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2.
Respir Res ; 20(1): 22, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704469

RESUMO

BACKGROUND: Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality, but the major problem associated with IDSA/ATS minor criteria might be a lack of consideration of weight in prediction in clinical practice. Would awarding different points to the presences of the minor criteria improve the accuracy of the scoring system? It is warranted to explore this intriguing hypothesis. METHODS: A total of 1230 CAP patients were recruited to a retrospective cohort study. This was tested against a prospective two-center cohort of 1749 adults with CAP. 2 points were assigned for the presence of PaO2/FiO2 ≤ 250 mmHg, confusion, or uremia on admission and 1 point for each of the others. RESULTS: The mortality rates, and sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores increased significantly with the numbers of IDSA/ATS minor criteria present and minor criteria scores. The correlations of the minor criteria scores with the mortality rates were higher than those of the numbers of IDSA/ATS minor criteria present. As were the correlations of the minor criteria scores with SOFA and PSI scores, compared with the numbers of IDSA/ATS minor criteria present. The pattern of sensitivity, specificity, positive predictive value, and Youden's index of scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria for prediction of mortality was the best in the retrospective cohort, and the former was better than the latter. The validation cohort confirmed a similar pattern. The area under the receiver operating characteristic curve of scored minor criteria was higher than that of IDSA/ATS minor criteria in the retrospective cohort, implying higher accuracy of scored version for predicting mortality. The validation cohort confirmed a similar paradigm. CONCLUSIONS: Scored minor criteria orchestrated improvements in predicting mortality and severity in patients with CAP, and scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria might be more valuable cut-off value for severe CAP, which might have implications for more accurate clinical triage decisions.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Pneumonia/diagnóstico , Pneumonia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Coortes , Confusão/etiologia , Confusão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Oxigênio/sangue , Valor Preditivo dos Testes , Padrões de Referência , Estudos Retrospectivos , Uremia/etiologia , Adulto Jovem
3.
Am J Med Sci ; 356(4): 329-334, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30360800

RESUMO

BACKGROUND: The Infectious Disease Society of America/the American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality. It is unclear whether the patients with non-severe CAP meeting the minor criteria most strongly associated to mortality should have the priority for treatment and intensive care. It is warranted to explore this intriguing hypothesis. METHODS: A retrospective cohort study of 1230 patients with CAP was performed. This was tested against a prospective 2-center cohort of 1749 adults with CAP. RESULTS: The patients with CAP fulfilling the predictive findings most strongly associated to mortality, i.e. PaO2/FiO2 ≤ 250 mm Hg, confusion, and uremia, showed higher mortality rates than those not fulfilling the predictive findings in subgroup analyses of the retrospective cohort. The more the number of predictive findings present, the higher the mortality rates. The prospective cohort confirmed a similar pattern. Interestingly, the patients with non-severe CAP meeting the predictive findings demonstrated unexpectedly higher mortality rates compared with the patients with severe CAP not meeting the predictive findings in the prospective cohort (P = 0.003), although there only existed death of an uptrend in the retrospective cohort. Two similar and intriguing paradigms about sequential organ failure assessment (SOFA) scores and pneumonia severity index (PSI) scores were confirmed in the 2 cohorts. CONCLUSIONS: The patients with non-severe CAP fulfilling the predictive findings most strongly associated to mortality demonstrated higher SOFA and PSI scores and mortality rates, and might have the priority for treatment and intensive care.

