CORRELATIVE ASSOCIATION OF OXYGENATION AND SEPSIS PANELS WITH THE USE OF ACE2 INHIBITORS AND WITHOUT IT IN THE CONDITIONS OF SEPTIC SHOCK IN COVID-19-INFECTED AND NON-INFECTED PATIENTS (COHORT STUDY).

Sepsis-associated hyperlactatemia (SAHL), Lactic acidosis, is a common problem in critically ill patients. The prevalence of Lactic acidosis is estimated to be approximately 1% of all hospitalized nonsurgical patients. The purpose of our study was to reveal possible associations between the level of Lactate with sepsis biomarkers: PCT, IL 6, and PO2 in the presence of ACE 2 inhibitors in Covid-19 infected and non-infected patients with Septic Shock. We conducted a cohort study, comparing outcomes of 212 critically ill patients with Septic shock, who were treated in the intensive care unit of First University Clinic of Tbilisi State Medical University during the 2020-2021 years. Inclusion criteria for the study were: Age>40ys; COVID-19 and other respiratory diseases associated with Septic shock, with respiration dysfunctions with prior exposure to ACE2 inhibitors o no history of treatment with the ACE2 inhibitors. Patients enrolled in the study were individuals who were diagnosed with COVID-19 infection and septic shock, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors; patients with septic shock who were not infected with COVID-19, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors. According to lactate level, the studied patients were divided into subgroups: lactate <3 mMol/l, and lactate > 3 mmol/l. In patients with septic shock who were not infected with COVID-19 the main Causative microorganisms were gram-negative bacteria. In patients' blood the Interleukin-6 (IL-6), lactate, procalcitonin (PCT), pO2, and pulmonary pressure were investigated. Results of the study show that the rise in lactate levels in COVID-19-infected and non-infected patients was accompanied by an increase in PCT content and a decrease in pO2 level in blood. Therefore, serum lactate levels can be used as a prognostic marker of the severity of septic shock in COVID-19-infected and noninfected patients. In COVID-19-infected patients together with the increased lactate level, increases the level of IL-6, which indicates the important link between the quality of immunological disorders, inflammation, and COVID-19 infection in patients with ARDS and sepsis. These alterations were not prevented by the prior use of the ACE2 inhibitors. In COVID-19-infected and noninfected patients who didn't use ACE2 inhibitors, high lactate levels were accompanied by decreased pulmonary pressure which was normalized in patients who prior used ACE2 inhibitors.

IMPACT OF THE ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS ON THE COURSE OF THE SEPTIC SHOCK DEVELOPED DURING COVID-19 AND OTHER SEVERE RESPIRATORY INFECTIONS IN PRESENCE OF HYPERFERRITINEMIA.

SARS-CoV-2 can cause sepsis regardless of the presence of secondary bacterial or fungal infections. The virus itself likely causes sepsis through a variety of possible mechanisms, including immune dysregulation, with respiratory dysfunction, which as a result of circulatory dysfunction leads to hypoxemia and metabolic acidosis. We conducted cohort study, comparing outcomes of 212 critically ill patients with Septic shock (134 men (63.3%) and 78 women (36.7%), with a mean age between 40-70 years) were evaluated, who were treated in the intensive care unit of First University Clinic during 2020-2021 years. All four groups had documented Hyperferritinemia (HF). Patients were divided according to ferritin concentrations: moderate HF (ferritin <1500ng/ml) and severe HF (ferritin >1500ng/ml). The study aimed to reveal the impact of the Angiotensin-Converting enzyme -2 (ACE2) inhibitors on the course of the Septic shock developed during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF). Study results show that severe HF in patients with Septic shock is associated with a high risk of mortality and can be considered an indicator of the severity of the disease. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock: ACE2 inhibitors reduce the levels of Ang II and C reactive protein (CRP) in the blood in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate and severe HF; regulate the activity of leukocytes and the blood pro-coagulation system in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate HF; reduce the expression of pro-inflammatory cytokines (IL-6), decrease the level of D dimer in СOVID-infected patients in conditions of moderate HF; Procalcitonin levels do not differ between COVID-19 infected and non-infected patients with Septic shock. Based on our study, we can assume that there is the important link between elevated Ang 2 and the quality of immunological disorders and inflammation. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock.

