INSULIN REGULATES CYTOKINES AND INTERCELLULAR ADHESION MOLECULE-1 GENE EXPRESSION THROUGH NUCLEAR FACTOR-kappa B ACTIVATION IN LPS-INDUCED ACUTE LUNG INJURY IN RATS

Diabetic patients have increased susceptibility to infection, which may be related to impaired inflammatory response observed in experimental models of diabetes, and restored by insulin treatment. The goal of this study was to investigate whether insulin regulates transcription of cytokines and intercellular adhesion molecule 1 (ICAM-1) via nuclear factor-kappa B (NF-kappa B) signaling pathway in Escherichia coli LIPS-induced lung inflammation. Diabetic male Wistar rats (alloxan, 42 mg/kg, iv., 10 days) and controls were instilled intratracheally with saline containing LPS (750 mu g/0.4 mL) or saline only. Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU, s.c.) 2 h before LIPS. Analyses performed 6 h after LPS included: (a) lung and mesenteric lymph node IL-1 beta, TNF-alpha, IL-10, and ICAM-1 messenger RNA (mRNA) were quantified by real-time reverse transcriptase-polymerase chain reaction; (b) number of neutrophils in the bronchoalveolar lavage (BAL) fluid, and concentrations of IL-1 beta, TNF-alpha, and IL-10 in the BAL were determined by the enzyme-linked immunosorbent assay; and (c) activation of NF-kappa B p65 subunit and phosphorylation of I-kappa B alpha were quantified by Western blot analysis. Relative to controls, diabetic rats exhibited a reduction in lung and mesenteric lymph node IL-1 beta (40%), TNF-alpha (similar to 30%), and IL-10 (similar to 40%) mRNA levels and reduced concentrations of IL-1 beta (52%), TNF-alpha (62%), IL-10 (43%), and neutrophil counts (72%) in the BAL. Activation of NF-kappa B p65 subunit and phosphorylation of I-kappa B alpha were almost suppressed in diabetic rats. Treatment of diabetic rats with insulin completely restored mRNA and protein levels of these cytokines and potentiated lung ICAM-1 mRNA levels (30%) and number of neutrophils (72%) in the BAL. Activation of NF-kappa B p65 subunit and phosphorylation of I-kappa B alpha were partially restored by insulin treatment. In conclusion, data presented suggest that insulin regulates transcription of proinflammatory (IL-1 beta, TNF-alpha) and anti-inflammatory (IL-10) cytokines, and expression of ICAM-1 via the NF-kappa B signaling pathway.

Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton and collagenase activity of human skin fibroblasts

The effects of verapamil modulating collagen biosynthesis have prompted us to study the role of this drug in cultured fibroblasts. In this article, we describe the effects of verapamil on fibroblast behaviour, with special emphasis to phenotypic modifications, reorganisation of actin filaments and secretion of MMP1. Human dermal fibroblasts treated with 50-mu M verapamil changed their normal spindle-shaped morphology to stellate. Treated cells showed discrete reorganisation of actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. We hypothesised that these effects would be associated to lower levels of cytosolic Ca(2+). Indeed, short time loading with calcium green confirmed that verapamil-treated fibroblasts exhibited lower intracellular calcium levels compared to controls. We also observed that verapamil increases the secretion of MMP1 in cultured fibroblasts, as demonstrated by zymography, specific substrate assays and immunoblot. The morphological alterations induced by verapamil are neither cytotoxic nor associated with other dramatic cytoskeleton alterations. Thus we may conclude that this drug enhances collagenase secretion and does not disrupt the major tracks necessary to deliver these enzymes in the extracellular space. The present results suggested that verapamil could be used at physiological levels to enhance collagen I breakdown, and maybe considered a potential candidate for intralesional therapy of wound healing and fibrocontractive diseases. (C) 2010 Elsevier Ltd and ISBI. All rights reserved.

