Background and ObjectivesAlthough many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem.MethodsTwo sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn2+ ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17β-estradiol in the serum was measured by radioimmunological method.ResultsThe Extent of Biological Availability (EBA), calculated on the base of AUC0−∞, showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted longer.ConclusionPerformed studies indicate that GnRH analogs in the form of suspension have higher bioavailability than their solution counterparts. It influences the effects of their action, especially in relation to LH and FSH.
INTROduCTION Immunosuppression with glucocorticoids is the method of choice in the treatment of active Graves' ophthalmopathy (GO). However, glucocorticoid therapy may have side effects, among others, it affects bone metabolism. ObjECTIvEs The aim of the study was to compare the effect of methylprednisolone pulse therapy (MPPT) with and without alendronate on bone turnover markers in patients with GO with normal and reduced bone mineral density (BMD). PATIENTs ANd mEThOds The study included 53 patients with GO and 20 sex-and age-matched healthy controls. Twenty patients with normal BMD (17 women, 3 men, aged 45 ±1.0 years) received only MPPT (8 g intravenously during 4 weeks). The remaining patients, with reduced BMD, were randomly assigned either to MPPT without alendronate (10 women, 2 men, aged 47 ±1.0 years) or MPPT with alendronate (18 women, 3 men, aged 47 ±1.0 years). BMD of the lumbar spine and femoral neck was assessed using dual energy X-ray absorptiometry (DEXA) before treatment. The markers of bone formation (serum osteocalcin, carboxyterminal propeptide of type I collagen [PICP], alkaline phospatase) and the markers of bone resorption (serum carboxyterminal telopeptide of type I collagen [ICTP], cross-linked C-terminal telopeptide of type I collagen [CTX], serum calcium [Ca] and potassium [P], as well as urinary excretion of deoxypyridinoline, Ca, and P) were determined before and after treatment. REsuLTs MPPT caused a decrease in bone formation markers and an increase in some bone resorption markers. MPPT with alendronate decreased bone formation and bone resorption markers. CONCLusIONs A negative effect of MPPT on bone turnover is observed both in patients with GO with normal and with reduced BMD. Simultaneous use of MPPT and alendronate in patients with GO and reduced BMD suppresses bone resorption caused by methylprednisolone.
Introduction. A precise and early diagnosis of the underlying cause of Cushing's syndrome is necessary for successful treatment. The treatment of choice in ACTH-dependent Cushing's syndrome of pituitary origin is transsphenoidal pituitary adenoma resection. In patients, without visible pituitary adenoma on magnetic resonance imaging (MRI), surgical treatment should only be considered if the results of dynamic tests are unequivocal. Objectives. To assess usefulness of the desmopressin test in comparison with high-dose dexamethasone suppression test and CRH test in establishing the diagnosis of ACTH-dependent Cushing's syndrome of pituitary origin. Patients and methods. 15 patients with ACTH-dependent Cushing's syndrome were studied. Pituitary microadenoma was surgically and histologically confirmed in all patients (only in 10 of them did pituitary MRI show a microadenoma). A control group consisted of 15 subjects, in whom Cushing's syndrome and other endocrine abnormalities were excluded. The following procedures were performed in all studied patients: daily rhythm of cortisol secretion, high-dose dexamethasone suppression test, CRH test and desmopressin test. Results. False negative responses were observed: in 1 patient to dexamethasone, in 1 patient to CRH and in 2 patients to desmopressin. In the other patients results of all 3 tests were positive. In 4 out of 5 patients without microadenoma seen on pituitary MRI, the desmopressin test yielded positive results. In the control group the results of dexamethasone and CRH test were positive in all patients, whereas the desmopressin test gave negative results (neither ACTH nor cortisol secretion increased after desmopressin administration in any patient). Conclusions. 1) The desmopressin test performed together with high-dose dexamethasone suppression test and CRH test may, in some cases, enhance the precision of final diagnosis of ACTH-dependent Cushing's syndrome of pituitary origin. 2) The desmopressin test allows a very precise identification of healthy subjects.
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