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1.
Ann Surg ; 254(6): 927-32, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21804381

RESUMO

BACKGROUND: Several studies have demonstrated the superiority of the laparoscopic approach in uncomplicated and complicated appendicitis with conflicting results. As a result the role of laparoscopy in the management of appendicitis in general and complicated or perforated appendicitis, in particular, is still undefined. METHODS: A retrospective, observational study design was used to analyze multicenter outcomes using the University HealthSystem Consortium database. A 3-year discharge data of all open appendectomy (OA) and laparoscopic appendectomy (LA) procedures from 2006 to 2008 in adult patients older than 18 years for complicated or uncomplicated appendicitis was accessed using International Classification of Diseases, Ninth Revision codes. Data on several surgical outcome measures such as observed mortality, overall patient morbidity, intensive care unit admission rate, 30-day readmission rate, length of hospital stay, and hospital costs were collected from the University HealthSystem Consortium database. Stratification by University HealthSystem Consortium-specific severity of illness groups and disease diagnosis of complicated or perforated and uncomplicated appendicitis was performed. RESULTS: A total of 40,337 appendectomy procedures performed during 2006 to 2008 in adult patients were included in the study. Laparoscopic appendectomy for uncomplicated appendicitis resulted in significantly better surgical outcomes. However, surprisingly, these outcomes resulted in comparable but not significantly reduced hospital costs (7825 ± 6,009 for LA vs 7841 ± 13,147 for OA; P > 0.05). Laparoscopic appendectomy for complicated or perforated appendicitis showed lower mortality, reduced overall morbidity (17.43% for LA vs 26.68% for OA; P < 0.001), relatively less 30-day readmission rate, fewer intensive care unit admissions, significantly shorter length of hospital stay (4.34 ± 4.84 days for LA vs 7.31 ± 9.43 for OA; P < 0.001), and reduced hospital costs (12,125 ± 14,430 for LA vs 17,594 ± 28,065 for OA; P < 0.001) compared with patients undergoing OA. On stratification for severity of illness in both complicated and uncomplicated appendicitis, laparoscopic appendectomy resulted in a greater or comparable clinical benefit than open appendectomy. Comparable clinical benefit was observed in minor severity patients and moderate and major/extreme severity patients showed vastly improved surgical outcomes with the laparoscopic approach. CONCLUSIONS: Laparoscopic appendectomy is superior or comparable to open appendectomy in terms of several surgical outcome measures for both uncomplicated and complicated appendicitis, across most illness severity groups. Thus, laparoscopic appendectomy may be the preferred technique, irrespective of appendicitis diagnosis or disease severity.


Assuntos
Apendicectomia/métodos , Apendicite/cirurgia , Laparoscopia/métodos , Adolescente , Adulto , Idoso , Apendicectomia/economia , Apendicite/economia , Comorbidade , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/economia , Unidades de Terapia Intensiva/estatística & dados numéricos , Laparoscopia/economia , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Readmissão do Paciente/economia , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos , Adulto Jovem
2.
Surg Endosc ; 25(5): 1466-71, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20976492

RESUMO

INTRODUCTION: There is scarce evidence regarding optimal treatment options for achalasia in patients with varying illness severity risk. The objective of this study was to evaluate and compare outcomes with laparoscopic esophagomyotomy with fundoplication (LM) and esophageal dilation (ED) for hospitalized patients with different illness severity. METHODS: The University HealthSystem Consortium (UHC) is an alliance of more than 100 academic medical centers and nearly 200 affiliate hospitals. UHC's Clinical Data Base/Resource Manager (CDB/RM) allows member hospitals to compare patient-level risk-adjusted outcomes for performance improvement purposes. The CDB/RM was queried for patients with achalasia who underwent LM (n=1,390) or ED (n=492) during a 3-year period between 2006 and 2008. RESULTS: Overall esophageal perforation rates were significantly higher for ED (0.4% LM vs. 2.4% ED; p<0.001). Patients undergoing LM with minor/moderate illness severity showed higher morbidity (9.42% LM vs. 5.15% ED; p<0.05). However, LM patients in this illness severity group showed significantly lower 30-day readmission rate (0.38% LM vs. 7.32% ED; p<0.001) and length of stay (2.23±1.78 LM vs. 4.88±4.42 days ED; p<0.001), but comparable cost ($9,539 LM vs. $8990 ED; p>0.05). In the major/extreme illness severity group mortality was comparable (1.37% LM vs. 2.44% ED; p>0.05). Overall morbidity was significantly greater in LM (50.48% LM vs. 19.57% ED; p<0.001). However, the length of stay was significantly increased in the ED group (8.96±7.86 LM vs. 11.72±11.05 days ED; p=0.04). CONCLUSION: In hospitalized patients with minor/moderate illness severity, laparoscopic myotomy for achalasia showed comparable or better outcomes than ED. For major/extreme illness severity, dilation showed comparable or better profile for hospitalized achalasia patients. These results highlight the importance and impact of illness severity on outcomes of achalasia patients.


