RESUMO
OBJECTIVE: The primary surgical techniques used to treat localized renal tumors are laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Obese patients have more intra-abdominal fat accumulation, which may make the localization and operation in minimally invasive surgery more complicated. Currently, limited research has been conducted on which method is more suitable for performing a partial nephrectomy on obese individuals. The aim of our investigation was to analyze and compare the perioperative results associated with both approaches to offer valuable information about the selection of LPN or RAPN as an optimal choice when performing a partial nephrectomy in obese patients. PATIENTS AND METHODS: We retrospectively collected clinical data from 78 cases of obese individuals [Body mass index (BMI) > 28] who underwent RAPN, as well as 50 cases of obese individuals (BMI > 28) who underwent LPN. The analysis covered various aspects, including initial patient characteristics, glomerular filtration rate (GFR), warm ischemia time (WIT), operation time, volume of blood loss during the surgical procedure, time taken to recover bowel function, positive surgical margin rate, incidence of postoperative complications, and postoperative hospital stay. RESULTS: We observed that RAPNs exhibited shorter warm ischemia time and reduced intraoperative blood loss in obese patients, along with decreased postoperative duration of abdominal drainage and hospitalization periods compared to LPNs. CONCLUSIONS: In obese patients, RAPN demonstrates advantages over LPN in minimizing intraoperative blood loss, WIT, and facilitating postoperative recovery. These findings may serve as valuable evidence when considering the choice between LPN or RAPN for partial nephrectomy in obese individuals.
Assuntos
Neoplasias Renais , Laparoscopia , Nefrectomia , Obesidade , Procedimentos Cirúrgicos Robóticos , Humanos , Nefrectomia/métodos , Nefrectomia/efeitos adversos , Obesidade/cirurgia , Obesidade/complicações , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Resultado do Tratamento , Idoso , Complicações Pós-Operatórias/epidemiologia , Adulto , Tempo de Internação , Duração da CirurgiaRESUMO
PURPOSE: Family with sequence similarity 83, member A (FAM83A) has been reported to play an important role in cancer progression and metastasis. The purpose of this study was to clarify the role and mechanism of FAM83A in pancreatic neuroendocrine tumors (PanNETs). METHODS: PanNET specimens and adjacent nontumor pancreatic tissues obtained from 68 patients who underwent curative surgery for PanNETs were assessed for FAM83A expression using immunochemical staining. The relationships between FAM83A expression, clinicopathological parameters and prognosis were statistically analyzed. PanNET cell lines were used to study the role of FAM83A in the progression and metastasis of PanNETs in vitro and in vivo. RESULTS: FAM83A was overexpressed in PanNET specimens compared with adjacent nontumor tissues. Furthermore, FAM83A expression was closely associated with lymph node metastasis (P = 0.02), perineural invasion (P = 0.001), WHO classification (P = 0.039), AJCC stage (P = 0.01) and shorter disease-free survival in patients with PanNETs (P < 0.001). FAM83A overexpression effectively promoted PanNET cell proliferation, migration, invasion and growth both in vitro and in vivo, whereas FAM83A inhibition exerted the opposite effects. Subsequent mechanistic investigations revealed that FAM83A promotes the progression and metastasis of PanNETs by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK pathways. CONCLUSIONS: FAM83A plays an important role in the progression and metastasis of PanNET by inducing the EMT via the activation of the ERK and PI3K/AKT pathways and may serve as a valuable molecular target in PanNET treatment.
Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Tumores Neuroendócrinos/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pancreáticas/metabolismo , Proliferação de Células , Movimento Celular , Linhagem Celular Tumoral , Proteínas de NeoplasiasRESUMO
It is essential to dissect an adequate number of lymph nodes (LNs) to ensure staging accuracy during esophagectomy with or without neoadjuvant therapy. We developed a statistical model to quantify the probability of precise nodal staging based on previous studies. Esophageal cancer patients who underwent esophagectomy were retrospectively reviewed in the Surveillance, Epidemiology, and End Results database. A ß-binomial distribution was adopted to estimate the number of understaged patients based on the numbers of positive and examined LNs. Using 6,252 patients, we estimated a 90% confidence of accurate N0 staging could be achieved by examining 17 LNs without neoadjuvant therapy. To obtain similar accuracy in N1 and N2, 20 and 25 LNs should be examined. For patients with neoadjuvant therapy, 18, 19, and 28 LNs could achieve the same accuracy. Staging accuracy was a significant prognostic factor. We found when 90% confidence had been achieved, patient survival did not improve with more LNs examined and the ratio and log odds of positive LNs did not have significant prognostic values. The statistical model we developed for precise staging in patients with different N stages is of great value in guiding lymphadenectomy. It provided risk assessment for underestimated LN metastases and guided subsequent adjuvant treatment.
Assuntos
Neoplasias Esofágicas/diagnóstico , Esofagectomia/estatística & dados numéricos , Excisão de Linfonodo/estatística & dados numéricos , Modelos Estatísticos , Estadiamento de Neoplasias/estatística & dados numéricos , Adulto , Idoso , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos , Programa de SEER , Estados UnidosRESUMO
An unusual communication between the lingual and mylohyoid nerves has been identified as one reason for incomplete mandibular anaesthesia, and for neuropathy. However, its anatomical features and function are poorly understood and its relations with neighbouring structures, which are valuable in reducing the side effects of surgical operations, have not been sufficiently described. The aim of this study, therefore, was to describe the communication between the nerves and to assess the implications for oral and maxillofacial surgery. We explored the communication between the mylohyoid nerves of 62 embalmed, and 16 fresh, hemifaces. The diameter, length of the communication, and other variables were measured, and the junctions with the two nerves microdissected. The nervous communications of fresh specimens and relative nerves were stained histochemically for acetylcholinesterase. Of the 62 embalmed specimens, 19 had a communication that pierced the mylohyoid muscle, and staining showed that this was a sensory nerve. Our results suggest that the sensory communication between the lingual and mylohyoid nerves pierces the mylohyoid muscle and connects these otherwise unrelated nerves, thereby contributing to the likelihood of operative side effects.
Assuntos
Nervo Mandibular , Língua , Cadáver , Humanos , Nervo Lingual , MandíbulaRESUMO
The tumor-suppressor protein p53 is tightly controlled in normal cells by its two negative regulators--the E3 ubiquitin ligase MDM2 and its homolog MDMX. Under stressed conditions such as DNA damage, p53 escapes MDM2- and MDMX-mediated functional inhibition and degradation, acting to prevent damaged cells from proliferating through induction of cell cycle arrest, DNA repair, senescence or apoptosis. Ample evidence suggests that stress signals induce phosphorylation of MDM2 and MDMX, leading to p53 activation. However, the structural basis of stress-induced p53 activation remains poorly understood because of the paucity of technical means to produce site-specifically phosphorylated MDM2 and MDMX proteins for biochemical and biophysical studies. Herein, we report total chemical synthesis, via native chemical ligation, and functional characterization of (24-108)MDMX and its Tyr99-phosphorylated analog with respect to their ability to interact with a panel of p53-derived peptide ligands and PMI, a p53-mimicking but more potent peptide antagonist of MDMX, using FP and surface plasmon resonance techniques. Phosphorylation of MDMX at Tyr99 weakens peptide binding by approximately two orders of magnitude. Comparative X-ray crystallographic analyses of MDMX and of pTyr99 MDMX in complex with PMI as well as modeling studies reveal that the phosphate group of pTyr99 imposes extensive steric clashes with the C-terminus of PMI or p53 peptide and induces a significant lateral shift of the peptide ligand, contributing to the dramatic decrease in the binding affinity of MDMX for p53. Because DNA damage activates c-Abl tyrosine kinase that phosphorylates MDMX at Tyr99, our findings afford a rare glimpse at the structural level of how stress-induced MDMX phosphorylation dislodges p53 from the inhibitory complex and activates it in response to DNA damage.
