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Biomedical subjects

M Spano

Publications and source records attributed to M Spano.

At least 19 recordsLinked to original sources
PubMed2006

Sperm DNA integrity in testicular cancer patients.

BACKGROUND: We evaluated the impact of testicular germ cell cancer (TGCC), its treatment and length of follow-up on sperm DNA integrity. METHODS: In 96 TGCC patients, semen was collected at specific intervals until 5 years after treatment. Sperm DNA integrity was assessed by the sperm chromatin structure assay (SCSA, n = 193) and by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL, n = 159) assay. Results were expressed as DNA fragmentation index (DFI). Controls comprised of 278 military conscripts. RESULTS: Post-surgery testicular cancer (TC) patients did not differ from controls. Compared with pretreatment values, radiotherapy induced a transient increase in SCSA(DFI) (medians: 12 versus 19%; P = 0.03), normalizing after 3-5 years. One year or more after therapy, 5/13 (38%) of normozoospermic, irradiated patients had SCSA(DFI) >27% compared with 7% of normozoospermic controls (P = 0.002). More than two cycles of chemotherapy decreased DFI 3-5 years post-therapy (median SCSA(DFI): 12 versus 9.1%, P = 0.02; median TUNEL(DFI): 11 versus 7.5%, P = 0.03). CONCLUSION: Irradiation increases sperm DNA damage 1-2 years after treatment, and 38% of irradiated patients with normozoospermia had high (>27%) DNA damage, which may affect the sperm-fertilizing ability. TC per se is not associated with an increase of DFI, and DFI is reduced by three or more cycles of chemotherapy.

Adult↗
PubMed2006

Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome.

BACKGROUND: The sperm chromatin structure assay (SCSA) has been suggested as a predictor of fertility in vivo as well as in vitro. The available data however, have been based on limited numbers of treatments. We aimed to define the clinical role of SCSA in assisted reproduction. METHODS: A total of 998 cycles [387 intrauterine insemination (IUI), 388 IVF and 223 ICSI] from 637 couples were included. SCSA results were expressed as DNA fragmentation index (DFI) and high DNA stainable (HDS) cell fractions. Outcome parameters were biochemical pregnancy (BP), clinical pregnancy (CP) and delivery (D). RESULTS: For IUI, the odds ratios (ORs) for BP, CP and D were significantly lower for couples with DFI >30% as compared with those with DFI < or =30%. No statistical difference between the outcomes of ICSI versus IVF in the group with DFI < or =30% was seen. In the DFI >30% group, the results of ICSI were significantly better than those of IVF. CONCLUSIONS: DFI can be used as an independent predictor of fertility in couples undergoing IUI. As a result, we propose that all infertile men should be tested with SCSA as a supplement to the standard semen analysis. When DFI exceeds 30%, ICSI should be the method of choice.

Adult↗
PubMed2006

Intra-individual variation in sperm chromatin structure assay parameters in men from infertile couples: clinical implications.

BACKGROUND: Sperm DNA integrity is an important factor in the prognosis of male fertility. In this study, we investigated intra-individual variation of sperm chromatin structure assay (SCSA) parameters in infertility patients undergoing assisted reproductive techniques (ARTs). METHODS: Retrospective study of 282 consecutive patients referred for ART [intrauterine insemination (IUI), IVF or ICSI] with repeated (between 2 and 5) SCSA measurements. RESULTS: Mean coefficient of variation (CV) of DNA Fragmentation Index (DFI) for repeated SCSA measurements was 29%. A high proportion [37%; 95% confidence interval (CI): 27%, 49%] of patients with DFI >30% in the first test had DFI <30% in the second test. Also, a considerable proportion (27%; 95% CI : 16%, 40%) of patients with 21-30% DFI values in the first test had DFI >30% in the second test. CONCLUSIONS: Intra-individual variability in DFI is significant, therefore repeated SCSA measurements are recommended. The biological mechanisms behind these variations remain to be elucidated.

Chromatin↗
PubMed2006

Sperm chromatin structure and male fertility: biological and clinical aspects.

Sperm chromatin/DNA integrity is essential for the accurate transmission of paternal genetic information, and normal sperm chromatin structure is important for sperm fertilizing ability. The routine examination of semen, which includes sperm concentration, motility and morphology, does not identify defects in sperm chromatin structure. The origin of sperm DNA damage and a variety of methods for its assessment are described. Evaluation of sperm DNA damage appears to be a useful tool for assessing male fertility potential both in vivo and in vitro. The possible impact of sperm DNA defects on the offspring is also discussed.

