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1.
J Trauma Acute Care Surg ; 90(3): 557-564, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507026

RESUMO

BACKGROUND: The Emergency Surgery Score (ESS) was recently validated as an accurate mortality risk calculator for emergency general surgery. We sought to prospectively evaluate whether ESS can predict the need for respiratory and/or renal support (RRS) at discharge after emergent laparotomies (EL). METHODS: This is a post hoc analysis of a 19-center prospective observational study. Between April 2018 and June 2019, all adult patients undergoing EL were enrolled. Preoperative, intraoperative, and postoperative variables were systematically collected. In this analysis, patients were excluded if they died during the index hospitalization, were discharged to hospice, or transferred to other hospitals. A composite variable, the need for RRS, was defined as the need for one or more of the following at hospital discharge: tracheostomy, ventilator dependence, or dialysis. Emergency Surgery Score was calculated for all patients, and the correlation between ESS and RRS was examined using the c-statistics method. RESULTS: From a total of 1,649 patients, 1,347 were included. Median age was 60 years, 49.4% were men, and 70.9% were White. The most common diagnoses were hollow viscus organ perforation (28.1%) and small bowel obstruction (24.5%); 87 patients (6.5%) had a need for RRS (4.7% tracheostomy, 2.7% dialysis, and 1.3% ventilator dependence). Emergency Surgery Score predicted the need for RRS in a stepwise fashion; for example, 0.7%, 26.2%, and 85.7% of patients required RRS at an ESS of 2, 12, and 16, respectively. The c-statistics for the need for RRS, the need for tracheostomy, ventilator dependence, or dialysis at discharge were 0.84, 0.82, 0.79, and 0.88, respectively. CONCLUSION: Emergency Surgery Score accurately predicts the need for RRS at discharge in EL patients and could be used for preoperative patient counseling and for quality of care benchmarking. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.


Assuntos
Serviço Hospitalar de Emergência , Hospitalização , Laparotomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Diálise Renal , Respiração Artificial , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Medição de Risco
2.
Am J Surg ; 221(5): 1069-1075, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32917366

RESUMO

INTRODUCTION: We sought to evaluate whether the Emergency Surgery Score (ESS) can accurately predict outcomes in elderly patients undergoing emergent laparotomy (EL). METHODS: This is a post-hoc analysis of an EAST multicenter study. Between April 2018 and June 2019, all adult patients undergoing EL in 19 participating hospitals were prospectively enrolled, and ESS was calculated for each patient. Using the c-statistic, the correlation between ESS and mortality, morbidity, and need for ICU admission was assessed in three patient age cohorts (65-74, 75-84, ≥85 years old). RESULTS: 715 patients were included, of which 52% were 65-74, 34% were 75-84, and 14% were ≥85 years old; 51% were female, and 77% were white. ESS strongly correlated with postoperative mortality (c-statistic:0.81). Mortality gradually increased from 0% to 20%-60% at ESS of 2, 10 and 16 points, respectively. ESS predicted mortality, morbidity, and need for ICU best in patients 65-74 years old (c-statistic:0.81, 0.75, 0.83 respectively), but its performance significantly decreased in patients ≥85 years (c-statistic:0.72, 0.64, 0.67 respectively). CONCLUSION: ESS is an accurate predictor of outcome in the elderly EL patient 65-85 years old, but its performance decreases for patients ≥85. Consideration should be given to modify ESS to better predict outcomes in the very elderly patient population.


Assuntos
Tratamento de Emergência/estatística & dados numéricos , Laparotomia/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tratamento de Emergência/efeitos adversos , Tratamento de Emergência/mortalidade , Feminino , Humanos , Laparotomia/efeitos adversos , Laparotomia/mortalidade , Masculino , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos
3.
J Trauma Acute Care Surg ; 89(1): 118-124, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32176177