Assuntos
Dano ao DNA , Proteínas Nucleares/química , Proteínas Proto-Oncogênicas/química , Proteína Supressora de Tumor p53/química , Sítios de Ligação , Proteínas de Ciclo Celular , Humanos , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/síntese química , Proteínas Nucleares/metabolismo , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Fosforilação , Fosfotirosina/química , Ligação Proteica , Conformação Proteica , Mapeamento de Interação de Proteínas , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas/síntese química , Proteínas Proto-Oncogênicas/metabolismo , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície , Proteína Supressora de Tumor p53/metabolismoRESUMO
In this study, we explored the gene and microRNA (miRNA) expressions profile of esophageal carcinoma. The expression data for messenger RNAs and miRNAs in normal and cancerous esophageal tissues were obtained from the Cancer Genome Atlas database and then the differentially expressed genes and miRNAs were identified. As a result, we identified 2962 genes and 45 miRNAs differentially expressed in esophageal carcinoma compared with normal esophageal tissues. Subsequently, the altered gene functions and signaling pathways were investigated using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and these differentially expressed genes were significantly enriched in the cell cycle, cell migration, mitogen-activated protein kinase (MAPK) and toll-like receptor signaling pathway, and so on. Then the regulatory relationships between the differentially expressed miRNAs and genes were examined with Targetscan and Miranda, and the potential target sites of transcription factors (TFs) in the promoter regions of these miRNAs and genes were identified using the TRANSFAC database. Finally the TF-miRNA-gene network in esophageal cancer was established, summarizing the regulatory links among the TFs, differentially expressed miRNAs and differentially expressed genes. Factors such as core promoter-binding protein (CPBP), nuclear factor of activated T-cells 1 (NFAT-1), miR-30c-5p, were located in the central hub of this network, highlighting their vital roles in esophageal tumorigenesis. These findings may extend our understanding of the molecular mechanisms underlying esophageal carcinoma and promote new perspectives for prevention, diagnosis and treatment.
Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Ciclo Celular/genética , Movimento Celular/genética , Bases de Dados Genéticas , Carcinoma de Células Escamosas do Esôfago , Redes Reguladoras de Genes , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Transdução de Sinais/genética , Receptores Toll-Like/genética , Fatores de Transcrição/genética , TranscriptomaRESUMO
Many studies have addressed the hazardous role of cigarette smoking on male fertility, but the exact molecular mechanisms involved in the impairments caused by nicotine remain unclear. To evaluate the detrimental effects of nicotine exposure on spermatogenesis, two-dimensional gel electrophoresis and mass spectrometry analysis were performed to screen and identify differentially expressed proteins from the testes of mice exposed to nicotine daily. Data mining analysis indicated that the 15 identified proteins were mainly involved in actin cytoskeleton regulation and in the tricarboxylic acid cycle, which are related to cell motility. Further investigation of a central regulatory factor in the cytoskeleton regulation, profilin 1 (PFN1), revealed that nicotine-induced Pfn1 over-expression in mouse testes, specifically in elongated spermatids, by Pfn1 promoter hypomethylation. Interestingly, elevated sperm motility parameters were observed in nicotine-treated mice. We assume that nicotine-induced PFN1 over-expression in mouse spermatids may promote actin polymerization and ultimately enhance sperm motility.