Assuntos
Dilatação , Acalasia Esofágica/terapia , Esôfago/cirurgia , Fundoplicatura , Laparoscopia , Adolescente , Adulto , Idoso , Dilatação/efeitos adversos , Acalasia Esofágica/cirurgia , Perfuração Esofágica/etiologia , Feminino , Fundoplicatura/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
3.
Surg Endosc ; 25(5): 1458-65, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21046157

RESUMO

BACKGROUND: Patients undergoing laparoscopic paraesophageal herniorrhaphy present with various esophageal and extraesophageal symptoms. Given a recurrence rate of up to 44%, reoperative intervention is necessary on a number of patients. The goal of this study is to determine whether patients proceeding with reoperative laparoscopic paraesophageal herniorrhaphy experienced symptom resolution equal to or better than patients undergoing first-time repair. METHODS: A frequency-based symptom assessment consisting of 24 esophageal and extraesophageal reflux symptoms was developed and administered pre- and postoperatively to patients undergoing initial or reoperative paraesophageal herniorrhaphy during a 7-year period. A composite score for esophageal and extraesophageal symptoms was calculated. Retrospective analysis of patient records including diagnostic studies, and operative and postoperative progress notes was performed. Data were analyzed using appropriate statistical tests. RESULTS: In 195 patients, 89.9% of patients had resolved or improved individual symptom scores at 6 months postoperatively after primary or reoperative paraesophageal herniorrhaphy. Paraesophageal herniorrhaphy resulted in improvements of both esophageal (16.1±8.5 preoperatively versus 3.5±5.0 at 6 months postoperatively; p<0.001) and extraesophageal (8.6±7.5 preoperatively versus 2.2±5.1 at 6 months postoperatively; p<0.001) composite scores and all individual symptom scores (p<0.05). Preoperatively, patients undergoing reoperative surgery had significantly higher solid dysphagia and abdominal discomfort, but lower odynophagia scores. Furthermore, reoperative patients had significantly lower preoperative composite extraesophageal scores (6.1±7.2 reoperative versus 9.1±7.5 primary; p<0.05) and individual symptom scores in laryngitis, hoarseness, and coughing. Only heartburn in reoperative patients was significantly higher at 12 months postoperatively. Otherwise, there was no significant difference in individual or composite symptom scores between groups postoperatively. All scores had significant improvement postoperatively when compared with preoperative scores. CONCLUSIONS: Our data demonstrate that reoperative laparoscopic paraesophageal herniorrhaphy can produce excellent results, comparable to first-time repair.