THE ROLE OF ANGIOTENSIN -2 IN THE PATHOGENESIS OF SEPTIC SHOCK DURING MULTIORGAN DYSFUNCTION SYNDROME (REVIEW).

Septic shock is an acute pathophysiological condition characterized by vasodilation, hypotension, decreased circulating blood volume, tissue hypoxia, organ failure, and high lethality. The causes of septic vasodilation, which can lead to vascular smooth muscle dysfunction or selective vasomotor imbalance, remain controversial. In septic vasodilation, optimal pharmacological intervention is needed. Expected vascular response to shock when various vasoconstrictors are used, requires further study of the therapeutic potential of these agents. Because of all the above, it is of great interest to study and compare the therapeutic effects of angiotensin-2 and already used catecholamine and non-catecholamine vasoconstrictors in the treatment of septic shock. Angiotensin 2, approved by the FDA in 2018, is the newest available vasopressor for the treatment of vasodilatory shock. In the setting of high-dose vasopressors, exogenously administered synthetic angiotensin 2 significantly improved mean arterial pressure, decreased background vasopressor dose, and lowered sequential organ failure assessment scores in patients with refractory septic shock, In the review, the role of angiotensin-2 and its correlation with markers of sepsis for adequate management of septic shock-induced multiorgan dysfunction and arterial hypotension with ACE inhibitors is evaluated.

[COMPARATIVE EVALUATION OF THE TREATMENT OF VASOMOTOR RHINITIS IN PATIENTS WITH AND WITHOUT COVID-19 INFECTION].

The aim of our study was to evaluate the effectiveness of treatment with the local antihistamine medicine Palada NS in patients with vasomotor rhinitis who have had COVID-19 infection (6 months after transfer) and have not. The diagnosis of vasomotor rhinitis was made on the basis of subjective (sneezing frequency, degree of difficulty in nasal breathing, nature, consistency, color of nasal discharge, as well as color of swelling of the nasal mucosa and turbinates, impaired olfactory function, general condition of the patient) and objective (anterior and posterior rhinoscopy, endoscopy, rhinomanometry) examination.Patients in both groups were treated with Palladium NS for 10 days (2 sprays, 2 times a day for 10 days). All studies were performed in patients before, 3-5 days after, and at the end of the treatment. The effectiveness of treatment was assessed according to patients' subjective complaints and objective indicators of instrumental examination. Symptoms before and after treatment were assessed on a 3-point scale. A positive result of treatment was revealed in the majority of patients. Which manifested itself in a decrease in the number of subjective and objective complaints. In patients who did not undergo COVID-19 infection, the subjective and objective indicators' improvement was revealed as early as on the 5th day of treatment, in patients with vasomotor rhinitis who underwent COVID-19 at least 6 months ago, the improvement was recorded only by the end of treatment. Based on the results of our studies, the proposed treatment regimen for vasomotor rhinitis with the local antihistamine medicine Palada NS can be recommended for patients with vasomotor rhinitis, both with and without COVID-19 infection.

LIPOMATOUS HYPERTROPHY OF THE INTERATRIAL SEPTUM - A BENIGN HEART ANOMALY CAUSING UNEXPECTED PROBLEM IN ELECTROPHYSIOLOGY (CASE REPORT).

Lipomatous Hypertrophy of the Interatrial Septum (LHIS) is an unusual and benign condition characterized by the excessive deposition of adipose tissue in the interatrial septum, which is most often detected as an incidental finding on echocardiography. The classic finding is a homogenous, bi-lobed configuration of the interatrial septum with sparing of the fossa ovalis. LHIS has been associated with various atrial arrhythmias, including multifocal atrial tachycardia, multiple premature atrial contractions, atrial fibrillation and rarely sudden death. The prevalence of LHIS is estimated to be between 1-8%. The incidence increases with age, body mass and chronic corticosteroid therapy. There may be a higher incidence in women. Here the authors describe a case report of a 73 year-old obese female who visited the cardiology department for planned cryoablation of paroxysmal atrial fibrillation. Difficulties raised during transseptal punction, a bidimensional tranthoracic echocardiography (TTE) showed the typical findings of LHIS. A 73 year-old asymptomatic woman was found to have an incidental cardiac mass, TTE findings were consistent with lipomatous hypertrophy of the interatrial septum. Given the characteristic appearance on TTE, biopsy or surgery was not indicated, the procedure of cryoablation has been stopped and the patient was managed conservatively.

