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A Tavani

Publications and source records attributed to A Tavani.

143 records · Page 8Linked to original sources
PubMed1983

Agonist and antagonist properties of some benzomorphans on nociceptive reaction and intestinal transit in rats.

The agonist and antagonist properties of bremazocine, ethylketazocine, Mr 2034 and Mr 2092, benzomorphans with the same pharmacological actions in vitro, were studied in vivo in rats. Overnight fasted animals were tested for nociceptive reaction on a 55 degrees C hot-plate and for the intestinal transit of a charcoal meal fed 5 min earlier. The antagonist activity was assessed by the drugs' ability to prevent morphine-induced constipation. Bremazocine was an agonist on the nociceptive reaction and a pure antagonist on intestinal propulsion; ethylketazocine and Mr 2034 were pure agonists in both tests and Mr 2092 was a mixed agonist-antagonist in the intestinal transit test. Thus the in vivo agonist-antagonist properties of opiates cannot always be predicted from their in vitro characteristics.

Analgesia↗
PubMed1983

Relative ability of N-methyl nalorphine and N-methyl levallorphan to prevent antinociception and intestinal transit inhibition in morphine treated rats.

Nalorphine, levallorphan and their quaternary analogs, N-(eq)allyl derivatives of the two diastereoisomers at the nitrogen atom (N-methyl nalorphine and N-methyl levallorphan) were tested for their peripheral selectivity. We compared their relative ability to prevent morphine-induced (5 mg/kg i.v.) antinociception (central antagonism) and constipation (peripheral antagonism) in the same rats. Nalorphine and levallorphan reduced morphine-induced antinociception to half maximal response at doses of 5.1 and 0.89 mg/kg s.c. and restored the intestinal transit to 50% of controls (AD50) respectively at doses of 0.25 and 0.12 mg/kg. N-methyl nalorphine up to 24 and N-methyl levallorphan up to 30 mg/kg given s.c. 10 min before morphine did not antagonize narcotic-induced antinociception, fully preventing constipation (AD50 0.65 and 0.32 mg/kg respectively), but when injected 50 min before morphine they partially lost their antagonist potency (AD50 2.3 and 2.6 mg/kg respectively) and peripheral selectivity. N-methyl nalorphine and N-methyl levallorphan thus seem more peripherally selective than their tertiary analogs and more potent than quaternary narcotic antagonists tested to date.

Analgesia↗
PubMed1983

Morphine tissue levels and reduction of gastrointestinal transit in rats. Correlation supports primary action site in the gut.

Overnight-fasted male rats given a single dose of tritium-labeled morphine either intraperitoneally or intravenously were fed a charcoal test meal by stomach tube. The drug remaining in tissues was assayed by liquid scintillation counting of thin-layer chromatograms from homogenates, and gastrointestinal transit was tested by measuring the portion of the small intestine traversed by charcoal in 5 min. Morphine, 0.15 mg/kg, given intraperitoneally either 10 min or 30 min before testing substantially reduced gastrointestinal transit (to 23% and 55% of drug-free controls, respectively), and produced maximum drug levels 5 min after administration in small intestine longitudinal muscle with attached myenteric plexus (500 +/- 42 ng/g, mean +/- SE, n = 4). Intact small intestine, plasma, and brain, respectively, contained decreasing drug concentrations that, in the latter, never exceeded 2%-3% of that in longitudinal muscle. Rats receiving 0.15 mg/kg morphine intravenously presented only minor and short-lived inhibition of gastrointestinal transit that was significantly below (approximately 35%) that of drug-free controls at 10 min, but not 30 min, after drug administration. Morphine levels in the brain and plasma of these rats were up to five times higher, and in the intact small intestine longitudinal muscle were up to 20 times lower than in intraperitoneally treated rats. Morphine concentration in the tissues assayed was plotted against the effect on gastrointestinal transit at the same interval for individual rats regardless of dose, administration route, and observation time: data analysis, in small intestine longitudinal muscle, but not in the brain or plasma, indicated a highly significant correlation and fitting of computer-generated curves described by a currently accepted equation according to the receptor occupation theory of drug response. In view of these findings, and of the complete prevention by the "peripherally selective" narcotic antagonist N-methyl naloxone of gastrointestinal transit inhibition after an intravenous analgesic dose of morphine (1 mg/kg), the investigated animal model is consistent with the primary role of a gut-located action site in opiate-induced constipation.

Animals↗
PubMed1982

Quaternary narcotic antagonists' relative ability to prevent antinociception and gastrointestinal transit inhibition in morphine-treated rats as an index of peripheral selectivity.

