Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The question of whether a 4 or 9 week premating treatment period is more suitable in studies for effects on fertility and early embryonic development, and the extent to which the screening of sperm parameters may contribute to the detection of effects, has been under discussion since the ICH guideline changed in 1994/1995. This study presents a comparison between 4 and 9 weeks treatment with known male reproductive toxicants with regard to sperm motility, count, morphology, abnormal movements and testicular and epididymal histopathology. Mating outcome was examined after 4 weeks treatment. Three compounds with different targets and mechanisms of action were chosen: two testicular toxicants, Pyridoxine and Adriamycin and the epididymal toxicant, alpha-Chlorohydrine. Sperm motility was reduced in males treated with Pyridoxine (markedly) and alpha-Chlorohydrine (slightly) after 4 weeks treatment and in males treated with Adriamycin after 9 weeks treatment. With Pyridoxine and Adriamycin, sperm count was significantly increased after 4 weeks. Histopathological examination after 4 weeks showed characteristic changes leading to marked testicular tubular atrophy at 8/9 weeks, which was confirmed by a significantly reduced sperm count at 8/9 weeks. With alpha-Chlorohydrine, sperm count was not affected and the results of the histopathological examination were equivocal. Changes in sperm morphology were observed after 4/9 weeks of treatment with Pyridoxine. Mating outcome after 4 weeks was markedly affected with both Pyridoxine and alpha-Chlorohydrine, but no effect was observed with Adriamycin. The results of this study indicate that the two testicular toxicants would have been detected as male reproductive toxicants in a 4-week general toxicity study with routine testicular histopathology and examination of sperm parameters, without the need for mating trials. For the epididymal toxicant, alpha-Chlorohydrine, there was slightly reduced sperm motility after 4 weeks treatment, but mating trials were necessary for confirmation of the toxic effect. Without sperm motility examination, this effect would have been missed in early drug development causing problems in clinical studies. Further comparisons of the validity of 4 or 9 weeks treatment require the testing of other compounds with different targets/mechanism of actions, as well as evaluation of dose-response relationships.
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PMID:Improved risk assessment by screening sperm parameters. 1131 77

Epididymal tumors are uncommon and usually benign, with only 25% of them being malignant. Undifferentiated epididymal carcinoma in particular is extremely rare. We report on a 54-year-old male patient presented with right testicular pain and scrotal mass for the last 6 months. Laboratory investigations were unremarkable but epididymal biopsy result was epididymal undifferentiated carcinoma. Inguinal radical orchidectomy was performed and pathological examination of the surgical specimen confirmed the presence of undifferentiated carcinoma. Then, adjuvant chemoradiotherapy (four cycles of cisplatin-etoposide chemotherapy and radiotherapy) was administered. After four months, lung metastases were detected and three doses ifosfamide-Adriamycin chemotherapy were given, but the patient died due to the disease progression. Reports of epididymal undifferentiated carcinoma are extremely rare and the present report emphasizes the need of including epididymal undifferentiated carcinoma in the differential diagnosis of an epididymal mass.
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PMID:Undifferentiated carcinoma of the epididymis. 2238 78