PubMed Health⌕ Search

Biomedical subjects

J L Bravo

Publications and source records attributed to J L Bravo.

At least 19 recordsLinked to original sources
PubMed2001

Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods using calculations at the B3LYP/6-31G level of theory and (1)H NMR spectroscopy. Both gas-phase and solvent studies predict a Z-anti conformation to be the lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alpha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears approximately 0.8 ppm further downfield than a proton situated gauche to the N-H proton. This finding, which could only be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.

Journal Article↗
PubMed2000

Understanding diastereofacial selection in carbohydrate-based domino cycloadditions: semiempirical and DFT calculations.

The sequential cycloaddition of nitroalkenes with methyl vinyl ether was investigated by semiempirical (PM3) and density functional methods (B3LYP/6-31G*). The asymmetric version was also examined with a threoconfigured carbohydrate auxiliary. This produces a larger, more flexible system that complicates the calculation. Most transition structures were then fully optimized at the PM3 level and further refinement was done at ab initio levels. This study represents a model case that enables the rationalization of the high facial selectivity observed in carbohydrate-based nitrone- and nitronate-alkene cycloadditions. The selective endo orientation of the [4+2] pathway results from Coulombic attraction and secondary orbital interactions in the transition state. The stereochemical outcome is largely influenced by a combination of steric shielding from the bulky chiral substituent at C4 and the anomeric effect that places the nitronate C6-alkoxy group in a pseudoaxial arrangement. The resulting conformation favors the subsequent exo approach of methyl vinyl ether to the less hindered re face of the nitronate. It is also remarkable to note that solvation energies stabilize significantly a particular transition structure, thereby explaining the marked stereoselection observed in a polar medium.

Carbohydrates↗
PubMedDate not supplied

Controlled release levodopa in Parkinson's disease: influence of selection criteria and conversion recommendations in the clinical outcome of 450 patients. STAR Study Group.

We present the results of an open, prospective, multicentric study including 450 patients with mild to moderate Parkinson's disease (PD) converted from standard Sinemet to Sinemet CR (controlled release; Dupont Pharma, Pavia, Italy). Patients with complex fluctuations and diphasic dyskinesias were excluded and the conversion was made after some recommendations, depending on the clinical problems and the daily dosage and administration schedule of standard (STD) Sinemet. The condition of more than 60% of the patients improved after the change and 80% of them preferred the CR formulation by the end of the study. We found a moderate, but significant, improvement in most of the efficacy parameters used, such as the Unified Parkinson's Disease Rating Scale (UPDRS), the Schawb and England scale, and dyskinesias and sleep questionnaires. Forty-five patients (10%) discontinued the study due to adverse effects (mainly gastrointestinal disturbances, functional deterioration, and dyskinesias). We conclude that Sinemet CR is a useful and safe therapeutic option in patients with mild and moderate PD. Selection of the patients is the most important outcome factor.

Aged↗
PubMedDate not supplied

Conversion to controlled-release levodopa/carbidopa treatment and quality of life as measured by the Nottingham Health Profile. The STAR Study Group.

BACKGROUND: Controlled-release levodopa-carbidopa (CRLC) improves some aspects of Parkinson's disease (PD) in patients previously treated with standard levodopa formulations (SL). However, little is known about the effect of this strategy on the health-related quality of life (QoL). OBJECTIVE: To assess the QoL and clinical changes due to the conversion of treatment from SL to CRLC in patients with mild to moderate PD. PATIENTS AND METHODS: Through the Nottingham Health Profile (NHP), QoL was measured in 276 non-selected PD patients included in a multicenter, open study. Guidelines for switching to CRLC and optimization of treatment were given. Assessment of patients was carried out by means of the Hoehn & Yahr, UPDRS, and Schwab & England scales, and questionnaires for dyskinesias and sleep. Examination of the NHP-Spanish Version-scaling properties by fitting data to the Rasch model, disclosed that 3 NHP scales (Emotional reactions, Pain, and Physical mobility) and the NHP distress index (NHPD) were suitable for efficacy analysis. RESULTS: Comparison of scores at baseline and at the end of the study showed significant improvement (paired Student t-test, p < 0.0001) in all these four scales associated with the change to CRLC. Responsiveness to change of the NHP was high. In the present study, changes in QoL were not contingent to baseline factors such as age, gender, stage of disease or ADL capabilities. CONCLUSION: Conversion to CRLC significantly improves the QoL of patients with mild to moderate PD.

Adult↗
PubMedDate not supplied

[Familial polyposis of the colon. Analysis of 17 cases].

Seventeen cases of familiar polyposis of the colon seen in the National Institute of Nutrition are reviewed. In 12 of the cases (70%) there were family histories of colonic polyposis. Ten patients (50%) developed carcinoma and of these 7 were located in the rectosigmoide. Ten patients underwent total colectomy with abdominoperineal resection. Seven already had carcinoma at operation; 5 localized and with survival rates of more than 5 years without evidence of recurrence; the other 2 had distant metastasis at operation. Four patients underwent colectomy with ileoproctoanastomosis. In 2 of these cases subsequent abdominoperineal resection was necessary; another died of recurrent carcinoma and the fourth is alive and asymptomatic. Familiar colonic polyposis is an hereditary disease of the autosomic dominant type with a tendency to develope malignant changes at an early age. The treatment of choice is colectomy; however, controversy exists as to whether or not the rectum should be conserved. Based on our results, and those of other authors, we feel that the treatment of choice is total colectomy with abdominoperineal resection, because of the high probability of malignant recurrence.

Adenocarcinoma↗