Atrophic Tubules Research Articles

64 Behind every healthy man, there's a woman: A qualitative inquiry

during the short-term follow-up, with 6 cystic fat nodules. The satisfaction rate for sexual function, morphology and global state were 79.8%, 78.9%, and 91.7%. Conclusions: Our technique shows very effective shortterm outcomes and patient’s satisfaction without serious complications. 62 A case of 47,XXY/46,XY Klinefelter syndrome H. Masuda1, Y. Katsuoka2. 1Aino Hospital, 2 Osaka Medical College, Japan Klinefelter syndrome represents the most commonly found human sex chromosomal abnormality. It is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Males with Klinefelter syndrome may have a 47,XXY or a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. We report here a case of a mosaic 47,XXY/46,XX infertile male. The patient was a 31-year-old male. Physical examination revealed perfect male-type of genitalia, almost normal penis and bilateral small testicles, being 1.0 × 2.0 × 1.0 cm sized for the right and 1.0 × 2.0 × 1.0 cm for the left. Chromosome analysis by means of culture of peripheral blood lymphocytes revealed twokinds of 46 chromosomes and of 47 chromosomes. The genotype of the former was XX and of the later was XXY, making XX/XXY mosaicism. Testicular sperm extraction was performed, but we could find the sperm in microdissection testicular sperm extraction procedure. Histologically the testicle showed atrophy of seminiferous tubules with hyalinizaition of the canaliculi. No spermatogenesis was observed at all. 63 Coenzyme Q10 treatment for oligoasthenoteratozoospemia in infertile men with varicocele Y. Kobori, H. Okada, G. Arai, S. Soh, H. Yagi. Dokkyo Medical University Koshigaya Hospital, Department of Urology, Japan Objective: To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men who have varicocele with infertility. Patients: Sixty-nine infertile patients (21–51 years of age) with the following baseline sperm selection criteria: concentration 30%. Patients underwent therapy with coenzyme Q10, 30mg/day. We investigated seminograms, background, hormonal analyses. We also investigated the modern ART used to overcome sterility. Results: Coenzyme Q10 and ubiquinol increased significantly sperm concentration, aswell as spermatozoa motility. Intracytoplasmic sperm injection (ICSI) was performed 2 patients, varicocelectomy was performed 1 patient, and total 10 patients are resulted pregnancy. Conclusions:The exogenous administration of coenzyme Q10 increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia with valicocele.

62 A case of 47,XXY/46,XY Klinefelter syndrome

during the short-term follow-up, with 6 cystic fat nodules. The satisfaction rate for sexual function, morphology and global state were 79.8%, 78.9%, and 91.7%. Conclusions: Our technique shows very effective shortterm outcomes and patient’s satisfaction without serious complications. 62 A case of 47,XXY/46,XY Klinefelter syndrome H. Masuda1, Y. Katsuoka2. 1Aino Hospital, 2 Osaka Medical College, Japan Klinefelter syndrome represents the most commonly found human sex chromosomal abnormality. It is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Males with Klinefelter syndrome may have a 47,XXY or a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. We report here a case of a mosaic 47,XXY/46,XX infertile male. The patient was a 31-year-old male. Physical examination revealed perfect male-type of genitalia, almost normal penis and bilateral small testicles, being 1.0 × 2.0 × 1.0 cm sized for the right and 1.0 × 2.0 × 1.0 cm for the left. Chromosome analysis by means of culture of peripheral blood lymphocytes revealed twokinds of 46 chromosomes and of 47 chromosomes. The genotype of the former was XX and of the later was XXY, making XX/XXY mosaicism. Testicular sperm extraction was performed, but we could find the sperm in microdissection testicular sperm extraction procedure. Histologically the testicle showed atrophy of seminiferous tubules with hyalinizaition of the canaliculi. No spermatogenesis was observed at all. 63 Coenzyme Q10 treatment for oligoasthenoteratozoospemia in infertile men with varicocele Y. Kobori, H. Okada, G. Arai, S. Soh, H. Yagi. Dokkyo Medical University Koshigaya Hospital, Department of Urology, Japan Objective: To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men who have varicocele with infertility. Patients: Sixty-nine infertile patients (21–51 years of age) with the following baseline sperm selection criteria: concentration 30%. Patients underwent therapy with coenzyme Q10, 30mg/day. We investigated seminograms, background, hormonal analyses. We also investigated the modern ART used to overcome sterility. Results: Coenzyme Q10 and ubiquinol increased significantly sperm concentration, aswell as spermatozoa motility. Intracytoplasmic sperm injection (ICSI) was performed 2 patients, varicocelectomy was performed 1 patient, and total 10 patients are resulted pregnancy. Conclusions:The exogenous administration of coenzyme Q10 increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia with valicocele.

