[Submicroscopic observations of the epithelial lining of human intestinal villus after small doses of x-rays].
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Adult↗
Biomedical subjects
G Gasbarrini
Publications and source records attributed to G Gasbarrini.
Plasma norepinephrine, weak neurotransmitters, and renin activity during active tilting in liver cirrhosis: relationship with cardiovascular homeostasis and renal function.
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Blood Pressure↗
Hepatocyte membrane-bound IgG and circulating liver-specific autoantibodies in chronic liver disease: relation to hepatitis B virus serum markers and liver histology.
Hepatocytes isolated from 101 biopsies were examined for membrane-bound IgG. The sera of the patients were tested for anti-liver-specific lipoprotein by radioimmunoassay and for liver membrane autoantibody (by indirect immunofluorescence on isolated rabbit hepatocytes. The seven patients with normal liver or minor nonspecific alterations were negative for membrane IgG and serum antibodies. Membrane IgG with granular distribution was found in 41 patients [21 hepatitis B virus-related chronic active hepatitis (CAH), 3 cryptogenic CAH, 3 chronic persistent hepatitis, 6 prolonged viral hepatitis, 1 alcoholic cirrhosis, and 6 primary biliary cirrhosis]. Membrane IgG with linear fluorescence pattern was detected in 12 cases (4 autoimmune CAH, 3 HBsAg-positive CAH, 2 alcoholic cirrhosis, 1 anti-HBc positive CAH, 1 cryptogenic CAH, and 1 prolonged viral hepatitis). A strong association between granular IgG and serum HBsAg was found. Nuclear localization of IgG was found in 34 patients and correlated with the positivity of granular membrane IgG. The highest prevalence of anti-liver-specific lipoprotein was found in primary biliary cirrhosis and autoimmune CAH cases which were also positive for liver membrane autoantibody. No relationship was found between the presence of membrane IgG and circulating liver-specific autoantibodies. Membrane IgG and anti-liver-specific lipoprotein correlated with the presence of moderate and severe portal inflammatory infiltration but not with piecemeal necrosis or transaminase levels. Eleven of the twelve patients with linear membrane IgG presented chronic active liver disease with moderate to severe signs of liver damage. Therefore, it is suggested that, while granular membrane IgGs are related to hepatitis B virus, antigenic expression on the hepatocyte surface and/or the presence of immune complexes, linear membrane IgG could play a role in the immunopathogenesis of liver cell damage particularly in "autoimmune" cases which present high percentages of positive cells liver-specific autoantibodies.
Adult↗
Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide.
Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. This is a potential advantage in the treatment of ascites in advanced cirrhosis since these patients have a low tolerance to sudden reductions of blood volume. Equivalent single, oral doses of furosemide (40 mg) and muzolimine (30 mg) were given to 10 cirrhotic patients with ascites and reduced renal perfusion (glomerular filtration rate = 30 to 75 ml per min). The study was preceded by 4 days of equilibration (dietary sodium 40 mmoles per day), and the drugs were alternated via a single-blind, cross-over protocol after a wash-out period of 3 days. Renal function was monitored under basal conditions and after diuretic administration through 4-hr clearance periods for 24 hr. The renin-aldosterone axis was evaluated before diuretic administration and after 8 and 24 hr. Muzolimine led to a 12-hr cumulative diuresis [AUC0-12 = 2.52 +/- 0.42 (S.E.) ml per min] and natriuresis (5.14 +/- 1.05 mmoles per hr), which were comparable to those of furosemide (2.85 +/- 0.29 ml per min and 6.75 +/- 1.63 mmoles per hr). Its effect, however, was distributed over a longer period (8 hr) than furosemide (4 hr). Muzolimine activity mainly differed from furosemide because of: significantly lower 12-hr potassium excretion (AUC0-12 = 0.28 +/- 0.82 vs. 2.69 +/- 0.46 mmoles per hr; p less than 0.005); greater sodium/chloride excretion ratio (0.45 +/- 0.08 vs. 0.26 +/- 0.06; p less than 0.025), and absence of rebound phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldosterone↗
Serum protease inhibitors in acute viral hepatitis.
Serum levels of alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-M) and, as controls, alpha 1-acid glycoprotein (alpha 1-AG) and haptoglobin were evaluated by means of laser nephelometry in 17 patients with acute viral hepatitis (AVH) type A, 16 with AVH-B, 12 with AVH-NANB and 8 with fulminant hepatitis B. On admission, alpha 1-AT levels were elevated in one third of AVH-A and AVH-B cases, but subsequently declined; alpha 2-M levels were elevated in about 40% of AVH-B patients during the 2nd, 3rd and 4th week after admission. No significant correlation was found between elevated levels of protease inhibitors and aminotransferase values or drug addiction and delta coinfection. alpha 1-acid glycoprotein and haptoglobin levels were always normal or low. Protease inhibitors did not show any elevation in fulminant hepatitis, while changes were found only in a few patients with AVH-NANB. Thus, no clearcut pattern of changes in protease inhibitors has been found in association with each type of hepatitis, although alpha 1-AT and alpha 2-M elevations are mainly found in AVH-B.
