Biomedical subjects

S Vega

Publications and source records attributed to S Vega.

At least 19 recordsLinked to original sources

PubMed2004

Incidence of Parkinson disease and parkinsonism in three elderly populations of central Spain.

BACKGROUND: A two-phase investigation method (screening followed by detailed examination) is the most accurate epidemiologic approach to estimate the epidemiology of Parkinson disease (PD) and secondary parkinsonism. The scarcity of statistics on the incidence of PD and other types of parkinsonism using this methodology led the authors to estimate them in three elderly populations. METHODS: A Spanish elderly parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were contacted by way of screening and clinical examination. RESULTS: The cohort consisted of 5,160 subjects (ages 65 to 85 and over): Eight hundred twenty-eight died before the examination, 3,685 completed the screening procedure, and 647 could not be screened because they refused (108) or were unreachable (539). Sixty-eight incident cases of parkinsonism were found: 30 PD (44.1%), 22 drug-induced parkinsonism (32.3%), 8 parkinsonism with associated features (11.7%), and 3 vascular parkinsonism (4.4%). The remaining five cases (7.3%) were classified as unspecified parkinsonism. Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 85 and over years, adjusted to the standard European population, was 409.9 (95% CI 299.0 to 520.8) for parkinsonism and 186.8 (95% CI 110.4 to 263.2) for PD. Incidence rates of parkinsonism increased with advancing age. For PD, incidence rates increased with age in men but decreased beyond the age of 79 in women. Age-adjusted relative risk in men compared with women was 1.56 (95% CI 0.97 to 2.51) for parkinsonism and 2.55 (95% CI 1.21 to 5.37) for PD. Sixteen (53.3%) patients with PD were detected through the screening and had not been diagnosed previously. CONCLUSIONS: Incidence estimates of PD based on two-phase investigation methodology are higher than those based on other approaches. Men had a risk of developing PD that was twice that of women. A large proportion of PD patients may never seek neurologic attention.

Aged↗

PubMed2004

Selective memory impairment on an adapted Mini-Mental State Examination increases risk of future dementia.

OBJECTIVE: To determine whether selective memory impairment (SMI) on an adapted Mini-Mental State Examination (aMMSE) test increases risk of future dementia in a population-based survey of central Spain. BACKGROUND: SMI is a strong predictor of dementia in the elderly. However, most approaches have used extensive memory batteries, which are not always suitable for screening purposes. METHODS: The basal cohort consisted of 2982 poorly educated individuals aged 65 or over. Dementia, stroke and parkinsonism cases were previously excluded. At entry, participants received a structured interview including an aMMSE. Two groups were created according to basal cognitive performance, namely: (1) aMMSE > 23 and no word remembered on the aMMSE delayed-recall task (SMI group); and (2) aMMSE > 23 and at least one word remembered on the delayed-recall task (control group). In a three-year follow-up wave, conversion rate to dementia was calculated and logistic regression was performed. RESULTS: Of a total of 2507 subjects who completed the two evaluations, 280 qualified for SMI at entry. In the SMI group, 25 subjects (8.9%) developed dementia vs 26 subjects (1.2%) in the control group. Taking the two groups together, and once demographic and medical variables had been controlled, a low delayed-recall score increased dementia conversion rate (OR 0.47, 95% CI 0.34-0.64). Alzheimer's disease was the main cause of dementia (79.8%). CONCLUSIONS: Memory impairment is a risk factor for future dementia in the neurologically-healthy elderly. This can be observed in a subgroup of subjects with SMI defined on the aMMSE delayed-recall subscore. Some other measurements should be added to the SMI construct to improve its predictive validity.

Aged↗

PubMed2004

High resolution heteronuclear correlation NMR spectroscopy between quadrupolar nuclei and protons in the solid state.

