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Biomedical subjects

G Ronco

Publications and source records attributed to G Ronco.

At least 55 records · Page 3Linked to original sources

Pharmacokinetic studies of N-butyric acid mono- and polyesters derived from monosaccharides.

The pharmacokinetics of seven butyric esters derived from monosaccharides were studied after iv administration of a bolus dose to rabbits. Results obtained showed that a constant plasma level of butyric acid is maintained due to the slow disappearance of butyric acid esters from the plasma in contrast to the case of salts, such as arginine butyrate, which are rapidly cleared. The maintenance of these covalent compounds in the body can increase concentrations of n-butyric acid in the tumor area for more efficient chemotherapy. These results seem to be directly related to the in vitro anticellular activity of butyric esters and the prolonged therapeutic protection in tumor-bearing animals.

Animals↗

The differential diagnosis of primary lung cancer: inter-observer agreement and contribution of specific diagnostic procedures.

In order to investigate inter-observer variability in the differential diagnosis of primary lung cancer among women and the contribution of specific diagnostic procedures to this diagnosis, a group of 449 suspect cases of this disease was studied. Based on a standard dossier (including clinical data and the reports, if present, of radiology, bronchoscopy and histology) six different physicians independently judged, for each woman, at each diagnostic step, the presence of a primary lung cancer. A final consensus was organized in order to define the true cases. Radiology and especially histology seem to give the most important contribution to the diagnosis. On the other hand bronchoscopy seems to be useful mainly as a guide for biopsy. A predictive value of 90% was found when both radiology and bronchoscopy were positive; in the other cases histology seems to be needed to reach an adequate discrimination. Inter-rater agreement increases with an increasing amount of information but is not very high even when histology is available.

Bronchoalveolar Lavage Fluid↗

Cancer risk among Danish and Italian farmers.

Cancer risk for farmers in Denmark and Italy was studied by linking occupational census data with incidence of cancer in Denmark and with cancer mortality in Italy. Farmers in the two countries had a consistent risk reduction for cancer of the lung, bladder, small intestine, colon, rectum, and prostate. No excess of stomach cancer was found among farmers in the two countries, which is in agreement with the most recent data from other surveys. The risk of oesophageal cancer was reduced among the Danish and increased among the Italian male farmers. This can probably be explained by differences in alcohol consumption between the Danish and Italian farmers compared with the general population. The risk of brain cancer was significantly reduced among Italian farmers. There was a significant risk reduction for Hodgkin's disease and no excess for non-Hodgkin's lymphoma in Denmark, whereas in Italy a statistically significant excess risk was found for the first and a slight excess risk for the second of these diseases. The per capita consumption of phenoxy-herbicides between 1950 and 1970 was lower in Italy than in Denmark but treatments were performed mainly by professional applicators in Denmark and by the farmers themselves in Italy. Risk of leukaemia among Italian female farmers was increased. In Denmark, this increase was limited to women who were themselves owners of a farm. Specific occupations in agriculture showing a high risk for cancers of the lymphopoietic system in Denmark mostly entailed contact with animals.

Adolescent↗

Interindividual variation in carcinogen metabolism and bladder cancer risk.

Epidemiological studies indicate that subjects of the genetically based slow acetylator phenotype may be at higher risk for bladder cancer than fast acetylators, particularly when they are exposed to carcinogenic arylamines: N-acetylation is a detoxification step in the metabolism of some arylamines. We describe two collaborative studies on tobacco smoking, in which markers of internal dose (arylamine-hemoglobin adducts) and markers of genetically-based metabolic polymorphism have been coupled. In the first investigation, we found that hemoglobin adducts formed by mononuclear arylamines have high reciprocal correlation coefficients, as do adducts from binuclear arylamines. This tendency of adducts with structurally similar arylamines to correlate reciprocally explains a large proportion of the residual variance seen after controlling for smoking habits (number and type of cigarettes). In the second study, the concentration of 4-amino-biphenyl-hemoglobin adducts varied according to three independent determinants: number of cigarettes, type of tobacco (air or flue cured), and acetylator phenotype (slow and fast). The dose-response relationship between the amount of tobacco smoked and level of 4-aminobiphenyl-hemoglobin adducts in the slow acetylators (with an immediate steep increase of the adducts) was different from that in the fast acetylators (with a more regular increase). These findings from "molecular epidemiology" may contribute to an understanding of the role of metabolic polymorphism in human carcinogenesis.

Acetylation↗

[Protective activity of monoacetone glucose 3-butyrate, prodrug of n-butyric acid, against the fatal effect of encephalomyocarditis virus in mice].

A comparative study was made, in the mouse, on antiviral properties of a prodrug of n-butyric acid derived from monosaccharides: monoacetone glucose 3-butyrate (MAG = 3but), and of a free form of n-butyric acid: arginine butyrate (BuO Arg). Preventive injection of MAG = 3but protected the mice twice as effectively as BuO Arg against the lethal effect of 100 LD50 of encephalomyocarditis virus. Under the same experimental conditions, monoacetone glucose (MAG) used as carrier of the biologically active moiety, was inactive on its own. Antiviral activity of MAG = 3but was shown not to be virucidal, but rather could involve stimulation of the immune system. This capability supplements known anticellular and antitumoral properties. In total these results indicate a prime therapeutic importance for this new molecule, pharmacokinetically suitable, with its very low toxicity, for clinical application. Combined use of MAG = 3but with biological response modifiers which have similar affinity, such as Interferon, is discussed.

