A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab.

It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.

Efficacy and safety of anti-CD20 antibody rituximab for patients with refractory systemic lupus erythematosus.

Objective We examined the efficacy and safety of rituximab in patients with refractory systemic lupus erythematosus (SLE). Methods The study enrolled 63 SLE patients who were treated with rituximab between 2002 and 2015. The participants underwent a battery of tests before treatment and at one year. Treatment ranged from two to four times at 500 or 1000 mg. Results Baseline characteristics were males:females = 6:57, age 33.9 years, and disease duration 87.2 months. The primary endpoint: The rate of major clinical response (MCR) was 60% while the partial clinical response (PCR) was 25%. Thirty of 36 (83%) patients with lupus nephritis (WHO II: 2, III: 5, IV: 22, V: 4, IV+V: 2, not assessed: 1) and 22 of 24 patients (92%) with neuropsychiatric SLE, who could be followed at one year, showed changes from BILAG A or B score to C or D score at one year. Multivariate analysis identified high anti-dsDNA antibody and shorter disease duration as significant determinants of MCR at one year. Repeat examination was conducted at five years. Primary failure was recorded in 8.8% and secondary failure in 32.4% (time to relapse: 24.4 months). Rituximab was well tolerated although 65 adverse events, mostly infections, were recorded within one year. Conclusion Rituximab is potentially efficacious for the treatment of patients with refractory SLE.

Effects of phosphodiesterase-5 inhibitor vardenafil on testicular androgen-binding protein secretion, the maintenance of foci of advanced spermatogenesis and the sperm fertilising capacity in azoospermic men.

We evaluated the effects of vardenafil on testicular androgen-binding protein secretion (ABP). Bilaterally obstructed azoospermic (OA)-men (n = 19) (group A) underwent unilateral testicular biopsy. A group of nonobstructed azoospermic (NOA)-men (n = 68) (group B) underwent bilateral testicular biopsy. ABP secretion in vitro by testicular tissue was assessed in each participant of every group. In addition, intracytoplasmic sperm injection (ICSI) cycles were performed in several couples of group A or group B using frozen/thawed spermatozoa from the biopsy material. Ten OA-men (group A1), 14 NOA-men (group B1), and nine different NOA-men (group B2) had been positive for spermatozoa in the biopsy but pregnancies were not achieved in the respective female partners. Men of groups A1, B1 and B2 were treated with vardenafil, vardenafil and L-carnitine respectively. Then, the men of groups A1, B1 and B2 underwent a second testicular (unilateral) biopsy. Within the group A1 and within the group B1, ABP secretion rate was significantly larger after vardenafil treatment than prior to vardenafil treatment. In addition, fertilisation rates in ICSI cycles within groups A1 or B1 were not affected by vardenafil administration. Vardenafil administration in NOA-men increased ABP secretion and did not affect detrimentally the presence of testicular foci of advanced spermatogenesis.

Erectile function and male reproduction in men with spinal cord injury: a review.

Spinal cord injury (SCI) in men results in defects in erectile function, ejaculatory process and male reproductive potential. There are alterations in the capacity of men with SCI to achieve reflexogenic, psychogenic and nocturnal erections. The sexual function in different stages after SCI and the types of erections depend mainly on the completeness of the injury and the level of neurological damage. Furthermore, most of the SCI men demonstrate defects concerning the entrance of semen into the posterior urethra and the expulsion of the semen through the penile urethra and the urethral orifice. In addition, SCI men develop defects in the secretory function of the Leydig cells, Sertoli cells and the male accessory genital glands. The overall result is a decreased quality of the semen is recovered either with penile vibratory stimulation (PVS) or with electroejaculation. Nowadays the therapeutic andrological approach of SCI men focuses on achievement of erectile function, recovery of spermatozoa and assisted reproductive technology. The first line of therapy recommended for infertility in SCI men is collection of semen via PVS with concomitant evaluation of total motile sperm yields for assisted conception which may include intravaginal insemination, intrauterine insemination, or in vitro fertilisation/intracytoplasmic sperm injection. Patients failing PVS may be referred for electroejaculation or surgical sperm retrieval.

