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1.
Anim Genet ; 52(5): 598-607, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34350996

RESUMO

Fat deposition is an important economic trait in farm animals. However, it is difficult to genetically improve intramuscular fat deposition via trait-based cattle breeding. The main objectives of this study were to analyze the factors about beef flavor, and to detect functional microRNA (miRNA, miR) associated with intramuscular fat deposition in Yanbian cattle. Longissimus dorsi samples from six steers were separated into high- and low-fat groups (n = 3 each) based on the marbling score, and transcriptomic analysis was performed using miRNA sequencing. A total of 33 miRNAs and 38 genes were found to be differentially expressed in the high- and low-fat groups. Quantitative real-time polymerase chain reaction was performed to validate the sequencing results. Integrated miRNA-mRNA analysis revealed that miRNA-associated target genes were primarily associated with skeletal muscle development. However, some of the miRNAs (miR-424 etc.) and genes (ATF3 etc.) were also associated with fat metabolism. A targeted relationship between miR-22-3p and the WFIKKN2 gene and its involvement in adipocyte differentiation were confirmed experimentally. The study findings may provide potential candidate molecular targets for the selection of cattle with improved meat quality.


Assuntos
Bovinos/genética , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , Desenvolvimento Muscular/genética , RNA Mensageiro/genética , Adipócitos , Animais , Células Cultivadas , Masculino , Transcriptoma
2.
Zhonghua Yi Xue Za Zhi ; 101(13): 926-933, 2021 Apr 06.
Artigo em Chinês | MEDLINE | ID: mdl-33789373

RESUMO

Objective: To classify and quantify IKZF1 mutant transcripts in B-cell acute lymphoblastic leukemia (B-ALL) by RNA sequencing (RNA-seq) and bioinformatics analysis. Methods: A cohort of 263 B-ALL cases was enrolled at Hebei Yanda Ludaopei Hospital from September 2018 to September 2020. An integrated bioinformatics pipeline was developed to adapt the classification and quantification of IKZF1 transcripts from RNA-seq and was applied to sequencing data of these cases. The IKZF1 mutant transcripts classified by RNA-seq analysis were compared with the qualitative reverse transcription PCR (RT-PCR). Results: IKZF1 mutant transcripts were identified in 53 B-ALL patients by RT-PCR and Sanger sequencing, among which IK6 and IK10 transcripts accounted for 67.9% (36/53) and 28.3% (15/53) respectively. Additionally, 2 patients were double positive for IK6 and IK10. RNA-seq analysis identified 51 patients with IKZF1 mutant transcripts. Compared with the RT-PCR result, the detection sensitivity and specificity of RNA-seq analysis reached 94.3% (50/53) and 99.5% (209/210), respectively. Among the 50 patients with IKZF1 mutant transcripts both in RNA-seq and RT-PCR analysis, the ratio of mutant transcripts to total IKZF1 transcripts in 6 patients was 0.14 (0.11, 0.35), which was significantly lower than that of the other 44 patients [0.88 (0.35, 0.97), Z=-3.945,P<0.001]. IKZF1 mutations mostly occurred in Ph+and Ph-like B-ALL, characterized by abnormal JAK-STAT pathway, and B-ALL with PAX5 translocation. Conclusions: Through the optimized bioinformatics analysis process, RNA-seq data can be used to classify and quantitatively analyze IKZF1 transcripts in B-ALL. Furthermore, the relative expression of mutant IKZF1 transcripts was found to cluster into two groups, and IKZF1 mutation was found often accompanied with PAX5 translocations.


