionuclide renography, and contrast-enhanced computed tomography are recommended. Until recently, patients with suspected renal artery thrombosis were treated with anticoagulant therapy and renal replacement therapy with hemodialysis, which is required constantly as renal function was usually irreversibly impaired. Surgical treatment is effective only in the first hours. The outcome is often unfavorable, the probability of hemorrhagic complications is high. Due to the rare frequency of detection and verification of renal infarction, no consensus has been reached regarding the diagnosis or treatment of this condition.

[Enoxaparin sodium for pharmacological prevention of postoperative venous thromboembolic complications in urological patients].

INTRODUCTION: Currently, there are paucity of reports on the success of medical prevention of venous thromboembolic complications after urological procedures. AIM: To evaluate the efficiency of enoxaparin sodium for prevention of postoperative venous thromboembolic complications in urological patients. MATERIALS AND METHODS: According to the medical records of 151 men and women aged 22 to 92 years old who were undergone to elective surgical treatment in April 2021, the results of the thrombin generation assay and ultrasound study of the inferior vena cava were retrospectively analyzed. All patients were divided into 6 study groups depending on the degree of risk of postoperative venous thromboembolism (very low, low, moderate, high, very high and extremely high). The data obtained during the thrombin generation assay in patients from different groups were compared with those in healthy volunteers (n=30, control group) and evaluated in dynamics. In addition, intergroup comparison was done. RESULTS: All study participants prior to surgery had a significant increase in peak thrombin and endogenous thrombin potential (ETP) by 5-26% and 13.5-21.5%, respectively. The postoperative findings were as following: 1) one hour after the procedure, a significant (by 9-28.6%) decrease in the normal bleeding time (Lag time); 2) a significant increase in the peak thrombin by 4.8-10.6% 1 hour after surgery and by 11-40.2% at the end of the first postoperative week; 3) reducing the time to peak thrombin (ttPeak) by 13-15%; 4) increase in ETP. According to the ultrasonic data, all study participants had no signs of thrombosis of the inferior vena cava system. CONCLUSION: In urological patients requiring surgical treatment, before and after procedure, there is almost always a shift in the hemostasis towards the predominance of the blood coagulation system. Under such conditions, to prevent the development of postoperative VTE, it is expedient and pathogenetically justified to use enoxaparin sodium in a single dose of 0.4 ml or 4000 anti-Xa IU administered once a day s/c 24 hours before the procedure and till full activation of a patient.

Effect of the "door-to-balloon" time on the results of treatment of patients with ST-segment elevation myocardial infarction, depending on the duration of the pre-hospital delay.

Aim    To analyze the effect of the door-to-balloon time on treatment outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) depending on the duration of pre-hospital delay.Material ad methods    The study used data of the hospital registry of percutaneous coronary interventions (PCI) in STEMI from 2006 through 2017. The analysis included 1333 patients. All patients were divided into two groups. The first group included 574 (43.1%) patients with the time from the pain syndrome onset to admission was ≤120 min. The second group consisted of 759 (56.9 %) patients with the time of pre-hospital delay exceeding 120 min. Results of the treatment were analyzed for each group depending on the door-to-balloon time, ≤60 min or >60 min.Results    In the group of patients with the prehospital delay less than 120 min and the door-to-balloon time ≤60 min vs. patients with the door-to-balloon time >60 min, the following was observed: decreased in-hospital mortality (1.3 % vs. 6.8 %, p=0.001), reduced incidence of major adverse cardiac effects (МАСЕ) (3.2 % vs. 8.3 %, p=0.008), and reduced incidence of the no-reflow phenomenon (3.9 % vs. 9.4 %, p=0.007). Also, immediate angiographic success of PCI was more frequently achieved in these patents (94.5 % vs. 87.5 %, p=0.003). In addition, in the group with the prehospital delay ≤120 min and the door-to-balloon time ≤60 min, a higher ejection fraction was noted at discharge from the hospital (48 [43; 51] % vs. 46 [42; 51] %, р=0.038). Comparison of treatment outcomes between the groups with different door-to-balloon time (≤60 min or >60 min) and a prehospital delay >120 min did not show any significant intergroup differences. According to a multivariate analysis, the door-to-balloon time ≤60 min did not predict in-hospital mortality. There was a strong correlation between the time of prehospital delay and the total time of myocardial ischemia (r=0.87; р<0.001) while the correlation between the door-to-balloon time and the total time of myocardial ischemia was moderate (r=0.41; р<0.001). At the same time, there was no correlation between the time of prehospital delay and the door-to-balloon time.Conclusion    In STEMI patients with a prehospital delay less than 120 min from the pain syndrome onset, a decrease in the door-to-balloon time was associated with better outcome of the hospital treatment. When the duration of prehospital delay was more than 120 min, a decrease in door-to-balloon time did not influence the treatment outcome. The time of prehospital delay strongly correlated with the total time of myocardial ischemia.

