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Biomedical subjects

F Rocco

Publications and source records attributed to F Rocco.

At least 19 recordsLinked to original sources

High prevalence of testicular cancer in azoospermic men without spermatogenesis.

BACKGROUND: An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. Our aim was to investigate the prevalence of testicular nodules and cancer in azoospermic subjects with different spermatogenetic patterns. METHODS: A total of 1443 consecutive infertile men were investigated, out of which 145 (10.0%) were found to be azoospermic. By using clinical examination and testicular ultrasound, 11 out of the 145 patients showed testicular nodules (2.8-26 mm). To obtain spermatozoa for assisted reproduction, 97 subjects required testicular sperm extraction (TESE) and biopsy, including the 11 patients with nodules. They were divided into two groups according to biopsy results: Group A (n = 38) with complete Sertoli cell-only syndrome (SCOS) and Group B (n = 59) with varying spermatogenetic patterns. Ten nodules were found in Group A and one in Group B. RESULTS: In azoospermic men, the overall prevalence of nodules was 7.5%. In complete SCOS, the prevalence of nodules and cancer was 10/38 (26.3%) and 4/38 (10.5%), respectively. Amongst the cancers, one embryonal carcinoma, one seminoma and two in-situ carcinomas were found. CONCLUSION: The prevalence of testicular nodules and cancer in azoospermic men with complete SCOS is very high. In these subjects, the role of clinical evaluation, ultrasound and biopsy should be emphasized.

Adult↗

Restoration of posterior aspect of rhabdosphincter shortens continence time after radical retropubic prostatectomy.

PURPOSE: Prolonged postoperative incontinence is a major drawback of RRP. Age, scars in the rhabdosphincter, nonnerve sparing surgery and postoperative sphincter insufficiency can cause temporary or definitive urinary incontinence. We believe that sphincter deficiency is the main cause of early incontinence. Urinary leakage results from the shortening of anatomical and functional sphincter length due to caudal retraction of the urethral sphincteric complex and disruption of the median posterior fibrous raphe. We describe a modification of the Walsh RRP that overcomes caudal retraction, reconstructs the posterior fibrous raphe and decreases time to continence. The primary study end point was early continence rate assessment. Long-term continence (1 year) and erectile function assessment were secondary end points. MATERIALS AND METHODS: To avoid caudal retraction of the urethrosphincteric complex, before completing the vesicourethral anastomosis the posterior semicircumference of the sphincter is joined to the residuum of Denonvilliers' fascia and fixed to the posterior bladder wall 1 to 2 cm cranial and dorsal to the new bladder neck. Vesicourethral anastomosis is subsequently performed with care taken not to involve the neurovascular bundles. A total of 161 patients with clinically confined disease underwent modified RRP (group 1). They were compared with a historical series of 50 patients who underwent standard RRP (group 2). Early continence was defined as no pad use but patients using 1 diaper were also considered continent. Continence, assessed prospectively as the number of pads daily, was evaluated 3, 30 and 90 days, and 1 year after catheter removal. The continence state was assessed by a multivariate logistic model. Erectile function was evaluated using the International Index of Erectile Function questionnaire preoperatively and after 18 months in patients younger than 65 years who underwent nerve sparing surgery. RESULTS: In group 1, 116 (72%), 127 (78.8%) and 139 patients (86.3%) were continent 3, 30 and 90 days after catheter removal compared with 7 (14%), 15 (30%) and 23 (46%), respectively, in group 2. One-year continence rates were 96% and 90%, respectively. Erectile function was similar in groups 1 and 2 (46% and 42%, respectively). Multivariate analysis showed that continence was significantly influenced by operation type, stage and patient age. CONCLUSIONS: Careful reconstruction of the posterior aspect of the rhabdosphincter markedly shortens time to continence.

Aged↗

Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography.

