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Biomedical subjects

S Vega

Publications and source records attributed to S Vega.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stimulation of the myelin basic protein gene expression by 9-cis-retinoic acid and thyroid hormone: activation in the context of its native promoter.

Thyroid hormone plays an important role in brain development, in part by regulating myelination. Previous studies have shown that the myelin basic protein (MBP) promoter is activated by thyroid hormone (T3) via a T3-response element (T3RE) at position -186. Surprisingly, although MBP levels are initially decreased in hypothyroid neonates, they approach later control levels, in most brain regions, despite persistent hypothyroidism. We have studied the T3-independent transcriptional regulation of this gene, using transient transfection assays. We found that, in the absence of T3, the RXR ligand, 9-cis-retinoic acid (9cRA) was able to stimulate transcription of the MBP promoter in a dose-dependent manner. This activation was unaffected by the mutation or deletion of the T3RE and required DNA sequences located between positions -162/+60. Accordingly, this MBP promoter fragment bound RXR in vitro. The 9cRA-dependent activation of the MBP promoter required the presence of both, the DNA binding and the ligand-dependent transactivation domain (AF-2) in RXR. Furthermore, as T3, 9cRA was able to stimulate MBP expression in the CG-4 cell line after differentiation to oligodendrocytes and increased the number of cells expressing the MBP protein in primary rat optic nerve glial cell cultures.

Alitretinoin↗
PubMed1999

Distance measurements between 13C nuclei in singly labeled p-xylene/Dianin's inclusion compound by 2D-RFDR.

Two-dimensional magnetization exchange experiments, with the radio-frequency-driven recoupling pulse sequence in the mixing time, have been performed for the detection of homonuclear 13C-13C distances between the singly 13C labeled methyl carbon of p-xylene and the natural abundant 13C nuclei of the host molecules in p-xylene/Dianin's complex. The intensities of the cross peaks between the methyl carbon and six host carbons were measured as function of the length of the mixing time and normalized by the intensities of their diagonal peaks. The results were compared with simulations based on the known distances in the complex. Good agreement was obtained, without taking the homonuclear zero-quantum linewidth (1/piTZQ2) into account. This can be understood by realizing that in this complex the 13C carbon pairs are significantly diluted.

Carbon Isotopes↗
PubMed1999

Deuterium REDOR: principles and applications for distance measurements

The application of short composite pulse schemes ( and ) to the rotational echo double-resonance (REDOR) spectroscopy of X-2H (X: spin 12, observed) systems with large deuterium quadrupolar interactions has been studied experimentally and theoretically and compared with simple 180 degrees pulse schemes. The basic properties of the composite pulses on the deuterium nuclei have been elucidated, using average Hamiltonian theory, and exact simulations of the experiments have been achieved by stepwise integration of the equation of motion of the density matrix. REDOR experiments were performed on 15N-2H in doubly labeled acetanilide and on 13C-2H in singly 2H-labeled acetanilide. The most efficient REDOR dephasing was observed when composite pulses were used. It is found that the dephasing due to simple 180 degrees deuterium pulses is about a factor of 2 less efficient than the dephasing due to the composite pulse sequences and thus the range of couplings observable by X-2H REDOR is enlarged toward weaker couplings, i.e., larger distances. From these experiments the 2H-15N dipolar coupling between the amino deuteron and the amino nitrogen and the 2H-13C dipolar couplings between the amino deuteron and the alpha and beta carbons have been elucidated and the corresponding distances have been determined. The distance data from REDOR are in good agreement with data from X-ray and neutron diffraction, showing the power of the method. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Synthesis and anti-HIV activity of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs): a new family of HIV-1 specific non-nucleoside reverse transcriptase inhibitors.

The anti-HIV activity of a novel series of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs) has been described. The compounds were synthesized via Curtius rearrangement of appropriate sulfamoylcarboxy azides which, in turn, were prepared from known starting materials. Several 4-substituted-2-benzyl-derivatives were found to selectively inhibit human immunodeficiency virus type 1 [HIV-1 (IIIB)] replication in MT-4 and CEM cells. These TTDs were also effective against other strains of HIV-1 (RF, HE, MN, NDK), including those that are resistant to AZT, but not against HIV-2 (ROD) or simian immunodeficiency virus [SIV(MAC251)] at subtoxic concentrations. Some of the test compounds exhibited antiviral activity against L100I RT mutant virus, but significantly lost antiviral activity against K103N, V106A, E138K, Y181C and Y188H RT mutant viruses. Compounds 6d, 6f and 6g were inhibitory to HIV-1 RT at concentrations that rank between 16.4 and 59.8 microM (nevirapine: IC50 = 4.5 microM against HIV-1 RT). Inhibition of HIV-1 RT by compound 6g was purely non-competitive with respect to the natural substrate (dGTP), which is in agreement with the nature of inhibition shown by other NNRTIs such as nevirapine and delarvidine. A structure-activity relationship was established for the anti-HIV activity of these heterocyclic compounds. TTDs represent a new chemical class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs).