Acute Disease↗
Serum binding activity for polymerized human albumin due to antibodies detected by enzyme-linked immunosorbent assay in acute and chronic type B, A and NANB viral hepatitis.
Polymerized human serum albumin (pHSA) binding activity due to antibodies was evaluated by a sensitive and specific enzyme-linked immunosorbent assay (ELISA) in well characterized cases of acute (AVH) and chronic active (CAH) viral hepatitis. Moreover, hepatitis B virus (HBV) infection serum samples were tested for the presence of HBsAg-associated pHSA receptors detected by radioimmunoassay. Specificity of ELISA in detecting pHSA binding activity due to antibodies was assayed by testing IgG fractions from positive serum samples and purified HBsAg particles. A very high prevalence (mean = 87%) of antibody response to pHSA was detected in serum samples of patients with type B, A and post-transfusion non-A, non-B (NANB) AVH and CAH. IgM antibodies were found in 75% of type B AVH, in 77% of type A AVH and in none of the NANB cases at the onset of illness. In CAH, IgM antibodies were found in 37.5% of HBsAg-positive cases and in 44% of NANB cases. In HBV-related AVH and CAH no correlation was found between anti-pHSA antibodies and HBsAg-associated pHSA receptors or the HBeAg/anti-HBe status. The antibody response detected by ELISA showed a cross-reactivity with monomeric human albumin and heterologous polymeric and monomeric albumins. However, in HBV infection the antibody binding was significantly higher for pHSA than for monomeric human albumin or albumins from other species, thus suggesting that the antigenic sites of pHSA evoking the antibody response may differ in relation to the etiology of viral hepatitis.
Autoantibodies↗
Clinical significance of antibodies to polymerized human albumin detected by enzyme-linked immunosorbent assay.
Antibodies directed against glutaraldehyde-polymerized human serum albumin (pHSA) were tested by a sensitive and specific enzyme-linked immunosorbent assay (ELISA) in serum samples from 196 patients with various hepatic and non-hepatic diseases and in 38 healthy control subjects. A very high prevalence (80.1%) of antibody response was found in the patient group, ranging from 60% in type non-A, non-B (NANB) chronic active hepatitis (CAH) and lymphomas to 95.5% in hemodialysis patients. A higher prevalence of anti-pHSA antibodies was found in hepatitis B virus (HBV)-related CAH and hemodialysis patients compared with NANB-related CAH, collagen diseases and lymphomas. Anti-pHSA antibodies were most frequent in HBsAg-positive cases, but no correlation between antibody response and the HBeAg/anti-HBe status was found among these patients. Anti-pHSA antibodies did not correlate with HBsAg-associated pHSA receptors determined by radioimmunoassay (RIA). Moreover, a significantly higher pHSA receptor expression was found in HBV-related CAH and hemodialysis patients compared with chronic HBsAg carriers and in HBeAg-positive patients compared with HBeAg-negative cases. The anti-pHSA response seems to be related to the presence of immunoregulation disorders which may be induced by several causes, such as autoimmunity and viral infections. In particular, as far as the HBV infection is concerned, there is no evidence that circulating anti-pHSA antibodies interfere with the natural course of the disease.
Autoantibodies↗
Role of prostaglandin E2 on defective interferon-gamma production during type B acute viral hepatitis.
Interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) production was evaluated in cultured peripheral blood mononuclear cells taken from patients with type B acute viral hepatitis at the onset of symptoms, at 1st and 2nd week of disease, and from healthy controls. Concanavalin A-stimulated cells cultured for 24, 48 and 72h showed significantly higher IFN-gamma levels compared to basal release in both groups, whereas no statistically significant differences were found in most experimental conditions as regard PGE2 synthesis. No differences were found in IFN-gamma production by comparing patients with acute viral hepatitis to the control group, whereas PGE2 was significantly increased during the disease. IFN-gamma and PGE2 levels did not show any significant change in acute viral hepatitis during the follow-up. A statistically significant correlation was found only in control group between IFN-gamma and PGE2 levels in unstimulated cultures. PGE2 seems to play a central role in regulating interferon production during viral infection. This may suggest a new therapeutic approach in viral hepatitis utilizing a combination of interferon and prostanoid inhibitory substances, above all in patients who do not respond to interferon therapy alone.
