Treatment of alcoholic fatty liver: is the metabolic effect of metadoxine the only reason for improved liver function?
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Biomedical subjects
Publications and source records attributed to G Gasbarrini.
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Dermatitis herpetiformis is a gluten-sensitive skin disease with intestinal lesions and malabsorption symptoms less severe than those found in celiac disease. While several studies have shown the occurrence of osteopenia in celiac disease, bone mass and metabolism have never before been evaluated in dermatitis herpetiformis. Therefore, in 16 untreated patients, 16 sex- and age-matched untreated celiac patients, and 16 sex- and age-matched healthy volunteers, lumbar and femoral bone mineral density were measured and bone and mineral metabolism and nutritional status were evaluated. All these parameters were significantly altered in the two groups of patients and although the degree of these alterations was milder in patients with dermatitis herpetiformis than in celiac patients, the presence of subtotal villous atrophy in patients with dermatitis herpetiformis was associated with the presence of more severe alterations. Bone mineral density was significantly correlated with nutritional status, and patients showing bone loss were characterized by a body mass index lower than 20. Alterations of bone mass and mineral metabolism complicate dermatitis herpetiformis when severe intestinal lesions coexist. A low nutritional status may be predictive of the presence of bone loss.
We compared the efficacy of two therapies to eradicate H. pylori infection including ranitidine bismuth citrate (400 mg twice daily), clarithromycin (500 mg twice daily), and tinidazole (500 mg twice daily), administered for six or seven days. Eighty H. pylori-positive patients were consecutively recruited and randomly subdivided into groups A and B, receiving one of the two treatment regimens. The H. pylori status was evaluated by means of histology and rapid urease test at entry, and by [13C]urea breath test alone eight weeks after treatment. All 40 patients in group A and 39/40 in group B completed the study. Thirty-six of 40 patients in the group A (90%) and 36 of 39 in the group B (92%) became H. pylori-negative. Slight or mild side-effects occurred in 4/40 patients (10%) of group A and in 5/39 (13%) of group B. In conclusion, both regimens we tested yielded high eradication rates with modest side effects. This is the first trial investigating a triple-drug RBC-based regimen administered for only six days.
BACKGROUND: Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin-resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance. AIM: To measure body composition, whole body glucose uptake and oxidation in Crohn's disease and ulcerative colitis patients with inactive disease. METHODS: All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn's disease (five males, aged 31.1 +/- 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 +/- 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group. RESULTS: Crohn's disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (micromol/kg/min) was found between groups (respectively 42.5 +/- 6.78 in Crohn's disease, 40.2 +/- 8.00 in ulcerative colitis and 41.4 +/- 10.8 in control subjects). Glucose storage and oxidation did not differ between groups. CONCLUSION: Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat-free mass preservation and low blood and tissue cytokine concentration.
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BACKGROUND: Between peripheral blood and tissue-infiltrating lymphocytes there is an intermediate compartment, the blood of the organ-draining vessels, which could show unusual features. The aim of the present study was to analyse the characteristics of the lymphocytes from the stomach-draining vessels and the cytokine secretion by these lymphocytes. The CagA-mediated lymphocyte activation in Helicobacter pylori-infected subjects and the humoral response to this antigen were evaluated and correlated with clinical data. METHODS: We studied lymphocyte proliferation either with mitogens or with the CagA antigen and cytokine production and IgG anti-CagA by means of an enzyme-linked immunosorbent assay in peripheral blood and gastric-vein blood obtained during surgical intervention. RESULTS: We showed higher proliferative response and cytokine production in lymphocytes from the gastric vein. The mitogenic response to the CagA antigen was highly specific but poorly sensitive for the H. pylori infection in both the compartments. The overall cytokine profile in our patients affected by non-ulcer disease was of the Th0 type. CONCLUSIONS: Gastric-vein-derived lymphocytes seem to show unusual features, as they behave like peripheral blood lymphocytes but show higher responses to all the tested stimuli. It is possible that the interaction of the lymphocytes with the mucosal environment could activate the synthetic mechanisms, making the cells more 'responsive' to the stimulation. The CagA antigen is able to induce a specific T-lymphocyte response and is therefore a valid candidate antigen for the development of a vaccine.
