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1.
Bratisl Lek Listy ; 119(12): 776-780, 2018.
Article in English | MEDLINE | ID: mdl-30686017

ABSTRACT

AIM: Kisspeptin is a reproductive peptide hormone that has anti-metastatic roles in several cancer types including colon, lung, and brain cancer. However, in breast cancer, increasing of kisspeptin expression induces aggressiveness of tumors, which in turn exacerbates breast cancer prognosis. MATERIAL AND METHODS: Breast cancer cell lines MCF7 and SKBR3 were cultured in MEM (phenol red free) containing 10 % fetal bovine. Treatments were performed, at 70 % confluency, after 24-hour serum deprivation in serum free medium for 6, 24 and 48 hours. Aromatase (CYP19A1) and kisspeptin receptor (GPR54) mRNA expression were determined by real time Taqman Assay. RESULT: Kisspeptin induced aromatase (CYP19A1) and kisspeptin receptor (GPR54) mRNA expression, while this induction was abolished by kisspeptin receptor inhibitor in MCF7 cells. In SKBR3 cells, however, even though there was an increase in GPR54 mRNA expression with kisspeptin, the induction of CYP19A1 was not observed. CONCLUSION: The inducing effect of kisspeptin on aromatase expression is possibly mediated via kisspeptin receptor and estrogen receptor dependent mechanisms (Fig. 5, Ref. 27).


Subject(s)
Aromatase , Breast Neoplasms , Kisspeptins , Animals , Aromatase/metabolism , Breast Neoplasms/metabolism , Cattle , Humans , Kisspeptins/physiology , Peptides , Receptors, Estrogen/physiology , Receptors, G-Protein-Coupled
2.
Herz ; 43(5): 455-460, 2018 Aug.
Article in English | MEDLINE | ID: mdl-28653113

ABSTRACT

BACKGROUND: Biomarkers play an important role in the risk stratification of patients with heart failure (HF). Recent studies have shown that soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin 1 receptor family, is associated with disease prognosis in acute and chronic HF. In this study we aimed to investigate the relation between sST2 level and functional capacity in outpatients with systolic HF. PATIENTS AND METHODS: This study included 120 HF patients with reduced ejection fraction (HFrEF; EF ≤ 40%). The mean age of patients was 66 ± 11 years. Advanced HF (New York Heart Association [NYHA] functional class III-IV) was observed in 35 patients (29%). RESULTS: sST2 levels were on average higher in patients with NYHA functional classes III and IV than in patients with NYHA functional classes I and II (51 [9-198] vs. 25 ng/ml [9-118], p < 0.001). In a multiple logistic regression model, sST2 level (OR: 1.044, p = 0.004, 95% CI: 1.014-1.075), hemoglobin level (OR: 0.590, p = 0.001, 95% CI: 0.433-0.805), total cholesterol level (OR: 0.977, p = 0.004, 95% CI: 0.962-0.993), and age (OR: 1.066, p = 0.047, 95% CI: 1.001-1.136) were associated with poor functional capacity. In receiver operating characteristic (ROC) curve analysis, the optimal cut-off value of sST2 for predicting poor functional capacity was >42 ng/ml, with 63% sensitivity and 88% specificity (AUC: 0.810, 95% CI: 0.728- 0.875). CONCLUSION: Higher sST2 levels were strongly associated with poor NYHA functional class, independent of cardiac risk factors, in outpatients with HFrEF.


Subject(s)
Biomarkers , Heart Failure , Aged , Biomarkers/blood , Female , Heart Failure/blood , Heart Failure/diagnosis , Humans , Interleukin-1 Receptor-Like 1 Protein , Male , Middle Aged , Outpatients , Prognosis , Stroke Volume , Ventricular Function, Left
3.
Bratisl Lek Listy ; 118(3): 149-152, 2017.
Article in English | MEDLINE | ID: mdl-28319409