Abortion, Spontaneous↗
PubMed2004

Toluidine blue cytometry test for sperm DNA conformation: comparison with the flow cytometric sperm chromatin structure and TUNEL assays.

BACKGROUND: Sperm DNA integrity (SDI) is an important factor in the prognosis of male fertility. Here we compare the toluidine blue (TB) image cytometry test, recently proposed by us for SDI assessment, with two other tests-the sperm chromatin structure assay (SCSA) and the terminal nick-end labelling (TUNEL) assay. METHODS: Sperm samples from 35 men were evaluated for standard sperm parameters and subjected to the TB test and SCSA. Eighteen of the 35 samples were also subjected to the TUNEL assay. RESULTS: The proportion of sperm cells with abnormal DNA integrity assayed by the TB test correlated strongly with the proportion of abnormal cells detected by the SCSA and TUNEL assay (rho=-0.84 and rho=0.80, P<0.001, respectively). Furthermore, the fractions of abnormal cells by the TB test corresponded closely to the sum of two SCSA parameters, the DNA fragmentation index (DFI) and the fraction of highly DNA-stainable cells (HDS) (medians 33.0 versus 32.0%, P=0.6). CONCLUSIONS: Abnormal cells in a TB test correspond to the sum of DFI and HDS fractions in the SCSA. TB-positive cells may represent sperm with fragmented DNA and/or abnormal chromatin structure. Because the TB test is an easy and inexpensive method, its potential use as a routine test for sperm DNA integrity, complementary to standard semen parameters, should be investigated further.

Chromatin↗
PubMed2004

The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI.

INTRODUCTION: Sperm chromatin integrity assessment has been suggested as a fertility predictor. The aim of this study was to examine the relationship between the results of sperm chromatin structure assay (SCSA) and the outcome of IVF, ICSI and intrauterine insemination (IUI). METHODS: A total of 306 consecutive couples undergoing assisted reproduction were included. IUI was performed in 131, IVF in 109 and ICSI in 66. SCSA results were expressed as DNA fractionation index (DFI) and highly DNA stainable (HDS) cell fractions. Reproductive outcome parameters were biochemical pregnancy (BP), clinical pregnancy (CP) and delivery (D). RESULTS: For IUI, the chance of pregnancy/delivery was significantly higher in the group with DFI 27% or HDS >10%. The odds ratios (ORs) (95% confidence intervals) were 20 (2.3-117), 16 (1.9-137) and 14 (1.6-110) for BP, CP and D, respectively. No statistical difference between the outcomes of IVF versus ICSI was observed in the group with DFI 27% group, however, the results of ICSI were significantly better than those of IVF. Comparing ICSI with IVF, the OR (95% CI) for BP was 26 (1.9-350). CONCLUSIONS: SCSA is a useful method for prediction of the outcome of assisted reproduction.

Adult↗
PubMed2002

The impact of testicular and accessory sex gland function on sperm chromatin integrity as assessed by the sperm chromatin structure assay (SCSA).

BACKGROUND: The sperm chromatin structure assay (SCSA) provides an objective assessment of sperm chromatin integrity, which is essential for normal sperm function. SCSA is valuable as a fertility marker in epidemiological studies and in the clinical situation. Little is known about the impact of testicular and post-testicular function on SCSA parameters. METHODS: Ejaculates from 278 military conscripts of median age 18.1 (range 18-21) years were included. Levels of reproductive hormones, the length of the CAG repeat of the androgen receptor gene, sperm concentration, abstinence period and biochemical parameters of epididymal and accessory sex gland secretions were correlated to the SCSA parameters, DNA fragmentation index (DFI) and highly DNA stainable (HDS) cells. RESULTS: Negative correlations were found between sperm concentration and DFI (r = -0.119, P = 0.049) and HDS (r = -0.513, P < 0.0001). DFI was negatively correlated with levels of estradiol (r = -0.19, P = 0.002) and free testosterone (r = -0.13, P = 0.03). DFI also correlated positively with abstinence time (r = 0.17, P = 0.005), and with seminal concentrations of fructose (r = 0.18, P = 0.004) and zinc (r = 0.12, P = 0.04). CONCLUSIONS: Sex steroid production, spermatogenic function, abstinence time and seminal vesicle function appear to impact on sperm chromatin integrity and thereby on sperm fertilizing capacity. These findings may improve present understanding of the pathophysiology of male infertility.

