RESUMO
UNLABELLED: INTRODUCTION: Some observations support the existence of epicardial connections (ECs) between ipsilateral pulmonary veins (vein to vein ECs [VVECs]), and we have observed venoatrial ECs inserted at distance from the pulmonary vein ostium (vein to atrium ECs [VAECs]). Our aim was to determine the prevalence of ECs and their relevance for pulmonary vein isolation. METHODS AND RESULTS: We studied 100 consecutive patients with drug-refractory atrial fibrillation who underwent ostial pulmonary vein isolation by cooled radiofrequency catheter ablation. A VVEC was identified if pulmonary vein pacing activated the ipsilateral vein before the atrium, requiring ablation of both venous ostia to isolate either pulmonary vein. A VAEC was identified if pacing produced atrial breakthrough located at distance from the venous ostium, requiring extraostial ablation to isolate the pulmonary vein. Patients with ECs (20%) were younger (P = 0.02) and had a higher prevalence of structural heart disease (P = 0.01) than patients without ECs. VVECs and VAECs were identified in 32 pulmonary veins (10%) and VAECs in 10 veins (3%). Veins with ECs had a higher rate of early recurrence of conduction following isolation (29% vs 11%; P = 0.01). CONCLUSION: Twenty percent of patients with atrial fibrillation had ECs resistant to ostial ablation in one or more pulmonary veins. Isolating veins with ECs may require a different ablation approach. These connections are associated with an increased rate of early recurrence of conduction. (J Cardiovasc Electrophysiol, Vol. 22, pp. 149-159, February 2011).
Assuntos
Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/cirurgia , Pericárdio/fisiopatologia , Veias Pulmonares/fisiopatologia , Mapeamento Potencial de Superfície Corporal , Feminino , Átrios do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/cirurgia , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
Paracrine interactions between ovarian theca-interstitial cells (TICs) and granulosa cells (GCs) play an important role in the regulation of follicular steroidogenesis. Androgens serve as substrates for aromatization as well as affect GC function. This study evaluated the effects of co-culture of GC with TICs and the role of testosterone (T) and 5-alpha-dihydrotestosterone (DHT), and estradiol (E2) in modulation of GC expression of genes involved in the production of progesterone: 3ß-hydroxysteroid dehydrogenase/Δ5-4 isomerase (Hsd3b) and cholesterol side-chain cleavage (Cyp11). GCs obtained from immature Sprague-Dawley rats and were cultured in chemically defined media without or with TICs, DHT, or T. Hsd3b and Cyp11 transcripts were analyzed by qt-PCR. Co-culture of GCs with TICs stimulated Hsd3b and CYP11 expression in GCs. DHT and T induced a concentration-dependent upregulation of Hsd3b and CYP11 expression, as well as increased progesterone concentrations in spent media. E2 also increased expression of Hsd3b, and Cyp11. Effects of androgens were abrogated in the presence of an anti-androgen bicalutamide and the antiestrogen ICI 182780 (ICI). In conclusion, present findings demonstrate that androgens upregulate production of progesterone in GCs; these effects are likely due to a combination of direct action on androgen receptors and effects mediated by estrogen receptors.
