Alterations In Men Research Articles

Screening of glucose/insulin metabolic alterations in men with multiple skin tags on the neck

Multiple skin tags appear associated with abnormalities in glucose/insulin metabolism. Clinical and metabolic glucose/insulin characteristics of men with multiple (8 or more) skin tags on the neck were compared with a control group with few or none. Both groups were divided in two subgroups according to normal or abnormal laboratory findings. In the study subgroup with normal laboratory findings the number of skin tags varied from 8-33, whereas in those with abnormal laboratory findings the range was 9-65. Eight or more skin tags were related with statistically significant laboratory glucose/insulin abnormalities: basal hyperinsulinemia (p<0.002), postprandial hyperinsulinemia (p<0.003), and postprandial hyperglycemia (p<0.01). In the multiple skin tag group 77 % had diverse laboratory abnormalities, including insulin resistance, basal hyperinsulinemia, postprandial hyperinsulinemia, glucose intolerance or type 2 diabetes, in contrast with the control group, where only 33 % showed laboratory abnormalities. One-third of the study group had acanthosis nigricans. Only 15 % of patients with metabolic abnormalities did not show any cutaneous expression of glucose/insulin alterations (9 or more skin tags on the neck, acanthosis nigricans, or waist circumference greater than 95 cm). Multiple skin tags were more sensitive than acanthosis nigricans in identifying those with alterations in the glucose/insulin metabolism (77 vs. 32 % respectively), although less specific (68 vs.100%). Multiple skin tags should raise suspicion of insulin resistance or hyperinsulinemia.

Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Altered expression of estrogen receptors alpha and beta (ERalpha and ERbeta) has been hypothesized to play a role in carcinogenesis. However, little is known about the sex-specific differences of ER expression in colorectal cancer (CRC). This study examined ERalpha and ERbeta protein levels in male and female patients with CRC. Using Western blot analysis, the intensity of ERalpha and ERbeta protein levels was determined in tumor tissue and in corresponding normal colon mucosa from patients with CRC. All 64 white patients (33 men, mean [SEM] age 64.1 [13.1] years, age range 26-90 years; 31 women, mean age 68.5 [14.5] years, age range 39-91 years [4 were premenopausal at time of surgery]) expressed ERalpha and ERbeta protein in normal colon mucosa, and there were no significant differences between men and women. In tumor tissue, a significantly increased ERalpha protein level was observed in men (P = 0.02 vs normal tissue), whereas in women, the ERalpha level did not differ significantly between tumor and normal tissue. The level of ERbeta protein in CRC was significantly reduced in both men and women, but more so in men (P = 0.04 vs women). Furthermore, in men, the ERbeta level was significantly lower in poorly differentiated tumors than in moderately differentiated tumors (P < 0.03), whereas in women, poor differentiation of the tumor was not associated with a significant decrease of ERbeta level. Altered levels of ER subtypes resulting in an increased ERalpha:ERbeta ratio were found in patients with CRC. The observation of significantly greater alterations in men than in women supports the hypothesis of sex-specific differences in the pathogenesis of CRC.

Sequence alterations in the YBX2 gene are associated with male factor infertility

To investigate YBX2 gene alterations in men with severe defects in spermatogenesis, including azoospermia or severe oligozoospermia, and protamine deregulation. MSY2 has been identified as a central component in the regulation of spermatogenesis in mice, but the potential role of its human orthologue, YBX2 or "Contrin," in human infertility is not known. A prospective cohort study. University infertility clinic and associated research laboratory. A total of 288 men were evaluated. Diagnoses were made of complete azoospermia, severe oligozoospermia, and protamine deregulation, or men were of known paternity. Deoxyribonucleic acid (from peripheral blood) and semen samples were collected and analyzed for gene mutations and semen parameters respectively. YBX2 gene alterations. YBX2 sequence analysis revealed 15 polymorphic sites, of which seven polymorphisms were present at a statistically higher frequency in one or both of the patient populations than in controls. Of these seven, two resulted in an amino acid substitution in the highly conserved cold shock domain and one resulted in a highly significant synonymous change in exon 8 of infertile patients. The frequency of single nucleotide polymorphisms was significantly elevated in patients with infertility, particularly in men with abnormal protamine expression. These data indicate a significant association between gene alterations in the YBX2 gene and abnormal spermatogenesis in humans, including a potential role in altering protamine expression, and implicate YBX2 gene alterations as a potential cause of male factor infertility.

