Cross-Talk Between Sirtuin 1 and High-Mobility Box 1 in Steatotic Liver Graft Preservation.

BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +-dependent histone deacetylase that regulates various pathways involved in ischemia-reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has also been involved in inflammatory processes during IRI. However, the roles of both SIRT1 and HMGB1 in liver preservation is poorly understood. In this communication, we evaluated the potential relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez solution (IGL-1) preservation solution enriched or not enriched with trimetazidine (TMZ). METHODS: Steatotic and non-steatotic livers were preserved in IGL-1 preservation solution (24 hours, 4°C), enriched or not enriched with TMZ (10 µmol/L), and then submitted to ex vivo reperfusion (2 hours; 37°C). Liver injury (AST/ALT) and function (bile output, vascular resistance) were evaluated. SIRT1, HMGB1, autophagy parameters (beclin-1, LC3B), PPAR-γ, and heat-shock protein (HO-1, HSP70) expression were determined by means of Western blot. Also, we assessed oxidative stress, mitochondrial damage (glutamate dehydrogenase), and TNF-α levels. RESULTS: Elevated SIRT1 and enhanced autophagy were found after reperfusion in steatotic livers preserved in IGL-1+TMZ when compared with IGL-1. However, these changes were not seen in the case of non-steatotic livers. Also, HO-1 increases in the IGL-1 + TMZ group were evident only in the case of steatotic livers, whereas HSP70 and PPAR-γ protein expression were enhanced only in non-steatotic livers. All reported changes were consistent with decreased liver injury diminution, ameliorated hepatic function, and decreased TNF-α and HMGB levels. In addition, the oxidative stress and mitochondrial damage were efficiently prevented by the IGL-1 + TMZ use. CONCLUSIONS: SIRT1 is associated with HMGB1 decreases and increased autophagy in steatotic livers, contributing to increased tolerance to cold IRI.

Sweet's syndrome with pulmonary involvement: Case report and literature review.

A 74 year old female presented with fever, associated with papules and plaque in her upper and lower extremities. Exams revealed blood leukocytosis and a positive urine culture. Antibiotic therapy was initiated with no clinical response. After 1 week, chest X-ray showed right upper lobe alveolar infiltrate. A skin biopsy of the lesion showed infiltration by neutrophils, consistent with Sweet's Syndrome. Patient's condition progressively worsened, requiring oxygentherapy. Bronchoscopy and bronchoalveolar lavage were normal, transbronchial biopsies suggested lung involvement of Sweet 's syndrome. Antibiotic therapy was stopped. Corticosteroid were started. Therapy resulted in rapid clinical and radiological improvement.

Dexmedetomidine as sole sedative during percutaneous carotid artery stenting in a patient with severe chronic obstructive pulmonary disease.

Carotid artery ballooning and stenting is a percutaneous interventional therapy for the treatment of patients with atherosclerotic occlusive disease of the carotid artery. Patients with severe comorbidities are usually considered candidates for this procedure. The carotid artery stenting can be done under either general or strict local anesthesia, or alternatively by using a combination of intravenous sedation and local anesthesia. Dexmedetomidine is a selective alpha-adrenergic agent that has both sedative and analgesic properties but lacks a depressive effect on respiratory drive. This article describes the case of a patient with severe chronic obstructive pulmonary disease and severe carotid stenosis, who underwent carotid stenting under monitored anesthesia care with dexmedetomidine. Only one episode of bradycardia and hypotension was observed, and this was successfully treated with glycopyrrolate.

Comparison of bronchoscopic bronchoalveolar lavage vs blind lavage with a modified nasogastric tube in the etiologic diagnosis of ventilator-associated pneumonia.