OBJECTIVE: Aim of the present study is to evaluate the effects of L-carnitine on insulin-mediated glucose uptake and oxidation in type II diabetic patients and compare the results with those in healthy controls. DESIGN: Fifteen type II diabetic patients and 20 healthy volunteers underwent a short-term (2 hours) euglycemic hyperinsulinemic clamp with simultaneous constant infusion of L-carnitine (0.28 micromole/kg bw/minute) or saline solution. Respiratory gas exchange was measured by an open-circuit ventilated hood system. Plasma glucose, insulin, non-esterified fatty acids (NEFA) and lactate levels were analyzed. Nitrogen urinary excretion was calculated to evaluate protein oxidation. RESULTS: Whole body glucose uptake was significantly (p<0.001) higher with L-carnitine than with saline solution in the two groups investigated (48.66+/-4.73 without carnitine and 52.75+/-5.19 micromoles/kg(ffm)/minute with carnitine in healthy controls, and 35.90+/-5.00 vs. 38.90+/-5.16 micromoles/kg(ffm)/minute in diabetic patients). Glucose oxidation significantly increased only in the diabetic group (17.61+/-3.33 vs. 16.45+/-2.95 micromoles/kg(ffm)/minute, p<0.001). On the contrary, glucose storage increased in both groups (controls: 26.36+/-3.25 vs. 22.79+/-3.46 micromoles/kg(ffm)/minute, p<0.001; diabetics: 21.28+/-3.18 vs. 19.66+/-3.04 micromoles/kg(ffm)/minute, p<0.001). In type II diabetic patients, plasma lactate significantly decreased during L-carnitine infusion compared to saline, going from the basal period to the end-clamp period (0.028+/-0.0191 without carnitine and 0.0759+/-0.0329 with carnitine, p<0.0003). CONCLUSIONS: L-carnitine constant infusion improves insulin sensitivity in insulin resistant diabetic patients; a significant effect on whole body insulin-mediated glucose uptake is also observed in normal subjects. In diabetics, glucose, taken up by the tissues, appears to be promptly utilized as fuel since glucose oxidation is increased during L-carnitine administration. The significantly reduced plasma levels of lactate suggest that this effect might be exerted through the activation of pyruvate dehydrogenase, whose activity is depressed in the insulin resistant status.
BACKGROUND: Although malnutrition is frequently observed in Crohn disease (CD), its cause is not clear. Regulation of energy metabolism and diet-induced thermogenesis (DIT) have not been adequately studied in CD. OBJECTIVE: The aim was to study DIT and substrate oxidation in patients with inactive ileal CD. DESIGN: After a test meal providing 50.2 kJ/kg body wt, DIT was assessed by indirect calorimetry performed over 360 min in 18 CD patients and 12 healthy volunteers matched for age, sex, weight, and height. Body composition was evaluated with the labeled-water-bolus injection technique. RESULTS: Fat-free mass did not differ significantly between groups, but CD patients had markedly lower fat mass than control subjects (13.8+/-5.63 compared with 19.0+/-3.49 kg; P < 0.001). Nonprotein respiratory quotient was lower in CD patients than control subjects (0.80+/-0.04 compared with 0.86+/-0.03; P < 0.001). Average respiratory quotient between 75 and 150 min after the test meal was 0.85+/-0.03 in CD patients and 0.91+/-0.02 in control subjects (P < 0.001). Lipid oxidation rate was higher in CD patients than in control subjects (2.26+/-1.13 compared with 1.50+/-0.75 kJ/min; P < 0.05). DIT was higher in CD patients than in control subjects (9.89+/-1.93% compared with 5.67+/-0.91% of energy intake; P < 0.001). CONCLUSIONS: Patients with inactive ileal CD had significantly higher DIT and lipid oxidation rate than do healthy volunteers. These results may explain why CD patients have difficulty maintaining adequate nutritional status, and the findings also suggest that a diet relatively rich in fat may attain better energy balance.