Assuntos
Fator de Transcrição Ikaros , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos B/metabolismo , Humanos , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Isoformas de Proteínas , Transcriptoma
3.
Zhonghua Yi Xue Za Zhi ; 100(43): 3443-3447, 2020 Nov 24.
Artigo em Chinês | MEDLINE | ID: mdl-33238676

RESUMO

Objective: To explore the application and discovery of genotyping, gene sequencing, and gene expression analysis in the determination of ABO blood group subtypes and antigen expression abnormalities in hematological malignancies patients. Methods: From June 2019 to May 2020, three clinical cases were found with forward and reverse ABO typing discrepancy or atypical serologic agglutination pattern in the laboratory and blood transfusion department of Hebei Yanda Ludaopei Hospital were selected. Sequence-specific primer PCR (PCR-SSP) and Sanger sequencing of ABO gene coding regions were performed to determine the ABO genotypes, and whole transcriptome sequencing was used to analyze ABO and FUT1 gene expression levels. Results: A 12-year-old female acute lymphoblastic leukemia patient was determined as O.01.02 and BA.04 sub-genotype, corresponding to the serological B(A) subtype, and her ABO gene expression was normal (354.80). A 41-year-old female acute myeloid leukemia patient was determined as A1.02 and B.01 genotype, corresponding to the serological A(1)B phenotype, and her ABO gene expression was significantly reduced (45.70). A 42-year-old male with myelodysplastic syndrome and myelofibrosis was determined as A1.02 and A2.05 sub-genotype, corresponding to the serological A(1) and A(2) phenotype, respectively, and his ABO expression was negative. FUT1 expression was in the normal range in all three cases. The clinical blood product infusion strategy was formulated according to the genotype and the corresponding immunological subtype, and no significant transfusion-related adverse reactions occurred. Conclusion: Blood group sub-genotypes or aberrant gene expression can lead to ambiguities in serological blood group determination in hematological malignancies patients. ABO genotyping and gene expression analysis can help in this scenario and escort blood product infusion safety.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas , Neoplasias Hematológicas , Sistema ABO de Grupos Sanguíneos/genética , Adulto , Alelos , Criança , Genótipo , Neoplasias Hematológicas/genética , Humanos , Masculino , Fenótipo
4.
Biochemistry (Mosc) ; 85(7): 749-757, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33040719

RESUMO

Yanbian yellow cattle are one of the top five largest breeds of cattle in China. We had previously found that bta-miR-1271 is differentially expressed in the longissimus dorsi muscles of Yanbian yellow bulls and steers. However, whether bta-miR-1271 affects bovine fat formation is unclear. In this study, we used target gene prediction, dual-luciferase reporter assay, and transfection-mediated overexpression and inhibition of bta-miR-1271 in a culture of Yanbian yellow cattle preadipocytes to investigate the role of bta-miR-1271 in adipogenesis. We showed that bta-miR-1271 directly targets the 3'-untranslated region (3'-UTR) of the activating transcription factor 3 (ATF3) mRNA and downregulates its expression. Overexpression of bta-miR-1271 enforced by the miRNA mimics promoted triglyceride accumulation and significantly upregulated expression of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα) genes at both the protein and mRNA levels, as demonstrated by RT-qPCR and Western blot analyses. Conversely, inhibition of bta-miR-1271 expression produced the opposite effect. Our results show that bta-miR-1271 regulates differentiation of Yanbian yellow cattle preadipocytes by inhibiting ATF3 expression, which highlights the importance of microRNA-mediated regulation of adipogenesis. miR-1271 and its target gene(s) may provide a new research direction for investigating biological agents affecting intramuscular fat deposition in cattle.


Assuntos
Fator 3 Ativador da Transcrição/genética , Adipócitos/citologia , Adipócitos/metabolismo , MicroRNAs/metabolismo , Fator 3 de Transcrição/metabolismo , Regiões 3' não Traduzidas , Fator 3 Ativador da Transcrição/metabolismo , Adipogenia/fisiologia , Animais , Bovinos , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Masculino , MicroRNAs/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator 3 de Transcrição/genética
5.
Eur Rev Med Pharmacol Sci ; 23(9): 3719-3725, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31114997

