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The Journal of Toxicological Sciences May 2003A 4-week intravenous repeated dose toxicity study of L-cysteine (L-Cys) was conducted in male Sprague-Dawley rats to investigate in detail the toxic effects of this...
A 4-week intravenous repeated dose toxicity study of L-cysteine (L-Cys) was conducted in male Sprague-Dawley rats to investigate in detail the toxic effects of this compound and to determine the dose level at which these toxic effects are observed following repeated intravenous administration. Male rats were randomly allocated to 4 groups to receive L-Cys by intravenous administration at dosages of 0, 100, 300, and 1,000 mg/kg body weight/day. Body weight gain was significantly suppressed throughout the study period in the 1,000-mg/kg group, although food consumption was reduced only on study day 3. A decrease in spontaneous activity, salivation, stereotypy, ptosis, and tremor were observed in the 1,000-mg/kg group. Mild anemia characterized by decreases in hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and an increase in the reticulocyte count was also noted in the 1,000-mg/kg group. Histopathological examination showed sperm granulomas in the epididymis and necrosis of the Purkinje cells and granular layer in the cerebellum in the 1,000-mg/kg group. Slight tubular basophilia with blood or hyaline casts was observed in the kidney in the 300-mg/kg and 1,000-mg/kg groups, associated with proteinuria or occult blood in urinalysis. Additional studies are needed to clarify the causes for these toxicological findings by excess of L-Cys.
Topics: Animals; Blood Cell Count; Blood Chemical Analysis; Body Weight; Cysteine; Eating; Injections, Intravenous; Male; Organ Size; Rats; Rats, Sprague-Dawley
PubMed: 12820541
DOI: 10.2131/jts.28.95 -
National Toxicology Program Technical... Sep 2000Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through...
Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 &mgr;m) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. The final mean body weights were similar among exposed and chamber control groups. Compared to chamber controls, the lung weights of males and females exposed to 10 mg/m(3) or greater were increased. Gallium ar senide particles were visible in alveolar spaces and macrophages in some mice exposed to 150 mg/m(3). Moderate proteinosis, mild epithelial hyperplasia, and histiocytic infiltration of the lung were observed in males and females exposed to 10 mg/m(3) or greater. In the larynx, mild squamous metaplasia was seen in mice exposed to 10 mg/m(3) or greater, and mild chronic inflammation occurred in mice exposed to 75 or 150 mg/m(3). 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. All rats survived until the end of the study. The final mean body weight and body weight gain of males exposed to 75 mg/m(3) were significantly less than those of the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in exposed groups of rats. There were also increases in platelet and neutrophil counts, a transient decrease in leukocyte counts, and increases in the serum activities of alanine aminotransferase and sorbitol dehydrogenase. These changes were of greater magnitude in male rats. The lung weights of all exposed groups of rats were increased, while testis, cauda epididymis, and epididymis weights of males exposed to 37 or 75 mg/m(3) were generally less than those of chamber controls. Total spermatid heads and spermatid counts were significantly decreased in males exposed to 75 mg/m(3), while epididymal spermatozoa motility was significantly reduced in males ees exposed to 10 mg/m(3) or greater. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of exposed rats. Minimal to marked proteinosis and minimal histiocytic cellular infiltration of the alveoli were observed in all exposed groups; minimal squamous metaplasia in the larynx and lymphoid cell hyperplasia of the mediastinal lymph node were observed in some males and females exposed to 37 or 75 mg/m(3). Exposure-related increases in the incidences of plasma cell hyperplasia of the mandibular lymph node, testicular atrophy, epididymal hypospermia, bone marrow hyperplasia (males), and hemosiderosis in the liver were observed in the 37 and 75 mg/m(3) groups. