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Objective: Evaluation of the interaction between alcohol intake and cofactors [hepatitis B virus (HBV), hepatitis C virus (HCV), body mass index] and coffee consumption on the risk of cirrhosis., Design: Seven hundred and forty-nine consecutive patients with chronic liver disease referring to units for liver or alcohol diseases in Italy during a 6-months period. Teetotalers were excluded. The odds ratios (OR) for cirrhosis were evaluated using chronic hepatitis cases as the control group., Results: An alcohol intake of more than 3 units/day resulted associated with the likelihood of cirrhosis both in males (OR 4.3; 95% CI=2.5-7.3) and in females (OR 5.7; 95% CI=2.3-14.5). A multiplicative interaction on the risk of cirrhosis between risky alcohol intake and HBsAg or HCV-Ab/HCV-RNA positivity was observed. A reduction of cirrhosis risk was observed in subjects consuming more than 3 alcohol units/day with increasing coffee intake. The OR for the association with cirrhosis decreased from 2.3 (95% CI=1.2-4.4) in subjects drinking 0-2 cups of coffee/day to 1.4 (95% CI=0.6-3.6) in those drinking more than 2 cups/day., Conclusions: In subjects with an alcohol intake >3 units/day the coexistence of HBV or HCV multiplies the risk of cirrhosis. Coffee represents a modulator of alcoholic cirrhosis risk.

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; R2=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.

The release of soluble circulating molecules represents a prominent feature during the course of immune-mediated clinical conditions. To further assess the relationship between serum concentrations of adhesion or apoptotic-related soluble structures and liver diseases, we evaluated the levels of intercellular adhesion molecule-1 (sICAM-1), Fas receptor (CD95) and Fas ligand (sCD95L) in a group of patients affected by Hepatitis C Virus (HCV)-induced chronic hepatitis (CH-C), HCV-positive liver cirrhosis with superimposed hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and alcoholic liver cirrhosis (ALC). Results show that sICAM-1 values were in all instances significantly elevated when compared to those seen in healthy donors. Similar findings were noted in subjects with liver diseases in terms of sCD95 concentrations, even if to a different degree of statistical significance. Finally, sCD95L amounts were augmented in AIH, PBC, ALC and CH-C in comparison to controls, while in the HCC counterpart sCD95L levels fell within normal range. All together, these findings emphasize the occurrence of circulating soluble molecules in patients with various chronic liver diseases, likely reflecting the involvement of several pathogenetic mechanisms.

Although it is well known that chronic ethanol abuse produces sexual dysfunction and impaired spermatogenesis, the mechanisms of ethanol-induced testicular alterations are not fully explained. Therefore, the aim of this study was to investigate the mechanisms of testicular oxidative damage in rats given drinking water containing 3% ethanol for 8 weeks. Control rats were pair-fed with saccharose. The mean daily ethanol intake was 4.05 g kg(-1), corresponding to the consumption of 41 of wine (10% alcohol) or 0.71 of whiskey (40% alcohol) by a man of 70 kg body wt. Exposure to ethanol caused a significant depletion in the testicular levels of glutathione (GSH), protein containing sulfhydryl groups, tocopherol and ascorbic acid, and an increase in the concentrations of malondialdehyde (index of lipid peroxidation) and carbonyl proteins (index of protein oxidation). Other effects were decreases in the concentration of adenosine 5'-triphosphate and in the activity of glutathione peroxidase, and an increase in the activity of alcohol dehydrogenase. In summary, this study shows that in the rat, daily consumption of ethanol in the drinking water increases lipid and protein oxidation. In addition to impaired antioxidant defence, an imbalance in energy production may also play a role in the toxic reaction to alcohol.

