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Biomedical subjects

E Colli

Publications and source records attributed to E Colli.

At least 19 recordsLinked to original sources
PubMed2004

Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia.

OBJECTIVE: Calcitriol analogues might represent an interesting new therapy for benign prostate hyperplasia (BPH). We here report the preclinical characterization of BXL-628, an analogue selected for an ongoing double-blind, randomized, placebo-controlled phase II trial in BPH. DESIGN: Experiments with BXL-628 were carried out in human BPH cells and in the ventral prostate of intact and castrated rats. METHODS: BPH cell and rat prostate growth were evaluated along with morphological and biochemical hallmarks of apoptosis. RESULTS: BXL-628 inhibited human BPH cell proliferation and induced apoptosis even in the presence of androgens or growth factors. It also decreased prostate growth to an extent similar to finasteride, inducing DNA fragmentation and apoptosis, both in intact and in testosterone-supplemented castrated rats. Accordingly, BXL-628, like finasteride, increased the expression of clusterin, a prostatic atrophy marker. However, BXL-628 did not inhibit 5 alpha-reductase 1 and 2, did not bind to the androgen receptor (AR) in BPH homogenates and did not affect AR-coupled luciferase activity. In addition, BXL-628 did not affect rat pituitary and testis activity or calcemia. CONCLUSIONS: BXL-628 inhibited in vitro and in vivo prostate cell proliferation, and therefore might represent a novel, interesting option for the treatment of BPH.

Animals↗
PubMed2001

Apaf-1 is a transcriptional target for E2F and p53.

Loss of function of the retinoblastoma protein, pRB, leads to lack of differentiation, hyperproliferation and apoptosis. Inactivation of pRB results in deregulated E2F activity, which in turn induces entry to S-phase and apoptosis. Induction of apoptosis by either the loss of pRB or the deregulation of E2F activity occurs via both p53-dependent and p53-independent mechanisms. The mechanism by which E2F induces apoptosis is still unclear. Here we show that E2F1 directly regulates the expression of Apaf-1, the gene for apoptosis protease-activating factor 1. These results provide a direct link between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels.

Animals↗
PubMed2001

Cigarette smoking: a risk factor for erectile dysfunction in diabetics.

OBJECTIVES: Diabetes is one of the systemic disorders most frequently associated with erectile dysfunction (ED). An extensive literature documents well the relationship between ED and several factors related to diabetic pathology, but the role of risk factors mainly related to life-style, e.g. cigarette smoking, is still not defined. METHODS: Eligible for the study were men aged 20-70 years with a diagnosis of insulin-dependent (type 1---IDDM) or non-insulin-dependent (type 2--NIDDM) diabetes who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 9,670 diabetic men. Of these 2,962 (30%) were never smokers, 2,877 (30%) current smokers and 3,831 (40%) ex-smokers. After taking into account the effect of age, the odds ratios of ED in comparison with never smokers was 1.4 (95% confidence interval 1.3-1.6) for smokers and 1.5 (95% confidence interval 1.3-1.6) for ex-smokers. Duration and intensity of the smoking habit was associated with an increased risk of ED. Among ex-smokers, the risk of ED significantly decreased; with increase in the number of years since the patient quit smoking. CONCLUSION: The study offers an assessment of the association between smoking habit and ED and its potential interaction with other risk factors in diabetic men.

Adult↗
PubMed2001

Polymorphism of the aromatase gene in postmenopausal Italian women: distribution and correlation with bone mass and fracture risk.

Conversion of C(19) steroids to estrogens is catalyzed by the aromatase enzyme. Inactivating mutations of the aromatase gene are associated with decreased bone mineral density in both men and women. Genetic studies suggest that several genes contribute to the regulation of bone mass via interaction with the modeling and remodeling processes. Among these genes, the aromatase gene is a potential candidate to be evaluated for segregation with bone metabolism and bone mass. A tetranucleotide simple tandem repeat polymorphism in intron 4 at the human aromatase cytochrome P-450 gene has been recently described. In the present study we evaluated the distribution of this polymorphism in a cohort of Italian postmenopausal women, both normal and osteoporotic. We observed that the NN genotype was significantly more frequent in nonosteoporotic women than in osteoporotic women (72.7% vs. 27.2%), whereas the DN genotype was significantly more represented in osteoporotic women (90.48% vs. 9.5%; Pearson's chi(2) test = 42.8; df = 10; P = or < 0.01). The allele containing the longer TTTA repeats was statistically more represented in nonosteoporotic women (Pearson's chi(2) test = 19.14; df = 2; P = 0.00007). In addition, women with a high number of TTTA repeats had a significantly higher lumbar bone mineral density than women with alleles containing 8-11 TTTA repeats (P = 0.03). Finally, considering the spine fractures, a significantly higher incidence was observed in women with shorter TTTA repeats than in those with longer TTTA repeats (Pearson's chi(2) test = 7.3; df = 2; P = 0.02), equivalent to a relative risk of 4.1 (95% confidence interval, 1.19-13.87). In conclusion, the aromatase gene can be one of the several genes potentially involved in the maintenance of bone mass and in the regulation of bone mass loss.