A high resolution two-dimensional solid state NMR experiment is presented that correlates half-integer quadrupolar spins with protons. In this experiment the quadrupolar nuclei evolve during t1 under a split-t1, FAM-enhanced MQMAS pulse scheme. After each t1 period ending at the MQMAS echo position, single quantum magnetization is transferred, via a cross polarization process in the mixing time, from the quadrupolar nuclei to the protons. High-resolution proton signals are then detected in the t2 time domain during wPMLG5* homonuclear decoupling. The experiment has been demonstrated on a powder sample of sodium citrate and 23Na-1H 2D correlation spectra have been obtained. From the HETCOR spectra and the regular MQMAS spectrum, the three crystallographically inequivalent Na+ sites in the asymmetric unit were assigned. This MQMAS-wPMLG HETCOR pulse sequence can be used for spectral editing of half-integer quadrupolar nuclei coupled to protons.

Journal Article↗

PubMed2004

Methods and demographic findings of the baseline survey of the NEDICES cohort: a door-to-door survey of neurological disorders in three communities from Central Spain.

OBJECTIVE: To describe the methods and general results of the baseline longitudinal survey in a defined cohort of elderly people from three areas of Central Spain (urban and rural). The survey was designed to study dementia, essential tremor, Parkinson's disease and stroke. STUDY DESIGN: A population-based longitudinal study with door-to-door interviews. METHODS: This study was carried out in two phases: Phase 1 (health status questionnaire and screening performed by lay interviewers) and Phase 2 (diagnosis of neurological illnesses by neurologists). RESULTS: The study flow chart, screening instruments for neurological disorders, main demographic data (age, sex, educational attainment, occupation) and general health status of the 5,278 screened participants (2,238 men and 3,040 women) are given for the two phases. The response rate was 85.3%, and participation was higher in men and in the urban area. CONCLUSIONS: Participation rates were good in both phases of the NEDICES baseline study, and this was influenced by age, sex and setting of the participants. Educational attainment, occupation and health status data are analogous to other Spanish studies performed in the elderly. As the study population was large and good participation rates were achieved, precise analysis of morbidity of the neurological disorders investigated will be possible.

Age Factors↗

PubMed2003

Interatomic distance measurement in solid-state NMR between a spin- 1/2 and a spin- 5/2 using a universal REAPDOR curve.

A universal curve for the solid-state NMR REAPDOR experiment on an isolated spin-1/2-spin-5/2 pair is proposed that provides a simple means to measure their interatomic distance. REAPDOR data were obtained at three separate REAPDOR experiments using different values of the rotor spinning frequency. All points were fitted simultaneously to the universal formula without a need for full density matrix calculations. The 13C-17O distance of 2.45 A was measured between the C6 carbon and the 17O label in a tyrosine sample. The error of 8% in the dipolar coupling (Dfit = 278 Hz) is well within the 15% theoretical tolerance of this curve.

Journal Article↗

PubMed2002

Improved narrowband dipolar recoupling for homonuclear distance measurements in rotating solids.

Recovery of the magnetic dipolar interaction between nuclei bearing the same gyromagnetic ratio in rotating solids can be promoted by synchronous rf irradiation. Determination of the dipolar interaction strength can serve as a tool for structural elucidation in polycrystalline powders. Spinning frequency dependent narrow-band (nb) RFDR and SEDRA experiments are utilized as simple techniques for the determination of dipolar interactions between the nuclei in coupled homonuclear spin pairs. The magnetization exchange and coherence dephasing due to a fixed number of rotor-synchronously applied pi-pulses is monitored at spinning frequencies in the vicinity of the rotational resonance (R(2)) conditions. The powder nbRFDR and nbSEDRA decay curves of spin magnetizations and coherences, respectively, as a function of the spinning frequency can be measured and analyzed using simple rate equations providing a quantitative measure of the dipolar coupling. The effects of the phenomenological relaxation parameters in these rate equations are discussed and an improved methodology is suggested for analyzing nbRFDR data for small dipolar couplings. The distance between the labeled nuclei in the 1,3-(13)C(2)-hydroxybutyric acid molecule is rederived using existing nbRFDR results and the new simulation procedure. A nbSEDRA experiment has been performed successfully on a powder sample of singly labeled 1-(13)C-L-leucine measuring the dipolar interaction between the labeled carboxyl carbon and the natural abundant beta-carbon. Both narrowband techniques are employed for the determination of the nuclear distances between the side-chain carbons of leucine and its carbonyl carbon in a tripeptide Leu-Gly-Phe that is singly (13)C-labeled at the leucine carbonyl carbon position.