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. One female mouse exposed to 75 mg/m(3) died before the end of the study. Final mean body weights and body weight gains of males in the 75 mg/m(3) group were signifi cantly less than the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide affected the circulating erythroid mass and induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in male and female mice. There were also increases in platelet and neutrophil counts. Compared to the chamber controls, the lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased. Testis, cauda epididymis, and epididymis weights, total spermatid heads, spermatid counts, and concentration and motility of epididymal spermatozoa were generally decreased. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of mice exposed to 1 mg/m(3) or greater. Mild to marked proteinosis, histiocytic infiltration, and epithelial hyperplasia were observed in the alveoli of males and females exposed to 1 mg/m(3) or greater. Minimal to mild suppurative inflammation and granuloma in the lung and squamous metaplasia in the larynx were present in males and females exposed to 10 mg/m(3) or greater. Min imal hyperplasia was observed in the tracheobronchial lymph node of males exposed to 10 mg/m(3) or greater and females exposed to 37 or 75 mg/m(3). Exposure- related increases in the incidences of testicular atrophy, epididymal hypospermia, hematopoietic cell proliferation of the spleen, and hemosiderosis of the liver and spleen were observed in groups of male and female mice exposed to 10 mg/m(3) or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.01, 0.1, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber controls. Mean body weights of males exposed to 1.0 mg/m(3) were generally less than those of the chamber controls throughout the study; females exposed to 1.0 mg/m(3) had slightly lower mean body weights during the second year. Pathology Findings: Compared to the chamber controls, the incidences of alveolar/bronchiolar neoplasms were significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control ranges. Exposure-related nonneoplastic lesions in the lungs of male and female rats included atypical hyperplasia, alveolar epithelial hyperplasia, chronic active inflammation, proteinosis, and alveolar epithelial metaplasia. In the larynx of males exposed to 1.0 mg/m(3), the incidences of hyperplasia, chronic active inflammation, squamous metaplasia, and hyperplasia of the epiglottis were significantly increased. The incidences of benign pheochromocytoma of the adrenal medulla occurred with a positive trend in female rats, and the incidence was significantly increased in the 1.0 mg/m(3) group and exceeded the historical control range. The incidence of mononuclear cell leukemia was significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control range. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 0.5, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 (males) or 106 (females) weeks. Survival and Body Weights: Survival of male and female mice was similar to the chamber controls. Mean body weights of exposed groups of males were similar to those of the chamber controls throughout the study; mean body weights of exposed groups of females were greater than those of the chamber controls from week 13 until the end of the study. Pathology Findings: Exposure-related nonneoplastic lesions in the lung of all groups of exposed mice included suppurative focal inflammation, chronic focal inflammation, histiocyte cellular infiltration, alveolar epithelial hyperplasia, and proteinosis. Increased incidences of minimal lymphoid hyperplasia of the tracheobronchial lymph node occurred in mice exposed to 1.0 mg/m(3) and in 0.5 mg/m(3)mg/m(3) males. GENETIC TOXICOLOGY: Gallium arsenide was not mutagenic in several strains of Salmonella typhimurium, with or without S9 metabolic activation enzymes, and no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to gallium arsenide by inhalation for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of gallium arsenide in male F344/N rats exposed to 0.01, 0.1, or 1.0 mg/m(3). There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of benign and malignant neoplasms in the lung. Increased incidences of benign neoplasms of the adrenal medulla and increased incidences of mononuclear cell leukemia were also considered to be exposure related. There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to 0.1, 0.5, or 1.0 mg/m(3). Exposure to gallium arsenide caused a spectrum of nonneoplastic lesions in the lung of rats and mice, the larynx of male rats and hyperplasia of the tracheobronchial lymph node in mice. Synonym: Gallium monoarsenide.
PubMed: 12563348
DOI: No ID Found -
Archives of Pathology & Laboratory... Oct 2000Genital rhabdomyoma is a rare tumor of skeletal muscle origin that is usually found in the vulvar area of young women. The English literature contains only 2 previous...