Assuntos
Androgênios/metabolismo , Di-Hidrotestosterona/metabolismo , Estradiol/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Testosterona/metabolismo , Células Tecais/efeitos dos fármacos , Células Tecais/metabolismo , Animais , Células Cultivadas , Feminino , RNA Mensageiro/metabolismo , Ratos Sprague-DawleyRESUMO
GLUT9 is a novel, facilitative glucose transporter isoform that exists as two alternative splice variants encoding two proteins that differ in their NH(2)-terminal sequence (GLUT9a and GLUT9b). Both forms of GLUT9 protein and mRNA are expressed in the epithelia of various tissues; however, the two splice variants are expressed differentially within polarized cells, with GLUT9a localized predominantly on the basolateral surfaces and GLUT9b expressed on apical surfaces. Protein expression of GLUT9 drops under conditions of starvation but increases with addition of glucose and under hyperglycemic conditions. The substrate specificity of GLUT9 is unique since, in addition to transporting hexose sugars, it also is a high-capacity uric acid transporter. Several recent large-scale human genetic studies show a correlation between SNPs mapped to GLUT9 and the serum uric acid levels in several different cohorts. The relationship between GLUT9 and uric acid is highly clinically significant. Elevated uric acid levels have been associated with metabolic syndrome, obesity, diabetes, hypertension, and chronic renal failure. Although some believe uric acid is elevated as a result of these diseases, there is now evidence that uric acid may play a role in the pathogenesis of these diseases. It is also known that GLUT9 is expressed in articular cartilage and is a uric acid transporter, and thus it is possible that GLUT9 plays a role in gout, a disease of uric acid deposition in the joints. In addition, some studies have suggested that intake of fructose plays an important role in causing elevated serum uric acid levels, especially in diabetes and obesity. It is possible that GLUT9, which seems to be both a fructose and a uric acid transporter, plays an important role in these conditions associated with hyperuricemia.
Assuntos
Proteínas Facilitadoras de Transporte de Glucose/fisiologia , Hexoses/metabolismo , Ácido Úrico/metabolismo , Animais , Transporte Biológico Ativo , Proteínas Facilitadoras de Transporte de Glucose/biossíntese , Proteínas Facilitadoras de Transporte de Glucose/química , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Isoformas de Proteínas/genética , Ácido Úrico/sangueRESUMO
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by theca cell hyperplasia and excessive androgen production. An increasing body of evidence has pointed to a close association between PCOS and low-grade chronic systemic inflammation. However, the mechanistic basis for this linkage is unknown. Therefore, we evaluated the effects of the inflammatory agents lipopolysaccharide (LPS) and IL-1ß on rat theca-interstitial cells (TICs). We found that incubation with either LPS or IL-1ß elicited a dose-dependent increase in both TIC viability and androgen production. Using RNA sequencing analysis, we found that both of these inflammatory agents also triggered profound and widespread shifts in gene expression. Using a stringent statistical cutoff, LPS and IL-1ß elicited differential expression of 5201 and 5953 genes, respectively. Among the genes upregulated by both LPS and IL-1ß were key regulatory genes involved in the cholesterol and androgen biosynthesis pathways, including Cyp17a1, Cyp11a1, Hsd3b, and Hmgcr. This provides a molecular explanation for the mechanism of action of inflammatory agents leading to increased androgen production. Gene ontology and pathway analysis revealed that both LPS and IL-1ß regulated genes highly enriched for many common functions, including the immune response and apoptosis. However, a large number of genes (n = 2222) were also uniquely regulated by LPS and IL-1ß, indicating that these inflammatory mediators have substantial differences in their mechanism of action. Together, these findings highlight the potential molecular mechanisms through which chronic low-grade inflammation contributes to the pathogenesis of androgen excess in PCOS.
Assuntos
Androgênios/biossíntese , Inflamação/complicações , Síndrome do Ovário Policístico/etiologia , Células Tecais/metabolismo , Animais , Feminino , Expressão Gênica , Interleucina-1beta , Lipopolissacarídeos , Ácido Mevalônico/metabolismo , Síndrome do Ovário Policístico/metabolismo , Ratos Sprague-DawleyRESUMO
BACKGROUND: Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man. METHODS AND FINDINGS: We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 microM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 microM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case-control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size -0.12 mm Hg, 95% CI -0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82). CONCLUSIONS: This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.
Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Ácido Úrico/metabolismo , Adulto , Idoso , Animais , Transporte Biológico/efeitos dos fármacos , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Cromatografia em Camada Fina , Ácidos Graxos Voláteis/farmacologia , Feminino , Frutose/metabolismo , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Hexoses/metabolismo , Humanos , Imuno-Histoquímica , Cinética , Estudos Longitudinais , Camundongos , Pessoa de Meia-Idade , Oócitos , Transportadores de Ânions Orgânicos/genética , Uricosúricos/farmacologia , Xenopus laevisRESUMO
BACKGROUND: Findings from animal studies and small series of patients support the greater safety of cryoenergy over radiofrequency in the ablation of arrhythmic substrates near the AV node. OBJECTIVES: The purpose of this study was to systematically evaluate the electrophysiologic effects of successive cryoenergy applications to the human AV node in order to better define the safety margin of cryothermal ablation. METHODS: In 15 patients referred for AV nodal ablation, 94 cryomapping and 105 cryoablation applications were delivered through a 6-mm-tip cryothermal ablation catheter (Freezor Xtra, CryoCath) at predefined sites of the triangle of Koch. RESULTS: Temporary effects on AV conduction were observed in 18 (19%) cryomapping and 38 (36%) cryoablation applications. Persistent effects were observed in 9 (9%) cryoablation applications. Persistent effects were associated with cryoablation at the superior third of the triangle of Koch (P = .05), nadir tip temperature < or = -79 degrees C (P = .007), and effect onset time < or =15 seconds (P = .03). Temperature and effect onset time remained statistically significant after multivariate adjustment (P = .01 and .02, respectively). Overall, persistent complete AV block was achieved with cryoenergy in only one patient. In two additional patients, AV conduction remained modified. In the remaining patients, persistent complete AV block was achieved with radiofrequency (median one application per patient). CONCLUSION: The low rate of persistent AV conduction impairment observed with attempts to cryoablate the AV node supports a great safety margin of perinodal cryothermal ablation.
Assuntos
Nó Atrioventricular/cirurgia , Criocirurgia/métodos , Taquicardia Atrial Ectópica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Nó Atrioventricular/fisiopatologia , Eletrocardiografia , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Índice de Gravidade de Doença , Taquicardia Atrial Ectópica/fisiopatologia , Resultado do TratamentoRESUMO
INTRODUCTION AND OBJECTIVES: The identification and ablation of atrial ectopic foci could complement the conventional empirical pulmonary vein approach and may increase the success rate of atrial fibrillation ablation. Although both adenosine and isoproterenol infusion have been reported to induce ectopics, no clear findings on their use during ablation have been published. Our aim was to investigate the utility of these two pharmacologic maneuvers in patients referred for atrial fibrillation ablation. METHODS: The effects of adenosine infusion, isoproterenol infusion, or both were evaluated in 53 patients with refractory atrial fibrillation referred for ablation. Patients were in sinus rhythm during evaluation. RESULTS: Administration of adenosine or isoproterenol induced atrial arrhythmias in 46 patients (87%). Arrhythmia inducibility was similar in those with paroxysmal and those with persistent atrial fibrillation (87% and 86%, respectively). Atrial ectopics alone were induced in 31 patients (65%), atrial tachycardia in four (8%), and atrial fibrillation in 13 (27%). In 10 patients (19%), ectopic foci were located outside the pulmonary veins and subsequently underwent ablation. In 32 of the 46 patients with inducible arrhythmias, only the induced ectopic foci were ablated (mean 1.4 [0.6] targets per patient). The long-term success rate of first procedures was 66%. CONCLUSION: Adenosine and isoproterenol infusion induced atrial ectopics in most patients with drug-refractory atrial fibrillation while they were in sinus rhythm. In almost 20%, the ectopic foci were located outside the pulmonary veins. The effectiveness of induced ectopic-guided ablation observed in our patient series supports the clinical utility of this approach.
