Human visceral leishmaniasis expresses Th1 pattern in situ liver lesions

The architectural and infiltrate pattern of liver human visceral leishmaniasis (HVL) have been systematically classified as typical, fibrogenic or nodular. Despite this histopathological classification, the immune response based on cytokines and cellular phenotypes have never been performed. The aim of this study was to determine the immunophenotypic pattern and cytokine profile of the nodular involvement of the Liver in HVL. We evaluated nine cases of the nodular form of HVL. In situ immune response was studied through cytokine analysis and immunohistochemical study for phenotype markers: IL-1, IL-4, IL-1 0, TNF-alpha, IFN-gamma, CD4+ T cells, CD8+ T cells, CD20, CD68, CD57 and macrophage activation was determined by evaluation of iNOS activity. HVL seems to be related to a better immune response. Amastigotes were rarely found on liver sections. Leishmania antigen expression was also rare and located in the inflammatory nodules. The lower expression of IL-4 and IL-10, moderate expression of TNF-alpha and IFN-gamma demonstrate a panorama of Th1 phenotype. The increased expression of NK cells could help in sustaining this model of response. This pattern of immune response is probably responsible for improvement in the parasite`s clearance from liver tissue and it is a prognostic marker of human visceral leishmaniasis. (C) 2008 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

One-stage laparoscopic bisegmentectomy 7-8 and bisegmentectomy 2-3 for bilateral colorectal liver metastases

Bisegmentectomy 7-8 is feasible even in the absence of a large inferior right hepatic vein. To our knowledge, this operation has never been performed by laparoscopy. This study was designed to present video of pure laparoscopic bisegmentectomy 7-8 and bisegmentectomy 2-3 in one-stage operation for bilateral liver metastasis. A 67-year-old man with metachronous bilobar colorectal liver metastasis was referred for surgical treatment after neoadjuvant chemotherapy. CT scan disclosed two liver metastases: one located between segments 7 and 8 and another one in segment 2. At liver examination, another metastasis was found on segment 3. We decided to perform a bisegmentectomy 7-8 along with bisegmentectomy 2-3 in a single procedure. The operation began with mobilization of the right liver with complete dissection of retrohepatic vena cava. Inferior right hepatic vein was absent. Right hepatic vein was dissected and encircled. Upper part of right liver, containing segment 7 and 8, was marked with cautery. Selective hemi-Pringle maneuver was performed and right hepatic vein was divided with stapler. At this point, liver rotation to the left allowed direct view and access to the superior aspect of the right liver. Liver transection was accomplished with harmonic scalpel and endoscopic stapling device. Bisegmentectomy 2-3 was performed using the intrahepatic Glissonian approach. The specimens were extracted through a suprapubic incision. Liver raw surfaces were reviewed for bleeding and bile leaks. Operative time was 240 minutes with no need for transfusion. Recovery was uneventful. Patient was discharged on the fifth postoperative day. Patient is well with no evidence of disease 14 months after liver resection. Tumor markers are within normal range. Bisegmentectomy 7-8 may increase resectability rate in patients with bilateral lesions. This operation can be performed safely by laparoscopy. Preservation of segments 5 and 6 permitted simultaneous resection of segments 2 and 3 with adequate liver remnant.

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology

Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee`s ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain.

Effects of Partial Liver Ischemia Followed by Global Liver Reperfusion on the Remote Tissue Expression of Nitric Oxide Synthase: Lungs and Kidneys

Hepatic ischemia followed by reperfusion (IR) results in mild to severe remote organ injury. Oxidative stress and nitric oxide (NO) seem to be involved in the IR injury. Our aim was to investigate the effects of liver I/R on hepatic function and lipid peroxidation, leukocyte infiltration and NO synthase (NOS) immunostaining in the lung and the kidney. We randomized 24 male Wistar rats into 3 groups: 1) control; 2) 60 minutes of partial (70%) liver 1 and 2 hours of global liver R; and 3) 60 minutes of partial (70%) liver I and 6 hours of global liver R. Groups 2 and 3 showed significant increases in plasma alanine and aspartate aminotransferase levels and in tissue malondialdehyde and myeloperoxidase contents. In the kidney, positive endothelial NOS (eNOS) staining was significantly decreased in group 3 compared with group 1. However, staining for inducible NOS (iNOS) and neuronal NOS (nNOS) did not differ among the groups. In the lung, the staining for eNOS and iNOS did not show significant differences among the groups; no positive nNOS staining was observed in any group. These results suggested that partial liver I followed by global liver R induced liver, kidney, and lung injuries characterized by neutrophil sequestration and increased oxidative stress. In addition, we supposed that the reduced NO formation via eNOS may be implicated in the moderate impairment of renal function, observed by others at 24 hours after liver I/R.