OBJECTIVE: Our objective was to compare the results of a blind lavage vs a bronchoscopic-guided bronchoalveolar lavage for the etiologic diagnosis of ventilator-associated pneumonia (VAP). DESIGN: Prospective study in consecutive patients with high probability of VAP. Every patient underwent both procedures, in a formally randomized fashion. The interpretation of quantitative cultures was done in a blind fashion. SETTING: Single center study, with a 20 bed medical and surgical Intensive Care Unit of the University Hospital in Monterrey, Mexico. PATIENTS: Twenty-five patients with high probability of VAP. INTERVENTIONS: Every patient underwent blind bronchoalveolar lavage with a modified nasogastric tube, and a bronchoscopic-guided bronchoalveolar lavage. RESULTS: Twenty-one patients underwent both procedures. Four patients were excluded due to contamination of the cultures. The quantitative cultures were compared in a paired fashion. Only two patients had discordant cultures. The correlation coefficient between the number of colonies was very high, r=0.90 (95% confidence interval [CI], 0.77-0.96; p=0.0001). CONCLUSIONS: The blind bronchoalveolar lavage with a modified nasogastric tube is a valuable tool for the identification of etiologic agent in VAP, particularly when trained bronchoscopists or the necessary resources for bronchoscopic-guided bronchoalveolar lavage are not readily available.

Comparison of bronchoscopic bronchoalveolar lavage vs blind lavage with a modified nasogastric tube in the etiologic diagnosis of ventilator-associated pneumonia / Comparison of bronchoscopic bronchoalveolar lavage vs blind lavage with a modified nasogastric tube in the etiologic diagnosis of ventilator-associated pneumonia

Objective. Our objective was to compare the results of a blind lavage vs a bronchoscopic-guided bronchoalveolar lavage for the etiologic diagnosis of ventilator-associated pneumonia (VAP). Design. Prospective study in consecutive patients with high probability of VAP. Every patient underwent both procedures, in a formally randomized fashion. The interpretation of quantitative cultures was done in a blind fashion. Setting. Single center study, with a 20 bed medical and surgical Intensive Care Unit of the University Hospital in Monterrey, Mexico. Patients. Twenty-five patients with high probability of VAP. Interventions. Every patient underwent blind bronchoalveolar lavage with a modified nasogastric tube, and a bronchospic-guided bronchoalveolar lavage. Results. Twenty-one patients underwent both procedures. Four patients were excluded due to contamination of the cultures. The quantitative cultures were compared in a paired fashion. Only two patients had discordant cultures. The correlation coefficient between the number of colonies was very high, r = 0.90 (95% confidence interval [CI], 0.77-0.96; p = 0.0001). Conclusions. The blind bronchoalveolar lavage with a modified nasogastric tube is a valuable tool for the identification of etiologic agent in VAP, particularly when trained bronchoscopists or the necessary resources for bronchoscopic-guided bronchoalveolar lavage are not readily available

Objetivo. Nuestro objetivo fue el de comparar los resultados de un lavado ciego frente a un lavado broncoalveolar guiado con broncoscopio para el diagnóstico etiológico de neumonía asociada a ventilador (NAV). Diseño. Estudio prospectivo en pacientes consecutivos con alta probabilidad de NAV. En todos los pacientes se llevaron a cabo ambos procedimientos de manera aleatorizada. La interpretación de los cultivos cuantitativos fue hecha a ciegas. Ámbito. Estudio en un único centro, en una Unidad de Cuidados Intensivos Quirúrgicos con 20 camas del Hospital Universitario de Monterrey, en México. Pacientes. Veinticinco pacientes con alta probabilidad de NAV. Intervenciones. A cada paciente se le realizó un lavado broncoalveolar ciego con una sonda nasogástrica modificada y un lavado broncoalveolar guiado con broncoscopio. Resultados. Se realizaron ambos procedimientos en 21 pacientes. Cuatro fueron excluidos debido a contaminación de los cultivos. Los cultivos cuantitativos fueron comparados en pares. Solo dos pacientes tenían cultivos discordantes. El coeficiente de correlación entre el número de colonias fue muy alto, r = 0,90 (intervalo de confianza [IC] del 95% 0,77-0,96; p = 0,0001). Conclusiones. El lavado broncoalveolar ciego con sonda nasogástrica modificada es una herramienta de mucho valor para la identificación del agente etiológico en NAV, especialmente cuando un broncoscopista experto o los recursos necesarios para lavado broncoalveolar guiado con broncoscopio no están fácilmente disponibles

Soluble receptors released during acute pancreatitis interfere with the detection of tumor necrosis factor-alpha.

