Apoptosis Gene Expression Profile in Early-Stage non Small Cell Lung Cancer
Non small cell lung cancer (NSCLC) is a highly aggressive malignancy with survival rates limited to some patients in early stages (I and II). Apoptosis resistance is a hallmark of solid tumors that is tightly concerned with their biology. We analyzed the expression of 84 apoptosis-related genes in a group of Bulgarian patients with early-stage NSCLC.
RNA samples extracted from 12 early-stage NSCLC patients [five squamous cell carcinomas (SCC) and seven adenocarcinomas (AC)] and eight adjacent non neoplastic pulmonary tissues were used for gene expression analysis. We applied pathway-focused expression profiling of 84 apoptosis-related genes using real-time PCR.
Apoptosis-related genes down regulated in NSCLC compared to non tumor lung tissue (p <0.05) included representatives of the tumor necrosis factor (TNF) ligand family [TNF superfamily 8 (TNFSF8)], caspase cascade (CASP8 and CASP10) and caspase recruitment domain (CARD) family (BCL10), the positive apoptosis regulator DAPK1 and BCL2 family member MCL1. The potential of apoptosis-related genes as prognostic and predictive markers should be validated in future studies.
The anticoagulant rodenticides are the most commonly used toxicants to control rodents nowadays. Therefore, developing resistance to them is an issue of great importance for pest control. The aim of this study was to investigate the sensitivity of synanthropic rodents in the Stara Zagora region, Bulgaria to some of the most significant first (warfarin and coumatetralyl) and second (bromadiolone and brodifacoum) generation anticoagulants. Resistance tests were carried out by a standard protocol using lethal feeding period tests and blood clotting response tests according to the European and Mediterranean Plant Protection Organization (Paris, France) standard. Studies were performed on 278 wild synanthropic rodents – 67 house mice (Mus musculus), 153 roof rats (Rattus rattus) and 58 brown rats (Rattus norvegicus). The rodents belonged to 11 populations inhabiting 9 animal farms in the region of Stara Zagora, Southern Bulgaria. High-level resistance to warfarinwas established in 100% of surveyed house mice and 92.1% of roof rats. Resistance to coumatetralyl was registered in 62.5% of the tested roof rats. Low-level resistance to bromadiolone was found in 38.5% of the surveyed roof rats and 23.1% of house mice. There was no resistance registered in brown rats. The sensitivity of all three rodent species to the strategic anticoagulant brodifacoum was high, and there were no signs of resistance. The results proved the resistance among synanthropic rodents and led to the conclusion that the resistance in house mice and roof rats to warfarin and coumatetralyl tends to be the main issue in pest control.
Ultrafiltration of skim cow’s milk with a UF10-PAN membrane at volume reduction ratios (VRRs) of 2 and 3 was performed. The ultrafiltration retentates obtained were used for production of probiotic yoghurts with three different starters. A control sample was prepared using skim cow’s milk. All yoghurts were analysed according to the following parameters: titratable acidity, dry matter, organoleptic characteristics, number of specific microorganisms (Lactobacillus bulgaricus and Streptococcus thermophilus) and the total count of viable lactic acid bacteria for 28 d of storage. The results showed that the increase in the VRR during ultrafiltration increased the titratable acidity, as well as the dry matter of all yoghurts. Ultrafiltration concentration led to an increase in the count of viable lactic acid bacteria in all yoghurts which improved their functional properties. The highest values of the total number of viable lactic acid bacteria were determined in yoghurts obtained with starter 1CM, followed by starters MZ2 and ZD for both VRRs. Probiotic yoghurts with the highest organoleptic evaluation were obtained from ultrafiltration retentates at VRR = 2 and starters 1CM and MZ2.