Anti-HIV Agents↗
PubMed1999

Nonsteroidal anti-inflammatory activity of 1,2,4-triazolyl-heterocarboxylic derivatives.

A series of 1,2,4-triazolyl-thiophene and 1,2,4-triazolyl-pyrazole carboxylic acid derivatives was tested for acute toxicity and nonsteroidal anti-inflammatory activity. Some of these compounds showed potent analgesic activity and interesting nonsteroidal anti-inflammatory properties in different acute and chronic inflammation models.

Analgesics, Non-Narcotic↗
PubMed1999

Study of the antidepressant activity of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

A series of 23 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives were tested for acute toxicity and antidepressant activity in mice. Eight of the 23 compounds tested clearly antagonised the tetrabenazine effects and four of them (5, 7, 19, 23) showed activity values ranging from 40 to 75%, close to those shown by imipramine and viloxazine, the drugs chosen as reference standards. Compounds 7, 19 and 23 were also notably effective in the Porsolt test, shortening the immobility period of mice by more than 20%. The values obtained were very close to those elicited by imipramine and viloxazine. The most effective compounds in these tests were found among those bearing a primary amine or a benzoylamino group at the position 3 of the thieno[2,3-d]pyrimidine general structure (7, 19 and 23). The substitution of the thioxocarbonyl group at position 2 by a methylmercapto substituent maintained the activity (23). Compounds 7, 19 and 23 were chosen as prototypes for the design of new molecules with better antidepressant activity. These compounds did not present the adverse anticholinergic effects found in most tricyclic antidepressant drugs.

Adrenergic Uptake Inhibitors↗
PubMed1998

Novel 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine derivatives as non-nucleoside reverse transcriptase inhibitors that inhibit human immunodeficiency virus type 1 replication.

The 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs) represent a recently discovered chemical class of non-nucleoside reverse transcriptase inhibitors that selectively block human immunodeficiency virus type 1 replication. In a search for a better understanding of their mode of binding and with the aim of obtaining novel lead compounds, a second series of TTD derivatives was synthesized and evaluated for antiviral activity. The design of the new compounds was based on a variety of chemical modifications which were carried out in the original prototype 20a (QM 96521). Substitution of a halogen at the meta position of the N-2 benzyl group resulted in an improvement of the antiviral activity by 1 order of magnitude. Compounds bearing at the N-4 position a cyanomethyl, propargyl, or benzyl substituent were found to be the most potent of the series. Modifying the thieno[3,4-e] ring fused to the 1,2,4-thiadiazine moiety to other heterocyclic ring systems decreased the potency. The results obtained in this investigation have provided new indications for the design of even more effective TTDs.

Cell Line↗
PubMed1998

Phase sensitive detection of 2D homonuclear correlation spectra in MAS NMR

A pulse scheme for phase sensitive detection of two-dimensional (2D) homonuclear correlation magic angle spinning (MAS) NMR spectra is proposed. This scheme combines the time proportional phase increment phase cycling scheme and the time reversal 2D MAS experiment. This approach enables the direct detection of purely absorptive 2D MAS spectra, containing cross peaks that connect only diagonal peaks of dipolar correlated spins. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Simulation of CPMAS signals at high spinning speeds.

The spin dynamics of an S(1/2)IN system during the CP mixing time of continuous wave and variable amplitude cross-polarization magic angle spinning (CWCPMAS and VACPMAS) experiments is discussed. The signal enhancement of a low abundant S spin, coupled to a set of N = 6 coupled spins with I = 1/2, is evaluated as a function of the length of the mixing time. For CWCPMAS this signal is first evaluated in the frequency domain and then transformed to the time domain. These calculations provide some additional insight into the CP spin dynamics and enable a practical approach toward the evaluation of CP signals of large spin systems. In addition the adiabatic character of the ramped VACPMAS experiments is discussed and S-spin signals of a spin system with N = 6 are simulated. Estimates of the upper bounds of the CP signals as a function of the number of I spins in an S(1/2)IN system are given and compared with the calculated values.

Magnetic Resonance Spectroscopy↗
PubMed1998

Proton MAS NMR spectra at high magnetic fields and high spinning frequencies: spectral simulations using floquet theory.

