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Biomedical subjects

Loredana Gandini

Publications and source records attributed to Loredana Gandini.

15 recordsLinked to original sources

Circulating monocyte oxidative activity is increased in patients with type 2 diabetes and erectile dysfunction.

PURPOSE: We investigated the relationship between oxidative stress and diabetic erectile dysfunction. MATERIALS AND METHODS: A total of 23 patients with a mean +/- SD age of 56.7 +/- 5.6 years, a history of type 2 diabetes for 10.0 +/- 8.3 years and erectile dysfunction, as tested by the International Index of Erectile Function questionnaire, but without vascular and neurological complications, and 15 age matched patients with diabetes without erectile dysfunction were recruited. Circulating monocyte oxidative activity by cytofluorometry, and endothelin-1, intercellular adhesion molecule-1, plasminogen activator inhibitor-1 by enzyme linked immunosorbent assay were evaluated in all patients in the study. RESULTS: Monocyte free radical production, and total and low density lipoprotein cholesterol were higher in patients with than in those without erectile dysfunction (p <0.03, <0.02 and <0.05, respectively). In all patients the International Index of Erectile Function score inversely correlated with low density lipoprotein (p <0.05), while in patients with erectile dysfunction it negatively correlated with age (p <0.03), body mass index (p <0.02), endothelin-1 (p <0.02) and intercellular adhesion molecule-1 (p <0.05). Endothelin-1, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 were not different in patients with diabetes with and without erectile dysfunction. CONCLUSIONS: In men with type 2 diabetes who have erectile dysfunction but are asymptomatic for cardiovascular disease oxidative activation of monocytes is increased and it is related to other risk factors of endothelial dysfunction.

Diabetes Complications↗

Effect of chemo- or radiotherapy on sperm parameters of testicular cancer patients.

BACKGROUND: The aims of our study were to investigate the short- and long-term effects of chemo- or radiotherapy on spermatogenesis in patients with testicular cancer and to establish any correlation between pre-therapy sperm parameters, histotype and treatment type/intensity and the progress of spermatogenesis during the post-therapy period. METHODS: We evaluated 166 patients affected by testicular cancer, who cryobanked about 1 month after the removal of the cancerous testis and before beginning chemo- (CH group; n = 71) or radiotherapy (RT group; n = 95). RESULTS: For the CH group, there was a statistically significant decrease in sperm parameters, which was most significant 3 months after the end of chemotherapy. For the RT group, this decrease was most relevant 6 months after the end of radiotherapy. Two years after therapy, 3% of the CH group and 6% of the RT group remained azoospermic. To evaluate whether spermatogenesis recovery is a function of baseline semen quality, we divided each group into two subgroups by pre-therapy total sperm count (A, <40 x 10(6)/ejaculate; B, >or=40 x 10(6)/ejaculate). At t(24), subgroup A of both the CH and RT groups showed improved sperm parameters over the baseline, whereas subgroup B for both CH and RT groups showed a return of sperm parameters to those of baseline values. CONCLUSIONS: In conclusion, the recovery of spermatogenesis after chemo- or radiotherapy in our group of testicular cancer patients was not a function of pre-therapy sperm parameter quality. Cryopreservation of sperm before performing such therapy is therefore imperative.

Antineoplastic Agents↗

Beta-chemokine receptors 5 and 3 are expressed on the head region of human spermatozoon.

Induction of human sperm chemotaxis is an established phenomenon, though signaling systems physiologically involved have not been identified. Recently, it has been demonstrated that RANTES is present in the follicular fluid and that this molecule is a chemoactractant for human spermatozoa. However, the presence of beta-chemokine receptors on human spermatozoa has never been reported. By cytometric, Western blotting and immunofluorescence analysis, we demonstrate the presence of CCR5 and CCR3 on ejaculated spermatozoa from healthy subjects. CCR5 was detected in the periacrosomal region of the sperm surface, whereas CCR3 was also present in the postacrosomal cap. Individual variability was observed on CCR5 and CCR3 positive sperm percentages. Presence of Delta32+/-) mutation was demonstrated in two subjects expressing CCR5 in half of the ejaculated spermatozoa. Our findings represent the missing information in favor of the possibility that beta-chemokines and their receptors are involved in sperm chemotaxis. Identification of molecular mechanisms of sperm chemotaxis may allow us to identify predictive parameters of sperm fertilizing ability in hypofertile or infertile subjects. Finally, both CCR5 and CCR3 expressed on the sperm cell surface may be involved in HIV-1 adhesion to spermatozoa, thus allowing these cells to perform as virion cellular carriers during sexual transmission of HIV-1 infection.

Blotting, Western↗

HIV-1 chemokine co-receptor CCR5 is expressed on the surface of human spermatozoa.

