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Biomedical subjects

G Perrone

Publications and source records attributed to G Perrone.

At least 37 records · Page 2Linked to original sources

Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.

Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.

Adolescent↗

The effects of cereal substrate and temperature on production of beauvericin, moniliformin and fusaproliferin by Fusarium subglutinans ITEM-1434.

One strain of Fusarium subglutinans (ITEM-1434) isolated from maize ear rot in Poland was tested for the ability to synthesize moniliformin (MON), beauvericin (BEA) and fusaproliferin (FP) on six cereal substrates (wheat, rye, barley, oat, maize and rice kernels) for 3 weeks at 25 degrees C and on rice at three different temperatures (20, 25 and 30 degrees C). Most MON (497 micrograms/g) was produced on rice; most BEA (704 micrograms/g) on wheat or rice, and most FP (422 micrograms/g) on rye. When cultured on rice, F. subglutinans produced the highest levels of BEA and FP at 20-25 degrees C, while MON production was best at 30 degrees C.

Anti-Bacterial Agents↗

Decreasing ascorbate intake does not affect the levels of glutathione, tocopherol or retinol in the ascorbate-requiring osteogenic disorder shionogi rats.

Levels of glutathione in liver and kidney, and other nutrients in plasma were evaluated in male and female ascorbate-requiring osteogenic disorder Shionogi (ODS) rats fed semipurified diets in which the concentrations of ascorbate were gradually decreased from 1965 to 180 mg/kg. Plasma ascorbate levels in ODS rats were unaffected when ascorbate levels in the diet were decreased from 1965 to 768 mg/kg. However, plasma ascorbate levels decreased progressively when levels of ascorbate in the diet were decreased from 527 to 180 mg/kg. Plasma ascorbate levels decreased up to 77% when the dietary ascorbate concentration decreased from 1965 to 180 mg/kg. Ascorbate levels in liver and kidney fell as much as 60-70% when the dietary ascorbate levels were reduced from 1965 to 180 mg/kg. However, the glutathione levels in these tissues were not affected. Plasma retinol and vitamin E levels were not affected by decreasing dietary ascorbate intake. Total cholesterol levels increased significantly in female rats as dietary ascorbate intake declined. Levels of glycated hemoglobin decreased significantly when dietary ascorbate levels decreased from 1965 to 527 mg/kg. This study suggests that levels of vitamin E, retinol and glutathione are not affected by decreased dietary intake of ascorbate under nonscorbutic conditions, whereas elevated ascorbate intake is associated with a decrease in levels of plasma cholesterol in female ODS rats. However, excessive intake of ascorbate may be associated with elevated glycation of hemoglobin. To achieve the maximal health benefit of ascorbate supplementation, further studies are necessary to define optimal ascorbate intakes.

Administration, Oral↗

Evaluation of the body composition and fat distribution in long-term users of hormone replacement therapy.

The aim of the study was to evaluate the body composition and fat distribution in long-term users of hormonal replacement therapy (HRT). 18 healthy menopausal women, long-term users of HRT (transdermal estradiol 50 microg continuously administered and 10 mg/day of medroxyprogesterone acetate for 12 days/month) and 18 healthy menopausal women, who had never used HRT were included in the study. Age, menopausal age, parity, weight and height (body mass index, weight/height2), and lifestyle habits were similar. Waist and hip circumference, body composition and waist/hip ratio were measured and the results were analyzed. No significant difference was demonstrated in fat and water percentage, and waist/hip ratio. Nevertheless, the waist circumference of long-term HRT users was significantly lower than that of non-users. In conclusion, abdominal fat in long-term HRT users is lower than that of non-users of similar age, menopausal age and body mass index.

Adipose Tissue↗

[Hormone substitution therapy. Side-effects and compliance of various therapeutic regimens].

BACKGROUND: The aim of this study is to evaluate the tolerability and long-term compliance of four Estrogen Progestin treatments (HRT) for menopause. METHODS: One hundred and ten symptomatic menopausal women were divided into four groups according to therapeutic regimens: A) Estradiol (E2) transdermal treatment 50 micrograms (TTS 50) continuously administered (cont.) plus Medroxyprogesterone Acetate (MPA) 10 mg/die for twelve days a month: 35 women. B) Conjugated Equine Estrogens (CEE) 0.625 mg/die cont. plus MPA for twelve days a month: 25 women. C) Estradiol transdermal 50 micrograms (cont.) plus MPA 2.5 mg/die cont.: 26 women. D) CEE 0.625 mg/die cont. plus MPA 2.5 mg/die cont.: 24 women. RESULTS: Menopausal symptoms were significantly reduced with all treatments. During the first year group C and D patients showed irregular bleeding (group C: 46%, group D: 61%). After 24 months the bleeding frequency was reduced (group C: 11%, group D: 13%). Mastodynia was the more frequent side-effect in particular among women who were utilizing cont.comb. regimens. The total percentage of drop out (D.O.) after 2 years was more than 30% (Group A: 31%, Group B: 33%, Group C: 39%, Group D: 35%). The most frequent reasons for abandoning HRT (79% of all DO) were not linked to therapy side-effects. 19% of DO switched to other hormonal regimens.