65 Effects of Clinacanthus nutans and mebeverine hydrochloride on bladder activity

during the short-term follow-up, with 6 cystic fat nodules. The satisfaction rate for sexual function, morphology and global state were 79.8%, 78.9%, and 91.7%. Conclusions: Our technique shows very effective shortterm outcomes and patient’s satisfaction without serious complications. 62 A case of 47,XXY/46,XY Klinefelter syndrome H. Masuda1, Y. Katsuoka2. 1Aino Hospital, 2 Osaka Medical College, Japan Klinefelter syndrome represents the most commonly found human sex chromosomal abnormality. It is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Males with Klinefelter syndrome may have a 47,XXY or a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. We report here a case of a mosaic 47,XXY/46,XX infertile male. The patient was a 31-year-old male. Physical examination revealed perfect male-type of genitalia, almost normal penis and bilateral small testicles, being 1.0 × 2.0 × 1.0 cm sized for the right and 1.0 × 2.0 × 1.0 cm for the left. Chromosome analysis by means of culture of peripheral blood lymphocytes revealed twokinds of 46 chromosomes and of 47 chromosomes. The genotype of the former was XX and of the later was XXY, making XX/XXY mosaicism. Testicular sperm extraction was performed, but we could find the sperm in microdissection testicular sperm extraction procedure. Histologically the testicle showed atrophy of seminiferous tubules with hyalinizaition of the canaliculi. No spermatogenesis was observed at all. 63 Coenzyme Q10 treatment for oligoasthenoteratozoospemia in infertile men with varicocele Y. Kobori, H. Okada, G. Arai, S. Soh, H. Yagi. Dokkyo Medical University Koshigaya Hospital, Department of Urology, Japan Objective: To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men who have varicocele with infertility. Patients: Sixty-nine infertile patients (21–51 years of age) with the following baseline sperm selection criteria: concentration 30%. Patients underwent therapy with coenzyme Q10, 30mg/day. We investigated seminograms, background, hormonal analyses. We also investigated the modern ART used to overcome sterility. Results: Coenzyme Q10 and ubiquinol increased significantly sperm concentration, aswell as spermatozoa motility. Intracytoplasmic sperm injection (ICSI) was performed 2 patients, varicocelectomy was performed 1 patient, and total 10 patients are resulted pregnancy. Conclusions:The exogenous administration of coenzyme Q10 increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia with valicocele.

63 Coenzyme Q10 treatment for oligoasthenoteratozoospemia in infertile men with varicocele

during the short-term follow-up, with 6 cystic fat nodules. The satisfaction rate for sexual function, morphology and global state were 79.8%, 78.9%, and 91.7%. Conclusions: Our technique shows very effective shortterm outcomes and patient’s satisfaction without serious complications. 62 A case of 47,XXY/46,XY Klinefelter syndrome H. Masuda1, Y. Katsuoka2. 1Aino Hospital, 2 Osaka Medical College, Japan Klinefelter syndrome represents the most commonly found human sex chromosomal abnormality. It is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Males with Klinefelter syndrome may have a 47,XXY or a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. We report here a case of a mosaic 47,XXY/46,XX infertile male. The patient was a 31-year-old male. Physical examination revealed perfect male-type of genitalia, almost normal penis and bilateral small testicles, being 1.0 × 2.0 × 1.0 cm sized for the right and 1.0 × 2.0 × 1.0 cm for the left. Chromosome analysis by means of culture of peripheral blood lymphocytes revealed twokinds of 46 chromosomes and of 47 chromosomes. The genotype of the former was XX and of the later was XXY, making XX/XXY mosaicism. Testicular sperm extraction was performed, but we could find the sperm in microdissection testicular sperm extraction procedure. Histologically the testicle showed atrophy of seminiferous tubules with hyalinizaition of the canaliculi. No spermatogenesis was observed at all. 63 Coenzyme Q10 treatment for oligoasthenoteratozoospemia in infertile men with varicocele Y. Kobori, H. Okada, G. Arai, S. Soh, H. Yagi. Dokkyo Medical University Koshigaya Hospital, Department of Urology, Japan Objective: To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men who have varicocele with infertility. Patients: Sixty-nine infertile patients (21–51 years of age) with the following baseline sperm selection criteria: concentration 30%. Patients underwent therapy with coenzyme Q10, 30mg/day. We investigated seminograms, background, hormonal analyses. We also investigated the modern ART used to overcome sterility. Results: Coenzyme Q10 and ubiquinol increased significantly sperm concentration, aswell as spermatozoa motility. Intracytoplasmic sperm injection (ICSI) was performed 2 patients, varicocelectomy was performed 1 patient, and total 10 patients are resulted pregnancy. Conclusions:The exogenous administration of coenzyme Q10 increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia with valicocele.