Proton magic angle spinning (MAS) spectra of a model spin system, consisting of six protons, were calculated for different values of the external magnetic field and the spinning frequencies. Floquet theory was used to evaluate these spectra. The reduction of the effective homonuclear dipolar interaction for increasing spinning frequency was investigated. The influence of an increase of the external magnetic field and the spinning frequencies on the linewidths of the centerband spectra is discussed. This Floquet description of the rotating proton spin system will assist us in our calculations of the CPMAS spin dynamics of a low abundant spin interacting with a set of coupled protons.

Magnetic Resonance Spectroscopy↗
PubMed1998

1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity.

We report the development of a new group of nonnucleoside reverse transcriptase inhibitors (NNRTIs). One of the most active congeners of this series of 1,1,3-trioxo-2H,4H-thieno[3,4-e] [1,2,4]thiadiazine (TTD) derivatives, i.e., 2-(3-fluorobenzyl)-4-cyanomethylen-l,1,3-trioxo-2H,4H- thieno [3,4-e] [1,2,4] thiadiazine) (QM96639) was found to inhibit human immunodeficiency virus (HIV) type 1 [HIV-1 (IIIB)] replication in MT-4 cells at a concentration of 0.09 microM. This compound was toxic for the host cells only at a 1,400-fold higher concentration. The TTD derivatives proved effective against a variety of HIV-1 strains, including those that are resistant to 3'-azido-3'-deoxythymidine (AZT), but not against HIV-2 (ROD) or simian immunodeficiency virus (SIV/ MAC251). HIV-1 strains containing the L100I, K103N, V106A, E138K, Y181C, or Y188H mutations in their reverse transcriptase (RT) displayed reduced sensitivity to the compounds. Their cross-resistance patterns correlated with that of nevirapine. 2-Benzyl-4-cyanomethylen-1,1,3-trioxo-2H,4H-thieno[3,4-e] [1,2,4]thiadiazine (QM96521) enhanced the anti-HIV-1 activity of AZT and didanosine in a subsynergistic manner. HIV-1-resistant virus containing the V179D mutation in the RT was selected after approximately six passages of HIV-1 (IIIB) in CEM cells in the presence of different concentrations of QM96521. From structure-activity relationship analysis of a wide variety of TTD derivatives, a number of restrictions appeared as to the chemical modifications that were compatible with anti-HIV activity. Modelling studies suggest that in contrast to most other NNRTIs, but akin to nevirapine, QM96521 does not act as a hydrogen bond donor in the RT-drug complex.

Anti-HIV Agents↗
PubMed1998

Antidepressant activity of new hetero[2,1]benzothiazepine derivatives.

A number of thieno and pyrazolo[2,1]benzothiazepine derivatives as well as several synthetic intermediate compounds were tested for acute toxicity and antidepressant activity in mice. Some of these compounds were effective in the tetrabenazine and Porsolt tests.

Adrenergic Uptake Inhibitors↗
PubMed1998

CNS effects of a series of 1,2,4-triazolyl heterocarboxylic derivatives.

A series of 1,2,4-triazolyl heterocarboxylic derivatives were tested for acute toxicity and CNS effects in mice. Several of these compounds demonstrated clear psychostimulant effects. Other components of the series, however, showed a definite central depressant activity. Some of the screened derivatives showed interesting anxiolytic properties.

Animals↗
PubMed1997

Glass-ionomer dental restorative: part I: a structural study.

A structural study of glass-ionomer cement (GIC) dental restoratives has been completed. Transmission electron microscopy, selected area electron diffraction, and X-ray diffraction studies indicate domain-like microstructure in a new experimental material, whereas a featureless amorphous gel-like microstructure exists in the conventional GIC. Nuclear magnetic resonance studies were also conducted. The new experimental GIC contains domains of (i) bonelike material (apatite), (ii) mesoporous material and (iii) other framework structures (aluminium phosphate in the high cristobalite structure), with its setting chemistry a restructuring of the aluminosilicate glass around the template of poly(acrylic acid). Conventional glass-ionomer cement may set by a similar but slower process. Leaching properties of glass-ionomer cements are also explained.

Journal Article↗
PubMed1997

Prevalence of stroke in two samples (rural and urban) of old people in Spain. A pilot door-to-door study carried out by health professionals.

The aim of this study was to present the prevalence of stroke from a pilot study in old people. The urban site sample (Madrid) was made up of 397 subjects and the rural site sample (Arévalo, Avila) of 862 subjects. The study was performed with a door-to-door methodology. In the urban sample, the prevalence of stroke was 8.5% (CI 95% = 5.5-11.5%) and that of TIA was 2.1% (CI 95% = 0.6-3.6%). In the rural location the prevalence of stroke was 7.1% (CI 95% = 5.4-8.8%). This prevalence of stroke is higher than in other Spanish studies. These results need to be confirmed in a wider investigation.

Aged↗