Effects of primary testicular damage on sperm DNA oxidative status and embryonic and foetal development.

We evaluated the development of embryos generated from the fertilisation of oocytes with spermatozoa isolated from animals with primary testicular damage (PTD). Embryos derived in vivo or in vitro from oocytes fertilised with spermatozoa produced by PTD rats that had undergone surgical treatment for the PTD (group A1), or PTD rats (group A2), or control rats (group B) were cultured and transferred to recipients. At the end of the experimental period, the fertilisation potential of each rat was assessed in vitro (IVF trials). Sperm 8-oxodG/dG ratio (a marker of DNA oxidative status) was significantly larger in group A2 than in groups A1 and B. Blastocysts of the group A2 transferred to recipients demonstrated a significantly larger loss before implantation than transferred blastocysts of groups A1 or B. In addition, the proportion of implanted blastocysts that could not complete the intrauterine development was significantly larger in group A2 than in groups A1 and B. This study reveals a post-fertilisation detrimental effect in animals with PTD on the capacity of oocytes (fertilised either in vitro or in vivo) to develop in vitro and implant after transferring them to recipients probably attributable to sperm DNA oxidative damage.

Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity.

The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.

A new effect of ionizing irradiation: anisotropic expansion of a peptide crystal.

Expansion of crystals resulting from X irradiation was studied in the case of a peptide, N-acetyl-D, L-alanine. This expansion was discovered by examining several irradiated organic solids for possible expansion, which was suggested by the recent observation of crystal imperfections in another peptide. The expansion, which occurred anisotropically along the c axis, was found to depend on dose, the maximum being as large as 20% when assisted by heat treatment.

Phase II study of intravesical chemoprophylaxis of epirubicin after transurethral resection of bladder tumors. Tottori University Oncology Group.

We performed intravesical instillation of epirubicin in 53 patients with the aim of preventing recurrence of bladder tumors. The patients had undergone transurethral resection of superficial bladder tumors (only transitional-cell carcinoma) within the preceding week, between January of 1990 and July of 1991. Recurrence was found in 11.3% (6/53) of cases during follow-up periods lasting from 1 to 20 months. Side effects occurred in 5.7% (3/53) of the patients. The cumulative nonrecurrence rate was 96.0% for a follow-up period of 6 months and 78.4% for 12 months. The results of this study suggest that intravesical instillation of epirubicin is very useful as adjuvant therapy after transurethral resection of superficial bladder tumors.

Evaluation of systemic chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin for advanced bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.

In a cooperative study of the Japanese Urological Cancer Research Group for Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent bladder cancer was examined. Evaluation of the clinical responses obtained in 86 evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor responses, 19 cases of no change, and 21 cases of progressive disease. The overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The clinical response to M-VAC therapy was not significantly influenced by the performance status of the patients, the dose intensity, or previous therapy. The median duration of response for the 42 responders was 22.7 weeks (range, 8.1-134.1 weeks), and the median duration of survival for the 86 evaluable patients was 9.8 months. Side effects were frequently encountered; the patients experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but all of these symptoms were tolerable.

Selection of single-stranded deoxyribonucleic acid spermatozoa via the SpermPrep filtration column.

Eighteen semen samples were collected from 18 normospermic men. Two aliquots (1 mL) were prepared from each ejaculate, washed with Ham's F-10, and each washed sperm pellet was reconstituted in 2 mL volume of Ham's F-10 medium. Each aliquot one was stained using the AO-staining method. Each aliquot two was filtered via the SpermPrep II method, and the recovered spermatozoa were stained similarly. The proportion of single-stranded DNA (red) spermatozoa to double-stranded (green) spermatozoa was significantly higher in aliquot one than in the postfiltered sample (aliquot two), suggesting that the SpermPrep filtration procedure selectively entrapped the spermatozoa with abnormal DNA.

Beneficial effects of electrical stimulation before round spermatid nuclei injections into rabbit oocytes on fertilization and subsequent embryonic development.