Muerte embrionaria temprana: ¿Tiene influencia el factor masculino?

To discuss the possible role of the male factor in early embryo death. A detailed bibliographic review has been put together to establish which alterations in spermatozoa can be associated with early embryo death. Before the fusion between plasma membranes of the sperm and the oocyte occurs, both germ cells must undergo a maturation process that allows successful fertilization and embryo development. The study of couples with early embryo loss is usually approached from the side of the woman due to the obvious relationship that exists between the female and the developing embryo. However, it is not illogical to suppose that a genetic or epigenetic alteration of the sperm could have important consequences on these losses due to the necessary contribution of the male gamete not only to embryonic but also to placental development. On the other hand, spermatozoa have certain characteristics such as a highly compact DNA, they undergo apoptosis and the seminal plasma contains antioxidants that protect the structural and functional integrity of the germ cell. These factors assure fertilization and embryo development. Nevertheless, epigenetic alterations of the sperm such as altered chromatin packing, mistakes in imprinting, absence or alteration of the centrosome, telomeric shortening and absence of sperm RNA, could affect functions leading to early embryo loss. Knowledge concerning sperm intervention previous to embryo development will provide the basis for better understanding and for possible diagnosis and treatment of diverse reproductive alterations in men that could impede embryo development.

Effects of exercise training modality on skeletal muscle fatigue in men with coronary heart disease

Cardiopulmonary and skeletal muscle effects of combined aerobic and resistance training vs. aerobic training were studied in men with coronary heart disease. Sixteen men with coronary heart disease underwent a cardiopulmonary exercise testing and a quadriceps skeletal muscle fatigue assessment. Patients were divided into two groups and trained in a combined aerobic and resistance or aerobic training group during 7 weeks. Maximal voluntary contraction and isometric endurance time were measured with electromyographic signals recorded from vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM) during isometric endurance time. Exercise tolerance increased only in the combined group ( p < 0.05). Maximal voluntary contraction and isometric endurance time did not change after training in either group but was performed at 5.8% higher force output for the combined group. After training, median frequency values were higher for the VL and VM ( p < 0.001) in the aerobic group and also higher for the VL, RF ( p < 0.001) and VM ( p < 0.05) in the combined group. Combined aerobic and resistance training was more effective to improve exercise tolerance, decrease skeletal muscle fatigue and correct neuromuscular alterations in men with coronary heart disease.

Effects of IL-6, adiponectin, CRP and metabolic syndrome on subclinical atherosclerosis

BackgroundInflammation has been implicated in the pathogenesis of cardiovascular disease. Since there have been few studies elucidating gender-specific effect of inflammation and metabolic syndrome (MetS) on subclinical atherosclerosis, we evaluated the relative contribution of these factors in healthy subjects. MethodsMetS components, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were evaluated in apparently healthy 714 men and 364 women (40–59 y). Serum levels of high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and adiponectin were also examined. ResultsIncrease in number of clustering MetS components was more clearly associated with worsening of IMT and PWV in women than in men. Serum IL-6 level was positively correlated with IMT and PWV, and adiponectin level was negatively correlated with IMT in men but not in women. The subjects either with a “high” IL-6 or hs-CRP, or a “low” adiponectin were associated with increase in IMT in the presence of MetS, though there was no significant effect of MetS in those with low inflammation. ConclusionsWhile IL-6 and adiponectin are the important risk factors for early arterial alterations in men, components of MetS present profound effects on subclinical atherosclerosis in women rather than in men.

