[Clinical trials: placebo in the treatment of osteoporosis and in the prevention of vertebral fractures].
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Clinical Trials as Topic↗
Biomedical subjects
M Sosa
Publications and source records attributed to M Sosa.
Lambda(0) polarization in 800-GeV/cpp --> p(f)(Lambda0K+).
We report results from a study of Lambda(0) polarization in the exclusive reaction pp --> p(f)(Lambda0K+) at 800-GeV/c. We observe a dependence of the polarization on the Lambda0K+ invariant mass with large (+71%) positive polarization at small mass (1.63-GeV/c(2)) and large (-43%) negative polarization at large mass (2.75-GeV/c(2)). This observation confirms the result of the CERN ISR R608 experiment and extends the range over which the effect is observed. The strong dependence of the polarization on the Lambda0K+ invariant mass suggests that the origin of the polarization is closely related to the production dynamics of the diffractively produced Lambda0K+ system.
Journal Article↗
Quantitative ultrasound calcaneus measurements: normative data and precision in the spanish population.
Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain.
Adolescent↗
Hyaluronidase inhibitory activity from the polyphenols in the fruit of blackberry (Rubus fruticosus B.).
The hyaluronidase inhibitory activity of different fractions obtained from aqueous extract of blackberry fruits was evaluated. We found that only fractions F3 and F7 inhibit the tested enzyme.
Enzyme Inhibitors↗
In vivo measurement of human skin absorption of topically applied substances by a photoacoustic technique.
A photoacoustic technique is used for studying topically applied substance absorption in human skin. The proposed method utilizes a double-chamber PA cell. The absorption determination was obtained through the measurement of the thermal effusivity of the binary system substance-skin. The theoretical model assumes that the effective thermal effusivity of the binary system corresponds to that of a two-phase system. Experimental applications of the method employed different substances of topical application in different parts of the body of a volunteer. The method is demonstrated to be an easily used non-invasive technique for dermatology research. The relative concentrations as a function of time of substances such as ketoconazol and sunscreen were determined by fitting a sigmoidal function to the data, while an exponential function corresponds to the best fit for the set of data for nitrofurazona, vaseline and vaporub. The time constants associated with the rates of absorption, were found to vary in the range between 10 and 58 min, depending on the substance and the part of the body.
Acoustics↗
Effect of two forms of alendronate administration upon bone mass after two years of treatment.
The efficacy of alendronate in slowing the loss of bone mass, or even in increasing it, in osteoporotic patients and thus reducing the risk of new fractures has been described. Nevertheless, the way of taking this drug, together with its side effects, sometimes produces withdrawals. In this study, we analyzed if an alternative way of taking the alendronate improves the follow-up of the treatment and if it had the same effect on bone mineral metabolism than the traditional way of prescription. An open, intention-to-treat study, with follow-up of 2 yr was conducted. Eighty women suffering from postmenopausal osteoporosis were included in the study. They were classified in a random manner into two groups, each one of them received 10 mg/d alendronate, together with 1.2 g of calcium and 800 IU of Vitamin D3. Group I received the drug fasting, before breakfast, as usually prescribed and group II received the alendronate fasting, at noon, before lunch. Biochemical markers of bone remodeling were determined. Total alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine calcium/creatinine ratio, crosslinked N-telopeptides of type I collagen/creatinine ratio, serum calcium, and parathyroid hormone were also determined, and a lateral dorsolumbar radiography of the spine was performed. Bone mineral density was determined in the lumbar spine by dual-energy X-ray absorptiometry and quantitative computed tomography and by dual-energy X-ray absorptiometry in the proximal femur. Both groups showed an increase in bone mineral density in the lumbar spine and in the proximal femur, which was statistically significant after 1 yr of treatment in the range between 1.5% and 4.3%, depending on the anatomical localization where bone mineral density was measured. There was also an important decrease in the biochemical markers of bone remodeling, between 5.6% and 42.5%, depending on the biochemical marker; the decrease of amino-terminal telopetide during the first year was more important. The group that received alendronate in the morning reported a significantly higher number of withdrawals than the group that received the drug at noon. The alternative administration of 10 mg alendronate at noon had the same effect on bone mineral metabolism than its traditional administration in the morning, but the rate of withdrawals was significantly lower.
Absorptiometry, Photon↗
Diffractively produced charm final states in 800-GeV/c pp collisions.
We report the first observation of diffractively produced open charm in 800-GeV/c pp collisions of the type pp-->pD*X. We measure cross sections of sigma(diff)(D*+) = (0.185+/-0.044+/-0.054) (mu)b and sigma(diff)(D(*-)) = (0.174+/-0.034+/-0.029) (mu)b. Our measurements are based on 4.3x10(9) events recorded by FNAL E690 in the fixed-target run of 1991. We compare our results with previous fixed-target charm experiments.
Journal Article↗
Transient increase in rab 3A and synaptobrevin immunoreactivity after mild hypoxia in neonatal rats.