Adolescent↗
PubMed2002

Sperm count and chromatin structure in men exposed to inorganic lead: lowest adverse effect levels.

OBJECTIVES: To obtain knowledge on male reproductive toxicity of inorganic lead at current European exposure levels and to establish lowest adverse effect levels, if any. METHODS: A cross sectional survey of the semen of 503 men employed by 10 companies was conducted in the United Kingdom, Italy, and Belgium. The mean blood lead concentration was 31.0 microg/dl (range 4.6-64.5) in 362 workers exposed to lead and 4.4 microg/dl (range below the detection limit of 19.8) in 141 reference workers. Semen volume and sperm concentration were determined in a fresh semen sample according to an agreed protocol subject to quality assurance. The sperm chromatin structure assay (SCSA) was performed at a centralised laboratory. Extraneous determinants including centre, period of sexual abstinence, and age were taken into account in the statistical analysis. If appropriate, possible thresholds were examined by iterative threshold slope linear regression. RESULTS: The median sperm concentration was reduced by 49% in men with blood lead concentration above 50 microg/dl. There was no indication of a linear trend of lower sperm concentration with increasing blood lead values, but threshold slope least square regression identified a blood lead concentration of 44 microg/dl (beta=-0.037, F=4.35, p=0.038) as a likely threshold. Abnormal sperm chromatin structure was not related to blood lead concentration, but some indications of deterioration of sperm chromatin was found in men with the highest concentrations of lead within spermatozoa. Biological monitoring data did not indicate long term effects of lead on semen quantity or sperm chromatin. CONCLUSION: Adverse effects of lead on sperm concentration and susceptibility to acid induced denaturation of sperm chromatin are unlikely at blood lead concentrations below 45 microg/dl. Effects of low level exposure to lead on other measures of testicular function cannot be ruled out.

Adult↗
PubMed1999

Change in semen quality and sperm chromatin structure following occupational styrene exposure. ASCLEPIOS.

OBJECTIVES: Organic solvents have been suspected to exert detrimental effects on human spermiogenesis. Styrene, which is both mutagenic and neurotoxic, was selected as a suitable organic solvent for further assessment of a possible effect on semen quality and sperm DNA damage. SUBJECTS AND METHODS: Semen samples were collected from 23 reinforced plastics workers at the time of employment and after 6 months of styrene exposure and from 21 nonexposed farmers. Intra-individual changes in conventional semen parameters and sperm-DNA denaturation patterns were related to the internal dose of styrene exposure as measured by postshift urinary mandelic acid. RESULTS: A statistically significant decline in sperm density was seen during styrene exposure from 63.5 to 46.0 million sperm/ml, whereas no decline was seen in the nonexposed subjects. The total sperm count was almost halved from an initial value of 175 million sperm/ejaculate. However, no relationship was apparent when the sperm parameters were related to internal levels of exposure. However, an exposure-response relationship was shown for DNA-denaturation patterns, but the numbers were small. CONCLUSION: A declining sperm count following styrene exposure is suggested. However, the findings of the internal and external comparisons are inconsistent, and this may be due to the high intraindividual variability of semen parameters and the limited study size but may also be attributable to a weak internal exposure gradient. Spermatogenesis may be vulnerable to styrene exposure. However, due to the small numbers these findings are only preliminary.

Adult↗
PubMed1997

DNA integrity in human sperm.

Since the 1970s there have been conflicting reports of decreasing sperm counts in man and increasing testicular cancer. There is a hypothetical link between apparent adverse trends in several measures of human reproductive health and exposure to endocrine disrupters. Rodent bioassays are not suited for the large-scale screening of such chemicals because of their costs, complexity, and ethical concerns. Various in vitro assays have been used to examine the effects of these chemicals, but none has directly used semen as one of the target tissues in man. The present study has examined in the alkaline Comet assay in human sperm the effect of two estrogens--beta-estradiol and the phytoestrogen daidzein--and 1,2-epoxybutene, a metabolite of 1,3-butadiene, and compared them with the effects of the known reprotoxin, dibromochloropropane, in two fertile and two infertile frozen sperm samples and two fresh fertile samples. While differences were detected in the frozen fertile and infertile samples with flow cytometry, in the Comet assay both frozen and fresh samples exposed to the chemicals in vitro from fertile and infertile men produced similar altered responses by comparison with untreated samples. The integrity of DNA is necessary not only for the noncancerous state, but also for the accurate transmission of genetic material to the next generation. Thus this assay may be useful for examination of chemicals in fresh and frozen sperm samples.

