Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-alpha and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-alpha and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

International Consensus Guidelines for Nutrition Therapy in Pancreatitis

Guidelines for nutrition support in pancreatitis have been inconsistently adapted to clinical practice. The International Consensus Guideline Committee (ICGC) established a pancreatitis task force to review published guidelines for pancreatitis in nutrition support. A PubMed search using the terms pancreatitis, acute pancreatitis, chronic pancreatitis, nutrition support, parenteral nutrition, enteral nutrition, and guidelines was conducted for the period from January 1999 to May 2011. Eleven guidelines were identified for review. The ICGC used the following process to develop unified guideline statements: summarize the strength of evidence (grading) of the guidelines; establish level of evidence for ICGC statements as high, intermediate, and low; assign published guideline levels of evidence; and define an ICGC grading system. International Pancreatitis Guideline Grades were established as follows: platinum-high level of evidence and consistent agreement among the guidelines; gold-acceptable level of evidence and no conflicting statements in guidelines; and silver-single existing guideline statement with no conflict in other guidelines. Eighteen ICGC statements were derived from the 11 published pancreatitis guidelines. Uniform agreement from widely disparate groups (United States, Europe, Japan, and China) resulted in 4 platinum-level guideline statements for nutrition in pancreatitis: nutrition support therapy (NST) is generally not needed for mild to moderate disease, NST is needed for severe disease, enteral nutrition (EN) is preferred over parenteral nutrition (PN), and use PN when EN is contraindicated or not feasible. This methodology provides a template for future ICGC nutrition guideline development. (JPEN J Parenter Enteral Nutr. 2012;36:284-291)

Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis?

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-alpha, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-alpha and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

Vitamin E Alters Inflammatory Gene Expression in Alcoholic Chronic Pancreatitis

Objective: To evaluate the effect of vitamin E supplementation on pancreatic gene expression of inflammatory markers in rats with alcoholic chronic pancreatitis. Methods: Wistar rats were divided into 3 groups: control (1), alcoholic chronic pancreatitis without (2) and with (3) vitamin E supplementation. Pancreatitis was induced by a liquid diet containing ethanol, cyclosporin A and cerulein. a-tocopherol content in plasma and liver and pancreas histopathology were analyzed. Gene expression of inflammatory biomarkers was analyzed by the quantitative real-time PCR technique. Results: The animals that received vitamin E supplementation had higher alpha-tocopherol amounts in plasma and liver. The pancreas in Group 1 showed normal histology, whereas in Groups 2 and 3, mild to moderate tissue destruction foci and mononuclear cell infiltration were detected. Real-time PCR analysis showed an increased expression of all genes in Groups 2 and 3 compared to Group 1. Vitamin E supplementation decreased the transcript number of 5 genes (alpha-SMA, COX-2, IL-6, MIP-3 alpha and TNF-alpha) and increased the transcript number of 1 gene (Pap). Conclusion: Vitamin E supplementation had anti-inflammatory and beneficial effects on the pancreatic gene expression of some inflammatory biomarkers in rats with alcoholic chronic pancreatitis, confirming its participation in the inflammatory response mechanisms in the pancreas. Copyright (c) 2012 S. Karger AG, Basel

Beyond "Cirrhosis" A Proposal From the International Liver Pathology Study Group

Cirrhosis is a moiphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus document by the International Liver Pathology Study Group challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment.

Performance characteristics of Pap test, VIA, VILI, HR-HPV testing, cervicography, and colposcopy in diagnosis of significant cervical pathology

We sought to evaluate the performance of diagnostic tools to establish an affordable setting for early detection of cervical cancer in developing countries. We compared the performance of different screening tests and their feasibility in a cohort of over 12,000 women: conventional Pap smear, liquid-based cytology, visual inspection with acetic acid (VIA), visual inspection with Iodine solution (VILI), cervicography, screening colposcopy, and high-risk human papillomavirus (HPV) testing (HR-HPV) collected by physician and by self-sampling. HR-HPV assay collected by the physician has the highest sensitivity (80 %), but high unnecessary referrals to colposcopy (15.1 %). HR-HPV test in self-sampling had a markedly lower (57.1 %) sensitivity. VIA, VILI, and cervicography had a poor sensitivity (47.4, 55, and 28.6 %, respectively). Colposcopy presented with sensitivity of 100 % in detecting CIN2+, but the lowest specificity (66.9 %). Co-testing with VIA and VILI Pap test increased the sensitivity of stand-alone Pap test from 71.6 to 87.1 % and 71.6 to 95 %, respectively, but with high number of unnecessary colposcopies. Co-testing with HR-HPV importantly increased the sensitivity of Pap test (to 86 %), but with high number of unnecessary colposcopies (17.5 %). Molecular tests adjunct to Pap test seems a realistic option to improve the detection of high-grade lesions in population-based screening programs.

Distinct placental malaria pathology caused by different Plasmodium berghei lines that fail to induce cerebral malaria in the C57BL/6 mouse

Background: Placental malaria (PM) is one major feature of malaria during pregnancy. A murine model of experimental PM using BALB/c mice infected with Plasmodium berghei ANKA was recently established, but there is need for additional PM models with different parasite/host combinations that allow to interrogate the involvement of specific host genetic factors in the placental inflammatory response to Plasmodium infection. Methods: A mid-term infection protocol was used to test PM induction by three P. berghei parasite lines, derived from the K173, NK65 and ANKA strains of P. berghei that fail to induce experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. Parasitaemia course, pregnancy outcome and placenta pathology induced by the three parasite lines were compared. Results: The three P. berghei lines were able to evoke severe PM pathology and poor pregnancy outcome features. The results indicate that parasite components required to induce PM are distinct from ECM. Nevertheless, infection with parasites of the ANKA Delta pm4 line, which lack expression of plasmepsin 4, displayed milder disease phenotypes associated with a strong innate immune response as compared to infections with NK65 and K173 parasites. Conclusions: Infection of pregnant C57BL/6 females with K173, NK65 and ANKA Delta pm4 P. berghei parasites provide experimental systems to identify host molecular components involved in PM pathogenesis mechanisms.