SIGNALING PATHWAYS AND MEDIATORS IN LPS-INDUCED LUNG INFLAMMATION IN DIABETIC RATS: ROLE OF INSULIN

Diabetic patients are more susceptible to infections, and their inflammatory response is impaired. This is restored by insulin treatment. In the present study, we investigated the effect of insulin on LPS-induced signaling pathways and mediators in the lung of diabetic rats. Diabetic male Wistar rats (alloxan, 42 mg/kg i.v., 10 days) and control rats received intratracheal instillation of LPS (750 mu g/0.4 mL) or saline. Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU s.c.) 2 h before LPS. After 6 h, bronchoalveolar lavage was performed for the release of mediators, and lung tissue was homogenized for analysis of LPS-induced signaling pathways. Relative to control rats, diabetic rats exhibited a significant reduction in the LPS-induced phosphorylation of extracellular signal-regulated kinase (64%), p38 (70%), protein kinase B (67%), and protein kinase C alpha (57%) and delta (65%) and in the expression of iNOS (32%) and cyclooxygenase 2 (67%) in the lung homogenates. The bronchoalveolar lavage fluid concentrations of NO (47%) and IL-6 (49%) were also reduced in diabetic rats, whereas the cytokine-induced neutrophil chemoattractant 2 (CINC-2) levels were increased 23%, and CINC-1 was not different from control animals. Treatment of diabetic rats with insulin completely or partially restored all these parameters. In conclusion, data presented show that insulin regulates mitogen-activated protein kinase, phosphatidylinositol 3`-kinase, protein kinase C pathways, expression of the inducible enzymes, cyclooxygenase 2 and iNOS, and levels of IL-6 and CINC-2 in LPS-induced lung inflammation in diabetic rats. These results suggest that the protective effect of insulin in sepsis could be due to modulation of cellular signal transduction factors.

Evidensbaserad munvård för att förebygga ventilatorassocierad pneumoni hos ventilatorbehandlande patienter : en systematisk litteraturstudie

Utgångspunkten för denna litteraturstudie är att ventilatorassocierad pneumoni (VAP) går att förebygga. Syftet med detta arbete var att kartlägga olika evidensbaserade munvårdsmetoder som används av intensivvårdssjuksköterskor för att förebygga VAP hos ventilatorbehandlade patienter. Syftet var också att belysa vilka faktorer som påverkar intensivvårdssjuksköterskans utförande av evidensbaserad munvård till ventilatorbehandlade patienter. Studien utfördes som en systematisk litteraturstudie. Till resultatet användes 16 vetenskapliga artiklar. För att kunna bedöma artiklarnas vetenskapliga kvalitet granskades artiklarna utifrån en modifierad granskningsmall. Samtliga artiklar fick höga kvalitetspoäng, vilket innebär hög vetenskaplig relevans. Resultatet av litteraturstudien visar att i flera av de evidensbaserade munvårdsprotokoll som publicerats den senaste tiden finns några återkommande punkter. Dessa punkter är; bedömning av munhålans status, tandborstning med barntandborste, munsköljmedel och att munnen fuktas med ett intervall av två till sex timmar. Flera faktorer påverkar intensivvårdssjuksköterskans utförande av evidensbaserad munvård. Genom att införa ett evidensbaserat munvårdsprotokoll för ventilatorbehandlade intensivvårdspatienter och ge personalen utbildning i munvård kan incidensen av VAP minska. Resultatet visar också att generellt sett är kunskapsnivån låg hos intensivvårdssjuksköterskor gällande förebyggande åtgärder för att förhindra VAP. Om sjuksköterskan anser att hon/han har tid att utföra munvård blir resultatet av högre kvalitet och hon/han upplever också åtgärden som mindre obehaglig. Detta innebär att försök att förbättra omvårdnaden och därmed minska antalet vårdrelaterade infektioner även är en organisatorisk fråga.

Dagbok på IVA-patienters upplevelser : En litteraturöversikt

Bakgrund: Många patienter uttrycker ett behov av att fylla den minneslucka som finns sedan intensivvårdstiden både vad gäller tid och innehåll. Detta var anledningen till att vårdpersonal på intensivvårdsavdelningar började använda dagbok till kritiskt sjuka patienter. Syfte: Att belysa patienters upplevelser av att ta del av sin dagbok från vårdtiden på intensivvårdsavdelning. Metod: Litteraturöversikt. Artikelsökning utfördes i databaserna CINAHL och PubMed. I resultatet ingick tio vetenskapligt granskade artiklar, sju kvalitativa och tre kvantitativa. Resultat: Patienterna upplevde det som värdefullt att läsa dagboken och att titta på fotografierna eftersom det gav dem en uppfattning om vad som hade hänt och hur sjuka de hade varit. Genom dagboken fick patienterna en större sjukdomsinsikt och en mer realistisk målsättning för tillfrisknandet. Det var krävande och det väcktes starka känslor och reaktioner hos patienterna när de läste i dagboken. Dagboken fungerade som ett stöd för lång tid framöver. Patienterna uppskattade detaljerad och kontinuerligt skriven information och att dagboken var skriven med en personlig och mänsklig ton samt med ett språk som var lätt att förstå. Fotografier upplevdes av de flesta patienterna som positivt och blev ett bevis på vad de gått igenom. Det uppföljande återbesöket på IVA mottagning beskrevs av patienterna som betydelsefullt för att öka förståelsen av innehållet i dagboken och av vad som hänt under vårdtiden på IVA. Slutsats/Konklusion: Tidigare kritiskt sjuka patienter upplever, genom att ta del av dagbok från vårdtiden på intensivvårdsavdelning, större förståelse och bearbetning av sin sjukdomsperiod, vilket skulle kunna medföra förbättrad hälsa och ökad livskvalitet.