ABSTRACT

4-methylimidazole is widely used in pharmaceuticals, photographic and agricultural chemicals. The substance is extensively found in many human and animals foods. In this research, anticancer effect of the 4-MEI was studded using MTT test using MCF-7 cell line. Effect of the 4-MEI on apoptosis or necrosis was analyzed by DNA fragmentation assay using Swiss Albino rats as a model organism. Antioxidant effect of the substance was investigated by assaying protective effect of the substance on circular plasmid DNA against H2O2 as an oxidative agent. 4-MEI showed inhibitory effect on proliferation of MCF-7 cell line by all concentrations and the decrement was significant and concentration dependent. Result of DNA fragmentation assay showed 4-MEI concentrations dependent of smear formation showing necrotic effects of the 4-MEI on mouse cells. Also, the 4-MEI showed a good antioxidant activity and protective effect against H2O2. CONCLUSION: The result of this study showed that 4MEI has significant antioxidant and anti-cancer effect. Also, according to the result, 4-MEI has necrotic effects on mouse cells (Fig. 3, Ref. 21).


Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , DNA Fragmentation/drug effects , Hydrogen Peroxide/pharmacology , Imidazoles/pharmacology , Oxidants/pharmacology , Animals , Humans , MCF-7 Cells , Mice , Necrosis , Rats
4.
Folia Morphol (Warsz) ; 76(2): 197-207, 2017.
Article in English | MEDLINE | ID: mdl-27714730

ABSTRACT

BACKGROUND: An understanding of the left main coronary artery (LMCA) anatomy is important for accurate diagnosis and therapy. We aimed to investigate LMCA anatomy via 128-multisliced coronary computed-tomography-angiography (CCTA) in patients with normal LMCA. MATERIALS AND METHODS: A total of 201 CCTA studies were included in this study. Anatomical features of LMCA including cross-sectional areas of the LMCA ostial, LMCA distal, left anterior descending artery (LAD) ostial and left circumflex artery (LCX) ostial, and degree of tapering and LMCA bifurcation angles (BA) in the form of LMCA-LCX BA, LMCA-LAD BA, LAD-LCX BA at end-diastole and end-systole. RESULTS: The mean age was 55 ± 11; 55.7% of patients were males. Right coronary artery was dominant in 173 (86.1%) patients. Mean LMCA length was 10.0 ± 4.5 mm. The mean values of LMCA ostial, LMCA distal, LAD ostial and LCX ostial areas were 18.2 ± 5.1 mm², 13.2 ± 4.0 mm², 9.0 ± 3.2 mm² and 7.6 ± ± 2.8 mm², respectively. LMCA ostial-distal area, LMCA distal-LAD ostial area and LMCA distal-LCX ostial area ratios were ≥ 1.44 - < 1.69 in 47 (23.4%), 53 (26.4%), 47 (23.4%) patients, respectively, and were ≥ 1.69 - < 1.96 in 19 (9.5%), 24 (11.9%), 40 (19.9%) patients respectively. Systolic motion modifies LMCA BAs; systolic motion begets an increment of LMCA-LAD angle in 72.6% of patients and decrement of LAD-LCX angle in 75.6% of patients. Patients with T-shaped LAD-LCX BA was shown to have significantly longer LMCA, larger LAD ostial area, larger LCX ostial area and higher diastolic-to-systolic range (DSR) of LAD-LCX BA compared to patients with Y-shaped LAD-LCX BA. CONCLUSIONS: LMCA with T-shaped distal BA was found to have significantly longer LMCA, larger LAD ostial area, larger LCX ostial area and higher DSR of distal BA compared to patients with Y-shaped distal BA. These findings may provide useful information for LMCA bifurcation stenting or designing dedicated stents for LMCA.


Subject(s)
Computed Tomography Angiography , Coronary Vessels/anatomy & histology , Coronary Vessels/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged
5.
Herz ; 42(3): 307-315, 2017 May.
Article in English | MEDLINE | ID: mdl-27460050