Highly debilitating natural Trypanosoma vivax infections in Brazilian calves: epidemiology, pathology, and probable transplacental transmission

Clinical, epidemiological, and pathological aspects of trypanosomiasis caused by Trypanosoma vivax in calves were reported for the first time in northeast Brazil. Clinical and epidemiological data, packed cell volumes (PCV), and parasitemia were assessed in 150 calves in May 2009 (rainy season-survey 1) and in 153 calves in November 2009 (dry season-survey 2) in three farms (A, B, and C). Prevalence of T. vivax in calves examined in the survey 1 was 63.3%, 65.0%, and 80.0% in farms A, B, and C, respectively. Morbidity varied from 63.3% to 80%, mortality from 15% to 30% and lethality from 23% to 37.5%. In survey 1, for all farms, high parasitemia (from 30.3 to 26.2x10(6) parasites/mL), fever (from 39.8 to 40.3 degrees C), low PCV (from 15.7% to 18.1%), and body score (from 2.5 to 3.5) were detected. Calves showed depression, weight loss, pale mucous membranes, enlarged lymph nodes, edema of the dewlap, cough, coryza, and diarrhea. The animals from farms A and B were treated with diminazene aceturate. Six months after, in survey 2, non-treated calves from farm C showed values for prevalence (81.82), morbidity (81.82), mortality (12.73), and lethality (15.55) similar to those in survey 1 (P>0.05). Also in survey 2, four calves aging merely 1-3 days old presented high parasitemia levels (from 32x10(6) to 74x10(6) parasites/mL), suggesting transplacental transmission. In conclusion, trypanosomiasis by T. vivax constitutes high prevalent disease for calves raised in Brazilian semiarid and may have transplacental transmission.

Academic and clinical preparation in speech-language pathology and audiology: a global training consortium

ABSTRACT: Purpose: To describe a research-based global curriculum in speech-language pathology and audiology that is part of a funded cross-linguistic consortium among 2 U.S. and 2 Brazilian universities. Method: The need for a global curriculum in speechlanguage pathology and audiology is outlined, and different funding sources are identified to support development of a global curriculum. The U.S. Department of Education’s Fund for the Improvement of Post-Secondary Education (FIPSE), in conjunction with the Brazilian Ministry of Education (Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior; CAPES), funded the establishment of a shared research curriculum project, “Consortium for Promoting Cross-Linguistic Understanding of Communication Disabilities in Children” for East Tennessee State University and the University of Northern Iowa and 2 Brazilian universities (Universidade Federal de Santa Maria and Universidade de São Paulo-Baurú). Results: The goals and objectives of the research-based global curriculum are summarized, and a description of an Internet-based course, “Different Languages, One World,” is provided Conclusion: Partnerships such as the FIPSE–CAPES consortium provide a foundation for training future generations of globally and research-prepared practitioners in speechlanguage pathology and audiology.

Surgical and postmortem pathology studies: contribution for the investigation of temporal lobe epilepsy

Pathology studies in epilepsy patients bring useful information for comprehending the physiopathology of various forms of epilepsy, as well as aspects related to response to treatment and long-term prognosis. These studies are usually restricted to surgical specimens obtained from patients with refractory focal epilepsies. Therefore, most of them pertain to temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and malformations of cortical development (MCD), thus providing information of a selected group of patients and restricted regions of the brain. Postmortem whole brain studies are rarely performed in epilepsy patients, however they may provide extensive information on brain pathology, allowing the analysis of areas beyond the putative epileptogenic zone. In this article, we reviewed pathology studies performed in epilepsy patients with emphasis on neuropathological findings in TLE with MTS and MCD. Furthermore, we reviewed data from postmortem studies and discussed the importance of performing these studies in epilepsy populations.

The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas

Abstract: Background Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors. Methods Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ≤ 0.05 were considered significant. Results In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival. Conclusions Pancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive. Virtual slides. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514

Unusual tomographic findings of complicated necrotizing pancreatitis

Acute pancreatitis (AP) is a potential life-threatening disease, which originates from inflammatory involvement of the pancreas and surrounding tissues. Serious complications eventuate and treatment is difficult. AP is classified in both interstitial edematous pancreatitis, which occurs in 70-80% of patients, and necrotizing pancreatitis, which occurs in 20-30% of patients. Diagnosis is based on the presence of two of the following criteria: abdominal pain, increased serum determination of amylase and/or lipase more than three times the reference value, and characteristic tomographic findings. Among the latter, there is the pancreatic and surrounding tissue damage as well as that related to distant organ involvement. This case report shows the fatal case of a male patient with a history of heavy alcoholic abuse admitted with the diagnosis of necrotizing pancreatitis. The authors call attention to the unusual tomographic findings; namely, a huge duodenal hematoma and a large hemoperitoneum, ischemic involvement of the spleen and kidneys, as well as pancreatic and peripancreatic necrosis.

In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology

BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT) and IL-10(-/-) C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb) infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/-) mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO) and MCP-1. For in vivo studies, IL-10(-/-) and WT mice were i.t. infected with 1×10(6) Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/-) mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/-) mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+) and CD8(+) T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/-) mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a detrimental effect to pulmonary PCM due to its suppressive effect on the innate and adaptive immunity resulting in progressive infection and precocious mortality of infected hosts.