PURPOSE: We compared [11C]choline-positron emission tomography (PET) with [18F]fluorodeoxyglucose-PET for re-staging prostate cancer in a group of 100 patients. MATERIALS AND METHODS: A total of 100 consecutive patients referred for whole body [18F]fluorodeoxyglucose-PET for clinical prostate re-staging after radical treatment for prostate cancer were retrospectively included in the study. Mean prostate specific antigen (PSA) was 6.57 ng./ml. In all cases [11C]choline-PET was also performed. PET studies were done with a multiring device 5 minutes after intravenous injection of approximately 370 MBq. [11C]choline and 60 minutes after injection of approximately 370 MBq. [18F]fluorodeoxyglucose. PET findings were compared with those obtained with different conventional imaging and with PSA assessed at the time of PET and 1 year later. RESULTS: Areas of abnormal focal increases were noted in 47% of patients on [11C]choline-PET and in 27% on [18F]fluorodeoxyglucose-PET. Of the 100 patients 49 had positive conventional imaging findings. All except 14 [11C]choline-PET findings were concordant with conventional imaging, including 6 negative and 8 positive conventional imaging results. All except 1 [11C]choline-PET negative cases also had negative conventional imaging after 1 year. PSA at 1 year remained stable or decreased in 80% and 62% of [11C]choline-PET negative and positive cases, respectively. CONCLUSIONS: [11C]choline-PET seems to be useful for re-staging prostatectomy cases with increasing serum PSA levels. It is superior to [18F]fluorodeoxyglucose-PET and complementary to conventional imaging but with the advantage of staging disease at a single step.

Aged↗

Subcellular localization of oxidosqualene cyclases from Arabidopsis thaliana, Trypanosoma cruzi, and Pneumocystis carinii expressed in yeast.

Cycloartenol synthase from Arabidopsis thaliana and lanosterol synthase from Trypanosoma cruzi and Pneumocystis carinii were expressed in yeast, and their subcellular distribution in the expressing cells was compared. Determination of enzymatic (oxidosqualene cyclase, OSC) activity and SDS-PAGE analysis of subcellular fractions proved that enzymes from T. cruzi and A. thaliana have high affinity for lipid particles, a subcellular compartment rich in triacylglycerols, and steryl esters, harboring several enzymes of lipid metabolism. In lipid particles of strains expressing the P. carinii enzyme, neither OSC activity nor the electrophoretic band at the appropriate M.W. were detected. Microsomes from the three expressing strains retained some OSC activity. Affinity of enzymes from A. thaliana and T. cruzi for lipid particles is similar to that of OSC of Saccharomyces cerevisiae, which is mainly located in this compartment. A different distribution of OSC in yeast cells suggests that they differ in some structural features critical for the interaction with the surface of lipid particles. Computer analysis supports the hypothesis of the structural difference since OSC from S. cerevisiae, A. thaliana, and T. cruzi lack or contain only one transmembrane spanning domain (a structural feature that makes a protein poorly inclined to associate with lipid particles), whereas OSC from P. carinii possesses six transmembrane domains. In the strain expressing cycloartenol synthase from A. thaliana, the accumulation of lipid particles largely exceeded that of the other strains.

Animals↗

Vinyl sulfide derivatives of truncated oxidosqualene as selective inhibitors of oxidosqualene and squalene-hopene cyclases.

Various vinyl sulfide and ketene dithioacetal derivatives of truncated 2,3-oxidosqualene were developed. These compounds, having the reactive functions at positions C-2, C-15 and C-19 of the squalene skeleton, were studied as inhibitors of pig liver and Saccharomyces cerevisiae oxidosqualene cyclases (OSC) (EC 5.4.99.7) and of Alicyclobacillus acidocaldarius squalene hopene cyclase (SHC) (EC 5.4.99.-). They contain one or two sulfur atoms in alpha-skeletal position to carbons considered to be cationic during enzymatic cyclization of the substrate and should strongly interact with enzyme nucleophiles of the active site. Most of the new compounds are inhibitors of the OSC and of SHC, with various degrees of selectivity. The methylthiovinyl derivative, having the reactive group at position 19, was the most potent and selective inhibitor of the series toward S. cerevisiae OSC, with a concentration inhibiting 500% of the activity of 50 nM, while toward the animal enzyme it was 20 times less potent. These results could offer new insight for the design of antifungal drugs.