Assuntos
Hérnia Hiatal/cirurgia , Laparoscopia , Feminino , Hérnia Hiatal/complicações , Hérnia Hiatal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Resultado do Tratamento
4.
Surg Endosc ; 25(4): 1127-35, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20927546

RESUMO

BACKGROUND: Laparoscopic surgery has been shown to offer superior surgical outcomes for most abdominal surgical procedures. However, there is hardly any evidence on surgical outcomes with patient risk stratification. This study aimed to compare outcomes of common laparoscopic and open surgical procedures for varying illness severity. METHODS: A retrospective analysis of surgical outcomes for six commonly performed surgical procedures including cholecystectomy, appendectomy, reflux surgery, gastric bypass surgery, ventral hernia repair, and colectomy was performed using the University HealthSystem Consortium (UHC) Clinical Database/Resource Manager (CDB/RM). The 3-year discharge data for the six commonly performed laparoscopic surgical procedures were analyzed for outcome measures including observed mortality, overall patient morbidity, intensive care unit (ICU) admissions, 30-day readmissions, length of hospital stay, and hospital costs. RESULTS: In this study, 208,314 patients underwent one of six common surgical procedures by either the open or the laparoscopic approach. Overall, the laparoscopic approach showed significantly lower mortality, reduced morbidity, fewer ICU admissions and 30-day readmissions, shorter hospital stay, and significantly reduced hospital costs for all the procedures. At stratification by illness severity, the laparoscopic group showed better or comparable surgical outcomes across all the illness severity groups. However, the observed mortality was comparable for the minor and moderate severity patients between laparoscopic and open surgery for most procedures. The 30-day readmission rate for major/extreme severity patients was comparable between the two groups for most surgical procedures. CONCLUSIONS: This study demonstrated the superiority of laparoscopy over conventional open surgery across all illness severity risk groups for common surgical procedures. The results in general show that laparoscopic surgery is safe, efficacious, and cost-effective compared with open surgery and suggest that laparoscopic surgery should be the procedure of choice for all common surgical procedures, regardless of illness severity.


Assuntos
Custos Hospitalares/estatística & dados numéricos , Laparoscopia/estatística & dados numéricos , Sistemas Multi-Institucionais/economia , Centros Médicos Acadêmicos/economia , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Idoso , Apendicectomia/efeitos adversos , Apendicectomia/economia , Apendicectomia/métodos , Apendicectomia/estatística & dados numéricos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/economia , Colecistectomia Laparoscópica/estatística & dados numéricos , Colectomia/efeitos adversos , Colectomia/economia , Colectomia/métodos , Colectomia/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Fundoplicatura/efeitos adversos , Fundoplicatura/economia , Fundoplicatura/métodos , Fundoplicatura/estatística & dados numéricos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/economia , Derivação Gástrica/métodos , Derivação Gástrica/estatística & dados numéricos , Hérnia Ventral/cirurgia , Hospitais Universitários/economia , Hospitais Universitários/estatística & dados numéricos , Humanos , Classificação Internacional de Doenças , Laparoscopia/efeitos adversos , Laparoscopia/economia , Masculino , Pessoa de Meia-Idade , Sistemas Multi-Institucionais/estatística & dados numéricos , Nebraska , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
5.
Toxicol Sci ; 91(2): 493-500, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16551643

RESUMO

Since inducible nitric oxide synthase (iNOS) and proximal tubule injury are known to be critical determinants of lipopolysaccharide (LPS)-induced renal failure, the role of nitric oxide (NO) in proximal tubule cell apoptosis was examined. An 18-h treatment with a combination of LPS (5 microg/ml) and interferon-gamma (IFN-gamma, 100 units/ml) synergistically induced iNOS and produced a 20-fold increase in NO generation in the TKPTS murine proximal tubule cell line. NO generation by LPS + IFN-gamma was blocked by a specific iNOS blocker, L-N6-(1-iminoethyl)-lysine (L-NIL, 1 mM). To assess the role of iNOS-derived NO in proximal tubule cell apoptosis, annexin V- and propidium iodide-labeled cells were analyzed by flow cytometry. Neither the induction of iNOS nor its inhibition produced significant apoptotic cell death in TKPTS cells. Two exogenous NO donors were used to examine the role of NO more directly in proximal tubule apoptosis. Although both sodium nitroprusside (SNP), an iron-containing, nitrosonium cation donor, and S-nitroso-N-acetylpenicillamine (SNAP), a noniron-containing, NO generator, produced a concentration-dependent increase in NO generation, only SNP increased apoptotic cell death in TKPTS cells (5.9 +/- 0.7% in control cells vs. 21.6 +/- 3.8% in SNP [500 microM]-treated cells; n = 4-9; p < 0.01). SNP-mediated tubule cell apoptosis was not dependent on the activation of caspases or p53 but was possibly related to the generation of reactive oxygen species by SNP. Thus, in TKPTS cells induction of iNOS and generation of NO by LPS does not lead to tubular epithelial cell death.