Animals↗

Butyric monosaccharide ester-induced cell differentiation and anti-tumor activity in mice. Importance of their prolonged biological effect for clinical applications in cancer therapy.

The interest of butyric salts is based on their capacity to promote differentiation of malignant cells and inhibition of tumor development. The phenotypic modifications are rapidly reversible and require the continuous presence of butyric salts in the target area, which raises problems for therapeutic applications. We show here that the covalent binding of n-butyric acid on natural polyhydroxylated compounds such as monosaccharides, especially 3- or 6-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose, retains the majority of the biological properties of n-butyric acid. The delayed degradation of these covalent compounds is associated with an improved maintenance of cell differentiation and anti-tumor protection in mice. These butyric complexes thus seem potentially useful for therapeutic applications.

Animals↗

New stable butyrate derivatives alter proliferation and differentiation in human mammary cells.

Two new butyric esters which were devised to extend the half-life of n-butyric acid in vivo, were used to study their effects on a number of phenotypic characteristics including cell morphology, cell proliferation, colony formation, cell-surface antigen and estrogen receptor expression in 3 normal immortalized cell lines and 2 carcinoma cell lines derived from the human mammary gland. When treated with butyric esters, human mammary cells acquired numerous cytoplasmic granules and vacuoles, reminiscent of secretory functions, and increased in volume. Modulation of the expression of membrane-associated antigens recognized by the monoclonal antibodies (MAbs) 115D8, 140C1 and 125B5 was also observed. Furthermore, butyrate derivatives inhibited the proliferation of all the cell lines tested and the colony-forming capacity of those that grew in soft agar. The inhibitory effects were, however, reversible upon removal of butyric esters from the culture medium. In the human breast carcinoma cell line, MCF-7, in which the cytostatic effects of butyric esters were the most pronounced, cells accumulated in the G0/G1 phase of the cell cycle. This cell line was the only one to contain estrogen receptors which decreased in number when treated with butyric esters without any modification in their binding affinity. Moreover, the stimulatory effects of estrogen on MCF-7 cell proliferation were antagonized by butyric esters. Our results demonstrate that many of the proliferative and differentiation changes previously reported for n-butyrates in tumor cells are similarly produced by the new stable butyrate derivatives in normal and malignant human mammary cell lines.

Antigens, Surface↗

The length of pregnancy: an echographic reappraisal.

A study of 998 pregnant women was conducted to estimate the random errors in dating pregnancy by menstrual history and by ultrasound measurements of the fetus (crown-rump length or biparietal diameter before 20 weeks, menstrual age) as well as the biological variability of pregnancy length. The latter was found to be 7.74 days. The random errors made when dating pregnancy by menstrual history and by ultrasound measurements were 7.16 days and 4.26 days, respectively. (All variabilities are expressed as standard deviations). The differences between the two methods were mainly attributable to some large errors occurring when dating pregnancy on the basis of menstrual history. Differences between methods of more than 10 days were observed in about 10% of our population. When the two methods were used on the same patients to define a pregnancy as preterm, at term, or postterm, discrepancies were found in about 7% of cases.

Female↗

Who has Pap tests? Variables associated with the use of Pap tests in absence of screening programmes.

Characteristics associated with the use of Pap tests were studied in a random sample of 581 women 18-69 years old; residents of Turin, Italy. There has been no organized screening programme in the area. (Tests possibly related to symptoms were not considered). Data were analysed by multiple logistic regression. Some 48% of women had never had a smear. The prevalence of women ever undergoing a Pap test was higher in middle-aged, married and more educated women (p less than 0.001 in all these cases). We found a linear trend (p less than 0.05) related to time since last visit to the family physician. A number of 'preventive' behavioural practices (physical exercise, no alcohol consumption) and experience of early diagnostic procedures for cancer e.g. BSE and mammography, were also associated with ever having had a Pap smear. The prevalence of ever-tested women was significantly lower among lifetime non-smokers than among ex-smokers and current smokers who planned to stop smoking but not lower than in current smokers who did not plan to stop. Results were similar when having had a test within the last three years was taken as the outcome. These results may be useful in planning screening strategies and educational programmes designed to improve attendance in an organized screening programme.

Adolescent↗

Practice of early diagnosis of breast and uterine cervix cancer in a northern Italian town.