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BACKGROUND: Nutritional evaluation of elderly people is of great importance. Two-component methods for body composition assessment, such as anthropometry and bioelectrical impedance (BIA), are widely used in clinical practice, but their fundamental assumptions may be invalid in older people. Dual-energy X-ray absorptiometry (DXA) is a relatively new method for reliable and direct measurements of body mass in its three basic components: total body bone mineral content (TBBMC), mineral free lean tissue mass (LTM), and fat. In this study, percent body fat (%BF) estimates from anthropometry and BIA in men of various ages were compared with corresponding measurements by DXA. METHODS: Body fat percentage was estimated in 67 men aged 20-95 by anthropometric measurements (skinfold thickness, body mass index, or BMI), BIA, and DXA. Age-specific equations were used for anthropometry and BIA. Limits of agreement were calculated between DXA and the other methods. RESULTS: The equations based on BMI and BIA systematically overestimated %BF with respect to %BF measured by DXA in people of all ages. Intermethod difference between DXA and skinfold thicknesses was less marked, but in over-80-year-olds %BF predicted by skinfold measurements underestimated %BF measured by DXA. Interindividual and age-related variation in TBBMC and in fat-free mass mineralization could partly explain the intermethod differences found between DXA and the other methods. CONCLUSIONS: Because of practical constraints, anthropometry and BIA are often the only available options for body composition assessment in clinical routine; therefore, further research on the validity and improvement of these methods in older people is indicated.
Mucosa-associated lymphoid tissue is absent physiologically in normal gastric mucosa, but it can develop in some pathologies (dyspepsia, celiac disease, autoimmune diseases) due to certain (Helicobacter pylori, gluten) or uncertain (viruses?) antigenic stimuli. Its importance is related to the consideration that it is the background for the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and its histologic progression to MALT lymphoma may be diagnosed using Isaacson's score. Monoclonal bands can be diagnosed in acquired gastric MALT as well as in gastric MALT lymphoma, but its role is unknown. To prevent development of MALT lymphoma from acquired MALT, currently anti-H. pylori treatment in all H. pylori- and MALT-positive patients is not suggested--only in patients with grade 3 of acquired MALT--due to the high risk of developing MALT lymphoma in these patients. At the same time, the etiology of gastric MALT in autoimmune extragastric diseases is not clear. Additional studies are needed to clarify this relation and its possible causes.
The liver can be considered an ideal target to design gene therapy strategies because of the unique properties of hepatic cells. The great amount of work carried out in this field clearly delineates the quality of the new approaches that have been developed in the last few years and demonstrates the feasibility of this strategy in a wide range of multi-factorial and inherited disorders. However, improvement of current vectors to specifically and efficiently deliver the therapeutic gene into the target cell remains a daunting problem. In this review, we will summarize the most important approaches that are currently under investigation, the pathological conditions that can be treated by this strategy and the most important drawbacks that remain to be overcome in order to achieve long-term and high-level gene expression.
BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; however, antibiotic absorption may be influenced by the disease. Helicobacter pylori, the most common gastric infection worldwide, is the main acquired factor in the pathogenesis of gastritis and peptic ulcer. The aim of the study was to compare the H. pylori eradication rate obtained with a standard 7-day antibiotic regimen in a group of IDDM H. pylori infected patients and in a control group of infected dyspeptic patients. METHODS: Thirty-one patients (18 male, 13 female, 39+/-12 years) affected by IDDM and H. pylori infection, and 50 dyspeptic infected patients (23 male, 17 female, 37+/-10 years) were evaluated. H. pylori infection was assessed through 13C-urea breath test. A triple therapy with amoxycillin (1 g b.i.d.), clarithromycin (250 mg t.i.d.) and pantoprazole (40 mg b.i.d.) was given to both groups at the time of diagnosis for 7 days. Cure was defined as the absence of H. pylori infection, assessed by 13C-urea breath test, 6 weeks after completing anti-microbial therapy. Effects of H. pylori eradication on gastrointestinal symptoms (pyrosis, epigastric pain, belching, bloating, halitosis and nausea) were also evaluated. RESULTS: All enrolled patients completed the study. When compared to dyspeptic patients, the eradication rate was significantly lower in IDDM patients: 92% (46/50) versus 65% (20/31), respectively (P < 0.002). IDDM patients infected by H. pylori showed a different prevalence of some of the gastrointestinal symptoms assessed when compared to the infected dyspeptic patients; in particular, pyrosis, epigastric pain and belching were significantly more prevalent in the infected dyspeptic group. After H. pylori eradication, both groups showed a significant reduction of the intensity of all the gastrointestinal symptoms evaluated, except for nausea. CONCLUSIONS: IDDM patients showed a significantly lower H. pylori eradication rate when compared to that observed in dyspeptic subjects. The dosage and/or the duration of a standard eradication regimen does not appear to be sufficient to eradicate the infection in IDDM patients. The impairment of the gastrointestinal mucosa microvasculature with a reduction of antibiotic absorption, or the frequent use of antibiotics for other infections with development of resistant strains, may be the mechanisms underlying the observation.