Perceived Self-Efficacy Among Liver Transplant Candidates and Recipients

Self-efficacy is defined as one`s belief that one can perform the necessary behaviors to achieve one`s goals. This belief is one of the most powerful motivational predictors of how well a person will perform at almost any endeavor. Limited information is available, however, about self-efficacy in the organ transplantation population. This study aimed to identify the self-efficacy belief among liver transplant candidates and recipients and compare these results with demographic characteristics. The authors analyzed 100 patients who were candidates and recipients for liver transplantation in a Brazilian center. The average self-efficacy score for the candidates was significantly lower than for the recipients. Future investigation is necessary to explore possible interventions to be taken before and after liver transplantation that could influence self-efficacy of the organ transplantation patients.

Liver transplantation at a University Hospital, Faculty of the Medicine of Ribeirao Preto, University of Sao Paulo: Results for the first 60 recipients

The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAR Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5 % among FAP and Child A patients (P <.05) and 16.6% for period B among 11. 1 % Child B patients and 5.5 % FAP patients; 3.3 % of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.

Acute chagasic myocardiopathy after orthotopic liver transplantation with donor and recipient serologically negative for Trypanosoma cruzi: A case report

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.

Quantitative and qualitative comparison of 3.0 T and 1.5 T MR imaging of the liver in patients with diffuse parenchymal liver disease

Purpose: The purpose of our study was to compare signal characteristics and image qualities of MR imaging at 3.0 T and 1.5 T in patients with diffuse parenchymal liver disease. Materials and methods: 25 consecutive patients with diffuse parenchymal liver disease underwent abdominal MR imaging at both 3.0 T and 1.5 T within a 6-month interval. A retrospective study was conducted to obtain quantitative and qualitative data from both 3.0 T and 1.5 T MRI. Quantitative image analysis was performed by measuring the signal-to-noise ratios (SNRs) and the contrast-to-noise ratios (CNRs) by the Students t-test. Qualitative image analysis was assessed by grading each sequence on a 3- and 4-point scale, regarding the presence of artifacts and image quality, respectively. Statistical analysis consisted of the Wilcoxon signed-rank test. Results: the mean SNRs and CNRs of the liver parenchyma and the portal vein were significantly higher at 3.0 T than at 1.5 T on portal and equilibrium phases of volumetric interpolated breath-hold examination (VIBE) images (P < 0.05). The mean SNRs were significantly higher at 3.0 T than at 1.5 T on T1-weighted spoiled gradient echo (SGE) images (P < 0.05). However, there were no significantly differences on T2-weighted short-inversion-time inversion recovery (STIR) images. Overall image qualities of the 1.5 T noncontrast T1- and T2-weighted sequences were significantly better than 3.0 T (P < 0.01). In contrast, overall image quality of the 3.0 T post-gadolinium VIBE sequence was significantly better than 1.5 T (P< 0.01). Conclusions: MR imaging of post-gadolinium VIBE sequence at 3.0 T has quantitative and qualitative advantages of evaluating for diffuse parenchymal liver disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Effects of a Low-Protein Diet on Plasma Amino Acid and Homocysteine Levels and Oxidative Status in Rats

Background/Aims: Transmethylation reactions and antioxidant metabolism are linked by transsulfuration, where homocysteine (Hcy) is converted to cysteine and reduced glutathione (GSH). Low protein intake can modulate the balance of this metabolic reaction. The aim of the present investigation was to study the effect of a low-protein diet on Hcy metabolism by monitoring levels of the amino acids involved in these pathways, and relating these levels to GSH levels and lipid peroxidation in rats. Methods: Sixteen rats were divided into 2 groups: control (C; standard AIN-93 diet, 20% protein) and low-protein diet (LPD; 8% protein diet). Rats in both groups were placed on the diets for 28 days. Results: A significant reduction (p < 0.05) in plasma Hcy concentration was found in LPD rats (0.16 +/- 0.04 mu mol/mg protein) versus C rats (0.25 +/- 0.03 mu mol/mg protein). Methionine levels were not significantly different between the 2 groups (C: 1.24 +/- 0.22 mu mol/mg protein; LPD: 1.03 +/- 0.27 mu mol/mg protein). A significant reduction (p ! 0.05) in hepatic GSH concentrations (C: 44 8 10 mu mol/mg protein; LPD: 17.4 +/- 4.3 mu mol/mg protein) was accompanied by an increase in lipid peroxidation (C: 0.13 +/- 0.01 mu mol/mg protein; LPD: 0.17 +/- 0.02 mu mol/mg protein; r = -0.62, p < 0.01). Conclusion: Hcy levels were reduced under a low-protein diet, resulting in modulated methyl balance and reduced GSH formation leading to increased susceptibility of hepatic cells to oxidative events. Copyright (C) 2009 S. Karger AG, Basel