We studied the practice of screening for breast and uterine cervix cancer in Torino where, currently, no kind of organized program exists and two projects of population screening programs, based on pap smear and mammography, have been developed. Fifty-two percent (95% confidence limits (C.L.): 47%-58%) of women 18-69 years old had had a pap test or colposcopy in the absence of symptoms during their lifetime. Among them 50% had had their last pap test within 18 months of the interview, 77% within 3 and 1/2 years, and only 14% was screened 5 and 1/2 years before or earlier. Thirty percent of never-screened women (95% C.L.: 25-35%) would not accept any of the proposed modalities for screening. Overall, 15% of women had had a mammography for screening purposes. Among women 50 to 59 years old, 23% (95% C.L.: 17-30%) had had at least one mammography for screening purposes in their lifetime, but only 18% (95% C.L.: 13-24%) had had at least 1 screening test at age 50 or after. Half of ever-screened women age 50-69 years had had the last mammography within 2 and 1/2 years. Among all respondents in the same age group this figure was 11% (95% C.L.: 7-15%). Forty-one percent of respondents reported to currently practice BSE (95% C.L.: 36-45%), but this proportion dropped to 10% in the age group 19-39 years and to 4% among women 40-69 years old when only those who had 10-13 examinations each year and judged their performance to be good were considered. Thirty-nine percent (95% C.L.: 34-44%) had had a physical examination of the breast performed by a medical doctor in the absence of symptoms within the last 18 months. Thirty-five percent (95% C.L.: 31-38%) of all women had never had a mammography, did not practice BSE, and had never consulted a physician for control in the absence of symptoms. Analysis by age, birth cohort, education, marital status and place of birth is presented.

Adolescent↗

Haemoglobin adducts formed by aromatic amines in smokers: sources of inter-individual variability.

In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. For this purpose we computed residuals from analysis of variance in order to adjust for individual smoking habits (type and amount of tobacco). Residuals were correlated within two clearly distinct groups: one formed by binuclear compounds (4-aminobiphenyl, 3-aminobiphenyl and 2-naphthylamine) and the other formed by all other (i.e. mononuclear) compounds. Within each group, highly statistically significant correlation coefficients were found, whereas compounds belonging to one group were not correlated to compounds in the other group. These results can be interpreted as a suggestion that two different metabolic pathways exist, one for binuclear and one for mononuclear arylamines, and that inter-individual differences in such pathways can explain part of inter-individual variability in adduct levels. This interpretation is consistent with recent animal experiments suggesting that there are different enzyme systems for the two classes of compounds.

2-Naphthylamine↗

Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer.

Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N-nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances.

Cotinine↗

Occupation and lung cancer in two industrialized areas of northern Italy.

A population-based case-control study on lung cancer was conducted in 2 industrialized areas of northern Italy. Cases (126) were all males who died from lung cancer between 1976 and 1980. Controls (384) were a random sample of males dying from other causes during the same period. Jobs held during working life have been analyzed according to a list of occupations already known to be causally associated with lung cancer (list A) and a list of occupations suspected of being so (list B). Attributable risk percentages in the population for occupations included in either list A or B were about 36% and 12% in the 2 areas. Welders or workers in industries in which welding is common showed elevated odds ratios: 2.9 for welders (95% CI 0.9-9.8); 4.9 (1.1-22.9) for structural metal workers; 11.4 (2.6-49.9) for workers in structural metal production. Other job categories associated with lung cancer included: electricians and workers in electrical machine production, woodworkers (in furniture or cabinet making, but not in carpentry or joinery) and cleaning services. Smoking did not seem to exert a substantial confounding effect. Attributable risk percentages for tobacco smoking were about 78% and 76% in the population of the 2 areas.

Adult↗

Use of magnesium silicate before gas-liquid chromatography for determination of "total estrogens" in urine during pregnancy.

The authors propose a simple, rapid, reproducible and reliable method for determination of "total estrogens" in urine during the last three months of pregnancy. The procedure consists of separation of free urinary estrogens, obtained after rapid hydrolysis, on a column of magnesium silicate. The estrogens are adsorbed on the column at acid pH and eluted by 1 M potassium hydroxide. Following extraction of the eluate by diethyl ether and formation of trimethylsilyl ether derivatives, the steroids are analysed by gas-liquid chromatography. This new procedure is used routinely in our laboratory, one assay being carried out in less than three hours. The results appear to be comparable to those obtained with classic methods. We wish to report the elimaination curves of "total estrogens" during normal pregnancies and their allowable limits.

Chromatography, Gas↗

Anti-hypertensive effect of acebutolol: its relation to sympathetic nervous system responsiveness and to plasma renin and dopamine-beta-hydroxylase activities.

1. Acebutolol, a beta1-receptor blocker, has, at a daily dose of 800 mg, a mild but significant anti-hypertensive effect in moderate sustained essential hypertension with normal or low plasma renin activity. 2. Prediction of its anti-hypertensive effect is better based on the evaluation of the sympathetic nervous system responsiveness to head-up tilt than on the evaluation of plasma renin activity or dopamine-beta-hydroxylase. 3. The anti-hypertensive effect of acebutolol is better explained on the basis of inhibition of the sympathetic nervous system activity than on the basis of suppression of plasma renin activity. 4. A positive correlation between plasma renin activity and dopamine-beta-hydroxylase in patients on diuretics suggests the common dependence of these two variables on sympathetic overactivity.

Acebutolol↗