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Biomedical subjects

C Alexandre

Publications and source records attributed to C Alexandre.

At least 91 records · Page 5Linked to original sources
PubMed1987

Inhibition of testosterone metabolism in the brain and cloacal gland of the quail by specific inhibitors and antihormones.

The effects of antioestrogens, antiandrogens and of various inhibitors of testosterone metabolism on testosterone metabolism in the quail hypothalamus and cloacal gland were studied by an in-vitro radioenzymatic assay. It was found that antioestrogens and antiandrogens generally had little or no effect on aromatase and 5 alpha- and 5 beta-reductases of testosterone, except when used at very high doses. The 5 alpha-reductase inhibitor, 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one, inhibited both 5 alpha- and 5 beta-dihydrotestosterone production without markedly affecting aromatase activity. Surprisingly, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, inhibited not only the production of oestradiol but also that of 5 beta-dihydrotestosterone and, to a lesser extent, 5 alpha-dihydrotestosterone. These unexpected properties should be taken into account when interpreting the results of in-vivo experiments using these compounds.

Androgen Antagonists↗
PubMed1987

Skeletal distribution and biochemical parameters of Paget's disease.

Quantitative bone scans were performed with 99mTc-EHDP in 170 untreated pagetic patients (93 men, 77 women; mean age, 65.4 years). The distribution of 863 pagetic skeletal locations was analyzed. Bone scans demonstrated 8.3% more pagetic sites than roentgenograms. The extent of Paget's disease was evaluated in each patient by a scintigraphic skeletal index. This index correlated with serum alkaline phosphatase (SAP) and urinary hydroxyproline (HyPro) levels, and also with hypocalcemic acute response to calcitonin. The correlation of SAP with an index of activity (extent index adjusted by uptake ratios) was better than with the nonadjusted index. Only 30.6% of pagetic sites were responsible for clinical symptoms. No correlation was found between age and skeletal index of the disease.

Adult↗
PubMed1987

[Interaction of androgens and estrogens in the control of reproduction].

Castrated male quail were injected with the synthetic oestrogen, diethylstylbestrol (DES) or the synthetic androgen, methyltrienolone (R 1881) or both compounds simultaneously. Both R 1881 and DES activated male sexual behaviour, inhibited LH and FSH secretion and increased hypothalamic aromatase activity. Additive effects between R 1881 and DES were observed for the induction of brain aromatase and for the inhibition of FSH secretion. As a consequence, mechanisms mediated by androgen and estrogen receptors must be involved in the control of these reproductive characteristics.

Androgens↗
PubMed1987

Effects of a 120 day period of bed-rest on bone mass and bone cell activities in man: attempts at countermeasure.

The effects of immobilization on bone mass and bone remodeling in patients with spinal cord injuries are known to simulate weightlessness-induced bone changes in astronauts. Nevertheless, immobilization has never been investigated using histomorphometric studies in healthy volunteers. Twenty healthy male volunteers participated in a '120 day bed-rest' experiment in the USSR. Bone biopsy cores of iliac crest were taken before and at the end of the period of bed-rest. The subjects were divided into five groups. Five subjects underwent a normal ambulatory life (control subjects); three subjects were placed on continuous bed-rest for 120 days (complete immobilization); four subjects were immobilized and underwent a controlled training program; four subjects were immobilized and received treatment with potassium diphosphonate (ethane-1,hydroxy-1,diphosphonate 900 mg/day, per os); and four subjects were immobilized and received diphosphonate plus physical exercise. Parameters of bone mass and bone cellular activities (osteoblastic formation and osteoclastic resorption) were measured using automatic and semi-automatic image analysis systems. Bone mass remained constant in each group. Cellular activity measurements showed that in completely immobilized men, the mineralization rate was lower than in controls without change in osteoid parameters; in contrast, osteoclastic parameters were increased. In immobilized men given the training program, bone formation was normal and bone resorption was increased. In immobilized men treated with diphosphonate, osteoid parameters and resorption activity were decreased. In immobilized men with diphosphonate plus training, the osteoid parameters and the resorption activity were reduced but to a lesser degree than in immobilized men with diphosphonate alone. Failure of bone loss in normal immobilized subjects differed from results found in paraplegic patients. However, a decrease in mineralization rate and an increase in bone resorption activity were found in both studies. Exercise stimulated bone resorption and diphosphonate inhibited the osteoclastic activity. These data emphasize the difficulties in finding good models to stimulate spaceflight conditions on earth. Comparative studies must be done using bone biopsies to determine more precisely the effects of weightlessness on the human skeleton.

