Development of hepatorenal syndrome in bile duct ligated rats

AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology. METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats wereplaced in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue. RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including signif icant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic f ibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue. CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.

Changes in cellular proliferation and plasma products are associated with liver failure

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute hepatitis.METHODS Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTS The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

Intrauterine Exposure to Chronic 22 kHz Sound Affects Inhibitory Avoidance and Serotonergic Parameters in Forebrain Areas of Dams and Rat Offspring

In the present study we evaluated the effects of chronic exposure to sounds at 22 kHz during pregnancy on the central serotonergic and behavioral parameters in Wistar rat dams after the suckling period and on their male rat offspring. In addition, we also assessed the effects of an acute 22 kHz sound, associated with the chronic intrauterine exposure, on the emotional responses of adult offspring. The primary hypothesis was that experiencing 22 kHz stimuli during an early stage of development would interfere with brain serotonergic parameters and, later, with the adult rat’s defensive responses. The corollary question was whether a 22 kHz sound exposure would differentially affect inhibitory avoidance and escape responses and central serotonergic parameters. Female rats were divided into four groups: non-pregnant control;non-pregnant chronic exposure;pregnant control;and pregnant chronic exposure. Male offspring were divided into four groups: chronic intrauterine sound exposure;acute sound exposure in adulthood;chronic intrauterine exposure with acute exposure in adulthood;and no exposure. Chronic sound exposure affected inhibitory avoidance and serotonergic parameters in female rats. For offspring, there was an interaction between chronic and acute sound exposure effects on inhibitory avoidance response but not on escape response. There were significant effects of chronic intrauterine exposure on serotonin turnover in the hippocampus and PFC of females. For offspring, the turnover was increased by chronic exposure only in PFC, and in amygdala it was increased by acute exposure. These results illuminate the potential of an early acoustic sound exposure for causing central serotonergic and emotional behavioral changes that can persist into later periods of life.

Isolation of Filamentous Fungi from the Caatinga Region and Production of Amylolytic Enzymes of Great Industrial Interest

The industrial importance and the high cost of the commercial amylase require the study of microorganisms that produce these enzymes. For this reason, the objective of this work was to isolate filamentous fungi from a region of the caatinga and evaluate their potential for the production of amylase. Four soil samples were collected from a deactivated dump located in the city of Diamantina, MG, in a region of the caatinga. The analysis of amylolytic production in a submerged medium at the ideal temperature of each microorganism was performed using the saccharification method, and the reducing sugars formed were quantified by DNS. Fourteen filamentous fungi were isolated, which had different morphological aspects. Regarding amylase production, a mean activity of 0.477 U·mL-1 was obtained with the isolates I 1.2.1 and I 4.4.1. These results bring important information regarding the biodiversity of the caatinga, in addition to the isolation of microorganisms that can be used as biological machinery to obtain metabolites with high biotechnological and industrial potential.