Assuntos
Metilação de DNA/efeitos dos fármacos , Nicotina/toxicidade , Profilinas/genética , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Animais , Fertilidade/efeitos dos fármacos , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , Proteômica/métodos , Fumar/efeitos adversos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espermatozoides/efeitos dos fármacos , Testículo/citologiaRESUMO
BACKGROUND: Osteosarcoma is a kind of highly malignant primary bone tumor which most common in the teenage, and holds strong aggressive, earlier organs metastases mainly to lung, prone to postoperative recur. Therefore for osteosarcoma, invasion and transfer mechanism and related factors' interaction remains to be a key research subject. AIM: We aim to find biological molecules marker can be used for osteosarcoma diagnosis through contrast of osteosarcoma sample and normal tissue samples. MATERIALS AND METHODS: This analysis using human osteosarcoma expression profile data and three lesions normal tissue samples (liver, kidneys, lymph) expression data and compare them, and find significant specifically expressed genes, according to their function. RESULTS: Research shows that the cancer cell proliferation, invasion, transfer and recurrent process involve many factors interaction, of which angiogenesis is the necessary condition of tumor growth, transfer and the recurrence. CONCLUSIONS: Now the most important positive regulatory factor of angiogenesis is VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor). Both of them are with a wide variety and close relationship of tumor angiogenesis and progress.
Assuntos
Neoplasias Ósseas/genética , Osteossarcoma/genética , Transcriptoma , Colágeno/genética , Conexina 43/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , HumanosRESUMO
It's frequently stated that the pyruvate kinase M2 (PKM2) and Warburg effect are important for cancer development by accumulating more raw materials for macromolecule biosynthesis. However, the correlation between PKM2 and cancer is poorly reported. Here, we investigated the PKM2 expression in esophageal squamous cell cancer (ESCC). We observed that the expression of PKM2 was much higher in ESCC than in control normal tissue, and it is highly associated with many clinical features and prognosis. Specially, we found that the expression of PKM2 was closely related to the differentiation state of ESCC, and we further confirmed this discovery in vitro. As a result, out data indicated that PKM2 might be a useful indicator for determining the survival of patients with ESCC. Considering previous researches on the link among PKM2, Warburg effect, and differentiation, our study inferred the direct roles of PKM2 and Warburg effect in the differentiation of cancer cells rather than only providing synthetic intermediates for the promotion of cancer's progression.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/metabolismo , Diferenciação Celular/fisiologia , Neoplasias Esofágicas/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Linhagem Celular Tumoral , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas de Ligação a Hormônio da TireoideRESUMO
Administrative data are readily available, inexpensive, computer readable, and cover large populations. Despite coding irregularities and limited clinical details, administrative data supplemented by tools such as the Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs) could serve as a screen for potential patient safety problems that merit further investigation, offer valuable insights into adverse impacts and risks of medical errors and, to some extent, provide benchmarks for tracking progress in patient safety efforts at local, state, or national levels.
Assuntos
Bases de Dados Factuais , Pesquisa sobre Serviços de Saúde/métodos , Erros Médicos , Coleta de Dados , Estudos Epidemiológicos , Humanos , Classificação Internacional de Doenças , Erros Médicos/estatística & dados numéricos , Garantia da Qualidade dos Cuidados de Saúde , Reprodutibilidade dos Testes , Risco Ajustado , Gestão da Segurança , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To develop Patient Safety Indicators (PSI) to identify potential in-hospital patient safety problems for the purpose of quality improvement. DATA SOURCE/STUDY DESIGN: The data source was 2,400,000 discharge records in the 1997 New York State Inpatient Database. PSI algorithms were developed using systematic literature reviews of indicators and hand searches of the ICD-9-CM code book. The prevalence of PSI events and associations between PSI events and patient-level and hospital-level characteristics, length of stay, in-hospital mortality, and hospital charges were examined. PRINCIPAL FINDINGS: PSIs were developed for 12 distinct clinical situations and an overall summary measure. The 1997 event rates per 10,000 discharges varied from 1.1 for foreign bodies left during procedure to 84.7 for birth traumas. Discharge records with PSI events had twofold to threefold longer hospital stays, twofold to 20-fold higher rates of in-hospital mortality, and twofold to eightfold higher total charges than records without PSI events. Multivariate logistic regression revealed that PSI events were primarily associated with increasing age (p < .001), hospitals performing more inpatient surgery (p < .001), and hospitals with higher percentage of beds in intensive care units (p < .001). CONCLUSIONS: The PSIs provide an efficient and user-friendly tool to identify potential inhospital patient safety problems for targeted institution-level quality improvement efforts. Until better error-reporting systems are developed the PSIs can serve to shed light on the problem of medical errors not limited solely to mortality because of errors.