DOUBLE ANEUPLOIDY (48,XXY,+21) OF MATERNAL ORIGIN IN A CHILD BORN TO A 13-YEAR-OLD MOTHER: EVALUATION OF THE MATERNAL FOLATE METABOLISM

Double aneuploidy, (48,XXY,+21) of maternal origin in a child born to a 13-year-old mother: evoluation of the maternal folate metabolism: The occurrence of non-mosaic double trisomy is exceptional in newborns. In this paper, a 48,XXY,+21 child, the parental origin of the extra chromosomes and the evaluation of the maternal folate metabolism are presented. The infant was born to a 13-year-old mother and presented with the typical clinical features of Down syndrome (DS). The origin of the additional chromosomes was maternal and most likely resulted from errors during the first meiotic division. Molecular analysis of 12 genetic polymorphisms involved in the folate metabolism revealed that the mother is heterozygous for the MTHFR C677T and TC2 A67G polymorphisms, and homozygous for the mutant MTRR A66G polymorphism. The maternal homocysteine concentration was 4.7 mu mol/L, a value close to the one considered as a risk factor for DS in our previous study. Plasma methylmalonic acid and serum folate concentrations were 0.17 mu mol/L and 18.4 ng/mL, respectively. It is possible that the presence of allelic variants for the folate metabolism and Hey concentration might have favored errors in chromosomal disjunction (hiring gametogenesis in this young mother. To our knowledge, this is the first patient with non-mosaic Down-Klinefelter born to a teenage mother, resulting from a rare fertilization event combining an abnormal 25,XX,+21 oocyte and a 23,Y spermatozoon.

Prospective analysis between the therapy of immunosuppressive medication and allogeneic microchimerism after liver transplantation

After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in pheripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was colleted from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p=0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donor-derived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction. (C) 2008 Elsevier B.V. All rights reserved.

Antioxidant Effect of Thiamine on Acutely Alcoholized Rats and Lack of Efficacy Using Thiamine or Glucose to Reduce Blood Alcohol Content

Although there is no consensus about the use of glucose and thiamine for the treatment of acute ethanol intoxication, this is a routine practice in many countries. Our objective was to determine the efficacy of this treatment and the changes it causes in the antioxidant status of the liver. Male Wistar rats were intoxicated with an ethanol dose of 5 g/kg and divided into three groups: ethanol (EtOH; untreated), EtOH+G (treated with glucose), and EtOH+B1 (treated with thiamine). Blood and urinary ethanol as well as hepatic malondialdehyde, reduced glutathione and vitamin E were determined in all animals. Blood alcohol levels did not differ between groups, although urinary excretion was about four times higher in the group treated with thiamine (EtOH+B1). The malondialdehyde, reduced glutathione and vitamin E values used here as parameters of the antioxidant system of the liver showed improvement for the thiamine-treated group (EtOH+B1). Treatment with glucose or thiamine was ineffective in reducing blood alcohol levels in rats with acute ethanol intoxication. However, the beneficial effect of thiamine as an antioxidant for ethanol metabolism was demonstrated. Further investigations are necessary to clarify the urinary excretion of ethanol reported here for the first time and the possibility of using thiamine as an antioxidant in situations of chronic alcohol use.

Effect of a thrombin receptor (protease-activated receptor 1, PAR-1) gene polymorphism in chronic hepatitis C liver fibrosis