THE PECULIARITY OF COVID- 19 GENOME AND THE CORONAVIRUS RNA TRANSLATION PROCESS AS APOTENTIAL TARGET FOR ETIOTROPIC MEDICATIONSWITH ADENINE AND OTHER NUCLEOTIDE ANALOGUES (REVIEW).

Despite the multifaceted effects of the medicines provided for COVID-19treatment, the number of the infected and mortality of patients increases which demonstrates the insufficient effectiveness of drugs used to fight coronavirus infections in medical practice, and clearly shows the need to develop new treatment tactics.In this review article are summarized and analyzed the literature data concerning specific features of COVID 19. Particular attention is given to genetic characteristic of this virus ,to mechanism of its invasion into the human organism, replication and interection with ACE-2 receptors ,as well as to the basic targets for the action of existing drugs with antiviral activity against COVID-19. Currently, the following medications are used to treat COVID-19: remdesivir, chloroquine, hydroxychloroquine (HCQ), ribavirin, lopinavir/ritonavir. According to a recent theory of coronavirus treatment, the starting point for the mechanism of action of a potential etiotropic drug is the inhibition of the coronavirus main protease (Mpro/3CLpro) and the papain-like protease (PLpro). Among the drugs listed above, lopinavir acts through this mechanism but is characterized by severe side effects.It is emphasized that remdesivir as adenosine analog provides inhibitory action on RNA dependent RNA-Polymerase,but there are controversial views about reduction in mortality during using of this drug against COVID-19. The present paper discusses the mechanism of action of a potential etiotropic drug against coronavirus, which implies the replacement of the nucleotides involved in the process of translation of the virus with their analogs with the aim to "inhibit" the ribosome and block the production of viral proteins.

SEPSIS: IMPORTANCE OF ETHNIC PROPERTIES AND PHENOTYPES (REVIEW).

Sepsis is a common and potentially lethal syndrome. Its global prevalence is rising during last decades, which is related to older population, comorbidities, such as diabetes, malignancies and increased numbers of interventions. Currently there is no specific treatment for sepsis. Lethal outcome is depending under several factors, such as site of infections, infectious agent, severity of sepsis, organ dysfunction, age, sex, social and economic factors, race and ethnicity. Severe sepsis is related to about 30% of lethality but outcome is not always predictable according to severity of sepsis. This paradox can be explained on basis of genetic, ethnic, race and phenotype properties of patient. Influence of these factors on sepsis outcome is not yet properly investigated. Future studies are needed for definition of correlation between different race, nation, genetic and phenotype properties and on this basis will be possible the development of more effective personal treatment of septic patients.

MANAGEMENT OF MEDIASTINAL-ABSCESS-INDUCED SEPSIS AND SEPTIC SHOCK (CLINICAL CASE REPORT).

Infection of the mediastinum is typically polymicrobial in nature resulting from a disruption of normal mucosal and tissue barriers. Infection may result from a rupture of the esophagus or trachea or from surgical intervention. Medaistinal abscess is the most lethal form of mediastinitis. A case report is presented: sepsis - induced polyorganic insufficiency with underlying severe somatic pathological condition and violation of hemodynamics. Clinically the insufficiency of all the organic systems developed at the background of cardio-respiratory-cerebral insufficiency, with functional insufficiency of all the organ systems and violation of buffer system. With reasonable pathognomic and symptomatic treatment eradication of vicious circle was possible. The patient was discharged from the clinic with positive clinical-laboratory recovery. The condition was stable. Neurological status -contacted, adequate, with high capacity to work. The fistula on the anterior wall of the trachea as well as stoma were removed.

VERY LATE STENT THROMBOSIS 2 YEARS AFTER IMPLANTATION OF A DRUG-ELUTING STENT (CASE REPORT).