4.
Medicine (Baltimore) ; 94(36): e1474, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26356705

RESUMO

It is not clear whether the IDSA/ATS minor criteria for severe community-acquired pneumonia (CAP) could be simplified or even be modified to orchestrate improvements in predicting mortality.A retrospective cohort study of 1230 CAP patients was performed to simplify and to modify the scoring system by excluding 4 noncontributory or infrequent variables (leukopenia, hypothermia, hypotension, and thrombocytopenia) and by excluding these variables and then adding age ≥65 years, respectively. The simplification and modification were tested against a prospective 2-center validation cohort of 1409 adults with CAP.The increasing numbers of IDSA/ATS, simplified, and modified minor criteria present in the retrospective cohort were positively associated with the mortality, showing significant increased odds ratios for mortality of 2.711, 4.095, and 3.755, respectively. The validation cohort confirmed a similar pattern. The sensitivity, specificity, positive predictive value, and Youden index of modified minor criteria for mortality prediction were the best pattern in the retrospective cohort. High values of corresponding indices were confirmed in the validation cohort. The highest accuracy of the modified version for predicting mortality in the retrospective cohort was illustrated by the highest area under the receiver operating characteristic curve of 0.925 (descending order: modified, simplified, and IDSA/ATS minor criteria). The validation cohort confirmed a similar paradigm.The IDSA/ATS minor criteria could be simplified to 5 variables and then be modified to orchestrate improvements in predicting mortality in CAP patients. The modified version best predicted mortality. These were more suitable for clinic and emergency department.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Adulto , Fatores Etários , Idoso , China/epidemiologia , Estudos de Coortes , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/fisiopatologia , Feminino , Humanos , Hipotensão/etiologia , Hipotermia/etiologia , Pulmão/diagnóstico por imagem , Masculino , Admissão do Paciente/normas , Pneumonia/sangue , Pneumonia/diagnóstico , Pneumonia/mortalidade , Pneumonia/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Radiografia , Projetos de Pesquisa , Taxa Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombocitopenia/etiologia
5.
Am J Med Sci ; 350(3): 186-90, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26280118

RESUMO

BACKGROUND: It is not clear whether low-blood pressure criterion could be removed from CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure and age ≥65 years) score to orchestrate an improvement in identifying patients with community-acquired pneumonia (CAP) in low-mortality rate settings. METHODS: A retrospective cohort study of 1,230 CAP patients was performed to simplify the CURB-65 scoring system by excluding low-blood pressure variable. The simplification was validated in a prospective 2-center cohort of 1,409 adults with CAP. RESULTS: The hospital mortalities were 1.3% and 3.8% in the retrospective and prospective cohorts, respectively. The mortality rates in the 2 cohorts increased directly with the increasing scores, showing significant increased odds ratios for mortality. The pattern of sensitivity, specificity, positive predictive value and Youden's index of a CUR-65 (Confusion, Urea >7 mmol/L, Respiratory rate ≥30/min and age ≥65 years) score of ≥2 for prediction of mortality was better than that of a CURB-65 score of ≥3 in the retrospective cohort. Higher values of corresponding indices were confirmed in the validation cohort. The higher accuracy of CUR-65 score for predicting mortality was illustrated by the area under the receiver operating characteristic curve of 0.937, compared with 0.915 for CURB-65 score in the retrospective cohort (P = 0.0073). The validation cohort confirmed a similar paradigm (0.953 versus 0.907, P = 0.0002). CONCLUSIONS: CURB-65 score could be simplified by removing low blood pressure to orchestrate an improvement in predicting mortality in CAP patients who have a low risk of death. A CUR-65 score of ≥2 might be a more valuable cutoff value for severe CAP.


Assuntos
Mortalidade Hospitalar , Pneumonia Bacteriana/mortalidade , Índice de Gravidade de Doença , Estudos de Coortes , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Confusão/diagnóstico , Confusão/epidemiologia , Feminino , Mortalidade Hospitalar/tendências , Humanos , Hipotensão/diagnóstico , Hipotensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Taxa Respiratória , Estudos Retrospectivos , Sensibilidade e Especificidade , Ureia/sangue , Uremia/diagnóstico , Uremia/epidemiologia
6.
Int J Infect Dis ; 38: 141-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26255891