ABSTRACT

BACKGROUND: The current study aimed to evaluate the influence of regular annual influenza vaccinations on cardiovascular (CV) death and heart failure-related hospitalizations (HFrH) in stable outpatients with heart failure with reduced ejection fraction. METHODS: The Turkish research team-HF (TREAT-HF) is a network undertaking multicenter, observational cohort studies in HF. This study is a subgroup analysis of TREAT-HF outpatient cohorts who completed a questionnaire on influenza vaccination status and for whom follow-up data were available. A total of 656 patients with available follow-up data for CV death and HFrH including recurrent hospitalization were included in the study. Patients were classified into two groups: those who received regular influenza vaccination (40 %) and those who did not receive vaccination. RESULTS: During a mean follow-up of 15 ±6 months, 113 (18 %) patients had CV death and 471 (72 %) patients had at least one HFrH. The CV death rate was similar in both groups of patients (16 vs. 19 %, p = 0.37), whereas, HFrH and recurrent HFrH were significantly less frequently encountered in patients who received regular influenza vaccination than in those who did not receive vaccination (43 vs. 92 % and 16 vs. 66 %, p < 0.001, respectively). In a multivariate Cox proportional hazards model - in addition to a few clinical factors - vaccination status (HR = 0.30, 95 % CI = 0.17-0.51, p < 0.001) and graduation from university (HR = 0.35, 95 % CI = 0.17-0.72, p = 0.004) remained independently associated with the risk of recurrent HFrH. CONCLUSION: Regular influenza vaccination does not influence CV deaths; however, it decreases HFrH including recurrent episodes of HFrH in outpatients with heart failure with reduced ejection fraction.


Subject(s)
Death, Sudden, Cardiac/epidemiology , Heart Failure/mortality , Influenza Vaccines/therapeutic use , Influenza, Human/mortality , Influenza, Human/prevention & control , Patient Readmission/statistics & numerical data , Vaccination/statistics & numerical data , Comorbidity , Death, Sudden, Cardiac/prevention & control , Female , Follow-Up Studies , Heart Failure/prevention & control , Humans , Male , Middle Aged , Prevalence , Risk Factors , Turkey/epidemiology
6.
Bratisl Lek Listy ; 117(7): 371-5, 2016.
Article in English | MEDLINE | ID: mdl-27546537

ABSTRACT

4-Methylimidazole (4-MEI) is a color widely found in cola drinks, roasted foods, grilled meats, coffee and other foods. This study was aimed to investigate the 4-MEI effects on the cell proliferation, purified circular DNA and DNA from cells of rats treated with the 4-MEI.In this study, mouse 3T3-L1 cell line was treated with 4-MEI at concentrations of 300, 450, 600 and 750 µg/mL for 24 hours and 48 hours periods, after that cytotoxic effect of the 4-MEI was studied by MTT test. Also, the effect of 4-MEI on purified circular DNA (pET22b) was investigated by treating of the DNA with 4-MEI concentrations of 300, 450, 600 and 750 µg/ml. DNA was extracted from liver cells of rats that have been treated with 4-MEI doses of 25 and 50 mg/kg for 10 week and it was subjected to agarose gel electrophoreses analyses.4-MEI significantly inhibited cell proliferation of 3T3-L1 cell line at highest concentration for 24 h and at all concentration for 48 h treatment time. DNA fragmentation assay showed that 4-MEI at 50 mg/kg concentration clearly produced characteristic DNA smear and no DNA laddering (200bp) was observed when mouse was exposed to 4-MEI. The results obtained from plasmid DNA damaging assay showed that 4-MEI has noeffect on the DNA, because the electrophoretic pattern of DNA treated with 4-MEI showed three bands on agarose gel electrophoresis as it was for untreated control. 4-MEI showed cytotoxic effect on 3T3-L1 cells but no effect on plasmid DNA breaking. According to DNA fragmentation assay 4-MEI has necrosis effects on mouse liver cells (Tab. 1, Fig. 4, Ref. 27).


