Oral immune regulation using colitis extracted proteins for treatment of Crohn＇s disease： Results of a phase I clinical trial

AIM: To evaluate safety and possible efficacy of induction of oral immune regulation using colitis extracted proteins(CEP) in Crohn‘s disease (CD) subjects.METHODS: Ten CDs were treated orally with autologous CEP thrice weekly for 16 wk. Subjects were monitored for CDAI and IBDQ. Immune modulatory effect was assessed by T-lymphocyte FACS analysis, CEP-specific IFNγ ELISPOT assay and cytokine levels.RESULTS: Induction of oral immune regulation significantly ameliorated disease activity. All (10/10) subjects had clinical response (CDAI≤70) and 7/10 achieved clinical remission (CDAI≤150). Significant increase in mean IBDQ score was noted (134±9vs 164±12). No treatment-related adverse events were noted. High levels of CEP-specific IFNγ spot forming colonies were detected in five subjects prior to treatment and in all five, a marked decrease was observed. The CD4+/CDS+ lymphocyte ratio and peripheral NKT cell numbers increased significantly, in 7/10 and in 5/10 subjects, respectively. Significant increase in serum IL-10 and IL-4 levels was observed in 7/10 subjects during treatment period.CONCLUSION: Immune regulation via oral administration of CEP is a safe and possibly effective treatment for subjects with moderate CD and may provide means of antigen-specific immune modulation.     

Myocardial revascularization. The evolution of 100 cases

The postoperative course of 100 pts. that underwent aorto-coronary bypass surgery was studied at the Instituto Nacional de Cardiología "Ignacio Chávez": 84 were men and 16 women between 37 and 74 years. 56 had previous history of myocardial infarction, while in 16 of them occurred within 30 days of the surgical procedure. 88 had symptomatic angina and 8 were in cardiac failure. The coronariography showed trivascular lesions in 73% and 8 pts. had stenosis of the left main coronary artery. Two pts. had 5 coronary grafts, 4 had 17, 3 had 37, two 35 and one 9 pts. All anterior descending coronary arteries were grafted. 61 of them and the 8 main left damaged were grafted with internal mammary artery Afert surgery; 15 pts had AMI, 4 profuse bleeding, one cardiac failure and shock. CPK enzyme levels of 500 were found in the majority of the pts with AMI with 81.2 positive predictive value and negative of 97.6. Three pts died, two at the OR with cardiac failure one of them had ventricular rupture, and the last at the ICU also with cardiac failure. We emphasize that CPK values of 500 UI or more in the postoperative course may be diagnostic of AMI.     

International Aid and Natural Disasters: A Pre- and Post-Earthquake Longitudinal Study of the Healthcare Infrastructure in Leogane,Haiti

The reconstruction of healthcare systems in developing countries after natural disasters is poorly understood. Using data collected before and after the 2010 Haiti earthquake, we detail the response of aid agencies and their interaction with local healthcare providers in Leogane, the city closest to the epicenter. We find that the period after the earthquake was associated with an increase in the total number of healthcare facilities, inpatient beds, and surgical facilities and that international aid has been a driving force behind this recovery. Aid has funded 12 of 13 new healthcare facilities that have opened since the earthquake as well as the reconstruction of 7 of 8 healthcare facilities that have been rebuilt. Despite increases in free, aid-financed healthcare, private Haitian healthcare facilities have remained at a constant number. The planned phase-out of several aid-financed facilities, however, will leave Leogane with fewer inpatient beds and healthcare services compared with the pre-earthquake period.     

The life cycle of the steroidogenic acute regulatory (StAR) protein: from transcription through proteolysis

The Steroidogenic Acute Regulatory (StAR) protein is a mitochondrial protein required for the transport of cholesterol substrate to the P450scc enzyme located in the inner mitochondrial membranes of steroid producing cells. This study suggests that the acute regulation of the rodent StAR gene in the ovary is mediated by two factors, C/EBPbeta and GATA-4. Once translated, the StAR precursor protein is either imported into the mitochondria, or it is rapidly degraded in the cytosol. We predicted that in order to perpetuate StAR activity cycles, imported StAR should turn over rapidly to avoid a potentially harmful accumulation of the protein in sub-mitochondrial compartments. Pulse-chase experiments in metabolically labeled cells showed that: (a) the turnover rate of mature mitochondrial StAR protein (30 kDa) is much faster (t(1/2) = 4-5 h) than that of other mitochondrial proteins; (b) dissipation of the inner membrane potential (-delta psi) by carbonyl cyanide m-chlorophenylhydrazone (mCCCP) accelerates the mitochondrial degradation of StAR; (c) unexpectedly, the mitochondrial degradation of StAR is inhibited by MG132 and lactacystin, but not by epoxomicin. Furthermore, StAR degradation becomes inhibitor-resistant two hours after import. Therefore, these studies suggest a bi-phasic route of StAR turnover in the mitochondria. Shortly after import, StAR is degraded by inhibitor-sensitive protease(s) (phase I), whereas at later times, StAR turnover proceeds to completion through an MG132-resistant proteolytic activity (phase II). Collectively, this study defines StAR as a unique protein that can authentically be used to probe multiple proteolytic activities in mammalian mitochondria.     

Inflammasomes and the microbiota—partners in the preservation of mucosal homeostasis

Seminars in Immunopathology - Inflammasomes are multiprotein complexes that serve as signaling platforms initiating innate immune responses. These structures are assembled upon a large array of...     

Management of Helicobacter pylori infection in Latin America: A Delphi technique-based consensus

AIM: To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature.METHODS: Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round Delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria.RESULTS: A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included: (1) when available, urea breath and stool antigen test (HpSA) should be used for non-invasive diagnosis; (2) detect and eradicate Helicobacter pylori (H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer; (3) further investigate implementation issues and health outcomes of H. pylori eradication for primary prevention of gastric cancer in high-risk populations; (4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment; (5) routinely assess eradication success post-treatment in clinical settings; and (6) select second- and third-line therapies according to antibiotic susceptibility testing.CONCLUSION: These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.