Search

The objective of this work is to evaluate in a selection of patients with erectile dysfunction the influence of alcohol consumption and the response to alcohol abstinence with and without sildenafil association. Materials and Methods. In a population of 150 consecutive patients with erectile dysfunction we studied 50 patients aged between 22 and 77 years (mean 56±14 SD). These 50 patients were divided into three different treatment groups and were screened for three different levels of alcohol risk with two questionnaires. All patients were evaluated with an International Index Erectile Dysfunction (IIEF) questionnaire before and after one month of treatment. Results. The 50 patients included 14 patients with high alcohol risk, 34 patients with low alcohol risk and only 2 patients with no alcohol risk. After one month, 29 patients responded to the therapy, and 21 did not respond. The IIEF questionnaire presented a statistically significant difference between the different risk groups before and after treatment (p≤0.05). All the patients were examined with a penile Doppler Ultrasound. Only 10 of them had an abnormal diastolic peak velocity (PDV) and only 1 presented both pathologic systolic peak velocity (PSV) and PDV. These 11 patients did not respond to therapies and 10 of them were at high alcohol risk. The alcohol consumption risk was directly correlated with PDV (p=0.00001; R=0.4). Conclusions. The results of this study demonstrated a significant relationship between alcohol consumption and erectile dysfunction. This underlines the important therapeutic issue of alcohol abstinence in treating patients with erectile dysfunction.

A lactose-free diet is commonly prescribed to subjects with hypolactasia. We tested the effectiveness of a single ingestion of tilactase (a beta-D-galactosidase from Aspergillus oryzae) in adults with hypolactasia, previously assessed by lactose H(2)-breath test.After measurement of orocecal transit time (OCTT, by lactulose H(2)-breath test) and lactose H(2)-breath testing plus placebo, a total of 134 subjects were positive to hypolactasia and underwent lactose H(2)-breath testing plus either low (6750 U) or standard (11,250 U) doses of tilactase. The appearance of gastrointestinal symptoms during the tests was monitored.OCTT was longer in malabsorbers (subjects without bloating, abdominal pain and/or diarrhoea, n = 25) than in intolerants (bloating, abdominal pain and/or diarrhoea, n = 109, P0.02). Malabsorbers had longer time to H(2) peak (P0.03), lower H(2) peak levels (P0.002) and smaller integrated H(2) excretion levels (P0.005) than intolerants. After tilactase ingestion, integrated H(2) levels were decreased by 75% (low dose) and 87% (standard dose) in malabsorbers, and by 74% (low dose) and 88% (standard dose) in intolerants. In the latter group, total symptom score were decreased by 76% (low dose) and by 88% (standard dose) (P0.0001).A single oral administration of tilactase is highly effective in decreasing symptoms and hydrogen excretion of hypolactasia assessed by lactose H(2)-breath test. If confirmed by long-term observations, ingestion of tilactase might be a better option than exclusion diets in intolerant subjects with hypolactasia.

The biological importance of the aquaporin family of water channels was recently acknowledged by the 2003 Nobel Prize for Chemistry awarded to the discovering scientist Peter Agre. Among the pleiotropic roles exerted by aquaporins in nature in both health and disease, the review addresses the latest acquisitions about the expression and regulation, as well as physiology and pathophysiology of aquaporins in the hepatobiliary tract. Of note, at least seven out of the thirteen mammalian aquaporins are expressed in the liver, bile ducts and gallbladder. Aquaporins are essential for bile water secretion and reabsorption, as well as for plasma glycerol uptake by the hepatocyte and its conversion to glucose during starvation. Novel data are emerging regarding the physio-pathological involvement of aquaporins in multiple diseases such as cholestases, liver cirrhosis, obesity and insulin resistance, fatty liver, gallstone formation and even microparasite invasion of intrahepatic bile ducts. This body of knowledge represents the mainstay of present and future research in a rapidly expanding field.

Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes.Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment.Compared with controls, patients showed lower levels of protein sulphydrils (28.9 +/- 7.1 vs. 65.6 +/- 1.8 nmol mg(-1) prot) and accumulation of carbonyls (4.7 +/- 1.7 vs. 1.4 +/- 0.1 nmol mg(-1) prot). Phosphatidylethanolamine level was lower in stage III-IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4.25 +/- 0.55 in the I-II stage and 2.89 +/- 0.44 in the stage III-IV vs. 1.61 +/- 0.30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P0.05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r=0.66, P0.05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters.This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.