Adult↗
PubMed1987

[Contribution of bone biopsy with histomorphometry in the evaluation of monoclonal gammopathy].

Histomorphometric analysis of bone specimen from the iliac crest was performed to determine total trabecular resorption surface (TTRS) in 46 patients presenting with a monoclonal gammopathy, which was benign in 17 cases and malignant in 29 others. In benign gammopathies, 14 patients had normal TTRS; no adverse progression, representing a malignant B-cell lymphoproliferative disorder occurred after 40 months of follow-up. The three other patients presented increased areas of resorption in contact with lymphoplasmocyte nodules or pure plasmocytes and had an unfavorable course: multiple myeloma, Waldenström's disease, and chronic lymphocytic leukemia. In myeloma, an increase in TTRS was observed when the bone marrow is invaded confirming the dominant local activity of an "osteoclast activating factor". TTRS is all the more extensive according to bone marrow invasion or in IgA or light chain myeloma, all of which are especially destructive of bone. It thus appears that determination of TTRS by bone histomorphometry is of diagnostic importance to recognize the benign or malignant nature of the disorder and has prognostic value in case of multiple myeloma. Bone histomorphometry thus appears as a useful tool in the thorough assessment of monoclonal gammopathies.

Biopsy↗
PubMed1987

[Effects of weightlessness on osseous tissue of the rat after a space flight of 5 days (Cosmos 1514)].

Five pregnant female growing rats have been orbited for five days aboard the Cosmos 1514 soviet biological satellite. They were compared to five female rats kept in vivarium and five female conditioned rats in synchronised way. Histomorphometric studies were performed in order to investigate: 1. The early effects of weightlessness on the bone mass in loading (tibiae and femur) and unloading bones (thoracic and lumbar vertebrae). 2. The changes of osteoblastic and osteoclastic activities. A short exposure does not induce changes in the bone mass and the inner structure of loading and unloading bones. These results fit in well with human data available in the literature: they show that weightlessness doesn't change bone mass in the early phase of a spaceflight. However extrapolation of animal results to men is discussed. In unloading bones (vertebrae) osteoblastic activity was not measurable. Osteoclasts detected by histoenzymologic method don't change as far as their number per mm3 of trabecular bone is concerned. However the number per mm2 of trabecular area increases. It seems likely that an increase of the osteoclastic population occurs in trabecular bone. In loading bones, formation activity (appreciated by the measurement of osteoid seam thickness) and total osteoclastic resorption surfaces were not modified. These results are different from those of longer flights.

Animals↗
PubMed1987

[The bone in non-corticoid-treated sarcoidosis. A histomorphometric study].

The sarcoidosis granuloma secretes 1-25 dihydroxyvitamin D (1-25(OH)2 D) at the origin of the hypercalcemia found in about 20 p. cent of sarcoidoses. Its mechanism was considered exclusively of a digestive nature, but the activity of osteoclastic stimulation of 1-25(OH)2 D must consider an associated bony origin. Nine patients with bouts of non-steroid sarcoidosis were studied by osseous histomorphometric analysis. In a patient with hypercalcemia and radiographic manifestations, a high degree of bone remodelling is demonstrated, with stimulation of osteoclastic and osteoblastic activity. In eight patients with normocalcemia, two subgroups are individualized: two patients present intramedullary sarcoidosis granulomas with increased contact resorption; six patients present a normal marrow: the total areas of resorption remain increased. It is concluded that the activity of osteoclastic resorption is increased in sarcoidosis, which may explain partially the hypercalcemia. The absence of titration of 1-25(OH)2 D in our study does not permit to precise the role of this enzyme in the genesis of hyperosteoclastosis, although this seems quite plausible.