Penile Length Changes in Men Treated With Androgen Suppression Plus Radiation Therapy for Local or Locally Advanced Prostate Cancer

We determined penile length alterations in men treated with androgen suppression plus radiation therapy for local or locally advanced prostate cancer. From November 2000 to November 2005, 47 patients were enrolled in this prospective study. After clinical staging all patients received hormonal therapy (luteinizing hormone releasing agonist, leuprolide acetate or goserelin every 3 months for a total of 3 injections) and at month 7 of hormonal therapy radiation therapy was begun (total 70 Gy) for 7 weeks. Stretched penile length measurements were performed before starting androgen suppression therapy and every 3 months thereafter with a paper ruler. With the initiation of therapy a gradual decrease in stretched penile length was observed. Penile shortening was statistically significant at a mean followup of 18 months (mean 14.2 to 8.6 cm, p <0.001). Our findings support observations of decreased penile length after neoadjuvant hormonal therapy plus external beam radiation therapy for local or locally advanced prostate cancer. Patients should be counseled before therapy that penile shortening may occur.

Characterization of wild‐type and mutant forms of human tryptophan hydroxylase 2

Tryptophan hydroxylase (TPH) catalyses the rate-limiting step in the biosynthesis of serotonin. In vertebrates, the homologous genes tph1 and tph2 encode two different enzymes with distinct patterns of expression, enzyme kinetics and regulation. Variants of TPH2 have recently reported to be associated with reduced serotonin production and behavioural alterations in man and mice. We have produced the human forms of these enzymes in Esherichia coli and in human embryonic kidney cell lines (HEK293) and examined the effects of mutations on their heterologous expression levels, solubility, thermal stability, secondary structure, and catalytic properties. Pure human TPH2 P449R (corresponds to mouse P447R) had comparable catalytic activity (V(max)) and solubility relative to the wild type, but had decreased thermal stability; whereas human TPH2 R441H had decreased activity, solubility and stability. Thus, we consider the variations in kinetic values between wild-type and TPH2 mutants to be of secondary importance to their effects on protein stability and solubility. These findings provide potential molecular explanations for disorders related to the central serotonergic system, such as depression or suicidal behaviour.

Computerized invasive measurement of time-dependent intraocular pressure

Several methods have been described to measure intraocular pressure (IOP) in clinical and research situations. However, the measurement of time varying IOP with high accuracy, mainly in situations that alter corneal properties, has not been reported until now. The present report describes a computerized system capable of recording the transitory variability of IOP, which is sufficiently sensitive to reliably measure ocular pulse peak-to-peak values. We also describe its characteristics and discuss its applicability to research and clinical studies. The device consists of a pressure transducer, a signal conditioning unit and an analog-to-digital converter coupled to a video acquisition board. A modified Cairns trabeculectomy was performed in 9 Oryctolagus cuniculus rabbits to obtain changes in IOP decay parameters and to evaluate the utility and sensitivity of the recording system. The device was effective for the study of kinetic parameters of IOP, such as decay pattern and ocular pulse waves due to cardiac and respiratory cycle rhythm. In addition, there was a significant increase of IOP versus time curve derivative when pre- and post-trabeculectomy recordings were compared. The present procedure excludes corneal thickness and error related to individual operator ability. Clinical complications due to saline infusion and pressure overload were not observed during biomicroscopic evaluation. Among the disadvantages of the procedure are the requirement of anesthesia and the use in acute recordings rather than chronic protocols. Finally, the method described may provide a reliable alternative for the study of ocular pressure dynamic alterations in man and may facilitate the investigation of the pathogenesis of glaucoma.

Leucocytospermia: Which Relationship with Male Infertility?

Leucocytospermia is usually associated with genito-urinary tract infections and its role on male infertility is currently under debate. The aim of this study was to investigate the relationship between leucocytospermia and seminal fluid alterations in men with fertility problems. We evaluated 40 consecutive spemiograms of leucocystospermic men, and another 40 from individuals without leucocytospermia, with regard to age, number, motility and sperm morphology, and presence of genito-urinary tract infections. There was a significant difference in terms of motility (23.27% in non-leucocytospermic pts vs. 15.57% in leucocytospermic pts., p=0.0034). Furthermore, asthenozoospermia was more frequent in leucocytospermic pts (45% vs. 72.,%, p=0.0231), as also teratozoospermia (32.5% vs. 62.5%, p=0.0138). The probability to have at least one of the major seminal alterations was greater in leucocytospermic pts (75.3% vs. 52.5%, p=0.0048). The incidence of infections in leucocytospermic group was 13%. Our study underlines the relationship between leucocytospermia, motility, and normal morphology reduction in human semen. These data might suggest the presence of a damage due to the ROS produced by seminal leucocytes on spermatozoa. Our analysis wants to emphasize the need to treat this condition, with special regard to the frequent use of PMA procedures.