In rodents, interleukins administration induces intestinal changes similar to those found in inflammatory bowel disease. We investigated the effects of in vivo subchronic treatment with IL-1 beta and IL-6 on rat colonic mucosa and circular smooth muscle.We evaluated transmucosal electrical parameters (Ussing chambers) and early changes of in vitro direct contractility induced by carbachol and tachykinins. Alterations in excitatory and inhibitory neurotransmission were studied with electrical field stimulation (EFS).Treatment with interleukins induces inflammation proved by fever, early signs of colonic histological damage and changes in mucosal ion transport. Concentration response-curve to carbachol was significantly lower in treated rats (P0.02) with significant difference in Emax between control (1.67+/-0.17 g) and treated preparations (1.20+/-0.13 g) (P0.05). Concentration response-curve to NK2 agonist was significantly lower in the treated rats (P0.005) with a significant difference in Emax between the control (0.26+/-0.04 g) and treated preparations (0.12+/-0.02 g) (P0.02). None of the drugs used induces changes in EC50. The contractile reflex response to electrically induced distension was significantly higher in the treated rats and more reduced after administration of atropine. Adding NK2 receptor antagonist resulted in a further reduction being observed in the treated and control rats (P=NS). Relaxation by EFS on cholinergic tone was not different between treatments, although pretreatment with L-NNA resulted in greater relaxation in the treated (-21.7%) than in the control rats (-14.8%).Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.

The interplay between contraction and relaxation in the gall-bladder muscularis leads to appropriate gall-bladder emptying and refilling during fasting and in the postprandial state in vivo. Several studies in both human and animal models have focused on cellular and molecular events in the gall-bladder wall in health and disease in vitro. Principal methods to study gall-bladder smooth muscle function include receptor binding studies (at the level of plasmamembranes or histological sections), phase contrast microscopy (at the level of isolated smooth muscle cells), and tensiometry (at the level of smooth muscle strips or the whole gall-bladder). At a very early stage, cholesterol gallstone disease is characterized by exposure of the gall-bladder wall to excess of biliary cholesterol and the cytotoxic effect of the bile salt deoxycholate. On a long-term basis, a form of gall-bladder leiomyopathy develops with defects involving the mechanisms of signal transduction at the level of plasmamembranes. The end-stage result is pathological contraction and/or relaxation of smooth musculature, impaired gall-bladder motility and gall-bladder stasis, all key factors in the pathogenesis of biliary cholesterol crystallization and gallstones.

Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics.Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients.Fasting gallbladder volume was significantly (P0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019).Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.

Purpose Hemolysis is a frequent adverse effect of ribavirin (RBV). Oxidative stress has been suggested to play a role, but mechanisms and predictive risk factors are unknown. Methods: Markers of redox status were determined in erythrocytes from hepatitis C infected patients with and without G6PD-deficiency before and during RBV treatment, and erythrocytes were incubated with RBV and dipyridamole, diethylmaleate or glutathione ester. Results: 5 out of 30 patients developed major RBV-induced hemolysis, which was associated with a more pronounced increase in thiobarbituric acid reactive substances (+22.5 vs. +9.4 nmol/gHb, p

In five dogs, provided with chronic pancreatic and gastric fistulas (Thomas' cannula), the effects on exocrine pancreatic secretion of an intravenous continuous perfusion of gastrin (Eurorga, hog gastrin I-II, 6 mug./kg./hr.) and secretin (GIH, 0.5 C.U./kg.hr.) was studied before and after 48 hours of reserpine treatment (0.1 mg./kg./24 hr.). When compared with the pretreated plateau levels, reserpine induced a significant pancreatic secretion dissociation, a depressive of the alkaline and a rising of the protein component. The former phenomenon suggests a participation of a catecholamines in the secretin-elicited pancreatic electrolyte secretion. The latter, an enhanced sensitivity of intranpancreatic and/or acinar cells of the "pancreon" to gastrin stimulation.

In dogs provided with chroinic pancreatic and gastric fistulas (Thomas canula), one of them vagotomized and alcohol-fed for 17 months with 50% (v/v) intragastric ethanol (0.2gm./kg.), an atropine perfusion (1.0 mg./hr.) superimposed on a continuous i.v. injection of secretion (GIH, 1.0 CU./kg./hr.) and CCK (GIH, Crick, Harper 3.0 U./kg./hr) prevents the excitatory effects on pancreatic secretion of an acute i.v. ethanol infusion (1.3 gm./kg.). In alcohol-fed dogs, the i.v. ehtanol-induced excitatory effect on 'pancreon' is exerted through a cholinergic mechanism, elicited at the hypothalamic bulbar centers and/or the intrapancreatic ganglia.