RESUMO

OBJECTIVE: Renal cancer represents about 3% of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. MicroRNAs (miRNAs) have been reported to play crucial roles in the carcinogenesis of human cancers. This study was aimed to investigate the expression of miR-1294 and the mechanisms underlying miR-1294-mediated ccRCC progression. MATERIALS AND METHODS: The miR-1294 expression levels in ccRCC cell lines were analyzed by quantified real time-PCR (qRT-PCR). The effect of the miR-1294 expression on the overall survival of ccRCC patients was analyzed by the Kaplan-Meier Plotter. Cell proliferation, colony growth, and cell invasion were examined by cell counting kit-8 assay, colony formation assay, and transwell invasion assay, respectively. The luciferase activity reporter assay and Western blot assay were conducted to validate the connection between miR-1294 and homeobox A6 (HOXA6). RESULTS: MiR-1294 was downregulated in ccRCC cell lines and correlated with the poor overall survival of ccRCC patients. The overexpression of miR-1294 inhibits ccRCC cell proliferation, colony growth, and cell invasion. HOXA6 was validated as a target of miR-1294 and negatively regulated by miR-1294. The overexpression of HOXA6 attenuated the miR-1294-mediated effects on ccRCC cellular functions. CONCLUSIONS: Our results indicated that miR-1294 functions as a tumor suppressor in ccRCC. MiR-1294 suppressed cell proliferation, colony formation, and invasion in ccRCC partially via targeting HOXA6.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Genes Supressores de Tumor , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Reação em Cadeia da Polimerase em Tempo Real
6.
J Econ Entomol ; 100(1): 20-5, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17370804

RESUMO

Xestia c-nigrum granulovirus (XcGV) was tested for its ability to increase Spodoptera litura nucleopolyhedrovirus (SINPV) infection in larvae of S. litura (F.). The interaction of XcGV with peritrophic matrix and SINPV in S. litura also was studied to account for the synergism. In dose-response bioassays with a constant XcGV concentration of 5-mg/ ml capsules and SINPV concentration that varied from 10(3) to 10(7) polyhedral inclusion bodies (PIB) per larva, XcGV increased the virulence of SINPV infection in fifth instars of S. litura. The lethal concentration of 50% individuals (LC50) of SINPV combined with XcGV was 3.35 x 10(5)PIB/ml, which was significantly lower than that of SINPV alone (2.17 x 10(6)). Compared with 10(7) PIB/ml SINPV alone, the lethal time of 50% individuals (LT50) of 10(7) PIB/ml SINPV combined with XcGV was not significantly shortened. In addition, no significant improvement in the activity and killing speed of SINPV progeny was noted after propagation with XcGV, indicating that native characters of SINPV associated with viral potency were not altered by XcGV. Investigation via environmental scanning electronic microscopy showed that the peritrophic matrix (PM) of S. litura exposed to XcGV or XcGV enhancin, or the combination treatment, was markedly disrupted. The outer surface of the PM was loose, or ruptured, which potentially facilitated the passage of virions through the PM. Therefore, it is reasonable to conclude that the synergy between XcGV and SINPV was closely associated with the disruption of the PM in S. litura.


Assuntos
Granulovirus/metabolismo , Nucleopoliedrovírus/metabolismo , Spodoptera/virologia , Proteínas Virais/metabolismo , Animais , Granulovirus/classificação , Larva/virologia , Controle Biológico de Vetores/métodos , Ligação Proteica
7.
J Heart Lung Transplant ; 25(12): 1402-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17178332