DNA↗
PubMed1997

Use of hematopoietic cytokines to accelerate the recovery of the immune system in irradiated mice.

In our previous studies aimed at designing appropriate strategies to accelerate recovery of the immune system after irradiation, we found that the hematopoietic cytokine recombinant murine (rmu) interleukin (IL)-3 was able to induce differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to x-rays (200-500 cGy). The recovery, however, was complete at 7 days only after a dose of 200 cGy, whereas 2, 3, and 4 weeks were necessary to achieve full recovery after 300, 400, and 500 cGy, respectively. These studies were extended to investigate the effects of another hematopoietic cytokine, recombinant human (rhu) IL-11, a bone marrow stromal-derived cytokine, administered together with IL-3 to irradiated mice. The synergistic effect of the two cytokines was evident when relatively small doses of rhu IL-11 were injected with an optimal dose of rmu IL-3.

Animals↗
PubMed1994

Clinical features and prognosis in childhood IgA nephropathy.

Clinical variables and laboratory and histologic findings were evaluated in 53 children with IgA nephropathy, of whom 44 were followed for a mean period of 6.2 years (range 1.2-14). At the end of the follow-up 8 patients (18.2%) had had no urinary anomalies for at least 1 year (stage A disease), 28 (63.6%) had microscopic hematuria with proteinuria < 1 g/m2/day (stage B), 5 (11.4%) had proteinuria > 1 g/m2/day (stage C), and 3 (6.8%) had chronic renal insufficiency (stage D). None of the patients in apparent remission presented with elevated serum IgA levels at disease onset. Gross or microscopic hematuria at onset correlated with stage A/B disease at the end of follow-up (p < .05) whereas the presence of proteinuria or nephritic syndrome at onset correlated with stage C/D disease after follow-up (p > .05). Presenting features of gross or microscopic hematuria without or with proteinuria (< 0.5 g/m2/day) correlated (p < .001) with minimal glomerular abnormalities at biopsy, whereas patients with nephritic syndrome had more severe histologic pictures. The presence of proliferative glomerulonephritis with crescents correlated (p < .0001) with poor outcome. The results demonstrate that the prognosis of IgA nephropathy in childhood must be viewed with caution and that outcome correlates with mode of onset and severity of the renal pathology.

Analysis of Variance↗
PubMed1994

[Observations on dietary intake of iron in young adults of the city of Bologna and evaluation of the risk of iron deficiency].

The dietary iron intake was studied in 50 volunteers sample of young adults in Bologna neighbourhood; thirty men, mean age 28.9, and 20 women, mean age 30.4. A structured questionnaire was proposed individually by a skilled dietary interviewer. The mean dietary iron daily intake results similar to that found in western industrialised countries, as reported in previous studies, respectively 15.1 mg and 14.0 in men and women. This study reveals a lower percentage of animal origin dietary iron than in northern and central Europe in both sexes, as previously reported (male: 32.8%; female: 27.3%), furthermore the iron intake per kcal was markedly lower (male: 4.91/1000 kcal, female: 5.97) than the level of 7 mg/1000 kcal reported for those countries. The authors argue that the described dietary habit can lead to iron loss balance, mostly in women whose iron intake is far lower than one recommended by LARN (Recommended daily dietary allowances by National Nutrition Italian Institute). It is considered the increasing chance of iron therapy need in women, particularly during long-lasting hypocaloric diets.

Adult↗
PubMed1992

DNA binding activity and inhibition of DNA-protein interactions. Differential effects of tetra-p-amidino-phenoxyneopentane and its 2'-bromo derivative.

In the present study are reported the differential DNA binding activity of the anti-tumor polyamidine tetra-p-amidinophenoxyneopentane (TAPP-H) and its 2'-halo derivative (TAPP-Br), and their effects on the binding of the recombinant Epstein-Barr virus (EBV) nuclear antigen to a synthetic oligonucleotide mimicking the target DNA sequence present in the EBV genome. In addition, the proliferation kinetics and cell cycle analysis of human leukemia K562 cells treated with TAPP-H and TAPP-Br are reported. The possible in vivo relationship between DNA binding affinity and cytotoxicity is also discussed.

Antigens, Viral↗