Assuntos
Hospitais/normas , Doença Iatrogênica/epidemiologia , Erros Médicos/classificação , Indicadores de Qualidade em Assistência à Saúde , Gestão da Segurança , Vigilância de Evento Sentinela , Adolescente , Adulto , Idoso , Algoritmos , Criança , Pré-Escolar , Feminino , Hospitais/classificação , Hospitais/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Erros Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , New York/epidemiologia , Desenvolvimento de Programas , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
Near infrared mammography is a new method for breast imaging for popular examination. Its merits are no radiation, without the necessaries of darkroom, etc. Based on the digital image processing and analysis system, the doctor can get informations more conveniently and with higher diagnosis reliability. In this paper, the near infrared image acquisition, processing and analysis system and its implementation are presented.
Assuntos
Diagnóstico por Computador , Interpretação de Imagem Assistida por Computador/instrumentação , Mamografia/instrumentação , Sistemas Computadorizados de Registros Médicos , Design de Software , Algoritmos , Desenho de Equipamento , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/instrumentação , Raios Infravermelhos , Mamografia/métodos , SoftwareRESUMO
In a previous randomized Phase III trial (P. O. Livingston et al, J. Clin. Oncol., 12: 1036-1044, 1994), we demonstrated that immunization with GM2 and bacille Calmette-Guerin reduced the risk of relapse in stage III melanoma patients who were free of disease after surgical resection and who had no preexisting anti-GM2 antibodies. That vaccine formulation induced IgM anti-GM2 antibodies in 74% but induced IgG anti-GM2 antibodies in only 10% of the patients. To optimize the immune response against GM2, a reformulated vaccine was produced conjugating GM2 to keyhole limpet hemocyanin (KLH) and using the adjuvant QS21 (GM2-KLH/QS21). In pilot studies, 70 microg of vaccine induced IgG anti-GM2 antibodies in 76% of the patients. We wished to define the lowest vaccine dose that induced consistent, high-titer IgM and IgG antibodies against GM2. Fifty-two melanoma patients who were free of disease after resection but at high risk for relapse were immunized with GM2-KLH/QS21 vaccine at GM2 doses of 1, 3, 10, 30, or 70 ILg on weeks 1, 2, 3, 4, 12, 24, and 36. Serum collected at frequent and defined intervals was tested for anti-GM2 antibodies. Overall, 88% of the patients developed IgM anti-GM2 antibodies; 71% also developed IgG anti-GM2 antibodies. GM2-KLH doses of 3-70 microg seemed to be equivalent in terms of peak titers and induction of anti-GM2 antibodies. At the 30-microg dose level, 50% of the patients developed complement fixing anti-GM2 antibodies detectable at a serum dilution of 1:10. We conclude that the GM2-KLH/QS21 formulation is more immunogenic than our previous formulation and that 3 microg is the lowest dose that induces consistent, high-titer IgM and IgG antibodies against GM2.