OBJECTIVE: To evaluate the interfering effect of tumor necrosis factor-alpha soluble receptor when measuring circulating concentrations of tumor necrosis factor-alpha in an experimental model of acute pancreatitis. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Saline was administered in a control group. Serums were overloaded with known amounts of tumor necrosis factor-alpha or macrophage inflammatory protein-2. MEASUREMENTS AND MAIN RESULTS: Three hours after induction, serum concentrations of free tumor necrosis factor-alpha, total tumor necrosis factor-alpha, and soluble receptor of tumor necrosis factor-alpha were measured. No detectable concentrations of free tumor necrosis factor-alpha were found in any experimental group. By contrast, significant increases in total tumor necrosis factor-alpha and soluble receptor of tumor necrosis factor-alpha were found after induction of pancreatitis. Overloading of serum with tumor necrosis factor-alpha resulted in detection of 50% of the expected concentrations of free tumor necrosis factor-alpha from control animals and only of 5% from the pancreatitis group. Overloading the serum with macrophage inflammatory protein-2 resulted in a detection of 100% of the expected concentrations in both control and treated animals. CONCLUSION: Circulating soluble receptor of tumor necrosis factor-alpha could interfere with the detection of tumor necrosis factor-alpha in some pathologies, such as pancreatitis, that are associated with increases in soluble receptor of tumor necrosis factor-alpha.

Absorption and effects of 3-(N-phenylamino)-1,2-propanediol esters in relation to toxic oil syndrome.

Toxic Oil Syndrome (TOS) was an epidemic disease related to the consumption of rapeseed oil denatured with aniline that made its sudden appearance in Spain in 1981. The fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP), which is a chemical class of by-products resulting from the reaction of aniline with oil components, have shown a strong association with TOS-related oils. These compounds also show some structural similarities to platelet-activating factor (PAF). In search of a toxic agent that could explain the widespread systemic effects observed in TOS patients, we investigated the intestinal absorption and biotransformation of the different PAP esters found in TOS-related oil samples and the possible pathophysiological effect of these mediators and their metabolic products if acting as PAF analogs. Results indicate that PAP esters are absorbed in the gastrointestinal tract and are distributed and stored in different organs, particularly in the liver and brown adipose tissue. PAP in these organs showed different patterns of fatty acids, indicating the ability of the gastrointestinal tract to modify the fatty acid composition of the parent PAP. Thus, the fatty acid profile of the PAP esters found in intestine appears to be related to the type of oil used as vehicle. Some of these PAP esters, when a long acyl chain was present in the sn-1 position of the molecule, showed an inhibitory effect on the PAF synthesis. This is an important observation in line with the systemic nature of the disease.

P-selectin expression and Kupffer cell activation in rat acute pancreatitis.

This work studied the activation of hepatic macrophages during acute pancreatitis and the involvement of these cells in the lung inflammatory response. Pancreatitis was induced in Wistar rats by intraductal administration of 5% sodium taurocholate. Three hours after pancreatitis induction, the degree of pulmonary inflammation, TNF-alpha levels, and P-selectin expression were evaluated. The generation of TNF-alpha by Kupffer cells was also measured. Pancreatitis increases the serum concentration of TNF-alpha, neutrophil infiltration, and P-selectin expression in pancreas and lung. In addition, Kupffer cells generate increased levels of TNF-alpha. When Kupffer cells were inhibited, the increase in serum TNF-alpha levels and the infiltration of neutrophils in the lung were prevented, but P-selectin expression remained unmodified. We conclude that pulmonary inflammation induced by acute pancreatitis is mediated by Kupffer cell activation and that pancreatitis induces the expression of P-selectin on pulmonary endothelial cells but this effect is not mediated by Kupffer cells.

Pancreatitis induces HSP72 in the lung: role of neutrophils and xanthine oxidase.