Animals↗

A preliminary pharmacokinetic study of docetaxel, carboplatin and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck.

This work investigates the pharmacokinetics and toxicity resulting from the concomitant use of low dose carboplatin (CBCA)/docetaxel (DTX) plus concurrent radiotherapy in patients with head and neck cancer. The study comprised 11 patients with stage III-IV head and neck cancer. All patients received 2 Gy radiotherapy daily, 5 fractions per week, up to a planned total of 70 Gy over 7 weeks. CBCA (AUC 0.4 mg/ml, min/day) was also administrated as 20 min i.v. infusion, starting 1 day before the first radiotherapy fraction. CBCA was administered for 5 consecutive days every 2 weeks (weeks 1, 3, 5 and 7). DTX 30 mg/m2 (1 h i.v. infusion) was given as a single dose on days 10, 24 and 38. CBCA on day 1 and DTX on day 10 were analysed to determine the concentration-time curves during the first 24 h. CBCA Cmax and Cmin in 2-5 days and on day 15 and 29, as well as total plasma platinum on days 2, 3, 4, 5, 29 and 43 were also assayed. By calculating the non-compartmental pharmacokinetic parameters of the two drugs from the available plasma concentrations we found in the first week values similar to those reported in the literature as single agents. In contrast, during subsequent weeks (weeks 3 and 5), a significant and progressive increase of platinum levels was observed. So, it could be assumed that after 2 weeks of CBCA and DTX treatment a bias in dose calculation occurred because the linear relationship between creatinine clearance (used to calculate the expected AUC through the Calvert formula) and CBCA clearance was no longer observed.

Antineoplastic Agents↗

[Anatomy of the urethral sphincteric vesico-prostatic complex].

As 27 different names have been proposed for the components of the urethral sphincter, it is difficult to build a clear anatomical model of it. Starting from a review of the literature and from some personal observations of surgical anatomy, our aim is to draw a vision as much organic as possible of the anatomy of the urethral sphincter. The components of the urethral sphincter are: the bladder neck (preprostatic sphincter), the smooth muscle urethral sphincter, the rhabdosphincter and levator ani muscle. Recently the rhabdosphincter has been proposed as a vertical structure that extends from the pelvic cavity (bladder base) to the perineal cavity. It can be round-shaped or omega-shaped. The anterior insertions are along the anterolateral aspect of the prostate (superiorly) and on the perineal fascia (inferiorly). The posterior insertions are on the Denonvilliers fascia and posterior aspect of the prostatic apex (superiorly) and on the central perineal tendon (inferiorly). The rhabdosphincter has strong means of fixations: anteriorly it is fixed to the pubis by the pubo-urethral ligaments, posteriorly it is supported by the medial fibrous raphe of the perineum. The anteromedial fibres of levator ani muscle are involved in the continence mechanism by their strong relation with the rhabdosphincter and the prostate.

Humans↗

[Physiology of the urethral sphincteric vesico-prostatic complex].

We propose a review of the literature about innervation and physiology of the urethral sphincteric complex. Parasympathetic innervation of the pelvic viscera comes from ventral branches of the sacral nerves (S2-S4). The orthosympathetic component derives from superior hypogastric plexus and runs down the hypogastric nerves to form the right and left pelvic plexus together with the parasympathetic component. The pelvic plexus is situated inferolaterally with respect to the rectum and runs on the surface of the levator ani muscle down to the prostatic apex. The pelvic plexus gives innervation to the rectum, the bladder, the prostate and the urethral sphincteric complex. The pelvic muscular floor is innervated by the somatic component (pudendal nerve) derived from the sacral branches (S2-S4). Bladder neck and smooth muscle urethral sphincter innervation is given mostly by the orthosympathetic component. The rhabdosphincter innervation comes from the pudendal nerve and from the pelvic plexus; its role in the continence mechanism is probably to give steady tonic urethral compression. Levator ani muscle takes part in the sphincteric complex with its anteromedial pubococcygeal portion. It plays its role strengthening the sphincteric tone during increase of the abdominal pressure or during active quick stop cessation of the urinary stream.