RESUMO

BACKGROUND: The utility of long-term endomyocardial biopsy surveillance in heart transplant recipients has been questioned. This study was undertaken to identify risk factors for late rejection and to examine the impact of different biopsy surveillance protocols on outcomes using the registry of the Cardiac Transplant Research Database. METHODS: The study group consisted of all adult patients who underwent heart transplantation at the 33 centers participating in this investigation between January 1, 1993 and January 1, 2002, survived past the second post-transplant year, and were followed-up by a defined surveillance biopsy protocol. RESULTS: During a follow-up that consisted of 24,137 patient-years, 1,626 late rejections occurred. Shorter time since transplant, history of rejection, younger age and African-American ethnicity of the recipient were strong risk factors for late rejection. The practice of surveillance biopsy varied among institutions. Continued surveillance increased the rate of diagnosis of late rejection (RR = 1.3, p = 0.002). There was no reduction in the incidence of hemodynamically compromising rejection and no increase in survival in patients with long-term vs intermediate-term surveillance. Short-term surveillance was associated with an increased incidence of hemodynamically compromising rejection, particularly among high-risk patients, and increased mortality in African-American patients. CONCLUSIONS: There are no apparent benefits from surveillance biopsy beyond 5 years post-transplant. Surveillance biopsy between 2 and 5 years post-transplant was found to reduce mortality in African-American recipients. Non-African-American recipients at high risk for late rejection will likely benefit from surveillance up to 5 years post-transplant.


Assuntos
Endocárdio/patologia , Transplante de Coração/efeitos adversos , Miocárdio/patologia , Vigilância da População/métodos , Adulto , Afro-Americanos/estatística & dados numéricos , Biópsia , Sistema Cardiovascular/fisiopatologia , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Transplante de Coração/etnologia , Humanos , Imunossupressão , Incidência , Pessoa de Meia-Idade , Período Pós-Operatório , Sistema de Registros , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
8.
Circulation ; 104(21): 2558-64, 2001 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-11714650

RESUMO

BACKGROUND: Chemokines play an essential role in regulating the infiltration of leukocytes into allografts in experimental models. Little is known of their expression or function after human cardiac transplantation. METHODS AND RESULTS: We analyzed 169 sequential human endomyocardial biopsies by immunocytochemistry for infiltration by CD3(+) T cells and the expression of the chemokine receptors CCR1, CCR3, CCR5, and CXCR3. In both cross-sectional and longitudinal analyses, the expression of each of the chemokine receptors correlated with the degree of CD3(+) T-cell infiltration. In particular, the expression of CXCR3 was temporally and spatially associated with CD3(+) T-cell infiltrates and correlated with the histopathological diagnosis of acute rejection (OR, 11.73 and 4.05, respectively; P<0.001). Of 7 patients followed up longitudinally for 1 year, 4 with consecutive biopsies developed intimal thickening by intravascular ultrasound. In these patients, there was a trend for persistent expression of CD3- and CXCR3-expressing infiltrates in the later part of the first posttransplant year. The chemokines eotaxin, IP-10, lymphotactin, MCP-1, Mig, RANTES, and SDF-1 were examined in an additional 35 biopsies by RT-PCR. Eotaxin, lymphotactin, MCP-1, Mig, and SDF-1 were present in both normal and rejecting biopsies. However, the CXCR3 ligand IP-10, which was rarely expressed in normal biopsies, was markedly induced in acute rejection (OR, 19.43; P=0.01). CONCLUSIONS: The presence of CXCR3(+) T cells and the CXCR3 ligand IP-10 within endomyocardial biopsies is strongly associated with acute rejection. The CXCR3-IP-10 interaction warrants consideration as a therapeutic target in the management of cardiac allograft recipients.


Assuntos
Quimiocinas CXC/biossíntese , Rejeição de Enxerto/metabolismo , Transplante de Coração , Receptores de Quimiocinas/biossíntese , Transcrição Genética , Adulto , Biópsia , Complexo CD3/análise , Quimiocina CXCL10 , Quimiocinas/biossíntese , Quimiocinas/genética , Quimiocinas CXC/genética , Estudos Transversais , Feminino , Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , RNA Mensageiro/biossíntese , Receptores CXCR3 , Receptores de Quimiocinas/genética , Linfócitos T/imunologia
9.
Hypertension ; 38(5): 1049-53, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11711496

