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Biomedical subjects

R Maldonado

Publications and source records attributed to R Maldonado.

105 records · Page 6Linked to original sources

Comparison of selective and complete inhibitors of enkephalin-degrading enzymes on morphine withdrawal syndrome.

We investigated the effects of thiorphan, a selective inhibitor of endopeptidase 24.11 'enkephalinase', kelatorphan ((R)-3-(N-hydroxy-carboxamido-2-benzylpropanoyl)-L-alanine), and RB 38 A ((R)-3-(N-hydroxycarboxamido-2-benzylpropanoyl)-L-phenylalanine) two almost complete inhibitors of enkephalin metabolism, on the naloxone-precipitated morphine withdrawal syndrome in rats. Inhibitors administered intracerebroventricularly reduced several symptoms of the withdrawal syndrome. Jumping, chewing and tooth chattering were decreased by all drugs. The rise in plasma corticosterone and the hypothermia were reduced by kelatorphan and RB 38 A whereas rhinorrhea was blocked by thiorphan, tremor by kelatorphan and diarrhoea by RB 38 A. Other signs remained unchanged. These data suggest that an increase in opioid receptor occupancy by endogenous opioid peptides, protected from biotransformation specially by mixed inhibitors reduced the severity of the morphine abstinence symptoms in rats.

Animals↗

Comparative study in mice of flunitrazepam vs. diazepam on morphine withdrawal syndrome.

1. There is some evidence that benzodiazepine may modify the opioid withdrawal syndrome. We have investigated the effect of two different benzodiazepines, diazepam and flunitrazepam, on the morphine withdrawal syndrome experimentally induced in mice. 2. Opiate dependence has been induced by administration of morphine s.c. over a period of five days. Two hours after last morphine administration withdrawal syndrome was induced by s.c. injection of naloxone (5mg/kg). The number of jumps, wet-dog-shakes and paw tremor, and the presence or absence of ptosis, diarrhea, teeth chattering and body tremor were evaluated after naloxone injection. 3. All the signs of morphine withdrawal syndrome was antagonized by flunitrazepam and diazepam, only wet-dog-shake was strongly increased by flunitrazepam.

Animals↗

Effect of mixed (RB 38A) and selective (RB 38B) inhibitors of enkephalin degrading enzymes on a model of depression in the rat.

This is a study of the effects of the endogenous opioid peptides, enkephalins, on learned helplessness, an experimental model of depression in rats. For this purpose, the responses induced by RB 38A, a mixed inhibitor of enkephalin catabolism, and RB 38B, a selective inhibitor of neutral endopeptidase EC 3.4.24.11, were compared with the antidepressive effect induced by imipramine. RB 38A and RB 38B induced an imipramine-like effect in reducing helpless behavior, as illustrated by the decrease in the number of escape failures. According to the different pharmacological potential of both inhibitors to reduce enkephalin metabolism, complete inhibition of enkephalins (RB 38A) produced a higher response than that obtained with a partial inhibitor (RB 38B). On the other hand, naloxone (NLX) was found to facilitate the induction of learned helplessness, and to antagonize the effect of both enkephalin-degrading enzyme inhibitors. These results suggest that modifications in the activity of the endogenous opioid system could take place in this model of depression. The antidepressant-like effects induced by RB 38B, and especially by RB 38A, in the learned helplessness paradigm suggest that new mixed enkephalinase inhibitors, able to cross the blood-brain barrier, could provide a new strategy in the treatment of affective disorders.

Animals↗

Upstream stimulators for recoding.

Recent progress in elucidation of 5' stimulatory elements for translational recoding is reviewed. A 5' Shine-Dalgarno sequence increases both +1 and -1 frameshift efficiency in several genes; examples cited include the E. coli prfB gene encoding release factor 2 and the dnaX gene encoding the gamma and tau subunits of DNA polymerase III holoenzyme. The spacing between the Shine-Dalgarno sequence and the shift site is critical in both the +1 and -1 frameshift cassettes; however, the optimal spacing is quite different in the two cases. A frameshift in a mammalian chromosomal gene, ornithine decarboxylase antizyme, has recently been reported; 5' sequences have been shown to be vital for this frameshift event. Escherichia coli bacteriophage T4 gene 60 encodes a subunit of its type II DNA topoisomerase. The mature gene 60 mRNA contains an internal 50 nucleotide region that appears to be bypassed during translation. A 16 amino acid domain of the nascent peptide is necessary for this bypass to occur.

Animals↗

The Mexican version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Mexican language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Mexican CHAQ was already published and therefore it was revalidated while the Mexican CHQ was derived from the European Spanish version with changing of the few words whose use is different in the 2 countries. A total of 182 subjects were enrolled: 89 patients with JIA (26% systemic onset, 47% polyarticular onset, 13.5% extended oligoarticular subtype, and 13.5% persistent oligoarticular subtype) and 93 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular onset subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular onset having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Mexican version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Adolescent↗

[Epidemic outbreak of hepatitis A related to a day care center].

The aim of this study was to describe an outbreak of hepatitis A in a family group which extended to a day care center and to the families of the children attending the same and to determine the risk of acquiring the disease based on exposure to one or several sources of infection. The temporary distribution of the cases and the rate of hepatitis A in the population at risk were analyzed. The risk of acquiring hepatitis by exposure to one or more sources of infection was studied by logistic regression, calculating the odds ratio and the confidence interval of 95%. Initiation of the outbreak was in May 1996, in a 25-year-old male and finalized in November, having affected 63 people. The rate of global attack was of 12% and the risk of infection 18-fold greater (CI 95% = 5.4-61.8) in those exposed to more than one source of infection than in those exposed to only one source and 3.5-fold greater (CI 95% = 1.2-9.9) in the group from 15 to 29 years of age than in those under 14. The massive administration of immunoglobulin was useful to control the hepatitis in the day care center and in the school. The size of this epidemic of hepatitis A was due to its occurrence in a population little exposed to the virus. The greatest involvement was observed in young adults, with person to person transmission and the greater risk of acquiring hepatitis A on exposure to several sources of infection characterizing the outbreak. The possible usefulness of designing prevention strategies with the vaccine should be considered.

Adolescent↗