Recommendations for the registration of agents to be used in the prevention and treatment of glucocorticoid-induced osteoporosis: updated recommendations from the Group for the Respect of Ethics and Excellence in Science.

Objectives: The Group for the Respect and Excellence in Science (GREES) has reviewed and updated their recommendations for clinical trials to evaluate the efficacy and safety of new chemical entities to be used in the treatment and prevention of glucocorticoid-induced osteoporosis (GIOP).

Methods: Consensus discussion of the committee.

Results: With the exception of steroid use posttransplantation, there is no need to differentiate between underlying diseases.

Total joint replacement of hip or knee as an outcome measure for structure modifying trials in osteoarthritis.

Objective: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working group to assess the value of time to joint surgery as a potential therapeutic failure outcome criterion for osteoarthritis (OA) of the hip or knee in the assessment of potential structure modifying agents.

Methods: PubMed was searched for manuscripts from 1976 to 2004. Relevant studies were discussed at a 1-day meeting.

Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis.

Background: Recent innovations in the pharmaceutical drug discovery environment have generated new chemical entities with the potential to become disease modifying drugs for osteoarthritis (DMOAD's). Regulatory agencies acknowledge that such compounds may be granted a DMOAD indication, providing they demonstrate that they can slow down disease progression; progression would be calibrated by a surrogate for structural change, by measuring joint space narrowing (JSN) on plain X-rays with the caveat that this delayed JSN translate into a clinical benefit for the patient. Recently, new technology has been developed to detect a structural change of the OA joint earlier than conventional X-rays.

Comparison of micronized fenofibrate and pravastatin in patients with primary hyperlipidemia.

Micronized fenofibrate lowers total cholesterol and low-density lipoprotein cholesterol to a similar extent as statins but raises high-density lipoprotein cholesterol and lowers triglycerides to a greater extent. The comparative lipid-modifying efficacy of micronized fenofibrate and pravastatin has not been evaluated in dyslipidemic patients. This prospective, multicenter, randomized trial compared the efficacy of 3 months' treatment with micronized fenofibrate (200 mg once daily) or pravastatin (20 mg once daily) in hypercholesterolemic type IIa and mixed dyslipidemic type IIb patients.

Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the calcium-sensing receptor gene.

The calcium-sensing receptor (Ca-R) is a G-protein-coupled surface receptor that plays a crucial role in calcium homeostasis via parathyroid hormone secretion. Mutations of this receptor can cause a gain in, or loss of, function, leading to hypo- or hypercalcemia, respectively. We report here a family with hypocalcemia in whom a heterozygous missense mutation in exon 4 was demonstrated, predicting a proline to leucine substitution (P221L) in the extracellular part of the Ca-R.

Glycosylated rat prolactin: isolation and structural characterization.

Isolation of glycosylated 26 kDa rat prolactin and subsequent proper carbohydrate characterization has so far not been reported. In the present work the hormone isoform was isolated to 95% homogeneity by preparative electrophoretic separation on Mini Prep Cell of rat pituitary homogenate. The isoform was then investigated by 2-mercaptoethanol gradient electrophoresis, Cleveland's sequential SDS-PAGE, digestion with endoproteinase Asp-N and N-glycanase.

Non-secreting atypical parathyroid adenoma.

Parathyroid tumors can be divided in adenomas and carcinomas, usually detected by hypercalcemia. We report a case of parathyroid adenoma in a young man, who complained of a pressure in the left neck region. Physical examination revealed a firm mass in the neck, without lymphnodes.

Cafeteria diet-induced obesity is associated with a low spontaneous growth hormone secretion and normal plasma insulin-like growth factor-I concentrations.

Pituitary growth hormone (GH) secretion has been shown to be blunted in human and animal obesity. With respect to human obesity, cafeteria diet-induced obesity might be an appropriate model to study spontaneous GH secretion. In 6 cafeteria diet-overfed obese male Wistar rats and 6 control rats with chronically implanted catheters, GH levels were measured every 15 min over 6 h by standard RIA.

Routing, processing and export of rat pituitary prolactin: identification of a 36 kDa disulphide-bridged oligomeric preprolactin.