Assuntos
Vacinas Anticâncer/administração & dosagem , Gangliosídeo G(M2)/administração & dosagem , Melanoma/prevenção & controle , Vacinas Conjugadas/administração & dosagem , Adulto , Idoso , Animais , Formação de Anticorpos , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Bovinos , Relação Dose-Resposta a Droga , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Gangliosídeo G(M2)/efeitos adversos , Gangliosídeo G(M2)/imunologia , Humanos , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/efeitos dos fármacos , Imunoglobulina M/sangue , Imunoglobulina M/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor/induzido quimicamente , Prurido/induzido quimicamente , Fatores de Tempo , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/metabolismo , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologiaRESUMO
The effect of nitric oxide (NO) on the hypertrophic response and the proto-oncogene c-fos expression induced by angiotensin II (AII) or endothelin-1 (ET-1) was investigated in the primary culture of neonatal rat cardiomyocytes. Total protein content of cardiomyocytes (used as the index of cardiac myocyte hypertrophy) was determined by the Bradford method. The proto-oncogene c-fos expression was assessed using reverse transcription-polymerase chain reaction (RT-PCR) standardized with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RT-PCR was performed in a single tube using gene-specific primers and the SuperScript One-Step RT-PCR System. Total protein content of cardiomyocytes increased significantly on day 5 after A II treatment or on day 3 after ET-1 treatment and the increased protein content was inhibited by SNP (NO donor). A II, ET-1 and PMA (protein kinase C activator) induced the c-fos gene expression of cardiomyocytes, while L-arginine inhibited it. The L-arginine effect was blocked by L-NAME (NOS inhibitor). SNP inhibited the c-fos gene expression of cardiomyocytes induced by A II,ET-1 or PMA as well. These results suggest that NO can inhibit the hypertrophic response and the proto-oncogene c-fos expression of cardiomyocytes induced by A II or ET-1 and the cross-link may be located at the site of protein kinase C.
Assuntos
Angiotensina II/farmacologia , Endotelina-1/farmacologia , Miócitos Cardíacos/metabolismo , Óxido Nítrico/farmacologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , Animais , Animais Recém-Nascidos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Sprague-DawleyRESUMO
This study investigated the role of nitric oxide(NO) in the prevention of myocardial hypertrophic response and its mechanisms. Left ventricular NO content decreases in the pathophysiogenesis of myocardial hypertrophy induced by pressure overload. Endogenous NO may attenuate cardiac hypertrophy induced by pressure overload, independent of cGMP mechanism. Angiotensin II (AII), endothelin-1 (ET-1) and norepinephrine(NE) can inhibit NOS activity and NO production, and induce hypertrophic response in cultured neonatal rat cardiomyocytes; these effects of AII, ET-1 and NE are mediated respectively by AII receptor, ETA receptor and alpha 1-adrenergic receptor; these effects of AII and ET-1 are mediated by PTX-sensitive G protein, while the effects of NE are mediated by PTX-insensitive G protein. eNOS gene is expressed in cultured neonatal rat cardiac myocytes and nonmyocytes. AII, ET-1 and NE can inhibit eNOS gene expression in cardiomyocytes. Exogenous NO can prevent hypertrophic response induced by AII, ET-1 and NE in cardiomyocytes. Both endogenous and exogenous NO can inhibit the expression of proto-oncogene c-fos induced by AII and ET-1, which may be involved in protein kinase C.
Assuntos
Cardiomiopatia Hipertrófica/prevenção & controle , Miocárdio/metabolismo , Óxido Nítrico/fisiologia , Dissertações Acadêmicas como Assunto , Angiotensina II/farmacologia , Animais , Cardiomiopatia Hipertrófica/fisiopatologia , GMP Cíclico/metabolismo , Endotelina-1/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/biossíntese , Norepinefrina/farmacologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , Ratos , Pressão Ventricular/fisiologiaRESUMO
The present study was to investigate the effects of angiotensin II on c-fos mRNA expression and protein synthesis in cultured neonatal rat myocardial cells. The results showed that angiotensin II induced c-fos mRNA expression, increased protein content in a dose-dependent manner and stimulated 3H-leucine incorporation rate. All these effects were blocked by angiotensin II receptor antagonist saralasin. The angiotensin II-induced expression of c-fos gene was also blocked by Ca2+ channel antagonist nicardipine.
