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Biomedical subjects

C di Padova

Publications and source records attributed to C di Padova.

10 recordsLinked to original sources

Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry.

In a double-blind, placebo-controlled crossover study, the effects of S-adenosyl-l-methionine (SAMe) on brain function measures of 12 normal elderly volunteers (6 m/6 f, aged 57-73 years, mean: 61 years) were investigated by means of EEG mapping and psychometry. In random order, the subjects were orally administered a pharmaceutical dose of 1600 mg SAMe, a nutraceutical dose of 400 mg SAMe and placebo, each over a period of 15 days, with wash-out periods of 2 weeks in between. EEG recordings, psychometric tests and evaluations of tolerability and side effects were carried out 0, 1, 3 and 6 h after drug administration on days 1 and 15. Multivariate analysis based on MANOVA/Hotelling T2 tests of quantitative EEG data demonstrated significant central effects of SAMe as compared with placebo after acute, subacute and superimposed drug administration of both the nutraceutical and the pharmaceutical dose. EEG changes induced by SAMe were characterized by an increase in total power, a decrease in absolute and relative power in the delta/theta and slow alpha frequencies, an increase in absolute and relative power in the alpha-2 and beta frequencies as well as an acceleration of the alpha centroid and the centroid of the total power spectrum. The delta/theta and the beta centroid showed variable changes over time. The dominant alpha frequency was accelerated, the absolute and relative power in the dominant alpha frequency attenuated after SAMe as compared with placebo. These acute and subacute pharmaco-EEG findings in elderly subjects are typical of activating antidepressants. Time-efficacy calculations showed that acute oral administration of SAMe in both the nutraceutical and the pharmaceutical dose induced the pharmacodynamic peak effect in the first hour with a subsequent decline. The 3rd and 6th hours still showed a significant encephalotropic effect after the 1600 mg dose. The maximum EEG effect was noted after 2 weeks of oral administration of both 1600 mg/die and 400 mg/die. The superimposed dose induced significant encephalotropic effects in the 3rd hour after 400 mg and in the 3rd and 6th hours after 1600 mg as compared with pre-treatment. Dose-efficacy calculations showed that the pharmaceutical dose of 1600 mg had a more pronounced effect on the CNS than the nutraceutical dose of 400 mg, with both doses being superior to placebo. Psychometric tests concerning noopsychic and thymopsychic measures as well as critical flicker fusion frequency generally demonstrated a lack of differences between SAMe and placebo, which reflects a good tolerability of the drug in elderly subjects. This was corroborated by the findings on side effects, pulse and blood pressure.

Aged↗

Pharmacodynamic studies on the central mode of action of S-adenosyl-L-methionine (SAMe) infusions in elderly subjects, utilizing EEG mapping and psychometry.

In a double-blind, placebo-controlled cross-over study, the acute and subacute effects of S-adenosyl-L-methionine (SAMe), or ademetionine, on brain function and behavior of 10 elderly normal healthy volunteers (5 males and 5 females, aged 56-71 years, mean: 59.3 years) were investigated by means of EEG mapping and psychometry. In random order they received infusions of 800 mg SAMe and placebo, administered over 30 minutes for 7 days, with a wash-out period of 3 weeks in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 hours after drug administration on days 1 and 7. Multivariate analysis based on MANOVA/Hotelling T(2) tests demonstrated significant central effects of SAMe as compared with placebo after acute, subacute and superimposed drug administration. Acute SAMe-induced changes were characterized by a decrease in total power, an increase in absolute delta and a decrease in absolute alpha power, further by an increase in relative delta and a decrease in relative alpha power, a slowing of the delta/theta centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. After one week of daily infusions there was a marked increase in total power, reminiscent of nootropic drug effects. One additional superimposed dosage mitigated these effects in the direction of an antidepressant profile, with the inter-drug differences waning in the 6(th) hour. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects underlying the antidepressant properties of SAMe well-documented in clinical trials. Psychometric tests concerning noopsychic and thymopsychic measures as well as critical flicker frequency generally demonstrated a lack of differences between SAMe and placebo, which again reflects a good tolerability of the drug in elderly subjects.

Aged↗

High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism.

After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant "first-pass metabolism" of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs = 0.659) between first-pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first-pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first-pass metabolism was virtually abolished. We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism.

Adult↗

Non-invasive treatment for retained common bile duct stones in patients with T tube in situ: saline washout after intravenous ceruletide.