[Features of the intestinal microbiota in the elderly in the development of coronary heart disease.]

The review is devoted to the influence of the microbiota on the development of such an age-dependent disease as coronary heart disease, the formation of which depends on atherogenesis in particular. According to the World Health Organization, cardiovascular disease is the leading cause of death worldwide. Statistical data from the Federal State Statistics Service also confirm that coronary heart disease is the leading cause of death in the Russian Federation today. It is known that the vast majority of cardiovascular diseases are atherosclerosis-associated pathologies. Atherogenesis and the state of the human gut microbiome are dynamically interrelated. The gut microbiota, which consists predominantly of bacteria, plays an important role in maintaining homeostasis. The pathogenesis of atherosclerosis is based on systemic inflammation. Aging is accompanied by a wide variety of clinical manifestations, including a basic pro-inflammatory state (i.e., «inflammation-aging¼), the activity of which is maintained by the microbiota in older individuals and increases their susceptibility to diseases. Intestinal microbiocenosis in elderly and senile people differs from those of young people. In persons of older age groups, there is an increase in microorganisms secreting endotoxins lipopolysaccharide and trimethylamine-n-oxide, initiating and maintaining chronic inflammation. More research is needed to study the mechanisms of action of microbial metabolites and their clinical application in various therapeutic interventions.

Role of PI3K, ERK1/2, and JAK2 Kinases in the Cardioprotective Effect of Deltorphin II during Cardiac Reperfusion.

The signaling mechanism of the cardioprotective effect of deltorphin II was studied in models of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used the selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg), which was administered intravenously 5 min before reperfusion, the PI3K inhibitor wortmannin (0.025 mg/kg), the ERK1/2 blocker PD-098059 (0.5 mg/kg), the inhibitor JAK2 AG490 (3 mg/kg). All kinase blockers were administered 10 min before reperfusion. The infarct-limiting effect of deltorphin II is associated with the activation of PI3K and ERK1/2 and does not depend on JAK2.

The Role of NO Synthase, MPT pore, and Protein Kinase A in the Cardioprotective Effect of the Opioid Receptor Agonist Deltorphin II.

In male Wistar rats, coronary occlusion (45 min) and reperfusion (120 min) were modeled. Selective δ2-opioid receptor agonist (deltorphin II, 0.12 mg/kg) was administered intravenously 5 min before reperfusion; NO synthase inhibitor (L-NAME, 10 mg/kg), MPT pore blocker (atractyloside, 5 mg/kg), and protein kinase A inhibitor (H-89, 10 µg/kg) were administered intravenously 10 min before reperfusion. Deltorphin II administered before reperfusion led to a 2-fold decrease in the infarct size. The infarct-limiting effect of deltorphin II was associated with blockade of MPT pore. Protein kinase A and NO synthase were not involved in the cardioprotective effect of deltorphin II.

Interstitial Edema of the Interatrial Septum in Patients with Atrial Fibrillation and Chronic Heart Failure.

We studied the presence of interstitial edema of the interatrial septum in patients with chronic heart failure (CHF) with atrial fibrillation (n=23) or without rhythm disturbances (n=9). The intensity of the MRI signal of the interatrial septum, interventricular septum, and skeletal muscle by T2-weighted MRI and the enhancement index of interatrial septum (the ratio of the signal intensity of the interatrial septum to the signal intensity of the skeletal muscle) were evaluated. The enhancement index of interatrial septum ⩾2 was regarded as an MRI sign of myocardial edema. The enhancement index of interatrial septum in patients with persistent atrial fibrillation was 2.4 (2.21; 2.69) and was higher than in CHF patients with paroxysmal atrial fibrillation and in CHF patients without arrhythmias and surpassed the control values (p<0.05), which indicates the presence of MRI signs of edema of the myocardium of the interatrial septum. The obtained data confirm the presence of myocardial edema of the interatrial septum in CHF patients and persistent form of atrial fibrillation, which expands the understanding of the pathogenesis of this condition.

[Gastroprotective and antidepressant-like effect of plum pectin (Prunus domestica L.) under water-immobilization stress in laboratory mice].