The effect of claustrum (CL) stimulation on the spontaneous unitary activity of ipsi and contralateral frontal oculomotor neurons, was studied in chloralose-anaesthetized cats. A total of 205 units was bilaterally recorded in the medial oculomotor area, homologous of the primate "frontal eye fields"; 127 neurons were identified as projecting to the superior colliculus; for 33 of these last units stimulation of the ipsilateral CL provoked an excitatory effect lasting 10-25 ms and appearing with a latency of 5-15 ms; on 8 units the excitatory effect was followed by an inhibition lasting 100-250 ms. Ninety-eight of the 127 neurons were also tested through activation of the contralateral CL: 13 cells showed an excitatory effect lasting 10-35 ms and appearing with a latency of 20-50 ms. In three of the thirteen units the excitatory effect was followed by an inhibition lasting 100-150 ms. Complete section of the corpus callosum abolished the contralateral CL effect, suggesting the existence of a direct claustro-contralateral oculomotor cortex pathway running through the corpus callosum. The results could support the hypothesis that the CL may play a role in the bilateral control of the visuomotor performance.

In chloralose-anaesthetized cats, the extracellular spontaneous unitary activity was recorded from 157 neurons, located in the medial oculomotor area. 98 units were identified as projecting onto the superior colliculus. Electrical stimulations of the contralateral claustrum provoked, on 13 of these cells, an excitatory effect, lasting 10-35 ms and appearing with a latency of 20-50 ms. Full length section of the corpus callosum totally abolished the contralateral claustrum effect. The results suggest that in the cat, the claustrum may have a role in the bilateral control of the visuo-motor performance.

In order to study the relationships between the claustrum and motor cortex neurons both of area 4 and area 6 in the cat, an experiment was performed in which the effect of claustral stimulation on pyramidal tract neurons was investigated. Single shock electrical activation of the claustrum caused an inhibition of the spontaneous activity of the neurons, or an inhibition preceded by short activation, or no effect. These evidences lead to the conclusion that the claustrum exerts a role in movement organization.

The electrophysiological relationships between the claustrum and the contralateral motor areas of the cerebral cortex were studied in anaesthetized cats. The extracellular unitary activity of 207 pyramidal tract neurons (PTNs) was recorded from area 4 (125 cells) and area 6 (82 cells). Single shock activation of the contralateral claustrum affected 26% of the total tested PTNs, causing long lasting inhibition (44 PTNs) or long lasting inhibition preceded by early excitation (10 PTNs). Forty-three neurons of the 54 were also influenced by ipsilateral claustrum stimulation. Surgical removal of motor and insular cortices ipsilateral to the stimulated claustrum did not modify claustrum inhibition on contralateral PTNs, whereas section of the corpus callosum abolished this effect, suggesting the existence of a direct claustro-contralateral motor cortex pathway passing through the corpus callosum. These results support the hypothesis that the claustrum may exert a bilateral control on motor coordination.

Glutamate (Glut), acetylcholine (ACh) and dopamine (DA) were iontophoretically applied on cat claustral neurons. Glut did not affect all the neurons; ACh had both excitatory and inhibitory effects, while DA was prevalently inhibitory. An analysis was made of the time-course of excitatory and inhibitory responses on the basis of the mean firing rate variations during and after ACh and DA release. Three types of responses are described for each drug: short lasting inhibition, long lasting inhibition and long lasting excitation. The experimental data were statistically elaborated. The effects of ACh and of DA were compared with those of activation obtained by sensorial peripheric and thalamic stimulations. ACh could be supposed to be the transmitter of most of the inhibitory terminals of these sensitive afferences to the claustrum.

In order to investigate the functional meaning of the connections between the claustrum and the controlateral motor areas, the extracellular spontaneous activity of 81 PTNs was recorded. Single shock controlateral claustrum stimulation inhibited twenty-two out of the 81 PTNs. On four of the twenty-two PTNs the inhibition was preceded by an early activation. The split of the corpus callosum was performed in 5 cats in order to study the pathway followed by claustrum fibers to the controlateral motor cortex. It is ipothesized that the relationship between the claustrum and controlateral area 4 and 6 PTNs might have the purpose of giving the pyramidal output the bilateral contribution of a plurisensory structure.