Subject(s)
Cell Proliferation/drug effects , DNA Breaks/drug effects , DNA Fragmentation/drug effects , Imidazoles/pharmacology , Animals , DNA , Male , Meat , Mice , Rats
7.
Bratisl Lek Listy ; 117(5): 290-4, 2016.
Article in English | MEDLINE | ID: mdl-27215965

ABSTRACT

4-Methylimidazole (4-MEI) is mostly used in beverages and coloring food, dark beers and common brands of cola drinks, which may contain more than 100 µg of this compound per 12-ounce serving. This study was aimed to investigate the antigenotoxic and anticytotoxic effects of 4-MEI (100, 130 and 160 mg/kg) against ethyl methanesulfonate (240 mg/kg) using chromosome aberrations (CAs) and Mitotic index (MI) tests in bone marrow cells of Swiss Albino Mice at 12 h and 24 h treatment periods. So, the t-test was used for the statistical analysis.In this research, 4-MEI at all concentrations for 12 h treatment period reduced chromosomal aberrations and at 130 and 160 mg/kg concentrations for 24 h treatment period increased chromosomal aberrations induced by EMS (240 mg/kg), but th ese reductions and increases were not significant. Also, intraperitoneal injection of 4-MEI at doses of 100, 130 and 160 mg/kg combined with EMS (240 mg/kg) showed that the mitotic index was decreased at 100 and 130 mg/kg for 12h and 130 mg/kg for 24 h treatment periods, when compared to positive sample (EMS), but did not show any statistically difference from the EMS treated group. It can be concluded that 4-MEI might not be antigenotoxic and protective effects in bone marrow cells of Swiss Albino Mice, because 4-MEI could not reduce the chromosomal aberrations induced by EMS.


Subject(s)
Bone Marrow Cells/drug effects , Cell Proliferation/drug effects , DNA Damage/drug effects , Ethyl Methanesulfonate/toxicity , Imidazoles/pharmacology , Mutagens/toxicity , Animals , Chromosome Aberrations , Female , Male , Mice , Mitotic Index
8.
Intensive Care Med ; 42(2): 147-63, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26370690

ABSTRACT

PURPOSE: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. RESULTS: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. CONCLUSION: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF.


Subject(s)
Acute Disease/therapy , Critical Care/standards , Heart Failure/therapy , Practice Guidelines as Topic , Shock, Cardiogenic/therapy , Heart Failure/diagnosis , Humans , Shock, Cardiogenic/diagnosis
9.
Balkan J Med Genet ; 18(1): 85-92, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26929910

ABSTRACT

Pentasomy X is an extremely rare sex chromosome abnormality, a condition that only affects females, in which three more X chromosomes are added to the normally present two chromosomes in females. We investigated the novel clinical findings in a 1-year-old female baby with pentasomy X, and determined the parental origins of the X chromosomes. Our case had thenar atrophy, postnatal growth deficiency, developmental delay, mongoloid slant, microcephaly, ear anomalies, micrognathia and congenital heart disease. A conventional cytogenetic technique was applied for the diagnosis of the polysomy X, and quantitative fluorescent polymerase chain reaction (QF-PCR) using 11 inherited short tandem repeat (STR) alleles specific to the chromosome X for the determination of parental origin of X chromosomes. A cytogenetic evaluation revealed that the karyotype of the infant was 49,XXXXX. Comparison of the infant's features with previously reported cases indicated a clinically recognizable specific pattern of malformations referred to as the pentasomy X syndrome. However, to the best of our know-ledge, this is the first report of thenar atrophy in a patient with 49,XXXXX. The molecular analysis suggested that four X chromosomes of the infant originated from the mother as a result of the non disjunction events in meiosis I and meiosis II. We here state that the clinical manifestations seen in our case were consistent with those described previously in patients with pentasomy X. The degree of early hypotonia constitutes an important early prognostic feature in this syndrome. The pathogenesis of pentasomy X is not clear at present, but it is thought to be caused by successive maternal non disjunctions.