Adult↗
PubMed1987

[Quantitative histological study of the bone mass and cellular activity after 120-days decubitus. Trial of preventive protocols].

Bone biopsies of iliac crests, performed at the beginning and the end of a decubitus period of 120 days, were studied in 20 healthy volunteers men. The purpose of this experiment is to simulate the bony alterations of astronauts. The bony mass of all bed-ridden patients remained constant. In strictly immobilized patients, the rate of bony mineralization is decreased and the osteoclastic resorption activity is stimulated. In bed-ridden patients subjected to preventive physical exercises, the bony formation and resorption are increased. When prevention is administered with the use of a diphosphonate, the osteoid and osteoclastic parameters are decreased. When both types of prevention are administered, the osteoid parameters and the resorption activity are decreased but less markedly than in patients treated with diphosphonate alone.

Adult↗
PubMed1986

[Effects of weightlessness on phosphorus and calcium metabolism and bone remodeling].

Weightlessness results in negative calcium balance which can only reflect a redistribution of calcium in the body: the loss of calcium in the faeces and/or urine is constant, but an increase in urinary hydroxyproline indicating bone collagen destruction is not always detectable; moreover, a slowing down of collagen maturation may be suspected. Bone analysis by histomorphometry in animals and by indirect, non-invasive methods in man shows a decrease in bone mass. However, this bone tissue atrophy might only reflect excessive ageing of the bone during weightlessness, as suggested by slow bone formation and lack of variation in bone resorption. Since the experimental results obtained in men and animals during simulated weightlessness on earth are not strictly identical with those observed in space- flights, their validity may be questioned. Additional studies (notably histomorphometric studies) are therefore required for a better knowledge, as well as prevention, of the problems raised by human life in space.

Animals↗
PubMed1986

Pharmacokinetics and bioavailability of ranitidine in normal subjects and cirrhotic patients.

Pharmacokinetic parameters of ranitidine were determined comparatively in nine cirrhotic patients and eight healthy volunteers after administration of a single oral (150 mg) or intravenous dose (50 mg). Bioavailability was virtually the same in patients and in normal subjects, and there was no significant difference between the two groups for total plasma clearance, intravenous elimination half-life, or volume of distribution. The mean maximum plasma concentration was 43% higher in patients than in volunteers, but the difference was not significant. The values for the kinetic parameters did not significantly differ between patients with and without ascites or with and without hepatocellular insufficiency. These results indicate that ranitidine kinetics are not appreciably altered in cirrhotic patients and that reduction of dosage is not required in such patients unless their renal function is impaired.

Adult↗
PubMed1986

Effects of metabolism inhibitors, antiestrogens and antiandrogens on the androgen and estrogen induced sexual behavior in Japanese quail.

The relative contribution of androgenic and estrogenic metabolites of testosterone to the activation of sexual behavior was studied in Japanese quail by using inhibitors of testosterone metabolism, antiestrogens and antiandrogens. These compounds were tested in castrated birds whose sexual behavior had been activated by silastic implants of testosterone (T) or daily injections of testosterone propionate (TP) or diethylstilboestrol (DES). The aromatase inhibitor ATD only depressed T-induced behavior when injected at high doses and the 5 alpha-reductase inhibitor, 4MA was inactive in this respect. The antiestrogens, tamoxifen (TAM) and nitromifene citrate (CI-628) strongly depressed sexual behavior but they also drastically reduced the crowing behavior which is typically androgen-dependent which throws some doubts on the specificity of their action. The antiandrogens, flutamide and cyproterone acetate (CA), only had limited inhibitory effects on the copulatory behavior but similarly decreased only marginally the crowing. As they strongly depressed the cloacal gland growth, it can be ascertained that they were injected in sufficient amounts and their lack of action on crowing questions the ability of these compounds to inhibit brain processes even when they are androgen-dependent. Taken together with the results of previous experiments which tested the behavioral effects of the testosterone metabolites, the present data confirm the implication of both androgenic and estrogenic metabolites of testosterone in the activation of behavior. Their interaction remains, however, poorly defined and its understanding will probably require the identification of the biochemical processes which in the brain mediate the behavior.