Clinical analyses of 81 infertile and 20 testicular tumor men with suspected X-chromosome-linked gene anomalies in Japan

A total of 101 cases of 81 infertile men and 20 men with testicular tumors were analyzed clinically for suspected X-chromosome-linked gene abnormalities. Among the 81 infertile men analyzed by testicular biopsy, 11 Klinefelter syndrome (KS) cases showed Leydig cell nodular hyperplasia with azoospermia. They had low levels of testosterone (131 ± 81 ng/dl) and high levels of luteinizing hormone (21 ± 7 mIU/ml) and follicle-stimulating hormone (36 ± 11 mIU/ml). From Leydig cell hyperplasia combined with atrophic tubules, X-linked androgen receptor dysfunctions in Sertoli and Leydig cells were judged in the KS cases. One azoospermia case of non-KS had primary yolk sac tumor of the mediastinum and liver. The removed yolk sac tumor showed complete necrosis after bleomycin, etoposide, and cisplatin (BEP) chemotherapy, which indicated cisplatin-sensitive apoptosis. X-linked inhibitor of apoptotic protein (XIAP) must exhibit an apoptosis-inducible mutation (XIAP-S87A) in the non-KS case. Subsequently, 20 testicular tumor cases were classified into ten with seminoma, eight with mixed germ cell tumors (MGCT), one with mature teratoma, and one with diffuse large B cell lymphoma. Although among the eight MGCT cases, six cases had high levels of α-fetoprotein (68–43647 ng/ml), their blood levels of human chorionic gonadotropin-β were <0.1 to 23 ng/ml with a good prognosis. Radiological examinations of the 20 cases showed nodular, hemorrhagic, or cystic changes in lung, liver, or periarterial lymph nodes, but no metastatic changes in bone or brain. Besides cisplatin-induced acute renal failure in one of the two seminoma cases treated with BEP chemotherapy, the two cases showed chronic renal failure (CRF) due to glomerular disturbance, but three treated MGCT cases did not. Their mutated humanin in spermatocytes, which located in X-chromosome and bound to podocytes, might have aggravated the CRF. Infertility and testis-related tumors were caused by X-chromosome-linked gene anomalies.

Assessment of the potential reproductive toxicity of long-term exposure of adult male rats to low-dose formaldehyde

Formaldehyde (FA), a ubiquitous environmental pollutant, is extensively used in hospitals, laboratories and many industrial settings. Previous studies have showed that short-term, high-dose FA exposure is toxic to male reproduction of mammals. In this paper, we evaluated the male reproductive toxicity of long-term, low-dose formaldehyde exposure in rats, and explored the potential mechanisms. A total of 30 Sprague-Dawley male rats were randomly allotted to three groups, rats were exposed to FA at a dose of 0 (control), 0.5, 2.46 mg/m³ respectively by inhalation for consecutive 60 days. The results indicated that the reproductive toxicity of FA is dose-dependent. Testicular, epididymal structure and function in rats of 0.5 mg/m³ FA exposure group showed no obvious difference compared with those in control group. However, sperm quantity and quality, testicular seminiferous tubular diameter, the activities of superoxide dismutase and glutathione peroxidase was significantly decreased whereas the level of malondialdehyde was significantly increased in rats of 2.46 mg/m³ FA exposure group compared with those in control group. Moreover, histopathological results showed atrophy of seminiferous tubules, decreases of spermatogenic cells and the lumina were oligozoospermic in testes of 2.46 mg/m³ FA exposure rats. In conclusion, the level of 0.5 mg/m³ can be considered as a safe level for FA exposure, but long-term FA exposure at a dose of 2.46 mg/m³ has a harmful effect on male reproduction by inducing oxidative stress in male rats.