Introduction. Since the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), a dramatic improvement in hematologic, cytogenetic and molecular responses was noted. Also, the overall survival increased significantly. Unfortunately, in certain patients, resistance to TKI develops relatively early, especially due to point mutations in the ABL kinase domain, among which the T315I mutation confers resistance to all three currently available TKIs (imatinib, dasatinib, nilotinib). Methods. We performed a prospective study on 74 patients diagnosed with chronic phase CML, for whom we analyzed the T315I mutation. Mutational analysis was performed using ARMS-PCR (with subsequent confirmation by direct sequencing) at regular intervals of 6 months or in case of suboptimal response, loss of response or progression. Correlations between the T315I mutation and disease characteristics, response to treatment and survival were analyzed. A comparative analysis between patients positive and negative for the mutation was performed. The patients were followed and evaluated according to European Leukemia Net (ELN) criteria. Results. T315I mutation was detected in 3 patients (4.05%) and its presence was correlated with younger age at diagnosis, second line TKI therapy, progressive disease and decreased survival from the moment of detection. Conclusions. ARMS-PCR is a sensitive, easy to use method for the detection of T315I mutation in chronic phase CML patients
Introduction: Tako-tsubo syndrome is a novel cardio-vascular disease affecting predominantly postmenopausal women exposed to unexpected strong emotional or physical stress, in the absence of significant coronary heart disease. It is characterized by acute onset of severe chest pain and/or acute left ventricular failure, ECG-changes, typical left ventricular angiographic findings, good prognosis and positive resolution of the morphological and clinical manifestations. First described in 1990 in Japan by Sato, Tako-tsubo cardiomyopathy is characterized by transient contractile abnormalities of the left ventricle, causing typical left ventricular apical ballooning at end-systole with concomitant compensatory basal hyperkinesia. There are also atypical forms, presenting with left ventricular systolic dysfunction which affects the mid-portions of the left ventricle.
The etiology of the disease still remains unclear. Many theories have been put forward about the potential underlying pathophysiological mechanisms that may trigger this syndrome among which are the theory of catecholamine excess, the theory of multivessel coronary vasospasm, the ischemic theory, and the theory of microvascular dysfunction and dynamic left ventricular gradient induced by elevated circulating catecholamine levels.
Adequate management of Tako-tsubo syndrome demands immediate preparation for coronary angiography. Once the diagnosis is made, treatment is primarily symptomatic and includes monitoring for complications. Patients with Tako-tsubo syndrome most frequently develop acute LV failure, pulmonary edema, rhythm and conductive disturbances and apical thrombosis. Treatment is symptomatic and includes administration of diuretics, vasodilators and mechanical support of circulation with intra-aortic balloon counterpulsation.
INTRODUCTION: Arterial hypertension is the most common chronic cardiovascular disease affecting about 25% of the adult population. Meta-analyses have demonstrated a linear relationship between blood pressure and the risk of cardiovascular events. Resistant hypertension defined as failure to reach blood pressure targets despite treatment with three antihypertensive drugs including a diuretic represents a serious clinical problem. It has been estimated that it affects between 8.9% and 12.8% of all treated hypertensive subjects. In resistant hypertension the optimal blood pressure is illusive despite very well tailored therapy.
OBJECTIVE: Management of resistant hypertension is exactly the fi eld where blood pressurecontrolling non-pharmacological methods fi t best. The present article aims at throwing light on these methods’ principles of action, on who the target patient groups are and the respective results. Two methods are especially reviewed here: the carotid barorefl ex stimulation and the transcatheter renal sympathetic denervation. Current results from the use of renal denervation suggest stable effi ciency of the method, the results becoming signifi cant 6 months after the procedure is applied and sustained for two years in the follow-up. As much as 90% of the treated patients respond to the procedure. The transcatheter renal denervation is associated with only 2.61% of procedural complications. The barorefl ex carotid stimulation, too, is known to produce a stable effect on blood pressure: the effect become obvious at 12 months in 88% of the treated subjects. The neurologic complications associated with the procedure are reported to occur in 4.4% of cases.
CONCLUSION: The present review article clearly demonstrates that non-pharmacological methods for treatment of resistant hypertension show great promise despite some open questions concerning their long term effects and procedural safety.