Stress effects activate the processes of free radical oxidation in the organism, lead to hyper production of reactive radicals and oxidative stress, provoking the development of an inflammatory process in various parts of the gastrointestinal tract. Pectin polysaccharides together with the enzyme components of the endogenous antioxidant system contribute to the elimination of the imbalance between prooxidants and antioxidants in the tissues of stressed animals and have a gastroprotective and antidepressant-like effect. The aim of the research was to evaluate the gastroprotective, antioxidant and antidepressant-like effect of plum pectin orally administered to white laboratory mice before stressful exposure. Material and methods. In the experiment on white BALB/c mice weighing 20-25 g (90 males, 10 in each group), pectin isolated from fresh plum fruits in an artificial gastric environment was used. It was administered orally to mice 24 h before the onset of stress exposure or behavioral activity asessment. 50 animals were subjected to 5 h of water immersion stress. After this corticosterone concentration in blood plasma, and the activity of superoxide dismutase, catalase and glutathione peroxidase in the tissue supernatants of the gastrointestinal tract were determined, and the condition of the gastric mucosa was also assessed. Behavioral activity of experimental mice (n=30) was assessed in the open field and forced swimming tests. Results. The stress effect was accompanied by an increase in plasma corticosterone concentration (more than 3 fold), in the activity of superoxide dismutase, glutathione peroxidase in the tissues of the stomach wall and small intestine (17.9-28.6%) and destructive damage in the gastric mucosa compared with the indices of intact animals. Preliminary oral administration of plum pectin to animals at a dose of 80 mg per 1 kg of body weight helped to reduce the level of corticosterone and the number of stress-induced hemorrhages on the gastric mucosa, normalized the activity of antioxidant enzymes and also decreased the immobility time of mice in the forced swimming test. Preliminary oral administration of plum pectin to animals at a dose of 80 mg per 1 kg of body weight prevented an increase in the activity of antioxidant enzymes, corticosterone in the blood and the development of stress-induced hemorrhages on the gastric mucosa, and reduced the time of immobility of mice in the forced swimming test. Conclusion. Plum fruit pectin pre-administered into mice before stress prevents stress-induced damage in the tissues of the gastrointestinal tract, contributing to an increase in the body's resistance to the stress factor. Plum pectin has an antioxidant, gastroprotective and antidepressant-like effect and can be used as an ingredient in functional foods that reduce the risk of inflammatory diseases of the gastrointestinal tract under stress.

[High-tone therapy in complex rehabilitation of patients with post-sternotomy syndrome after coronary artery bypass surgery. (Open-label, prospective, randomized controlled trial)]. / Vysokotonovaya terapiya v kompleksnoi reabilitatsii bol'nykh s poststernotomicheskim sindromom posle aortokoronarnogo shuntirovaniya. (Otkrytoe prospektivnoe randomizirovannoe kontroliruemoe issledovanie).

INTRODUCTION: At present it remains relevant to develop new rehabilitation technologies for patients with circulatory system diseases who have undergone a cardiac surgery to restore the functions of the cardiorespiratory system more quickly, improve physical and mental health, and prevent the development of the atherosclerotic process. AIM: To study the effectiveness and safety of the new rehabilitation technology for the inpatient stage of medical rehabilitation of patients with post-sternotomy syndrome after coronary artery bypass surgery (CABS) using high-tone therapy. MATERIAL AND METHODS: The study included 85 men (the average age was 56.8±2.46 years old) with post-sternotomy syndrome after CABS. They were divided into two groups by simple randomization: the first/main (42 patients) and the second/control (43 patients). The control group of the patients had a standard rehabilitation complex; the main group was additionally prescribed a high-tone therapy according to a local method. The immediate results of the treatment were assessed by the dynamics of the clinical picture, the six-minute walk test, respiratory function, echocardiography, the level of cytokines, C-reactive protein and natriuretic peptide (NT-proBNP); distant - by QOL endpoints (questionnaire MOS SF-36). RESULTS: The groups of the patients were comparable in all baseline parameters. After the course of the procedures in the main group of patients there were positive reliable (p<0.05-0.001) shifts in clinical (pain, shortness of breath, general weakness), functional (forced expiratory vital capacity, forced expiratory volume1, effusion separation) and laboratory parameters (leukocytes, interleukin-2 and 10, NT-proBNP). The intergroup analysis of long-term results registered significant (p<0.05) differences in the QOL of patients in the main group by subscales: the role of somatic problems, vitality and mental health. Compliance to the III stage of medical rehabilitation (outpatient/home) was noted with 95.2% of the patients in the first group and 93.0% in the second. CONCLUSION: The additional appointment of a high-tone therapy to the rehabilitation standard for the patients with post-sternotomy syndrome after CABS significantly improves the immediate and long-term results of the treatment (QOL) contributing to a more pronounced reverse development of inflammatory and edematous syndromes, an increase in physical activity and psychosomatic health. The absence of adverse reactions with all the patients indicates the safety of rehabilitation complexes.