OBJECTIVE: Peptic stenosis, a complication of peptic ulcer disease, is treated by endoscopic balloon dilation or surgery. However, recent reports showed that Helicobacter pylori eradication may resolve peptic stenosis. Thus, we carried out a prospective study on a cohort of patients with peptic stenosis and H. pylori infection to evaluate the efficacy of anti- H. pylori therapy in the treatment of peptic stenosis. DESIGN/METHODS: From May 1995 to May 1998 we studied 22 consecutive patients with benign peptic stenosis (16 with duodenal stenosis and six with pyloric stenosis) and H. pylori infection. Searches for H. pylori were made at first diagnosis of peptic stenosis and at every endoscopic control. All patients were treated with an anti- H. pylori treatment (13 with omeprazole/clarithromycin/ metronidazole and nine with omeprazole/amoxycillin/ clarithromycin), followed by 8 weeks' therapy with a proton-pump inhibitor. Endoscopic controls were performed after the end of H. pylori-eradication therapy, at 2 and 6 months, and then every 6 months. RESULTS: H. pylori eradication was achieved in all patients. Peptic stenosis disappeared completely in 20/22 cases (17/20 after 2 months and 3/20 after 6 months), and in all these patients the symptoms disappeared within 2 months. At the median follow-up of 12.4 months (range 2-24), the patients remained asymptomatic, without recurrence of the stenosis, and needed no medication. In one patient the stenosis disappeared partially and symptoms improved, and it was successfully treated with cisapride. In one patient the stenosis did not disappear despite H. pylori eradication and continuous proton-pump inhibitor treatment. The patient was treated with a liquid diet due to old age, but he died 4 months after H. pylori eradication due to stroke. CONCLUSIONS: H. pylori eradication is a safe and effective therapy for peptic stenosis. Endoscopic balloon dilation or surgery should be used only after failure of this conservative treatment.
OBJECTIVE: To evaluate the predictive value of demographic and clinical features and of the results of an office-based test for Helicobacter pylori antibodies, in the presence of organic dyspepsia. DESIGN: Over a 1-week period, 2206 consecutive patients first referred for endoscopy in 246 Italian centres were included. METHODS: Demographic and clinical features, endoscopy findings, and histological diagnosis of H. pylori infection were recorded for all patients. IgG antibodies to H. pylori were determined in 2128 cases by a rapid, immunochromatographic method (Flex Sure HP, S.K.D., San Jose, CA). RESULTS: Endoscopic abnormalities were found in 939 patients (42.6%). Histologically assessed H. pylori infection was predictive for duodenal ulcer (odds ratio (OR), 6.79; 95% confidence interval (CI), 4.4-10.5). Being male (OR, 1.97; 95% CI, 1.7-2.3), older than 40 years (OR, 1.81; 95% CI, 1.5-2.2), a smoker (OR, 1.88; 95% CI, 1.6-2.3), and presenting nocturnal awakening (OR, 1.62; 95% CI, 1.3-2.0) were independently associated with secondary dyspepsia. Epigastric (OR, 1.50; 95% CI, 1.2-1.9) and retrosternal pain (OR, 1.39; 95% CI, 1.1 -1.8) severe enough to affect the usual activities were predictive of organic diseases. The results of the Flex Sure HP test correlated poorly with histological findings. CONCLUSIONS: Male gender, older age, cigarette smoking, a family history of peptic ulcer, symptoms severe enough to induce awakening, epigastric/retrosternal pain severe enough to influence the usual activities are all independently (although weakly) associated with organic dyspepsia. H. pylori infection is strongly associated with duodenal ulcer, but the rapid test we used was not sensitive enough to achieve clinical utility.