Electrophysiologic interactions between claustrum and motor cortex neurons were investigated in the cat. A total of 136 neurons was recorded from the motor cortex in area 4 (90 cells) and in area 6 (46 cells). Ninety-eight of the total neurons were identified as pyramidal tract neurons (PTNs). Stimulation of the claustrum by single shocks or by trains of stimuli imposed on the tested PTNs a pure long-lasting inhibition, or a long-lasting inhibition preceded by a short early activation, or no effect. No functional localization of the effects of claustrum activation were found within the motor areas. The observed results are consistent with the hypothesis that the claustrum may play a role in movement organization.

The connections between the claustrum and the contralateral motor areas were electrophysiologically investigated in cats under chloralose anesthesia. The extracellular unitary activity of 81 pyramidal tract neurons (PTNs) was recorded; 22 PTNs were inhibited by activation of the contralateral claustrum; inhibition was preceded by an early activation of 4 out of the 22 inhibited PTNs. Section of the corpus callosum abolished the contralateral claustrum effect, while the action of the ipsilateral homologous structure persisted.

Responses were evoked in the lateral geniculate body (L.G.B.) of "encéphale isolé" cats by single-shock stimulation of either the geniculate body or the optic tract of the other side. Responses to optic tract stimulation were modified following excitability changes in the contralateral L.G.B. due to topical application of strychnine and KCl. Laminar stimulation and recording in different layers (A, A1, and B) suggested the existence of a certain homotopic organization of L.G.B. interconnections. The activity evoked in the L.G.B. was found to be abolished by electrocoagulation of the posterior commissure and intermediate gray matter. These results point to the presence of a transthalamic pathway which might mediate L.G.B. activity to the contralateral visual cortex.

Sequential changes in chloride and bicarbonate concentrations in pancreatic juice were evaluated after gradually increased doses of: 1) synthetic secretin in men 2) natural secretin in dogs 3) natural CCK in dogs. The results suggest that the increase in bicarbonate concentration is accompanied by a proportional chloride concentration decrease. The total anionic concentration is constant and it is not affected by different hormonal stimulation.

Electrophysiological relationships between the claustrum and the motor cortex were studied in cats preliminarily anesthetized with ketamine and then with chloralose. Single shock electrical activation of the claustrum induced a decrease of the spontaneous unitary activity of the pyramidal tract neurons (PTNs) both in area 4 and in area 6. Eighty percent of the total number of PTNs was inhibited whereas the remaining 20% was unaffected. The inhibitory effect lasted about 200 msec and appeared about 19 msec after claustrum activation. The results show a functional linkage between the claustrum and the efferent cells of the motor cortex. This relationship suggests the hypothesis that the claustrum, a multisensory structure, may be involved in motor activity integration.

The influence of claustrum stimulation on spontaneous unitary activity of the ipsilateral frontal oculomotor area was analyzed in anesthetized cats. Sixty-five neurons were isolated, 37 of which (57%) were identified as projecting to the superior colliculus; on 12 of these last units (32%), electrical activation of the dorsal claustrum provoked an excitatory effect, which appeared after a latency of 5-15 ms and lasted 10-25 ms. These data could suggest the involvement of the claustrum in the visuomotor coordination function.

S-Adenosyl-L-methionine (SAMe) is a physiologic precursor of thiols and sulfurated compounds, which are known to be decreased in patients with liver disease. The effect of its administration on the hepatic glutathione content of liver patients was investigated. Four groups of subjects were selected: a) 9 patients with alcoholic liver disease treated with SAMe (1.2 g/day orally for 6 months); b) 7 patients with non-alcoholic liver disease treated as above; c) 8 placebo-treated patients with alcoholic liver disease; and d) 15 normal subjects as a control group. Total and oxidized glutathione were assayed by high-performance liquid chromatography of liver biopsy specimens before and after the treatment period. In all patients pre-treatment hepatic glutathione was significantly decreased as compared with controls. SAMe therapy resulted in a significant increase of hepatic glutathione levels both in patients with alcoholic and in those with non-alcoholic liver diseases as compared with placebo-treated patients. SAMe may therefore exert an important role in reversing hepatic glutathione depletion in patients with liver disease.