10.
Herz ; 40 Suppl 2: 119-24, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25256054

ABSTRACT

OBJECTIVE: Elevated cancer antigen 125 (CA-125) levels are associated with cardiopulmonary disorders such as acute and chronic heart failure (HF), coronary artery disease, chronic obstructive pulmonary disease, and atrial fibrillation (AF). The development of atrial fibrillation (AF) is related to morbidity and mortality in patients with HF: therefore, it is important to identify patients with increased risk for development of AF. We investigated whether plasma CA-125 levels in patients with hospitalized systolic HF could predict the development of AF. PATIENTS AND METHODS: A total of 149 consecutive patients with sinus rhythm who were admitted to the emergency department with hospitalized systolic HF were evaluated prospectively. Serum CA-125 levels were obtained after initial stabilization during their hospital stay. RESULTS: AF developed in 36 (% 24.2) patients during a follow-up period of 22.1 ± 11  months (range 3-61). CA-125 levels were significantly higher in patients who developed AF than in patients with sinus rhythm [99 U/ml (48-172) vs. 47 U/ml (18-108), p = 0.001]. The optimal cut-off level of CA-125 to predict development of AF was found to be > 68.49 U/ml. CA-125 > 68.49 U/ml, left atrial diameter, right ventricular dilatation, moderate to severe mitral and tricuspid regurgitations were found to have prognostic significance in univariate analysis. In a multivariate Cox proportional hazards model with the backward stepwise method, CA-125 > 68.49 U/ml (HR = 2.693, % 95 CI = 1.285-5.641, p = 0.009) and moderate to severe mitral regurgitation (HR = 2.708, % 95 CI = 1.295-5.663, p = 0.008) were associated with an increased risk of new-onset AF after adjustment for variables found to be statistically significant in univariate analysis and correlated with CA-125 level. CONCLUSION: CA-125 level is associated with the development of AF in patients with hospitalized systolic HF.


Subject(s)
Atrial Fibrillation/blood , Atrial Fibrillation/epidemiology , CA-125 Antigen/blood , Heart Failure/blood , Heart Failure/epidemiology , Hospitalization/statistics & numerical data , Atrial Fibrillation/diagnosis , Biomarkers/blood , Comorbidity , Female , Heart Failure/diagnosis , Humans , Incidence , Male , Middle Aged , Prognosis , Reproducibility of Results , Risk Assessment/methods , Sensitivity and Specificity , Turkey/epidemiology
11.
Eur Rev Med Pharmacol Sci ; 17(23): 3132-47, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24338454

ABSTRACT

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and occurs in 3.3%-10% of emergency admissions. It is frequently quoted for people over the age of 75, but the cases of AF in young subjects without structural heart disease are also increasing, therefore, leading to the evaluation of "lonely atrial fibrillation" as a new challenge for the clinician. The first diagnosis and treatment often occur in the emergency room and the emergency physician has therefore to evaluate the initial step towards the therapeutic decisions. Although international standard guidelines are available, AF treatment in the Emergency Department (ED) is still heterogeneous in terms of the management strategy chosen. There are two main strategies for the management of AF: rate and rhythm control. Moreover, antithrombotic treatment is pivotal in AF to prevent cardioembolic stroke and it is considered a primary objective after an accurate assessment of antithrombotic treatment risks and benefits. The introduction of innovative echocardiographic approach, directly in ED, seems to improve the management and risk stratification of patients with AF. This review aims to provide an overview about the current approach and the future expectations in the management of AF in ED. This manuscript represents a synopsis of the lectures on AF management in the ED of the Third Italian GREAT Network Congress, that was hold in Rome, 15-19 October 2012. We decided to use only the most relevant references for each contribution as suggested by each participant at this review.


Subject(s)
Atrial Fibrillation/therapy , Cardiology Service, Hospital/trends , Emergency Service, Hospital/trends , Algorithms , Atrial Fibrillation/diagnosis , Cardiology Service, Hospital/standards , Emergency Service, Hospital/standards , Forecasting , Humans , Practice Guidelines as Topic , Predictive Value of Tests , Time Factors , Treatment Outcome
13.
J Laryngol Otol ; 127(1): 33-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23171692

ABSTRACT

OBJECTIVE: Mutations in the genes for connexin 26 (GJB2) and connexin 30 (GJB6) play an important role in autosomal recessive, non-syndromic hearing loss. This study aimed to detect the 35delG and 167delT mutations of the GJB2 gene and the del(GJB6-D13S1830) mutation of the GJB6 gene in paediatric patients diagnosed with congenital, non-syndromic hearing loss and treated with cochlear implantation in Mediterranean Turkey. MATERIALS AND METHOD: We included 94 children diagnosed with congenital, non-syndromic hearing loss and treated with cochlear implantation. Blood samples were collected, DNA extracted and an enzyme-linked immunosorbent assay performed to enable molecular diagnosis of mutations. RESULTS: Of the 94 children analysed, the 35delG mutation was detected in 12 (12.7 per cent): 10 (83.3 per cent) were homozygous and 2 (16.7 per cent) heterozygous mutant. The 167delT and del(GJB6-D13S1830) mutations were not detected. CONCLUSION: The GJB2-35delG mutation is a major cause of congenital, non-syndromic hearing loss in this study population.


