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S Simi

Publications and source records attributed to S Simi.

At least 19 recordsLinked to original sources
PubMed2005

Testosterone replacement therapy in male late onset hypogonadism: available pharmacological strategies.

During the last few years, the general aging of the population and the growing knowledge about male hormonal changes in older age have lead the scientific community to focus on the clinical aspects of secondary hypogonadism in aging males. This syndrome is well defined by the term late-onset hypogonadism (LOH). Although the pathophysiology and the diagnostic aspects have been studied and defined and various preparations are available, the debate on androgen supplementation therapy is still ongoing. As the spectrum of effects of endogenous testosterone is essentially based on its metabolism to dihydrotestosterone and estradiol, testosterone is the treatment of choice for male hypogonadism. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Here we examine the indications for therapy, the characteristics of the different routes of administration and how to monitor therapy in order to make the treatment safe and effective.

Adult↗
PubMed2003

Diethylsulphate and methylnitrosourea affect different targets in Chinese hamster fibroblasts: possible mechanisms of aneuploidy induction by these agents.

It has been shown that the ethylating agent diethylsulphate (DES) induces centromere-containing micronuclei with kinetics suggesting that molecules other than DNA could be targets. In quiescent Chinese hamster fibroblasts CHEF/18, O6-alkylated bases inhibit ribosomal protein S6 kinase (S6K1), the terminal member of a kinase cascade responsible for an increased rate of protein synthesis, but not extracellular signal-activated kinases (ERK1/2) or terminal kinases of a second cascade which activates transcription. The inhibition correlates with the appearance of abnormal metaphases at the following mitosis, suggesting that alkylation of the nucleotide pool and inhibition of S6K1 could be one of the mechanisms leading to chromosome loss by alkylating agents. To clarify the role of protein kinases in chromosome loss induced by alkylating agents, we have studied the effects of DES and methylnitrosourea (MNU) on S6K1 and ERK1/2 activation by growth factors. The alkylating agents were studied in a battery of Chinese hamster fibroblasts (CHEF/18, CHO and ClB) with normal and mutated p53 to control for DNA damage-induced activation of p53, which could indirectly inhibit protein kinases. The role of repair in induction of micronuclei was studied in mismatch repair-proficient CHO and repair-deficient ClB cells. Our results indicate that DES induced micronuclei in a mismatch repair-independent manner, within 8 h of treatment, in agreement with a role for S6K1 inhibition in micronucleus formation. MNU induced centromere-containing micronuclei only in CHO cells, one cell cycle after treatment, without any detectable influences on either kinase cascade, suggesting a role for mismatch repair in chromosome loss.

Alkylating Agents↗
PubMed2003

A low molecular weight enterotoxic hemolysin from clinical Enterobacter cloacae.

Seven of 50 Enterobacter cloacae strains from clinical isolates produced small turbid zones of hemolysis in horse and sheep blood agar plates, and the culture supernatants were also positive for hemolytic activity. The hemolysin was partially purified from the culture supernatant of E. cloacae by ultrafiltration (PM-10 membrane) and extraction with acetone. Semipurified hemolysin was stable to heating (100 degrees C, 30 min) and was soluble in organic solvents (acetone, ethanol, and methanol). The toxin showed no loss of biological activity after treatment with trypsin and was stable to acid treatment at pH 2.0 but not at a pH greater than 7.0. In the rat intestinal loop assay, the hemolysin caused hemorrhagic fluid accumulation and severe histological alterations. These findings indicate that this hemolysin may be a putative virulence factor in E. cloacae infections.

Agar↗
PubMed2003

Spontaneous chromosome loss and colcemid resistance in lymphocytes from patients with myotonic dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is one of the many inherited human diseases whose molecular defect is the expansion of a trinucleotide DNA sequence. DM1 shares with fragile X syndrome (FMR1), another "unstable triplet syndrome", several molecular features not present in the remaining triplet diseases. As FMR1 is also characterised by chromosome instability at the site of the expanded triplet, lymphocytes from DM1 patients and healthy donors were cultured for micronucleus (MN) analysis, in order to verify if DM1 is also prone to chromosome instability. A FISH analysis was also carried out to detect the presence of centromeric sequences in the observed MN. The data indicate that DM1 patients present a percentage of centromere-positive MN significantly higher than controls, suggesting that chromosome loss is the main mechanism underlying the origin of the increased spontaneous instability. To further assess the proneness to instability of cells of DM1 patients, cultures from patients and controls were treated in vitro with growing concentrations of two different mutagens: colcemid, a "pure" aneugen compound whose target is tubulin, and mytomicin C, a strong clastogen. The results show that the patient group is significantly less sensitive to colcemid. These data, together with FISH analysis, suggest the presence, in DM1 patients, of an already damaged tubulin, which becomes no more sensitive to the effect of colcemid and which could be the main defect underlying the aneugenic effects in DM1.