1. In the present work we describe the short term effects of mild neonatal hypoxia on the synapse as assessed by the immunoreactivity (IR) of two synaptic proteins: rab 3A and synaptobrevin (VAMP). 2. Using the sensitive methodology of immunoblotting, we measured rab 3A and VAMP-IR in homogenates from the cerebral cortex, hippocampus, and corpus striatum of control (breathing room air) and hypoxiated (breathing 95.5% N2-6.5% O2 for 70 min) 4-day-old rats at 1, 2, and 6 h after the end of the hypoxia. Immunostaining with examination by light microscopy was performed using the synaptic protein-specific antibodies on fixed brain sections from animals belonging to the same litter and submitted to hypoxia. 3. A transient increase of VAMP-IR was observed in the hippocampus and corpus striatum, and for rab 3A in the striatum, 1 h after initiating reoxygenation. At the following time points the values returned to control levels. This effect was less clearly observed in the immunostained sections. 4. Mild hypoxia has an effect on sensitive brain regions, eliciting an increase in the IR of at least two proteins involved in the synaptic vesicle cycle. The transient nature of this effect possibly indicates the activation of endogenous neuroprotective mechanisms.
Animals↗
The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism.
INTRODUCTION: The bb genotype of the BsmI polymorphism of the vitamin D receptor (VDR) is more common in primary hyperparathyroidism (HPT) than in the general population in Swedish and German women. However, little is known about the association of HPT with the start codon polymorphism of the VDR (defined by FokI). OBJECTIVE: To study the distribution of the VDR genotypes in a group of women with HPT compared with a control group. The bone mineral density (BMD) of different genotypes was also investigated. METHODS: VDR alleles were typed by polymerase chain reaction (PCR) assay around the polymorphic BsmI or FokI restriction sites in 67 control women (48.5 +/- 10 years) and 53 women with HPT (61.4 +/- 11 years). They were all Caucasian and born in the Canary Islands. Lumbar and proximal femur BMDs were measured by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). RESULTS: The 'bb' genotype was equally frequent in controls and HPT subjects (46.3 and 45.3%, respectively). There was a trend towards a lower prevalence of the FF genotype amongst women with HPT as compared with controls (41.5 vs. 57.1%; P = 0.09). BMD was lower in patients with HPT compared with controls in the lumbar spine and the proximal femur. CONCLUSIONS: The association of the BsmI polymorphism of the VDR gene with HPT is not applicable to all geographical areas. In Canarian postmenopausal women suffering from HPT, VDR genotype distribution is similar to that found in controls. A possible association of HPT with the FokI polymorphism deserves further investigation.
Aged↗
The effect of 25-dihydroxyvitamin D on the bone mineral metabolism of elderly women with hip fracture.
As there is little evidence of the efficacy of 25-hydroxyvitamin D3 (25-HCC) in reducing the risk of new fractures in osteoporotic women, we performed an open, prospective study with a follow-up of 1 yr in 58 females over 65 yr of age with osteoporosis and proximal femoral fractures. The patient group received 1 g calcium per day and 10 640 IU 25-HCC per week, while the control group received 1 g calcium daily. Biochemical markers of bone remodelling, serum calcium and parathyroid hormone were determined. Bone mineral density was assessed in the lumbar spine and in the proximal femur by two methods. After 1 yr of treatment, 25-HCC corrected secondary hyperparathyroidism, increased urine calcium excretion, and increased bone mass in the femoral neck, but had no effect upon the appearance of new fractures.
Absorptiometry, Photon↗
The 46-kDa mannose 6-phosphate receptor contains multiple binding sites for clathrin adaptors.
The two known mannose 6-phosphate receptors (MPR46 and MPR300) both mediate the transport of Man-6-P-containing lysosomal proteins to lysosomes. However, the MPRs cannot be detected in lysosomes, instead they recycle between the plasma membrane and endosomes and between endosomes and the trans-Golgi network. Both, endocytosis from the plasma membrane and budding of transport vesicles from the trans-Golgi network involves the interaction of the receptor with the clathrin-coated vesicles-associated protein complexes AP1 and AP2. We have analyzed this interaction between the Golgi-restricted AP1 complex and the plasma membrane-restricted AP2 complex with the MPR46 tail in vitro by using a biosensor. AP1 and AP2 both bind to and dissociate from the MPR46 tail with similar kinetics. Using synthetic peptides corresponding to different MPR receptor tail regions in inhibition and binding studies, a common high affinity binding site for AP1 and AP2 and two separate high affinity binding sites for AP1 and AP2, respectively, were identified.
Adaptor Protein Complex 1↗
Methyl inosine monophosphate (MIMP) augments T-lymphocyte mitogen responses and reverses various immunosuppressants.