[Complete atrioventricular block as the first manifestation of dermatomyositis].

Dermatomyositis is a rare systemic autoimmune disease characterized by primary damage of the skin and striated muscles with the development of chronic muscle weakness. Due to the polymorphic nature of the clinical picture, early diagnosis of dermatomyositis is challenging since patients may visit different specialists depending on predominating symptoms. This entails a late diagnosis and, as a result, the absence of necessary treatment. The article presents a clinical case of a late diagnosis of dermatomyositis, which resulted in the development of autoimmune myocarditis with complete atrioventricular block in a female patient.

[Comparative study of the influense of stone size and volume on the duration of thulium laser percutaneous nephrolithotripsy].

OBJECTIVE: The aim of the investigation was to determine the influence of such parametric characteristics of the stone such as size and volume on the duration of tulium laser disintegration of the urinary stone and to determine which of these parameters is more effective to use like prognostic criterion for the duration of the planned surgical intervention in the percutaneous nephrolithotripsy. MATERIALS AND METHODS: Overall 52 patients (27 females and 25 males) with an average age of 56,9 (25-79) years participated in the present study. All patients underwent percutaneous nephrolithotripsy with disintegration of the kidney stone by thulium energy. Inclusion criteria were: stone size more or equal 2 cm, stone density >1100 HU. Exclusion criteria were: patients with a single kidney, urinary tract divertions, coagulopathy. The average operation time was 30 (15-100) minutes, with an average puncture time of 3.15 (1-10) minutes and lithotripsy time of 28 (14-98) minutes. To determine the volume we used the method of automatic lithometry according to CT data using the software: Vitrea ver. 4.1.52. The size of the stone was determined by the longest length in one of the plane. During the study it was found that the average size of the stone was 28.25 (20-58) mm and the average volume was 2579.4 (250-9990) mm3. To confirm our assumption, we decided to determine the dependence of the time of disintegration of the stone on the size and volume of the stone. For this purpose, we graphically presented the correlation of these parameters. RESULTS: We have drawn 2 graphs reflecting the dependence of lithotripsy time parameters on the size and volume characteristics of the stone. As a result of comparing these parameters we found that size is a prognostically less reliable predictor of lithotripsy time, and is not characterized by a linear distribution, in contrast to the stone volume. CONCLUSIONS: Thereby, the main stereoscopic characteristic of a stone is a volume, which should be the primary guide in selecting the preferred method of treatment as well as in predicting the operative time and associated risks.

Efficacy and Safety of Anticoagulant Therapy in Patients With Various Forms of Atrial Fibrillation After Interventional Treatment. Results of a Three-Year Follow-up.

Aim      To evaluate efficacy and safety of the anticoagulant therapy in patients with atrial fibrillation (AF) during a 36-month follow-up after an interventional treatment.Material and methods  This study included 302 patients aged 29 to 81 years with various forms of AF. Catheter ablation (CA) of AF foci was performed for all patients. The patients were divided into 3 groups: group 1 with paroxysmal AF, group 2 with persistent AF, and group 3 with longstanding persistent AF. Two subgroups were isolated in each group, with effective and ineffective CA. Results of the follow-up were analyzed at 12, 24, and 36 months after discharge from the hospital. The follow-up interview recorded complaints of palpitation attacks, effectiveness of administered CA, compliance with the treatment, adverse clinical outcomes, including thromboembolic complications (TEC), bleeding, and hospitalizations.Results Efficacy of the interventional treatment for 36 months was 65.3 % in patients with paroxysmal AF, 59.7 % in patients with persistent AF, and 57.1 % in patients with longstanding persistent AF. Patients with paroxysmal AF and effective CA had no adverse events throughout the same period during the antithrombotic treatment (ATT). In contrast, the group with ineffective ablation had both TEC and hemorrhagic complications during the ATT. In the group with persistent AF and effective CA throughout the follow-up period, TECs were less frequent than in the group of ineffective ablations during the ATT treatment. Patients with longstanding persistent AF and effective CA throughout the follow-up period, had no TECs in contrast to patients with ineffective ablation during the ATT treatment. There were no fatal outcomes in patients with effective procedure.Conclusion      A successful CA procedure for AF provides a significant decrease in the risk of ischemic stroke. Furthermore, the invasive strategy does not increase the risk of major and minor bleedings.