Subject(s)
Cochlear Implantation , Connexins/genetics , DNA/genetics , Hearing Loss/genetics , Mutation , Adolescent , Child , Child, Preschool , Connexin 26 , Connexin 30 , Connexins/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Gene Frequency , Genotype , Hearing Loss/congenital , Hearing Loss/surgery , Humans , Infant , Male , Polymerase Chain Reaction , Retrospective Studies , Turkey
14.
Herz ; 37(7): 796-800, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22699995

ABSTRACT

BACKGROUND: Acute heart failure (AHF) with systolic dysfunction is associated with increased morbidity and mortality, and optimal therapy is not well established, despite the findings of evidence-based medicine. Beta blockers provide a mortality and morbidity benefit in patients with chronic systolic HF, and are currently indicated in all stages of patients with systolic HF. We evaluated therapies before discharge, in particular beta blockers, in patients hospitalized with AHF with and without accompanying chronic obstructive pulmonary disease (COPD). METHODS: The hospital discharge records of 959 consecutive de novo AHF patients, hospitalized and treated for systolic HF (ejection fraction < 45%), were retrospectively reviewed in three cardiovascular institutions. RESULTS: The presence of accompanying COPD was associated with significantly lower prescription of beta blockers before discharge (p < 0.001). Furthermore, with regard to the type of beta blocker, patients with accompanying COPD were less frequently prescribed nonselective beta blockers (29% vs. 48%, p < 0.001). The presence of accompanying COPD among AHF patients increased the risk of omitting (not prescribing) beta blockers before discharge by a factor of 1.785. CONCLUSION: Beta blockers, a proven life-saving therapy in the setting of chronic systolic HF, were found to be less frequently prescribed before discharge in the presence of de novo AHF with accompanying COPD.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Heart Failure/drug therapy , Heart Failure/epidemiology , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Acute Disease , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Treatment Outcome , Turkey/epidemiology
15.
Mol Cell Endocrinol ; 362(1-2): 85-90, 2012 Oct 15.
Article in English | MEDLINE | ID: mdl-22705581

ABSTRACT

In the brain, a 36-kb distal promoter (I.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for estrogen biosynthesis. Local estrogen production in the brain regulates critical functions such as gonadotropin secretion and sexual behavior. The mechanisms that control brain aromatase production are not well understood. Here we show that the glucocorticoid dexamethasone robustly increases aromatase mRNA and protein by up to 98-fold in mouse hypothalamic cell lines in a dose- and time-dependent fashion. Using deletion mutants of the brain-specific promoter I.f and chromatin immunoprecipitation-PCR, we isolated a distinct region (-500/-200 bp) which becomes enriched in bound glucocorticoid receptor upon dexamethasone stimulation. A glucocorticoid antagonist or siRNA based knockdown of glucocorticoid receptor ablated dexamethasone stimulation of aromatase expression. Our findings demonstrate how glucocorticoids alter aromatase expression in the hypothalamus and might indicate a mechanism whereby glucocorticoid action modifies gonadotropin pulses and the menstrual cycle.


Subject(s)
Aromatase/genetics , Glucocorticoids/physiology , Hypothalamus/enzymology , Promoter Regions, Genetic , Transcriptional Activation , Animals , Aromatase/metabolism , Cell Line , Dexamethasone/pharmacology , Enzyme Induction , Gene Knockdown Techniques , Genes, Reporter , Glucocorticoids/pharmacology , Luciferases, Renilla/biosynthesis , Luciferases, Renilla/genetics , Mice , Organ Specificity , RNA Interference , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Up-Regulation
16.
Genet Mol Res ; 11(2): 1424-32, 2012 May 18.
Article in English | MEDLINE | ID: mdl-22653589