Assuntos
Adenosina/administração & dosagem , Fibrilação Atrial/cirurgia , Ablação por Cateter , Isoproterenol/administração & dosagem , Fibrilação Atrial/fisiopatologia , Interpretação Estatística de Dados , Eletrofisiologia , Seguimentos , Humanos , Fatores de Tempo , Resultado do TratamentoRESUMO
The X-Sizer thromboatherectomy catheter represents an important advance for thrombectomy in thrombus-containing lesions, especially in patients who require primary and rescue angioplasty. Although it is safe, some complications have been reported as its use becomes more widespread. To our knowledge, the intracoronary breakage and retention of the angioplasty guidewire has not been reported. We describe a case of this rare complication and analyze the causes, prevention and treatment alternatives.
Assuntos
Angioplastia Coronária com Balão/instrumentação , Aterectomia Coronária/instrumentação , Adulto , Falha de Equipamento , Humanos , Masculino , Infarto do Miocárdio/terapiaRESUMO
BACKGROUND AND OBJECTIVES: The adverse effects of systemic hypertension and diabetes mellitus in coronary patients are well known, although their long-term prognostic influence on patients with unstable angina (UA) undergoing percutaneous coronary intervention (PCI) with coronary stenting is uncertain. The aim of this study was to determine the influence of these pathologies in this population at 3-year follow-up. PATIENTS AND METHOD: We studied 279 consecutive patients with UA who underwent coronary stenting. 129 (46.2%) of them had hypertension and 60 (24.7%) had diabetes. Clinical follow-up was obtained in 92.14% after 3 years. RESULTS: Although the need for new PCI at the target lesion was higher for patients with hypertension and diabetes (12.1 vs 8.4%; p=0.31, and 14.5 vs 8.6%; p=0.16, respectively), the differences were not significant with respect to the control groups. Multivariate analysis showed hypertension (OR=4.71; CI 95%, 1.01-42.2; p=0.04) and ejection fraction (OR=0.95; CI 95%, 0.91-0.99; p=0.03) to be predictors of mortality, and diabetes to be a predictor of myocardial infarction and infarction resulting in death (OR=3.01; CI 95%, 1.13-8.02; p=0.02, and OR=2.68; CI 95%, 1.03-6.95; p=0.04, respectively). CONCLUSIONS: Hypertension was the only independent long-term predictor of mortality in our series of patients with UA who underwent coronary stenting. Diabetes was the only predictor of myocardial infarction or for the combined event of infarction and death. Risk of myocardial infarction was threefold as high in this diabetic patient population, and was the main cause of mortality.
Assuntos
Angina Instável/complicações , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Complicações do Diabetes , Angiopatias Diabéticas/complicações , Hipertensão/complicações , Stents , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Few data exist regarding IVF in women who have undergone bariatric surgery. Our experience with five patients suggests that IVF is a safe and effective fertility treatment for these women, although special considerations should be made when treating patients who have undergone bariatric surgery. Considering the type of bypass procedure the patient underwent is particularly important should a patient develop concerning symptoms during her IVF cycle.
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Cirurgia Bariátrica/reabilitação , Fertilização in vitro , Infertilidade/terapia , Adulto , Doenças das Tubas Uterinas/complicações , Doenças das Tubas Uterinas/terapia , Feminino , Humanos , Infertilidade/etiologia , Leiomioma/complicações , Leiomioma/terapia , Masculino , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Gravidez , Neoplasias Uterinas/complicações , Neoplasias Uterinas/terapiaAssuntos
Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Infarto do Miocárdio/etiologia , Idoso , Angioplastia/métodos , Angiografia Coronária , Anomalias dos Vasos Coronários/cirurgia , Humanos , Masculino , Resultado do TratamentoRESUMO
Facilitative glucose transporters (GLUTs) including GLUT9, accelerate the facilitative diffusion of glucose across the plasma membrane. Studies in GLUT2-deficient mice suggested the existence of another GLUT in the mammalian beta-cell responsible for glucose sensing. The objective of this study was to determine the expression and function of GLUT9 in murine and human beta-cells. mRNA and protein expression levels were determined for both isoforms of GLUT9 in murine and human isolated islets as well as insulinoma cell lines (MIN6). Immunohistochemistry and subcellular localization were performed to localize the protein within the cell. Small interfering RNA knockdown of GLUT9 was used to determine the effect of this transporter, in the presence of GLUT2, on cell metabolism and insulin secretion in MIN6 and INS cells. In this report we demonstrate that GLUT9a and GLUT9b are expressed in pancreatic islets and that this expression localizes to insulin-containing beta-cells. Subcellular localization studies indicate that mGLUT9b is found associated with the plasma membrane as well as in the high-density microsome fraction and low-density microsome fraction, whereas mGLUT9a appears to be located only in the high-density microsome and low-density microsome under basal conditions. Functionally GLUT9 appears to participate in the regulation of glucose-stimulated insulin secretion in addition to GLUT2. small interfering RNA knockdown of GLUT9 results in reduced cellular ATP levels that correlate with reductions in glucose-stimulated insulin secretion in MIN6 and INS cells. These studies confirm the expression of GLUT9a and GLUT9b in murine and human beta-cells and suggest that GLUT9 may participate in glucose-sensing in beta-cells.
Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Expressão Gênica , Glucose/farmacologia , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Imuno-Histoquímica , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microssomos/metabolismo , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
PURPOSE OF REVIEW: It has been known for decades that diabetic women have somewhat decreased fertility and that their offspring have an increased risk of being born with developmental abnormalities. We review results from studies examining the impact of maternal hyperglycemia and diabetes on oocyte and early embryo development. We focus on the effects of the maternal milieu on metabolism, cell signaling and the regulation of glucose-transporter expression in the developing oocyte and embryo. RECENT FINDINGS: Offspring of diabetic mothers have metabolic disease at higher rates than can be explained by genetic inheritance alone. Oocytes from hyperglycemic animals display several abnormalities and are of lower quality than oocytes from control animals. There appears to be a decrease in glucose transport in embryos exposed to a hyperglycemic environment, which may lead to programmed cell death. SUMMARY: Maternal hyperglycemia and diabetes have detrimental effects on the developing embryo at several stages of development. Although the exact pathophysiology of the developmental defects seen in infants born to diabetic mothers remains unclear, the role of glucose transport and regulation seems to play a critical role in early growth and development.
Assuntos
Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Glucose/metabolismo , Gravidez em Diabéticas/metabolismo , Animais , Feminino , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Homeostase , Humanos , Oócitos/metabolismo , Oócitos/patologia , Gravidez , Gravidez em Diabéticas/patologiaRESUMO
INTRODUCTION AND OBJECTIVES: Contemporary atrial pacemakers incorporate pacing modes for treating atrial arrhythmias. Because atrial fibrillation in the right atrium can exhibit an organized pattern, it can be difficult to differentiate from atrial flutter. We assessed criteria for discriminating between atrial flutter and organized atrial fibrillation when using a bipolar electrode in the right atrium. METHODS: Simultaneous bipolar electrograms of the right and left atria were obtained in 45 patients: Group I comprised 15 patients with atypical flutter, Group II comprised 15 with typical flutter, and Group III, 15 with organized atrial fibrillation in the right atrium. The mean cycle length and the mean variation in cycle length observed over 15 seconds in electrograms of the right atrium were recorded. RESULTS: The mean cycle length was longer in Groups I and II than in Group III (232 [21] ms and 234 [24] ms, respectively, versus 183 [16] ms; P< .001). The mean variation in cycle length was less in Groups I and II than in Group III (16 [7] ms and 13 [4] ms, respectively, versus 22 [7] ms; P< .01). A cycle length > or =203 ms discriminated atrial flutter from atrial fibrillation with a sensitivity of 97% and a specificity of 87%. A cycle length variation < or =18 ms discriminated atrial flutter from atrial fibrillation with a sensitivity of 70% and a specificity of 80%. CONCLUSIONS: Cycle length was better than the variation in cycle length for differentiating atrial flutter from organized atrial fibrillation.