OBJECTIVE: To evaluate the effects of electrical stimulation of rabbit oocytes before round spermatid nuclear injection procedure on oocyte activation and fertilization. DESIGN: The ratio of activated oocytes to the number of successfully injected oocytes and the proportion of offspring to the number of activated oocytes after round spermatid nuclear injections into oocytes stimulated via mechanical stimulation (group A) or a combination of electrical and mechanical stimulation (group B) was compared. INTERVENTIONS: Round spermatid nuclei were isolated from mature male rabbits and microinjected into the oocytes of groups A and B. Injected oocytes were cultured for 24 hours. The embryos developed from groups A and B were transferred to synchronized recipient does. RESULTS: Embryos that developed normally through implantation in groups A and B were carried successfully through complete gestation in the recipient does. The ratio of the activated oocytes to the number of successfully injected oocytes and the proportion of offspring to the number of activated oocytes were significantly higher in group B. CONCLUSION: Electrical stimulation of oocytes before ooplasmic spermatid nuclear injections and ET procedures has beneficial effects on oocytes activation, fertilization, and subsequent embryonic development.

Confocal scanning laser microscopy of morphometric human sperm parameters: correlation with acrosin profiles and fertilizing capacity.

OBJECTIVES: To develop quantitative criteria for assessing sperm morphology and to determine the correlation between the percentage of morphologically normal spermatozoa and the outcome of the sperm hypo-osmotic swelling test, sperm acrosin profile, and sperm capacity for fertilization. DESIGN: The maximal length and width of the sperm head, the length of the midpiece and principal piece of the sperm tail, and the ratio of the surface of the acrosomal region to the total surface of the head were determined in specimens obtained from a group of infertile men and a group of fertile men using a confocal scanning laser microscope. Group A consisted of 53 infertile men who were participating in an IVF program, and group B consisted of 98 fertile men. The mean +/- 2 SD of the morphometric parameters in group B was established as representing the lowest and highest normal values in both groups. A normal spermatozoon was defined as one with morphometric parameters within normal levels. The lowest percentage of morphologically normal spermatozoa, hypo-osmotic swelling test result, and acrosin activity in group B were also taken as the lowest normal values in group A. SETTING: In vitro fertilization program at the Tottori University School of Medicine, Yonago, Japan. MAIN OUTCOME MEASURES: Sperm morphometric parameters, percentage of morphologically normal spermatozoa, hypo-osmotic swelling test, and acrosin activity. RESULTS: The length of the midpiece, ratio (x 100) of the surface of the acrosomal region to the total surface of the sperm head, percentage of morphologically normal spermatozoa, outcome of hypo-osmotic swelling test, and acrosin activity were significantly higher in group B than in group A. The maximal width of the head was significantly lower in group B than in group A. Strongly positive correlations were observed between percentage of morphologically normal spermatozoa or length of midpiece and the proportion of fertilized oocytes in group A and between ratio (x 100) of the surface of the acrosomal region to the total surface of the head and acrosin activity in groups A and B. Sperm morphology showed high positive and negative predictive values for acrosin activity (normal/abnormal) and fertility potential (present/absent). CONCLUSIONS: Using quantitative strict criteria, we found that sperm morphology was an important predictor of sperm fertilizing capacity. The confocal scanning laser microscope provided useful information about the sperm cytoskeleton and its importance in fertilization.

Differences in seminal parameters in specimens collected via intercourse and incomplete intercourse (coitus interruptus)

Whatever the mechanism of such improvements may be, the results in this study point out that coitus interruptus in the human may not be the method of choice for collection of semen specimens, especially in patients with spermatogenic dysfunctions such as hypospermia, oligospermia, and asthenospermia. It should also be noted at this point that, for whatever purpose (semen analysis or artificial insemination by husband), the collected specimen should as closely as possible resemble the ejaculate delivered during intercourse. The complete coitus method, as applied in this study, showed that completion of the ejaculatory process during intercourse as compared with the coitus interruptus method, may assist in the improvement of the collected specimen and should closely resemble the ejaculate obtained during intercourse without the use of Silastic condoms. Furthermore, on the basis of the results generated in this study, the complete coitus method should always be the method of choice for male infertility patients with ejaculatory and spermatogenic dysfunctions as well as for scientists and clinicians who deal in the field of infertility diagnosis and treatment.

Endocrinological, biophysical, and biochemical parameters of semen collected via masturbation versus sexual intercourse.

