APPLICATION OF GALVANOENTEROSORPTION IN MULTIMODAL TREATMENT OF PATIENTS WITH THERMAL BURNS

Aim – to investigate the influence of enterosorption and its combination with intra-tissue electrophoresis (ITE) of antibacterial preparations on the proteolytic and fibrinolytic activity of blood plasma in patients with common thermal burns. Material and methods. Enterosorbtion detoxification by enterosgel was used in the multimodal treatment of 28 patients with thermal burns of II-IV stages. The drug was prescribed from 2-3 days after burn for 7-14 days, depending on the severity of the injury and manifestations of the intoxication syndrome. In 24 patients the treatment was complemented by galvanization of burn wounds with the preliminary introduction of antibacterial drugs. ITE began with 3-4 days after burn, taking into account the sensitivity of the microflora to antibiotics. The comparison group was made up of 30 patients with similar areas and depths of thermal burns receiving traditional treatment. Results and discussion. It was discovered that the inclusion of enterosorption in multimodal therapy of burns diminished the level of unlimited proteolysis, favoured the increase of the level of blood plasma fibrinolytic activity. Its combination with ITE of antibacterial agents (galvanoenterosorption) ensured a higher therapeutic effect. Common deep thermal burns are accompanied by a significant increase in proteolytic and fibrinolytic activity (FA) of blood. Inclusion of enterosorbtion in the integrated therapy of burns provides reduction of proteolytic activity and maintenance of a high level of FA of plasma, which reduces the risk of thromboembolic complications. Conclusion. Combined use of enterosorption and ITE of antibacterial agents (galvanoentersorption) with thermal burns provides a higher therapeutic effect.

V600EBRAF Inhibition Induces Cytoprotective Autophagy through AMPK in Thyroid Cancer Cells

The dysregulation of autophagy is important in the development of many cancers, including thyroid cancer, where V600EBRAF is a main oncogene. Here, we analyse the effect of V600EBRAF inhibition on autophagy, the mechanisms involved in this regulation and the role of autophagy in cell survival of thyroid cancer cells. We reveal that the inhibition of V600EBRAF activity with its specific inhibitor PLX4720 or the depletion of its expression by siRNA induces autophagy in thyroid tumour cells. We show that V600EBRAF downregulation increases LKB1-AMPK signalling and decreases mTOR activity through a MEK/ERK-dependent mechanism. Moreover, we demonstrate that PLX4720 activates ULK1 and increases autophagy through the activation of the AMPK-ULK1 pathway, but not by the inhibition of mTOR. In addition, we find that autophagy blockade decreases cell viability and sensitize thyroid cancer cells to V600EBRAF inhibition by PLX4720 treatment. Finally, we generate a thyroid xenograft model to demonstrate that autophagy inhibition synergistically enhances the anti-proliferative and pro-apoptotic effects of V600EBRAF inhibition in vivo. Collectively, we uncover a new role of AMPK in mediating the induction of cytoprotective autophagy by V600EBRAF inhibition. In addition, these data establish a rationale for designing an integrated therapy targeting V600EBRAF and the LKB1-AMPK-ULK1-autophagy axis for the treatment of V600EBRAF-positive thyroid tumours.

Comorbid Bipolar and Alcohol Use Disorder—A Therapeutic Challenge

Comorbidity rates in Bipolar disorder rank highest among major mental disorders, especially comorbid substance use. Besides cannabis, alcohol is the most frequent substance of abuse as it is societally accepted and can be purchased and consumed legally. Estimates for lifetime comorbidity of bipolar disorder and alcohol use disorder are substantial and in the range of 40–70%, both for Bipolar I and II disorder, and with male preponderance. Alcohol use disorder and bipolarity significantly influence each other's severity and prognosis with a more complicated course of both disorders. Modern treatment concepts acknowledge the interplay between these disorders using an integrated therapy approach where both disorders are tackled in the same setting by a multi-professional team. Motivational interviewing, cognitive behavioral and socio- therapies incorporating the family and social environment are cornerstones in psychotherapy whereas the accompanying pharmacological treatment aims to reduce craving and to optimize mood stability. Adding valproate to lithium may reduce alcohol consumption whereas studies with antipsychotics or naltrexone and acamprosate did not affect mood fluctuations or drinking patterns. In summary, there is a continuous need for more research in order to develop evidence-based approaches for integrated treatment of this frequent comorbidity.

