A doença do enxerto contra o hospedeiro (DECH) é uma complicação rara, porém grave, após transplante de fígado, caracterizada pela reação imunológica dos linfócitos T do doador contra os tecidos do receptor. Essa resposta pode causar acometimento multissistêmico, principalmente da pele, trato gastrointestinal e fígado, com evolução frequentemente agressiva e alta mortalidade. Relato de Caso Um paciente masculino de 64 anos, com infecção crônica por hepatite C, cirrose alcoólica e carcinoma hepatocelular, recebeu transplante hepático de doador cadáver compatível ABO. O regime imunossupressor inicial incluiu tacrolimo e corticosteroides. No nono dia pós-transplante, apresentou elevação das enzimas hepáticas, sendo diagnosticada rejeição celular aguda e iniciada pulsoterapia com metilprednisolona. Após melhora inicial e alta hospitalar, no 31º dia pós-transplante, readmitiu-se com exantema maculopapular generalizado, febre, leucopenia grave, anemia, hipotensão e diarreia. Biópsias de pele confirmaram DECH grau III. O mielograma evidenciou hipoplasia medular evoluindo para aplasia. A análise de DNA revelou macroquimerismo de linfócitos T do doador. Foi iniciado tratamento com metilprednisolona em altas doses e globulina antitimócito, sem resposta clínica. Evoluiu com insuficiência pulmonar e renal, falência múltipla de órgãos e óbito no 36º dia pós-transplante. Discussão A DECH ocorre quando linfócitos T do doador atacam os tecidos do receptor, sendo mediada por citocinas pró-inflamatórias. O macroquimerismo está associado ao desenvolvimento da doença. Os sinais iniciais incluem exantema cutâneo e febre, progredindo para acometimento multissistêmico e pancitopenia devido à medula óssea comprometida. O diagnóstico exige avaliação clínica, histológica e imunohistoquímica. O tratamento convencional com corticosteroides e imunossupressores, como globulina antitimócito, frequentemente apresenta resposta insatisfatória. A alta mortalidade da DECH reforça a necessidade de diagnóstico precoce, manejo multidisciplinar e desenvolvimento de novas terapias para melhorar os desfechos.

encefalite por caxumba foi diagnosticada com morte cerebral e seus órgãos foram oferecidos para transplante .O Dr. Moore,

Mitochondrial dysfunction is a recognized feature of sepsis, characterized by ultrastructural damage, diminished oxidative phosphorylation, and depletion of mitochondrial antioxidant capacity observed in deceased septic patients. LPS tolerance induces a controlled response to sepsis. This study aimed to evaluate the function of tolerant mitochondria after cecal ligation and puncture (CLP)-induced sepsis. Mytochondrial oxygen consumption was determined using polarography. Extraction and quantification of RNA for the expression of Tfam, Nrf-1, and Ppargc-1 alpha, and respiratory complex activity were measured. CLP-tolerant animals presented preserved respiratory rates of S3 and S4 and a ratio of respiratory control (RCR) compared to CLP-nontolerant animals with reduced oxidative phosphorylation and increased uncoupled respiration. Complex I Vmax was reduced in septic animals; however, CLP animals sustained normal Vmax. Mitochondrial biogenesis was preserved in CLP-tolerant animals compared to the CLP-nontolerant group, likely due to increased TFAM expression. LPS tolerance protected septic animals from mitochondrial dysfunction, favoring mitochondrial biogenesis and preserving mitochondrial respiration and respiratory complex I activity.

Background The swine is a valuable model for preclinical research and surgical technique training. Induction of Type I diabetes is achieved by total pancreatectomy, therefore these animals may be used in several research studies, including islet transplantation field. Given the lack of information in the literature, the purpose of this work is to describe anatomic aspects of swine pancreas, the total pancreatectomy surgical technique, intra- and postoperative complications and the autopsy results. Material and Methods Five hybrid male pigs, 20-35 kg, submitted to total pancreatectomy with duodenum, bile duct, and spleen preservation. Postoperatively, daily clinical assessment and capillary blood glucose collection were performed. At the end of the 30-day period or in the occurrence of serious clinical complications, euthanasia and autopsy were performed. Results The average duration of surgery was 128 minutes, without intraoperative deaths or anesthesia induction failures. The median survival was 6.6 days. Postoperative complications were weight loss (3), emesis (2), constipation (2), abdominal distension (2), diarrhea (1), and loss of appetite (1). All animals were euthanized due to serious complications. Two animals presented surgical complications (duodenal necrosis with gastroparesis and internal hernia with intestinal necrosis). The other 3 animals presented serious clinical complications related to exocrine pancreatic insufficiency due to deficiency of pancreatic enzymes. Glycemic values above 200 mg/dL were found on the first postoperative day and above 300 mg/dL on the seventh day in all animals. Conclusion A model of total pancreatectomy with duodenum, spleen, and bile duct preservation in pigs was established. All animals became diabetic, however, animals without postoperative complications were euthanized due to serious complications related to pancreas exocrine insufficiency.