Assuntos
Angiotensina II/farmacologia , Genes fos , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Animais , Animais Recém-Nascidos , Células Cultivadas , Expressão Gênica , Miocárdio/citologia , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND DATA: In this study, we evaluated a new intracellular type (IT-K) solution containing trehalose in a rabbit free skin flap storage model. Trehalose is a nonreducing disaccharide that can stabilise cell membranes under various stressful conditions. MATERIAL AND METHOD: Seventy-two free skin flaps of the ear of rabbits were preserved in Euro-Collins (EC) solution or in IT-K solution for 24, 48, and 72 h at 4 degrees C. After completion of preservation, these flaps were replanted to the other ear by microsurgical techniques. Viability study and photo documentation were performed daily for 7 days. Tissue specimens were taken 24 h after vascular anastomosis, fixed in 10% formaldehyde and stained with haematoxylin and eosin (HE). Survival rates were analysed by Fisher's exact test for comparison of the two experimental groups. Values of P < 0.05 were considered to be statistically significant. RESULTS: After 7 days, a survival rate of 100% of flaps were observed in both solutions after 24 h of preservation. After preservation for 48 h in IT-K solution the survival rate was 100%. However, in EC solution survival decreased to 75% (9 of 12 preserved flaps survived). This difference increased to 33.3% (4 of 12 flaps) in EC solution and 91.6% (11 of 12 flaps) (P < 0.01) in IT-K solution when the flaps were stored for 72 h. Light microscopic examination also showed less damage in flaps preserved in IT-K solution than in these preserved in EC solution. CONCLUSION: IT-K solution was superior to EC solution in the preservation of free skin flaps on rabbit ears when stored for 48 and 72 h.
Assuntos
Soluções para Preservação de Órgãos , Transplante de Pele , Retalhos Cirúrgicos , Preservação de Tecido/métodos , Trealose , Animais , Avaliação Pré-Clínica de Medicamentos , Sobrevivência de Enxerto , Masculino , Soluções para Preservação de Órgãos/química , Coelhos , Transplante de Pele/patologia , Fatores de TempoRESUMO
Trehalose is a disaccharide that can stabilise cell membranes under various stressful conditions. We have studied the effect of trehalose on the ischaemic tolerance of fat skeletal muscle flaps. A rat gracilis model was used to evaluate the prolongation of ischaemic preservation of the modified solution in which trehalose was substituted for glucose in Euro-Collins solution. Four groups of animals were studied. In two groups, flaps were preserved in Euro-Collins solution or trehalose Euro-Collins solution for various ischaemic intervals (6, 12, 24, 48, 72, and 96 hours). In two additional groups, after storage for various periods in the two solutions, muscle flaps were replanted into the original animals with microvascular anastomoses, and were investigated by light and electron microscopy on the seventh postoperative day. Trehalose Euro-Collins solution significantly prolonged ischaemic tolerance compared with Euro-Collins solution alone at 24 and 48 hours.
Assuntos
Soluções para Preservação de Órgãos , Retalhos Cirúrgicos , Preservação de Tecido , Trealose , Animais , Soluções Hipertônicas , Masculino , Microscopia Eletrônica , Músculo Esquelético/ultraestrutura , Soluções para Preservação de Órgãos/química , Ratos , Ratos Wistar , Reimplante , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/patologia , Fatores de TempoRESUMO
To evaluate the efficacy of treatment of heroin addicts (n = 100) by "Qingjunyin" (QJY) detoxification (10 days program). Methadone detoxification (10 days program) group (n = 50) and colonidine treated group (n = 50) serve as controls. QJY group is given 180 ml P. O daily. The dosage of the two comparatine groups is given according to Documentation, the method of abserving the treatment protocols and detoxification standard is according to current regulation. The scores of abstinence syndrome in QJY detoxification group are lower than those in colonidine treated group in the first three days of potocol, but this difference disappear in the late stage of treatment. While QJY detoxification is effective as methadone detoxification in the control of abstinece syndrome during the first five days of treatment but the difference in the scores of abstinence syndrome between QJY and methadone group is observed during the late five days of protocol. QJY does not result in potential dependence and has definite curative effect in the treatment of heroin addiction.