RESUMO

BACKGROUND: The Emergency Surgery Score (ESS) was recently developed and retrospectively validated as an accurate mortality risk calculator for emergency general surgery. We sought to prospectively validate ESS, specifically in the high-risk nontrauma emergency laparotomy (EL) patient. METHODS: This is an Eastern Association for the Surgery of Trauma multicenter prospective observational study. Between April 2018 and June 2019, 19 centers enrolled all adults (aged >18 years) undergoing EL. Preoperative, intraoperative, and postoperative variables were prospectively and systematically collected. Emergency Surgery Score was calculated for each patient and validated using c-statistic methodology by correlating it with three postoperative outcomes: (1) 30-day mortality, (2) 30-day complications (e.g., respiratory/renal failure, infection), and (3) postoperative intensive care unit (ICU) admission. RESULTS: A total of 1,649 patients were included. The mean age was 60.5 years, 50.3% were female, and 71.4% were white. The mean ESS was 6, and the most common indication for EL was hollow viscus perforation. The 30-day mortality and complication rates were 14.8% and 53.3%; 57.0% of patients required ICU admission. Emergency Surgery Score gradually and accurately predicted 30-day mortality; 3.5%, 50.0%, and 85.7% of patients with ESS of 3, 12, and 17 died after surgery, respectively, with a c-statistic of 0.84. Similarly, ESS gradually and accurately predicted complications; 21.0%, 57.1%, and 88.9% of patients with ESS of 1, 6, and 13 developed postoperative complications, with a c-statistic of 0.74. Emergency Surgery Score also accurately predicted which patients required intensive care unit admission (c-statistic, 0.80). CONCLUSION: This is the first prospective multicenter study to validate ESS as an accurate predictor of outcome in the EL patient. Emergency Surgery Score can prove useful for (1) perioperative patient and family counseling, (2) triaging patients to the intensive care unit, and (3) benchmarking the quality of emergency general surgery care. LEVEL OF EVIDENCE: Prognostic study, level III.


Assuntos
Emergências , Cirurgia Geral , Medição de Risco/métodos , Ferimentos e Lesões/cirurgia , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Pontuação de Propensão , Estudos Prospectivos , Ferimentos e Lesões/mortalidade
4.
Am Surg ; 85(11): 1246-1252, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31775966

RESUMO

When endoscopy is performed for acute GI bleeding, therapeutic endoscopic procedures are infrequently required (only 6% of cases). We sought to determine the natural history of GI hemorrhage in patients who have undergone therapeutic endoscopy. We queried our hospital database for inpatients with acute GI bleeding who underwent therapeutic endoscopy between 2015 and 2017. The primary endpoints were recurrence of bleeding and the subsequent need for repeated endoscopic interventions, angioembolization, or surgery. Demographic information was collected. We reviewed 205 hospitalized patients: mean age was 70 years, 58 per cent were male, and mean hemoglobin was 9 g/dL. Patients had medical conditions predisposing them to bleeding in 59 per cent and history of previous GI bleeding in 37 per cent of cases. Sixty per cent were on antiplatelet/anticoagulation medications, and 10 per cent were receiving nonsteroidal anti-inflammatory medications. Blood transfusions were given to 78 per cent of patients, with an average of 2.3 units of packed red blood cells transfused per patient before intervention. Recurrence of hemorrhage after therapeutic endoscopy was seen in 9 per cent of patients. Only 2 per cent underwent a second therapeutic endoscopic procedure, and 5 per cent had surgery or angioembolization (half of these patients then had a further recurrence of bleeding). In total, seven patients died (3%). Recurrence of GI bleeding after therapeutic endoscopies is uncommon (9%). Surgery and angioembolization are not commonly necessary, but when used are only successful in 50 per cent of cases.


Assuntos
Hemorragia Gastrointestinal/terapia , Hemostase Endoscópica/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia/métodos , Anticoagulantes/uso terapêutico , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Hemoglobina A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Recidiva , Retratamento , Estudos Retrospectivos , Adulto Jovem
5.
J Trauma Acute Care Surg ; 87(1): 100-103, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31259870