Integrated therapy as a tool to help fight asymptomatic COVID-19: A case report

COVID-19 is a rapidly changing and evolving situation and is extremely challenging to the humankind since it is highly infectious. Around 80% of the COVID-19 patients are asymptomatic but still need special care so that they don’t develop any further serious complications in due course of infection. The aim of present case study was to assess the effect of integrated therapy of yoga and Ayurveda on vital parameters of a COVID-19 positive asymptomatic patient. He was found to be COVID-19 positive with ORF CT value of 29.85. He remained asymptomatic throughout the course of disease. Vital parameters such as body temperature, oxygen saturation, and heart rate remained optimal throughout the course of infection. This was probably due to physical activity such as walking, yoga and Ayurvedic medications which helped in building of immunity. This further prevented progression of the disease to moderate/severe stage and there were no unanticipated events. The patient was rechecked after 8 days and was found to be COVID-19 negative. This implies that Yoga and Ayurveda treatment is effective in controlling symptoms of COVID-19 and prevention of disease progression.

PREVENTION OF COMPLICATIONS IN PATIENTS WITH MYOCARDIAL INFARCTION AND CONCOMITANT METABOLIC SYNDROME

In Ukraine, coronary heart disease is still occupying the first place in the structure of the causes of death and primary disability (22.8%), and the incidence of myocardial infarction among people of working age is 48.9 per 100 thousand. The aim of this study was to increase the effectiveness of the treatment and prevention of complications in patients with acute coronary syndrome (myocardial infarction) and concomitant metabolic syndrome by including L-carnitine and L-arginine to the integrated therapy. The study involved 71 patients with acute coronary syndrome (ACS) with ST-segment elevation and concomitant metabolic syndrome. Among the 37 individuals who were prescribed a course of cytoprotective therapy additional to the standard drug therapy according to the protocol of the Ministry of Health, formed a test group. The control group consisted of 34 patients who only received standard protocol treatment with corticosteroids (MI). The diagnosis of acute myocardial infarction was verified according to the ESC recommendations (2017). Diagnosis of metabolic syndrome (MS) was established based on the recommendations of the International Diabetes Federation (IDF, 2016). It was found that due to the integrated therapy including L-arginine and L-carnitine, the patients with ACS (MI) and concomitant MS achieved a significant improvement in central cardiohemodynamics and the restoration of vascular endothelial function that was often accompanied by the following complications of corticosteroids (MI) as reperfusion arrhythmias and blockades and acute heart (left ventricular) failure. The patients with acute myocardial infarction and concomitant MS demonstrated pronounced deterioration of morpho-functional parameters of the heart, and namely the development of its post infarction remodelling with subsequent impairments of systolic and diastolic heart function and the development of heart failure and endothelial vascular dysfunction. A mixture of L-arginine and L-carnitine added to the standard therapy significantly reduces the incidence and severity of complications of acute MI such as reperfusion arrhythmias and acute left ventricular failure.

EFFICIENCY OF ANTIOXIDANTS IN INTEGRATED THERAPY OF ACUTE ODONTOGENIC OSTEOMYELITIS IN CHILDREN

This paper presents the comparative generalization of the results obtained by studying the activation of the processes of lipid peroxidation and the state of antioxidant protection factors in the peripheral blood and unstimulated oral fluid fraction in patients having a complicated course of odontogenic mandibular osteomyelitis. To determine the effectiveness of natural antioxidants, which were additionally included in the therapy protocol for patients with this the disease, we created two similar groups of participants (22 and 23 people in each) aged 7 to 15 years. Based on our previous reports, on admission to the hospital, these patients demonstrated the activation of the lipid peroxidation processes and the reduction of antioxidant protection factors in biological substrates. The scope of the treatment measures described in the protocol did not allow us to normalize their components for the time of clinical recovery. This prompted us to prescribe tocopherol acetate and ascorbic acid as components of the integrated complex therapeutic measures. This helped to stabilize the levels of all indicators up to the time of clinical recovery in this group of patients and supported the feasibility of these pharmaceuticals as important components in the therapy of odontogenic inflammatory diseases.

Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

There is growing interest in cytokine-induced killer (CIK) cells on the integrated therapy of patients with RCC, especially those in the late stage or refractory to conventional chemotherapy and radiotherapy. In this review, a total of 15 clinical studies including 681 patients enrolled in CIK cell immunotherapy were outlined. Three-hundred-and-eighty-two patients with RCC were treated with CIK cells alone or in combination with DC vaccination, targeted agents sunitinib or sorafenib, and the PD-1 inhibitor pembrolizumab. Significantly improved 3-year overall survival rate was reported in four trials, whereas remarkably longer median progression-free survival was observed in three studies. Adverse reactions were mild and usually controllable fever and fatigue. Besides, preclinical research progresses were reviewed to increase our understanding about the underlying mechanisms of CIK cell cytotoxicity and identify potential targets to enhance their anti-tumor activity. These studies suggest that CIK cell-based immunotherapy has potential clinical benefits with a good safety profile and could become a promising approach in the combined therapies of RCC patients. However, further large-scale studies are required to evaluate the clinical efficacy of CIK cells and more efforts should be performed to identify the optimal CIK cell-based therapeutic regimen for RCC patients.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Breast Cancer: A Preliminary Report on 4 Cases

Background: Breast cancer (BC) has the highest morbidity and the fifth mortality rate among women in China. Peritoneal metastases from BC is a rare disease and no guideline or international consensus for it. Objective: To summarise our experiences in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat breast cancer peritoneal carcinomatosis (BC PC).Methods: 4 BC PC patients underwent CRS+HIPEC were enrolled in this study. The clinic-pathologic characteristics and overall survival (OS) were collected and analysed.Result: The average age at CRS+HIPEC was 59.8 years. The average time of CRS+HIPEC was 8.8 h. The median number of resected organ areas was 7. OS from CRS+HIPEC were 31, 28, 16 and 52 months. There were no serious adverse events (SAEs) during the perioperative period.Conclusions: The 4 cases provided evidence that integrated therapy with CRS+HIPEC may be a promising strategy to improve the outcome for BC PC patients.

Assessment Synergistic Effects of Integrated Therapy with Epigallocatechin-3-Gallate (EGCG) & Arsenic Trioxide and Irradiation on Breast Cancer Cell Line

Background: Breast cancer is the most common invasive malignancy among women in the world. The current breast cancer therapies pose significant clinical challenges. Low-dose chemotherapy represents a new strategy to treat solid tumors in combination with natural products such as green tea catechins. Epigallocatechin-3-gallate (EGCG) is the major polyphenolic extract from green tea with potent anticancer and antioxidant effects. The purpose of this study was to investigate the effects of EGCG, Arsenic trioxide (ATO) and gamma radiation on MCF-7 cell line. Methods: The anti-proliferative effects of EGCG and ATO individually, moreover in combination with radiation on MCF-7 cells were evaluated with MTT assay. The expression of apoptotic gens (Bax, Bcl-2, Caspase-3 and Fas) was assessed by real-time PCR. Results: Based on the results of MTT assay, EGCG and ATO exhibited dose and time-dependent antiproliferative effects on MCF-7 cells. The combined therapy of EGCG and ATO in presence and absence radiation could rise cell death up to 80%. Moreover, integrated therapy made Bax up-regulated and Bcl-2 downregulated. Conclusion: In assessment synergistic effects of integrated therapy with EGCG and ATO and irradiation had been significant impact on low dose chemotherapy for breast cancer treatment.