RESUMO

Arterial elasticity is determined by structural characteristics of the artery wall and by vascular smooth muscle tone. The identity of endogenous vasoactive substances that regulate elasticity has not been defined in humans. We hypothesized that NO, a vasodilator released constitutively by the endothelium, augments arterial elasticity. Seven healthy young men were studied. A 20-MHz intravascular ultrasound catheter was introduced through an arterial sheath to measure brachial artery cross-sectional area, wall thickness, and intra-arterial pressure. After control was established, indices of elasticity (pressure-area relationship, instantaneous compliance, and stress-strain, pressure-incremental elastic modulus (E(inc)), and pressure-pulse wave velocity relationships) were examined over 0 to 100 mm Hg transmural pressure obtained by inflation of an external cuff. Thereafter, the basal production of endothelium-derived NO was inhibited by N(G)-monomethyl-L-arginine (L-NMMA) (4 and 8 mg/min). Finally, nitroglycerin (2.5 and 12.5 microgram/min), an exogenous donor of NO, was given to relax the vascular smooth muscle. Elasticity was measured under all of these conditions. L-NMMA (8 mg/min) decreased brachial artery area (P=0.016) and compliance (P<0.0001) and increased E(inc) (P<0.01) and pulse wave velocity (P<0.0001). Nitroglycerin (12.5 microgram/min) increased brachial artery area (P<0.001) and compliance (P<0.001) and decreased pulse wave velocity (P=0.02). NO, an endothelium-derived vasodilator, augments arterial elasticity in the human brachial artery. Loss of constitutively released NO associated with cardiovascular risk factors may adversely affect arterial elasticity in humans.


Assuntos
Artérias/fisiologia , Endotélio Vascular/metabolismo , Óxido Nítrico/fisiologia , Adulto , Anatomia Transversal , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/anatomia & histologia , Artéria Braquial/fisiologia , Doenças Cardiovasculares/etiologia , Complacência (Medida de Distensibilidade)/efeitos dos fármacos , Elasticidade/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Humanos , Masculino , Doadores de Óxido Nítrico/farmacologia , Nitroglicerina/farmacologia , Fatores de Risco , Estresse Mecânico , ômega-N-Metilarginina/farmacologia
10.
Circulation ; 104(10): 1114-8, 2001 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-11535565

RESUMO

BACKGROUND: Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries. METHODS AND RESULTS: In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01). CONCLUSIONS: ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Endotelina-1/fisiologia , Vasoconstrição/fisiologia , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Antagonistas dos Receptores de Endotelina , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Nitroglicerina/farmacologia , Peptídeos Cíclicos/farmacologia , Receptor de Endotelina A , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologia
11.
FEBS Lett ; 482(1-2): 154-8, 2000 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-11018540

RESUMO

The binding of glycosaminoglycans to a synthetic peptide (SKAQKAQAKQAKQAQKAQKAQAKQAKQW-CONH(2)), consisting of a hybrid consensus heparin binding sequence, is studied using circular dichroism, fluorescence anisotropy and nuclear magnetic resonance techniques. The results unveil certain novel features, most importantly, the peptide binds preferentially to iduronic acid containing glycosaminoglycans and the dissociation constant for the peptide-heparin complex was found to be 30 nM. Interestingly, higher order intermolecular association(s)/aggregation was not observed, especially at saturating concentrations of the ligand. The helical structure of the peptide backbone, induced upon binding to a particular glycosaminoglycan is directly related to their binding affinity. In our opinion, studies on such unconventional hybrid peptide sequences containing low density basic amino acid residues would lead to the design of sequence specific glycosaminoglycan binding peptides.


