Background: The study of the endotoxin tolerance phenomenon in light of the recently defined roles of mast cells and toll-like receptors as essential components of the innate immune response and as orchestrators of acquired immunity may reveal potentially useful mechanisms of immunomodulation of infectious and allergic inflammatory responses, such as sepsis or asthma. Here we evaluated the phenomenon of direct tolerance of endotoxins, as well as the induction of cross-tolerance and synergism by stimulation with toll-like receptor-2 (TLR2) and FcεR1 agonists, in murine mast cells prestimulated with lipopolysaccharide (LPS). Additionally, we evaluated some stimulatory and inhibitory signaling molecules potentially involved in these phenomena. Methods: MC/9 cells and primary bone marrow-derived mast cells obtained from C57BL/6 and TLR4^-/- knock-out mice were sensitized to DNP-HSA (antigen) by incubation with DNP-IgE and were prestimulated with LPS for 18 hr prior to stimulation. Cultures were stimulated with LPS or Pam3Cys-Ser-(Lys)4 3HCl (P3C), a TLR2 agonist, individually or in combination with antigen. The production of IL-6 and TNFα, the phosphorylation of NFκB and p38 MAPK, and the expression of TLR4 and SOCS-1 and -3 were analyzed. Results: We found that production of TNFα and IL-6 in murine mast cells that have been pretreated with LPS and challenged with TLR4 (LPS) or -2 (P3C) agonists was reduced, phenomena described as endotoxin tolerance (LPS) and cross-tolerance (P3C), respectively. The expression of TLR4 was not affected by LPS pretreatment. Our results show that the FcεR1 agonist DNP-HSA (antigen) interacts synergistically with LPS or P3C to markedly enhance production of cytokines (TNFα and IL-6). This synergistic effect with LPS and P3C was also attenuated by LPS pretreatment and was mediated by TLR4. These results may be attributed to the reduction in phosphorylation of the mitogen-activated protein kinase (MAPK), p38, and the transcription factor NFκB, as well as to an increase in the expression of the suppressors of cytokine signaling (SOCS)-1 and -3 proteins in LPS-pretreated mast cells. Conclusions: These findings can be explored with respect to the modulation of inflammatory responses associated with infectious and allergic processes in future studies.

Chagas disease, caused by a Trypanosona cruzi infection, is one of the main causes of heart failure in Latin America. It was originally a health problem endemic to South America, predominantly affecting residents of poor rural areas. With globalization and increasing migratory flows from these areas to large cities, the immigration of T. cruzi chronically-infected people to developed, non-endemic countries has occurred. This issue has emerged as an important consideration for heart transplant professionals. Currently, Chagas patients with end-stage heart failure may need a heart transplantation (HTx). This implies that in post-transplant immunosuppression therapy to avoid rejection in the recipient, there is the possibility of T. cruzi infection reactivation, increasing the morbidity and mortality rates. The management of heart transplant recipients due to Chagas disease requires awareness for early recognition and parasitic treatment of T. cruzi infection reactivation. This issue poses challenges for heart transplant professionals, especially regarding the differential diagnosis between rejection and reactivation episodes. The aim of this review is to discuss the complexity of the Chagas disease reactivation phenomenon in patients submitted to HTx for end-stage chagasic cardiomyopathy.

Introduction: The objective of this study was to investigate regional organ perfusion acutely following uncontrolled hemorrhage in an animal model that simulates a penetrating vascular injury and accounts for prehospital times in urban trauma. We set forth to determine if hypotensive resuscitation (permissive hypotension) would result in equivalent organ perfusion compared to normotensive resuscitation.Methods: Twenty four (n=24) male rats randomized to 4 groups: Sham, No Fluid (NF), Permissive Hypotension (PH) (60% of baseline mean arterial pressure - MAP), Normotensive Resuscitation (NBP). Uncontrolled hemorrhage caused by a standardised injury to the abdominal aorta; MAP was monitored continuously and lactated Ringer’s was infused. Fluorimeter readings of regional blood flow of the brain, heart, lung, kidney, liver, and bowel were obtained at baseline and 85 minutes after hemorrhage, as well as, cardiac output, lactic acid, and laboratory tests; intra-abdominal blood loss was assessed. Analysis of variance was used for comparison.Results: Intra-abdominal blood loss was higher in NBP group, as well as, lower hematocrit and hemoglobin levels. No statistical differences in perfusion of any organ between PH and NBP groups. No statistical difference in cardiac output between PH and NBP groups, as well as, in lactic acid levels between PH and NBP. NF group had significantly higher lactic acidosis and had significantly lower organ perfusion.Conclusions: Hypotensive resuscitation causes less intra-abdominal bleeding than normotensive resuscitation and concurrently maintains equivalent organ perfusion. No fluid resuscitation reduces intra-abdominal bleeding but also significantly reduces organ perfusion.

Inflammation plays a major role in the multifactorial process of trauma associated coagulopathy. The vagus nerve regulates the cholinergic anti-inflammatory pathway. We hypothesized that efferent vagus nerve stimulation (VNS) can improve coagulopathy by modulating the inflammatory response to hemorrhage.

Perianal fistula, usually has a criptoglandular etiology, developing from a perianal abscess and communicating the anal mucosa with the perianal skin. The aim of this paper is to study retrospectively 241 cases of perianal fistula (172 men and 69 women; 2,5:1) aging from 7 and 80 years old (average: 37,4 years), operated on at the Hospital da Clínicas - UFMG, from 1977 to 1996. The surgical techniques and post-operative outcome have been analysed. Perianal abscesses with spontaneous drainage were the predominant etiology (132 patients; 54,8%). Eighty percent were submitted to fistulectomy as the first surgical treatment. Among early complications (78; 32,4%), local pain was the most frequent (60; 24,9%). Among the late complications (136; 56,4%) fistula recurrence (101; 41,9%) was the most frequent. There were 141 reoperations in 80 patients. Fistulectomy was the predominant surgical technique employed for the treatment (101; 71,6%). The average hospitalization time was 6,3 days until 1990 and 1,5 day from 1991 to 1996, after the advent of day-surgery beds in HC-UFMG. The surgical treatment of perianal fístula has a significant rate of post-operative complications and a high recurrence rate, in spite of the short stay in hospital