Humans↗

[Personal research: reconstruction of the urethral striated sphincter].

OBJECTIVE: Incontinence is one of the drawbacks of radical prostatectomy. The causes of post-operative incontinence are sphincter deficiency (SD) and bladder dysfunction (BD). SD seems to be the main cause of incontinence and long time to continence. We present a surgical modification of the anatomical radical retropubic prostatectomy consisting in the reconstruction of the posterior aspect of the striated urethral sphincter in order to obtain a quick recovery of continence postoperatively. MATERIALS AND METHODS: Caudal retraction of the urethro-sphincteric complex after apical dissection of the prostate often occurs. Furthermore posterior fibrous raphe interruption can cause shortening of anatomical and functional urethral length and affect continence. In order to avoid caudal retraction of the sphincteric complex, after completing vesico-urethral anastomosis, the posterior emicircumference of the striated sphincter is fixed to the posterior aspect of the bladder one centimeter cranially and posteriorly to the urethro-vesical anastomosis. The rabdosphincter is sutured separately from the urethro-vesical suturing. This technical modification makes it possible to obtain an anatomical length of the urethra of about a centimeter more than with the standard technique, replacing it in a more anatomical position. Furthermore, this technique provides the new posterior platform for the urethro-sphincteric complex. Twenty-four patients with clinical organ confined disease and age range 54-74 years (mean 64 years) underwent Walsh's anatomical radical retropubic prostatectomy with reconstruction of the rabdosphincter (group A). Catheter was removed 7 to 11 days postoperatively. Early continence was assessed objectively with the number of pads per day as follows: 0-1 mini pad = continent; 1-2 pads per day = mild incontinence; 2 or more pads per day = severe incontinence. Continence was evaluated at 3 days and one month after catheter removal. Group A compared to 21 patients (group B) who underwent standard anatomical RPP (historical control group). RESULTS: In group A 16/24 patients (66.7%) and 19/24 patients (79.2%) were continent respectively at three days after removal of the catheter and after one month; mild incontinence (1-2 pads/day) was present in 6/24 patients (25%) and 3/24 (12.5%) respectively, 2/24 patients (8.3%) suffered from severe incontinence after 3 days and one month. In group B 7/21 patients (33%) were continent at hospital discharge, 11/21 (52%) after one month. CONCLUSIONS: Careful reconstruction of the posterior aspects of the rabdosphincter shortens time to continence after RRP.

Aged↗

Stereospecific syntheses of trans-vinyldioxidosqualene and 3-hydroxysulfide derivatives, as potent and time-dependent 2,3-oxidosqualene cyclase inhibitors.

trans-Vinyldioxidosqualene and beta-hydroxysulfide derivatives were synthesized stereospecifically and evaluated as inhibitors of animal and yeast oxidosqualene cyclases. Only trans-vinyldioxidosqualene and 2,3-epoxy-vinyl-beta-hydroxysulfides, having the reactive function at crucial positions 14,15 and 18,19, were active as inhibitors of animal and yeast cyclases. (14-trans)-28-Methylidene-2,3: 14,15-dioxidoundecanorsqualene 27 was the most potent inhibitor of the series of pig liver cyclase, with an IC50 of 0.4 microM, and it behaved also as the most active time-dependent inhibitor of the animal enzyme.

Animals↗

Paradoxical stimulation of prolactin secretion by L-dopa in metastatic prostate cancer and its possible role in prostate-cancer-related hyperprolactinemia.