Segregation of chromosomes in sperm of Robertsonian translocation carriers

Robertsonian translocations are the most frequent structural chromosomal abnormalities in humans and can affect fertility, with various degrees of sperm alterations in men; or the pregnancy outcome of the carriers. The studies on meiotic segregation of chromosomes in sperm of Robertsonian translocation males find a majority of normal or balanced spermatozoa for the chromosomes related to the translocation (mean 85.42%; range 60–96.60%). Furthermore, recent studies suggest an interchromosomal effect. Studies on spermatozoa from translocation carriers, and in mouse models help the comprehension of the meiotic segregation mechanisms. Results of meiotic segregation analysis in man could be integrated in genetic counselling especially when assisted reproductive technology is required.

Colour Doppler ultrasonographic location of the bulbourethral artery, and its impact on surgical outcome

To assess the location of bulbourethral arteries in men with a 'normal' urethra and to study anatomical alterations in men with urethral stricture. A linear-array transducer was used on the ventral surface of the penis to study the urethra. Fifteen men with a normal urethra and 15 with a stricture of the bulbar urethra were assessed. After conventional grey-scale imaging to evaluate the extent of disease, the urethral artery in the bulbar urethra was located by colour Doppler ultrasonography. The site of the urethral arteries in 'normal' men varied among individuals; they were at the 10-2 o'clock position in six men, 8-10 o'clock and 2-4 o'clock in six, and at the 4-8 o'clock position in three. In normal men the symmetry of arteries was maintained and the mean distance from the lumen was 2.67 mm. In men with urethral stricture, there was a loss of symmetry in all cases. In a dense stricture the urethral arteries could not be detected on either side in three of cases, while only a single artery was seen in three. In two men, both the arteries were on one side. The mean distance of the urethral artery from the lumen of urethra was 1.88 mm. Contrary to the popular belief that the urethral arteries are located at the 3 and 9 o'clock position, we found that there was no predictable pattern for their anatomy. These observations might have implications for treating urethral stricture disease with visual internal urethrotomy, as they could help to avoid injury to the bulbourethral artery.

ACUTE RESPONSE OF LIPID AND LIPOPROTEIN CONCENTRATIONS FOLLOWING TREADMILL AND CIRCUIT RESISTANCE EXERCISE

In men, unfavorable total cholesterol (TC) or high-density lipoprotein-cholesterol (HDL-C) concentrations have been acutely improved during the 48-h following aerobic exercise requiring 350 kcal of energy expenditure. PURPOSE To determine the acute response of serum lipid and lipoprotein concentrations following treadmill and circuit resistance exercise. METHODS Moderately active, non-smoking men (n = 8; mean ±SD, age = 27.9 ± 10.9 yrs, body fat = 23.7 ± 10.9%, VO2peak = 41.6 ± 4.8 ml*kg−1*min−1) were recruited without respect to lipoprotein profiles. Control (45-min seated rest), treadmill (65%VO2peak), and circuit resistance (30–35% IRM; 8 upper body and 4 lower body resistance exercises) sessions were performed with at least one week separating each. Each exercise session was terminated when 350 kcal were expended. Throughout each session, VO2 and RER were measured to determine energy expenditure. Blood was collected after a 12-h fast immediately before and 24-h and 48-h following each session. Serum was assayed for triglyceride (TG), TC, and HDL-C concentrations. Each concentration was corrected for changes in plasma volume. The Friedwald equation was used to calculate LDL-C concentration. Dietary records were recorded for 48-h before and after each session. A repeated-measures MANOVA was employed to determine statistically significant differences across time and the three sessions. The criterion reference for statistical significance was set at p < 0.05. RESULTS There were no significant differences between sessions for TG, TC, HDL-C, and LDL-C concentrations at any time point. The percent of kcal consumed as carbohydrate, protein, fat and saturated fat did not differ between sessions. CONCLUSION These data suggest that 350 kcal of treadmill or circuit resistance exercise were not sufficient to alter the lipoprotein profile. These data do not agree with previous reports of exercise induced lipoprotein alterations in men with unhealthy lipoprotein concentrations.