Aged↗
PubMed2000

Prevalence and risk factors for urinary incontinence in Italy.

OBJECTIVES: To analyze the frequency and risk factors for urinary incontinence (UI) in Italy. METHODS: Eligible for this cross-sectional study were men aged >/=50 years and women aged >/=40, randomly identified among registered subjects of a network of general practitioners during the period March-October 1997. All subjects were invited by telephonic interview to determine the presence of UI, reported by the subjects as loss of urine in the last year. The subjects with UI were further questioned at home for evaluation of the type, degree and frequency of UI episodes. RESULTS: Of the 5,488 subjects interviewed (2,767 women and 2,721 men), 92 (3%) men and 316 (11%) women reported at least one episode of UI during the year before the interview. The frequence of UI increased with age both in men and women, being 2 and 11% in men and women, respectively, aged 50-60 years and 7 and 16% in those aged >/=70. Of the subjects with UI identified, 229 women and 64 men and a group of 289 subjects without UI were questionned at home using a detailed questionnaire. Six and 55% of men and women, respectively, reported stress incontinence, 20 and 12% urge incontinence and 20 and 24% mixed incontinence. The risk of UI increased with body mass index in women. A history of recurrent urinary infection was associated with UI in men and less markedly in women. No association emerged between education, smoking and alcohol or coffee consumption and risk of UI. Parity was directly associated with the risk of UI in women. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of UI and its main risk factors in this Italian population.

Adult↗
PubMed2000

Frequency and determinants of erectile dysfunction in Italy.

OBJECTIVE: To analyze the prevalence and risk factors for erectile dysfunction (ED) in Italy in a cross-sectional study. METHODS: Eligible for the study were men aged 18 years or more, randomly identified by 143 general practitioners among their registered patients during the period January 1996 to February 1997. ED was defined as the impossibility to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: Of the 2, 010 men interviewed, 257 (12.8%) reported ED. The prevalence increased with age, from 2% in men aged 18-39 to 48% in those >70 years (tested for trend, p = 0.0001). A history of cardiopathy, diabetes, hypertension, neuropathy, thrombotic/hemorrhagic stroke, peripheral vascular disorders, pelvic/medullary injury and pelvic surgery/radiation all increased the risk of ED. The association of hypertension and diabetes tends to increase the risk of ED. In comparison with nondiabetic and nonhypertensive men, the odds ratio (OR) was 1.4 (95% confidence interval (CI), 0.7-3.2) for hypertensive men without diabetes, 4.6 (95% CI, 1.6-13.7) for diabetic men without hypertension and 8.1 (95% CI, 1.2-55.0) for men with diabetes and hypertension. In comparison with never smokers, the OR of ED was 1.7 (95% CI, 1.2-2.4) for current smokers and 1.6 (95% CI, 1.1-2.3) for ex-smokers and increased with duration of the habit. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men.

Adolescent↗
PubMed2000

Risk factors for urinary incontinence in women.

OBJECTIVES: To review the epidemiological evidence on risk factors for urinary incontinence (UI) in women. METHODS: Using Medline and a manual search we identified the main papers published in English up to 1998. RESULTS: There is consistent evidence that the frequency of UI increases with age, but there is little information on the frequency of different types of UI in different age groups. With regard to other risk factors, there is a clinical consensus that vaginal delivery and, more in general, obstetric traumas are associated with UI, although epidemiological studies are not always consistent. Less defined is the role of race, menopausal status, history of gynecological surgery, body mass index, smoking, and coffee and alcohol consumption on the risk of UI. CONCLUSION: In the coming years, epidemiological research should focus particularly on the potential differences in the epidemiological characteristics of different types of UI in order to gain insight into the pathogenic mechanisms.