RESUMO

OBJECTIVES: The individual 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality. It is not clear whether the combinations of predictive findings might imply diverse severities or different mortalities. METHODS: A prospective two centre cohort study was performed of 385 severe CAP patients fulfilling three or more IDSA/ATS minor criteria amongst 1430 patients. RESULTS: Hospital mortality rose sharply from 5.7%, 9.9%, and 16.5%, respectively, for patients with none of three predictive findings most strongly associated to mortality (PaO2/FiO2 ≤ 250mm Hg, confusion and uraemia), one of those, and two of those to 38.6% for patients with all those (p<0.001). The number of three predictive findings present had a significantly increased odds ratio for mortality of 2.796 (p<0.001), and had the degree of positive association with sequential organ failure assessment scores at 72hours, incurring significantly longer hospital stay and higher costs. CONCLUSIONS: Different combinations of 2007 IDSA/ATS minor criteria for severe CAP were associated to diverse severities and different mortalities. The combination of PaO2/FiO2 ≤ 250mm Hg, confusion and uraemia predicted more severity and higher mortality compared with others.


Assuntos
Infecções Comunitárias Adquiridas/mortalidade , Pneumonia/mortalidade , Idoso , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
7.
Arch Med Sci ; 10(4): 725-32, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-25276157

RESUMO

INTRODUCTION: The associations of radiological features with clinical and laboratory findings in Mycoplasma pneumoniae infection are poorly understood. The purpose of this study was to assess the associations. MATERIAL AND METHODS: A retrospective cohort study of 1230 patients with community-acquired pneumonia was carried out between January 2005 and December 2009. The diagnosis of M. pneumoniae infection was made using the indirect microparticle agglutinin assay and enzyme-linked immunosorbent assay. RESULTS: Females were more susceptible to M. pneumoniae infection. Ground-glass opacification on radiographs was positively associated with M. pneumoniae-IgM titres (rank correlation coefficient (r s) = 0.141, p = 0.006). The left upper lobe was more susceptible to infection with M. pneumoniae compared with other pathogens. More increases in the risk of multilobar opacities were found among older or male patients with M. pneumoniae pneumonia (odds ratio, 1.065, 3.279; 95% confidence interval, 1.041-1.089, 1.812-5.934; p < 0.001, p < 0.001; respectively). Patients with M. pneumoniae pneumonia showing multilobar opacities or consolidation had a significantly longer hospital length of stay (r s = 0.111, r s = 0.275; p = 0.033, p < 0.001; respectively), incurring significantly higher costs (r s = 0.119, r s = 0.200; p = 0.022, p < 0.001; respectively). CONCLUSIONS: Our study highlighted female susceptibility to M. pneumoniae pneumonia and the association of ground-glass opacification with higher M. pneumoniae-IgM titres. The left upper lobe might be more susceptible to M. pneumoniae infection. Older or male patients with M. pneumoniae pneumonia were more likely to show multilobar opacities. Multilobar opacities and consolidation were positively associated with hospital length of stay and costs.

8.
Intern Med ; 51(18): 2521-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22989821

RESUMO

OBJECTIVE: The CURB-65 score is a simple well validated tool for the assessment of severity in community-acquired pneumonia (CAP). The weight of each criterion in very low-mortality-rate settings is unclear. The purpose of this study was to determine the weight in such setting. METHODS: This study retrospectively reviewed 1,230 adult patients admitted for CAP from 2005 to 2009. RESULTS: The 30-day mortality rose sharply from 0%, 1.0%, 8.2% and 16.7%, respectively, for patients with CURB-65 scores of 0, 1, 2 and 3 to 100.0% for patients with the scores of 4 (x(2) = 219.494, p<0.001). Confusion had the strongest association with mortality (odds ratio, 22.148). The presence of low blood pressure was not associated with mortality. Confusion, urea >7 mmol.L(-1) and age ≥ 65 yrs showed independent relationships with mortality (Odds ratio, 11.537, 5.988 and 10.462; respectively). Urea >7 mmol.L(-1) was most strongly associated with the sequential organ failure assessment (SOFA) scores [rank correlation coefficient (r(s)), 0.352]. Confusion had the closest relationship with hospital length of stay (r(s), 0.114). Age ≥ 65 yrs had the strongest association with costs (r(s), 0.223). Conclusion The individual CURB-65 criteria were of unequal weight for predicting the 30-day mortality, SOFA scores, hospital length of stay and costs in a very low-mortality-rate setting, and a low blood pressure was not associated with mortality.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Pacientes Internados , Pneumonia/diagnóstico , Pneumonia/mortalidade , Índice de Gravidade de Doença , Adulto , Fatores Etários , Idoso , Infecções Comunitárias Adquiridas/psicologia , Confusão/epidemiologia , Feminino , Custos de Cuidados de Saúde , Mortalidade Hospitalar , Humanos , Incidência , Pacientes Internados/psicologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia/psicologia , Estudos Retrospectivos , Taxa de Sobrevida
9.
Clin Lung Cancer ; 13(4): 280-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22178381