The combination of ceruletide-induced relaxation of the sphincter of Oddi plus flushing with saline has recently been proposed as a novel procedure for the treatment of residual common bile duct (CBD) stones. In this study we have administered intravenous ceruletide (2 ng kg-1 body weight min-1 for 1 h) plus intraductal saline (800-3000 ml, infused at a rate that kept biliary pressure below 30 cmH2O) to a group of 14 patients. The treatment induced the passage of residual stones in 11 subjects (79 per cent) with complete clearance in 7 (50 per cent). The majority of the cleared concretions (11/15) had a diameter less than 10 mm. No severe side-effects were recorded during the treatment. Four of the seven subjects who exhibited incomplete CBD clearance underwent a short cycle of mono-octanoin administration in order to reduce the size of residual radiolucent stones. This course of treatment was followed by another attempt with intravenous ceruletide and saline washout which gave a successful response in an additional three cases. These data indicate that the combination of ceruletide and flushing is a safe and inexpensive method for treatment of residual stones. The procedure is feasible for both radiolucent and radio-opaque stones and is mainly eligible for small concretions of diameter less than 10 mm. Larger (greater than 10 mm) radiolucent stones may be partially dissolved with mono-octanoin and then eliminated by the washout technique.

Adult↗

S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies.

S-Adenosylmethionine (SAMe), a physiologic compound that ranks with ATP as a pivotal molecule in biology, offers physicians an innovative approach to the treatment of osteoarthritis. Experimental investigations suggest that the administration of SAMe exerts analgesic and antiphlogistic activities and stimulates the synthesis of proteoglycans by articular chondrocytes with minimal or absent side effects on the gastrointestinal tract and other organs. The results of extensive clinical trials, which have enrolled about 22,000 patients with osteoarthritis in the last five years, support the clinical effectiveness and the optimal tolerability of SAMe administration. The intensity of therapeutic activity of SAMe against osteoarthritis is similar to that exerted by nonsteroidal anti-inflammatory drugs, but its tolerability is higher. Based on these findings, SAMe is proposed as the prototype of a new class of safe drugs for the treatment of osteoarthritis.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of a concomitant treatment with ethynylestradiol and ascorbic acid on bile secretion in female hamsters.

The administration of large doses (5 mg/kg b.wt./day) of ethynylestradiol to adult female hamsters did not induce cholestasis or modifications of bile lipid composition. These findings are in contrast with the data of other authors who in different experimental conditions described the sensitivity of hamsters to the estrogen-induced hepatobiliary toxicity. Ascorbic acid alone or added to ethynylestradiol did not impair bile secretion. However, it significantly increased the plasma levels of radioactivity tested 24 hours after the oral administration of a tracer dose of radiolabelled ethynylestradiol. These results confirm previous data showing in humans the capability of ascorbic acid to favour the rise of plasma concentrations of ethynylestradiol.

Animals↗

Effects of methyltestosterone on bile secretion in female and male rats.

No adverse effect on bile secretion was noted in methyltestosterone-treated female rats. In male rats, methyltestosterone administration exerted a cholestatic effect, which is not only due to the decrease of bile salt excretion rate, but also to a possible interference of the steroid with bile salt micelle size.

Animals↗

Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration.

Previous investigations have indicated that S-adenosyl-L-methionine (SAMe) leads to reversal of estrogen-induced bile flow impairment in rats. This randomized, single-blind clinical trial was performed to determine whether SAMe reverses intrahepatic cholestasis of pregnancy (ICP) which occurs in hypersensitive women associated with increased estrogen levels in late pregnancy. Eighteen women with ICP were randomly divided into three groups of six and treated for 20 days as follows: Group I received 200 mg per day of i.v. SAMe; Group II received 800 mg per day of i.v. SAMe; Group III served as control. At the beginning of the study, clinical and biochemical parameters were similar among groups. After 10 and 20 days of treatment with the higher dose of SAMe, the mean values of serum transaminases, conjugated bilirubin and total bile acids fell significantly in respect to initial levels; opposite results were found in the other two treatment groups. The final values of these selected parameters were lower in the group of subjects treated with 800 mg per day SAMe than in the other two groups of women. Pruritus graded on a 0 to 4+ scale significantly was reduced only in patients treated with the higher dose of SAMe. These results indicate a trend toward remission of ICP in women treated with 800 mg per day SAMe and suggest that SAMe administration may be a new therapeutic modality for ICP.

Adult↗