FK 506 modulates D-galactosamine-induced hepatitis in rats.
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Alanine Transaminase↗
Biomedical subjects
A Gasbarrini
Publications and source records attributed to A Gasbarrini.
[Effect of CDP-choline on senile mental deterioration. Multicenter experience on 237 cases].
The efficacy of CDP-choline (1000 mg/die) administered for two 21-day treatment cycles, with a one-week wash-out period between them, was evaluated in out and in-patients suffering from mild to moderate brain aging. The study was performed on 237 fully evaluable patients with the use of the reduced geriatric scale of Plutchik and al., for clinical evaluation of the symptomatology. The clinical data obtained demonstrate that treatment with CDP-choline is able to determine an improvement of symptomatology since the 1st cycle of therapy (p less than 0.001), and a further improvement in the 2nd cycle (p less than 0.001). Particularly, the therapeutic effect of the 1st cycle is persistent in the intermediate wash-out period (suspension of treatment) with a further decrease, of symptomatology regarding some items of Plutchik's scale (p less than 0.01). Finally, treatment with CDP-choline 1000 mg/die for two 21-day cycles in 237 patients suffering from brain aging determined a statistically significant improvement of the cognitive and behavioural parameters taken into consideration: independence/autonomous life; human relations/social life; interest and attentive capacity; individual behaviour. Therefore citicoline is confirmed as a valid therapeutic remedy for the clinical, functional and social recovery of these patients.
Activities of Daily Living↗
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↗
Prenatal exposure to ethanol in rats: effects on liver energy level and antioxidant status in mothers, fetuses, and newborns.
The fetal alcohol syndrome is a clinical condition that affects newborns from alcoholic mothers. It is not clear, however, whether ethanol consumption during gestation can affect liver functions of fetuses and newborns. In this study, we aimed to assess the effects of ethanol administration on body weight, liver energy level, and antioxidant status of mothers, fetuses, and newborns. Pregnant rats were exposed to ethanol during the third week of gestation. Body weight, survival, and liver concentration of gluthatione (GSH) and adenosintriphosphate (ATP) were measured. No differences were observed in body weight or in liver ATP and GSH between mothers exposed to ethanol and control animals. Conversely, fetuses from rats exposed to ethanol showed a marked decrease in GSH, ATP, and body weight when compared to those from control rats. Newborns exposed prenatally to ethanol were no different from those born to control mothers. This study suggests that an amount of ethanol that is not sufficient to determine a significant effect on mothers can, nevertheless, cause a marked decrease in growth and in liver antioxidant and energy status in fetuses. These parameters, however, return to control value one week after ethanol discontinuation.
Adenosine Triphosphate↗
Helicobacter pylori is an aetiological factor for ischaemic heart disease: the case against.
Helicobacter pylori is one of four organisms often investigated for ari association with ischaemic heart disease. The four, including Chlamydia pneumoniae, Cytomegalovirus and Herpes virus, cause low-grade, life-long infections that can produce a persistent inflammation, the kind that leads to heart disease. Several studies suggest an association, but others suggest none. Patients with poor access to medical care are more likely to become infected and also more likely to suffer from coronary artery disease. Although the literature data are provocative and interesting, the two things may not be related. Helicobacter pylori infection is quite prevalent among individuals without ischaemic heart disease and absent in many of those with ischaemic heart disease. Thus, more definite answers about whether there is any link between Helicobacter pylori and cardiovascular disease are needed. It would be essential to establish the specific mechanisms that possibly confer vulnerability or protection toward coronaropathy. But a definite answer could come from clinical trials designed to test whether antibiotics can prevent the disease. Until now, no randomised trial has suggested a positive effect of Helicobacter pylori eradication in reducing the incidence of cardiac events.
Global Health↗
Metolazone-induced cholestatic liver disease.
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Adult↗
Helicobacter pylori and ischemic heart disease: current evidences.
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Helicobacter Infections↗
Six-day therapy with ranitidine bismuth citrate plus low-dose clarithromycin and tinidazole to cure Helicobacter pylori infection.
BACKGROUND/AIMS: Short-term ranitidine bismuth citrate-based triple regimens have been shown to be effective for the eradication of H. pylori. We investigated the efficacy of an eradicating therapy including ranitidine bismuth citrate, low-dose clarithromycin and tinidazole, administered for only 6 days. METHODOLOGY: Forty-five consecutive patients, who underwent gastroscopy for symptoms and were found to be H. pylori-positive, were recruited. They received ranitidine bismuth citrate 400 mg b.i.d. plus clarithromycin 250 mg b.i.d. plus tinidazole 500 mg b.i.d., given for 6 days. The medications given in twice daily doses were taken after meals with an interval of 12 h. The H. pylori status was evaluated by means of histology and rapid urease test on admission, and by 13C-urea breath test alone 8 weeks after treatment. RESULTS: All 45 enrolled patients completed the study. Thirty-nine of 45 patients returned H. pylori-negative (both per protocol and intention-to-treat analysis = 87%; 95% confidence interval = from 73-95%), while 6 of 45 were still H. pylori-positive (13%). Slight or mild side effects occurred in 5/45 patients (11%). CONCLUSIONS: Ranitidine bismuth citrate-based triple therapy, containing low-dose clarithromycin and tinidazole, given for only 6 days, yielded high eradication rates with modest side effects. Regimens based on ranitidine bismuth citrate plus two antibiotics at low dosages, administered for less than 7 days, constitute highly promising strategies for eradication of H. pylori.
Adult↗
Efficacy and tolerability of antibiotics in patients undergoing H. pylori eradication.
BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is one of the most common gastrointestinal diseases. An increasing number of people undergo different treatment options. Unfortunately, H. pylori therapy may be troublesome for drug side effects and inefficacious for resistance to antibiotics. METHODOLOGY: One hundred and ninety-three (193) H. pylori-positive patients were randomly assigned to one of the following 7-day treatments: Group A (N = 64): amoxicillin, clarithromycin and rabeprazole; Group B (N = 64): tinidazole, clarithromycin and ranitidine bismuth citrate; Group C (N = 65): tinidazole, clarithromycin and rabeprazole Eradication was assessed by 13C-Urea Breath Test 6-8 weeks after the end of the therapy. Not-eradicated patients underwent a second cycle with tinidazole, tetracycline, bismuth and rabeprazole. All patients were asked to complete a validated questionnaire regarding presence and intensity of drug side effects. RESULTS: One hundred and eighty-eight out of the 193 H. pylori-positive patients (96%) completed therapy. No significant difference in eradication rates was observed among the three groups both in intention to treat analysis and in per protocol analysis. No significant difference in incidence of side effects occurred among groups after the first-line regimens: 48% in group A, 44% in group B and 46% in group C. Twenty-two out of the 193 enrolled subjects (11%) were not eradicated after the first-line therapy. Among them, 86% were successfully eradicated by the tinidazole, tetracycline, bismuth and rabeprazole therapy. Moreover, during quadruple therapy, a higher prevalence and intensity of side effects than in each one of the groups submitted to the first-line triple therapy was observed. CONCLUSIONS: This study shows that triple rabeprazole-based eradicating regimens are effective and safe. Incidence of side effects seems low and similar in different three-drug regimens used. Quadruple therapy, which appear highly efficacious as a second line therapy, is associated with a significantly higher incidence of side effects when compared to first-line treatment.
Adult↗
An apparent idiopathic case of relapsing acute pancreatitis.
We describe a case of relapsing acute pancreatitis apparently idiopathic in a 55-year-old man. The patient did not smoke and was a modest and irregular drinker of wine. Endoscopic retrograde cholangiopancreatography showed an initial dilatation of secondary ducts like a chronic pancreatitis of class I of Cremer. Ultrasound and computed tomography resulted negative for pancreatic lesions. In the follow-up however, magnetic resonance cholangiopancreatography detected the presence of an intraductal mucin-hypersecreting neoplasm, a duct-ectatic mucinous cystic tumor of the pancreas, in the uncinate process. This is a benign lesion clearly recognized nowadays by magnetic resonance cholangiopancreatography, because this radiological technique shows the grape-like clusters of cystic lesions in secondary ducts communicating with the main duct on the same plane. The radiological picture above excludes a malignant lesion and a biopsy specimen is not required. Furthermore, an intraductal mucin-hypersecreting neoplasm of the pancreas does not require an immediate surgical resection because of its slow evolution and can be followed-up. Conversely cystoadenocarcinoma spreads in peripheral ducts and does not communicate with the Wirsung duct. It requires both surgical resection and a biopsy specimen for histological diagnosis. In the last episode of acute pancreatitis, a sphincterotomy was performed at endoscopic retrograde cholangiopancreatography and our patient had no more pain for one year.
Acute Disease↗
[Helicobacter pylori and gastric carcinoma].
Among the suspected bacterial causes of cancer, H. pylori is the agent more consistently linked to malignancy. After its discovery in 1983 and the later confirmation as the leading cause of chronic gastritis, several studies were performed to prove an association between H. pylori infection and gastric carcinoma. The epidemiological data have been so strong that in 1994 the International Association for Research on Cancer stated that "there was sufficient evidence" to classify H. pylori as a group I carcinogen in humans. However, the exact mechanisms underlying the link between H. pylori infection and gastric carcinoma remain still to be elucidated. The natural history of H. pylori infection shows that, although roughly half of the world's human population bears the organism, only a minority of individuals develop clinically important outcomes (e.g. peptic ulcer, lymphoproliferative diseases, atrophic gastritis and gastric carcinoma): host's genetic make-up, duration of infection, diet and differences between H. pylori strains have been proposed as factors potentially able to influence the outcomes in different individuals. The damaging agents by which H. pylori could promote gastric carcinogenesis are produced either by the organism or as a consequence of the host inflammatory response to the infection. Gastric mucosal chronic damage may, therefore, lead to changes in the pattern of epithelial cell kinetic (increase in cell proliferation and induction of apoptosis) in gastric glands which may induce DNA injury with irreversible genetic lesions. Finally, a direct association between H. pylori infection and the induction of gastric carcinoma has been recently demonstrated in an animal model, giving further credence to the role of this organism in gastric carcinogenesis.
Helicobacter Infections↗
Idiopathic chronic constipation: pathophysiology, diagnosis and treatment.
Constipation is one of the most common disease in Western countries. Its prevalence is widely variable (5-30%), depending on criteria utilized for diagnosis. Usually constipated patients have mild-moderate symptoms and are self-treated. Only patients that do not benefit from simple therapy (dietary supplementation of fiber and water, laxatives) need examinations such as blood tests, colonoscopy, radiography with bario-enemas, intestinal transit time and manometry. These tests are able to differentiate idiopathic from secondary constipation. Idiopathic chronic constipation is a collective term that involves different functional disorders. More specific investigations (oro-cecal transit time, manometry, electromyography) allow one to distinguish between two different patterns of idiopathic chronic constipation (slow transit constipation and pelvic floor disease) and to utilize the appropriate treatment of disease. The aims of this paper are to review the recent world literature on chronic constipation and to propose a diagnostic and a therapeutic flow chart for this disorder.
Chronic Disease↗