Epididymosomes thus transit along the excurrent duct, and vesicles collected distally represent a mixed population.
Aims: Flickering light is strongly aversive to many individuals with migraine. This study was designed to evaluate other abnormalities in the processing of temporally modulating visual stimulation.Methods: We measured psychophysical thresholds for detection of a flickering target and for the discrimination of suprathreshold flicker contrasts (increment thresholds) in 14 migraineurs and 14 healthy controls with and without prior adaptation to high-contrast flicker. Visual discomfort (aversion) thresholds were also assessed.Results: In the baseline (no adaptation) conditions, detection and discrimination thresholds did not differ significantly between groups. Following adaptation, flicker detection thresholds were elevated equivalently in both groups; however, discrimination thresholds were more strongly affected in migraineurs than in controls, showing greater elevation at moderate contrasts and greater threshold reduction (sensitisation) at high contrast (70%). Migraineurs also had significantly elevated discomfort scores, and these were significantly correlated with number of years with migraine.Discussion: We conclude that visual flicker not only causes discomfort but also exerts measurable effects on contrast processing in the visual pathways in migraine. The findings are discussed in the context of the existing literature on habituation, adaptation and contrast-gain control.
Humans are extremely sensitive to radial deformations of static circular contours (F. Wilkinson, H. R. Wilson, & C. Habak, 1998). Here, we investigate detection and identification of periodic motion trajectories defined by these radial frequency (RF) patterns over a range of radial frequencies of 2-5 cycles. We showed that the average detection thresholds for RF trajectories range from 1 to 4 min of arc and performance improves as a power-law function of radial frequency. RF trajectories are also detected for a range of speeds. We also showed that spatiotemporal global processing is involved in trajectory detection, as improvement in detection performance with increasing radial deformation displayed cannot be accounted for by local probability summation. Finally, identification of RF trajectories is possible over this RF range. Overall thresholds are about 6 times higher than previously reported for static stimuli. These novel stimuli should be a useful tool to investigate motion trajectory learning and discrimination in humans and other primates.
Two enzymes are involved in the polyol pathway: an aldose reductase that reduces glucose in sorbitol followed by its oxidation in fructose by sorbitol dehydrogenase. It has been previously shown that both enzymes are presented in the bovine epididymis, where they are associated with membranous vesicles called epididymosomes. Based on the distribution of these enzymes, it has been hypothesized that the polyol pathway can modulate sperm motility during the epididymal transit. In the present study, polyol pathway was investigated in semen and along the epididymis in humans in order to determine if sperm maturation can be associated with this sugar pathway. Western blot analysis shows that both aldose reductase and sorbitol dehydrogenase are associated with ejaculated spermatozoa and prostasomes in humans. These enzymes are also associated with epididymosomes collected during surgical vasectomy reversal. Western blot, Northern blot, and reverse transcriptionpolymerase chain reaction analysis show that aldose reductase and sorbitol dehydrogenase are expressed at the transcriptional and translational levels along the human epididymis. Unlike what occurs in the bovine model, distribution of these enzymes is rather uniform along the human excurrent duct. Immunohistological studies together with Western blot analysis performed on epididymosomes preparations indicate that the polyol pathway enzymes are secreted by the epididymal epithelium. These results indicate that the polyol pathway plays a role in human sperm physiology.