Administration, Cutaneous↗

Glutathione and catalase provide overlapping defenses for protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae.

Glutathione (GSH) is an abundant and ubiquitous low-molecular-weight thiol which has proposed roles in many cellular processes including protection against the deleterious effects of reactive oxygen species. Our experiments have addressed the role of GSH in protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae, and have shown that GSH and catalase provide overlapping defense systems. GSH appears to be the primary antioxidant for protection against hydrogen peroxide since mutants lacking GSH (gsh1) or glutathione reductase (glr1) are sensitive, whereas, strains lacking catalase A (cta1) or catalase T (ctt1) are unaffected in resistance to this oxidant. Furthermore, following treatment with hydrogen peroxide, the levels of oxidized, protein-bound and extracellular GSH were all increased at the expense of intracellular GSH. However, there are two lines of evidence that indicate catalases are required in the absence of GSH; firstly, strains that lack both catalase A and T accumulate increased levels of oxidized glutathione following treatment with hydrogen peroxide; and secondly, deletion of catalase genes exacerbates the hydrogen peroxide sensitivity of glr1 and gsh1 mutants.

Antioxidants↗

The effects of aging and calorie restriction on plasma nutrient levels in male and female Emory mice.

We examined the effect of diet, age (4.5, 13 and 23 months), and sex on plasma levels of retinol, tocopherol, ascorbate, cholesterol, glucose and glycohemoglobin in male and female Emory mice which were fed control (C) and 50% calorie restricted (R) diets. Results showed that C fed animals tended to have higher levels of plasma ascorbate (50-71%), cholesterol (23-71%), glucose (38-81%) and glycohemoglobin (50%). However, these diet differences varied with the age and sex of the animals. Plasma retinol levels were lower only in R males vs. C males (50%). Novel sex-related differences in levels of plasma retinol (2-fold higher in C male mice than in C or R female mice) are described. Aging was associated with trends towards lower levels of plasma ascorbate (14-25%), glucose (34-36%) and glycohemoglobin (47-57%) from 4.5 to 23 months of age. However, these age differences depended upon the diet and sex of the animals. These data suggest that lower plasma levels of glucose, glycosylated hemoglobin and cholesterol may be causally related to the life extension noted in R animals since elevated levels of these moieties have been related to aging. Since oxidative stress is thought to be causally related to aging it appears unlikely that retinol, tocopherol and ascorbate are causally related to R-induced life-extension.

Aging↗

Bax immunohistochemical expression in breast carcinoma: a study with long term follow-up.

Bax and Bcl2 are functionally antagonistic proteins which control apoptosis, whose expression in human tumours could be of prognostic value. We evaluated Bax and Bcl2 expression in 239 breast carcinomas (99 N0, 140 N1/2) with long term follow-up (median 79 months, range 11-140) in relation to clinico-pathologic parameters, clinical outcome, adjuvant therapy and expression of oestrogen receptor protein and p53. The prognostic value of Bax was investigated in the whole series of patients and in subgroups of homogeneously staged and treated patients (i.e., node-negative, N1/2 CMF-treated, N1/2 tamoxifen-treated). Bax immunostaining was cytoplasmic and heterogeneous. Cases were scored as Bax-positive if there were more than 20% reacting cells. High Bax expression was associated with positive nodal status (p = 0.03) and high Bcl2 expression (p = 0.01) and was more frequent in high-grade tumours. In the node-negative subgroup, Bax expression was associated with small tumour size. No association was seen with other parameters or with clinical outcome in any subgroup of patients. Since the apoptotic rate of a tumour is influenced by the ratio Bcl2/Bax, we investigated the combined effects of Bax and Bcl2 expression in relation to clinical outcome. However, no differences in survival were seen in the Bcl2-negative and Bcl2-positive groups when they were subdivided on the basis of the level of Bax expression and vice versa. In experimental systems, p53 is a direct transcriptional activator of the human bax gene. However, we could not observe any relation between Bax and p53 expression. We investigated whether the combined p53/Bax expression could have any prognostic value since it is predicted that tumours with normal p53 expression and concurrent high levels of Bax should be less aggressive and more susceptible to therapy. However, while p53 itself was of prognostic value, Bax expression was not related to prognosis in p53-negative or in p53-positive groups.