RESUMO

UNLABELLED: By using immunohistochemistry in tissue microarrays of 137 cases, we evaluated the prognostic power of a 3-marker epithelial-mesenchymal transition­related model in patients with stage I non-small-cell lung cancer who underwent radical surgical resection. The Twist/Slug/Foxc2 coexpression model accurately prognosticated these patients and may be helpful in refining current treatment strategy for stage I non-small-cell lung cancer. BACKGROUND: Lung cancer is the leading cause of cancer-related death in the world. Only about 60% of patients with stage I non-small-cell lung cancer (NSCLC) can be cured by surgery alone. Current clinical and molecular markers are inadequate prognosticators. We developed a 3-marker model that closely approximates survival probability of patients with stage I NSCLC. METHODS: Expression of Twist, Slug, and Foxc2 was assessed by immunohistochemistry in tissue microarrays that contained paired tumor and peritumoral lung tissue from 137 patients who underwent surgical resection for stage I NSCLC. The prognostic value of Twist, Slug, and Foxc2, and the cumulative effects of the 3 markers on survival were evaluated. RESULTS: Increased expression of Twist, Slug, and Foxc2 was observed in 38.0%, 18.2%, and 27.7% of primary tumors, respectively. Overexpression of Twist, Slug, and Foxc2 in stage I NSCLC was associated with a worse overall survival (P = .001, P = .002, P < .001, respectively) and correlated with a shorter recurrence-free survival (P < .001, P = .001, P < .001 respectively). The cumulative influence of these markers on outcome was analyzed; a combination of more than 2 positive markers was an independent predictor of recurrence-free and overall survival (P = .002 and P = .009, respectively). CONCLUSIONS: The Twist/Slug/Foxc2 model is useful in predicting survival of stage I NSCLC and may be helpful in refining current treatment strategy.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Prognóstico , Fatores de Transcrição da Família Snail , Fatores de Transcrição/genética , Proteína 1 Relacionada a Twist/genética
10.
Respir Med ; 105(10): 1543-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21764276

RESUMO

BACKGROUND: The 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) guidelines defined severe community-acquired pneumonia (CAP) when patients fulfilled three out of nine minor criteria. Whether each of the criteria is of equal weight is not clear. The purpose of this study was to determine the weight of the minor criteria. METHODS: 1230 adult patients admitted to our hospital from 2005 to 2009 for CAP were reviewed retrospectively. RESULTS: Hospital mortality rose sharply from 0.3%, 1.0% and 3.3%, respectively, for patients with none, one and two minor criteria to 10.5% for patients with three minor criteria. Arterial oxygen pressure/fraction inspired oxygen (PaO(2)/FiO(2)) ≤ 250 mm Hg, confusion, and uremia had the strongest association with mortality (Odds ratio, 22.162, 22.148, 16.343; respectively). Leukopenia, hypothermia, and hypotension were not associated with mortality. Confusion and uremia showed independent relationships with mortality (Odds ratio, 9.296, 8.493; respectively). Sequential organ failure assessment (SOFA) scores and costs increased significantly with the number of minor criteria present. Uremia and PaO(2)/FiO(2) ≤ 250 mm Hg were most strongly associated with SOFA scores [rank correlation coefficient (r(s)), 0.352, 0.336; respectively]. PaO(2)/FiO(2) ≤ 250 mm Hg and confusion were in closest relation to hospital length of stay (LOS) (r(s), 0.114, 0.114; respectively). PaO(2)/FiO(2) ≤ 250 mm Hg and multilobar infiltrates were most strongly associated with costs (r(s), 0.257, 0.196; respectively). CONCLUSIONS: The individual 2007 IDSA/ATS minor criteria for severe CAP were of unequal weight in predicting hospital mortality, SOFA scores, hospital LOS, and costs.