Cardiovascular effects of desflurane following acute hemorrhage in dogs

Objective: To determine the cardiovascular effects of desflurane in dogs following acute hemorrhage.Design: Experimental study.Animals: Eight mix breed dogs.Interventions: Hemorrhage was induced by withdrawal of blood until mean arterial pressure (MAP) dropped to 60 mmHg in conscious dogs. Blood pressure was maintained at 60 mmHg for 1 hour by further removal or replacement of blood. Desflurane was delivered by facemask until endotracheal intubation could be performed and a desflurane expiratory end-tidal concentration of 10.5 V% was maintained.Measurements and main results: Systolic, diastolic, and mean arterial blood pressure (SAP, DAP and MAP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), cardiac index (0), systemic vascular resistance (SVR), heart rate (HR), respiratory rate (RR), partial pressure of carbon dioxide in arterial blood (PaCO2), and arterial pH were recorded before and 60 minutes after hemorrhage, and 5, 15, 30, 45 and 60 minutes after intubation. Sixty minutes after hemorrhage, SAP, DAP, MAP, CVP, CO, Cl, SV, PaCO2, and arterial pH decreased, and HR and RR increased when compared with baselines values. Immediately after intubation, MAP and arterial pH decreased, and PaCO2 increased. Fifteen minutes after intubation SAP, DAP, MAP, arterial pH, and SVR decreased. At 30 and 45 minutes, MAP and DAP remained decreased and PaCO2 increased, compared with values measured after hemorrhage. Arterial pH increased after 30 minutes of desflurane administration compared with values measured 5 minutes after intubation.Conclusions: Desflurane induced significant changes in blood pressure and arterial pH when administered to dogs following acute hemorrhage.

Continuous infusion of ketamine in hypovolemic dogs anesthetized with desflurane

Objective: To evaluate the cardiorespiratory effects of continuous infusion of ketamine in hypovolemic dogs anesthetized with desflurane.Design: A prospective experimental study.Animals: Twelve mixed breed dogs allocated into 2 groups: saline (n=6) and ketamine (n=6).Interventions: After obtaining baseline measurements (time [T] 0) in awake dogs, hypovolemia was induced by the removal of 40 mL of blood/kg over 30 minutes. Anesthesia was induced and maintained with desflurane (1.5 minimal alveolar concentration) and 30 minutes later (T75) a continuous intravenous (IV) infusion of saline or ketamine (100 mu g/kg/min) was initiated. Cardiorespiratory evaluations were obtained 15 minutes after hemorrhage (T45), 30 minutes after desflurane anesthesia, and immediately before initiating the infusion (T75), and 5 (T80), 15 (T90), 30 (T105) and 45 (T120) minutes after beginning the infusion.Measurements and main results: Hypovolemia (T45) reduced the arterial blood pressures (systolic arterial pressure, diastolic arterial pressure [DAP] and mean arterial pressure [MAP]), cardiac (CI) and systolic (SI) indexes, and mean pulmonary arterial pressure (PAP) in both groups. After 30 minutes of desflurane anesthesia (T75), an additional decrease of MAP in both groups was observed, heart rate was higher than T0 at T75, T80, T90 and T105 in saline-treated dogs only, and the CI was higher in the ketamine group than in the saline group at T75. Five minutes after starting the infusion (T80), respiratory rate (RR) was lower and the end-tidal CO(2) (ETCO(2)) was higher compared with values at T45 in ketamine-treated dogs. Mean values of ETCO(2) were higher in ketamine than in saline dogs between T75 and T120. The systemic vascular resistance index (SVRI) was decreased between T80 and T120 in ketamine when compared with T45.Conclusions: Continuous IV infusion of ketamine in hypovolemic dogs anesthetized with desflurane induced an increase in ETCO(2), but other cardiorespiratory alterations did not differ from those observed when the same concentration of desflurane was used as the sole anesthetic agent. However, this study did not evaluate the effectiveness of ketamine infusion in reducing desflurane dose requirements in hypovolemic dogs or the cardiorespiratory effects of ketamine-desflurane balanced anesthesia.

Effects of nutritional support on hospital outcome in dogs and cats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Alternative Intrabladder Manometry Technique for the Indirect Measurement of Intra-abdominal Pressure in Horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vivências de familiares do paciente internado em unidade de terapia intensiva: estudo fenomenológico