Assuntos
Glicosaminoglicanos/química , Peptídeos/química , Sequência de Aminoácidos , Configuração de Carboidratos , Dicroísmo Circular , Sequência Consenso , Polarização de Fluorescência , Heparina/química , Lisina , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/síntese química , Conformação Proteica , Dobramento de Proteína
14.
Expert Opin Pharmacother ; 1(6): 1171-94, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11249486

RESUMO

Gastro-oesophageal reflux disease (GERD) is the most common peptic acid disease in the western world and is the commonest indication for acid suppression therapy. Major advances have been made over the past 30 years in the understanding of lower oesophageal sphincter function and the mechanism of acid secretion. Developments in surgical and pharmacological therapy have paralleled these advances. Pharmacotherapy for GERD has evolved from antacids to H2-receptor antagonists (H2RAs) to prokinetics to proton pump inhibitors (PPIs). The H2RAs, while modestly effective in symptom relief and healing of GERD, are limited by pharmacological tolerance. The prokinetics (metoclopramide and cisapride) are limited by low efficacy, pharmacological tolerance and toxicity. The PPIs have emerged as the most effective therapy for symptom relief, healing and long-term maintenance. They have also proved to be remarkably safe and cost-effective in long-term therapy. This review evaluates the pharmacology, efficacy, tolerability, safety and cost-effectiveness of the four currently available PPIs, lansoprazole, omeprazole, pantoprazole and rabeprazole, in the treatment of GERD.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Inibidores da Bomba de Prótons , Animais , Ensaios Clínicos como Assunto , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Refluxo Gastroesofágico/complicações , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/farmacologia , Humanos
15.
Curr Opin Cardiol ; 15(6): 422-9, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11198625

RESUMO

Cardiac transplantation has emerged as a valuable therapy for various end-stage cardiac disorders. Cardiac allograft vasculopathy (CAV), an unusually accelerated and diffuse form of obliterative coronary arteriosclerosis, determines long-term function of the transplanted heart. Cardiac allograft vasculopathy is a complicated interplay between immunologic and nonimmunologic factors resulting in repetitive vascular injury and a localized sustained inflammatory response. Dyslipidemia, oxidant stress, immunosuppressive drugs, and viral infection appear to be important contributors to disease development. Endothelial dysfunction is an early feature of CAV and progresses over time after transplantation. Early identification of CAV is essential if long-term prognosis is to be improved. Annual coronary angiography is performed for diagnostic and surveillance purposes. Intravascular ultrasound is a more sensitive diagnostic tool for early disease stages and has revealed that progressive luminal narrowing in CAV is in part due to negative vascular remodeling. Because of the diffuse nature of CAV, percutaneous and surgical revascularization procedures have a limited role. Prevention of CAV progression is a primary therapeutic goal.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Transplante de Coração , Complicações Pós-Operatórias/fisiopatologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Progressão da Doença , Endotélio Vascular/fisiopatologia , Humanos , Hiperlipidemias/epidemiologia , Lipídeos/sangue , Fatores de Risco , Transplante Homólogo , Ultrassonografia de Intervenção
16.
Circulation ; 100(3): 219-21, 1999 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-10411842

RESUMO

BACKGROUND: In the presence of atherosclerosis, the coronary endothelial vasomotor response to acetylcholine is frequently abnormal but is variable between patients. We tested the hypothesis that the plasma concentration of alpha-tocopherol is associated with the preservation of nitric oxide-mediated endothelium-dependent vasomotion. METHODS AND RESULTS: We studied 15 men and 6 women (mean age 61+/-10 years) at coronary angiography who were not taking vitamin supplements. Coronary endothelium-dependent and -independent vasomotion was assessed by intracoronary infusions of acetylcholine and nitroglycerin. The vasomotor responses were compared with the plasma concentration of alpha-tocopherol and the plasma alpha-tocopherol concentration relative to total lipid (total cholesterol plus triglycerides). The mean plasma alpha-tocopherol was 25.6+/-6.1 micromol/L, total cholesterol 193+/-27 mg/dL, triglycerides 115+/-66 mg/dL, and alpha-tocopherol to total lipid 4. 2+/-0.9 micromol. L(-1). (mmol/L)(-1). The mean vasomotor response to acetylcholine was -1% (range -33% to 28%) and to nitroglycerin 22% (range 0% to 54%). Plasma alpha-tocopherol was significantly correlated with the acetylcholine response (r=0.49, P<0.05) but not the nitroglycerin response (r=0.13, P>0.05). The acetylcholine response remained significant after adjustment for other potential sources of oxidant stress (total cholesterol, diabetes mellitus, smoking, angina class) (P<0.01). The relative concentration of alpha-tocopherol to total lipid was not related to endothelial function (r=0.24, P=0.3, n=20). CONCLUSIONS: alpha-Tocopherol may preserve endothelial vasomotor function in patients with coronary atherosclerosis. This effect may be related primarily to the action of alpha-tocopherol in the vascular wall. Further studies that assess the impact of alpha-tocopherol supplementation as therapy of endothelial dysfunction are justified.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiologia , Sistema Vasomotor/fisiologia , Vitamina E/sangue , Acetilcolina , Colesterol/sangue , Doença da Artéria Coronariana/sangue , Vasos Coronários/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitroglicerina , Triglicerídeos/sangue , Sistema Vasomotor/efeitos dos fármacos
17.
Gut ; 44(5): 603-7, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10205193