OBJECTIVE: In addition to sex steroids, prolactin (PRL) may also stimulate prostate cancer growth. Abnormally high blood levels of PRL have been noted in metastatic prostate cancer patients. However, most studies have been limited to the evaluation of basal levels of PRL rather than to investigate its secretion in response to classical endocrine dynamic tests. This study was carried out to analyze PRL secretion in metastatic prostate cancer patients both at basal conditions and in response to L-Dopa and metoclopramide, which represents the most classical inhibitory and stimulatory tests for PRL secretion, respectively. METHODS: The study included 12 patients with metastatic prostate cancer. On separate occasions, PRL secretion was evaluated in response to L-Dopa (500 mg orally) and to metoclopramide (10 mg i.v. as a bolus). Serum levels of PRL were measured by RIA. RESULTS: Mean PRL concentrations significantly increased after metoclopramide administration, even though no PRL response occurred in 6 of 12 patients. L-Dopa was unable to reduce PRL levels, which, in contrast, paradoxically significantly increased in response to L-Dopa, with mean values comparable to those achieved after metoclopramide injection. CONCLUSION: By showing a paradoxical stimulatory effect of L-Dopa on PRL secretion and a lack of response to metoclopramide in some patients, this study would suggest the existence of evident alterations in the neuroendocrine regulation of PRL release in advanced prostate cancer.

Aged↗

Evaluation of analgesic and anti-inflammatory activity of novel beta-lactam monocyclic compounds.

We have examined the in vivo anti-inflammatory and analgesic activity of a new series of monocyclic beta-lactams (azetidinones), similar to others which have been demonstrated to be inhibitors of human leukocyte elastase (HLE), an enzyme involved in degradation processes of connective tissue. Our new compounds have been administered orally (15 mg/kg) to albino rats 30 min before injecting carrageenin in the plantar aponeurosis. Tested compounds have demonstrated a certain activity and stability to gastric hydrolysis, in particular two of them markedly reduced paw edema formation, even if slightly less effectively than indomethacin (reference compound, 5 mg/kg). To evaluate the analgesic activity we carried out the acetic acid writhing test, pretreating rats orally with our compounds 30 min before injecting the acid solution i.p. The same two molecules which showed the anti-inflammatory activity demonstrated a very light analgesic activity. These results suggest the possibility of carrying out further studies, particularly in vitro, on the mechanism of action of our compounds, mechanism which could be the HLE inhibition.

Analgesics↗

Systematic analysis of yeast strains with possible defects in lipid metabolism.

Lipids are essential components of all living cells because they are obligate components of biological membranes, and serve as energy reserves and second messengers. Many but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of the yeast Saccharomyces cerevisiae have been cloned and gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes or the turnover and degradation of complex lipids. To obtain more insight into lipid metabolism, regulation of lipid biosynthesis and the role of lipids in organellar membranes, a group of five European laboratories established methods suitable to screen for novel genes of the yeast Saccharomyces cerevisiae involved in these processes. These investigations were performed within EUROFAN (European Function Analysis Network), a European initiative to identify the functions of unassigned open reading frames that had been detected during the Yeast Genome Sequencing Project. First, the methods required for the complete lipid analysis of yeast cells based on chromatographic techniques were established and standardized. The reliability of these methods was demonstrated using tester strains with established defects in lipid metabolism. During these investigations it was demonstrated that different wild-type strains, among them FY1679, CEN.PK2-1C and W303, exhibit marked differences in lipid content and lipid composition. Second, several candidate genes which were assumed to encode proteins involved in lipid metabolism were selected, based on their homology to genes of known function. Finally, lipid composition of mutant strains deleted of the respective open reading frames was determined. For some genes we found evidence suggesting a possible role in lipid metabolism.

Antifungal Agents↗

19-Azasqualene-2,3-epoxide and its N-oxide: metabolic fate and inhibitory effect on sterol biosynthesis in Saccharomyces cerevisiae.