Viruses adhering to the sperm surface are described in the semen of HIV-1-infected individuals, although viral adhesion mechanisms have yet to be fully understood. We demonstrate, by cytometric analysis and immunofluorescence microscopy, the presence of beta-chemokine receptor 5 (CCR5) on the periacrosomal region of ejaculated spermatozoa. CCR5 expressed on the sperm cell surface may allow sperm to act as virion cellular carriers during the sexual transmission of HIV-1 infection.

Flow Cytometry↗

PHGPx in spermatogenesis: how many functions?

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a unique intracellular enzyme that directly reduces lipid hydroperoxides in membranes and has the ability to use protein thiol groups as donor substrates. Three isoforms of PHGPx have so far been identified, namely, a mitochondrial, a cytosolic and a nuclear variant. This article is focused on recent evidence demonstrating that (1) mitochondrial and nuclear PHGPx isoforms display a different pattern of expression during male germ cell differentiation; (2) different PHGPx isoforms play specific and independent functions during sperm maturation. The data are discussed in light of the idea that PHGPx is a moonlighting protein, changing roles depending on the intracellular localization, expression in a specific cell type and different partners which it interacts with.

Animals↗

Treatment of sexual dysfunctions secondary to male infertility with sildenafil citrate.

With the assumption that infertility and related diagnostic and therapeutic processes are stressful, an uncontrolled pilot study was designed to evaluate the effect of sildenafil citrate on sexual compliance and reproductive outcome. A group of sexually healthy men were studied after the administration of 50 mg sildenafil before semen collection for intrauterine artificial insemination (n = 25) or planned intercourse for a postcoital test (n = 12). We demonstrated that sexual dysfunction is highly prevalent in patients undergoing diagnostic procedures for infertility, and that sildenafil is effective in reversing stress-induced transitory impotence. Furthermore, sildenafil improved some seminal parameters, such as the percentage of spermatozoa with linear progressive motility, as well as the number of spermatozoa penetrating the cervical mucus. Two pregnancies were obtained after sildenafil administration.

Adult↗

A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia.

OBJECTIVE: To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia. DESIGN: Placebo-controlled double-blind randomized trial. SETTING: University tertiary referral center. PATIENT(S): Sixty infertile patients (aged 20-40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study. INTERVENTION(S): Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up. MAIN OUTCOME MEASURE(S): Variation in the semen parameters that were used for patient selection. RESULT(S): Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate). CONCLUSION(S): Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.

Acetylcarnitine↗

Sperm tail agenesis in a case of consanguinity.

OBJECTIVE: To report a case of 100% teratozoospermia in a patient whose family history presented a high degree of consanguinity. DESIGN: Case report. SETTING: University-based andrology clinic. PATIENT(S): A 27-year-old man undergoing infertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum hormone analysis, standard (World Health Organization) semen quality evaluation, sperm ultrastructure, lymphocytic karyotype, and polymerase chain reaction screening for Y chromosome microdeletions in peripheral blood. RESULT(S): One hundred percent teratozoospermia characterized by shape alterations of the heads and tail agenesis on standard morphology evaluation, which was confirmed using electron microscopy. CONCLUSION(S): A case of familial infertility in a consanguineous patient characterized by morphological abnormalities of spermatozoa such as tail agenesis, chromatin subcondensation, and residual cytoplasmic droplets.

Adult↗

Antisperm immunity in assisted reproduction.

Antisperm antibodies (ASA) can impair the fertilising capacity of human spermatozoa, acting negatively on sperm motility and cervical mucus penetration, and at the level of in vitro gamete interaction. Several methods attempt to improve the potentially deleterious effects of ASA-mediated infertility: by decreasing ASA production, by removing ASA already bound to sperm, artificial insemination (AIH) and fertilisation (IVF, ICSI). Only ICSI seems able to overcome the problem, with fertilisation and pregnancy rates of ASA-positive patients undergoing this technique in the same range as ASA-negative patients. As immunological infertility is relatively rare, literature in the field is quite scarce and more studies need to be conducted to confirm that embryo quality is not impaired.

Antibodies↗

Native specific activity of glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo- and hypomotile human sperm samples.

Glutathione-dependent selenoenzymes in human spermatozoa are responsible for a generalized protection against reactive oxygen species (ROS) as well as some other metabolic and structural regulation during spermiogenesis and sperm cell maturation. Glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (GPx-4 or PHGPx) and glutathione reductase (GR) native specific activities have been studied in human Percoll-purified spermatozoa from healthy fertile subjects and asthenozoospermic patients. The mean values obtained for the three enzymes in normal specimens are 1.52 +/- 0.90 mU/10(6) sperm cells (PHGPx), 4.26 +/- 1.73 mU/10(6) sperm cells (GPx-1) and 1.95 mU/10(6) sperm cells (GR). No statistically significant differences for any of the three enzymes were encountered between these values and those of asthenozoospermic patients. These results are discussed and compared with recent literature data on both rescued and native PHGPx specific activity in human spermatozoa, as well as with data obtained for GPx in human seminal plasma.