RESUMO

BACKGROUND: Atropine, an anticholinergic agent with central and peripheral actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of transient lower oesophageal sphincter relaxation (TLOSR). AIMS: To compare the effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic agent, with atropine on the rate and mechanism of GOR in patients with GORD. METHODS: Oesophageal motility and pH were recorded for 120 minutes in 10 patients with GORD who were studied on three separate occasions. For the first two recording periods, either atropine (15 microg/kg bolus, 4 microg/kg/h infusion) or saline were infused intravenously. MSB (5 mg orally, four times daily) was given for three days prior to the third recording period. RESULTS: Atropine significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg), and the number of TLOSR (8.1 (0.56) to 2.8 (0. 55)) and reflux episodes (7.0 (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS pressure (12.6 (0.17) to 8.7 (0. 15) mm Hg, p<0.005), but had no effect on the frequency of TLOSR (8. 1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to 4.9 (0. 60)) (p>0.05). CONCLUSION: In contrast to atropine, MSB has no effect on the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of TLOSR and GOR is most likely mediated through a central cholinergic blockade.


Assuntos
Atropina/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Refluxo Gastroesofágico/prevenção & controle , N-Metilescopolamina/uso terapêutico , Parassimpatolíticos/uso terapêutico , Adulto , Junção Esofagogástrica/efeitos dos fármacos , Junção Esofagogástrica/fisiopatologia , Esôfago/fisiopatologia , Feminino , Refluxo Gastroesofágico/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Masculino , Manometria , Pessoa de Meia-Idade , Relaxamento Muscular/efeitos dos fármacos , Peristaltismo/efeitos dos fármacos , Pressão
18.
Am J Cardiol ; 82(4): 444-50, 1998 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9723631

RESUMO

Recipient-to-donor atrioatrial conduction across a suture line has been rarely reported after orthotopic heart transplantation. The relation of such conduction to symptomatic arrhythmias and its prevalence are not known. Recipient-to-donor atrioatrial conduction was demonstrated in a 28-year-old woman with paroxysmal supraventricular tachycardia 7 years after orthotopic heart transplantation. Atrial tachycardia in the recipient atria conducted 2:1 to the donor atria and was eliminated by radiofrequency catheter ablation of a left-sided atrioatrial electrical connection. The electrocardiogram at rest and during exercise, recorded before ablation of the recipient-to-donor connection, showed frequent atrial premature complexes, with variable coupling to the preceding sinus beats, and a change in P-wave morphology during exercise, which reverted to normal during the recovery period. These findings were eliminated by ablation of the recipient-to-donor connection. To determine the prevalence of recipient-to-donor atrioatrial conduction late after transplantation, we evaluated the exercise electrocardiograms of 50 subjects > 5 years after heart transplantation for these features of recipient-to-donor conduction. At least 1 feature was present in 5 subjects, and both were present in 1 subject. Electrical conduction can occur across surgical suture lines in the atria. Recipient-to-donor atrioatrial conduction may occur in < or = 10% of patients late after heart transplantation. It is a potential cause of arrhythmias that can be effectively treated with radiofrequency catheter ablation.