19-Azasqualene-2,3-epoxide was more inhibitory than the corresponding N-oxide against 2,3-oxidosqualene cyclase (OSC) solubilized from Saccharomyces cerevisiae (IC50 7+/-2 and 25+/-5 microM, respectively). Both compounds showed a reversible, noncompetitive-type inhibition on solubilized OSC. Different inhibitory properties between the compounds were especially evident when measuring [14C]acetate incorporation into nonsaponifiable lipids extracted from treated cells. In cells treated with 19-azasqualene-2,3-epoxide at 30 microM, the radioactivity associated with the oxidosqualene fraction, which was negligible in the controls, rose to over 40% of the nonsaponifiable lipids, whereas it remained at a slightly appreciable level in cells treated with the N-oxide derivative under the same conditions. 19-Azasqualene-2,3-epoxide was also more effective than the N-oxide as a cell growth inhibitor (minimal concentration of compound needed to inhibit yeast growth: 45 and >100 microM, respectively). The two inhibitors underwent different metabolic fates in the yeast: while 19-azasqualene-2,3-epoxide did not undergo any transformation, its N-oxide was actively reduced to the corresponding amine in whole and in "ultrasonically stimulated" cells. The N-oxide reductases responsible for this transformation appear to be largely confined within the microsomal fractions and require NADPH for their activity. A possible relationship between the inhibitory properties of the two compounds and their metabolic fates is discussed.

Enzyme Inhibitors↗

Medical decision making for melanoma of the glans penis.

This case report describes a rare presentation of penile melanoma in which 3 successive primaries arose and were operated from an area of melanosis on the glans penis and prepuce. One of the major factors accounting for the poor prognosis of this patient was the long delay in presentation. This was largely due to the patient's reluctance because of the site of the disease. When diffuse melanotic areas are present in the genital region, in particular given the reluctance of patients with skin lesions in this region to present, the index of suspicion should be high with respect to the risk of transformation and an aggressive follow-up policy should be advocated. Treatment guidelines should not significantly differ from the usual approach of cutaneous melanoma.

Aged↗

29-Methylidene-2,3-oxidosqualene derivatives as stereospecific mechanism-based inhibitors of liver and yeast oxidosqualene cyclase.

Two pairs of isomers (18Z)- (8), (18E)-29-methylidene-2,3-oxidohexanorsqualene (21), and (18Z)- (31), (18E)-29-methylidene-2,3-oxidosqualene (34), have been obtained in a fully stereospecific manner, as inhibitors of rat and yeast oxidosqualene cyclase. A new method for the synthesis of C22 squalene aldehyde 2,3-epoxide is reported, as well as that of other 19-modified 2,3-oxidosqualene analogues. We found that the activity is the opposite in the two series: the (E)-hexanormethylidene 21 and the (Z)-methylidene 31 are potent and irreversible inhibitors of oxidosqualene cyclase, while (Z)-hexanormethylidene 8 and (E)-methylidene 34 are almost completely inactive. Reduction of the 18,19-double bond, such as in 39, eliminates the activity, while removal of both of the 19-linked groups such as in heptanor derivative 40 greatly reduces inhibition of the enzyme. (E)-Hexanormethylidene 21 results the first irreversible inhibitor of the series toward the yeast enzyme.

Animals↗

Long-term results of intrarenal surgery for branched calculi: is such surgery still valid?