Deconditioning fails to explain peripheral skeletal muscle alterations in men with chronic heart failure

ObjectivesIt remains controversial whether the skeletal muscle alterations in chronic heart failure (CHF) are due to disease pathophysiology or result from chronic deconditioning. The purpose of this study was to compare the skeletal muscle of CHF patients to peak oxygen consumption (peak VO2) matched sedentary controls. BackgroundIt has been established that skeletal muscle abnormalities are related to the exercise intolerance observed in patients with CHF. MethodsWe studied the skeletal muscle of sedentary controls and patients with CHF matched for age, gender and peak VO2. ResultsHypothesis testing for the effects of group (CHF vs. normal), gender, and the interaction group × gender were performed. For capillary density only gender (p = 0.002) and the interaction of group × gender (p = 0.007) were significantly different. For 3-hydroxyl coenzyme A (CoA) dehydrogenase only group effect (p = 0.004) was significantly different. Mean values for capillary density were 1.46 ± 0.28 for CHF men versus 1.87 ± 0.32 for sedentary control men, 1.40 ± 0.32 for CHF women versus 1.15 ± 0.35 for sedentary control women. The activities for 3-hydroxyl CoA dehydrogenase were 3.09 ± 0.88 for CHF men versus 4.05 ± 0.42 for sedentary control men, 2.93 ± 0.72 for CHF women versus 3.51 ± 0.78 for sedentary control women. ConclusionsThis study suggests that women and men adapt to CHF differently: men develop peripheral skeletal muscle abnormalities that are not attributable to deconditioning; women do not develop the same pathologic responses in skeletal muscle when compared with normal women matched for aerobic capacity.

Low frequency noise and whole-body vibration cause increased levels of sister chromatid exchange in splenocytes of exposed mice.

Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV) induces both physiological and psychological alterations in man. Recently, we have shown that long-term occupational exposure to LF noise and WBV produces genotoxic effects in man expressed as an increase in sister chromatid exchange (SCE) levels in lymphocytes. The objectives of the present study were to investigate whether the observed effect could be reproduced in a murine model and, if so, which of the agents, LF noise alone or in combination with WBV, would be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An effect at the cell cycle kinetics level was also investigated. The results revealed significant increases in the mean SCE number per cell and in the proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice submitted to combined noise and WBV over controls. No significant differences were found between single noise-exposed and control mice. A cell cycle delay was observed exclusively in the noise and WBV exposure groups. In conclusion, we demonstrated that, as in exposed workers, prolonged exposure to the combination of LF noise and WBV determines an increase in SCE level in mice while LF noise alone is not effective in SCE induction.

Development of new molecular procedures for the detection of genetic alterations in man

The Restriction Site Mutation (RSM) procedure is a DNA-based method for detecting mutations at any unselected locus. Mutations are identified as alterations of the DNA sequence at a chosen restriction site. DNA from cells exposed to mutagenic treatment is exhaustively digested with the restriction enzyme (RE). Sequences containing the mutated target site are specifically amplified using the polymerase chain reaction (PCR), whereas DNA without mutations at this site will have been cleaved and can not therefore provide a substrate for PCR. We have developed this procedure using both bacterial and mammalian cells. With bacteria, in plasmid reconstruction experiments we were able to detect mutations at a frequency of 10 −6 at an EcoRl site in the AraA locus of Salmonella typhimurium. The detection limit with an Rsal site in the lacI gene of Escherichia coli was 10 −5, and we were able to detect DNA damage and repair after treatment with N-methyl- N-nitrosourea (MNU). With mammalian cells, we have detected mutations induced by ethyl methanesulphonate (EMS) at a TaqI site in the aprt gene of Chinese hamster cells. In extensive studies with normal and repair-deficient human cells, we have detected and sequenced mutations induced by UV-C or UV-B in fibroblasts and lymphoblastoid cells from repair-deficient xeroderma pigmentosum (XP) donors. Similar results were obtained at TagI sites in three genes, hprt, c-Ha- rasI and p53. These results demonstrate that the system is able to detect and analyse mutations induced at high frequencies. In our extensive attempts to extend the work to conditions of lower mutation frequencies, we have encountered several obstacles, the most serious being false-positive mutant DNA in totally untreated cells. This appeared to be a cell-line specific phenomenon, which we have not been able to eliminate by altering conditions. We propose therefore that, at present, RSM is a suitable method for studying high mutation frequencies at different loci and could be used for mutagen testing with repair-deficient cells. As yet, however, its sensitivity and specificity is not sufficient for population monitoring.

