S12911-2 reduces bone loss induced by short-term immobilization in rats.

Skeletal immobilization induces trabecular bone loss resulting from increased bone resorption and decreased formation. In this study we determined the effect of S12911-2, a compound containing two atoms of stable strontium, on trabecular bone loss induced by short-term immobilization of hind limbs in rats. Male Sprague-Dawley rats were randomly allocated to six groups (n = 25 per group).

Pulsed estrogen therapy: pharmacokinetics of intranasal 17-beta-estradiol (S21400) in postmenopausal women and comparison with oral and transdermal formulations.

Pharmacokinetics of estradiol and estrone were assessed in postmenopausal women receiving S21400, a novel 17beta-estradiol formulation administered by nasal route; the results were compared with those obtained with oral and transdermal routes. Thirty six women received three treatments: a specified dose of 17beta-estradiol (100, 300 or 450 microg) given once and as 2 doses, 12 h apart, using three parallel dose groups in a randomised, crossover study. Thereafter, a reservoir patch (50 microg/day of 17beta-estradiol) or a tablet of 2 mg micronised 17beta-estradiol were randomly administered.

Influence of alveolar ventilation changes on calculated gastric intramucosal pH and gastric-arterial PCO2 difference.

Objective: To evaluate the influence of changes in alveolar ventilation on the following tonometry-derived variables: gastric intramucosal CO2 tension (PtCO2), gastric arterial CO2 tension difference (PgapCO2), gastric intramucosal pH (pHi) and arterial pH-pHi difference (pHgap).

Design: Clinical prospective study.

Setting: A medical intensive care unit in a university hospital.

Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration.

The analysis of the interaction of strontium (Sr) with bone mineral is of interest because a new agent containing Sr (S 12911) has shown positive effects on bone mass in various animal models of osteoporosis and is currently being developed for preventive and curative treatment of postmenopausal osteoporosis. Iliac bone samples were obtained from 20 male monkeys: 4 untreated control animals, 12 animals sacrificed at the end of a 13-week treatment with high dose levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6 weeks after the end of a 13-week treatment with S 12911 (750 or 100 mg/kg/day orally). The distribution of Sr was determined and quantified by X-ray microanalysis.

The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro.

In this study, we have determined the effect of the divalent strontium salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3H-thymidine for the last 6 h of culture or treated with S12911 for 24 h and labeled for 24 h with 3H-proline 24-48 h after the removal of the agent. Calvariae were then processed for histomorphometry.

Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect.

Low doses of strontium and fluoride were shown to increase bone formation and trabecular bone density in rodents. To assess whether strontium or fluoride affect the quality of the mineral at doses known to increase bone density, we have determined the effects of low doses of strontium and fluoride on bone formation and bone mineral characteristics in rats. Adult rats were given strontium alone (0.

Blood pressure and arterial lactate level are early indicators of short-term survival in human septic shock.

Objective: To identify early prognostic markers of septic shock among catheterization-derived hemodynamic and metabolic data.

Design: Prospective cohort study.

Setting: A medical intensive care unit in a university hospital.

Comparison between bone density and bone strength in glucocorticoid-treated aged ewes.

In order to assess if bone densitometry could be used as an indicator to evaluate bone fragility in short term studies performed on glucocorticoid-treated ewes, correlations between DXA measurements and biomechanical parameters obtained on the same bones were established in 27 aged ewes including sixteen animals treated with methylprednisolone 15 mg/day for 4 months and eleven untreated animals. DXA measurements were performed ex-vivo on HOLOGIC QDR-1000+ device. Biomechanical testings included a three-point bending test on the femur and a compression test on cylinders of cancellous bone excised from two lumbar vertebrae selected between L6 and L4.

[Prognosis of acute tuberculous respiratory distress syndrome. 4 cases].

Objectives: We examined the characteristics of 4 cases of adult respiratory distress syndrome in patients with tuberculosis in an attempt to improve prognosis.

Methods: Four new cases of adult respiratory distress syndrome were described together with a review of the cases reported in the literature. Inclusion criteria were the presence of the syndrome as defined according to the American-European consensus conference and the criteria described by Murray et al.

An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats.

Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency.

Pharmacokinetic profile of fotemustine in rat plasma by electrochemical detection.

1. A differential pulse polarographic (DDP) assay of diethyl-1-[3-(2-chloroethyl)-3-nitrosoureido] ethylphosphonate (fotemustine) was developed to determine the kinetics of this nitrosourea in plasma, brain, liver, lung and kidney. The optimized polarographic determination, previously applied to BCNU and CCNU, attained a limit of detection of 0.

In vitro chemosensitivity testing of Fotemustine (S 10036), a new antitumor nitrosourea.

Fotemustine (S 10036) is a new anti-tumor nitrosourea characterized by a phosphonoalanine carrier group coupled to the nitrosourea moiety, which potentially increases the cellular penetration of the drug. Using human tumor cell lines, the activity of S 10036 was compared with that of the more established nitrosoureas BCNU and CCNU. Growth-inhibiting effects were evaluated by the [3H]-thymidine incorporation test.

Cytotoxicity and DNA damaging effects of a new nitrosourea, fotemustine, diethyl- 1-(3-(2-chloroethyl)-3-nitrosoureido) ethylphosphonate-S10036.

Fotemustine is a new chloroethylnitrosourea which has recently entered a Phase II clinical trial. Using standard cytotoxicity analyses, Fotemustine was shown to be preferentially active in two Mer- cell lines, human colon BE and human lung A427. Comparative cell kill in the Mer+ counterparts HT29 and A549 (respectively) was significantly lower.

[Study of the clinical pharmacokinetics of fotemustine in various tumor indications].

Fotemustine (S 10036) is a new nitrosourea compound whose antitumoral activity has been demonstrated, particularly in disseminated malignant melanoma. Pharmacokinetic parameters of this drug were investigated during phase II clinical trials and compared according to tumor type. Twenty-six patients entered the study and received an induction treatment (weekly 100 mg/sq.

[Clinical pharmacokinetics of nitrosoureas].

The pharmacokinetic characteristics of chloroethylnitrosourea anti-cancer agents are based on their high chemical reactivity and subsequent rapid breakdown in the plasma; and on a widespread tissue distribution due to the molecules' lipophilic properties. These physico-chemical properties explain the main problems that one may face during pharmacokinetic studies (assay method, isolation of high reactive intermediates) and that are related to the typical pharmacokinetic profile of these agents: rapid gastro-intestinal absorption, short half-life, widespread pulmonary and renal distribution, passage through the blood-brain barrier with levels within a therapeutic range, lipoprotein fixation, mainly hepatic and pulmonary metabolism, renal excretion. A drug interaction with phenobarbital has been described in the rat.