Do the Effects of Pentoxifylline on the Inflammatory Process and Pancreatic Infection Justify Its Use in Acute Pancreatitis?

Severe acute pancreatitis is associated with high morbidity and mortality rates. At the present time, no specific therapy has been shown to be uniformly effective in reducing morbidity and mortality in this disease. The aim of this study was to determine the effects of pentoxifylline on the pancreatic and systemic inflammatory process, pancreatic infection, and mortality rate in severe acute pancreatitis in rats. Methods: One hundred and twenty male Wistar rats were divided into 3 groups: sham, pancreatitis, and pentoxifylline (acute pancreatitis induction plus administration of 25 mg/kg pentoxifylline). Inflammatory response was measured by histological studies, inflammatory cytokine production (IL-6, IL-10, and TNF-alpha), and mortality rate. Pancreatic infection was evaluated by bacterial cultures expressed in colony-forming units per gram. Results: Pentoxifylline-treated animals had a statistically significant reduction of inflammatory cytokine levels, pancreatic histological damage, occurrence of bacterial translocation and pancreatic infection (p < 0.05), associated with a significant reduction in mortality rate. Conclusions: Pentoxifylline administration in this experimental model of acute pancreatitis reduces local and systemic inflammatory responses and decreases the pancreatic infection and the mortality rate. Copyright (C) 2009 S. Karger AG, Basel and IAP

The role played by the parietoocciptal cortex in the process of sensory-motor integration: An electroencephalographic study

Introduction. A fundamental aspect of planning future actions is the performance and control of motor tasks. This behaviour is done through sensory-motor integration. Aim. To explain the electrophysiological mechanisms in the cortex (modifications to the alpha band) that are involved in anticipatory actions when individuals have to catch a free-falling object. Subjects and methods. The sample was made up of 20 healthy subjects of both sexes (11 males and 9 females) with ages ranging between 25 and 40 years (32.5 +/- 7.5) who were free of mental or physical diseases (previous medical history); the subjects were right-handed (Edinburgh Inventory) and were not taking any psychoactive or psychotropic substances at the time of the study. The experiment consisted in a task in which subjects had to catch freely falling objects. The experiment was made up of six blocks of 15 tests, each of which lasted 2 minutes and 30 seconds before and two seconds after each ball was dropped. Results. An interaction of the factors moment and position was only observed for the right parietooccipital cortex, in the combination of electrodes P4-O2. Conclusion. These findings suggest that the right parietooccipital cortex plays an important role in increasing expectation and swiftness in the process of preparing for a motor task.

Ultrasound Propagation Velocity and Broadband Attenuation Can Help Evaluate the Healing Process of an Experimental Fracture

Ultrasonometry seems to have a future for the evaluation of fracture healing. Ultrasound propagation velocity (USPV) significantly decreases at the same time that bone diameter decreases as healing takes place, thus approaching normal values. In this investigation, both USPV and broadband ultrasound attenuation (BUA) were measured using a model of a transverse mid-diaphyseal osteotomy of sheep tibiae. Twenty-one sheep were operated and divided into three groups of seven, according to the follow-up period of 30, 60, and 90 days, respectively. The progress of healing of the osteotomy was checked with monthly conventional radiographs. The animals were killed at the end of the period of observation of each group, both operated-upon and intact tibiae being resected and submitted to the measurement of underwater transverse and direct contact transverse and longitudinal USPV and BUA at the osteotomy site. The intact left tibia of the 21 animals was used for control, being examined on a symmetrical diaphyseal segment. USPV increased while BUA decreased with the progression of healing, with significant differences between the operated and untouched tibiae and between the periods of observation, for most of the comparisons. There was a strong negative correlation between USPV and BUA. Both USPV and BUA directly reflect and can help predict the healing of fractures, but USPV alone can be used as a fundamental parameter. Ultrasonometry may be of use in clinical application to humans provided adequate adaptations can be developed. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:444-451, 2011

Schistosoma mansoni encodes SMT3B and SMT3C molecules responsible for post-translational modification of cellular proteins