Genital rhabdomyoma is a rare tumor of skeletal muscle origin that is usually found in the vulvar area of young women. The English literature contains only 2 previous case reports involving men, both of whom were 19 years old. One of these lesions originated in the tunica vaginalis of the testis, and the other originated in the prostate gland. We present the clinical, histologic, and immunohistochemical findings of an epididymal rhabdomyoma in a 20-year-old man. To our knowledge, this is the first such case reported in this location.
Topics: Adult; Biomarkers, Tumor; Cystadenoma; Diagnosis, Differential; Epididymis; Granuloma; Humans; Immunohistochemistry; Male; Mesothelioma; Neoplasm Proteins; Rhabdomyoma; Spermatozoa; Teratoma; Testicular Neoplasms; Treatment Outcome; Tuberculosis, Male Genital
PubMed: 11035587
DOI: 10.5858/2000-124-1518-ER -
Fertility and Sterility May 2000To recommend further research on vasectomy based on a systematic review of the effectiveness and safety of vasectomy. (Review)
Review
OBJECTIVE
To recommend further research on vasectomy based on a systematic review of the effectiveness and safety of vasectomy.
DESIGN
A systematic MEDLINE review of the literature on the safety and effectiveness of vasectomy between 1964 and 1998.
MAIN OUTCOME MEASURE(S)
Early failure rates are <1%; however, effectiveness and complications vary with experience of surgeons and surgical technique. Early complications, including hematoma, infection, sperm granulomas, epididymitis-orchitis, and congestive epididymitis, occur in 1%-6% of men undergoing vasectomy. Incidence of epididymal pain is poorly documented. Animal and human data indicate that vasectomy does not increase atherosclerosis and that increases in circulating immune complexes after vasectomy are transient in men with vasectomies. The weight of the evidence regarding prostate and testicular cancer suggests that men with vasectomy are not at increased risk of these cancers.
CONCLUSION(S)
Publications to date continue to support the conclusion that vasectomy is a highly effective form of contraception. Future studies should include evaluations of the long-term effectiveness of vasectomy, evaluating criteria for postvasectomy discontinuation of alternative contraception for use in settings where semen analysis is not practical, and characterizing complications including chronic epididymal pain syndrome.
Topics: Adolescent; Adult; Contraindications; Counseling; Humans; MEDLINE; Male; Prostatic Neoplasms; Testicular Neoplasms; United States; Vasectomy; Vasovasostomy
PubMed: 10785217
DOI: 10.1016/s0015-0282(00)00482-9 -
Journal of Andrology 2000Estrogen has been shown to have an important role in fluid reabsorption in efferent ductules of the testis. Our previous study of the estrogen receptor-alpha knockout...
Estrogen has been shown to have an important role in fluid reabsorption in efferent ductules of the testis. Our previous study of the estrogen receptor-alpha knockout mouse (ERKO) showed that the efferent ductules and rete testis were primary targets of estrogen receptor function. In the present study, a more comprehensive evaluation of the ERKO male reproductive tract was performed to determine the severity of effects in efferent ductules as well as the epididymis. The following observations were found in ERKO males: 1) blind-ending efferent ductules were more prevalent in ERKO than in wild type (WT) tissues; 2) glycogen-containing cells were observed at the rete testis-efferent ductule junction; 3) the tubular diameters of the efferent ductules and initial segment epididymides were dilated; 4) efferent ductules were dilated between 130 to 300% over wild type ductules; 5) efferent ductule epithelial height was reduced nearly 50%; 6) microvilli of nonciliated cells of efferent ductules were 64% shorter in length; 7) cilia were reduced in number; 8) initial segment epithelium was displaced into regions adjacent to the rete testis and in short segments of the common region of efferent ductule; 9) apical, narrow, and clear cells of the epididymis also were abnormal in some regions; 10) in the corpus and cauda regions, sperm granulomas were noted in one third of the ERKO males. In conclusion, the entire reproductive tract is affected in ERKO males. The cells showing the greatest effects were estrogen receptor-positive cells. It appears that in the ERKO mouse there are developmental anomalies that must be considered separately from adult dysfunctional changes in the male reproductive tract.