ABSTRACT

The number of trinucleotide repeats [CAG (coding for polyglutamine), GGC (coding for polyglycine)] in the first exon of the androgen receptor (AR) gene and prostate-specific antigen (PSA) gene androgen response element I A/G polymorphism are both related to prostate cancer prognosis. We investigated whether these genomic changes occur in the AR and PSA genes, which are usually found in individuals with prostate cancer, of Turkish patients and to find out their distribution in the population. We used PCR and PCR-RFLP assays for AR and PSA genes, respectively, to detect molecular changes in 44 prostate cancer patients. Our findings indicate that individuals with prostate cancer tend to have around 18 CAG trinucleotide repeats. We observed significant differences between 22 controls, 33 benign prostate hyperplasia (BPH) patients and 44 adenocarcinoma patients for long CAG repeats. However, we did not find any significant differences in GGC repeats between controls, BPH and adenocarcinoma patients (P = 0.408). We also did not observe significant differences in the PSA A/G polymorphism frequency between controls, BPH and adenocarcinoma patients (P = 0.483). In conclusion, CAG and GGC repeats in the AR and PSA gene polymorphisms may be associated with prostate cancer risk and BPH in the Turkish population.


Subject(s)
Prostate-Specific Antigen/genetics , Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , Trinucleotide Repeats/genetics , Genetic Predisposition to Disease/genetics , Humans , Male , Polymerase Chain Reaction , Prostatic Neoplasms/epidemiology
17.
Cardiovasc J Afr ; 22(6): 310-2, 2011.
Article in English | MEDLINE | ID: mdl-22159318

ABSTRACT

OBJECTIVE: In this study, 12 patients who were diagnosed as having cardiac tumours and were operated on in the Department of Cardiovascular Surgery following referral from the Department of Cardiology were enrolled between January 1995 and October 2007. METHODS: The symptoms, clinical findings, diagnostic methods, localisation of masses and surgical applications were recorded retrospectively. RESULTS: There were 10 female (83%) and two (17%) male patients; their ages ranged from 35 to 70 years (mean 68.7 years). Twelve patients were diagnosed with myxomas, nine of which were located within the left atrium and three in the right atrium. The most common symptoms at clinical presentation were those associated with heart failure or embolisation. Diagnosis of the tumours was made by echocardiography in all patients. The masses were completely resected in eight patients and the interatrial septae were partially excised with mass resection in two patients. The defect was reconstructed with a pericardial patch in one of the patients, and primarily reconstructed in the other. We carried out debridement with mass resection in another case. Femoro-popliteal aorto-iliac thrombo-endarterectomy was performed with mass resection in a further case. CONCLUSION: Atrial myxomas are the most common primary cardiac tumours. They can cause valvular or inflow-outflow tract obstruction, thrombo-embolism, arrhythmias, or pericardial disorders. Most atrial myxomas are benign but due to non-specific symptoms, early diagnosis may be a challenge and they must be removed by surgical resection. Diagnosis and follow up with the collaboration of cardiology and cardiovascular surgery departments is important for meticulous care of these patients.


Subject(s)
Heart Neoplasms , Myxoma , Adult , Aged , Female , Heart Atria , Heart Neoplasms/diagnosis , Heart Neoplasms/surgery , Humans , Male , Middle Aged , Myxoma/diagnosis , Myxoma/surgery , Retrospective Studies
18.
Genet Mol Res ; 10(3): 1999-2008, 2011 Sep 09.
Article in English | MEDLINE | ID: mdl-21948762