Adolescent↗
PubMed1999

Dual-colour FISH analysis to characterize a marker chromosome in cytochrome P450 2B1 recombinant V79 Chinese hamster cells.

Recombinant V79 Chinese hamster cell lines have been constructed for the expression of useful functions, e.g. cytochromes P450, in order to study metabolism-dependent toxicity. Recombinant cell lines are derived as single clones upon gene transfer and selection from the parental V79 cell line. It is of fundamental importance for a reliable application of the recombinant cell lines to show that the original biological characteristics of the parental line are maintained. As part of these efforts, fluorescence in situ hybridization with Chinese hamster chromosome-specific DNA libraries was performed in order to identify the origin of the chromosomes from which a marker chromosome present in the recombinant cell line V79MZr2B1 was derived, which could not be identified by standard cytogenetic techniques.

Animals↗
PubMed1998

Fragile sites at the centromere of Chinese hamster chromosomes: a possible mechanism of chromosome loss.

On the basis of our previous observations showing that fragile sites (FS) mapped essentially in the centromeric regions of Chinese hamster chromosomes, we consider the possibility that the presence of FS at the centromere might be a source of chromosome loss. In this model a centromeric FS causes a centromeric break giving rise to two chromosome arms which could be lost or maintained with different consequences on the ploidy of daughter cells. To test this hypothesis, Chinese hamster cells have been treated both with N-methyl-N-nitrosourea (MNU), a mutagenic agent which also induces aneuploidy, and vinblastin (VBL), a pure aneugen, used as a control compound, which is supposed not to interact with DNA. The results show that MNU induces the formation of translocated and/or truncated chromosomes, on the contrary VBL is not able to induce chromosome rearrangements. The sites most involved in MNU-induced breaks are the centromeric regions of chromosomes where FS are also present. These breaks cause essentially the loss of one chromosome arm, so that the resulting cells are numerically diploid but presenting partial monosomies. The implications of these results are discussed.

Animals↗
PubMed1998

Comparison between plasma concentrations of testosterone, nitric oxide and endothelin 1-2 in penile and brachial venous blood: preliminary results in men with psychogenic impotence.

In the present study venous plasma concentrations of testosterone (T), nitric oxide (NO) and endothelin 1-2 (ET1-2) in the flaccid penis and brachial blood were measured in men with psychogenic impotence. T and NO were significantly lower in the penile venous blood, while ET1-2 showed no statistical difference. These data support the hypothesis of testosterone dependence of penile nitric oxide synthesis (NOS).

Adult↗
PubMed1995

No statistical association between fragile sites and constitutional chromosome breakpoints.

Ten thousand four hundred ninety-two constitutional breakpoints available from the cytogenetic literature were analyzed for their coincidence with known fragile sites (FS) at 303-band resolution. In this analysis we have taken into account the stochastic connections of some features of chromosome bands with both the presence of FS and constitutional breakage. Our results suggest that there is no particular association between FS and constitutional chromosome rearrangements.

Chromosome Aberrations↗
PubMed1995

Clastogenicity of anthraquinones in V79 and in three derived cell lines expressing P450 enzymes.

The clastogenicity of seven anthraquinones was investigated in a V79 Chinese hamster cell line expressing only the reductive pathway enzymes and in three derived cell lines transfected and expressing three rat cytochrome P450 (1A1, 1A2, 2B1). The results have shown that chromosomal aberrations are modulated in similar manner both in parental and transfected V79 cell lines, suggesting that the clastogenicity of these compounds is not mediated by cytochrome P450 dependent monooxygenases.

Animals↗
PubMed1993

Localization of the Chinese hamster CAD gene reveals homology between human chromosome 2p and Chinese hamster 7q.