Adolescent↗
PubMed2000

Erectile dysfunction in type 1 and type 2 diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici.

BACKGROUND: Several studies reported data on the increased risk of erectile dysfunction (ED) in populations of diabetic men, but few presented data separately for Type 1 and Type 2 subjects. No comparison data for these diabetic subgroups are available with regard to risk factors for ED. METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of insulin-dependent (Type 1) or non-insulin-dependent (Type 2) diabetes who were observed on randomly selected days in 178 diabetes centres in Italy. Erectile dysfunction was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 1383 Type 1 and 8373 Type 2 men. The prevalence of ED increased with age for both groups. After taking into account the effect of age Type 2 men (37/100 men) tend to report ED less frequently than Type 1 men (51/100 men). A significant positive relationship was reported between ED and poor metabolic control and smoking for both Type 1 and Type 2 men, whereas high body mass index (BMI) increased only the risk of ED in Type 1 cases. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and its main risk factors in Type 1 and Type 2 diabetic subgroups.

Adult↗
PubMed2000

[Subclinical hyperthyroidism and hypothyroidism].

Currently, technical methods to obtain precocious and reliable diagnosis of thyroid disorders are available for physicians. Therefore today, patients affected by mild hypo- or hyperthyroidism are more often diagnosed when they are still asymptomatic; these mild forms of thyroid disorder are known as subclinical hypo- and hyperthyroidism. In comparison with '80ties, over the last few years we have observed that patients come to endocrinological examination for subclinical forms of thyroid disorders (particularly for hypothyroidism) more frequently than for severe thyroid diseases. However, before to start a therapy, it is necessary for these patients to determine the causes of subclinical hypo- and hyperthyroidism. The main goals of therapy are to reduce the prevalence of cardiac arrhythmia and osteoporosis of patients with subclinical hyperthyroidism, and to slow down the course of arteriosclerotic disease (linked to hyperlipidemia and/or to hyperhomocysteinemia) of patients with subclinical hypothyroidism.

Biomarkers↗
PubMed1999

Reasons for contraceptive discontinuation in women 20-39 years old in New Zealand.

To estimate the frequency and the medical and nonmedical reasons for discontinuation of oral contraceptive (OC), intrauterine device (IUD), and injectable depot medroxyprogesterone acetate (DMPA) use, data from a cohort of experienced contraceptive users in New Zealand are reported. The current analysis consists of 2469 OC, 2072 IUD, and 1721 DMPA users followed over a period of 5 years. The percentage of women who discontinued the use of the method within 24 months after entry into the cohort were 42%, 44%, and 48%, respectively, for OC, IUD, and DMPA; these differences were not statistically significant. The most common reasons given for discontinuing a contraceptive method, regardless of which method was in use, were the desire to conceive, patient preference, no longer needing contraception, and vasectomy. Among the medical reasons, menorrhagia and intermenstrual bleeding were the reasons for discontinuing use of the method in 1.5 and 1.1 times per 100 women-years among DMPA users and in 1.8 and 4.7 times per 100 women-years among OC users. Pelvic pain and infection were reasons for discontinuing contraceptive method, respectively, 4.4 and 4.3 times per 100 women-years among IUD users. In conclusion, the present study confirms, in this New Zealand population, the high discontinuation rate of contraceptive methods reported elsewhere. In contrast with previous suggestions, in this study, irregular bleeding was not an important medical reason for discontinuation of DMPA use.

Adult↗
PubMed1999

Different sensitivity of in vivo acetylcholine transmission to D1 receptor stimulation in shell and core of nucleus accumbens.

We investigated whether D1 dopaminergic receptors modulate in vivo acetylcholine output in the shell and core areas of rat nucleus accumbens using the microdialysis technique. Subcutaneous injection (1, 2 and 3 mg/kg) of the D1 agonist SKF 82958 enhanced acetylcholine output in both areas of the nucleus accumbens while the selective D1 antagonist SCH 39166 (0.15 and 0.30 mg/kg, s.c.) lowered it. Both SKF 82958 and SCH 39166 were more effective in the shell than in the core region. The increase in acetylcholine release induced by SKF 82958 in the shell was tetrodotoxin-sensitive. The dopamine release inducer d-amphetamine (1 and 2mg/kg, s.c.) and the dopamine uptake inhibitor cocaine (10 and 20 mg/kg, i.p.) dose-dependently raised acetylcholine release in the shell and core areas. The dopaminergic stimulants, like the direct-acting D1 compounds, were more effective in the shell than in the core compartment of the nucleus accumbens. The acetylcholine increases in the shell induced by d-amphetamine (2 mg/kg), cocaine (20 mg/kg) and SKF 82958 (3 mg/kg) were antagonized by the D1 antagonists SCH 39166 (5 microM) and SCH 23390 (10 microM), applied locally by reverse dialysis. The results suggest that dopamine acting at the D1 receptors exerts a tonic stimulatory control over the cholinergic function of the shell and core compartments of the nucleus accumbens with the shell being more strongly influenced.