In clinical programs of assisted reproduction involving infertile males, it is essential to obtain semen of maximum quality. To evaluate ways of achieving this objective, and to assess the fertilizing capacity of the sperm, six semen samples were collected from each of 38 infertile men via masturbation. Six more samples were then collected from each man at sexual intercourse using a semen collection device (SCD). We confirmed that the volume of seminal plasma, total sperm count, sperm motility, and percentage of morphologically normal spermatozoa were significantly higher in samples collected at intercourse than masturbation, as reported previously. In addition, the markers of the secretory function of the prostate and the outcome of sperm function tests (hypoosmotic swelling test, acrosin assay, and sperm penetration assay) were significantly higher for the samples collected at intercourse. There were no significant differences in markers of the secretory function of the seminal vesicles and epididymis between the samples. The improved spermatozoal parameters in the samples collected at intercourse may reflect a higher prostatic secretory function at that time. There were no significant differences in the serum concentrations of gonadotropins, or in the serum or seminal plasma concentrations of testosterone, before or after masturbation or sexual intercourse. Therefore, the differences in prostatic secretory function and semen parameters may not be attributed to differences in hormonal levels. Semen collection during intercourse using an SCD appears to be the method of choice for selecting semen samples for artificial insemination.

Effect of ischemia-reperfusion on contractile function of rat urinary bladder: possible role of nitric oxide.

Because there are increasing evidences that nitric oxide (NO) plays important roles in ischemia-reperfusion injury in several systems, we investigated the role of NO in ischemia-reperfusion injury of the rat urinary bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the rat bladder dome. In functional studies, contractile responses to carbachol were cumulatively measured after the urinary bladder was treated with various duration (0, 30, 60, and 90 min) of ischemia. The injury of rat bladder functioning was dependent on ischemic periods. Significant decreases in the Emax (maximum contractile response) values were observed in the bladder subjected to 60 or 90 min ischemia. Furthermore, the subsequent 30 min reperfusion caused additional damages of the contractile response in bladder muscles. To investigate the role of NO in the ischemia (30 min)-reperfusion (30 min) injury, NG-nitro-L-arginine methylester (L-NAME) was injected intraperitoneally 30 min before the ischemia. Treatment of L-NAME (30 and 100 mg/kg) partly but significantly prevented the reduction contractile responses to carbachol of the rat bladder dome. In histological studies, the ischemia-reperfusion caused infiltration of leukocytes and rupture of microcirculation in the regions of submucosa and smooth muscle without a corresponding sloughing of mucosal cells. The histological damages were also prevented by treatment with L-NAME. Therefore, these data suggested that ischemia-reperfusion of the urinary bladder may result in dysfunction of the contractile response to autonomic nervous system and that nitric oxide may act as a cell/tissue damaging agent in ischemia-reperfusion injury.

Bile acids of patients with renal failure receiving chronic hemodialysis.

Bile acids in serum, urine and dialysate of 8 patients with renal failure in chronic hemodialysis were analyzed by gas chromatography and gas chromatography-mass spectrometry. The following results were obtained: 1. Lithocholic acid, 3 beta-hydroxy-5-cholen-24-oic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and cholic acid were identified in hemodialysate as well as in serum and urine. 2. The serum bile acid concentration of the patients was 2.78 +/- 0.57 micrograms/mL before hemodialysis and 1.34 +/- 0.48 micrograms/mL after a 5-h period hemodialysis with cuprophane membrane. The proportions of secondary bile acids in predialysis and postdialysis serum of patients were significantly higher than those of healthy subjects. 3. Two out of 8 patients excreted urine. But the amounts of bile acids in urine of the patients were very small compared to those of healthy subjects. 4. The amount of bile acids removed from blood by hemodialysis was 0.70 +/- 0.25 mg. In dialysate, cholic acid constituted a larger proportion of the total bile acids, and lithocholic acid a smaller proportion, when compared to those in urine of patients and healthy subjects.

Bilateral effect of unilateral vasectomy on testicular testosterone biosynthesis.