Androgens↗
PubMed1986

Uncalcified cartilage resorption in human fetal cartilage canals.

In the human fetus, epiphyses appear as a solid avascular cartilaginous mass until the eleventh week of development. Around the third fetal month of development, vascular canals coming from the perichondrium are recognized in the mineralized epiphyseal cartilage. Whether cartilage canals develop by passive inclusion or active chondrolysis is still a matter of controversy. We studied the relationships between the intracanalar cells and the surrounding matrix on human fetal epiphyses embedded in glycol methacrylate. At the blind end of canals both stellate fibroblast-like cells and vacuolated macrophages are observed. These cellular foci show all characteristics of active chondrolysis (loss of metachromasia, lacunae containing cells intimately associated with matrix, and presence of granular debris). Similar resorptive foci have been observed in the pannus of rheumatoid joints and in the embryonic chick growth plate composed of uncalcified cartilage. A cellular cooperation (fibroblast/macrophage) is necessary for uncalcified cartilage breakdown. In the human fetus, monocytes/macrophages have been recognized in the peripheral blood as early as the twelfth week of gestation. Our observations support the view that chondrolysis due to both fibroblasts (of mesenchymal origin) and macrophages is the basic mechanism for cartilage canal development.

Abortion, Spontaneous↗
PubMed1986

Importance of quantitative histology of bone changes in monoclonal gammopathy.

Quantitative histology of bone changes, using undecalcified transiliac bone biopsies (UTBB), was performed blindly in 46 individuals with monoclonal gammopathy (MG), including 17 with MG of undetermined significance (MGUS) and 29 with overt multiple myeloma (MM). Three MGUS presented an excess of osteoclastic resorption (OR) in the vicinity of clusters of tumour cells and developed overt B cell malignancies, chronic lymphocytic leukaemia, Waldenström's disease and MM respectively. On the other hand, MGUS with normal OR remained stable (median follow-up = 28 months), with one exception who developed a systemic amyloidosis. In MM, excessive OR was only observed in areas invaded by myeloma cells. OR was frequently normal in active MM lacking myeloma cells in UTBB. Active MM without lesions on radiography had excessive OR. IgA and pure Bence Jones MM appeared more osteoclastic than IgG cases (P less than 0.05). Of major interest was the finding that one third of MM presented histological bone changes similar to osteoporosis, osteosclerosis or osteoblastic metastasis. Two major findings must be emphasized from the current data: UTBB could be of major interest for the early detection of a B cell malignancy; heterogeneity of myeloma bone condition is unexpected. If some changes appear directly related to the tumour (i.e. excessive OR or osteoblastic dysfunction), some others are probably accidentally associated with it (i.e. osteoporosis), both needing treatment other than chemotherapy.

Aged↗
PubMed1986

Permanent preservation of whole alizarin red S skeletons by clearing and embedding in polyester resins.

A one-step clearing and embedding procedure for alizarin red S stained skeletons is described. Embryos are fixed in formalin, skinned and eviscerated. After staining in a 10 mg/liter solution of alizarin red S in 5% aqueous KOH, specimens are dehydrated in a graded series of acetone-polyester monomer solutions. Finally, the specimens are embedded at room temperature in the polyester resin. A special reusable metallic mold is described for embedment of large fetuses. Specimens previously cleared in glycerol can be processed with this method.

Anthraquinones↗