Single doses of naloxone (0.025 to 0.5 mg/kg) or of one of four quaternary narcotic antagonists (i.e. nalorphine allobromide, nalorphine methobromide, naloxone methobromide or naltrexone methobromide, 1 to 60 mg/kg) were given s.c. to rats before morphine, 5 mg/kg i.v. In the absence of antagonists morphine reduced G.I. transit of a charcoal meal to about 15% of drug-free controls and consistently delayed nociceptive reactions (55 degrees C hot plate) in all animals. Doses of antagonists slightly reducing morphine antinociception (centrally effective = A) and restoring G.I. transit to about 50% of drug-free rats (peripherally effective = B) were estimated. The A:B ratio, indicating peripheral selectivity, was at least 8 for any of the quaternary antagonists given 10 min before morphine, but prolonging this interval may have resulted in a lower figure (i.e. less peripheral selectivity) because of reduced A and increased B. This was definitely so for naltrexone methobromide (A:B, greater than 60 at 10 min, about 1 at 80 min) and was not apparent for nalorphrine methobromide according to available data, which for nalorphrine allobromide and to a lesser extent for naloxone methobromide showed only an increase in B at intervals longer than 10 min. Both morphine-induced antinociception and inhibition of G.I. transit were reduced by naloxone at the lower doses tested and were fully prevented at the higher. These findings indicated that, unlike naloxone, the investigated quaternary narcotic antagonists are interesting prototype drugs for selective blockade of opiate receptors outside the CNS, although certain critical aspects, possibly biological N-dealkylation to the corresponding tertiary antagonists, condition peripheral selectivity.

Analgesia↗
PubMed1979

Morphine no longer blocks gastrointestinal transit but retains antinociceptive action in diallylnormorphine-pretreated rats.

Diallylnormorphine (DANM) the quaternary N-allyl derivative of nalorphine, administered to rats, 8 mg/kg i.p., 20 min before i.v. injection of the potent opiate buprenorphine (1 microgram/kg, tritrium-labeled), reduced in vivo binding of the latter (63% of controls at 30 min) in small intestine longitudinal muscle including myenteric plexus, but not in cerebrum. Naloxone, 1 mg/kg s.c., had the same effect of buprenorphine binding in the two sites (52 and 54% of controls respectively). The marked slowing in the transit of a forced charcoal meal through the small intestine of rats given 10 mg/kg morphine, i.v. was prevented to comparable extents by DANM and naloxone; the latter also abolished the delay in hot plate reaction induced in these animals by morphine which, however, retained considerable antinociceptive effect in DANM-pretreated rats.

Analgesics↗
PubMedDate not supplied

Body weight and risk of nonfatal acute myocardial infarction among women: a case-control study from northern Italy.

BACKGROUND: The relationship between nonfatal acute myocardial infarction (AMI) and self-reported body weight and body mass index (BMI; Quetelet index, kg/m2) has been investigated. METHODS: A case-control study was conducted between 1983 and 1992 in northern Italy on 432 women with nonfatal AMI and 867 controls in hospital for acute, noncardiovascular, nonneoplastic, nondigestive, non-hormone-related conditions. Odds ratios (OR), with their 95% confidence intervals (CI), were computed by unconditional multiple logistic regression analysis, including terms for age, education, and smoking, plus history of selected diseases. RESULTS: Women with body weight and BMI in the highest quartile had an increased risk of AMI after allowance for age, education, and smoking status (OR 1.5, 95% CI 1.0 to 2.2, and OR 1.7, 95% CI 1.2 to 2.4, respectively). Compared with leaner women, the risk was higher among women with BMI above the median, in association with a history of diabetes (OR 5.2) or hyperlipidemia (OR 6.0). Hypertensive women had similar OR in the two strata of BMI (OR 5.1 and 4.8). The association of BMI with risk of AMI was apparently stronger among women younger than 50 years and among less educated women, but was similar among smokers and never smokers. CONCLUSIONS: The results of this study confirm that AMI among women is related to excess BMI, with a population attributable risk of 17%. The excess risk was substantial among overweight women with history of diabetes or hyperlipidemia, stressing the importance of controlling body weight among these women.

Adolescent↗
PubMedDate not supplied

Morphine inhibits gastrointestinal transit in the rat primarily by impairing propulsive activity of the small intestine.

The effect of a single dose of morphine on small intestinal transit was studied in fasted rats by feeding a charcoal test meal either by stomach tube to normal animals or through a duodenal cannula to chronically implanted rats. The percentage of small intestine traversed by charcoal in 5 min was reduced by morphine (0.7 mg/kg s.c.) given 5 min before the meal to a similar extent in normal and implanted rats. In contrast administration of atropine (0.8 mg/kg s.c.) 30 min before the meal reduced charcoal transit only in normal rats fed the test meal by stomach tube. Inhibition of gastrointestinal transit in the rat by systemically administered morphine is mainly due to impaired small intestinal propulsion and does not depend to any significant extent on a direct action on the stomach delaying gastric emptying.

Animals↗
PubMedDate not supplied

Inhibition of gastrointestinal transit by morphine and FK 33-824 in the rat and comparative narcotic antagonist properties of naloxone and its N-methyl quaternary analog.

