Sex-specific effects of spironolactone on blood pressure in gonadectomized male and female Wistar rats.

A low-salt diet is known to decrease and salt excess to increase blood pressure in humans and rodents. Sex steroids seem to play a role in salt dependent hypertension. However, little is known about sex differences in mineralocorticoid receptor blockade between male and female rats. The objective of the work was at first to investigate the effects of a low-salt vs. a high-salt diet on blood pressure without the influence of gonadal steroids in male and female rats. Second, to determine the sex-specific effects of mineralocorticoid receptor blockade by spironolactone in high-salt and low-salt fed gonadectomized male and female animals. Normotensive male and female Wistar rats were gonadectomized and put on a low (NaCl<0.03%) or high (NaCl=4%) salt diet. On each diet animals received spironolactone or placebo. Blood pressure was measured by tail-cuff-method; 24-h urine samples were collected in metabolic cages and blood was collected for hormonal measurements. High-salt diet significantly increased systolic blood pressure in both sexes. This effect could be blocked effectively by spironolactone only in male rats. Spironolactone treatment significantly increased aldosterone levels in males and females independent of the sodium content of the diet. High sodium diet significantly increased relative kidney weight, which was not altered by spironolactone treatment. Independently of gonadal steroids a high-salt diet increased blood pressure in gonadectomized male and female rats. Spironolactone lowered blood pressure only in male not in female rats on a high-salt diet clearly indicating sex-specific effects of the mineralo-corticoid antagonist spironolactone.

Novel PHEX nonsense mutation in a patient with X-linked hypophosphatemic rickets and review of current therapeutic regimens.

INTRODUCTION: The most common form of familial hypophosphatemic rickets is X-linked. PHEX has been identified as the gene defective in this phosphate wasting disorder leading to decreased renal phosphate reabsorption, hypophosphatemia and inappropriate concentrations of 1,25-dihydroxyvitamin D in regard to hypophosphatemia. Clinical manifestation are skeletal deformities, short stature, osteomalacia, dental abscesses, bone pain, and loss of hearing. SUBJECTS AND METHODS: We report 3 cases of hypophosphatemic rickets with genetic mutational analysis of the PHEX gene. In 1 male patient an unknown nonsense mutation was found in exon 7, codon 245 (c.735T>G, Tyr245Term, Y245X). In both female patients known mutations were found: c.682delTC (exon 6, codon 228) and c.1952G>C (exon 19, codon 651, R651P). Age at diagnosis ranged from early childhood to the age of 35 years. Clinical complications were hip replacement in 1 patient, mild nephrocalcinosis in 2 patients and loss of hearing in 1 patient. All 3 patients have been treated with phosphate supplements and receive 1,25-dihydroxyvitamin D. Under this regimen all patients show stable biochemical markers with slight hyperparathyreoidism. In all patients at least one family member is affected by rickets, as well. CONCLUSIONS: We report a novel nonsense mutation of PHEX that has not been identified so far. The recent discovery of FGF23 and MEPE has changed our understanding of the kidney-bone metabolism, but also raises concerns about the efficacy of current therapeutic regimens that are reviewed in this context.

Management of steroid replacement in adrenal insufficiency.

Adrenal insufficiency is caused by either primary adrenal failure, mostly due to autoimmune adrenalitis, or by hypothalamic-pituitary impairment of the corticotropic axis, predominantly by long-term pharmacodynamic glucocorticoid treatment or by pituitary tumour growth and related treatment. Despite optimized life-saving glucocorticoid and mineralocorticoid replacement therapy, health-related quality of life in adrenal insufficiency is more severely impaired than previously thought and patients with adrenal insufficiency are also threatened by an increased mortality. Optimizing hormone replacement remains one of the most challenging tasks in endocrinology. Monitoring of glucocorticoid replacement quality is hampered by lack of objective assessment tools and therefore largely based on clinical grounds. Thus, long-term management of patients with adrenal insufficiency remains a continuous challenge asking for the experienced specialist. However, diagnosis and management of suspected acute adrenal failure is an important task for all physicians. This review explains the rationale behind the current hormone replacement scheme, points to the deficits and hints at possible future therapies.