and in this year as Professor of Surgery, University of Cambridge, being only 34 years-old.His interest in transplanation began when he was a medical student, observing many fatal diseases in young people when all they required was new organs.The inspiration for transplantation came from Sir Peter Medawar (brazilian-born Nobel Prize in Physiology or Medicine,1960) after he attended a science lecture given by Medawar in 1956 telling the exciting story of immunological tolerance, with beatiful illustrations.Medawar suggested to Calne a stage in

ABSTRACT BACKGROUND: After validation in multiple types of liver disease patients, the MELD score was adopted as a standard by which liver transplant candidates with end-stage liver disease were prioritized for organ allocation in the United States since 2002, and in Brazil, since 2006. AIMS: To analyze the mortality profile of patients on the liver transplant waiting list correlated to MELD score at the moment of transplantation. METHODS: This study used the data from the Secretary of Health of the São Paulo State, Brazil, which listed 22,522 patients, from 2006 (when MELD score was introduced in Brazil) until June 2009. Patients with acute hepatic failure and tumors were included as well. We also considered the mortality of both non-transplanted and transplanted patients as a function of the MELD score at presentation. RESULTS: Our model showed that the best MELD score for patients on the liver transplant waiting list associated to better results after liver transplantation was 26. CONCLUSIONS: We found that the best score for applying to liver transplant waiting list in the State of São Paulo was 26. This is the score that minimizes the mortality in both non-transplanted and liver transplanted patients.

PURPOSE:After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation.METHODS:Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet).RESULTS:Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity.CONCLUSIONS:Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment （HF）,trisulfated disaccharide （TD）,that acts on sodium-calcium exchanger（NCX） decreasing intracellular Ca 2+ ,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],

São Paulo is the first Brazilian state to perform liver transplantation in 1968 (Machado, 1972). Since then, the recipient waiting list has increased; now approximately 150 new cases per month are referred to the single list at the central organ procurement organization. Official data have shown 37.3 monthly deaths on the waiting list in the state of São Paulo. The number of liver transplants has increased after the creation of São Paulo transplant notification centers but is insufficient to deal with the increasing waiting list. The aim of this study was to demonstrate the performance of our state liver transplantation program and analyze when the number of liver transplantations will meet our waiting list demand.

Since liver transplantation was first performed in Brazil at the University of Sao Paulo School of Medicine, the patient waiting list for liver transplantation has increased at a rate of 150 new cases per month. Liver transplantation rose 1.84-fold (from 160 to 295) from 1988 to 2004. However, the number of patients on the liver waiting list jumped 2.71-fold (from 553 to 1500). Consequently the number of deaths on the liver waiting list moved to a higher level, from 321 to 671, increasing 2.09-fold (Chaib and Massad, 2005).

In this paper we analyze, through a mathematical model, the potential impact of HCV antiviral therapy on the liver transplantation waiting list (LTWL) in the State of Sao Paulo, Brazil.In previous papers, we projected the size of the waiting list by taking into account the incidence of new patients per year, the number of transplantations carried out in that year, and the number of patients that died in the waiting list.In the present work, we projected the LTWL size for the next 30 years and we introduced the anti-HCV treatment, which was assumed to half the incidence of patients in the LTWL and that the recovery of patients in the list would triple.The liver transplantation rate was assumed to not be affected by the anti-HCV treatment.Our mathematical model demonstrates that anti-HCV therapy would have a remarkable impact on the size of the LTWL, in the State of Sao Paulo, dropping from twenty-four thousand to approximately twelve hundred patients in the next 30 years.