Morphine and the enkephalin-like peptide FK 33-824 given i.p. to rats potently inhibit gastrointestinal transit of a charcoal test meal, the doses inhibiting transit by 50% being respectively about 10 and 1 microgram/kg. These intestinal effects are opiate-specific, locally elicited and presumably involve the same action site since they are reversed by the "peripherally selective" narcotic antagonist N-methyl naloxone with apparent pA2 values of 7.34 and 7.10 respectively against morphine and FK 33-824. The calculated pA2 value for naloxone/morphine with the same in vivo test procedure (8.83) and the relative ability of naloxone and N-methyl naloxone to prevent 3H-etorphine binding to rat brain membranes (IC50 43 and 541 nM), indicate different potency ratios between the two narcotic antagonists in the in vitro binding cell-free system (about 1:10) and in vivo (about 1:30), but the latter ratio agrees with published findings in the isolated guinea pig ileum.

Animals↗
PubMedDate not supplied

Risk factors for esophageal cancer in lifelong nonsmokers.

Information on the etiology of esophageal cancer in lifelong nonsmokers is of interest to understand and quantify risk factors for the disease in the absence of the residual confounding by tobacco. Of a total of 316 cases with histologically confirmed incident cancers of the esophagus, 46 (17 males and 29 females) who described themselves as lifelong nonsmokers were selected to assess esophageal cancer risk in the absence of potential confounding and interactive effects of smoking. These patients were compared to 230 lifelong nonsmoker controls (85 males and 145 females) admitted to hospital for acute, nonneoplastic, non-alcohol-related conditions. The major risk factor for cancer of the esophagus in lifelong nonsmokers was elevated alcohol consumption: compared to drinkers of fewer than 4 drinks per day the relative risk (RR) was 2.7 (95% confidence interval, 1.1-6.8) for 4 to fewer than 8 drinks, and 5.4 (95% confidence interval, 1.4-21.0) for 8 or more drinks, with a significant trend in risk. Among selected indicator foods considered, significant protective effects were observed for fish (RR = 0.5 for the highest consumption tertile), green vegetables (RR = 0.6), and fresh fruit intake (RR = 0.3). Consequently, there was a significant inverse relationship with an estimate of beta-carotene intake (RR = 0.5 and 0.4, respectively, for the middle and highest tertiles of intake versus the lowest), with a significant trend in risk. The estimated RR for the highest alcohol consumption and lowest beta-carotene intake category was 8.6, and these two factors together explained over 45% of cases. Gastrectomy and family history of cancer of the esophagus were also associated with increased risk (RR = 4.6 and 4.3, respectively).

Adult↗
PubMedDate not supplied

Attributable risk for oral cancer in northern Italy.

Using data from a case-control study conducted between 1984 and 1992 in the provinces of Milan and Pordenone, northern Italy, on 439 cases of oral and pharyngeal cancers and 2106 hospital controls, we computed the population attributable risk for oropharyngeal cancer in relation to tobacco, alcohol, and a measure of low beta-carotene intake. Two different models were used for estimating relative risks, one assuming that the three factors act multiplicatively on the relative risk and the second estimating separately each combination of alcohol and tobacco and assuming a multiplicative model only for beta-carotene. The estimated attributable risks were similar for the two models considered. For both models and both sexes, the single factor with the highest attributable risk was smoking, which accounted for 81-87% of oral cancers in males and for 42-47% in females. Alcohol explained about 60% of male cases, but only 15% of female ones, and low beta-carotene accounted for 24% of total cases (25% of males, 17% of females). Together the three factors were responsible for 91-94% of oropharyngeal cancers in males, 51-57% in females, and 85-88% in both sexes combined. The present knowledge of major identified risk factors could, in principle, reduce the burden of the disease in Italy from 2400 to about 200 deaths per year for males and from 500 to 230 for females, thus explaining the difference in incidence and mortality between the two sexes.

Adult↗
PubMedDate not supplied

Epidemiology of renal-cell carcinoma.

Renal-cell cancer is responsible for about 2% of all cancer deaths in developed countries and represents 80-85% of all tumors of the kidney. Its etiology is still largely undefined. Recently the results of a large international population-based case-control study (International Renal-Cell Cancer Study), conducted between 1989 and 1991 in Australia, Denmark, Germany, Sweden and USA, including 1732 cases and 2309 controls, showed an increased risk of renal-cell cancer in relation to tobacco smoking, elevated body mass index, a few medical conditions, the use of beta-blockers, a family history of the disease, high intake of dairy products and low intake of fruit and vegetables and, in women, multiparity. Most other studies agree about a causal role of cigarette smoking in the etiology of renal-cell cancer, although its association is less strong than for several other tobacco-related neoplasms, with a relative risk of about 2 for current smokers. Other established risk factors are elevated body mass index (mainly in women) and a family history of the disease. Occupational exposure to chemicals appears to have little significance, although associations with specific products, such as asbestos fibres, have been reported. Some relationship has been observed between renal-cell cancer and hypertension, use of anti-hypertensives and kidney diseases, although this issue remains open to discussion. Data are inconsistent on the role of nutrition, mainly for fats and proteins, while vegetable and fruit consumption seems to convey some protection on renal-cell cancer risk. The risk of renal-cell cancer was not materially elevated in relation to coffee, tea and alcohol intake and, in women, oral contraceptive use, hormone replacement therapy, and menstrual factors.

Carcinoma, Renal Cell↗