Rivne Nuclear Power Plant (NPP) is located in western Ukraine. Construction of the station began in 1976. Totally four power generating units are operating on the station. Complicated geological conditions and display of man-made karst led to the need for monitoring of sediments and deformations on Rivne NPP. Since 1984 on the Rivne NPP there were conducted geodetic observations on the conditions of height reference network consisting of nine deep fixed reference points, which are installed in basaltic rocks. Totally 110 cycles of observations were conducted. The heights of fixed reference points were determined by leveling of I-st class. It is necessary to assess the kinematics of the reference height network and implement zoning of station territory according to a speed of inclination of the earth's surface. An average annual rates of displacement which appear as a linear trend weredetermined on the results of measurements for each fixed reference point by the least squares method. Excluding these values the vertical displacements of fixed reference points were derived and only the periodic component that is changing according to the periodic law remained present there. For each fixed reference point it was determined amplitude and optimum oscillation period and the coefficients of regression equations. Using the annual velocity of displacement of fixed reference points it was done the zoning of the Rivne NPP. There were allocated areas, which were characterized by different rates of inclinations and frequency of oscillations
Influence of the SCN1A IVS5N + 5 G>A Polymorphism on Therapy with Carbamazepine for Epilepsy
Carbamazepine (CBZ) blocks neuronal sodium channels in a voltage- and frequency-dependent manner, delaying the recovery of the channels from the inactivated state, reducing the number of action potentials within a burst, and decreasing burst duration. The α-subunit of the first neuronal sodium channel (SCN1A) is a major gene in different epilepsies. A synonymous polymorphism (SCN1A IVS5N + 5 G>A or rs3812718) is common in exon 5 of this gene. Mutations in the α-unit of this gene are associated with CBZ-resistant epilepsy and a higher maintenance dose of CBZ. We have investigated the association of this single nucleotide polymorphism (SNP) and epilepsy, efficacy and dose-dependence of CBZ therapy in 147 adult Macedonian patients and 137 non epileptic controls. No significant differences in allelic frequencies and genotype distribution were found between patients and controls (p = 0.94278), or between CBZ-responsive and unresponsive patients (p = 0.55449). An association between the A allele and a higher maintenance dose in CBZ-responsive patients was detected. No statistical difference was found between the plasma levels of CBZ and genotype of patients receiving the same dose, indicating that the variant exerts its effect at the level of receptor responsiveness. The predictive value of pretreatment testing showed a minor insignificant difference between patients with different genotypes, primarily due to a small number of patients.
Background: Familial hypercholesterolaemia (FH) is a genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease (CVD). This retrospective observational study examined the clinical characteristics and management of FH subjects in Bulgaria over a 12-month period.
Materials and methods: Twelve cardiology sites participated in this study from May 2015 to May 2016. Eligible subjects had at least two routine low-density lipo-protein cholesterol (LDL C) measurements and a prescription for lipid-lowering therapy (LLT) at the start of the observation period. Mean values for gender, age and cardiovascular (CV) event history at baseline and LDL-C over time were estimated.
Results: Of the 220 eligible subjects, 196 fulfilled the criteria for FH diagnosis: 27 definite, 94 probable and 75 possible. Mean age at enrolment was 54.4 years and 64.1% of subjects were male. Mean CV risk classification at baseline was 26.8% high-risk (HR) and 73.2% very high-risk (VHR). Mean LDL-C was 5.6 mmol/L at enrolment and 4.1 mmol/L at last observation visit (12 months). The ESC/EAS Guideline LDL-C targets (applicable at the time of the study) were achieved by 14.5% of HR and 5.0% of VHR subjects. Most subjects (n=219) received statins. One subject was statin intolerant (ezetimibe therapy). Intensive statin treatment (atorvastatin 40–80 mg/daily and rosuvastatin 20–40 mg/daily) was used in 38.6% of individuals during the observation period and 10% of subjects received combination therapy (statin plus ezetimibe or other LLT).
Conclusions: Most subjects with FH do not reach the ESC/EAS defined LDL-C targets. Early identification and physician education may improve FH management.
Background: Production of Bla OXA-23, OXA-24, OXA-58 and hyperexpression of OXA-51 due to ISAba1 insertion sequence are the leading causes of carbapenem resistance in Acinetobacter baumannii. The loss of OprD transmembrane protein and the overexpression of some effl ux pumps are considered to be the main factors for carbapenem resistance in Pseudomonas aeruginosa whereas metallo-enzymes’ production has a secondary role. Aim: Тo examine the carbapenem resistance due to carbapenemase production among clinically signifi cant Gram-negative non-fermenters from St George University hospital, Plovdiv: A. baumannii and P. aeruginosa. Materials and methods: Forty three A. baumannii and 43 P. aeruginosa isolates, resistant or with intermediate resistance to imipenem and/or meropenem were included in the study. They were collected from patients admitted in 14 various hospital wards between 2010 and 2014. Both phenotypic and genetic methods were used for identifi cation and antimicrobial susceptibility testing. Results: All A. baumannii demonstrated carbapenemase production determined by a modifi ed Hodge test whereas P. aeruginosa isolates did not show this phenomenon. OXA-23 genes were determined in 97.7% (42 out of 43) of A. baumannii isolates indistinguishable from the sequence of the classical ARI-1 gene. OXA-24, OXA-58 and overexpression of OXA-51 were not registered in any of the isolates. All P. aeruginosa were negative for blaVIM and blaIMP genes. Conclusion: The leading cause of carbapenem resistance in A. baumannii isolates from our hospital is the carbapenemase production due to the expression of OXA- 23 gene, whereas in P. aeruginosa - the loss of transmembrane OprD protein and the effl ux pumps’ hyperexpression are suspected to be the main mechanisms.