Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on the pituitary-thyroid-axis.

The lack of estrogen during menopause is associated with various symptoms including osteoporosis, cardiovascular diseases, and menopausal symptoms. For many years, conventional hormone replacement therapy has been successfully used to treat these conditions. However, in light of recent studies that draw attention to potential hazards of conventional HRT, various attempts were undertaken to search for alternatives of classical HRT. Phytoestrogens are supposed to ameliorate various discomforts associated with menopause. Resveratrol (RES) is present in red wine, grapes and peanuts and has been implicated in cardioprotection and prevention of adverse side effects observed after regular HRT. As the pituitary-thyroid axis is a target of estrogen action, we first assessed the effects of E2 administration on thyroid hormone stimulating hormone releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the TRH-induced TSH secretion. We furthermore designed a long-term study of three months to assess the effects of subcutaneous and oral administration of 17beta-estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in ovariectomized (OVX) female rats. Our results demonstrate that serum levels of 1.0 and 8.1 microM RES lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2 benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all animals, we could not detect changes in thyroid morphology as assessed by hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.     

Incidence of asthma and net change in symptoms in relation to changes in obesity.

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl.

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Rhabdomyolysis: a manifestation of cyclobenzaprine toxicity

A case of cyclobenzaprine (flexeril) overdose and the resultant rhabdomyolysis is presented. A review of the range of clinical toxicity, management of overdose is described. The similarity of cyclobenzaprine to the tricyclic antidepressant class is emphasized; this report attempts to disseminate related information on this commonly prescribed centrally acting muscle relaxant.     

1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck

BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25.     

Rehabilitative Maßnahmen bei Patienten mit Pankreaskarzinom

Rehabilitative and palliative measures in the follow-up care of pancreatic cancer patients will remain the dominant medical focus as long as potentially curative measures (recurrence prophylaxis, early detection and therapy of recurrence) have failed to show a significant survival benefit. Rehabilitative measures are possible for patients undergoing potentially curative as well as palliative treatment. Their aim is to alleviate the negative effects of the cancer and its therapy, not only physically, but also psychologically, socially and vocationally. The spectrum of possible somatic handicaps ranges from metabolic disorders, malnutrition and under-nutrition, as well as gastrointestinal symptoms to pain. Assistance in coping with illness, alleviating fears and depression and strengthening compliance are the main areas which are dealt with in psycho-oncology. Assessment of vocational fitness and the capacity to work depends on tumor location, whether R0 or R1 resection has taken place, the extent of pancreas resection, accompanying illnesses, whether or not adjuvant therapy has been given, and the physical condition of the patient     

Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity

Human Molecular Genetics (2006) 15, 921–931;     

Vaginal stenosis in patients treated with radiotherapy for carcinoma of the cervix

The aim of our study was to determine the incidence, timing, and severity of vaginal stenosis in patients with carcinoma of the cervix who had received pelvic and/or vaginal radiotherapy as part of their treatment. We also sought to determine if there were any predisposing factors for the development of stenosis. A retrospective chart review was undertaken for all the patients diagnosed with carcinoma of the cervix between January 1, 1990, and December 31, 2000 and treated with pelvic and/or vaginal radiation at Westmead Hospital. Since January 1, 1990, data regarding vaginal stenosis has been prospectively recorded on all the patients. Data collected included patient demographics, stage of disease, treatments administered, and incidence, timing, and severity of vaginal stenosis. One hundred and eighty-eight patients were treated. Mean age was 58.6 years. Thirteen percent of patients had stage IB disease, 45% had stage II disease, 39.5% had stage III disease, and 1.5% had stage IV disease. One hundred and seventy-nine patients returned for follow-up, and data regarding vaginal toxicity were available in 98%. Twenty-seven percent had grade 1 toxicity (partial stenosis or shortening but not complete occlusion), and 11% had grade 2 (complete occlusion). Stenosis of any grade was noted at a mean of 9.6 months and median of 7.5 months (range, 26 days-5.6 years) from completion of treatment. The only prognostic factor associated with increased risk of stenosis was age greater than 50 years (odds ratio 2.26). Vaginal stenosis is a common complication of pelvic and vaginal radiotherapy, occurring in 38% of patients. Stenosis occurs most often in the first year after treatment. Patients over the age of 50 are most at risk.