Immunopotentiation and antitumor effects of a ginsenoside Rg 3-fortified red ginseng preparation in mice bearing H460 lung cancer cells

Antitumor effects of a ginsenoside Rg 3-fortified red ginseng preparation (Rg 3-RGP) were investigated in human non-small cell lung carcinoma (H460) cells using in vitro cytotoxicity assay and in vivo nude mouse xenograft model. Immunomodulatory effects of the preparation were also assessed by measuring the facilitating activities on the nitric oxide (NO) release from peritoneal macrophages, in vitro and in vivo lymphocyte proliferation, and the carbon clearance from circulating blood. In a cell level, Rg 3-RGP exerted H460 cytotoxicity and facilitated splenocyte proliferation at very high concentrations, without affecting NO production. However, oral administration of Rg 3-RGP (100–300 mg/kg) enhanced carbon particle-phagocytic index of blood macrophages up to 360–397% of control value. In addition, Rg 3-RGP significantly increased the splenocyte proliferation (23% at 100 mg/kg). In tumor-bearing mice, 28-day oral treatment with Rg 3-RGP (100 mg/kg) remarkably suppressed the tumor growth, leading to the decrease of the tumor volume and weight by 30–31%, which was comparable to the effect (27–29% reduction) of doxorubicin (2 mg/kg at 3-day intervals). While Rg 3-RGP did not cause adverse effects, intravenous injection of doxorubicin markedly decreased body and testes weights, and exhibited severe depletion of spermatogenic cells in the atrophic seminiferous tubules. These results indicate that Rg 3-RGP exerts antitumor activities via indirect immunomodulatory actions, without causing adverse effects as seen in doxorubicin.

Pharmacokinetics of p-Aminohippuric Acid and Inulin in Rabbits with Aristolochic Acid Nephropathy.

The characteristics of aristolochic acid nephropathy (AAN) are interstitial fibrosis and atrophy of the proximal tubules, but with no change in glomeruli. To investigate the effects of AA on renal functions and the pharmacokinetics (PKs) of p-aminohippuric acid (PAH) and inulin, New Zealand white rabbits were used in this study. The plasma concentrations of PAH and inulin were determined by validated HPLC methods. After a single intravenous administration of 0.5 mg/kg aristolochic acid sodium (AANa), rabbits exhibited mild to moderate nephrotoxicity on the 7th day. Significant tubulointerstitial damage to kidney specimens was found, but there were no remarkable glomerular changes. Clearance rates of PAH and inulin both significantly decreased in AANa-treated rabbits. In addition, there was a significant correlation among the degree of tubulointerstitial changes and PK parameters of PAH after AANa administration, but no correlation was noted with the PKs of inulin. With mild to moderate AAN in rabbits, the renal plasma flow significantly decreased by 55%, and the glomerular filtration rate also significantly decreased by 85%. In conclusion, major renal lesions were found on proximal tubules after AANa administration. The PKs of PAH and inulin significantly changed, and kidney functions, including the RPF and GFR, were reduced.

Growth, Reproductive Condition, and Digestive Tubule Atrophy of Pacific OysterCrassostrea gigasin Gamakman Bay off the Southern Coast of Korea

ABSTRACT Spat of Pacific oysters (Crassostrea gigas) were collected from Gamakman Bay, Korea, and raised in a spat hardening facility located in the low intertidal zone of the bay for a “hardening/stunting” period of 10 mo. Seasonal changes in growth, reproductive condition, and digestive tubule atrophy (DTA) of these “hardened/stunted” oysters were monitored for more than a year after transplanting to a suspended longline system in a grow-out area in the bay. After transplantation, the hardened/stunted oysters showed a logarithmic increase in shell size for the first 4 mo, from June to October, and growth remained stable from late fall to early spring. During the 12 mo of the grow-out, the shell size of the hardened/stunted oysters increased from 15.4–74.2 mm, and tissue weight increased from 0.49–12.85 g. Histological analysis revealed that gametogenesis of hardened/stunted oysters commenced as early as February when water temperature remained at 10°C, and spawning occurred from July to September when w...