The sumoylation pathway is a post-translational modification of nuclear proteins widespread among several organisms. SMT3C is the main protein involved in this process and it is covalently conjugated to a diverse assortment of nuclear protein targets. To date, 3 SUMO paralogues (SMT3C, A/B) have been characterized in mammals and plants. In this work we characterized two SUMO related genes, named SMT3B and SMT3C throughout Schistosoma mansoni life cycle. The SmSMTB/C encodes for proteins sharing significant amino acid homology with SMT3. Phylogenetical analyses revealed that both SmSMT3B/C are distinct proteins. Additionally, SmSMT3B and C are expressed in cercariae, adult worms, eggs and schistosomula however SinSMT3C gene showed an expression level 7 to 9 fold higher than SmSMT3B in eggs, schistosomula and adult worms. The comparison between the SmSMT3C genomic and cDNA sequences established that the encoding sequence is interrupted by 3 introns of 70, 37 and 36 bp. Western Blot has shown SMT3 conjugates are present in nuclear and total protein fractions of adults and cercariae. Therefore our results suggest a functional sumoylation pathway, and the presence of two paralogues also suggests the specificity of substrates for SMT3 in S. mansoni. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA(1,2). Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in E mu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc- overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap- dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site ( IRES)- dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic- specific expression of the endogenous IRES- dependent form of Cdk11 ( also known as Cdc21 and PITSLRE)(3-5), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in E mu-Myc/+ mice. When accurate translational control is re- established in E mu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post- genomic level.

Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution

Aim To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced intestinal mucositis. Materials and methods Wistar rats received 5-FU (150 mg kg(-1), i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage, apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment, gastric emptying in vivo was measured by scintilographic method, and stomach or duodenal smooth muscle contractions induced by CCh were evaluated in vitro. Results On the third day of treatment, 5-FU induced a significant villi shortening, an increase in crypt depth and intestinal MPO activity and a decrease in villus/crypt ratio and GSH concentration. On the first day after 5-FU there was an increase in the apoptosis index and a decrease in the mitosis index in all intestinal segments. After the 15th day of 5-FU treatment, a complete reversion of all these parameters was observed. There was a delay in gastric emptying in vivo and a significant increase in gastric fundus and duodenum smooth muscle contraction, after both the 3rd and 15th day. Conclusions 5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.

Abnormal cell-cycle expression of the proteins p27, mdm2 and cathepsin B in oral squamous-cell carcinoma infected with human papillomavirus

Since the role of human papillomavirus (HPV) infection in oral carcinogenesis is still unclear, the purpose of this study was to verify the association between the expression of p27, mdm2 and cathepsin B and by HPV-related oral lesions. Fifty-five oral biopsies were studied and HPV detection and typing (6/11, 16, 18, 31 and 33) were performed using polymerase chain reaction techniques. The distribution p27, mdm2 and cathepsin B was determined by immunohistochemistry. Twenty-one (38%) out of the 55 oral lesions tested positive for HPV, of which 6(33%) were HPV 6/11, 1 (5%) was HPV 16,14 (72%) were HPV 18 and none was HPV 33/31. Among the 55 biopsies, immunopostivity for p27, mdm2 and cathepsin B was observed in 17 (30.9%), 37 (67.2%) and 37 (67.2%), respectively. Among 21 HPV-positive oral lesions, immunopostivity of mdm2, p27 and cathepsin B was found, respectively, in 6 (33%) out of 18 benign lesions (BL), 4(22%) out of 18 potential malignant epithelial lesions (PMEL) and 11(57.9%) out of 19 malignant lesions (ML). High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B. (C) 2009 Elsevier GmbH. All rights reserved.

Elongated styloid process and atheroma in panoramic radiography and its relationship with systemic osteoporosis and osteopenia

Association between the presence of an elongated styloid process, vascular calcification (atheroma) and the potential risk factor for osteoporosis was studied. Presence of an elongated styloid process was found to be correlated with systemic osteoporosis and also between elongated styloid process and atheroma. The association between the presences of an elongated styloid process and vascular calcification (atheroma) with the potential risk factor assessment for osteoporosis was studied. Bone mineral density obtained by dual energy X-ray absorptiometry diagnosed osteopenia/osteoporosis on at least two of three sites (column, hips, and forearm) of 50 female patients. Panoramic maxillomandibular radiographs were taken and analyzed. Elongation of the styloid processes was measured and the presence of atheromas in the carotid was investigated. Eighty percent of the patients presented at least one side with elongated styloid process and the highest prevalence (87.5%) occurred in individuals between 60 and 69 years. Atheroma was found in four patients, three of which presented elongated styloid on at least one side and had diagnosed osteoporosis on at least two of the evaluated sites. Correlation was found between the elongation of the styloid process and systemic osteoporosis, and between elongated styloid process and atheroma. The method in this study might be used as part of a method for osteopenia/osteoporosis and atheroma risk assessment.

Specification and Evaluation of Safety Properties in a Component-Based Software Engineering Process

Over the past years, component-based software engineering has become an established paradigm in the area of complex software intensive systems. However, many techniques for analyzing these systems for critical properties currently do not make use of the component orientation. In particular, safety analysis of component-based systems is an open field of research. In this chapter we investigate the problems arising and define a set of requirements that apply when adapting the analysis of safety properties to a component-based software engineering process. Based on these requirements some important component-oriented safety evaluation approaches are examined and compared.