Acute Disease↗
Improvement of mortality rate and decrease in histologic hepatic injury after human cord blood stem cell infusion in a murine model of hepatotoxicity.
BACKGROUND AND AIMS: Because of their plasticity potential local and systemic application of cord blood stem cells may represent excellent candidates for cell-based therapeutic strategies in toxic liver injuries. It is already known that intraperitoneal administration of hematopoietic stem cells provides rapid liver homing in animal models of hepatic injury. We sought to assess the efficacy of a hematopoietic stem cell infusion to decrease the histologic damage and the mortality rate of animals previously damaged by allyl alcohol. MATERIAL AND METHODS: NOD/SCID mice were divided into two groups. (1) animals treated by intraperitoneal administration of allyl alcohol and (2) animals treated with allyl alcohol and 24 hours later with an intraperitoneal infusion of human cord blood cells. Flow cytometry, histology, immunohistochemistry, and RT-PCR were performed to monitor human cell engraftment by evidences of human hepatic markers. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, improve liver regeneration after damage, and reduce the mortality rate even when requiring qualitative and quantitative differences in the transdifferentiation processes. The mortality rate decreased from 70% to 20%, with a significant improvement in the histologic findings. CONCLUSION: We demonstrated that the infusion of hematopoietic stem cells into the liver in the early stage of damage might initiate endogenous hepatic tissue regeneration that oppose the injury inflicted by toxicants.
Animals↗
Improvement of mitochondrial function evaluated by ketoisocaproic acid breath test in patients with HCV infection undergoing albumin dialysis.
BACKGROUND AND AIM: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. MATERIALS AND METHODS: Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). RESULTS: MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion. CONCLUSION: Liver mitochondrial function appears to be beneficially affected by MARS treatment.
Adult↗
Transdifferentiation of stem cells in pancreatic cells: state of the art.
Among the different approaches for diabetes mellitus-pancreas and pancreatic islet transplantation-the use of stem cells represent a renewable alternative source of insulin-producing cells. Stem cells capable of differentiating into beta-like cells can be isolated namely from embryonic cells, bone marrow, and umbilical cord blood, but also from adult organs such as pancreas, liver, and spleen. Several studies have demonstrated that by manipulating culture conditions and using growth and transcription factors of beta-cell lineage (in particular pdx-1 and pax4), embryonic stem cells can differentiate in vitro after formation of embryoid bodies. Bone marrow stem cells can give rise to mesenchymal; endodermal-, and ectodermal-derived cells. In vivo it has been shown that after bone marrow transplantation, using a murine sex-mismatched model, insulin-producing cells expressing the Y chromosome can be detected in the donor pancreas, although not in a significantly number. Cells characterized by a group of markers (Nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) important for beta-cell differentiation have been detected in umbilical cord blood. The recent evidence of the possibility to transdifferentiate stem cells to beta cells encourages further studies in animal models to exhaustively determine the differentiation pathways of stem cells to insulin producing cells. These findings might open the way to a successful human investigation.
Adult↗
The decrease in cytokine concentration during albumin dialysis correlates with the prognosis of patients with acute on chronic liver failure.
BACKGROUND AND AIM: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. MATERIALS AND METHODS: Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). RESULTS: MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related. CONCLUSIONS: We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.
Adult↗
Catholic university experience with molecular adsorbent recycling system in patients with severe liver failure.
BACKGROUND AND AIM: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. MATERIALS: Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients. RESULTS: MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. CONCLUSIONS: Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.
Bilirubin↗
No evidence of hematopoietic stem cell mobilization in patients submitted to hepatectomy or in patients with acute on chronic liver failure.
BACKGROUND: Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. METHODS: We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. RESULTS: White blood cell counts remained in the normal range (4.1-9.8 x 10(9)/L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. CONCLUSIONS: Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.
Adult↗
Human cordonal stem cell intraperitoneal injection can represent a rescue therapy after an acute hepatic damage in immunocompetent rats.
BACKGROUND AND AIM: Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. MATERIALS AND METHODS: Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. RESULTS: Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. CONCLUSIONS: Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.
Animals↗
Scalloped duodenal folds in childhood celiac disease.
Unlike the adult form, childhood celiac disease has not hitherto been associated with a particular endoscopic pattern. The upper gastrointestinal tracts of 46 children with various stages of celiac disease and of 27 children with conditions other than celiac disease were examined by an endoscopist unaware of the clinical details of the patients. The scalloped configuration of duodenal folds was shown to have a sensitivity of 88% and a specificity of 87% in the diagnosis of subtotal villus atrophy. Attention to this finding, described here for the first time in childhood celiac disease, may be helpful for the diagnosis of this condition.
Adolescent↗
Enteroscopy and celiac sprue.
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Celiac Disease↗
Duodenal folds and untreated adult celiac disease.
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Adult↗