Assuntos
Apoptose , Interferon gama/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Óxido Nítrico/biossíntese , Animais , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Camundongos , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo II/biossíntese , Nitritos/metabolismo , Nitroprussiato/farmacologia , Penicilamina/análogos & derivados , Penicilamina/farmacologia , Espécies Reativas de Oxigênio/metabolismo
6.
Am J Infect Control ; 40(1): 51-4, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21802780

RESUMO

BACKGROUND: Despite the well-recognized role of urinary catheters in nosocomial urinary tract infections, data on risk factors associated with inappropriate urinary catheter use are scarce. METHODS: A prospective review of electronic medical records of 436 patients admitted to an adult medical-surgical unit between October and December 2007 was performed to examine the appropriateness of urinary catheter use. RESULTS: The use of 157 urinary catheters in 144 patients was observed. A total of 557 urinary catheter-days were recorded in these patients, of which 175 (31.4%) were found to be inappropriate based on the study criteria. The total number of catheters used and the total duration of catheterization were risk factors for inappropriate urinary catheter use (P < .05). Inappropriate catheter use was not associated with such adverse events as mortality, readmission, intensive care unit admission, catheter complications, or urine culture rates, but was associated with a trend toward longer duration of hospitalization. CONCLUSIONS: Significant rates of inappropriate urinary catheter use and a trend toward longer duration of hospitalization with inappropriate catheter use were observed. These findings underscore the importance of establishing guidelines and effective policy implementation for the appropriate use of urinary catheters in hospitalized patients.


Assuntos
Cateteres de Demora , Cateterismo Urinário/métodos , Cateterismo Urinário/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Cateterismo Urinário/efeitos adversos
7.
Surg Obes Relat Dis ; 7(3): 290-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21130046

RESUMO

BACKGROUND: Limited evidence exists regarding the outcomes of patients undergoing laparoscopic adjustable band placement (LAGB) with hiatal hernia (HH) and concomitant hiatal hernia repair (HHR). The present study evaluated the safety, efficacy, and cost-effectiveness of primary LAGB (pLAGB) and revisional LAGB (rLAGB) in patients with HH. METHODS: The University HealthSystem Consortium is an alliance of >100 academic medical centers and nearly 200 affiliate hospitals. The University Health System Consortium database was queried for patients undergoing LAGB with and without HH from 2006 through 2009. RESULTS: The patients undergoing rLAGB had a significantly greater prevalence of HH than patients undergoing pLAGB (18.9% for pLAGB with HH versus 26.3% for rLAGB with HH; P <.001). The mortality (.04% for pLAGB without HH versus 0% for pLAGB with HHR; P >.05), morbidity (3.39% pLAGB without HH versus 2.63% for pLAGB HHR; P >.05), and length of stay (1.33 ± 2.25 days for pLAGB without HH versus 1.17 ± 0.56 days for pLAGB with HHR; P >.05) were comparable in the patients undergoing pLAGB with or without HHR. A trend was seen toward increased morbidity in patients undergoing rLAGB HHR than in those undergoing pLAGB HHR (2.63% for pLAGB HHR versus 13.33% for rLAGB HHR; P = .08). The length of stay (1.17 ± 0.56 days for pLAGB HHR versus 1.73 ± 1.49 days for rLAGB HHR; P <.01) and hospital costs ($12,178 ± 4451 for pLAGB HHR versus $14,616 ± 3538 for rLAGB HHR; P = .04) were increased for the rLAGB HHR group compared with the pLAGB HHR group. CONCLUSION: The results of the present study have demonstrated the safety of HHR concomitant with pLAGB. In addition, rLAGB was associated with increased morbidity and cost. These data suggest the safety, efficacy, and cost-effectiveness of crural repair of HH simultaneously with pLAGB.