A serious long-term complication of drug-eluting stent (DES) implantation is the occurrence of very late stent thrombosis (VLST) beyond 1 year after implantation. While VLST has been observed as late as 1 year following the initial procedure, it remains unknown whether DES thrombosis is a finite phenomenon that abates over time or is a risk that persists indefinitely. Very late stent thrombosis is an infrequent yet potentially fatal complication associated with drug-eluting stents. We report the case of a 40-year-old man who sustained an ST-segment-elevation myocardial infarction 2 years after initial paclitaxel-eluting stent implantation. Focal incomplete endothelialization of the stent struts is the likely cause of VLST; neointimal formation, neoatherosclerosis, and late stent malapposition might also have contributed. According to the current guidelines 12 months of dual antiplatelet therapy (DAPT) is recommended following DES implantation. However, there are uncertainties surrounding the optimal duration of dual antiplatelet therapy in patients who suffer from drug-eluting very late stent thrombosis. Clinicians face challenges in treating these patients, particularly when competing medical demands necessitate the discontinuation of dual antiplatelet therapy.

CORRELATION OF RED BLOOD FACTORS IN POLYTRAUMA INDUCED SEPSIS AND SEPTIC SHOCK PATIENTS.

In polytrauma induced sepsis/septic shock patients, early verification and diagnosing anemia, is an important factor for the outcome of pathology. The purpose of our study was: to study the dynamic correlation of the red blood markers and inflammatory indicators. We consider that knowing these mechanisms will be helpful in the management/treatment method selection and in making prognosis of the final outcomes of polytrauma induced sepsis /septic shock patients. The purpose of our study was to study the characteristic dynamic correlations of polytrauma induced red blood and inflammation indicators. The abovementioned information will play an important and crucial role in the management of hypoxemic changes in different types of anemia. The red blood markers and inflammatory indicators dynamic correlations were studied in 21 Polytrauma induced Septic Shock patients during the first 45 days after hospital admission. Pearson Scheme was used for data analysis. All the patients were adults and were treated by the International Guidelines for Management of Severe Sepsis and Septic Shock, considering the bacterial spectrum. In the initial period of polytrauma injury, the deficit of red blood markers was a result of trauma induced hemorrhage and sequential surgical interventions. The dynamic reduce in red blood markers were in negative correlation with the elevation of systematic inflammatory factors, indicating polytrauma induced septic complication. In the period of reconvalescence, the concentration of red blood markers was normalizing, in negative correlation with the specific inflammatory factors. Our study revealed, that non-specific inflammatory marker, like fibrinogen is in strong correlation with the tissue oxygenation. Also the study demonstrated the correlation of Oxymetric parameters with the inflammatory factor metabolites. In particular, the elevation of fibrinogen concentration is in positive correlation with the tissue oxygenation quality.

THE ROLE OF PROCALCITONIN AND BLOOD LACTIC ACID VALUES IN PROGNOSIS OF SEPSIS AND SEPTIC SHOCK IN POLYTRAUMA PATIENTS.

Recently, the role of biomarkers to assist in the diagnosis and management of infections has been extensively explored. Based on the studies, Procalcitonin and Blood Lactic Acid can provide supportive data to clinical assessment in Polytrauma induced infectious pathology prevention, early evaluation, management of complications and predicting outcomes. We studied the cases of 21 patients who developed Polytrauma induced Sepsis/Septic shock during different stages of hospitalization. We intended to study the dynamic level changes of Procalcitonin and Blood Lactic Acid in terms of Sepsis/Septic shock - induced by different types of trauma, in survived patients. At the initial stage Blood Lactate level in polytrauma patients was high, which was dynamically normalized after starting optimization of ventilation/oxygen therapy. It was totally different in case of Biomarker Procalcitonin. So we monitored the dynamic changes of it and made the correlation between the other factors/indicators. The data was registered during the first 45 days after the admission in the ICU (intensive care unit), as all the patients who survived during this period of time had good outcome. In order to see the dynamic changes, the levels of biomarkers were measured in every 5 days and were studied using Pearson correlation scheme. The study revealed that normalization of Blood Lactic Acid is in positive correlation with reconvalescence. Procalcitonin is an indicator of illness progression severity. It has strong positive correlation with White Blood Cells (WBC) and C-reactive protein (CRP) and negative correlation with Lymphocytes (LYM). In cases of Polytrauma induced sepsis or septic shock, the level started to increase within first 72 hours after traumatic injury, pick concentration was achieved within first 25 days high from the beginning and dynamically increases within first 25 days, the tendency of gradual decrease was seen after 30 days. C - reactive protein as a nonspecific indicator of severity in pathology progression, was manifested with high levels first, followed by the procalcitonin level changes. The systematic inflammation factors, like the number of Leukocytes and Lymphocytes, concentration of C-reactive protein are in correlation with procalcitonin and can play a significant role in early evaluation and management of polytrauma induced Sepsis and Septic Shock.