Sex-specific regulation of ENaC and androgen receptor in female rat kidney.

With the beginning of puberty blood pressure increases and is persistently higher in men than in premenopausal women. Sex steroids are known to have complex effects on the renal and cardiovascular system and are involved in blood pressure regulation. The epithelial sodium channel (ENaC) modulates sodium reabsorption in the kidney, but little is known about sex-specific regulation of ENaC subunit expression. Regulation of the androgen receptor (AR) is known to be tissue-specific and age-dependent, but not well studied in the kidney. We investigated the effects of sex steroids on ENaC subunits and renal AR expression in an in vivo rat model. Ovariectomized female Wistar rats were treated with placebo, testosterone, 5 alpha-dihydrotestosterone (DHT) or 17 beta-estradiol (E2) for 14 days, and quantitative PCR and Western immunoblots were performed. DHT significantly decreased expression of all ENaC subunits in female rats, whereas testosterone showed only a trend to lower ENaC expression. These results are in contrast to previous studies where stimulating effects of androgens on the alpha-subunit of ENaC were seen. AR mRNA expression showed a trend to lower levels in females after testosterone treatment in this study. However, estrogen treatment significantly downregulated AR mRNA expression. In male control animals we were able to show a significantly increased expression of AR mRNA upon testosterone treatment. Our data demonstrate that AR and ENaC are regulated by sex steroids. That way sex steroids might modulate renal sodium reabsorption and therefore provide a possible explanation for sex differences in blood pressure.

[Onychomycosis: experiences with atraumatic nail avulsion]. / Onychomykose: Erfahrungen mit atraumatischer Nagelentfernung.

Patients with onychomycosis (tinea) of finger- and toenails underwent combined treatment: avulsion of nail plate, local antimycotic and systemic griseofulvin treatment. Avulsion of the involved nails was performed by the patients themselves chemo-mechanically using 50% KI-ointment. 1,500 nails were successfully removed. Out of 250 patients 101 were clinically and mycologically cured after a median delay of 6.5 months. Only 50% of the 101 patients remained cured up to one year after cessation of therapy. Atraumatic nail avulsion in combination with chemotherapy is a reliable, inexpensive, painless, and effective alternative method to surgical excision treating onychomycosis.

High-grade malignant lymphoma arising from Sézary's syndrome. A case report.

Skin infiltrates and tumors characteristic of mycosis fungoides, together with other clinical features typical of Sézary's syndrome (such as erythroderma, itching and Sézary cells in the peripheral blood), were found in a 76-year-old female. Histologically, there was a shift from a well-differentiated to a poorly-differentiated lymphoblastic infiltration indicating the transformation from a low-grade to a high-grade malignant (T-cell) lymphoma.

[Swimming-pool granuloma]. / Schwimmbadgranulom.

The swimming pool granuloma is a chronic granulomatous skin disease, caused by atypical quick growing mycobacteria in areas of minor injuries with high self-healing rate.

[Oral kallikrein-therapy of asthenozoospermia]. / Orale Kallikrein-Therapie der Asthenozoospermie.

Over a period of 7 weeks 51 men with idiopathic asthenozoospermia were treated with Kallikrein (600 Kallikrein units per day). A statistically significant improvement of sperm motility was observed with a maximum 1 month after the therapy. The conception rate was 31%. Stimulation of sperm motility may be caused by a positive effect on spermatogenesis, by an improvement of the nutritional functions of the tubulus apparatus and by an improvement of sperm maturation in the eqididymis.

[Circumscribed skin necroses following intramuscular injections. Review and case reports]. / Umschriebene Hautnekrosen nach intramuskulärer Injektion. Ubersicht und Kasuistik

In rare instances local hemorrhagic necroses may be observed after intramuscular injection. The clinical features of this side reaction - lividoid dermatitis progressing to hemorrhagic necrosis and prolonged wound healing - are presented in the light of four of our own observations. With regard to the etiology, functional vascular spasm, embolism or/and local thromboses are discussed.