Topics: Animals; Epididymis; Epithelium; Estrogen Receptor alpha; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Mice; Mice, Knockout; Microscopy, Electron; Receptors, Estrogen; Reference Values; Rete Testis
PubMed: 10670526
DOI: No ID Found -
Journal of Andrology 1999It is known that a spermatic granuloma is induced by the inflammatory reaction following leakage of spermatozoa outside the germ cell ducts and is the main clinical...
It is known that a spermatic granuloma is induced by the inflammatory reaction following leakage of spermatozoa outside the germ cell ducts and is the main clinical complication of vasectomy. In the present study, we found that spermatic granulomata were experimentally induced in the epididymides of mice treated with high-dose testosterone. Testosterone powder (0.02, 0.2, or 2 mg per gram body weight) was implanted into ICR male mice, which were then killed from 7 to 63 days after the treatment for histological examination at the light-microscopic level. The results showed that the testis exhibited little or no degenerative change; however, the epididymides were frequently affected by spermatic granulomata after day 35 in mice implanted with high-dose testosterone (2 but not 0.2 or 0.02 mg per gram body weight). Observation of the early histological changes revealed that the ductal epithelium of the epididymides became vacuolated around day 25. Thereafter, the basement membrane of the epididymal ducts was ruptured after day 30, followed by leakage of spermatozoa into the adjacent interstitial tissue. The extravasated spermatozoa were then surrounded by macrophages (= epithelioid cells) and lymphocytes, resulting in the formation of a spermatic granuloma. In contrast, other mice treated with the same dose of deoxycorticosterone or estradiol did not show the induction of spermatic granulomata. Therefore, this study demonstrated that a spermatic granuloma is specifically formed in the epididymis by testosterone and that the lesion is started by vacuolation of the epididymal duct epithelium.
Topics: Animals; Drug Implants; Epididymis; Granuloma; Male; Mice; Mice, Inbred ICR; Spermatozoa; Testis; Testosterone
PubMed: 10452600
DOI: No ID Found -
American Family Physician Jul 1999Vasectomy can be performed by means of various techniques, although each vasectomy technique requires isolation and division of the vas and operative management of the... (Review)
Review
Vasectomy can be performed by means of various techniques, although each vasectomy technique requires isolation and division of the vas and operative management of the vasal ends. Removal of at least 15 mm of vas is recommended, although division of the vas without removal of a segment is effective when this technique is combined with other techniques for handling the vasal ends, such as thermal luminal fulguration and proximal fascial interposition. Ligation of the ends without the aid of surgical clips may result in necrosis and sloughing of the ends, which may cause early failure. Leaving the testicular end of the vas open has been shown to be effective and to result in a lower incidence of epididymal congestion and sperm granuloma. The no-scalpel technique offers shorter operating time, less pain and swelling, and faster recovery.
Topics: Humans; Male; Patient Education as Topic; Teaching Materials; Vasectomy
PubMed: 10414634
DOI: No ID Found -
The Anatomical Record Jan 1999The development of the testes was studied in rats following prepubertal obstruction of the epididymis. Male rats received bilateral ligation of the corpus epididymidis...
The development of the testes was studied in rats following prepubertal obstruction of the epididymis. Male rats received bilateral ligation of the corpus epididymidis or a sham operation at 10 days of age, and temporal changes in testicular morphology and weights of reproductive organs were determined at intervals spanning sexual maturation. Development of the testes was normal through 35 days of age. The initial histological changes in the testes of ligated animals, observed at 56 days, included an increased diameter of the seminiferous tubule lumen, depletion of spermatids, and the presence of multinucleate spermatids. Subsequently, germ cells were greatly depleted in the testes of 91- and 128-day-old rats with ligated epididymides. After puberty, testicular weight and volume declined relative to corresponding sham-operated animals. On the other hand, the weights of the epididymides in ligated animals prior to puberty significantly exceeded those of sham-operated rats but weighed significantly less than those of rats in the sham group after sexual maturation. Testicular alterations occurred after increases in the weights of the epididymides. Testicular changes may have contributed to rather than resulted from an autoimmune response to spermatozoa because testicular alterations preceded increases in antisperm autoantibodies.