Copper Metabolism Disorders Affect Testes Structure and Gamete Quality in Male Mice

In the present study, animals with a genetic defect in copper metabolism were used as a model organism to study the role of copper in reproduction and to determine whether the disturbances in copper and zinc metabolism affect the testicular tissue and gamete quality in males. Mice with an X-linked mosaic mutation (Atp7amo-ms) exhibit pathological features characteristic of affected copper metabolism. This mutation usually leads to lethality of the mutant males which generally expire on about day 16. Only 4% of mutant animals survive the critical period, achieve maturity, and become fertile. To improve the mutants' viability they were treated with subcutaneous injections of cupric chloride. We measured copper and zinc concentration in the gonads of young (14-day-old) and adult (5-month-old) mutant and control males. Results indicate that copper content was increased but zinc was decreased in the mutant testes. Analysis of the morphology of the testis of the young animals indicate that apoptosis (characteristic for the gonads of young males) was increased in the gonads of the 14-day-old mutants. This process was less advanced in the group of 14-day-old copper treated control males. Apoptosis was also increased in the testes of the adult mutants. Moreover in adult mutants we observed pathological changes in testes morphology (atrophic and sclerotic tubules). Copper and zinc disorders also negatively influenced semen quality parameters, including sperm motility, head morphology, tail cytoplasmic membrane integrity, and number of viable spermatozoa. Poor semen quality of the mutant males seems to be responsible for affected in vivo fertilization efficiency. Treatment with cupric chloride did not influence semen quality except in maturation rate, which was even slower in both mutant and control males after treatment. Additionally, in mutants, copulatory plugs and fertile copulation outcome were decreased after copper treatment.

Di-n-butyl phthalate (DBP) exposure induces oxidative stress in epididymis of adult rats

Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a plasticizer in many products including plastics, cosmetics and medical devices. Previous studies have shown that DBP has potential testicular toxicity. Epididymis is known to play an important role in the maturation and storage of sperm. However, the effect and mechanism of action of DBP on epididymis is unclear. The present study was designed to investigate the effect of DBP on structure and function of epididymis in adult male rats by histological and biochemical study. Oxidative stress was also assessed in rat epididymis as an underlying mechanism. Forty SD adult rats were randomly allotted to four groups, and DBP was administered to each group by oral gavage at doses of 0 (control), 100, 250 and 500 mg/kg/day for 2 consecutive weeks. The results indicated that the epididymal toxicity of DBP is dose-dependent. Epididymal weight, activities of epididymal alpha-glucosidase and glutathione peroxidase (GSH-Px) was significantly decreased in rats of 500 mg/kg DBP exposure group compared to the control. The activity of superoxide dismutase (SOD) was significantly decreased while the level of malondialdehyde (MDA) was significantly increased in the epididymal tissue of the 250 and 500 mg/kg DBP exposure groups compared with the control group. Moreover, microscopy with hematoxylin and eosin (HE) staining showed that atrophy of epididymal tubules, the interstitial vascular was hyperemia and the lumina were oligozoospermic in rats of 500 mg/kg DBP exposure group. In conclusion, DBP exposure alters the epididymal structure and function by inducing oxidative stress in epididymis of adult rats.

Increased plasma levels of phthalate esters in women with advanced-stage endometriosis: a prospective case-control study

We performed the present prospective case-control study to evaluate whether the plasma concentrations of phthalate esters are elevated in women with advanced-stage endometriosis in a Korean population. Measuring plasma levels of monoethylhexyl phthalate and di-(2-ethylhexyl) phthalate in 97 women with advanced-stage endometriosis and 169 control women by liquid chromatography-tandem mass spectrometry, we found that the concentrations of monoethylhexyl phthalate, as well as di-(2-ethylhexyl) phthalate, are significantly higher in those with advanced-stage endometriosis, which supports the hypothesis that exposure to phthalate might play a role in the establishment of endometriosis.