Assuntos
Gastroplastia/métodos , Hérnia Hiatal/cirurgia , Herniorrafia/métodos , Laparoscopia , Obesidade Mórbida/cirurgia , Reoperação/métodos , Adolescente , Adulto , Idoso , Feminino , Hérnia Hiatal/complicações , Hérnia Hiatal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nebraska/epidemiologia , Obesidade Mórbida/complicações , Prevalência , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Surg Obes Relat Dis ; 7(3): 277-82, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21459686

RESUMO

BACKGROUND: Although several risk factors affecting weight loss outcomes with bariatric procedures have been identified, the effect of age, gender, race, and illness severity on postoperative outcomes of laparoscopic gastric bypass has not been extensively examined. METHODS: The University HealthSystem Consortium database is an administrative and financial database that provides information on the inpatient stay. A retrospective analysis of patient outcomes was performed using 4-year discharge data from the University HealthSystem Consortium database. RESULTS: A total of 37,765 patients underwent laparoscopic gastric bypass. The women exhibited significantly reduced mortality, morbidity, intensive care unit (ICU) admissions (9.87% male versus 6.73% female; P <.001), duration of hospitalization (2.72 ± 4.03 d for men versus 2.59 ± 2.88 d for women; P <.001), and hospital costs ($17,346 ± $15,397 for men versus $14,383 ± $11,170 for women; P <.001). Blacks demonstrated significantly greater 30-day readmission rates, duration of hospitalization, and costs compared with whites. Hispanics had lower ICU admission and hospital costs compared with whites. With increasing age, an increased risk of overall morbidity, ICU admissions, duration of hospitalization, and costs was observed. Compared with the minor severity group, the major/extreme severity group had significantly greater observed mortality, overall morbidity, ICU admissions, duration of hospitalization, and hospital costs. CONCLUSION: The present study identified gender, race, age, and illness severity as risk factors affecting postoperative outcomes after laparoscopic gastric bypass. Male gender and increasing age were overall associated with an increased risk of complications. Significant racial disparities in the outcome measures were observed with blacks having an increased risk of adverse events. Illness severity was shown to adversely affect the surgical outcomes in laparoscopic gastric bypass.


Assuntos
Derivação Gástrica/métodos , Laparoscopia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Derivação Gástrica/economia , Custos Hospitalares/tendências , Humanos , Incidência , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/economia , Readmissão do Paciente/tendências , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto Jovem
9.
World J Gastrointest Surg ; 2(6): 217-23, 2010 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-21160878

RESUMO

Natural orifice translumenal endoscopic surgery (NOTES) is the integration of laparoscopic minimally invasive surgery techniques with endoscopic technology. Despite the advances in NOTES technology, the approach presents several unique instrumentation and technique-specific challenges. Current flexible endoscopy platforms for NOTES have several drawbacks including limited stability, triangulation and dexterity, and lack of adequate visualization, suggesting the need for new and improved instrumentation for this approach. Much of the current focus is on the development of flexible endoscopy platforms that incorporate robotic technology. An alternative approach to access the abdominal viscera for either a laparoscopic or NOTES procedure is the use of small robotic devices that can be implanted in an intracorporeal manner. Multiple, independent, miniature robots can be simultaneously inserted into the abdominal cavity to provide a robotic platform for NOTES surgery. The capabilities of the robots include imaging, retraction, tissue and organ manipulation, and precise maneuverability in the abdominal cavity. Such a platform affords several advantages including enhanced visualization, better surgical dexterity and improved triangulation for NOTES. This review discusses the current status and future perspectives of this novel miniature robotics platform for the NOTES approach. Although these technologies are still in pre-clinical development, a miniature robotics platform provides a unique method for addressing the limitations of minimally invasive surgery, and NOTES in particular.