RESUMO

BACKGROUND: Postoperative outpatient narcotic overprescription plays a significant role in the opioid epidemic. Outpatient opioid prescription ranges from 150 to 350 oral morphine equivalent (OME) for a laparoscopic cholecystectomy or appendectomy, with 75 OME (10 pills of 5 mg of oxycodone) being the lowest recommendation (National Institute on Drug Abuse, 2018). We hypothesized that the addition of nonopioid medications to the outpatient pain control regimen would decrease the need for narcotics. METHODS: In this prospective, observational pilot study, we prescribed a 3-day regimen of ibuprofen and acetaminophen to patients after uncomplicated laparoscopic cholecystectomies and appendectomies. An additional opioid prescription for 5 pills of 5 mg of oxycodone (37.5 OME) was written for breakthrough pain. During their postoperative visit, we evaluated patients' adherence to the pain control regime, their postdischarge opioid use, and the adequacy of their pain control. RESULTS: Sixty-five patients were included in the study (52% male). The majority (80%) of surgeries were performed urgently or emergently. The visual analog scale pain score at home was significantly better than upon discharge (3.7 vs. 5.5, p = 0.001). The average number of oxycodone pills taken postdischarge was 1.8 pills. Half (51%) of the patients did not take any opioids. All but four patients reported that their pain was adequately controlled. No patient required additional opioid prescriptions or visited the emergency department. CONCLUSION: This study demonstrated that opioids can be eliminated in at least half of the patients and that five pills of 5 mg of oxycodone (37.5 OME) is sufficient for outpatient pain control when a 3-day course of ibuprofen and acetaminophen is prescribed. LEVEL OF EVIDENCE: Therapeutic study, level V.


Assuntos
Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Ibuprofeno/uso terapêutico , Manejo da Dor/métodos , Dor Pós-Operatória/terapia , Analgésicos Opioides/uso terapêutico , Apendicectomia/efeitos adversos , Apendicectomia/métodos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxicodona/uso terapêutico , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos
6.
Am Surg ; 85(3): 306-311, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30947780

RESUMO

MRI after a CT scan for thoracolumbar spine (TLS) trauma has become commonplace because of the concerns for detection of posterior ligamentous complex injuries in the absence of substantial scientific evidence to support its use. We hypothesized that MRI scans were not necessary in the clinical management of TLS fractures. A prospective study was conducted at our Level I trauma center. A total of 39 neurologically intact patients with TLS fracture on CT were enrolled. The patients' CT scan and neurological examination were reviewed by a senior neurosurgeon, who determined clinical management based on these data. Assessment was repeated after an MRI of the spine was performed, and a second clinical plan was devised. The two treatment schemes were then compared. MRI resulted in a change in clinical management in 15 per cent of patients. Ten per cent of patients changed from requiring a brace to no brace and merely observation alone. In no patient planned for nonoperative care was surgery deemed necessary after completion of MRI. Among five patients with initial plans for operative intervention, two avoided surgery after the MRI. MRI has little impact on the management of patients with CT-proven thoracic and lumbar spine fractures. Only when surgery is planned based on CT studies does an MRI seem to assist with determining optimal care.


Assuntos
Vértebras Lombares/lesões , Imageamento por Ressonância Magnética , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , Adulto Jovem
7.
J Emerg Med ; 55(2): 165-171.e1, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29753571

RESUMO

BACKGROUND: Between 1990 and 2003, there were 668 subway-related fatalities in New York City. However, subway-related trauma remains an understudied area of injury-related morbidity and mortality. OBJECTIVE: The objective of this study was to characterize the injuries and events leading up to the injuries of all patients admitted after subway-related trauma. METHODS: We conducted a retrospective case series of subway-related trauma at a Level I trauma center from 2001 to 2016. Descriptive epidemiology of patient demographics, incident details, injuries, and outcomes were analyzed. RESULTS: Over 15 years, 254 patients were admitted for subway-related trauma. The mean (standard error of the mean) age was 41 (1.0) years, 80% were male (95% confidence interval [CI] 74-84%) and median Injury Severity Score was 14 (interquartile range [IQR] 5-24). The overall case-fatality rate was 10% (95% CI 7-15%). The most common injuries were long-bone fractures, intracranial hemorrhage, and traumatic amputations. Median length of stay was 6 days (IQR 1-18 days). Thirty-seven percent of patients required surgical intervention. At the time of injury, 55% of patients (95% CI 49-61%) had a positive urine drug or alcohol screen, 16% (95% CI 12-21%) were attempting suicide, and 39% (95% CI 33-45%) had a history of psychiatric illness. CONCLUSIONS: Subway-related trauma is associated with a high case-fatality rate. Alcohol or drug intoxication and psychiatric illness can increase the risk of this type of injury.