To gain an insight in the routing, processing and export of rat prolactin, rat pituitary cells were cultured in serum-free medium in the presence of cycloheximide, carbonyl cyanide m-chlorophenylhydrazone, Brefeldin A and monensin. The potential influence of these perturbants, whose well documented effects are the altering of protein synthesis and transport, was studied on rat prolactin molecular size isoforms appearing in cellular extracts and in culture medium. The outcome of the culture experiments as recorded in vertical SDS-PAGE, thiol gradient electrophoresis and sequential SDS-PAGE followed by prolactin specific immunoblotting and densitometry, was as follows: (1) at the cellular level we were able to characterize a novel 36 kDa protein as a disulphide-bridged oligomeric precursor prolactin, which is presumably rapidly transformed in the cis/medial Golgi; to designate monomeric rat prolactin as an early Golgi protein and t o advance evidence that the main processing of the glycosylated rat prolactin is a cis/medial Golgi event; (2) in release none of the perturbants disturbed the relative distribution of monomeric and glycosylated rat prolactin, the main molecular size isoforms currently secreted by untreated pituitary cells, or induced the appearance of transformed molecular size isoforms; (3) the secretion mode indicates that rat prolactin is released via the regulated pathway in the presence of the perturbants used.

Calcitonin reserve in different stages of atrophic autoimmune thyroiditis.

The objective of this study was to determine the calcitonin (CT) hormone reserve in different severity of atrophic autoimmune thyroiditis (AAT). Forty-eight female patients with AAT were divided into four groups based on basal and peak thyrotropin (TSH) values (after oral thyrotropin-releasing hormone [TRH], free triiodothyronine (FT3) and free thyroxine (FT4) ranging from normal in group 1 to overt hypothyroidism in group 4. All had thyroid antibodies.

[Postmenopausal osteoporosis in women].

Postmenopausal osteoporosis is now considered a major public health problem in aging women, due to the burden related to the consequent fractures. Over recent years, several pharmacological approaches were developed for the prevention and treatment of osteoporosis. Besides regular physical exercise and calcium rich diet, calcium supplementation can be suggested to both genders, after seventy years as well as systematic vitamin D supplementation in order to cope with the frequent lack observed in our country.

[How to evaluate osteoporosis: bone densitometry and biochemical tests].

The use of bone densitometry, by dual energy x-ray absorptiometry, allows the identification, at an early stage, of subjects who will, 15-20 years later, present a fracture event. Furthermore, this technique is the most appropriate to confirm the efficacy of preventive or curative therapeutic approaches of osteoporosis. A balanced utilisation of biochemical tests is mandatory to exclude a secondary cause of osteoporosis, to help in the choice of the most appropriate therapeutic strategy and to evaluate the early response of patients to the administered drugs.

Two years of replacement therapy in adults with growth hormone deficiency.

Objectives: Although several studies have shown beneficial short-term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated.

Design: 148 adult GHD patients were enrolled in a multicentre 2-year rhGH replacement study which was placebo controlled for the first six months.

The weight gain and ultimate adiposity in cafeteria diet-induced obesity is unrelated to the central serotoninergic tonus.

Early detection of subjects with a propensity to obesity might be of great help for setting up preventive intervention studies. In this study we tested whether the development of obesity in Wistar rats, given ad libitum cafeteria foods, could be predicted by a low prolactin (PRL) response to 5-hydroxytryptophan (5HTP), as an index of low hypothalamic serotoninergic tonus. Basal and 5HTP-stimulated (50 mg/kg body weight i.

Effect of N omega-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, on stress- and morphine-induced prolactin release in male rats.

1. The effect of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was investigated on stress- and morphine-induced prolactin (PRL) secretion in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2.

Molecular heterogeneity and glycosylation modulation of rat pituitary prolactin isoforms synthesized and secreted in vitro in postnatal ontogeny, gestation, lactation and weaning.