10.
Int J Med Robot ; 6(3): 324-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20812272

RESUMO

BACKGROUND: Controlling surgical task speed and maintaining accuracy are vital components of robotic surgical skills. This study was designed to investigate the relationship between accuracy and speed for robot-assisted surgical skills. METHODS: Ten participants were asked to alternately touch two circular targets with various dimensions and distances between two targets, using the da Vinci Surgical System. The design of this study was based on Fitt's law. Statistical correlations between the index of difficulty (ID) and the movement time (MT), as well as the ID and the smoothness of the movement, were analysed. RESULTS: A significant linear correlation between MT and ID was shown. Speed was reduced to maintain accuracy as the level of task difficulty increased. There was no significant correlation between the smoothness of the movement and ID. CONCLUSIONS: The trade-off between speed and accuracy plays an important role in robot-assisted surgical proficiency.


Assuntos
Robótica/instrumentação , Robótica/normas , Procedimentos Cirúrgicos Operatórios/normas , Fenômenos Biomecânicos , Educação Médica , Educação de Pós-Graduação em Medicina , Humanos , Atividade Motora , Análise e Desempenho de Tarefas , Fatores de Tempo , Resultado do Tratamento
11.
Mol Cell Biochem ; 297(1-2): 1-8, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17003950

RESUMO

Despite the recognized role of bradykinin (BK)-induced calcium and chloride conductance in regulating salt transport in the kidney, the signaling pathway involved has not been well examined. Patch clamp of murine proximal tubule (TKPTS) cells revealed that BK (10 nM) produced an increase in an outwardly rectifying current from a basal level of 2.9 +/- 0.6 to 13.8 +/- 1.1 pA/pF following addition of BK (n = 8; p < 0.001). The shift in reversal potential seen with BK on changing the intracellular solution to 152 mM chloride and significant inhibition of the current by 100 microM 4,4'-di-isothiocyanato-stilbene-2,2'-disulphonic acid (DIDS) suggested that BK activated a chloride current. BK-induced current was blocked by B2 receptor antagonist but not by B1 antagonist or pertussis toxin indicating that the current was mediated by B2 receptors possibly through Gq activation. TMB-8 completely blocked the BK-calcium rise in fura-2 studies but did not block the BK-chloride response indicating that BK-mediated chloride current is calcium-independent. BK-induced current was dependent on phospholipase C (PLC) since U73122, a PLC-beta blocker (10 microM) blocked it completely. Furthermore, chloride conductance was not modulated by bisindolylmaleimide, an inhibitor of protein kinase C (PKC), but was enhanced by dibutyryl cAMP. We conclude that BK-induced rise in chloride current is mediated by B2 receptors and dependent on PLC activation but not dependent on calcium rise. Furthermore, the current can be modulated by cAMP but not PKC.


Assuntos
Bradicinina/farmacologia , Cloretos/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Animais , Cálcio/metabolismo , Células Cultivadas , Canais de Cloreto/metabolismo , Condutividade Elétrica , Ativação Enzimática/efeitos dos fármacos , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Túbulos Renais Proximais/citologia , Camundongos , Técnicas de Patch-Clamp , Receptor B2 da Bradicinina/metabolismo , Fosfolipases Tipo C/metabolismo
12.
Am J Physiol Renal Physiol ; 292(1): F261-8, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16926442

RESUMO

The mortality rate for septic patients with acute renal failure is extremely high. Since sepsis is often caused by lipopolysaccharide (LPS), a model of LPS challenge was used to study the development of kidney injury. Intravital video microscopy was utilized to investigate renal peritubular capillary blood flow in anesthetized male C57BL/6 mice at 0, 2, 6, 10, 18, 24, 36, and 48 h after LPS administration (10 mg/kg ip). As early as 2 h, capillary perfusion was dramatically compromised. Vessels with continuous flow were decreased from 89 +/- 4% in saline controls to 57 +/- 5% in LPS-treated mice (P < 0.01), and vessels with intermittent flow were increased from 6 +/- 2% to 31 +/- 5% (P < 0.01). At 2 h, mRNA for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were elevated 50- and 27-fold, respectively, suggesting that vascular inflammation is an early event that may contribute to capillary dysfunction. By 10 h, vessels with no flow increased from 5 +/- 2% in saline controls to 19 +/- 3% in LPS-treated mice (P < 0.05). By 48 h, capillary function was returning toward control levels. The decline in functional capillaries preceded the development of renal failure and was paralleled by induction of inducible nitric oxide synthase in the kidney. Using NAD(P)H autofluorescence as an indicator of cellular redox stress, we found that tubular cell stress was highly correlated with the percentage of dysfunctional capillaries (r(2) = 0.8951, P < 0.0001). These data show that peritubular capillary dysfunction is an early event that contributes to tubular stress and renal injury.


