Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis

Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice, obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice exclusion from gut exacerbates Akt/nuclear factor-kB (NF-kB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n=7/group). Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-kB (I-kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IkB, and NF-kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic juice replacement (ANOVA, P<0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis. Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster).     

Donor‐specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients

Cell therapy with autologous donor‐specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor‐specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR‐Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor‐specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts. Tregs expressing an irrelevant or anti‐HLA‐A2‐specific CAR were administered to Bl/6 mice at the time of transplanting an HLA‐A2⁺ Bl/6 skin graft. Donor‐specific CAR‐Tregs, but not irrelevant‐CAR Tregs, significantly delayed skin rejection and diminished donor‐specific antibodies (DSAs) and frequencies of DSA‐secreting B cells. Donor‐specific CAR‐Treg–treated mice also had a weaker recall DSA response, but normal responses to an irrelevant antigen, demonstrating antigen‐specific suppression. When donor‐specific CAR Tregs were tested in HLA‐A2‐sensitized mice, they were unable to delay allograft rejection or diminish DSAs. The finding that donor‐specific CAR‐Tregs restrain de novo but not memory alloreactivity has important implications for their use as an adoptive cell therapy in transplantation.     

The value of parental report for diagnosis and management of dehydration in the emergency department

STUDY OBJECTIVES: We define the predictive value of parents' computer-based report for history and physical signs of dehydration for a primary outcome of percentage of dehydration (fluid deficit) and 2 secondary outcomes: clinically important acidosis and hospital admission. We also sought to compare the reports of physical signs related to dehydration made by parents and nurses. METHODS: We performed a prospective observational trial in an urban pediatric emergency department. A convenience sample of parents completed a computer-based interview covering historical details and physical signs (ill appearance, sunken fontanelle, sunken eyes, decreased tears, dry mouth, cool extremities, and weak cry) related to dehydration. Nurses independently completed an assessment of physical signs for enrolled children. The primary outcome was the degree of dehydration (fluid deficit), which was defined as the percentage difference between initial ED weight and stable final weight after the illness. Secondary outcomes included clinically important acidosis (defined as a serum CO(2) value of 相似文献   

Peritoneal and intestinal tuberculosis: an ancestral disease that poses new challenges in the technological era. Case report and review of the literature

Tuberculosis is a public health problem. The most common presentation is pulmonary disease. The diagnosis of any extrapulmonary forms are quite difficult. Clinical manifestations of gastrointestinal tuberculosis are non-specific and compatible with pathologies such as inflammatory bowel disease, advanced ovarian cancer, deep mycosis, yersinia infection and amebomas. Abdominal form is located at 6th place of the extrapulmonary forms, after lymphatic, genitourinary, osteoarticular, miliary and meningeal infections. Eventually, 25 to 75% of patients with abdominal tuberculosis will require surgery. These procedures should be limitated with the purpose to preserve small bowel. Resection should be limitated for complicated cases. The surgical indications include: Intestinal occlusion (15-60%), perforation (1-15%), abscesses and fistulas (2-30%) and hemorrhage (2%). CONCLUSIONS: In most of the cases, the diagnosis of peritoneal or intestinal tuberculosis is made during a laparoscopy or laparotomy even during surgery performed by different purposes. Excessive manipulation of the intraabdominal organs may produced unexpected bowel lesions, increasing morbidity and mortality. Medical treatment is highly effective in the resolution of moderate complications such as bowel obstruction. Resectional procedures should be reserved for complications like perforation, bleeding or stenosis non-suitable for stricturoplasty.     

Successful delivery following myocardial ischemia during the second trimester of pregnancy

Acute myocardial infarction during pregnancy is considered to be associated with approximately 50% mortality of both mother and fetus. However, there are not enough data regarding the role of acute myocardial ischemia. We present a 36-year-old, pregnant, white female who was admitted twice at 18 and 20 weeks of gestation with acute myocardial ischemia. Cardiac catheterization revealed 70–80% stenosis of the mid left anterior descending artery (LAD) with normal antegrade flow and very good retrograde filling of the LAD from distal collaterals of the right coronary artery. Therefore, due to angiographic suggestion of protected LAD territory, we recommended medical therapy and scheduled a vaginal delivery that was successfully completed without cardiovascular complications. A stress thallium test performed 6 months later was normal, supporting our clinical judgment. In conclusion, every case of a pregnant woman with coronary insufficiency should be treated according to individual coronary anatomy and blood supply to the territory of the diseased artery, and should not be based on the old data in the literature. The decision for revascularization prior to delivery versus medical therapy, or Caesarean section versus natural delivery, should be made by a team of a cardiologist and an obstetrician.