The trifunctional enzyme CAD catalyzes the first three steps of pyrimidine biosynthesis. By using fluorescence in situ hybridization we have localized the Chinese hamster CAD gene on chromosome 7q11-q13 of diploid fibroblasts. Other genes previously assigned to chromosome 7 include acid phosphatase-1, the M2 subunit of ribonucleotide reductase and ornithine decarboxylase. These genes are also syntenic with CAD on human chromosome 2p. We have then mapped CAD on the pericentromeric region of two different rearranged chromosomes (Z8p and R2q) in a cell line derived from Chinese hamster ovary. The presence of CAD on Z8 and R2 indicates that they derive from rearrangements involving chromosome 7.

Animals↗
PubMed1993

Analysis of electroporation-induced genetic damages in V79/AP4 Chinese hamster cells.

Electroporation is a recent technique used to introduce exogenous DNA into eukaryotic cells. It is important to establish that the gene of interest is transferred into a functional, non-mutated recipient cell. V79/AP4 Chinese hamster cells were exposed to high-voltage pulsed electric fields and some biological and genetic effects were measured. The results showed that cytotoxicity was related in a dose-dependent manner to the number of applied pulses. Thioguanine-resistant colony-forming cells as well as chromosomal aberrations were also induced whereas ouabain resistants and sister-chromatid exchanges were not or slightly induced. Spontaneous and electroporation-induced clones that were phenotypically TGR/HATS were used to investigate the hprt locus. Molecular screening of the locus showed that the number of deleted exons was significantly higher in induced than in spontaneous TG-resistant clones, suggesting that the genetic damages induced by electroporation concern the loss of regions well over the size of the hprt locus.

Animals↗
PubMed1992

Metabolic consequences of adenine-phosphoribosyl transferase deficiency in V79 hamster fibroblasts.

Two APRT- clones (V79-E3 and V79-E1A) were isolated from V79 hamster fibroblasts treated with ethyl methanesulfonate. Selection involved sequential exposure of the mutagenized cells to the adenine analogues 8-azaadenine and 2,6-diaminopurine. To examine the influence of APRT deficiency on cell metabolism we determined the size and turnover of adenine ribonucleotide pools, the deoxyribonucleoside triphosphate pools, the rate of DNA synthesis, and the length of the cell cycle. Clone V79-E3 was hemizygous for aprt and carried a new chromosome, 3p-. Clone V79-E1A was quasi-tetraploid with a cell volume more than twice that of the WT cells. When the difference in size was taken into account, both clones behaved similarly. While WT V79 cells released no adenine into the medium, they excreted adenine at a rate of 6 pmol/min. This did not affect the size of the ATP pool. The main change in the deoxynucleotide pools was a marked decrease of the concentration of dCTP. The rate of DNA synthesis was the same in WT cells and in the diploid V79-E3 clone. APRT is known to recycle adenine produced during polyamine synthesis, but the enzyme apparently contributes little to the maintenance of adenine ribonucleotide pools of V79 fibroblasts.

Adenine↗
PubMed1992

Specific chromosomal aberrations correlated to transformation in Chinese hamster cells.

Cytogenetic changes were investigated during the spontaneous progression of CHEF18 Chinese hamster cells towards tumorigenicity. We further report the chromosomal characterization of a series of spontaneous anchorage-independent clones, as well as of a series of tumor-derived cell lines resulting from injection of late passage cells in nude mice. The high karyotypic homogeneity (presence of four marker chromosomes strictly associated in all the metaphases analyzed) in all clones and tumor-derived cell lines prompted us to alter the specific pattern of chromosomal aberrations in order to identify which if any of the aberrations were more strictly related to transformation. For this purpose we treated a tumor-derived cell line with Colcemid and analyzed the reversion of anchorage-independent phenotype in the subclones showing an altered association of the four marker chromosomes. We conclude that two of four marker chromosomes contribute to anchorage independence.

Animals↗
PubMed1991

Reduction of proliferative heterogeneity of CHEF18 Chinese hamster cell line during the progression toward tumorigenicity.

Doubling time and generation time represent two parameters by which the proliferation of cultured mammalian cells can be monitored. In this study we report the characterization of CHEF18 Chinese hamster cell line during the progression toward tumorigenicity by analysis of doubling time and generation time. The two parameters reveal that the proliferation was initially different, indicating the presence of a proliferative heterogeneity among the cycling cells. The progressive reduction up to the disappearance of this discrepancy suggests that a modification of the length of some phases of the cell cycle may have occurred during the progression toward tumorigenicity. However, the hypothesis that the shortening of doubling time might be due to a continuous coming out of cells from the cell cycle rather than to a shortening of the cell cycle is presented.

Animals↗