RECENT PRINCIPLES OF ANTIMICROBIAL TREATMENT IN POLYTRAUMA INDUCED SEPSIS AND SEPTIC SHOCK (REVIEW).

20% of trauma deaths occur late after the injury. It is usually the result of sepsis, multi-system organ failure, or other complications. In Polytrauma induced sepsis and septic shock patients, antibacterial management is crucial. The knowledge of recent aspects of treatment is decreasing the costs and the resistance of pathogens, morbidity and mortality. Different models of treatment are suggested by authors, basically they are depended on: the patients age, there health condition, the factors of immunodeficiency, at the location of infection and others. Using the key words, the search engines produced articles. The review was made on the studies about Polytrauma induced sepsis and septic shock patients, about their antimicrobial treatment dosage and duration, about the source control and about the methods of early identification of pathogens (Bacteria and Candida). The advantages and disadvantages of early identification were also studied. Also the role if biomarkers were also reviewed. Based on the review, recommendations are given about the recent principles of antibacterial treatment of Polytrauma induced sepsis and septic shock patients.

DYSFUNCTION OF VARIOUS ORGAN SYSTEMS INDUCED BY SEPSIS WITH UNDERLYING SEVERE MYELOMIC DISEASES AND PROSTATE CANCER (CASE REPORT).

A 65-year-old male patient, unconscious, was admitted into the clinic by the Ambulance. From the patient's medical history it was revealed that several hours before the admission in the clinic the following symptoms were present: shortness of breath, fever, hypotonia, consciousness inhibition, because of which emergency brigade was called and was brought by the Emergency Brigade. The history is loaded by chronic pathologies: myeloma disease, prostate cancer, ciliary arrhythmia, heart failure; received several courses of polichemotherapy, last ten days has been treated for pneumonia with antibiotics of ceftriaxone group in outpatient setting. It is also noteworthy that for the last three months dysfunction of musculoskeletal system with muscle weakness, restricted motion has been present. Clinically there was present dysfunction syndrome of several organs: disorder of function of several organs that required emergency intervention, recovery chance was very low, correlation with morbidity in PIRO was high. By investigation it is known, that as SIRS aggravates, and turns into septic shock, lethal index increases, especially when the underlying severe diseases are present. On basis of certain data we can conclude that the severity of the disease may have some compatibility with results, although it is alteration of further clinical status of initial stage that has the closest compatibility with results. Sepsis toward MODS experiences progress with lethal results. Mortality rate in the patients with acute respiratory deficiency increases from 50% to 80%. In most patients with sepsis syndrome, who have 3 or more organs damaged, lethality is more than 90%. In this certain case organ systems that are mostly involved in the process during the sepsis, are respiratory, blood, renal and cardiovascular systems, were all involved , in the mentioned case a reasonable symptomatic and pathognomic treatment and the appropriate measures led to the recovery of the above mentioned patient. Sepsis syndrome is developed when the balance between the substances that contribute to the inflammation and anti-inflammatory substances is violated. By the mentioned case there is sepsis - induced polyorganic insufficiency with underlying severe somatic pathological condition, with violation of hemodynamics. Clinically the insufficiency of all the organic systems developed at the background of cardio-respiratory-cerebral insufficiency, with functional insufficiency of all the organ systems and violation of buffer system. With reasonable pathognomic and symptomatic treatment eradication of vicious circle was possible. The patient was discharged from the clinic with positive clinic-laboratory recovery. The condition is stable. Neurological status -contact, adequate, with high capacity to work, and with an achievement of 2 year remission.

ALTERED MICROCIRCULATION IN SEPTIC SHOCK.