δ2-Opioid Receptors as a Target in Designing New Cardioprotective Drugs: the Role of Protein Kinase C, AMPK, and Sarcolemmal KATP Channels.

In rats anesthetized with α-chloralose, coronary artery occlusion (45 min) and reperfusion (120 min) were modeled. The selective δ2-opioid receptor agonist deltorphin II was administered 5 min before reperfusion. Protein kinase C inhibitor chelerythrine, AMP-activated protein kinase inhibitor compound C, and ATP-sensitive K+ channel blockers glibenclamide, 5-hydroxydecanoate, and HMR 1098 were administered 10 min before reperfusion. It was found that the infarct-limiting effect of deltorphin II is associated with activation of protein kinase C and opening of sarcolemmal ATP-sensitive K+ channel.

[Evaluation of the results of sodium fumarate, furosemide, and mannitol on the initiation and outcome of renal warm ischemia in an experimental study].

While performing surgical treatment of the localized form of renal cell cancer by means of open or laparoscopic partial nephrectomy, renal warm ischemia is an important issue. Using renal warm ischemia allows to prevent parenchymal bleeding, to optimize conditions for resection of the tumor and to increase significantly the efficiency of hemostasis. However, an important problem is the probability of ischemic hypoxic damage of the remaining part of the kidney tissue during renal warm ischemia and renal functional impairment in the postoperative period. AIM: To compare nephroprotective activity of sodium fumarate, mannitol and furosemide using experimental model of 30- and 60-minute renal warm ischemia in rabbits. MATERIALS AND METHODS: The experiments were carried out on 360 conventional male-rabbits of the "Chinchilla" breed weighed 2,6+/-0,3 kg which were allocated into 10 groups. The control group No1 included intact animals, the control group No2 included the rabbits in which renal artery was not clamped. For the animals from the trial groups (No3-No10) the experimental model of 30- and 60-minute renal warm ischemia was used. In groups No3 and No4 no drugs were provided. Other rabbits undergone renal warm ischemia with a protection by sodium fumarate (groups No5 and No6 - 1,5 ml/kg IV), lasix (groups No7 and No8 - 3,0 mg/kg IV) and mannitol (No9 and No10 - 1,0 g/kg IV). The influence of renal warm ischemia on the renal tissue ultrastructure and the levels of NGAL, Cystatin-C and creatinine in blood and urine were studied. RESULTS: During experimental pharmacologically uncorrected 30-minute renal warm ischemia in animals, edema of the terminal part of microvilli of the proximal tubules epithelium, an increase of lysosome number in the hyaloplasm of epithelial cells, appearance of flaky content of medium electronic density in the lumens of distal tubules and collecting tubules, as well as sharp peak-like increase of NGAL and cystatin-C in blood and urine were observed. Increasing the time of ischemia up to 60 minutes was accompanied by more severe disturbances. In groups where sodium fumarate, lasix and mannitol were used the observed ultrastructural disturbances were expressed to lesser extent, whereas sodium fumarate demonstrated the best nephroprotective activity. After using mannitol the severity of disturbances was less than in the groups where mannitol, lasix or sodium fumarate were not given. Lasix and sodium salt of fumaric acid showed a higher nephroprotective activity. The best results were received in the animals received sodium fumarate. CONCLUSIONS: The studied drugs provided a nephroprotective effect regarding ischemia of rabbit kidney. The effect of sodium fumarate was the most pronounced, followed by furosemide and, to a lesser extent, mannitol. Use of sodium fumarate allows to protect and stimulate the kidney tissue effectively during oxygen deprivation under ischemic state.

Parameters of Oxidative Stress and Activity of Antioxidant Enzymes in the Saliva of Patients with Type 1 Diabetes Mellitus.

Glucose concentration in the saliva is increased in type 1 diabetes mellitus. This parameter directly correlates with markers of the disease in the blood serum. Increased concentration of 8-oxo-2'-deoxyguanosine (8-OHdG) and diene conjugates, markers of oxidative stress, and reduced activities of superoxide dismutase and catalase were also observed in this pathology. Correlation analysis revealed a strong positive correlation between glucose concentration and the levels of oxidative stress markers and a negative correlation between activity of antioxidant enzymes and glucose concentration. The results indicate that the level of 8-OHdG, diene conjugates, and superoxide dismutase and catalase activities can serve as diagnostic markers of pathophysiological changes in the body in type 1 diabetes mellitus.