Assuntos
Saúde Pública/normas , Ferrovias/estatística & dados numéricos , Saúde da População Urbana/normas , Ferimentos e Lesões/etiologia , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/psicologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Ferrovias/instrumentação , Estudos Retrospectivos , Centros de Traumatologia/organização & administração , Centros de Traumatologia/estatística & dados numéricos
8.
Am J Surg ; 210(1): 45-51, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26025750

RESUMO

BACKGROUND: The objective of this study was to characterize variations in packed red blood cell (PRBC) transfusion practices in critically ill patients and to identify which factors influence such practices. We hypothesized that significant variation in transfusion triggers exists among acute care surgeons. METHODS: A survey of PRBC transfusion practices was administered to the American Association for the Surgery of Trauma members. The scenarios examined hemoglobin thresholds for which participants would transfuse PRBCs. RESULTS: A hemoglobin threshold of less than or equal to 7 g/dL was adopted by 45% of respondents in gastrointestinal bleeding, 75% in penetrating trauma, 66% in sepsis, and 62% in blunt trauma. Acute care surgeons modified their transfusion trigger significantly in the majority of the modifications of these scenarios, often inappropriately so. CONCLUSIONS: This study documents continued evidence-practice gaps and wide variations in the PRBC transfusion practices of acute care surgeons. Numerous clinical factors altered such patterns despite a lack of supporting evidence (for or against).


Assuntos
Competência Clínica , Transfusão de Eritrócitos/normas , Padrões de Prática Médica , Traumatologia , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Sociedades Médicas , Traumatologia/educação , Estados Unidos
9.
Am J Surg ; 206(6): 929-33; discussion 933-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24139671

RESUMO

BACKGROUND: Flexion-extension radiographs are often used to assess for removal of the cervical collar in the setting of trauma. The objective of this study was to evaluate their adequacy. We hypothesized that a significant proportion is inadequate. METHODS: This was a retrospective review of C-spine clearance at a level 1 trauma center. A trauma-trained radiologist interpreted all flexion-extension radiographs for adequacy. Studies performed within 7 days of injury were considered acute. RESULTS: Three hundred fifty-five flexion-extension radiographs were examined. Ninety-five percent% of these studies were inadequate (51% because of the inability to visualize the top of T1, whereas 44% had less than 30° of angulation from neutral). Two hundred ten studies were performed acutely; of these, 97% were inadequate. When performed 7 days or longer from injury, 91% were inadequate. CONCLUSIONS: Injury to the C-spine may harbor significant consequences; therefore, its proper evaluation is critical. The majority of flexion-extension films are inadequate. As such, they should not be included in the algorithm for removal of the cervical collar. If used, adequacy must be verified and supplemental radiographic studies obtained as indicated.


Assuntos
Algoritmos , Vértebras Cervicais/lesões , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Filme para Raios X/estatística & dados numéricos , Adulto , Vértebras Cervicais/diagnóstico por imagem , Feminino , Humanos , Masculino , Estudos Retrospectivos
10.
Nutr Clin Pract ; 28(3): 387-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23459609

RESUMO

BACKGROUND: In 2009, the Society of Critical Care Medicine (SCCM)/American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) published "Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient." To improve our surgery residents' understanding of intensive care unit (ICU) nutrition, we developed a nutrition education program based on these guidelines. The purpose of this pilot study was to assess its effectiveness. We hypothesized that our nutrition education program would improve our residents' knowledge of ICU nutrition. MATERIALS AND METHODS: This was a prospective observational pilot study performed in the surgical ICU of an academic medical center. Based on the SCCM/A.S.P.E.N. nutrition guidelines, we developed a nutrition education program (lectures covering selected guidelines and interactive case studies). Pre- and posttesting were performed to assess short-term comprehension. Long-term retention was assessed 3 months after the initial education program. The primary outcome measure was the change in ICU nutrition knowledge. Significance was set at P < .05. RESULTS: Over 12 months, 8 surgery residents completed the nutrition education program. Their mean age was 27.8 ± 1.2 years, and 50% were male. The mean test scores were as follows: pretest, 45% ± 9%; posttest, 81% ± 5%; and 3-month test, 65% ± 8%. The differences between the pretest and both posttest scores were significant (P < .01). CONCLUSION: Residents have little understanding of ICU nutrition. This is confirmed by the pretest results of the current study. Our nutrition education program improved both short-term and long-term ICU nutrition knowledge of our surgery residents. Future studies should evaluate the effect such education has on the clinical outcomes of ICU patients.