BACKGROUND: At present few data are available on the total body water (TBW) content and in particular on the distribution of water in the intra- and extracellular compartments (ICW and ECW) of alcoholics. The aim of this study was to evaluate TBW, ICW, and ECW in chronic alcoholic patients. METHODS: Thirty-six alcoholics meeting DSM-III-R criteria for diagnosis (20 men, 16 women; body mass index [BMI] 22.3+/-2.57 kg/m2) were enrolled. Fifty-four healthy social drinkers (31 men, 23 women; BMI 23.7+/-1.68 kg/m2) matched for age and height were used as controls. Systolic and diastolic blood pressure was measured for all cases. All patients were assessed using specific anthropometric measurements. The waist-to-hip ratio (WHR) was used as an indicator of body fat distribution. TBW was measured by isotopic dilution by giving 100 microCi of tritiated water. ICW and ECW were assessed by multifrequence bioelectric impedance analysis (BIA). Basal metabolic rate (BMR) was measured by indirect calorimetry. RESULTS: Body weight was lower in the alcoholics than in the controls (61.9+/-5.5 kg vs. 65.8+/-5.2 kg;p < 0.01), essentially due to a reduction in fat mass. Significantly higher WHR values were found in both male (p < 0.001) and female (p < 0.001) alcoholics than in healthy subjects. A higher ECW/TBW ratio was found in the alcoholics compared with the controls, both as a whole (0.53+/-0.04 vs. 0.41+/-0.03; p < 0.0001) and separated by gender (p < 0.001). CONCLUSIONS: The increased ECW could derive from an increase in cellular permeability related to endothelial damage linked to the vasoconstriction present in the alcoholics and/or to a direct toxic effect of ethanol on cellular membranes. In addition, because the high ECW volumes correlated positively with WHR in the alcoholics, a potential association of these two factors in determining an increased risk of liver disease, hypertension, and cardiovascular disease may exist. Finally, the lower TBW characteristic of women may be one of the reasons for the observed greater rate of toxic effects of ethanol that occur in women.
OBJECTIVES: Because there is controversy regarding the prevalence, familial occurrence, and possible factors inducing splenic hypofunction in celiac disease, we have reassessed them in a large series of untreated patients and their first-degree relatives. METHODS: Pitted red cell counting was used to measure splenic function and the effect that age at diagnosis has on it, while severity of intestinal lesions and nutritional status were estimated by multiple linear regression analysis. Moreover, serum tuftsin activity was assayed by measuring its ability to stimulate phagocytosis of opsonized Staphylococcus aureus. RESULTS: We found that 32.8% of untreated celiacs and none of their relatives had pitted red cell values in the range of splenic hypofunction (>4%). Only age at diagnosis, but not the other two covariates, was significantly associated with the degree of splenic hypofunction. Tuftsin activity was depressed in celiac disease and this reduction was significantly greater in hyposplenic patients. CONCLUSIONS: In celiac disease the prevalence of splenic hypofunction is lower than formerly believed. The duration of preexposure to gluten is a crucial factor for the prevalence and severity of this complication that does not affect celiac relatives. In celiac disease splenic hypofunction is accompanied by a reduced phagocyte activity linked to the decreased release of tuftsin.
In the past year, several studies have been carried out on the association between Helicobacter pylori infection and a miscellany of extradigestive diseases, such as cardiovascular, immunological, and various other pathologies. In particular, a higher prevalence of H pylori infection in patients affected by ischaemic heart disease has been described and there is growing evidence for an association between H pylori and some autoimmune diseases. Moreover, recent studies have shown that various helicobacter species have been detected in human bile; if confirmed, this finding could revise the diagnostic and therapeutic approach to diseases of the biliary tract.