Acetylcholine↗
PubMed1999

FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women.

A novel T/C polymorphism (ATG to ACG) at the translation initiation site of the vitamin D receptor (VDR) gene, defined by FokI restriction endonuclease, has been recently associated with variation in bone mineral density (BMD) and rates of bone loss in a group of postmenopausal Mexican-American women. The presence of the restriction site, designated as f, allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at a second ATG. In this study, we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic (n = 164), osteopenic (n = 117), and normal (n = 119) groups. There were 159 (41%) FF homozygotes, 55 (14%) ff homozygotes, and 186 (45%) Ff heterozygotes. In the whole population, we observed a weak association between FokI polymorphism and lumbar BMD (p = 0.06, analysis of covariance [ANCOVA]) but not with femoral neck BMD (p = 0.5, ANCOVA). Interestingly, the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause (p = 0.04, ANCOVA), progressively declining afterward. In addition, a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed (p = 0.04, Chi-square test). Finally, ff genotype resulted significantly over-represented in the group of women with a vertebral fracture as compared with controls (p = 0.003, Chi-square test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36-4.91). We conclude that in this population, FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.

Aged↗
PubMed1998

Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women.

Recognition of a major genetic component in bone mass determination represented the basis for studies aiming to the identification of underlying major and minor genes. Bone mineral density (BMD) represents the continuous trait to be quantified in order to evaluate segregation of candidate genes with risk of osteoporosis. Polymorphisms at the vitamin D receptor (VDR), estrogen receptor, (ER), collagen type I, and interleukin 6 (IL6) gene loci have been correlated to BMD. However, in a polygenic disorder, such as osteoporosis, the number of genes expected to influence BMD is very large. In the present study we examined the presence of restriction fragment length polymorphisms (RFLPs) for the calcitonin receptor (CTR) gene in postmenopausal women. We identified a polymorphic (Tt) site at the CTR gene locus using the Taq I restriction fragment enzyme. Three genotypes were observed, whose Tt was the most frequent in our population (49.7%). In addition, Ancova analysis and Tukey's test showed that women with tt genotype had significantly lower lumbar BMD in comparison with Tt genotype (Tukey's test: p = 0.005). In conclusion, evidence of RFLPs at the CTR gene locus in Caucasian postmenopausal women of Italian origin made it possible to identify the involvement of another gene, the CTR gene, in the determination of bone mass.

Aged↗
PubMed1998

Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women.

Bone mass could be under control of several polymorphic genes which can modulate bone turnover via reciprocal interactions. One of the genes that can be involved in this process is the calcitonin receptor (CTR) gene. Evidence from cDNA cloning has shown that CTRs have seven potential transmembrane domains and they are known to be expressed in several tissues. In a Japanese population was discovered a novel Restriction Fragment Length Polymorphism (RFLP) at the CTR gene by Alu I restriction enzyme at the 1377th nucleotide expressing either proline (CC genotype) or leucine (TT genotype) as the 463rd amino acid. The heterozygote genotypes were indicated as TC. In the present study we analyzed the presence of this CTR gene RFLP in 307 postmenopausal Italian women. We observed that TC and TT genotypes represented the most frequent CTR genotypes in Italian women. In addition, Duncan's test used to compare the genotypes showed that TT genotype has significant lower lumbar BMD in comparison with CC genotype.

Alleles↗
PubMed1998

Hematotoxicity on human bone marrow- and umbilical cord blood-derived progenitor cells and in vitro therapeutic index of methoxymorpholinyldoxorubicin and its metabolites.