Assuntos
Cuidados Críticos/métodos , Ciências da Nutrição/educação , Médicos , Inanição/prevenção & controle , Adulto , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Estudos Observacionais como Assunto , Nutrição Parenteral/métodos , Projetos Piloto , Guias de Prática Clínica como Assunto , Estudos Prospectivos
11.
J Trauma Acute Care Surg ; 73(6): 1457-60, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23188238

RESUMO

BACKGROUND: Studies have documented a correlation between hypothyroxinemia and mortality in critically ill patients; however, there are limited data in sepsis. The objective of this study was to assess baseline thyroid function studies and their association with mortality in surgical sepsis. We hypothesized that the relatively decreased levels of free thyroxine (T4), decreased levels of triiodothyronine (T3), and increased thyrotropin-stimulating hormone levels would be associated with mortality. METHODS: This was a retrospective review of prospectively collected data in a surgical intensive care unit. Data evaluated included patient demographics, baseline thyroid function studies, and mortality. Patients were categorized as having sepsis, severe sepsis, or septic shock. A value of p < 0.05 was considered significant. RESULTS: Within 24 months, 231 septic patients were accrued. The mean age was 59 ± 3 years, and 43% were male. Thirty-nine patients were diagnosed as having sepsis, 131 as having severe sepsis, and 61 as having septic shock. There were no statistically significant differences between the T3, free T4, or thyrotropin-stimulating hormone levels at baseline and the different categorizations of sepsis.T4 levels were increased in all patients but to a significantly lesser extent in those who died. Similarly, T3 levels were significantly decreased in patients who died. CONCLUSION: In surgical sepsis, decreased T3 levels at baseline are associated with mortality. These data do not support the administration of levothyroxine (T4) because it is already elevated and would preferentially be converted to reverse T3 (inactive) in critical illness; however, replacement with liothyronine (T3) might be rational. LEVEL OF EVIDENCE: Epidemiologic study, level III.


Assuntos
Síndromes do Eutireóideo Doente/diagnóstico , Sepse/complicações , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/etiologia , Síndromes do Eutireóideo Doente/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/sangue , Sepse/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
12.
J Trauma Nurs ; 19(2): 102-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22673077

RESUMO

Blunt pancreatic trauma is rare; however, if missed, it can lead to devastating consequences such as fistula, pancreatitis, and pseudocyst. Blunt trauma accounts for 30% of all pancreatic injuries. High-speed motor vehicle collisions make up the greatest proportion of blunt pancreatic trauma, whereas other causes could be easily overlooked because of being so rare. In this case report we present a case of full-thickness transection of pancreatic tail after being kicked by a horse. The injury was timely identified and successfully treated by completing transection with a stapler. Considering that delay in diagnosis leads to a morbidity rate of 20%, physicians must have high level of suspicion and knowledge of invasive and noninvasive modalities to ensure early detection of pancreatic trauma and a positive outcome.


Assuntos
Enfermagem em Emergência , Cavalos , Pâncreas/lesões , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/enfermagem , Animais , Feminino , Humanos , Centros de Traumatologia , Ferimentos não Penetrantes/cirurgia , Adulto Jovem
13.
Free Radic Biol Med ; 49(5): 757-69, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20633346