The development of an effective vaccine for hepatitis C is of paramount importance, given the global disease burden and its public health impact (Jawaid et al., 2008; Stoll-Keller et al., 2009). The hepatitis C virus infects some 170 million people worldwide and is responsible for approximately 20% of cases of acute hepatitis and 70% of cases of chronic hepatitis (Boyer et al., 2000). Hepatitis B virus (HBV) infection is now preventable by a highly effective vaccine that induces long-term memory (Hilleman, 1993). As HBV is a stable virus and has no animal reservoir, it is theoretically eradicable if the vaccine is sufficiently and widely applied for a long time (Hilleman, 2011). As an important cause of liver failure, it should be expected that HBV eradication would have a significant impact on the number of liver transplantation.

As mentioned in the previous chapters, liver failure occurs when large parts of the liver become damaged beyond repair, and the liver is no longer able to function. It may be caused by infections, toxic substances, inherited diseases, or malnutrition (Chaib et al., 2012). The chronic aggression of liver tissue by one of the causes of liver failure can end up in primary hepatocellular carcinoma (HCC), a deadly condition to which liver transplantation is the only option, with variable success rate of a close-to-normal life after the surgery (Chaib and Massad, 2008a,b,cChaib and Massad, 2008aChaib and Massad, 2008bChaib and Massad, 2008c).

Medawar, a biologist from Oxford, noted that allografts were a practical means of covering burn defects based on Gibson's work of pinch grafts from allogenic sources. He also noted that their dissolution was accelerated at a second exposure. The term “second set,” which ascribes memory to the immune system, dates to this work and has become an important aspect of immunologic research. Next, he became interested in recipients of progressively young ages. He showed that mice exposed to allogenic cells while in utero became tolerant to the tissue even into adult life (Billingham et al., 1953).

Background: Neointimal hyperplasia development after vascular procedures such as angioplasty and stenting is a cellular proliferative process that is initiated and potentiated by inflammation and leads to arterial restenosis.However, the role of gut microbiota in regulating this process is unknown.We previously demonstrated that germ-free (GF) mice have diminished neointimal hyperplasia development after carotid ligation that is associated with increased M2 macrophage infiltration, reduced proportion of mature neutrophils, and altered systemic inflammatory cytokine profile compared to conventionally-raised (CONV-R) mice.To further understand the causative role of microbiota in neointimal hyperplasia development, we reconstituted bacterial colonization in GF mice with microbiota from CONV-R mice by fecal transplantation.Methods: Fourteen-week-old C57BL/6 male GF mice underwent oral gavage of a fresh slurry of homogenized stool from donor CONV-R mice.Six weeks later, fecal transplanted GF (GF-FT) mice underwent unilateral carotid artery ligation.Age-, sex-and strain-matched CONV-R and GF mice served as the comparison groups.Neointimal hyperplasia was assessed by morphometric analysis of carotid artery sections four weeks after injury.Calculated measurements included neointima (NI) area, NI+media (NI+M) area, and NI/(NI+M).Maintenance of sterility in the GF cohort was confirmed by cultivation and 16S rRNA gene RT-PCR of stool.Morphometric parameters were compared using the Mann-Whitney U-test.P ≤ 0.05 was considered statistically significant.Results: As anticipated, the GF cohort developed significantly less neointimal hyperplasia than the CONV-R cohort (mean NI, GF 0.005 ± 0.002 mm 2 vs. CONV-R 0.021 ± 0.004 mm 2 , P = 0.01; mean NI+M, GF 0.029 ± 0.003 mm 2 vs. CONV-R 0.055 ± 0.005 mm 2 , P = 0.005; and mean NI/[NI+M], GF 0.120 ± 0.031 vs. CONV-R 0.290 ± 0.047, P = 0.02).Fecal transplantation of donor CONV-R stool to GF mice attenuated this difference.GF-FT mice had similar neointimal hyperplasia to CONV-R mice, as assessed by NI (GF-FT, 0.014 ± 0.003 mm 2 ; P=0.8), NI+M (GF-FT, 0.049 ± 0.007 mm 2 ; P=0.5) and NI/(NI+M) (GF-FT, 0.249 ± 0.04; P=0.5).All GF mice remained sterile during the entire study period.Conclusions: We provide evidence that strengthens the proposed connection between gut microbiota and arterial remodeling after injury.Further investigation into the impact of bacterial colonization on arterial inflammation and on the roles of specific microbial community members in arterial remodeling is warranted.