Topics: Animals; Autoantibodies; Epididymis; Granuloma; Ligation; Male; Organ Size; Rats; Rats, Inbred Lew; Seminiferous Epithelium; Sexual Maturation; Spermatozoa; Testis
PubMed: 9892420
DOI: 10.1002/(SICI)1097-0185(19990101)254:1<76::AID-AR10>3.0.CO;2-# -
Fertility and Sterility Oct 1998To report an unusual case of intermittent azoospermia associated with epididymal sarcoidosis.
OBJECTIVE
To report an unusual case of intermittent azoospermia associated with epididymal sarcoidosis.
DESIGN
Retrospective case analysis.
SETTING
Wilford Hall Medical Center.
PATIENT(S)
A 36-year-old male with secondary infertility and epididymal sarcoidosis.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURES(S)
An analysis of sperm count in relation to steroid courses.
RESULTS(S)
Epididymalgia, and to a lesser extent, sperm counts were noted to fluctuate temporally around steroid courses given for pulmonary flares of sarcoidosis. Epididymal sarcoidosis can be associated with intermittent azoospermia. Presumably, epididymal granulomas undergo exacerbations and remissions and cause intermittent ductal obstruction.
CONCLUSIONS(S)
Because of the unpredictable effect of sarcoidosis on the male genital tract, all patients interested in paternity should obtain a semen analysis at the time of disease diagnosis. If oligospermia is noted or if there is clinical evidence of epididymal involvement, the patient should be offered sperm banking for possible future assisted reproductive techniques.
Topics: Adult; Epididymis; Humans; Male; Oligospermia; Periodicity; Sarcoidosis; Testicular Diseases
PubMed: 9797115
DOI: 10.1016/s0015-0282(98)00272-6 -
Journal of Andrology 1998An autoimmune response to sperm occurs after vasectomy, but there is little information on whether similar reactions occur after obstruction of the male reproductive...
An autoimmune response to sperm occurs after vasectomy, but there is little information on whether similar reactions occur after obstruction of the male reproductive tract at other points. Male Lewis rats received bilateral ligation of the corpus epididymidis or a sham operation at age 10 days, and the subsequent systemic antisperm autoantibody responses were compared to those observed following obstruction of the vas deferens. After sexual maturation, rats with epididymal ligations had antisperm antibodies on an enzyme-linked immunosorbent assay that were significantly higher than those of sham-operated animals and did not differ from antibody levels in vasectomized rats at the same ages. Western blot analysis showed that certain sperm proteins were recognized by antisperm antibodies after both epididymal ligation and vasectomy, including the previously identified "dominant" autoantigens at 73-83, 68-72, 48, 42, and 22 kDa. On the other hand, sera from rats with epididymal ligations recognized 60 and 52 kDa proteins that were not bound by most postvasectomy sera. Conversely, 42-48 and 38-42 kDa bands were more strongly and frequently stained after vasectomy than after epididymal ligation. The results demonstrate that antisperm antibodies are produced after obstruction of the epididymis and that the magnitude of the response is comparable to that after vasal obstruction. Differences in autoantigens recognized after epididymal and vasal obstructions may reflect maturational changes in sperm components that take place during the passage of spermatozoa through the epididymis.
Topics: Animals; Autoantibodies; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Epididymis; Granuloma; Male; Rats; Rats, Inbred Lew; Sexual Maturation; Spermatozoa
PubMed: 9570736
DOI: No ID Found