The aim of this work was to evaluate the systemic Hsp72 expression in rat lung and liver in vivo in a model of acute pancreatitis and investigate the possible involvement of xanthine oxidase and neutrophils in this process. Pancreatitis was induced by intraductal administration of 5% sodium taurocholate and samples of lung and liver were obtained 1 and 3 h later. In some groups of rats circulating xanthine oxidase was inhibited with oxypurinol, and neutrophil recruitment was blocked with a monoclonal antibody against P-selectin. Hsp72 expression was assessed by means of Western blot and immunohistochemistry. Results showed Hsp72 induction in lung, but not in liver, shortly after pancreatitis. Hsp72-induced expression was located in bronchial epithelium, alveolar macrophages, infiltrating neutrophils, and blood vessels. Oxypurinol and the antibody against P-selectin prevented pancreatitis-induced lung Hsp72 overexpression suggesting that Hsp72 induction is mediated by neutrophil infiltration into the lungs.

H(2)O(2) and PARS mediate lung P-selectin upregulation in acute pancreatitis.

P-selectin and circulating xanthine oxidase are involved in the process of neutrophil infiltration into the lung associated with acute pancreatitis. This study investigated the mediators that trigger the upregulation of P-selectin in this process. Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. P-selectin expression was measured using radiolabeled antibodies. Neutrophil infiltration and PAF levels were also evaluated. The role of superoxide radical, H(2)O(2), or the enzyme poly (ADP-ribose) synthetase (PARS) on these processes was determined in groups of animals treated with the corresponding inhibitors. Pancreatitis was associated with an increase in P-selectin expression in the lung. Inhibition of PARS or H(2)O(2) abrogated P-selectin upregulation, PAF generation, and neutrophil recruitment. Superoxide dismutation prevented neutrophil recruitment and PAF generation, but had no effect on P-selectin expression. We conclude that during acute pancreatitis, upregulation of P-selectin in the pulmonary endothelium is triggered by H(2)O(2) and PARS activity.

Effect of peritoneal lavage and lymph ligature on systemic complications of experimental acute pancreatitis.

We studied the involvement of ascitic fluid on the systemic effects of experimental acute pancreatitis. This has been achieved by comparing the effectiveness of either peritoneal lavage or lymphatic ligature on preventing changes in systemic vascular permeability. Three hours after induction of pancreatitis, we found increases in vascular permeability in the pancreas, lung, and intestine. Both peritoneal lavage and lymphatic ligature were able to prevent the changes observed in the lung and intestine and the increases on plasma levels of lipase and amylase, suggesting a similar involvement for lymphatic draining and peritoneal absorption pathways. In addition, we evaluated the effect of intraperitoneal deposition into health rats of pancreatitis-associated ascitic fluid collected from rats with experimental acute pancreatitis. A significant increase in plasma amylase and lipase levels could be observed but no changes in vascular permeability were found. Altogether, these results indicate that transperitoneal absorption of toxic mediators from the ascitic fluid is not enough to explain the systemic damage induced by acute pancreatitis.

Role of P-selectin and ICAM-1 in pancreatitis-induced lung inflammation in rats: significance of oxidative stress.

OBJECTIVE: To investigate the role of P-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of lung injury associated with pancreatitis, and the relation between xanthine oxidase-derived oxidants and expression of these adhesion molecules. SUMMARY BACKGROUND DATA: In acute pancreatitis, acute respiratory distress syndrome occurs in the early stages of disease. This process is mediated by neutrophil infiltration. METHODS: Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. ICAM-1 and P-selectin expression was measured using radiolabeled monoclonal antibodies. Neutrophil infiltration and plasma levels of xanthine oxidase were also evaluated. RESULTS: Pancreatitis induces increases in P-selectin expression in lung, whereas ICAM-1 is unchanged from baseline levels. Immunoneutralization of either P-selectin or ICAM-1 prevents the infiltration of neutrophils into the lung. Xanthine and xanthine oxidase activity were increased after induction of pancreatitis. Xanthine oxidase inhibition prevents the upregulation of P-selectin in lung and neutrophil infiltration. CONCLUSIONS: During acute pancreatitis, P-selectin is upregulated in the pulmonary endothelium and is a key determinant of leukocyte recruitment. Constitutive ICAM-1 is also involved in the process of cell infiltration into the lung. The increased expression of P-selectin appears to be triggered by a mechanism dependent on free radicals generated by xanthine oxidase released by the damaged pancreas.

Free radicals generated by xanthine oxidase mediate pancreatitis-associated organ failure.