Retrospective data analysis of microcirculation in septic shock was conducted. Sepsis is characterized by a severe microvascular dysfunction that persists despite fluid resuscitation and leads to multi-organ failure even after normalization of hemodynamics in response to fluid resuscitation, vasopressors and the treatment of infection. Several clinical studies suggest that microcirculatory alterations in severe sepsis are stronger predictors of outcome than global hemodynamic variables. Microvascular dysfunction under septic shock is related to: increased capillary permeability that manifests as a breakdown of the microvascular endothelial barrier (factors which may contribute to capillary leak syndrome include endogenous proinflammatory cytokines, angiopoietin 2, vascular endothelial growth factor); arteriolar hyporesponsiveness to vasoconstrictors and vasodilators, the loss of adrenergic sensitivity and tone of smooth muscle cells lining the arterioles; loss of the anti-adhesive function of endothelial surfaces; decreased density of perfused capillaries (due to several contributing factors: decreased deformability of erythrocytes and neutrophils; activation of the clotting cascade with fibrin deposition and the formation of microthrombi; dysfunction of vascular autoregulatory mechanisms by nitric oxide; enhanced functional arteriovenous shunting of the microcirculation).

Vasoplegia in septic shock (review).

Vasoplegia is considered as a key factor responsible for the death of patients with septic shock, due to persistent and irreversible hypotension. The latter associated with vascular hyporeactivity to vasoconstrictors is a significant independent prognostic factor of mortality in severe sepsis. Loss of control of the vascular tone occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators. The aim of this review is to discuss in detail the recent suggested alternative mechanisms of vasoplegia in severe sepsis: Overproduction of nitric oxide (NO) by activation of inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; significantly elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) during septic shock and their involvement in vascular dysfunction. The review also discusses some therapeutic approaches based on pathogenetic mechanisms of severe sepsis and their efficacy in treatment of patients with septic shock. The loss of vascular tone control occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators in the pathogenesis of septic shock. Overproduction of nitric oxide (NO) by the inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) and their involvement in vascular dysfunction - all these factors combined together lead to steady refractory shock with the lethal outcome in patients.

Myocardial dysfunction during septic shock (review).

Patients with septic shock frequently develop myocardial dysfunction evidenced by severely depressed ejection fraction with ventricular dilatation, as measured by an increase in mean systolic and end diastolic ventricular volumes. The pathophysiology of myocardial dysfunction is complex and involves a multitude of factors. The current review describes individual contributing factors and mechanisms such as upregulation of proinflammatory cytokines (IL-1, TNFα, IL-2, IL-6, IFN-γ), reduced myocardial responsiveness to ß-adrenergic stimulation, elevated circulating endothelin levels, Impaired calcium uptake and release from calcium sarcoplasmic reticulum storage, and decreased calcium channel sensitivity, overexpression of inducible NOS and increased production of Nitric oxide. We also discuss possible reasons for apparently detrimental effect of NO inhibition on cardiovascular function in large clinical trials with sepsis patients.

Peculiarities of cardiovascular disease in women.

In a review article peculiarities of cardiovascular disease among women are considered. The analysis of published data showed that cardiovascular disease (CVD) is common in women. Gender-specific risk factors include oral contraceptives and menopause. Clinical manifestations, major causes of various forms of cardiovascular disease in women are revealed. It was found that women most often than men have coronary micro vascular disease - X Syndrome, which affects the tiny coronary arteries. Coronary microvascular dysfunction is prevalent in women with chest pain. There is a greater prevalence of no coronary causes of chest pain in the female population, and chest pain is frequently accompanied by abdominal pain, dyspnea, nausea, fatigue, and greater functional disability. Women tend to suffer from more single vessel and two-vessel disease as opposed to the three-vessel disease seen more often in men. It is concluded that specific research is required to identify risk factors of cardiovascular disease in women in Georgia.

Some aspects of pathogenesis of nonalcoholic fatty liver disease in postmenopausal women.