Background and Aim: Tissue injury leads to activation of coagulation and generation of thrombin. Inhibition of thrombin receptor protease-activated receptor 1 (PAR-1) has been shown to reduce liver fibrosis in animals. This study aimed to evaluate the effect of PAR-1 gene polymorphism on rate of liver fibrosis (RF) in chronic hepatitis C. Methods: Polymorphisms studied: C > T transition 1426 bp upstream of translation start site (-1426C/T), 13 bp repeat of preceding -506 5`-CGGCCGCGGGAAG-3` sequence (-506I/D), and A > T transversion in intervening sequence (IVS) 14 bp upstream of exon-2 start site (IVS-14A/T). A total of 287 European and 90 Brazilian patients were studied. Results: 1426C/T polymorphism: There was a trend to higher RF in patients with the TT genotype (P = 0.06) and an association between genotype CC and slow fibrosis (P = 0.03) in Europeans. In males, RF was significantly higher in those with the TT genotype compared to CT (P = 0.003) and CC (P = 0.007). There was a significant association between TT and fast fibrosis (P = 0.04). This was confirmed in an independent cohort of Brazilians where RF was higher in TT than in CC (P = 0.03). Analysis of -506I/D showed no difference in RF and distribution of slow/fast fibrosis among different genotypes in both populations. Analysis of IVS-14A/T showed no difference between genotypes. Conclusion: In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis.

Creatine Supplementation Prevents the Accumulation of Fat in the Livers of Rats Fed a High-Fat Diet

The aim of the present study was to examine the effects of creatine supplementation on liver fat accumulation induced by a high-fat diet in rats. Rats were fed 1 of 3 different diets for 3 wk: a control liquid diet (C), a high-fat liquid diet (HF), or a high-fat liquid diet supplemented with creatine (HFC). The C and HF diets contained, respectively, 35 and 71% of energy derived from fat. Creatine supplementation involved the addition of 1% (wt:v) of creatine monohydrate to the liquid diet. The HF diet increased total liver fat concentration, liver TG, and liver TBARS and decreased the hepatic S-adenosylmethionine (SAM) concentration. Creatine supplementation normalized all of these perturbations. Creatine supplementation significantly decreased the renal activity of L-arginine:glycine amidinotransferase and plasma guanidinoacetate and prevented the decrease in hepatic SAM concentration in rats fed the HF diet. However, there was no change in either the phosphatidylcholine:phosphatidylethanolamine (PE) ratio or PE N-methyltransferase activity. The HF diet decreased mRNA for PPAR as well as 2 of its targets, carnitine palmitoyltransferase and long-chain acylCoA dehydrogenase. Creatine supplementation normalized these mRNA levels. In conclusion, creatine supplementation prevented the fatty liver induced by feeding rats a HF diet, probably by normalization of the expression of key genes of beta-oxidation. J. Nutr. 141: 1799-1804, 2011.

3.0-T MRI evaluation of patients with chronic liver diseases: initial observations

Purpose: To describe the use of 3.0-T magnetic resonance imaging (MRI) for the evaluation of chronic liver diseases. Materials and Methods: Two groups of patients who had chronic liver diseases and underwent 3.0-T MRI for evaluation of the liver were included in the study. The first group of patients included 66 consecutive patients (33 male, 33 female; mean age +/- standard deviation, 56 +/- 11). The second group of patients included 30 consecutive patients (18 males, 12 females; mean age +/- standard deviation, 53 +/- 10) in whom Variable-Rate Selective Excitation (VERSE) pulses and improved adjustments procedure were used during the acquisitions. Imaging findings of chronic liver diseases, predetermined artifacts and image quality of all individual sequences in the first group and predetermined artifacts and image quality of T2-weighted sequences in the second group were reviewed retrospectively and independently by two reviewers. chi-Square tests were used to compare the findings between two groups of patients and individual sequences. Kappa statistics were used to determine the extent of agreement between the reviewers. Results: Fifteen dysplastic nodules in 6 of 66 (9%) patients and 12 hepatocellular carcinomas in 11 of 66 (17%) patients were detected. Excluding motion artifacts, three-dimensional (313) T1-weighted gradient-echo (GE) sequence was the least affected sequence by the artifacts. Image quality of T1-weighted 3D-GE sequences was excellent in 43 of 66 (65%) patients. In-phase and out-of-phase T1-weighted spoiled GE (SGE) images were fair in 62 of 66 (94%) and 61 of 66 (92%) patients, respectively. The image quality of short tau inversion recovery (STIR) and half-Fourier rapid acquisition with relaxation enhancement (RARE) sequences were fair in 31 of 66 (47%) and 53 of 66 (80%) patients. STIR and half-Fourier RARE sequences in the second group demonstrated significantly better image quality (P=.03 and P<.0001). Conclusion: 3.0-T MRI allows the acquisition of very high quality postgadolinium 3D-GE sequence, which permitted the detection and characterization of lesions in the setting of chronic liver diseases. The use of VERSE pulses and improved adjustments procedure improved the image quality of T2-weighted sequences. In-phase/out-of-phase SGE sequences are at present of fair quality. (C) 2008 Elsevier Inc. All rights reserved.