Adult↗

Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial.

OBJECTIVE: To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility. DESIGN: Placebo-controlled, double-blind, crossover trial. SETTING: University tertiary referral center. PATIENT(S): One hundred infertile patients (ages 20-40 years) with the following baseline sperm selection criteria: concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study. INTERVENTION(S): Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy. MAIN OUTCOME MEASURE(S): Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL. CONCLUSION(S): Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.

Carnitine↗

Psychosocial factors discriminate oligozoospermic from normozoospermic men.

OBJECTIVE: To compare the profile of psychosocial variables in a group of oligozoospermic and normozoospermic men for assessing the hypothesis of a relationship between impaired seminal status and psychosocial factors. DESIGN: Double-blind investigation of the psychosocial differences between oligozoospermics and normozoospermics. SETTINGS: Healthy volunteers in a clinical environment. PATIENT(S): Two hundred eighty men attending their first seminal examination. INTERVENTION(S): We selected 37 oligozoospermic patients on the basis of sperm concentration and 37 normozoospermic controls for comparison. OUTCOME MEASURE(S): Differences in alexithymia (difficulty identifying feelings, difficulty describing feelings, externally oriented thinking), personality traits (extroversion, neuroticism, psychoticism), and coping style toward stressors (task-oriented coping, emotion-oriented coping, avoidance-oriented coping) were assessed in the two groups. RESULT(S): Wilk's Lambda (.79) of the discriminant analysis showed a statistically significant difference between the two groups. The following variables met the inclusion criterion in the discriminant function: psychoticism and difficulty describing feeling. This analysis also showed a high probability of correct classification of oligozoospermic men on the basis of the psychosocial variables. CONCLUSION(S): The relationship between psychosocial variables and seminal status has been confirmed in a group of oligozoospermic and normozoospermic men.

Adaptation, Psychological↗

Testicular cancer and Hodgkin's disease: evaluation of semen quality.

BACKGROUND: The aim of our study was to establish whether there is a difference in semen quality between patients with testicular cancer (TC) and Hodgkin's disease (HD). METHODS: We evaluated 342 patients affected by TC (n = 232) or HD (n = 110) who cryobanked sperm before initiating chemo- or radiotherapy. All TC patients were evaluated approximately 1 month after orchidectomy. RESULTS: A total of 14 patients were azoospermic or cryptozoospermic. In the TC group (n = 222) the mean of the semen parameters was normal according to the World Health Organization (1992). However, dividing the cases into total sperm count > or =40x10(6)/ejaculate and <40x10(6)/ejaculate, 35.5% of the patients showed an impaired semen quality. The quality of sperm parameters was higher in seminoma patients than for the other histological groups. A significant difference for all semen variables was observed between patients with serum betahCG levels classified as pathological (>5 mIU/ml) and those with normal serum betahCG. Comparison of semen parameters between TC stages I and II showed no significant differences. In the HD group (n = 106), we found that by and large they showed normal spermatogenesis, with only 24.5% having a total sperm count <40x10(6)/ejaculate. There was a significant decrease in semen quality in stages III and IV of HD. CONCLUSIONS: Better semen quality was observed in patients with HD than in those with TC. The semen quality observed in our TC and HD groups seems better than previous results reported in the literature.

Acrosome Reaction↗

Enzymatic and immunochemical evaluation of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in testes and epididymal spermatozoa of rats of different ages.

Selenium (Se) and selenoproteins such as glutathione peroxidases are necessary for the proper development and fertilizing capacity of sperm cells. Phospholipid hydroperoxide glutathione peroxidase (PHGPx, E.C. 1.11.1.12) is a monomeric seleno-enzyme present in different mammalian tissues in soluble and bound form. Its function, like the other glutathione peroxidases, was originally viewed as a protective role against hydroperoxides, but direct and indirect evidence indicates that it has additional regulatory roles. PHGPx is present in testis cells and sperm cells, and its appearance is hormone regulated. We present here biochemical data, which clearly indicate that the enzyme specific activity in rat is age-dependent during the life-span monitored (from 36 to 365 days), with a maximum at 3 months of age in the testis germ cells and at 6 months of age in the isolated epididymal sperm cells. Western blotting and immunocytochemical analysis by means of anti-PHGPx antibodies show the different distribution and the strong binding of PHGPx in the testes and sperm cell subcellular compartments (nucleus, acrosome, mitochondria and residual bodies) of rats of different age. The presence of the protein exhibits in the testis cells a pattern different from that of the catalytic activity, with a maximum at 6 months of age. The subcellular distribution of PHGPx is qualitatively, but not quantitatively, unchanged during ageing. These different behaviours are compared and discussed.

Aging↗