RESUMO

Nitric oxide (NO) and related reactive nitrogen species (RNS) play a major role in the pathophysiology of stroke and other neurodegenerative diseases. One of the poorly understood consequences of stroke is a long-lasting inhibition of synaptic transmission. In this study, we tested the hypothesis that RNS can produce long-term inhibition of neurotransmitter release via S-nitrosylation of proteins in presynaptic nerve endings. We examined the effects of exogenous sources of RNS on the vesicular and nonvesicular L-[(3)H]glutamate release from rat brain synaptosomes. NO/RNS donors, such as spermine NONOate, MAHMA NONOate, S-nitroso-L-cysteine, and SIN-1, inhibited only the vesicular component of glutamate release with an order of potency that closely matched levels of protein S-nitrosylation. Inhibition of glutamate release persisted for >1h after RNS donor decomposition and washout and strongly correlated with decreases in the intrasynaptosomal ATP levels. Post-NO treatment of synaptosomes with thiol-reducing reagents decreased the total content of S-nitrosylated proteins but had little effect on glutamate release and ATP levels. In contrast, post-NO application of the end-product of glycolysis, pyruvate, partially rescued neurotransmitter release and ATP production. These data suggest that RNS suppress presynaptic metabolism and neurotransmitter release via poorly reversible modifications of glycolytic and mitochondrial enzymes, one of which was identified as glyceraldehyde-3-phosphate dehydrogenase. A similar mechanism may contribute to the long-term suppression of neuronal communication during nitrosative stress in vivo.


Assuntos
Neurotransmissores/metabolismo , Terminações Pré-Sinápticas/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , S-Nitrosotióis/metabolismo , Animais , Cisteína/análogos & derivados , Cisteína/metabolismo , Cisteína/farmacologia , Ditiotreitol/farmacologia , Regulação para Baixo/efeitos dos fármacos , Gliceraldeído-3-Fosfato Desidrogenase (NADP+)(Fosforiladora)/metabolismo , Masculino , Terminações Pré-Sinápticas/efeitos dos fármacos , Ácido Pirúvico/farmacologia , Ratos , Ratos Sprague-Dawley , S-Nitrosotióis/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Fatores de Tempo
14.
Biochemistry ; 46(51): 15123-35, 2007 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-18047298

RESUMO

Fifty-nine RNA duplexes containing single-nucleotide bulge loops were optically melted in 1 M NaCl, and the thermodynamic parameters DeltaH degrees, DeltaS degrees, DeltaG 37 degrees, and TM for each sequence were determined. Sequences from this study were combined with sequences from previous studies [Longfellow, C. E., et al. (1990) Biochemistry 29, 278-285; Znosko, B. M., et al. (2002) Biochemistry 41, 10406-10417], thus examining all possible group I single-nucleotide bulge loop and nearest-neighbor sequence combinations. The free energy increments at 37 degrees C for the introduction of a group I single-nucleotide bulge loop range between 1.3 and 5.2 kcal/mol. The combined data were used to develop a model for predicting the free energy of a RNA duplex containing a single-nucleotide bulge. For bulge loops with adjacent Watson-Crick base pairs, neither the identity of the bulge nor the nearest-neighbor base pairs had an effect on the influence of the bulge loop on duplex stability. The proposed model for prediction of the stability of a duplex containing a bulged nucleotide was primarily affected by non-nearest-neighbor interactions. The destabilization of the duplex by the bulge was related to the stability of the stems adjacent to the bulge. Specifically, there was a direct correlation between the destabilization of the duplex and the stability of the less stable duplex stem. The stability of a duplex containing a bulged nucleotide adjacent to a wobble base pair also was primarily affected by non-nearest-neighbor interactions. Again, there was a direct correlation between the destabilization of the duplex and the stability of the less stable duplex stem. However, when one or both of the bulge nearest neighbors was a wobble base pair, the free energy increment for insertion of a bulge loop is dependent upon the position and orientation of the wobble base pair relative the bulged nucleotide. Bulge sequences of the type ((5'UBX)(3'GY)), ((5'GBG)(3'UU)) and ((5'UBU)(3'GG)) are less destabilizing by 0.6 kcal/mol, and bulge sequences of the type ((5'GBX)(3'UY)) and ((5'XBU)(3'YG)) are more destabilizing by 0.4 kcal/mol than bulge loops adjacent to Watson-Crick base pairs.


Assuntos
Nucleotídeos/química , Estabilidade de RNA , RNA/química , RNA/genética , Sequência de Bases , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Nucleotídeos/genética , Termodinâmica
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