Methyl inosine monophosphate (MIMP) augments preferentially the in vitro responses of human and murine lymphocytes to a T-cell mitogen such as phytohemagglutinin (PHA) and inconsistently to a B-cell mitogen such as pokeweed or lipopolysaccharide (LPS). In a normal interleukin-2-dependent cell line (CTLL), MIMP showed little or no effect on IL-2 action; however, in a murine CTLL line exhibiting impaired responses to IL-2, MIMP stimulated thymidine incorporation and restored the response to IL-2. MIMP augments the PHA responses of both CD4+ and CD8+ human peripheral blood T-cells. The effect of MIMP to augment the PHA response of human lymphocytes is paralleled by the parent molecule, IMP. MIMP, but not IMP, is resistant to hydrolysis by 5'nucleotidase; thus, MIMP appears to be a protected analogue of IMP which is capable of in vivo action. MIMP (100 micrograms/ml) augments the PHA responses of 15 to 24 elderly humans. MIMP also augments the PHA responses of eight HIV-infected pre-AIDS patients but not of eight AIDS patients. When PHA responses of human lymphocytes are suppressed in vitro by an HIV-derived immunosuppressive peptide, interferon alpha, or prostaglandin PGE2, MIMP (0.1-100 micrograms/ml) progressively restores the depressed response; however, when the suppression is severe (greater than 50%), MIMP cannot restore the response. These data indicate that MIMP potentiates normal T-lymphocyte mitogen responses and restores those impaired by a variety of inflammatory and immunosuppressive influences.
Animals↗
Immunotherapy with natural interleukins and/or thymosin alpha 1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice.
Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha 1 or fraction 5 (T alpha 1, TF5), or the combinations of NCM plus T alpha 1 and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha 1 in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha 1 augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha 1 increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha 1 alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.
Age Factors↗
Heterologous transformation of Zalerion arboricola.
A heterologous DNA-mediated transformation system was developed for the pneumocandin-producing fungus Z. arboricola that was based on either conferral of hygromycin B resistance or complementation of a nitrate reductase mutant. Hygromycin-resistant transformants were selected with plasmid pCSN43 which contains the E. coli hygromycin B phosphotransferase gene under the control of Aspergillus nidulans trpC transcription signals. Transformation frequencies were about four transformants per microgram of circular DNA and could be improved four- to six-fold by linearizing the transforming DNA. The transformants differed from one another with respect to the copy number of the integrated plasmid and the site of integration. Adding an autonomously-replicating sequence (AMA1) from A. nidulans to pCSN43 enhanced transformation three-fold and produced, in addition, numerous abortive transformants. However, it is unlikely that the AMA1 sequence promoted plasmid replication in Z. arboricola. Nitrate reductase mutants of Z. arboricola were isolated by positive selection on chlorate-containing medium, and one mutant was subsequently transformed with pSTA700 which contains the nitrate reductase gene (niaD) from Cephalosporium acremonium. Introduction of the niaD gene restored sensitivity to chlorate in the mutant; therefore, using the niaD gene as a selectable marker provides a system for both positive and negative selection. To our knowledge, this is the first report describing transformation of a member of the genus Zalerion.
Acremonium↗
Immunopharmacologic properties of inosine 5'-methyl monophosphate (MIMP).
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Animals↗
Epidemiology of proximal femoral fracture in Gran Canaria (Canary Islands).
An epidemiological survey of proximal femoral fracture (PFF) was carried out in Gran Canaria (Canary Islands) in 1990. We identified 211 cases of PFF affecting residents, which gave an incidence of 161 per 100,000 per year (92 per 100,000 per year for men and 176 for women). Three quarters of all fractures occurred to residents of urban areas and nearly all fractures were caused by falls indoors. There was a higher incidence in winter than in summer months.
Africa, Western↗
Mixed interleukins and thymosin fraction V synergistically induce T lymphocyte development in hydrocortisone-treated aged mice.
Analysis of the role of interleukins in T cell ontogeny in vitro indicates that the regulation of T cell development involves interleukins (ILs) as well as thymic hormones (THs). In order to assess their respective roles in T lymphocyte development in vivo, chemically thymectomized mice were treated with ILs and THs. After 2 days of hydrocortisone treatment, aged mice showed acute thymic involution (weight was less than 30% of control) and reduced spleen size (less than 80% of control) with progressive recovery to 8 days. After 2 days of hydrocortisone treatment, adult mice were injected for 5 days with mixed buffy coat interleukins (BC-IL; 50 units IL2 equivalence), purified IL2 (50 units), rIL1 beta (4 ng), and thymosin fraction V (TF5; 100 micrograms). The animals were sacrificed and spleens and thymuses were analyzed for weight, cellularity, T cell number, subsets, and function as determined by proliferative responses to concanavalin A and ILs. BC-IL treatment increased the recovery of spleen and thymus weights and cellularity with corresponding augmentation of number and function of T lymphocytes; neither IL1 or IL2 or their combination had this effect. TF5 had no effect alone but strongly potentiated the effect of BC-IL on T lymphocyte function. These data indicate that BC-IL in combination with thymic peptides potently promotes T lymphocyte development. The combination may be therapeutically relevant for immunorestoration.
Aging↗