Breast Neoplasms↗

Tissue carcinoembryonic antigen and oestrogen receptor status in breast carcinoma: an immunohistochemical study of clinical outcome in a series of 252 patients with long-term follow-up.

Carcinoembryonic antigen (CEA) is a well-known tumour marker whose immunohistochemical expression could be prognostically relevant in breast carcinomas. We evaluated CEA immunohistochemical expression, using the specific T84.66 monoclonal antibody, in a series of 252 consecutive cases of infiltrating breast carcinomas (104 N0, 148 N1/2) with median follow-up of 84 months. Oestrogen receptor (ER) status has been evaluated with the immunohistochemical method (ER1D5 antibody, 10% cut-off value): 121 cases were ER negative, 128 cases were ER positive and in three cases ER status was unknown. CEA staining was cytoplasmic; staining intensity and percentage of reacting cells were combined to obtain a final score (CEA score). The difference between the distribution of CEA score within the modalities of the other variables was not statistically significant. Univariate survival analysis has been performed on the series of node-negative and node-positive patients. In the latter subgroup, this has been performed separately for patients treated with systemic adjuvant hormonal therapy or chemotherapy. A multivariate analysis was only performed for node-positive patients treated with adjuvant therapy. CEA immunoreactivity was not prognostically relevant in any subset of analysed patients. The most important prognostic markers were nodal status and tumour size.

Antibodies, Monoclonal↗

Susceptibility and genetic relatedness of invasive Haemophilus influenzae type b in Italy.

Haemophilus influenzae type b (Hib) still causes a large portion of meningitis in children less than 5 year old in Italy because vaccination against this agent has not been fully implemented in the country. We have studied 78 Hib strains and 4 nontypable H. influenzae (NTHi) isolated from the cerebrospinal fluid of subjects with meningitis for susceptibility to ampicillin, chloramphenicol, and ceftriaxone. The macrorestriction profiles of chromosomal DNA obtained by pulsed-field gel electrophoresis (PFGE) following digestion with SmaI and ApaI were also determined. All strains except one were equally susceptible to the antibiotics tested. One Hib strain, the only beta-lactamase producer, showed an intermediate susceptibility to ampicillin (MIC = 2 microg/ml), while maintaining full susceptibility to chloramphenicol and ceftriaxone. The analysis of the PFGE patterns showed that most of the Hib isolates, including the beta-lactamase-positive Hib strain, belonged to the same clone or to closely related subclones. For three PCR-confirmed NTHi isolates, we obtained completely different PFGE profiles. In conclusion, resistance to ampicillin still appears to be a rare finding in Hib strains causing meningitis in Italy; moreover, PFGE showed that the population structure of invasive Hib is essentially clonal.

Adult↗

The yeast Saccharomyces cerevisiae contains two glutaredoxin genes that are required for protection against reactive oxygen species.

Glutaredoxins are small heat-stable proteins that act as glutathione-dependent disulfide oxidoreductases. Two genes, designated GRX1 and GRX2, which share 40-52% identity and 61-76% similarity with glutaredoxins from bacterial and mammalian species, were identified in the yeast Saccharomyces cerevisiae. Strains deleted for both GRX1 and GRX2 were viable but lacked heat-stable oxidoreductase activity using beta-hydroxyethylene disulfide as a substrate. Surprisingly, despite the high degree of homology between Grx1 and Grx2 (64% identity), the grx1 mutant was unaffected in oxidoreductase activity, whereas the grx2 mutant displayed only 20% of the wild-type activity, indicating that Grx2 accounted for the majority of this activity in vivo. Expression analysis indicated that this difference in activity did not arise as a result of differential expression of GRX1 and GRX2. In addition, a grx1 mutant was sensitive to oxidative stress induced by the superoxide anion, whereas a strain that lacked GRX2 was sensitive to hydrogen peroxide. Sensitivity to oxidative stress was not attributable to altered glutathione metabolism or cellular redox state, which did not vary between these strains. The expression of both genes was similarly elevated under various stress conditions, including oxidative, osmotic, heat, and stationary phase growth. Thus, Grx1 and Grx2 function differently in the cell, and we suggest that glutaredoxins may act as one of the primary defenses against mixed disulfides formed following oxidative damage to proteins.

Amino Acid Sequence↗

Microanatomy of the female reproductive organs in postmenopause by scanning electron microscopy.

