Protective Effect of Oral Acetylcysteine against the Hepatorenal Toxicity of Carbon Tetrachloride Potentiated by Ethyl Alcohol

Considering the well-documented protection of acetylcysteine (AC) in hepatotoxicity related to acetaminophen, we studied the preventive potential of AC against mild hepatotoxicity of CCl4, potentiated with ethyl alcohol (ETH) and the role of tissue glutathione. Rats fed a liquid diet with 30% of energy from ETH, had-intraperitoneal CCl4 administered in three injections, at 7-day intervals. AC was ingested at the level for acetaminophen overdose. ETH markedly potentiated the injury induced by CCl4, as evidenced by higher values of serum alanine aminotransferase (ALT), urinary bile acids (BA), serum creatinine, histological score of liver cell necrosis, mortality and by lower body weights and lower liver glutathione, when compared with CCl4 alone. Protective effect of AC consisted of a lesser hepatocytic necrosis, better body weights and higher liver glutathione. We conclude, that AC favorably modifies liver damage induced by CCl4 and potentiated with ETH. There is a preventive role for AC in subjects who combine ETH overuse with exposure to hepatotoxic xenobiotics, whose toxicity is modified by tissue glutathione.     

Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-β1–induced collagen synthesis

Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid by cyclooxygenases (COX) and synthases (PGES), acts as both an inflammatory mediator and fibroblast modulator. Although PGE2 has known antifibrotic effects in the lower airway, its role in dermal fibrosis in general, and keloid formation in particular, remains unclear. This study focused on: (1) the effects of PGE2 on keloid fibroblast migration, contraction, and collagen synthesis and (2) endogenous PGE2 synthesis in response interleukin-1beta. PGE2 decreased keloid fibroblast migration and contraction via an EP2/EP4-cAMP mechanism that disrupted actin cytoskeletal dynamics and reversed transforming growth factor-beta1-induced collagen I and III synthesis. Impaired fibroblast PGE2 production has been linked to lower airway fibrosis and recently to keloid formation. Here, we showed that interleukin-1beta stimulation leads to nuclear factor-kappaB translocation to the nucleus, resulting in up-regulation of COX-2 and microsomal PGE2 synthase 1. Up-regulation of COX-2 in, and secretion of PGE2 by keloid fibroblasts are diminished compared with their normal fibroblast counterparts. We suggest that the antifibrotic effects of PGE2 during keloid formation are potentially diminished due to aberrant paracrine fibroblast signaling. Exogenous PGE2 may supplement decreased endogenous levels and inhibit keloid formation or progression.     

Infectious lymphocytes in lymphocytic choriomeningitis virus carrier mice.

The infectivity of blood and lymphoid organs of mice persistently infected with lymphocytic choriomeningitis virus was found to be predominantly associated with lymphocytes and both T and B cells were infectious. A hypothesis is presented in which it is assumed that lymphocytes in carrier mice are infected via their LCM virus-specific antigen receptors, thereby leading to their antigen-triggered clonal expansion followed by infection and functional inactivation.     

The epithelial-mesenchymal transition induces aggressivity of mucinous cystic neoplasm of the pancreas with neuroendocrine component: An immunohistochemistry study

Background

Pancreatic mucinous cystic neoplasms (MCN) are rare tumors that are usually diagnosed in females.

Heterogeneity of Borrelia burgdorferi sensu lato demonstrated by an ospA-type-specific PCR in synovial fluid from patients with Lyme arthritis

Borrelia burgdorferi sensu lato, the etiological agent of Lyme borreliosis, has been divided into three genospecies: B. burgdorferi sensu stricto (OspA-type 1), B. afzelii (OspA-type 2) and B. garinii (OspA-type 3–7). Whereas in Europe B. afzelii (OspA-type 2) is predominant among human skin isolates and B. garinii (OspA-type 3–7) among human CSF isolates, some previous serological studies suggested that Lyme arthritis is also associated with B. burgdorferi sensu stricto in Europe. In the present study we designed ospA type-specific PCRs and identified four different ospA types associated with Lyme arthritis. Our study group consisted of 20 patients with positive serology (ELISA and immunoblotting) and clinical criteria for Lyme arthritis. B. burgdorferi DNA was detected in 13 patients and in none of 10 control patients from synovial fluid. We identified ospA-type 1 (26.6%), ospA-type 2 (33.3%), ospA-type 4 (6.6%) and ospA-type 5 (33.3%). Our conclusion is that in Europe B. burgdorferi sensu lato strains causing Lyme arthritis are considerably heterogeneous and that there is no prevalence of certain genospecies or OspA-types among this strains. Received: 14 May 1998     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

Viability assessment and utilization of declined donor kidneys with rhabdomyolysis using ex vivo normothermic perfusion without preimplantation biopsy

The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m²), at 2 months posttransplant.     

BCL-2--general considerations

BCL-2 protein is a oncoprotein considered to have an important role in the regulation of programmed cell death--apoptosis. The intracellular localization, the relation with other oncoproteins, the antioxidant function and the pathological implications are discussed.     

The xenotransplantation of goat and human hematopoietic cells to sheep fetuses

Hematopoietic xenografts were carried out in three experiments using goat fetal liver (44-48 days, experiments I and II) or purified human CD 34+ cells (experiment III) as the donor cells. Recipients were sheep fetuses at 41-47 days of gestation. Goat fetal liver cells were either injected without any pretreatment or stimulated by preincubation in a culturing in goat phytohemagglutinin-stimulated lymphocyte supernatant. Human CD 34+ myeloid progenitor cells were purified from bone marrow by minimacs immunomagnetic purification and cultured in medium supplemented with stem cell factor, IL3, and IL6. Goat-sheep chimerism was assessed by flow cytometry analysis (FCA) of peripheral blood and bone marrow cells using a mouse anti-goat CD 45 monoclonal antibody and by karyotype analysis of peripheral blood from goat/sheep chimeras. Human cell engraftment was assessed by polymerase chain reaction amplification of the human DAX1 gene in blood and bone marrow DNA from sheep which had received human cells. In the three experiments, a mean of 76% (26 of 34) of injected fetuses were born alive without any clinical evidence of graft-versus-host disease. Three lambs were found to be goat/sheep chimeric after flow cytometry analysis (peripheral blood and bone marrow) and karyotype (peripheral blood) analysis. Both tissues continued to express goat cells at 6 or 12 months (last assessment) depending on the experiment. No human chimerism was detected using polymerase chain reaction amplification in peripheral blood and bone marrow of any of the six sheep grafted with human cells. These data and those also obtained on other species (human, pig/sheep) show that it is possible to carry out hematopoietic xenografts using the sheep fetus as recipient provided both donor and recipient fetal cells are processed during the period of tolerance to foreign antigens.