Corticosterone does not cause testicular toxicopathology in the rat: relevance to methylxanthines, ACTH and stress.

1. Methylxanthines, ACTH and stress are well known to produce testicular pathology (e.g. seminiferous tubule atrophy). Methylxanthines, ACTH and stress alter hormone secretion, particularly from the pituitary-adrenocortical system. Consequently, it has recently been suggested that there may be a causal relationship between changes in endogenous physiological adrenocortical secretions, particularly corticosterone, and testicular pathology. 2. This study tested the hypothesis that corticosterone mediates the testicular effects of both methylxanthine treatment and stress. Corticosterone was administered daily by subcutaneous injection to groups of 10 male rats at dose levels of 2 or 20 mg kg-1 in propylene glycol (1 ml kg-1) for 1 month (the shortest duration of methylxanthine or ACTH exposure known to produce testicular pathology). The highest dose of corticosterone resulted in plasma concentrations that closely matched values resulting from stress (200-700 ng ml-1) compared with controls (< 25 ng ml-1). 3. The highest dose of corticosterone caused reduced body weight gain, lower thymus, adrenal, seminal vesicle and prostate weights, but did not induce any testicular pathology. 4. That a high, but physiologically relevant, dose of corticosterone did not cause testicular pathology in this experiment excludes this steroid in the direct aetiology of methylxanthine, ACTH and stress-induced testicular pathology. Other steroids secreted from the adrenal, in combination with corticosterone, may be involved.     

Finite element analysis of the effects of thermal obturation in maxillary canine teeth.

OBJECTIVE: The purpose of the present study was to determine the distribution and level of temperature, in a model of a maxillary canine, the surrounding periodontal tissues, and the bones, during a System B heat obturation technique simulation. STUDY DESIGN: The temperature distribution was determined by using a three-dimensional finite element analysis. The tooth was assumed to have undergone an endodontic treatment before the application. Heat applications of 200 degrees C and 100 degrees C were considered. RESULTS: By using the virtual model and the simulation technique, the maximum temperature in the periodontal ligament was found to be 43.5 degrees C. CONCLUSIONS: Within the assumptions and the limitations of the study, it was determined that the simulation of System B technique created no potentially harmful levels of temperature throughout the maxillary canine model.     

Experience with and outlook for the use of cisplatin in the combined therapy of osteogenic sarcoma

The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.      

Two large French pedigrees with non syndromic sensorineural deafness and the mitochondrial DNA T7511C mutation: evidence for a modulatory factor

Hearing impairment is the most frequent sensory defect in children, with a genetic basis in about 50% of cases. Several point mutations and deletions in mitochondrial DNA (mtDNA) have been identified in non-syndromic sensorineural hearing loss (NSSNHL). Beside the frequent A1555G mutation, a number of mutations in tRNAs have been reported recently, but their incidence remains unknown. We identified the T7511C mutation in the tRNASer(UCN) gene in two French families with isolated deafness. Maternal transmission was obvious in both. The 15 patients with hearing impairment exhibited a variable disease phenotype in terms of onset, severity, and progression. T7511C was present in all the patients screened. Homoplasmic and heteroplasmic levels were observed and did not correlate with the severity of the disease. T7511C was also present in 12 hearing offspring of the oldest deaf mothers, confirming the existence of modulatory factors. Our data suggest that this mtDNA mutation should be screened for in all cases of familial NSSNHL compatible with maternal transmission.