Assuntos
Células Epiteliais/fisiologia , Nefropatias/fisiopatologia , Túbulos Renais/fisiopatologia , Lipopolissacarídeos/toxicidade , Animais , Nitrogênio da Ureia Sanguínea , Western Blotting , Capilares/fisiologia , Creatinina/metabolismo , Células Epiteliais/efeitos dos fármacos , Imuno-Histoquímica , Nefropatias/induzido quimicamente , Túbulos Renais/citologia , Túbulos Renais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Vídeo , NADP/metabolismo , Nitratos/sangue , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Nitritos/sangue , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/fisiopatologia , Estresse Fisiológico/fisiopatologia
13.
J Pharmacol Exp Ther ; 313(2): 798-805, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15665141

RESUMO

Despite the recognized physiological role of bradykinin (BK) in the kidney in maintaining glomerular and tubule function and its role in pathological states such as endotoxemia, diabetes, and other diseases, relatively little is known about the mechanisms by which BK can impact kidney function. Furthermore, the signaling of BK receptors in the murine nephron has not been fully characterized. The present studies were undertaken to examine BK-stimulated Ca(2+) signaling using Fura-2 in the murine proximal tubule epithelial cell line TKPTS. BK produced a concentration-dependent rise in intracellular Ca(2+) ([Ca(2+)])(i) (pEC(50) = 8.39 +/- 0.04). Selective antagonists showed the rise in [Ca(2+)](i) was mediated through B2 receptors. The rise in [Ca(2+)](i) was rapid and reversible and was maximally stimulated at 1 microM (697 +/- 70 nM above basal level of 115 +/- 6 nM). Studies with thapsigargin and EGTA showed Ca(2+) mobilization was dependent on two events: release and influx. Both U73122 (1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) [a phospholipase C (PLC) inhibitor] and genistein (a tyrosine kinase inhibitor) partially inhibited BK-stimulated rise in [Ca(2+)](i). When combined, both agents produced a further decrease, suggesting multiple pathways for PLC activation may be involved. The ability of Ni(2+) to inhibit influx indicated the activation of a Ca(2+) release-activated channel (CRAC). Ca(2+) mobilization did not seem to be affected by cyclic nucleotides or protein kinase C. In summary, the TKPTS murine proximal tubule cell line expresses functional B2 receptors linked to Ca(2+) mobilization that is dependent on phospholipase C and activation of CRAC.


Assuntos
Bradicinina/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Linhagem Celular , Relação Dose-Resposta a Droga , Células Epiteliais/fisiologia , Túbulos Renais Proximais/fisiologia , Camundongos
14.
Am J Physiol Renal Physiol ; 289(6): F1324-32, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15998845

RESUMO

Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS (Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a significant decrease in peritubular capillary perfusion. Vessels with no flow increased from 7 +/- 3% in the saline group to 30 +/- 4% in the LPS group (P < 0.01). Both the inducible NO synthase inhibitor L-N(6)-1-iminoethyl-lysine (L-NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion deficits. Renal failure was also associated with an increase in renal caspase-3 activity and an increase in renal apoptosis. Both L-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by L-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.


Assuntos
Injúria Renal Aguda/fisiopatologia , Caspases/fisiologia , Óxido Nítrico/fisiologia , Circulação Renal/fisiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Inibidores de Caspase , Modelos Animais de Doenças , Ativação Enzimática , Interferon gama/sangue , Córtex Renal/irrigação sanguínea , Córtex Renal/patologia , Lipopolissacarídeos , Lisina/análogos & derivados , Lisina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Fator de Necrose Tumoral alfa/análise
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