Assuntos
Função Atrial , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Transplante de Coração , Adulto , Idoso , Fatores de Confusão Epidemiológicos , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Descanso
19.
Am Heart J ; 135(6 Pt 1): 980-7, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9630101

RESUMO

BACKGROUND: Transplant-associated arteriosclerosis is the major limitation to long-term survival in the cardiac transplant recipient, and annual surveillance angiography is used in many centers to monitor its progression. Noninvasive methods would be preferable because angiography is invasive, costly, and insensitive; however, the reliability of such methods has been questioned. METHODS: All publications relating to the assessment of the cardiac allograft by noninvasive testing were identified through MEDLINE and a review of references from the published literature on transplant-associated arteriosclerosis. RESULTS: Resting and stress ECG, radionuclide scintigraphy, echocardiography, and positron emission tomography have all been used in cardiac transplant recipients with variable results. Most techniques are insensitive, but this limitation may be improved with pharmacologic stress imaging like dobutamine echocardiography. Although insensitive, some methods have good specificity (i.e., radionuclide scintigraphy). The noninvasive measurement of absolute coronary blood flow is promising as a specific and sensitive technique but is limited by availability and cost. CONCLUSIONS: In general, noninvasive techniques to assess transplant-associated coronary arteriosclerosis are limited by variable sensitivity and specificity. However, certain methods, such as dobutamine echocardiography and radionuclide scintigraphy, can provide important adjunctive physiologic information to angiography. Such techniques can therefore help to guide the care and treatment of the cardiac transplant recipient with allograft coronary arteriosclerosis.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Transplante de Coração/efeitos adversos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia , Eletrocardiografia , Teste de Esforço , Humanos , Complicações Pós-Operatórias , Tomografia Computadorizada de Emissão
20.
Am J Cardiol ; 82(12): 1479-83, 1998 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9874051

RESUMO

We sought to explore the relation between Chlamydia pneumoniae, cytomegalovirus (CMV), and cardiac transplant-associated arteriosclerosis. Serologic evidence of past Chlamydia pneumoniae infection was investigated in 3 patient groups at the time of cardiac catheterization: cardiac transplant recipients (n=49), patients having coronary artery bypass grafting (CABG) (n=39), and a control group free of angiographic coronary artery disease (n=21). High Chlamydia pneumoniae immunoglobulin G titers (> or =1:160) were more frequently observed in cardiac transplant recipients (odds ratio[OR] 13.7; 95% confidence intervals [CI] 1.6 to 117.4, p <0.05) and CABG patients (OR 21.7; 95% CI 1.6 to 287.0, p <0.05) than in controls. However, high Chlamydia pneumoniae titers did not distinguish between cardiac transplant recipients with or without angiographic transplant-associated arteriosclerosis or CABG patients with or without bypass vein graft disease. Furthermore, there was no significant relation between elevated Chlamydia pneumoniae titers and the presence or progression of transplant-associated arteriosclerosis in the subgroup of patients who were also CMV positive. Yet, analysis of the same angiograms demonstrated an association between CMV infection and the recent progression of transplant-associated arteriosclerosis. Thus, patients with cardiac transplantation have evidence of past Chlamydia pneumoniae and CMV infection but Chlamydia pneumoniae does not appear to have an independent role or synergistic relation to CMV in the development of transplant-associated arteriosclerosis.


Assuntos
Infecções por Chlamydia/complicações , Chlamydophila pneumoniae/isolamento & purificação , Doença da Artéria Coronariana/microbiologia , Infecções por Citomegalovirus/complicações , Citomegalovirus/isolamento & purificação , Transplante de Coração , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Infecções por Chlamydia/imunologia , Chlamydophila pneumoniae/imunologia , Ponte de Artéria Coronária , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Soroepidemiológicos
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