The modulation of both the molecular size heterogeneity and the relative distribution of rat prolactin variants, synthesized and secreted in vitro by rat pituitary cells in the course of postnatal ontogeny and in gestation, lactation and weaning was investigated by SDS-PAGE, immunoblotting, radioimmunological techniques and O-sialoendopeptidase digestion. The outcome of the experiments is as follows: 1) from day 1 of postnatal life 20-, 23-, 26-, 40-44 kDa and oligomeric rat prolactin isoforms were stored and secreted; 2) perinatal life is characterized by a high degree of variability of prolactin size isoforms and their respective repartition in storage and release; in addition to the major variants, transient ones of M, 25-, 28-, 33- and 36 kDa were secreted and/or stored; 3) O-sialoglycoprotease digestion of pituitary cell lysate gave good evidence for 25 kDa prolactin being a glycoform; 4) at 1 month of age 16 kDa rat prolactin appeared and persisted over the whole postnatal span (1 day-->1 year) but only in stored form; 5) the physiology of gestation was essentially characterized by the M(r)-modulation of the glycoform (26 kDa-->26.3 kDa) and the virtual absence of stored 26 kDa rat prolactin at week 1 of pregnancy; 6) in lactation and weaning uncommon multiple banding was observed in secreted oligomeric prolactin; 7) in pregnancy, lactation and weaning the differential distribution of released and stored prolactin isoforms displayed a considerable intra- and intervariability; 8) in the vast array of size isoforms observed in all our experiments monomeric 23 kDa prolactin was always the dominating variant.

The weight gain and ultimate adiposity in cafeteria diet - induced obesity is unrelated to the central serotoninergic tonus.

Early detection of subjects with a propensity to obesity might be of great help for setting up preventive intervention studies. In this study we tested whether the development of obesity in Wistar rats, given ad libitum cafeteria foods, could be predicted by a low prolactin (PRL) response to 5-hydroxytryptophan (5HTP), as an index of low hypothalamic serotoninergic tonus. Basal and 5HTP-stimulated (50 mg/kg body weight i.

Secretion of 23 kDa and glycosylated prolactin by rat pituitary cell culture in serum-free media: a comparative morphological, cyto- and immunochemical study.

The secretion of 23 kDa prolactin by rat pituitary cells has been thoroughly investigated, but secretion of glycosylated rat prolactin is not currently known. This is mainly due to the lack of an antiserum which is solely specific for glycosylated rat prolactin and therefore we studied the basal secretion of this variant by an indirect method. Rat pituitary cells were cultured in total culture medium and three different serum-free media (DMEM, keratinocyte-serum-free medium, protein-free hybridoma medium) and secretion of 23 kDa and glycosylated rat prolactin was recorded by radioactive techniques and immunoblotting.

5-Hydroxytryptophan-stimulated prolactin levels in cafeteria diet fed rats: an in vivo evaluation of the central serotonergic tonus.

Hyperphagia in rats fed a cafeteria diet might be related to the palatability of the diet or to diet-induced changes in central neurotransmitters regulating the feeding behavior. In this study the central serotonergic tonus in adult male Wistar rats was evaluated in vivo after 6 weeks of feeding a cafeteria diet by the prolactin response to the administration of 5-hydroxytryptophan (5HTP), the immediate serotonin precursor. Blood was taken just before, 30, 60 and 90 min after the ip injection of 50 mg/kg 5HTP for the determination of prolactin concentrations were comparable between cafeteria fed rats and control rats, fed normal laboratory chow (12.

Upper airway obstruction due to inoperable intrathoracic goitre treated by tracheal endoprosthesis.

Thyroidectomy is the treatment of choice in patients with thyroid enlargement complicated by compression or displacement of the trachea because of the risk of complete airway obstruction due to sudden enlargement of the goitre by, for example, haemorrhage. In patients who are medically inoperable an endoscopically inserted tracheal endoprosthesis may provide longstanding airway patency, as reported here.

Effect of pituitary adenylate cyclase-activating polypeptide 38 on growth hormone and prolactin expression.

Time- and dose-dependent effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on prolactin (PRL) and growth hormone (GH) release were examined in static and dynamic rat pituitary cell incubations and on different pituitary cell (sub)populations separated according to their density on a discontinuous Percoll gradient. Quantitative in situ hybridization histochemistry allowed us to examine in parallel the effects of PACAP on PRL and GH gene expression. PACAP did not alter GH or PRL secretion in a dynamic superfusion system, in any cell population tested.