In the present study we evaluate the possibility that xanthine oxidase released by damaged pancreas could act as a source of oxidative damage in systemic tissues during the early stages of acute pancreatitis. This was accomplished by evaluating the effects of xanthine oxidase inhibition with oxypurinol infused into the portal vein. Under these conditions, we inhibited the enzyme before it reached the liver and other distant organs, without inducing changes in the severity of pancreatic damage. Results indicate that pancreatitis parallels increases in xanthine oxidase activity in plasma. Superoxide radicals generated by this enzyme appears to be involved in the decrease of reduced glutathione levels in the plasma and liver. In addition, xanthine oxidase inhibition prevents the infiltration of neutrophils into the lungs. We conclude that oxygen free radicals generated by xanthine and xanthine oxidase released to the bloodstream are involved in the systemic organ failure associated with acute pancreatitis.

Leukotriene generation and neutrophil infiltration after experimental acute pancreatitis.

The role of 5-lipoxygenase metabolites of arachidonic acid in the inflammatory response associated with experimental acute pancreatitis has been evaluated. For this purpose, an experimental necrohemorrhagic pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. Neutrophil infiltration was detected in pancreas at 1 and 3 h after the induction of pancreatitis. This was concomitant with increased levels of leukotriene B4 and peptide leukotrienes (C4, D4 and E4). In lung, similar increases in neutrophil infiltration were detected but only 3 h after acute pancreatitis induction, and no changes in leukotriene B4 nor peptide leukotrienes were apparent at this time. These results suggest that after induction of acute pancreatitis, 5-lipoxygenase metabolites could play a role in the inflammatory response in the pancreas, but they are not involved in the inflammatory response in lung.

Comparison of cytospat and pipelle endometrial biopsy instruments.

OBJECTIVE: To compare two endometrial biopsy techniques, based on the quality of material obtained, cost effectiveness, and pain during the procedure. STUDY DESIGN: A single blind, randomized prospective study. RESULTS: A total of 365 women with peri/postmenopausal bleeding were randomized into two groups: 174 biopsied cytospat (C) and 191 biopsied with pipelle (P). Both procedures were then followed by either dilatation and curettage (D&C) or hysterectomy. Pain was evaluated in 379 patients, with the result being better tolerance for P vs. C (3.55 vs. 4.06, P = 0.07). With C, the sensitivity in histological evaluation was 82% for benign endometrium, 60% for endometrial hyperplasia and 60% for corpus uterine neoplasia as compared to the D&C and hysterectomy material. With P the sensitivity was 84, 71 and 60%, respectively for the three diagnoses, as compared to the D&C and hysterectomy material. Insufficient tissue for pathologic evaluation was present in 24% of C, 25% of P and 9.8% of D&C samples. CONCLUSIONS: Cost effectiveness for pipelle is slightly higher than for Cytospat.

[Maternity ward routines in Barcelona]. / Rutinas de las maternidades de Barcelona.

Twenty-one maternity wards in Barcelona were visited in order to evaluate the degree of compliance with the OMS/UNICEF guidelines for breast-feeding protection. Breast-feeding is initiated within the first hour after birth in only 2 of these hospitals. In only 5 cases is demand feeding encouraged. In only 6 of these maternity wards do the newborn babies remain with their mothers all day long and in only one are newborn babies not given water or dextrose. In only two hospitals is the pacifier discouraged. Furthermore, only two of the hospitals do not receive free formula supplies from the industry. Immediate changes are needed if the mother's right to breast-feed is to be protected.

[Solitary ulcer of the rectum. Apropos of a case in childhood and review of bibliography]. / Ulcera solitaria de recto. A propósito de un caso en edad pediátrica y revisión de la bibliografía.

A case of a chronically constipated 10 year-old-girl, who had severe rectal bleeding associated with her monthly bowel movement is presented. Barium enema revealed an irregular and rigid area in rectal and sigmoid wall. Endoscopy showed an irregular erosion of 4 by 2 cm, from which biopsies were taken. These were reported as compatible with solitary ulcer of rectum. Patient was treated with dietetic management and clinically and psychiatrically controlled. Two years after initial admission she had no clinical or endoscopic evidence of disease.