Assuntos
Admissão do Paciente/estatística & dados numéricos , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Guias como Assunto , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
12.
Sheng Wu Gong Cheng Xue Bao ; 23(6): 1097-101, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18257243

RESUMO

The random amplified polymorphic DNA (RAPD) technique was used to amplify DNA fragment, aiming at finding markers linked to the sex trait in Cycas tanqingii D. Y. Wang. A total number of 160 random primers were screened in the RAPD-PCR and more than 2500 RAPD fragments were generated from the male or the female plants. One fragment of about 500 bp was amplified steadily and repeatedly by the S0465 (CCCCGGTAAC) primer only from female plants but not male plants. The RAPD marker was then converted into female-linked dominant SCAR (Sequence Characterized Amplified Regions) marker named STQC-S465-483. The development of this sex-linked SCAR marker provides a possibility of identifying the sex of Cycas tanqingii before sexual maturation, which is very important to in situ or ex situ conservation.


Assuntos
Cycas/genética , Genes de Plantas , Marcadores Genéticos/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Processos de Determinação Sexual , Sequência de Bases , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos
13.
Neuroscientist ; 12(5): 375-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16956999

RESUMO

Neurons and glia are the principal cellular components of the nervous system. Although the glia are 10 times more numerous than neurons, until recently they were thought to be passive cells that monitor and support the active neurons by taking up used neurotransmitters from the synapses. In the past few years, this concept has been challenged by the findings that Ca(2+) waves spread from one astrocyte to another via Ca(2+)-and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-dependent gliotransmitter release in pure cultures of astrocytes, raising the possibility that glia are not so passive as previously thought. This hypothesis was further advanced by two recent reports, which demonstrated that astrocytes release glutamate via vesicular exocytosis in response to stimuli. The kinetics of single vesicle exocytosis is distinct from its neural equivalent, because in response to physiological stimulation, gliotransmitter release is exclusively in the mode of "kiss and run." These advances were made possible by newly available techniques for single vesicle recordings, which will also be briefly reviewed here.


Assuntos
Astrócitos/metabolismo , Animais , Cálcio/metabolismo , Diagnóstico por Imagem , Eletrofisiologia/métodos , Exocitose , Ácido Glutâmico/metabolismo , Humanos , Proteínas SNARE/metabolismo
14.
Nat Neurosci ; 8(9): 1160-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16116443

RESUMO

Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca2+ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive G(i/o) protein, leading to activation of G(betagamma) subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G(q) pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca2+-evoked secretion at specific steps in fusion pore formation.