Journal Article↗

PubMed2001

Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes.

The vast majority of HIV-1 infections in Africa are caused by the A and C viral subtypes rather than the B subtype prevalent in the United States and Western Europe. Genomic differences between subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease. Because some amino acid polymorphisms occur at sites that have been associated with drug resistance in the B subtype, it is important to assess the effectiveness of protease inhibitors that have been developed against different subtypes. Here we report the enzymatic characterization of HIV-1 proteases with sequences found in drug-naive Ugandan adults. The A protease used in these studies differs in seven positions (I13V/E35D/M36I/R41K/R57K/H69K/L89M) in relation to the consensus B subtype protease. Another protease containing a subset of these amino acid polymorphisms (M36I/R41K/H69K/L89M), which are found in subtype C and other HIV subtypes, also was studied. Both proteases were found to have similar catalytic constants, k(cat), as the B subtype. The C subtype protease displayed lower K(m) values against two different substrates resulting in a higher (2.4-fold) catalytic efficiency than the B subtype protease. Indinavir, ritonavir, saquinavir, and nelfinavir inhibit the A and C subtype proteases with 2.5-7-fold and 2-4.5-fold weaker K(i)s than the B subtype. When all factors are taken into consideration it is found that the C subtype protease has the highest vitality (4-11 higher than the B subtype) whereas the A subtype protease exhibits values ranging between 1.5 and 5. These results point to a higher biochemical fitness of the A and C proteases in the presence of existing inhibitors.

Adult↗

PubMed2001

Peptide torsion angle measurements: effects of nondilute spin pairs on carbon-observed, deuterium-dephased PM5-REDOR.

Reintroducing dipolar coupling between spin-1/2 nuclei (e.g., (13)C, (15)N) and spin-1 (2)H, using phase-modulated deuterium dephasing pulses, provides a simple and efficient basis for obtaining peptide backbone torsion angles (phi, psi) in specific stable-isotope enriched samples. Multiple homonuclear spin-1/2 interactions due to isotopic enrichment can arise between neighboring molecules or within a multiply labeled protein after folding. The consequences of (13)C homonuclear interactions present during (13)C-observed, (2)H-dephased REDOR measurements are explored and the theoretical basis of the experimentally observed effects is investigated. Two tripeptides are taken to represent both the general case of (2)H(alpha)-alanine (in the tripeptide LAF) and the special case of (2)H(alpha)(2)-glycine (in the tripeptide LGF). The lyophilized tripeptides exhibit narrowed spectral linewidths over time due to reduced conformational dispersion. This is due to a hydration process whereby a small fraction of peptides is reorienting and the bulk peptide fraction undergoes a conformational change. The new molecular packing arrangement lacks homonuclear (13)C spin interactions, allowing determination of (phi, psi) backbone torsion angles.

Algorithms↗

PubMed2001

The effect of spin relaxation on ENDOR spectra recorded at high magnetic fields and low temperatures.

