Background/aim. Ganaxolone is an allopregnanolone analogue devoid of hormonal activity which potentiates inhibitory action of GABA through positive allosteric modulation of GABA-A receptor. This review summarizes preclinical and clinical development of ganaxolone for treatment of epilepsy in children and adults. Methods. Published preclinical and clinical studies with ganaxolone were retrieved from multiple searches of MEDLINE and SCINDEKS databases of published scientific articles. Published European and USA patents with ganaxolone were also used as data source for writing this article, as well as the feedback from the company which is developing ganaxolone (Marinus Pharmaceuticals). Results. Ganaxolone prevented seizures in animal models of partial and generalized tonic-clonic seizures, while in the models of absence seizures it was either ineffective or prolonged spike wave discharge. Phase I clinical trials pointed to linear pharmacokinetics of ganaxolone, its high protein-binding and metabolism in the liver, and predominant excretion in feces. Ganaxolone showed certain efficacy as add-on therapy against partial seizures with or without secondary generalization in adult patients and a phase III clinical trial is currently being prepared to test ganaxolone in this indication. Although tried in several small studies on children suffering from infantile spasms, it failed to produce significant response. Conclusions. If future clinical trials confirm efficacy of ganaxolone as add-on therapy in adult patients with partial onset seizures, it could become useful adjunct to existing anti-epileptic therapy of patients who did not achieve satisfactory seizure control. [Projekat Ministarstva nauke Republike Srbije, br. 175007]
Background/Aim. Acute pancreatitis is an inflammatory condition having the significant mortality rate in the case of severe forms of the disease. The aim of this study was to investigate putative factors of increased mortality in patients with acute pancreatitis with contradictory prior evidence, and to reveal factors that were insufficiently explored previously. Methods. This prospective cohort study with nested case/control design included all adult patients treated for acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the 3-year period (from October 2011 to December 2014). The cases (n = 19) were patients who died, while the controls (n = 113) were patients who survived. The associations between putative risk factors and the study outcomes were tested by univariate and multivariate logistic regressions, and expressed as crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). Results. Significant association with the lethal outcome in acute pancreatitis was found for advanced age (adjusted OR 1.12, 95%CI 1.02–1.23), presence of significant comorbidities (adjusted OR 10.62, 95%CI 1.01–111.39), higher interleukin- 8 (IL-8) value on third day from onset of symptoms (adjusted OR 1.05, 95%CI 1.02–1.08), use of tramadol and/or morphine (adjusted OR 47.34, 95%CI 3.21–699.08), the Bedside index for severity in acute pancreatitis (BISAP) score ≥ 3 in the first 24 hours (adjusted OR 48.11, 95%CI 3.14–736.29), and prophylactic use of antibiotics (adjusted OR 0.07, 95%CI 0.01–0.85). Conclusion. Advanced age, significant comorbidities, use of tramadol and/or morphine and more severe disease as assessed by BISAP score can increase the risk of death in acute pancreatitis, while prophylactic use of antibiotics may have a protective role.
Kosana D. Stanetić1, Suzana M. Savić1, Bojan M. Stanetić2, Olja M. Šiljegović3, Bojana S. Đajić4 1Primary Health Center Banja Luka, Department of family medicine, Medical faculty, University of Banja Luka, Bosnia and Herzegovina 2Department of Cardiology, University Clinical Center of the Republic of Srspka, Banja Luka, Bosnia and Herzegovina 3Primary Health Center Doboj, Bosnia and Herzegovina 4Primary Health Center Gradiška, Bosnia and Herzegovina The prevalence of polypharmacy in elderly: a cross section study from Bosnia and Herzegovina Оригинални радови / Original Articles
Aim: The objective of this study was to determine the oxidative status of saliva and plasma in diabetic children, by analyzing advanced oxidation protein products (AOPPs) and total antioxidant capacity (TAC). Materials and methods: Study included 60 patients with diabetes mellitus type I (DMT1) aged 12.45 ± 2.65 years, and 40 healthy age-matched controls. The AOPP and TAC of the plasma and saliva samples were determined using a commercial QuantiChromTM Antioxidant Assay Kit (DTAC-100) for TAC determination, and Immunodiagnostic AG [enzyme-linked immunosorbent assay kit for AOPP]. Results: Values of salivary and plasma AOPP were lower in diabetic patients than in healthy controls, while value of TAC was clinically and significantly higher in plasma of controls, and clinically higher in saliva of healthy control group, compared with diabetic patients. Average value of hemoglobin A1c (HbA1c) was 7.58 ± 0.85%. Conclusion: Results of this study showed that diabetes mellitus as a condition, with well-controlled HbA1c, has no influence on AOPP levels in saliva and plasma, while TAC levels of saliva and plasma are lower in diabetic patients, which means that DMT1 has an influence on the TAC.
Health-Related Quality Of Life (HRQOL) of oncology contains subjective experience of the positive and negative aspects of disease on the physical, emotional, social and cognitive function, and the frequency of the symptoms and side effects of the treatment. The patient is the best source for information about the quality of life and it is necessary that the patient’s value system evaluates and qualitative terms. The effect of chemotherapy is the system, which means that the blood is transported to where the whole body where reacted to the malignant cells in the process of cell division and a variety of other normal tissues. Thus become supporting undesirable advent such as fatigue, which is almost always present, loss of appetite, reduced resistance to infection, and the most common and best known, nausea, vomiting, and hair loss. All of these complications affect the reduction in quality of life, and this applies to all aspects of life: emotional status, social life, physical limitations in daily performance of physiological actions. The role of nurses in the application of chemotherapy is extremely important. From the beginning, the patient and the nurse gain a relationship of trust and security to the patient feel comfortable and safe.
Introduction/Objective Activation of insulin-like growth factor receptor (IGF-1R) results in cell transition from growth phase to synthesis phase of cell cycle. Breast cancer is categorized into prognostic and therapeutic subtypes based upon hormone receptor, estrogen receptor (ER), and progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (HER-2) expression. The objective of this study was to examine the expression of IGF-1R in а specific subtype invasive breast cancer and its correlation with basic histopathological and immunohistochemical prognostic parameters. Methods Formalin-fixed paraffin-embedded tumor samples were obtained from 129 female patients with invasive breast cancer (I–III disease stage) with the follow-up ranging 36–108 months (average 48 months). For immunohistochemical staining, we used monoclonal antibodies for ER, PR, IGF-1R, and polyclonal antibody for HER-2. Results IGF-1R inversely correlated with tumor stage (p = 0.017), tumor grade (p = 0.001), HER-2 (p = 0.003), whereas significant positive correlation was found with multifocality/multicentricity of breast cancer (p = 0.036), ER (p = 0.001) and PR (p = 0.0001) expression. Cox-regression analysis for relapse-free survival (RFS) showed that disease stage (p = 0.039) and HER-2 (p = 0.033) were independent prognostic factors. IGF-1R did not predict clinical outcome in patients with breast cancer (p = 0.488, Kaplan–Meier test for RFS). Conclusion Patients with low stage and grade hormone-dependent breast cancer had a significantly higher IGF-1R expression than patients with triple negative or HER-2 overexpressed cancer. The present findings also highlight that IGF-1R expression in multicentric/multifocal breast cancer supports the key roles in tumor initiation.
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