In view of the reversibility of steatosis and steatohepatitis, their early diagnosis is one of the most significant problems of modern medicine. The aim of the study was the establishment futures of the pathogenesis of NAFLD in postmenopausal women. The study was conducted on postmenopausal women (n=5), with metabolic syndrome and rate of ALT in the blood at least 4 times greater than its normal maximal value. Patients had to fulfill the following inclusion criteria: at least 12 month of amenorrhea. Verification of the diagnosis of NAFLD was based on abdominal ultrosonografic examination. In addition to collecting history, study of blood lipid profile and ALT, AST, estrogen content in patients enrolled in the study free nitric oxide content in the blood and liver bioptants was determined by Electron Paramagnetic Resonance (EPR) method. The study protocol approved by the Ethics Committee of the Tbilisi State Medical University. Patients by written form confirmed their agreement to participate in the study. In patients with NAFLD levels of total cholesterol, LDL-cholesterol and triglycerides were generally increased in the blood serum, direct correlation revealed between level of NO EPR signal intensity in liver bioptat and triglycerides content in blood (r=0,96; p=0,009). It was concluded that estrogen-dependent factors, such as impaired lipid metabolism and increase expression of iNOS induce accumulation of triglycerides and free fatty acids in the liver, generation excess amounts of NO, which in oxidative stress reveal their cytotoxity and promote progression of NAFLD in postmenopausal women.

The role of estrogens in pathogenesis of age-related arterial hypertension.

Several factors are contributing to menopausal hypertensión; the role of estrogens in patogénesis of hypertensión in menopausal women have not completely established. The aim of the present investigation was to study some aspects of the role of estrogens in the pathogenesis of hypertension during menopause. 93 women with hypertension, who are referred to the Central Clinic of Tbilisi State Medical University (Georgia) during 2009-2011 were investigated. Women were divided into 2 groups: 1 - reproducvtive age group (43 patients); 2 - menopause age group (50 patients). In each group we investigated estradiole, oxygen (O2-), lipid (LOO.) reactive species, NO and endotheline content and antioxidant enzymes (SOD, catalase, GR) activity. The results of study reveal increased of superoxide - and lipoperoxide - radicals, as well as of endothelin сontent in blood of menopausal women, while concentration of free nitric oxide decreased; at the same time activity of catalase increased (by 50%), GR reduced significantly (by 38%) and SOD's activity didn't change in comparision to reproductive aged group. Negative correlation between the HbNO and estradiole content in blood of reproductive aged women was established (r=-0,60, p=0.03); no dependence between these two parameters in menopausal aged women was revealed (r=-0, 29, p=0,12). It was concluded, that in women of reproductive age probability and risk of hypertension grows in the presence of additional risk factors, such as oxidative stress and/or fluctuations in estrogen's level towards insufficiency, which leads to reduction of nitric oxide content due to its oxidative transformation in peroxinitrite, or enhanced inclusion in HbNO complexes, whereas development of hypertension in postmenopausal women may develop by different mechanisms, might including inflammation.

Antiinflammatory activity of lymphomyosot during chronic deseases.

UNLABELLED: Every pathology generally refers to an inadequate response to the influence brought by endo- and exotoxins, which is carried out via natural compensative and protective pathways of the body. Scientific conception of bioregulative therapy and homotoxicology implies treatment by modulation of own protective mechanisms and neutralization of already existing toxins. This endo- and exogenic homotoxins influence on the development of various immune responses of immunocompetent cells. Lymphomyosot, a complex nutural detoxifier drug, providing the effective detoxication of extracellular matrix via lymphatic system. As a huge amount of immunocompetent cells are located in the lymphatic system are, regulation of their immune responses by Lymphomyosot is very the essence of the treatment applicable to different chronic pathologies. AIM: determining of dose-dependent immunomodulating activity of Lymphomyosot on T lymphocytes modelled system of Jurkat cells. The modelled systems of Jurkat cells, incubated under moderate oxidative stress conditions inherent chronic inflammatory processes, and stimulated with mytogene Phytohemaglutinine (PHA) was used. Effectiveness of Lypmhomyosot was studied by regulatory capacity of the cells bioviability (MTT test) immunological activity (cytokine expression, respiratory burst) and of mytogene-induced apoptosis intensity of Jurkat cells. Lymphomyosot shows antioxidant effect and dose-dependent immunomodulatory activity. Lymphomyosot, as anti-inflammatory, recovering agent is effective for profilactic aims. Low (therapeutic) doses of lymphomyosot are effective for the treatment of.