PURPOSE: MMDX [3'-deamino-3'-[2(S)-methoxy-4-morpholinyl] doxorubicin], an anthracycline derivative active in vitro and in vivo against multidrug-resistant tumors, is currently under investigation in phase I clinical trials. In vivo it is metabolically activated, resulting in more cytotoxic compounds. We determined in vitro the toxic concentration of a 1-h period of exposure to doxorubicin (DX), MMDX, and bioactivated MMDX on hematopoietic progenitors and tumor cell lines. METHODS: DX and MMDX were tested on both bone marrow- (BM) and cord blood (hCB)-derived clonogenic cells, whereas the metabolites were tested on hCB only. All substances were tested on seven tumor cell lines. RESULTS: BM cells proved to be twice as sensitive as hCB cells to cytotoxics, and MMDX was twice as toxic as DX against hCB cells; MMDX activated with normal rat-liver microsomes and with dexamethasone-induced rat microsomes were, respectively, 70 and 230 times more toxic than MMDX. A comparison of the cytotoxic concentrations on hematopoietic progenitors and tumor cells, revealed that DX and MMDX had 5-fold stronger activity on tumor cell lines than on granulocyte/macrophage colony-forming cells (GM-CFCs), whereas bioactivated MMDX showed comparable cytotoxicity against tumor cells and hematopoietic progenitors. CONCLUSIONS: MMDX metabolites are very potent but display a lower degree of tumor selectivity than MMDX. Strategies to reduce MMDX metabolization should be developed to optimize the therapeutic index of this new anthracycline.

Antibiotics, Antineoplastic↗
PubMed1998

In vitro schedule-dependency of myelotoxicity and cytotoxicity of Ecteinascidin 743 (ET-743).

BACKGROUND: Ecteinascidin (ET-743) is a marine derived compound with an interesting preclinical profile currently completing phase I clinical trials. The present study was undertaken to compare the toxicity of different schedules of ET-743 against human hemopoietic progenitors and tumour cell lines. MATERIALS AND METHODS: Human hemopoietic progenitors and solid tumour cell lines were incubated with ET-743 for one hour, 24 hours and one hour daily for five consecutive days to define by comparison an 'in vitro therapeutic index'. Additional experiments were set up to assess whether incubation for 24 hours or five days could change either the sensitivity of cells or the activity of ET-743. RESULTS: Prolonged or repeated exposures were more toxic than a single one hour exposure (P < 0.001), but due to the higher sensitivity to prolonged exposure of several tumor cell lines, prolonged treatment yielded a more favorable in vitro therapeutic index. After incubation for 24 hours, ET-743 showed a significantly (P < 0.01) lower inhibiting capacity. Incubation before treatment rendered progenitors more resistant, but incubation after treatment increased their sensitivity, so that overall the toxicity of ET-743 on hemopoietic cells appears to be close to AUC dependency. CONCLUSIONS: Despite the possible effect of some experimental artefacts, prolonged exposure could represent the best schedule of administration of ET-743.

Antineoplastic Agents, Alkylating↗
PubMed1998

Erectile dysfunction in diabetic subjects in Italy. Gruppo Italiano Studio Deficit Erettile nei Diabetici.

OBJECTIVE: Our objective was to analyze the prevalence and risk factors for erectile dysfunction (ED) in men with diabetes in Italy in a cross-sectional study. RESEARCH DESIGN AND METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of IDDM or NIDDM who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: Of the 9,868 diabetic men interviewed, 3,534 (35.8%) reported ED. The prevalence increased with age, from 4.6% in men aged 20-29 to 45.5% in those aged > or =60 years (test for trend, P = 0.0001). After taking into account the confounding role of age, men with NIDDM reported ED less frequently than did men with IDDM (odds ratio [OR], 0.7; 95% CI 0.6-0.8). In comparison with men reporting diabetes lasting < or =5 years, the ORs for ED were 1.3 and 2.0 for subjects with diabetes lasting 6-10 and 11-30 years, respectively. In comparison with men with good metabolic control, the ORs for ED were 1.7 and 2.3 in men with fair and poor control, respectively. A history of diabetes-related arterial, retinal, or renal diseases and neuropathy was associated with an increased risk of ED. Finally, in comparison with never-smokers, the ORs for ED were 1.5 (95% CI 1.3-1.6) for current smokers and 1.4 (95% CI 1.3-1.6) for ex-smokers. The OR increased with number of cigarettes smoked per day: in comparison with men smoking <12 cigarettes per day, the OR was 1.5 (95% CI 1.3-1.7) for those smoking > or =30 cigarettes day. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men with diabetes.

Adult↗