ABSTRACT

Many clinical conditions, including osteoporosis, are associated with serum levels of sex steroids. Enzymes that regulate rate-limiting steps of steroidogenic pathways, such as CYP17 and CYP19, are also regarded as significant factors that may cause the development of these conditions. We investigated the association of two common polymorphisms, in the promoter region (T→C substitution) of CYP17 and exon 3 (G→A) of CYP19, with bone mineral density (BMD) in the lumbar spine and femoral neck and serum androgen/estradiol, in a case-control study of 172 postmenopausal women aged 62.3 ± 9.6 years (mean ± SD). The CYP17 TC genotype was significantly overrepresented in patients compared to controls, and TC genotype neck T-score and lumbar T-score values were significantly higher in patients compared to controls. CYP17 TC and TT genotype testosterone and DHEA-SO(4) levels were lower in patients compared to controls. All three genotypes of CYP19 had almost the same distribution among patients. The CYP19 AG genotype, however, was most frequent among controls. CYP19 lumbar BMD levels were close to each other among the different genotypes; however, AA and AG genotypes were significantly lower in patients. Testosterone and DHEA-SO(4) levels in the CYP19 GG genotype were higher compared to those of the other genotypes in patients but not in controls. CYP19 GA individuals had lower E(2) levels and lower BMD in controls and patients. Femoral neck BMD and lumbar T-score were also diminished with GA transition. In conclusion, CYP17 and CYP19 gene polymorphisms were found to be associated with osteoporosis in postmenopausal women in Turkey.


Subject(s)
Aromatase/genetics , Bone Density/genetics , Gonadal Steroid Hormones/blood , Osteoporosis, Postmenopausal/genetics , Steroid 17-alpha-Hydroxylase/genetics , Aged , Aged, 80 and over , Androgens/blood , Case-Control Studies , Dehydroepiandrosterone Sulfate/blood , Estradiol/blood , Female , Femur Neck , Genotype , Humans , Lumbar Vertebrae , Middle Aged , Polymorphism, Single Nucleotide , Postmenopause , Testosterone/blood , Turkey
19.
Intensive Care Med ; 37(4): 619-26, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21210078

ABSTRACT

PURPOSE: We performed a survey on acute heart failure (AHF) in nine countries in four continents. We aimed to describe characteristics and management of AHF among various countries, to compare patients with de novo AHF versus patients with a pre-existing episode of AHF, and to describe subpopulations hospitalized in intensive care unit (ICU) versus cardiac care unit (CCU) versus ward. METHODS AND RESULTS: Data from 4,953 patients with AHF were collected via questionnaire from 666 hospitals. Clinical presentation included decompensated congestive HF (38.6%), pulmonary oedema (36.7%) and cardiogenic shock (11.7%). Patients with de novo episode of AHF (36.2%) were younger, had less comorbidities and lower blood pressure despite greater left ventricular ejection fraction (LVEF) and were more often admitted to ICU. Overall, intravenous (IV) diuretics were given in 89.7%, vasodilators in 41.1%, and inotropic agents (dobutamine, dopamine, adrenaline, noradrenaline and levosimendan) in 39% of cases. Overall hospital death rate was 12%, the majority due to cardiogenic shock (43%). More patients with de novo AHF (14.2%) than patients with a pre-existing episode of AHF (10.8%) (p = 0.0007) died. There was graded mortality in ICU, CCU and ward patients with mortality in ICU patients being the highest (17.8%) (p < 0.0001). CONCLUSIONS: Our data demonstrated the existence of different subgroups based on de novo or pre-existing episode(s) of AHF and the site of hospitalization. Recognition of these subgroups might improve management and outcome by defining specific therapeutic requirements.


Subject(s)
Heart Failure/drug therapy , Heart Failure/physiopathology , Outcome Assessment, Health Care , Acute Disease , Aged , Aged, 80 and over , Female , Heart Failure/epidemiology , Hospital Mortality , Humans , Intensive Care Units , Internationality , Male , Middle Aged , Prognosis , Surveys and Questionnaires
20.
Phys Rev Lett ; 105(1): 017602, 2010 Jul 02.
Article in English | MEDLINE | ID: mdl-20867478

ABSTRACT

We demonstrate angle-resolved, tunable, two-photon photoemission (2PPE) to map a bulk unoccupied band, viz. the Cu sp band 0 to 1 eV below the vacuum level, in the vicinity of the L point. This short-lived bulk band is seen due to the strong optical pump rate, and the observed transition energies and their dispersion with photon energy ℏω, are in excellent agreement with tight-binding band-structure calculations. The variation of the final-state energy with ℏω has a measured slope of ∼1.64 in contrast to values of 1 or 2 observed for 2PPE from two-dimensional states. This unique variation illustrates the significant role of the perpendicular momentum ℏk_{⊥} in 2PPE.

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