This study originated from my concerns as critical care nurse, regarding the lived experience of the family member of the patient that is hospitalized in the intensive care unit - ICU. The purpose of the study was to comprehend the experience of the family members while having a loved one interned in an ICU, and to identify the common elements of the phenomenon, based on the descriptions of their experiences. Considering that the object of study involves subjective and social questions, the study was conducted using some fundamental ideas of descriptive phenomenology as a referential and the situated phenomenon as suggested by Martins and Bicudo (1989). Ten (10) family members of patients that were interned in the ICU of private hospital in Natal, RN were interviewed using the following leading question: What is it like to have a member of your family interned in the ICU? Five thematic structural categories emerged from the comprehensive analysis of the interviews: Fear of the family member s death; Lack of humanization; Social isolation; Confidence in the ICU; and Overload to the personal life. The description of the phenomenon enabled a new look at how the care team relates to the family members of the patients interned in the ICU, providing some guidance on how to construct a humanized care that involves the family and that is based on affective human relations. This involves a rethinking of the care provided by team to the family and stimulates the reformulation of personal and social attitudes, and of hospital organizational norms

Positive end-expiratory pressure in acute respiratory distress syndrome: should the 'open lung strategy' be replaced by a 'protective lung strategy'?

In patients with acute respiratory distress syndrome, positive end-expiratory pressure is associated with alveolar recruitment and lung hyperinflation despite the administration of a low tidal volume. The best positive end-expiratory pressure should correspond to the best compromise between recruitment and distension, a condition that coincides with the best respiratory elastance.

Lung ultrasound in acute respiratory distress syndrome and acute lung injury

Purpose of reviewLung ultrasound at the bedside can provide accurate information on lung status in critically ill patients with acute respiratory distress syndrome.Recent findingsLung ultrasound can replace bedside chest radiography and lung computed tomography for assessment of pleural effusion, pneumothorax, alveolar- interstitial syndrome, lung consolidation, pulmonary abscess and lung recruitment/de-recruitment. It can also accurately determine the type of lung morphology at the bedside (focal or diffuse aeration loss), and therefore it is useful for optimizing positive end-expiratory pressure. The learning curve is brief, so most intensive care physicians will be able to use it after a few weeks of training.SummaryLung ultrasound is noninvasive, easily repeatable and allows assessment of changes in lung aeration induced by the various therapies. It is among the most promising bedside techniques for monitoring patients with acute respiratory distress syndrome.

Multiplane ultrasound approach to quantify pleural effusion at the bedside

To assess the accuracy of a multiplane ultrasound approach to measure pleural effusion volume (PEV), considering pleural effusion (PE) extension along the cephalocaudal axis and PE area.Prospective study performed on 58 critically ill patients with 102 PEs. Thoracic drainage was performed in 46 patients (59 PEs) and lung computed tomography (CT) in 24 patients (43 PEs). PE was assessed using bedside lung ultrasound. Adjacent paravertebral intercostal spaces were examined, and ultrasound PEV was calculated by multiplying the paravertebral PE length by its area, measured at half the distance between the apical and caudal limits of the PE.Ultrasound PEV was compared to either the volume of the drained PE (59 PE) or PEV assessed on lung CT (43 PE). In patients with lung CT, the accuracy of this new method was compared to the accuracy of previous methods proposed for PEV measurement. Ultrasound PEV was tightly correlated with drained PEV (r = 0.84, p < 0.001) and with CT PEV (r = 0.90, p < 0.001). The mean biases between ultrasound and actual volumes of PE were -33 ml when compared to drainage (limits of agreement -292 to +227 ml) and -53 ml when compared to CT (limits of agreement -303 to +198 ml). This new method was more accurate than previous methods to measure PEV.Using a multiplane approach increases the accuracy of lung ultrasound to measure the volume of large to small pleural effusions in critically ill patients.

Fatores de risco para mortalidade na lesão renal aguda

OBJETIVO: Este trabalho tem como objetivo avaliar a evolução de pacientes com lesão renal aguda (LRA) por Necrose Tubular Aguda internados no Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. MÉTODOS: Trata-se de estudo de coorte retrospectivo, no qual foram avaliados 477 pacientes maiores de 18 anos, no período de janeiro de 2001 a dezembro de 2008. LRA foi definida de acordo com os valores de creatinina sérica, conforme proposto pelo Acute Kidney Injury Network (AKIN). RESULTADOS: A média de idade da população estudada foi de 65,5 ± 16,2 anos, com predomínio de homens (62%) e com idade > 60 anos (65,2%). Diabetes mellitus ocorreu em 61,9%, hipertensão arterial em 44,4% e doença renal crônica em 21,9%. A mortalidade foi de 66%. Após análise multivariada, foram variáveis associadas ao óbito a necessidade de diálise, internação em UTI, idade > 60 anos e menor tempo de acompanhamento nefrológico. A recuperação renal entre os sobreviventes foi de 96,9%. CONCLUSÃO: Este trabalho mostra que a evolução dos pacientes com LRA provenientes de enfermarias clínica e cirúrgica é semelhante à literatura. Porém, a alta mortalidade do grupo mostra a necessidade da identificação de fatores de risco para o desenvolvimento de LRA nesses pacientes e capacitação da equipe assistente para o diagnóstico precoce dessa síndrome.