A simple theoretical model that describes the pulsed Davies electron-nuclear double resonance (ENDOR) experiment for an electron spin S = (1/2) coupled to a nuclear spin I = (1/2) was developed to account for unusual W-band (95 GHz) ENDOR effects observed at low temperatures. This model takes into account the thermal polarization along with all internal relaxation processes in a four-level system represented by the electron- and nuclear-spin relaxation times T(1e) and T(1n), respectively, and the cross-relaxation time, T(1x). It is shown that under conditions of sufficiently high thermal spin polarization, nuclei can exhibit asymmetric ENDOR spectra in two cases: the first when t(mix) >> T(1e) and T(1n), T(1x) >> T(1e), where ENDOR signals from the alpha manifold are negative and those of the beta manifold positive, and the second when the cross- and/or nuclear-relaxation times are longer than the repetition time (t(mix) << T(1e) << t(R) and T(1n), T(1x) > t(R)). In that case the polarization of the ENDOR signals becomes opposite to the previous case, the lines in the alpha manifolds are positive, and those of the beta manifold are negative. This case is more likely to be encountered experimentally because it does not require a very long mixing time and is a consequence of the saturation of the nuclear transitions. Using this model the experimental t(mix) and t(R) dependencies of the W-band (1)H ENDOR amplitudes of [Cu(imidazole)(4)]Cl(2) were reproduced and the values of T(1e) and T(1x) >> T(1e) were determined. The presence of asymmetry in the ENDOR spectrum is useful as it directly provides the sign of the hyperfine coupling. The presented model allows the experimentalist to adjust experimental parameters, such as t(mix) and t(R), in order to optimize the desired appearance of the spectrum.

Journal Article↗

PubMed2001

Bovine viral diarrhoea virus genotype 1 can be separated into at least eleven genetic groups.

Seventy-eight bovine viral diarrhoea viruses (BVDV) recently collected in Austria, France, Hungary, Italy, Slovakia, Spain and UK were genetically typed in the 5'-untranslated (5'UTR) and autoprotease (Npro) regions of the pestivirus genome. Seventy-six of the isolates were BVDV-1 and two French isolates were of the BVDV-2 genotype. Phylogenetic analysis of the 5'UTR (245 nt), including additional BVDV-1 sequences from USA, Canada, Germany, New Zealand, Mozambique and Sweden, taken from GenBank and from our previous works, indicated that these viruses were clustered not only into the two generally accepted groups (BVDV-1a-"NADL like" and BVDV-1b-"Osloss like"), but altogether into 11 phylogenetic groups. Similar clustering was observed with Npro region sequences (385 nt) and the highest bootstrap values (over 95%) were obtained by phylogeny combining 5'UTR and Npro sequences. Some associations between the genetic grouping and the origin of the isolates were apparent, probably reflecting historical trade contacts. Considering the variability of isolates it is recommended that diagnostic PCR primers should be re-examined to ensure coverage of all BVDV-1 groups. The genogroups were less clearly differentiated by monoclonal antibody typing, suggesting significant antigenic similarities within the BVDV-1 genotype.

5' Untranslated Regions↗

PubMed2001

Problems and issues with door-to-door, two-phase surveys: an illustration from central Spain.

In 1994-1995, a screening and examination survey was conducted to ascertain the prevalence of dementia, Parkinson's disease and stroke in two urban communities and one rural community of central Spain. We use this survey to illustrate many nonclinical aspects of conducting two-phase prevalence surveys. Special emphasis is given to two common weaknesses in such surveys: screening nonparticipation and screening validation.

Aged↗

PubMed2000

[Orthostatic hypotension in the aged and its association with antihypertensive treatment].

BACKGROUND: To assess the prevalence of orthostatic hypotension (OH) in an elderly population and to evaluate the influence of hypertension control and of the type of antihypertensive drug used. METHODS: 2,700 elderly patients (> 65 years) from the EPICARDIAN study were included. Blood pressure (BP) was measured twice with the patient seated and once again 1 to 3 minutes afterwards with the patient standing. Hypertension is defined as BP > or = 140/90 mmHg or if the patient received antihypertensive treatment. Orthostatic hypotension was defined as a fall of SBP > or = 20 mmHg and/or DBP > or = 10 mmHg 1 to 3 minutes after the postural change. RESULTS: 71.6% of the patients were classified as hypertensive and 57.1% were receiving pharmacological treatment. The overall prevalence of OH was 6.8% among hypertensive patients, 8.1% and 3.4% in normotensives patients (p < 0.05). No significant difference was found in the prevalence of OH between those receiving (7.7%) or not (8.6%) antihypertensive medication. No association was found either between the prevalence of OH and the type or number of antihypertensive drugs used. 17.6% of the patients reached hypertension optimal control (SBP < 140 and DBP < 90 mmHg), the prevalence of OH in these patients was 5.3%, among the uncontrolled the prevalence was 8.9% (p < 0.05). The adjusted OR was 1.91 (1.1-3.3) for the prevalence of OH in the uncontrolled patients versus the controlled. CONCLUSIONS: The prevalence of OH in the elderly is not very high, being greater among hypertensive than normotensive patients. No association was found between the prevalence of OH and the number of drugs received. Reaching hypertension control reduces the prevalence of OH.