Twelve immature male dogs underwent a left vasectomy (group A). An additional five underwent a sham operation (group B). Sixteen weeks after the surgery, the bilateral mean values for caudal epididymal sperm content, the percentage of motile spermatozoa, intratesticular testosterone concentration, and testicular secretion of androgen-binding protein (in vitro) were significantly lower in group A. The mean peripheral serum testosterone responses 3 hours after human chorionic gonadotropin stimulation (3,000 IU) were significantly lower in group A than in group B (6.3 ng/mL v 9.5 ng/mL). These findings indicate a bilateral deficiency in both Leydig and Sertoli cell secretory function in unilaterally vasectomized dogs, resulting in impaired bilateral spermatogenesis and sperm maturation. The authors suggest that unilateral injuries of the vas deferens during hernia operations in children may result in bilateral testicular dysfunction.

An artificial testis for production of rat haploid cells.

PURPOSE: We attempted to apply the microgravity cell culture system for rat testicular germ cell maturation in vitro. METHODS: Primary spermatocytes were isolated from immature male rat by sedimentation velocity. Sertoli cells were isolated from another immature male by enzyme digestions. Sertoli cell aggregates were plated into conventional tissue culture flasks and incubated at 37 degrees C for 48 hours. These pretreated Sertoli-enriched monocultures were used in preparing Sertoli cell-primary spermatocyte cocultures. And then, primary spermatocytes and Sertoli cells were cocultured in a microgravity cell culture device for 28 days. RESULTS: Cell viability rate is more than 50 % after a 28-day long period of incubation. Furthermore, about 23 % haploid germ cells are observed. CONCLUSIONS: These results using primary spermatocyte coculture with Sertoli cell aggregates under microgravity show that it is possible to mature these cells up to the round spermatid and even to elongating/elongated steps. It may be possible to overcome the male sterility due to maturation arrest at the primary spermatocyte stage.

[Clinical studies on cefmenoxine concentration in prostatic tissue and bladder wall].

Clinical studies on cefmenoxime (CMX) concentration in prostatic tissue and bladder wall were made and the following results were obtained. In 40 patients undergoing operation, 1 g of CMX was administered intravenously by bolus technique and CMX levels in peripheral blood, prostatic tissue and bladder wall were examined. The maximum level of prostatic tissue was 35 micrograms/g after 0.41 hour and bladder wall was 62 micrograms/g after 0.37 hour, and T1/2 was 1.41 hours both. CMX, a new broad spectrum cephalosporin, can be considered as one of the highly useful antibiotics for the treatment of postoperative infection.

[Serum prostate-specific antigen in a urological outpatient clinic. Efficacy of age-specific and prostate volume-specific reference range in detection of prostate cancer].

BACKGROUND: Prostate specific antigen (PSA) is the most available marker for early detection of prostate cancer. Nevertheless, the standard upper range of PSA (4.0 ng/ml) does not demonstrate sufficient specificity. Thus, we evaluated the distribution of PSA by age and prostate volume in urological patients, and determined PSA reference ranges by the each parameter. Diagnostic efficacy was also evaluated. METHODS: Three-hundred-seventy-five patients who visited the urological outpatient clinic between January, 1994 and February, 1996, and were considered not to have prostate cancer, were analyzed PSA levels by age. Among them, two-hundred-seventy-six patients in whom prostate volumes were presumed by means of transabdominal ultrasonography, were evaluated a correlation of PSA values with prostate volumes. Using the age-specific and volume-specific reference ranges determined by this analysis, sensitivity, specificity, and positive predictive value were compared with those in case using the 0.0 to 4.0 ng/ml reference range and the 0.0 to 11.7 ng/ml reference range, in 72 patients (cancer 24, noncancer 48) in whom histological examinations were performed in the same period. RESULTS: We found statistically significant slight correlations among age, prostate volume, and PSA. By using the age-specific reference range, volume-specific reference range, and 0.0 to 11.7 ng/ml reference range, we could elevate the specificity and positive predictive value approximately by 65% and 35%, respectively, compared with those of the 0.0 to 4.0 ng/ml reference range. CONCLUSION: In order to decrease the number of rather invasive than necessary prostate biopsies, age-specific and volume-specific reference ranges are useful in urological outpatient clinic.