Assuntos
Células Cromafins/metabolismo , Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Proteína Quinase C/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Medula Suprarrenal/citologia , Analgésicos Opioides/farmacologia , Animais , Cálcio/metabolismo , Células Cultivadas , Células Cromafins/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Interações de Medicamentos , Dinaminas/farmacologia , Estimulação Elétrica/métodos , Eletroquímica/métodos , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Subunidades beta da Proteína de Ligação ao GTP/farmacologia , Ionomicina/farmacologia , Ionóforos/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/efeitos da radiação , Muscarina/farmacologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Técnicas de Patch-Clamp/métodos , Toxina Pertussis/farmacologia , Cloreto de Potássio/farmacologia , Proteínas Quinases/farmacologia , Ratos , Proteínas Recombinantes de Fusão/farmacologia , Somatostatina/farmacologia , Tionucleotídeos/farmacologia
15.
J Physiol ; 548(Pt 1): 191-202, 2003 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-12576496

RESUMO

A comparative study was carried out on the inactivation of Na+ channels in two types of endocrine cells in rats, beta-cells and adrenal chromaffin cells (ACCs), using patch-clamp techniques. The beta-cells were very sensitive to hyperpolarization; the Na+ currents increased ninefold when the holding potential was shifted from -70 mV to -120 mV. ACCs were not sensitive to hyperpolarization. The half-inactivation voltages were -90 mV (rat beta-cells) and -62 mV (ACCs). The time constant for recovery from inactivation at -70 mV was 10.5 times slower in beta-cells (60 ms) than in ACCs (5.7 ms). The rate of Na+-channel inactivation at physiological resting potential was more than three times slower in beta-cells than in ACCs. Na+ influx through Na+ channels had no effect on the secretory machinery in rat beta-cells. However, these 'silent Na+ channels' could contribute to the generation of action potentials in some conditions, such as when the cell is hyperpolarized. It is concluded that the fractional availability of Na+ channels in beta-cells at a holding potential of -70 mV is about 15 % of that in ACCs. This value in rat beta-cells is larger than that observed in mouse (0 %), but is smaller than those observed in human or dog (90 %).


Assuntos
Glândulas Suprarrenais/metabolismo , Células Cromafins/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Bloqueadores dos Canais de Sódio/farmacologia , Glândulas Suprarrenais/citologia , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Células Cultivadas , Células Cromafins/efeitos dos fármacos , Eletrofisiologia , Cinética , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Tolbutamida/farmacologia
16.
J Biol Chem ; 278(15): 12624-33, 2003 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-12547831

RESUMO

A novel conotoxin, kappa-conotoxin (kappa-BtX), has been purified and characterized from the venom of a worm-hunting cone snail, Conus betulinus. The toxin, with four disulfide bonds, shares no sequence homology with any other conotoxins. Based on a partial amino acid sequence, its cDNA was cloned and sequenced. The deduced sequence consists of a 26-residue putative signal peptide, a 31-residue mature toxin, and a 13-residue extra peptide at the C terminus. The extra peptide is cleaved off by proteinase post-processing. All three Glu residues are gamma-carboxylated, one of the two Pro residues is hydroxylated at position 27, and its C-terminal residue is Pro-amidated. The monoisotopic mass of the toxin is 3569.0 Da. Electrophysiological experiments show that: 1) among voltage-gated channels, kappa-BtX is a specific modulator of K(+) channels; 2) among the K channels, kappa-BtX specifically up-modulates the Ca(2+)- and voltage-sensitive BK channels (252 +/- 47%); 3) its EC(50) is 0.7 nm with a single binding site (Hill = 0.88); 4) the time constant of wash-out is 8.3 s; and 5) kappa-BtX has no effect on single channel conductance, but increases the open probability of BK channels. It is concluded that kappa-BtX is a novel specific biotoxin against BK channels.


Assuntos
Conotoxinas/química , Conotoxinas/farmacologia , Canais de Potássio Cálcio-Ativados/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Sequência de Bases , Canais de Cálcio/fisiologia , Células Cultivadas , Células Cromafins/efeitos dos fármacos , Células Cromafins/fisiologia , Cromatografia em Gel , Conotoxinas/isolamento & purificação , Primers do DNA , DNA Complementar/genética , Canais de Potássio Ativados por Cálcio de Condutância Alta , Dados de Sequência Molecular , Moluscos , Canais de Potássio/fisiologia , Ratos , Ratos Wistar , Canais de Sódio/fisiologia , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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