Biomedical subjects
Publications and source records attributed to P Muti.
Gender differences in coronary heart disease frequency is dramatic during the reproductive age of the woman. The main biological difference during this age depends on the endogenous sexual hormone pattern. This paper discusses the possible role of these hormones in determining the coronary risk and the coronary heart disease.
Little experience is available to solve methodological and organizational problems when setting up a biological specimen bank as a support to prospective studies on chronic diseases. Sample aliquots preparation, processing procedures and storage system are discussed in the present paper. Problems related to the quality of biological material stored, as to the influence of the very low temperature freezing physico-chemical effects, are discussed also in the appendix.
Some procedures and methods for the measurement of cardiovascular risk factor are described; in particular of anthropometric measurements (weight, height, arm circumference, wrist circumference, hip circumference) of blood pressure, of electrocardiogram and of blood samples for the preservation of biological specimens. Some advice for the quality control during screening activities are reported.
Intra-individual variability for serum and urinary hormones has been inadequately considered in previous studies. Therefore, in the planning phase of a prospective study of Hormones and Diet in the Etiology of Breast Cancer (ORDET study), androgen levels have been examined at two different times in 56 women (26 in premenopause and 30 in postmenopause). Hormonal measurements in serum showed a good level of agreement for both premenopause (pre) and postmenopause (post): androstenedione pre r = 0.70 (p less than 0.0001), post r = 0.77 (p less than 0.0001); testosterone pre r = 0.73 (p less than 0.0001), post log values r = 0.74 (p less than 0.0001). Dihydrotestosterone showed a good level for premenopause only: log values pre r = 0.82 (p less than 0.0001), post r = 0.41 (p less than 0.05). Agreement levels in urine were inferior to those of serum: testosterone pre r = 0.53 (p less than 0.05), post r = 0.41 (p less than 0.05); androstanediol log values r = 0.46 (p less than 0.001), post log values r = 0.57 (p less than 0.05). Correlation between the two measurements improves considering age, parity, time of blood collection and, for urine, the interval of sample collections.
This present work aims to give a critical description of the organization and operative aspects of project ORDET (prospective study on diet and hormones in the aetiology of breast cancer). A number of problems which could arise when carrying-out a prospective study are described: they concern participant recruitment, laboratory organization, planning of a biological bank plus relative security checks in order to ensure full workability and personnel standardization in questionnaire administration and anthropometrical measurements. The methods adopted by ORDET, or at least some of them, could be useful for those engaged in the planning phase of a similarly designed project using a biological bank.
The cross-sectional association between consumption of various fats (eg, butter, olive oil, and vegetable oil) and risk factors for coronary heart disease was analyzed in a sample of 4903 Italian men and women 20 to 59 years of age. The intake of fats was ascertained by an interviewer-administered questionnaire. Increased consumption of butter was associated with significantly higher blood pressure and serum cholesterol and glucose levels for men; in women only the association with glucose reached statistical significance. In both sexes consumption of olive oil and vegetable oil was inversely associated with serum cholesterol and glucose levels and systolic blood pressure. These findings were adjusted for confounding effects of other risk factors for cardiovascular disease. These cross-sectional findings from a large population sample suggest that consumption of butter may detrimentally affect coronary risk factors, while polyunsaturated and monounsaturated fats may be associated with a lower coronary risk profile.
In this paper we present a study of the diurnal variation of testosterone (T) and estradiol (E2) in women, carried out as part of the design of a prospective study on the hormonal and nutritional etiology of breast cancer. Blood samples were obtained 5 times on the same day, in the morning and early afternoon, from 23 women aged between 25 and 63 yr. Twelve were sampled within the first days following daylight-saving time (SUMTI) introduction. In postmenopause, T mean values decreased from 08:00 h to 15:00 h and the effect of blood drawing time was statistically significant (p less than 0.01), with no significant effects of SUMTI. For E2 mean values, no significant effect was found for either blood drawing time or SUMTI. In premenopause, T mean values decreased from morning to afternoon (p less than 0.01), while no effect of SUMTI was found. A significant decrease was observed for E2 during the day (p less than 0.01), with no significant influence of SUMTI. These results indicate that diurnal variation of T and E2 are such, that one must not neglect the possible effects of timing procedures on hormonal measurements, when hormonal hypotheses are tested in comparative studies on cancer etiology.