Effect of formaldehyde exposure on structure and function of epididymis in adult rats: a histological and biochemical study

Formaldehyde (FA), a ubiquitous environmental pollutant, is extensively used in hospitals, laboratories, and industrial settings. Previous studies showed that FA exerts adverse effects on testicular function and as epididymis is known to play an important role in the maturation and storage of sperm, the effects of FA were examined on epididymis. In particular, this study was designed to investigate the influence of FA on structure and function of epididymis in adult male rats using histological and biochemical methods. Sprague-Dawley adult rats were randomly allotted to three groups and exposed to FA at a 0 (control), 0.5, or 10 mg m−3 by inhalation for 28 days. The results indicated that epididymal toxicity of FA was concentration dependent. Epdididymal structure and function in rats of 0.5 mg m−3 FA exposure group showed no apparent difference from control. However, epididymal weight, sperm count and motility, the activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were significantly decreased, whereas the levels of malondialdehyde (MDA) was significantly increased in epididymis of rats exposed to 10 mg m−3 FA. Moreover, microscopy with hematoxylin and eosin (H&E) staining showed atrophy of epididymal tubules, disintegration of epididymal epithelium, disorganization, and even vacuolar denaturalization of epididymal epithelial cells. There was hyperemia in interstitial vasculature and lumina were oligozoospermic in rats of 10 mg m−3 FA exposure group. In conclusion, FA exposure alters the epididymal structure and function by inducing oxidative stress in epididymis of adult rats.

Apoptosis contributes to testicular toxicity induced by two isomers of bromopropanes

The aim of this study was to investigate the different testicular toxicity and the role of apoptosis in the possible mechanism induced by the two isomers of bromopropanes (BPs) in the same dosage. Following the 14-day treatment with a single dose of 1-BP and 2-BP (1 g/kg), male rats were killed and a series of experiments were performed. 1-BP and 2-BP both significantly decreased the epididymal sperm count, while only 2-BP induced an increase in sperms with abnormal heads. Morphological evaluation showed that 1-BP did not cause morphological changes in seminiferous epithelium, but 2-BP treatment resulted in the disappearance of spermatogonia, atrophy of the seminiferous tubules and degeneration of germ cells. 2-BP significantly increased the TUNEL-positive cells and the activation of caspase-3 and decreased the genes and proteins expression of Bax, Bcl-2 and p53. In contrast, there were no significant changes in the expression of apoptosis-related genes and proteins in 1-BP group, though the TUNEL-positive cells were significantly increased. Taken together, this study indicated that those two isomers both have toxicity in male rats, however, the testicular toxicity and the role of apoptosis in the toxic mechanism induced by 1-BP and 2-BP may be different.

Protective effects of melatonin and Glycyrrhiza glabra extract on ochratoxin A—induced damages on testes in mature rats

The effect of Glycyrrhiza glabra extract (GgE) as a natural antioxidant and melatonin (MEL) on ochratoxin A (OTA)-induced histopathological damages on the testes and oxidative stress was evaluated in male rats. The animals were assigned into four groups (n = 8) including control and test groups. The rats in control group received saline and the animals in the test groups received (200 µg/kg) of OTA, (15 mg/kg) of MEL + (200 µg/kg) OTA and (100 mg/kg) of GgE + (200 µg/kg) OTA, respectively, during 28 consecutive days. The serum total antioxidant power (TAOP) and total thiol molecules (TTM) production were assessed. Moreover, histopathological and histochemical studies were also performed. The results showed that the TAOP and TTM were decreased in OTA-exposed rats, while the animals that received MEL + OTA or GgE + OTA showed an enhancement in the serum TAOP and TTM levels. Histopathological analyses demonstrated that in OTA-exposed rats, the testicular degeneration, seminiferous tubule atrophy, dissociation of germinative epithelium, vasodilatation with vascular thrombosis, perivascular immune cell infiltration, hypertrophied leydic cells, giant cell formation, and negative tubular differentiation index (TDI) were observed. Surprisingly, both the biochemical and histopathological examinations showed that MEL and GgE, albeit with some differences, exerted a protective effect on OTA-induced damages. In conclusion, this data suggest that OTA contamination in animal feeds and human foods could cause reproductive abnormalities. Our data also indicate that OTA, at least partly by interfering in oxidative stress system, exerts its toxic effects on testes whereas MEL and GgE with antioxidant properties could fairly protect rats against OTA toxic effects.