OBJECTIVE: To evaluate whether intrarenal surgery for branched calculi remains valid in the light of current new techniques, e.g. percutaneous nephrolithotomy and extracorporeal shockwave lithotripsy. PATIENTS AND METHODS: Between January 1978 and October 1984, 44 patients (24 male and 20 female, mean age 42.5 years, range 14-66) underwent complex surgery for large stones, requiring opening of the renal pelvis and a transparenchymal approach to the calices; 47 renal units were operated in 49 procedures. The evaluation before surgery included creatinine and blood nitrogen levels, blood pressure measurement, urine culture, abdominal plain X-ray (44 patients), intravenous urography (42) and isotopic renography with renal scintigraphy (five). Renal lithiasis was categorized and all patients underwent extended pyelolithotomy with a transparenchymal approach, achieved by partial nephrectomy (six patients), radial paravascular nephrotomy (10), posterior lower nephrolithotomy (29), resection of the posterior segment (two), and posterior segmentotomy and reconstruction (2); 16 operations were performed under ischaemia. In October 1996, the patients were clinically evaluated by serum creatinine levels (42), urine cultures (42), abdominal plain X-ray (42), IVU (34), isotopic renography (eight), renal ultrasonography (eight) and blood pressure measurement (44). The mean follow-up was 14.8 years. RESULTS: The major postoperative complications were; residual stones (six patients), fistula with ureteric stenosis (one, with a permanent nephrostomy), toxic temporary hepatic failure (one), femoral arterial embolism (one, resolved using a Fogarty catheter) and recurrent large stones (two, operated 1 and 5 years later). From 1984 to 1996, 19 patients had recurrent stones and two underwent dialysis. In October 1996, the renal function of 47 renal units was stable or normal in 36 (77%), reduced in seven (15%) and lost in four (8%); 24 patients were hypertensive (12 preoperatively), nine have urinary tract infection, three are positive for hepatitis B or C virus, and lithiasis has recurred in 15 renal units. CONCLUSIONS: Intrarenal surgery, conducted using modern anatomical guidelines, was an effective treatment for renal branched stones. The long-term results are satisfactory after appropriate correction of the urinary tract, with the consequent prevention of stasis and chronic infection. The definitive comparison between surgical and combined endoscopic/extracorporeal methods will only become clear when there is a comparable follow-up. Currently, surgery remains preferable in patients with giant calculi, a small pelvis and prevalent calyceal development.

Adolescent↗

Antioxidant systems in rat epididymal spermatozoa.

Mammalian caput and cauda epididymidal spermatozoa exhibit diverse stages of maturation, and their plasma membrane shows diverse composition and stability levels, thus enabling these spermatozoa to undergo the acrosomal reaction after transit through the epididymis. As a result, the study of antiperoxidative mechanisms is quite relevant, since epididymal spermatozoa must be properly protected against agents such as reactive oxygen species, which can impair the complex maturation process. We considered activities of certain enzymes (glutathione peroxidase [GPx], phospholipid hydroperoxide glutathione peroxidase [PHGPx], glutathione reductase [GR], superoxide dismutase [SOD], and catalase [CAT]) and the vitamin E content in isolated rat caput and cauda epididymidal spermatozoa. The results indicate that caput epididymidal sperm have significantly greater PHGPx (3.5x), GPx (2.4x), and SOD (1.7x) activities, as well as a greater amount of vitamin E (3.8x). There were no detectable differences in the GR and CAT activities of caput and cauda epididymidal spermatozoa. The substantial drop in PHGPx activity during epididymal transit is discussed in relation to an additional function of this enzyme: the use of caput sperm protamines as a sulfhydryl substrate. In vitro peroxidation of the two sperm populations by the free radical generator (azo-initiator) 2,2'-azobis(2-amidinopropane) dihydrochloride revealed that only about 13% of the vitamin E content of the caput epididymidal spermatozoa was consumed, which contrasts with the greater consumption (about 70%) of the vitamin in cauda epididymidal spermatozoa. Selective inhibition of PHGPx, SOD, or CAT did not change this picture. The higher susceptibility of cauda epididymidal spermatozoa to radicals is discussed in relation to the diverse enzymatic activities, vitamin E content, and peroxidative response. These factors are correlated with the different stages of sperm cell maturation, which are characterized-from caput to cauda epididymidis-by progressive destabilization of the plasma and acrosomal membranes.

Animals↗