Objectives: Advances in surgical techniques have improved the outcome of microsurgical vasovasostomy (VV). We performed a retrospective analysis of surgical procedures to determine outcomes and predictors of VV success, to develop Kaplan-Meier Curves for predicting VV outcomes and to evaluate the use of α-glucosidase (AG) to predict outcomes. Patients and Methods:We undertook a retrospective analysis of 747 modified 1-layer microsurgical VV procedures performed between 1984 and 2000. Obstructive interval, partner status, social status preoperatively and method of vasal obstruction, vasal fluid quality and sperm granuloma intraoperatively were compared with outcome results. Parameters evaluated at follow-up included semen analysis, AG concentration in ejaculate fluid and pregnancy rates. Results:The overall patency rate was 86% and pregnancy rates were 33% and 53% at 1 and 2 years after primary VV, respectively. Preoperative factors associated with successful outcome and pregnancy included shorter obstructive interval and same female partner (p < 0.05). Intraoperative factors predicting success included the use of surgical clips instead of suture at vasectomy, the presence of a sperm granuloma, the presence and quality of vasal fluid, and the presence and quality of sperm in vasal fluid. Further, increased AG in the postoperative semen predicted improved patency and pregnancy outcomes. Conclusion:This study confirms the effectiveness of VV for vasectomized men who wish to father children. It also demonstrates that preoperative and intraoperative factors are predictive of the VV outcome. Postoperative AG is also a useful marker of patency and it appears to predict pregnancy outcome. IntroductionVasectomy is a simple and reliable method of permanent contraception that has achieved widespread acceptance. The popularity of the operation combined with increasing marital and relationship separation has resulted in a growing number of men requesting vasectomy reversal.1,2 There are studies demonstrating acceptable patency and pregnancy rates of vasovasostomy (VV) without optical magnification 3,4 and improved success rates with optical loupe assisted VV. 5,6 Modern microsurgical techniques, as popularized by Silber, 7 remain the standard with which all other methods of vasectomy reversal are compared. Patency is over 80% in most microsurgical series, with patency approaching 100% in some reports.3,7-13 However, prediction of patency and preg- with semen analysis (performed according to WHO methods 17 ) including the measurement of AG in ejaculate. Patients were excluded if they did not provide a semen analysis (101 patients) or if they did not attempt to achieve a pregnancy (41 patients). The remaining 605 patients (81%) provided a minimum of 1 semen analysis; all of the samples were analyzed at the same andrology laboratory within our institution, which has previously reported on the use of AG in men with azoospermia. 15,18 Demographic data included patient's age at vasectomy and VV, the obstructive interval be...
We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.
Sperm surface proteins involved in fertilization can be added or modified during epididymal transit. P34H, a human epididymal-sperm protein, appears on the sperm acrosomal cap in the distal caput-proximal corpus epididymis. In previous studies, it was shown that P34H is present on spermatozoa in men of proven fertility, is absent in 50% of men presenting with idiopathic infertility, and that a high proportion of men with normospermic vasovasectomy produce spermatozoa deficient in this sperm surface protein. P34H mRNA was expressed in the principal cells of the epididymis of normal men, predominantly in the corpus region. Recently, results coming from the assisted reproductive technologies have questioned the importance of the human epididymis in sperm maturation. In order to understand the effect of obstruction on the physiological state of the human epididymis and its function in sperm maturation, we have analyzed the expression of P34H mRNA at the level of the vas deferens and along the epididymis of normal and vasectomized men. In situ hybridization experiments showed that obstruction of the vas deferens alters the pattern of P34H mRNA expression compared with the tract of normal tissues. The P34H transcript was detected in the proximal caput epididymis of vasectomized men at a much higher intensity than that observed in the same region of normal tissues, being restricted to the principal cells of the epididymal epithelium. Compared with the normal duct, the lumen of vasectomized men was distended throughout the duct and the height of the epithelium was maximal in the caput. P34H mRNA was detectable in vas deferens, was not affected by vasectomy, and a 912-base pair P34H transcript was restricted to the epithelial cells of the vas deferens. Thus, using P34H as a marker, these results show that vasectomy alters the pattern of gene expression along the human epididymis, and suggest that the vas deferens can be a major contributor to sperm maturation in certain situations.
Anatomically, the human epididymis is unusual when compared with the excurrent duct of other eutherian mammals. Furthermore, clinical observations suggest that it may not be as important for sperm maturation as is the case for laboratory animals. In contrast, hierarchical clustering of microarray data of epididymides from normal men revealed 2274 modulated qualifiers between the epididymal segments, 1184, 713, and 269 of them being highly expressed in the caput, corpus, and cauda, respectively. The organization of qualifiers according to their similarities by gene ontology indicated that caput transcripts are dedicated to cell-cell adhesion, whereas the corpus is characterized by genes involved in response to other organisms (ie, defense mechanisms) and the cauda transcriptome is specialized in muscle contraction and establishment of localization. A region-specific gene expression pattern thus characterizes the human epididymis as in animal models. In humans, vasectomies have consequences on the epididymal transcriptome. Cluster analysis revealed that 1363 genes are expressed in both normal and vasectomized epididymides, whereas 911 and 660 of them are specifically expressed in normal and vasectomized epididymides, respectively. Three of the affected genes are particularly interesting because of their involvement in sperm biochemical remodeling during epididymal transit: dicarbonyl/L-xylulose reductase, Niemann-Pick disease, type C2, and cysteine-rich secretory protein 1. In some vasovasostomized men, these modifications in gene expression induced by vasectomy are irreversible, thus affecting the biochemical parameters, and potentially, the function of their ejaculated sperm. This may explain the discrepancies between a surgically successful vasovasostomy and fertility recovery.
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