The detailed three-dimensional ultrastructural features of the reproductive organs of menopausal and postmenopausal women were studied by means of integrated transmission and scanning electron microscopy (SEM) and reported in a new colored microtopographical fashion. These methods revealed significant alterations in the microanatomy of the various reproductive organs specifically related to the decline of plasma estrogen levels. In particular, the ovary progressively showed characteristic wide areas of loss of epithelium with consequent exposure of the underlying connective tissue. Both endometrial and tubal mucosa demonstrated a gradual but often dramatic decrease in the number of ciliated cells which was more evident in the tube. In addition, the non-ciliated (microvillous secretory) cells of the uterus, including both endocervix and tubal mucosa, became flattened and, in some instances, their apical poles developed unusual wrinkles (microridges or microplicae). The ectocervix and vaginal squamous cells presented a reduction in the number of their microridges and changes in the typical structural organization. These microtopographical results showed that the decline of estrogen during the menopause and postmenopause induces important and complex structural changes of the woman's reproductive system, much more detailed than those revealed to date by the use of only conventional optical and transmission electron microscopy (TEM). The three-dimensional findings offer the opportunity to re-evaluate the classic histopathology of the above aging organs using more refined microtopographical and morphophysiopathological parameters.

Cervix Uteri↗

[A mammographic evaluation of the morphostructural variations of the breast during hormone-replacement therapy in the postmenopause].

INTRODUCTION: Exogenous hormones may cause breast tissue changes, generally increasing its density. We used mammography to detect the to early effects of hormone replacement therapy in postmenopausal women. MATERIAL AND METHODS: We examined 300 postmenopausal women (group A: 70 women in surgical menopause treated with estrogen replacement therapy; group B: 230 women in spontaneous menopause receiving estrogen and progestin replacement therapy). The mammographic patterns, according to Wolfe's classification, were compared with those of group C (case control group of 300 women) and group X after 1 year of therapy. The modification were classified as total and partial changes in mammographic density. The results were analyzed with Pearson's chi 2 test. RESULTS: The evidence of a change in parenchymal pattern was found in 103/300 women (34.3%). Twenty-one women in group A and 82 in group B showed increased mammographic density (the DY breast by Wolfe). Partial changes were observed in 64 cases (21.3%). Comparing groups A and B to groups C and X (before therapy), the changes were statistically significant (p < .001), while comparing groups A and B the difference was not significant (p = 1.000). CONCLUSIONS: The likely widespread use of hormone replacement therapy in the future will require an increase in the number of mammograms and a possible re-evaluation of sensitivity. To improve follow-up timing and to avoid a decrease in sensitivity, radiologists will have to consider both general and specific factors and to pay attention to the patterns of global increase in breast tissue density, the DY pattern of Wolfe's classification.

Breast↗

Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake.

PURPOSE: Given the recent correlation between nutrition and risk for eye disease, there is keen interest in a possible correlation between nutrient intake and eye-tissue nutrient levels. In this work, the objective was (1) to determine, for the first time, the relation between dietary intake of vitamin C and eye tissue levels of the vitamin in free-living humans, (2) to determine the relation between levels of the vitamin in plasma, lens and aqueous, and (3) to compare this information to data gathered for a carefully reared group of guinea pigs that were fed different levels of vitamin C. METHODS: Two hundred sixty-five cataract patients (mean age = 72 years) from a clinical practice were recruited for this study. One hundred thirty-two patients provided the dietary intake data via a food frequency questionnaire, which we used for this work. Plasma, aqueous humor, and lens samples were obtained at the time of lentectomy and preserved for vitamin C analysis. Comparable samples were obtained from male Hartley white guinea pigs that were fed known amounts of vitamin C. Linear and log10-linear statistical models were also used to characterize the relation between vitamin C intake and human ocular tissue levels of the vitamin and to examine potential confounding and the effect of modification by age and sex. RESULTS: In humans, plasma and aqueous vitamin C concentrations were related to intake in a log-linear fashion, with slopes of 0.03 mM plasma vitamin C/log10-mg daily vitamin C intake and 0.41 mM aqueous vitamin C/log10-mg daily vitamin C intake. The best fit of vitamin C levels in lens and diet predicts a linear relationship with a sex-adjusted slope of 0.00094 mM lens vitamin C/mg daily vitamin C intake, although a log-linear relation can also be modeled. In guinea pigs, diet was related to eye tissue and plasma levels of the vitamin by a log10 linear relationship in all cases. Vitamin C in human lens was linearly related to plasma and aqueous vitamin C with slopes of 8.8 and 0.23, respectively. Vitamin C in aqueous was related to plasma in a log10-linear fashion with a slope of 1.6 mM aqueous vitamin C/log10 mM plasma vitamin C. In guinea pigs, vitamin C in plasma was related to aqueous and lens vitamin C by log10-linear relationships, whereas lens and aqueous vitamin C were clearly linearly related. CONCLUSIONS: Plasma and aqueous appear to be saturated in humans with intakes of < 250 mg vitamin C/day. However, a saturating relationship between lens vitamin C and dietary intake in humans was not indicated in this study, although such a relationship is seen in guinea pigs. Intertissue relations between vitamin C levels in humans and guinea pigs are similar for some but not all relations.