Adrenergic alpha-Antagonists↗

PubMed2000

Efficient deuterium-carbon REDOR NMR spectroscopy.

Phase modulated pulses for deuterium recoupling in (2)H-(13)C REDOR NMR spectroscopy have been introduced to improve dephasing of the detected (13)C nuclei. The deuterium inversion properties of phase modulated recoupling pulses have been studied experimentally on l-alanine-2-d(1) and theoretically using average Hamiltonian theory and exact simulations of the equation of motion of the density matrix. The best (13)C dephasing was observed when XYXYX (PM5) deuterium recoupling pulses were applied. A comparison to the 90 degrees -180 degrees -90 degrees (CPL) composite pulse scheme revealed an improvement of recoupling on the order of 2.5. Simple CW recoupling pulses of the same length of PM5 and CPL pulses showed the weakest (13)C dephasing. Simulations have shown that the (2)H recoupling efficiency of PM5 REDOR experiments approach the very efficient REAPDOR results. However, in our case a REAPDOR study of l-alanine-2-d(1) resulted in a significant decrease of the (13)C signal intensity due to pulse imperfections of (13)C pi-pulses. The new PM5-REDOR technique has been employed to study the torsion angle between C1/2 and C5 in ethylmalonic acid-4-d(2).

Alanine↗

PubMed2000

Two-dimensional ENDOR-ESEEM correlation spectroscopy

A two-dimensional (2D) experiment that correlates electron-nuclear double resonance (ENDOR) and electron spin-echo envelope modulation (ESEEM) frequencies, useful for unraveling and assigning ENDOR and ESEEM spectra from different paramagnetic centers with overlapping EPR spectra, is presented. The pulse sequence employed is similar to the Davies ENDOR experiment with the exception that the two-pulse echo detection is replaced by a stimulated echo detection in order to enhance the resolution in the ESEEM dimension. The two-dimensional data set is acquired by measuring the ENDOR spectrum as a function of the time interval T between the last two microwave pulses of the stimulated echo detection scheme. This produces a series of ENDOR spectra with amplitudes that are modulated with T. Fourier transformation (FT) with respect to T then generates a 2D spectrum with cross peaks connecting spectral lines of the ESEEM and ENDOR spectra that belong to the same paramagnetic center. Projections along the vertical and horizontal axes give the three-pulse FT-ESEEM and ENDOR spectra, respectively. The feasibility of the experiment was tested by simulating 2D ENDOR-ESEEM correlation spectra of a system consisting of an electron spin (S = (1/2)) coupled to two nuclei (I(1) = I(2) = (1/2)), taking into account experimental conditions such as pulse durations and off-resonance irradiation frequencies. The experiment is demonstrated on a single crystal of Cu(2+) doped l-histidine (Cu-His), containing two symmetrically related Cu(2+) sites that at an arbitrary orientation exhibit overlapping ESEEM and ENDOR spectra. While the ESEEM spectrum is relatively simple and arises primarily from one weakly coupled (14)N, the ENDOR spectrum is very crowded due to contributions from two nonequivalent nitrogens, two chlorides, and a relatively large number of protons. The simple ESEEM projection of the 2D ENDOR-ESEEM correlation spectrum is then used to disentangle the ENDOR spectrum and resolve two sets of lines corresponding to the different sites. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Spinning-frequency-dependent narrowband RF-driven dipolar recoupling