The relationship between consumption of foods high in saturated fats and cholesterol and a number of coronary heart disease risk factors (blood pressure, serum glucose, serum cholesterol, and triglycerides) was analyzed in a large sample (4,917) of Italian men and women, ages 20-59 years. The dietary habits of the participants were ascertained with a food frequency questionnaire. Intake of atherogenic foods (foods high in cholesterol and saturated fats) was evaluated for each participant. In both sexes, systolic blood pressure, serum glucose, and serum cholesterol increased with higher consumption of atherogenic foods. These findings were independent of any possible confounding effect of age, adiposity, alcohol intake, and cigarette smoking. The present article confirms previous findings that consumption of foods high in saturated fats and cholesterol is associated with an increased risk for atherosclerosis.
A number of cancers, such as cancer of the large bowel, breast and other hormonal dependent organs, are less frequent in Mediterranean countries than in northern Europe. It has been hypothesized that a low dietary intake of saturated fat, accompanied by a higher intake of unrefined carbohydrates, and possibly other protective nutrients could be the cause of such risk differences. Cohort and case control studies based on individual dietary intake, however, cannot definitely corroborate the theory, nor disprove it. Analytical studies on fat, fibre and breast and colon cancers are reviewed and priorities for further studies are discussed.
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High calorie and fat consumption and the production of free radicals are two major mechanistic pathways between diet and disease. In this study we evaluated the effect of a plant-based diet poor in animal fat and rich in (n-3) fatty acids on fatty acids of serum phospholipids and on the production of reactive oxygen metabolites (ROMs). One hundred and four healthy female postmenopausal volunteers were recruited and randomized to a dietary intervention or a control group. Dietary intervention included a program of food education and biweekly common meals for 18 weeks. When the intervention and control groups were compared, it was seen that dietary intervention resulted in a significant reduction of saturated fatty acids (-1.5%) and a significant increase in (n-3) fatty acids (+20.6%), in particular docosahexaenoic acid (+24.8%). We observed that arachidonic acid decreased (-7.7%), while (n-6) fatty acids did not, and the (n-3)/(n-6) polyunsaturated ratio increased significantly (+24.1%). As expected, ROMs decreased significantly in the intervention group (-6%). The results indicated that a plant-based diet can improve the serum fatty acid profile and decrease ROMs production. These results suggest that a plant-based diet may reduce the body's exposure to oxidative stress.
The objective of this study is to evaluate the effect of cryopreservation at different storage temperatures on urinary 6-sulfatoxymelatonin (aMT6s) concentration. Overnight urine from 28 postmenopausal women participating in the ORDET cohort study was filtered and separated into 6 mL aliquots. Urine samples were stored at -80 degrees C and at -30 degrees C for an average of 14 years. Urinary aMT6s concentration was assessed using a competitive immunoassay. Mean aMT6s values of samples stored at -30 degrees C were systematically lower than those of samples stored at -80 degrees C (10.7 ng/mL versus 15.8 ng/mL, p<0.001). Bland Altman plots showed disagreement between determinations at different storage temperatures at the highest levels of the metabolite concentration. The degree of agreement evaluated in terms of intraclass correlation coefficient was 0.68 (95% CI 0.41-0.84, p<0.0001). Pearson's correlation coefficient between aMT6s values of the two differently stored samples was 0.93 (p<0.001), while the Kendal tau coefficient for rank distribution was 0.73 (p<0.001). Our data suggest that storage temperatures might affect degradation of aMT6s during storage. However, individual characterization by melatonin levels does not seem to be affected by cryopreservation conditions.
Prospective studies based on the storage of biological samples at low temperature have opened new perspectives in etiological research on cancer. In planning these studies a crucial question is to evaluate whether the long-term preservation of samples is able to affect the categorization of the subjects involved. In the frame of the ORDET project, a prospective study of hormones and diet in the etiology of breast cancer provided with a -80 degrees C biological bank, we have evaluated the stability of estradiol, free and total testosterone, and prolactin in serum and plasma samples over 3 years of cryoconservation. Study results showed that the subjects maintained almost the same rank by hormonal concentration throughout the 3-year period for all hormones. Looking at the stability over time, estradiol, prolactin, and total testosterone had fairly good performance for both serum and plasma. Serum-free testosterone increased in time up to 30%, whereas progesterone decreased by about 40% of the initial concentration. However, the reliability of the individual categorization by hormonal level suggests the validity of low temperature storage for epidemiological purposes, at least for hormonal parameters.