Quantitative Electroencephalographic Correlates of Steroid Administration in Man

Elevated levels of circulating corticosteroids are frequently associated with behavioral alterations in man, although the mechanisms by which corticosteroids may affect behavior are poorly understood. To evaluate possible effects of exogenous corticosteroids on brain electrophysiological functioning and the relationship of such effects to behavioral and biochemical changes, we administered prednisone (80 mg p.o. daily for 5 days) in a double-blind manner to 11 medically healthy volunteers. Quantitative electroencephalogram analysis was performed following 4 days of prednisone administration and during the preceding and ensuing placebo administration periods. Central theta wave brain electrical activity significantly increased following prednisone administration and returned to baseline following prednisone withdrawal. This effect was directly correlated with prednisone-induced increases in subjective sadness ratings and with decreases in self-rated energy and well-being. Prednisone-induced reductions in peak alpha wave activity were also directly correlated with increases in subjective sadness and Symptom Checklist-90 ratings and with decreases in self-rated 'hypomanic' symptoms. Further, prednisone-induced increases in theta activity were significantly correlated with prednisone-induced decreases in CSF levels of somatostatin-like immunoreactivity, and prednisone-induced decreases in peak alpha activity were significantly correlated with decreases in CSF levels of norepinephrine and with relative increases (or lesser decreases) in CSF levels of beta-endorphin and beta-lipotropic hormone. This preliminary report of the concomitant development of prednisone-induced changes in brain electrical activity, neurochemistry and behavior highlights areas for future exploration in the study of corticosteroid effects on behavior in man.

Utility of zona pellucida drilling in cases of severe semen alterations in man

Utility of zona pellucida drilling in cases of severe semen alterations in man

Utility of zona pellucida drilling in cases of severe semen alterations in man

To evaluate the utility of zona drilling for human severe sperm alterations in in vitro fertilization (IVF). A prospective randomized study was conducted according to random assignment of collected oocytes to a control or zona drilling procedure. Reproductive Biology Laboratory, University Hospital of Nantes, France. Twenty infertile couples with severe semen defects and previous IVF failure. Ultrasound-guided transvaginal follicular aspiration. Fertilization rates were compared to assess the advantages of zona drilling: 93% (80/86) drilled oocytes survived and 18.75% (15) were fertilized, whereas only 3% (3/100) control oocytes were fertilized. The polyspermy rate for fertilized drilled oocytes was high (10/15; 66.6%). The normal fertilization rate after zona drilling remained very low (5/86; 5.8%) and was not statistically different from that of control oocytes (3/100; 3%). One implantation occurred after replacement of five drilled embryos in three patients but resulted in early miscarriage. Replacement of the single control embryo led to a progressive pregnancy and normal male birth. This study indicates that zona drilling does not improve IVF results in cases of severe semen alterations.

Skeletal muscle lactate dehydrogenase isozyme alterations in men and women marathon runners.

Total lactate dehydrogenase (LD) and LD isozyme activities in gastrocnemius muscle from trained men and women runners were measured in response to the chronic stress of training for a marathon race (42.2 km). Following 9 wk of training, total LD activity in skeletal muscle from men and women runners significantly (P less than 0.02) decreased 2.26 and 2.25 U/mg protein, respectively. However, men's total LD activities were significantly (P less than 0.001) less than the women's both before and after training. Significant (P less than 0.05) increases in LD1 activities in skeletal muscle in men and women runners were also observed after training. No significant correlations were detected between percent fiber type composition in men or women vs. the changes in total LD activity, changes in LD1 activity, maximal O2 consumption or training distance averaged per week after the training period. The biochemical adaptations in skeletal muscle that occurred in the LD isozyme composition in both men and women runners make the runners skeletal muscle appear similar to heart muscle in LD1 and LD2 activities.