Adult↗

Hormone replacement therapy affects various immune cell subsets and natural cytotoxicity.

The effects of hormone replacement therapy (HRT) on lymphocytes and granulocytes have never been determined in detail. Ten healthy menopausal women (age 49-51 years; menopause less than 2 years) were treated for 6 months by administering transdermal estradiol (100 micrograms/day for 21 consecutive days) and oral medroxyprogesterone acetate (10 mg/day from day 10 to day 21). Days 22-28 were therapy-free. All subjects were examined during the first and the last month of treatment: evaluations were carried out on days 0, 8, 21 and 28. CD4+CD45RO+ cells were found to be significantly reduced on day 8. CD56+ cells and CD8+CD11b+ cells were decreased on day 21 and recovered basal level on day 28. Natural killer cell function was transiently increased on day 8 and greatly reduced on day 21. During the first month of therapy, the expression of Leu8 and CD11b antigens on granulocyte membranes was significantly affected by HRT. Taken together, the results indicate that HRT selectively affects various immune cell subsets.

Cytotoxicity, Immunologic↗

[The effect of neoplastic hyperprolactinemia on bone density].

In young hyperprolactinaemic patients a reduction of bone mass density is frequently shown. However, until now the real mechanism has not been clarified (a direct role of PRL has been suggested). To better clarify the origin of the bone demineralization during hyperprolactinaemia we evaluated the BMD in a group of 24 proved PRL secreting pituitary adenomas. Based on menstrual characteristics the patients were subdivided in 3 groups: 1) oligomenorrhoea (OM), 2) amenorrhea lasting less than 2 years (AMa), 3) long-lasting amenorrhea (AMb). Twelve women with normal menstrual cycles served as controls. The BMD values at L2-L4 and thighbone levels were significantly reduced in the AMb group with respect to the other subgroups. The results support the hypothesis that BMD reduction in aPRL patients is secondary to hypoestrogenism and to the duration of amenorrhea rather than to hyperprolactinaemia.

Adenoma↗

[Severe hypertriglyceridemia in pregnancy. A clinical case report].

Cholesterol (TC) and triglyceride (TG) plasma levels physiologically increase during pregnancy. The lipid increment is respectively 23%-53% above pregravidic level for TC and two-three fold the pre-pregnancy level for TG. If the TC and TG are higher than normal values in pregnancy the patient must be carefully monitored. Acute pancreatitis is the main consequence of hyperlipidemia and it can occur either during pregnancy, in the third trimester, or in the puerperium. Mortality is high both for the mother (21%) and the fetus (20%). The authors report a case of 37-year-old pregnant woman at 35 week gestation with hypercholesterolemia (TC = 425 mg/dl) and severe hypertriglyceridemia (TG = 3315 mg/dl). The patient was admitted to the hospital for treatment with an appropriate diet and drug lowering lipid levels (gemfibrozil). The baby was delivered by cesarean section at week 36. The neonatal weight at birth was 2670 g and the Apgar score was 9 at the first minute. After delivery the maternal triglyceride levels showed a remarkable reduction. According to a review of the literature, severe hypertriglyceridemia in pregnancy should be treated with a careful restriction of calories and fat; for preventing acute pancreatitis hospitalization for intravenous fluid therapy and plasma exchange must be required.

Acute Disease↗

Production of neosolaniol by Fusarium tumidum.

Extracts from autoclaved maize culture of Fusarium tumidum strain R-5823 were toxic towards Artemia salina. Bioassay-guided fractionation of the organic extract led to the isolation of the toxic compound that was identified as the trichothecene toxin neosolaniol (NEOS) by 1H, 13C nuclear magnetic resonance spectroscopy and low-resolution electronic impact mass spectrometry. The amount of NEOS produced by the strain R-5823 was 300 mg/kg maize culture. NEOS was also detected by HPLC in cultures of four out of seven additional strains of F. tumidum and Gibberella tumida with different origin, in amounts ranging from 1 to 311 mg/kg. This is the first report on the production of a trichothecene toxin by F. tumidum.

Animals↗