Dipolar recoupling techniques of homonuclear spin pairs are commonly used for distance or orientation measurements in solids. Accurate measurements are interfered with by broadening mechanisms. In this publication narrowband RF-driven dipolar recoupling magnetization exchange experiments are performed as a function of the spinning frequency to reduce the effect of zero-quantum T(2) relaxation. To enhance the exchange of magnetization between the coupled spins, a fixed number of rotor-synchronous pi-pulses are applied at spinning frequencies approaching the rotational resonance (R(2)) conditions. The analysis of the powder averaged dipolar decay curves of the spin magnetizations as a function of the spinning frequency provides a quantitative measure of the dipolar coupling. An effective Hamiltonian for this experiment is derived, taking into account all chemical shift parameters of the spins. The length of the nbRFDR mixing time and the number of rotor cycles per pi-pulse are optimized by numerical simulations for sensitive probing of the dipolar coupling strength. The zero-quantum T(2) relaxation time can easily be taken into account in the data analysis, because the overall exchange time is almost constant in these experiments. Spinning-frequency-dependent nbRFDR experiments near the m = 1 and m = 2 R(2) condition are shown for doubly (13)C-labeled hydroxybutyric acid. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

The influence of the radiofrequency excitation and conversion pulses on the lineshapes and intensities of the triple-quantum MAS NMR spectra of I = 3/2 nuclei.

A rigorous examination of the various multiple-quantum magic angle spinning sequences is carried out with reference to sensitivity enhancement in the isotropic dimension and the lineshapes of the corresponding MAS peaks in the anisotropic dimension. An echo efficiency parameter is defined here, which is shown to be an indicator of the performance aspects of the various sequences. This can be used in the design of further new experiments in this field. A consequence of such a systematic analysis has been the combination of a spin-lock pulse for excitation of multiple-quantum coherences and an amplitude-modulated pulse for their conversion to observable single-quantum coherences. This approach has resulted in an improved performance over other sequences with respect to both the anisotropic lineshapes and the isotropic intensities.

Anisotropy↗

PubMed2000

Antigenic characterization of bovine viral diarrhoea virus isolates from Spain with a panel of monoclonal antibodies.

A group of 47 bovine viral diarrhoea virus (BVDV) strains isolated from a variety of bovine tissues from eight different geographical areas of Spain and two BVDV strains isolated from a cell line were characterized antigenically with a panel of 23 monoclonal antibodies (mAbs). The mAbs were directed at one of three viral proteins: E2, Erns and NS2-3. A peroxidase-linked assay was used to test the mAbs for reactivity against infected cell monolayers. The data were analysed by two computational methods: the Antigenic Distance Program (MAP) and the Phylogeny Inference Package (PHYLIP), and compared with those obtained previously using the same mAbs with other pestiviruses, including reference strains and UK field isolates. All the Spanish field strains studied appeared to be broadly similar to reference strains of BVDV and were included in the subgroup of classical BVDV, meanwhile the two strains isolated from a cell line were included in the subgroup of atypical pestiviruses.

Animals↗

PubMed2000

Pharmacological effects of triazolo[4,3-d] and tetrazolo[1,5-a][1,4]benzodiazepines on the central nervous system.

A series of tricyclic 1,4-benzodiazepines, fundamentally 5H-s-triazolo[4,3-d] and tetrazolo[1,5-a][1,4]benzodiazepines, were tested for acute toxicity and central nervous system effects in mice. All of these compounds, but especially 3, 4 and 5, showed a clear central depressant activity. Compounds 3, 4 and 5 also showed a moderate activity in antagonizing the deleterious effects produced by cardiazol but were ineffective in counteracting those elicited by strychnine. These same compounds 3, 4 and 5 presented a remarkable benzodiazepine-like action with a pharmacological profile similar to that of chlordiazepoxide.

Animals↗