Omi/HtrA2 protease is associated with tubular cell apoptosis and fibrosis induced by unilateral ureteral obstruction.

Kidney fibrosis, a typical characteristic of chronic renal disease, is associated with tubular epithelial cell apoptosis. The results of our recent studies have shown that Omi/HtrA2 (Omi), a proapoptotic mitochondrial serine protease, performs a crucial function in renal tubular epithelial apoptotic cell death in animal models of acute kidney injury, including cisplatin toxicity and ischemia-reperfusion insult. However, the role of Omi in tubulointerstitial disease-associated fibrosis in the kidney remains to be clearly defined. We evaluated the potential function and molecular mechanism of Omi in ureteral obstruction-induced kidney epithelial cell apoptosis and fibrosis. The mice were subjected to unilateral ureteral obstruction (UUO) via the ligation of the left ureter near the renal pelvis. UUO increased the protein level of Omi in the cytosolic fraction of the kidney, with a concomitant reduction in the mitochondrial fraction. UUO reduced the X-linked inhibitor of apoptosis protein (XIAP), a substrate of Omi, and pro-caspase-3, whereas it increased cleaved poly(ADP-ribose) polymerase (cleaved PARP) and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells. When mice were treated with ucf-101, an inhibitor of the proteolytic activity of Omi (6.19 microg/day ip), on a daily basis beginning 2 days before UUO and continuing until the end of the experiment, the Omi inhibitor protected XIAP cleavage after UUO and reduced the increment of PARP cleavage and the numbers of TUNEL-positive cells. Furthermore, the Omi inhibitor significantly attenuated UUO-induced increases in fibrotic characteristics in the kidney, including the atrophy and dilation of tubules, expansion of the interstitium, and increases in the expression of collagens, alpha-smooth muscle actin, and fibronectin. In conclusion, Omi/HtrA2 is associated with apoptotic signaling pathways in tubular epithelial cells activated by unilateral ureteral obstruction, thereby resulting in kidney fibrosis.

Genotype–phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Chronic Progressive Nephropathy: Functional, Morphological, and Morphometrical Studies

Some aspects of the functional, morphological, and morphometrical characteristics of chronic progressive nephropathy occurring in 18- to 26-month-old male rats and in 3-month-old control rats were studied. Rats with chronic progressive nephropathy were proteinuric and showed a slight increase in serum creatinine and no changes in blood pressure. The morphological changes were studied by light microscopy, high-resolution light microscopy, and electron microscopy. They showed focal and segmental or global glomerulosclerosis, the three types of atrophic tubules (“classic,” “thyroid-like,” and “endocrine”) described by Nadasdy et al, as well as interstitial fibrosis with mononuclear cell infiltrates. On certain occasions, small vessels showed hyalinosis. Glomerular morphometrical studies showed a biphasic pattern in the glomeruli progressing toward obsolescence. Vascular morphometrical studies showed significant increase in media wall thickness and media cross-sectional area in the 18- to 26-month-old rats. These results support the hypothesis that changes in the vascular system are not of utmost importance in the pathogenesis of chronic progressive nephropathy, and that glomerular sequential changes seem to be of paramount significance in the progression of the disease.

Effects and mechanism of irbesartan on tubulointerstitial fibrosis in 5/6 nephrectomized rats

Tubulointerstitial fibrosis (TIF) is a common pathological feature of end-stage kidney disease. Previous studies showed that upregulation of TGFbeta1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction. This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFbeta1 in the rodent model of chronic renal failure involving 5/6 nephrectomy. The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model. Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group, but the lesion was attenuated mostly in irbesartan-treated group. Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFbeta1 which was up-regulated in operation groups. Western blot showed that irbesartan treatment down-regulated the expression of TGFbeta1, phosphorylated smad2 (p-smad2), AT1R and phosphorylated p38 (p-p38) MAPK, but significantly up-regulated the protein expression of smad6 as compared with operation group. These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6, TGF-beta1, p-smad2, AT1 and p-p38 MAPK.

New Approaches to Pathogenesis and Management of Hypertension

New Approaches to Pathogenesis and Management of Hypertension