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Biomedical subjects

J Pascual

Publications and source records attributed to J Pascual.

At least 181 records · Page 10Linked to original sources
PubMed1997

[Neurochemistry of Parkinson's disease and parkinsonism plus].

The neurochemistry of Parkinson's disease and other degenerative parkinsonisms is reviewed, emphasizing the changes described in the dopaminergic system. Presynaptic dopaminergic markers are reduced over the striatum in all these degenerative parkinsonisms, dopamine receptor changes being more heterogeneous. While in Parkinson's disease D1 and D2 receptors remain preserved as compared to controls, in progressive supranuclear palsy there is a loss of nigral D1 receptors and of striatal D2 receptors. This finding has also been described in striatonigral degeneration. There are no clear data about the status of D3, D4 and D5 dopamine receptors in these conditions. The alterations in other neurotransmission systems, cholinegic, adrenergic, serotoninergic and peptidergic are, in general, less dramatic, although they have not been studied in detail. To conclude, further studies are necessary in these field, in these moment, however, the preservation of striatal D2 dopamine receptors is the neurochemical finding with the best correlation with the response to levodopa or other dopaminergic agonists.

Acetylcholine↗
PubMed1997

[Bimanual mirror letter writing: a post-traumatic case].

Mirror writing is inverse writing that can only be read with the help of a mirror. It is generally associated with dominant hemisphere lesions and affects only one hand. We describe the case of a patient who, after cranial injury, developed bimanual mirror writing for letters but no other focal neurological symptom. The only abnormal complementary finding was a zone of left parieto-occipital hypoperfusion visibly by SPECT. No signs of psychological disorder were present to which the dysgraphia could be attributed. Symptoms disappeared after three months. We conclude that isolated bimanual mirror letter writing may be an expression of reversible parieto-occipital dysfunction of the dominant hemisphere.

Adolescent↗
PubMed1997

[Headaches due to cough, exertion and sexual intercourse].

The aim of this study was to review the advances in cough, exertional and sexual headaches. We perform a critical analysis of the literature and of our experience with 72 patients. About one-half of patients having cough headache will have benign cough headache. The remaining half suffer from Chiari type I malformation. Benign cough headache begins typically in men above age 50, while symptomatic cough headache begins under 50 and appears with the same frequency in both sexes. Indomethacin is the treatment of choice of benign cough headache, but has no effect in symptomatic cases, which respond to suboccipital craniectomy. Although also showing male predominance, exertional and sexual headaches begin under age 50. Subarachnoid bleeding due to aneurism is the most frequent etiology for exertional and sexual headaches. Cough headache and exertional headache are separate clinical entities, whereas exertional headache and sexual headache seem to be different expressions of the same clinical entity. These data allow, in addition, the clinical differentiation between benign and symptomatic cough headache.

Adult↗
PubMed1996

Effects of freezing storage time on the density of muscarinic receptors in the human postmortem brain: an autoradiographic study in control and Alzheimer's disease brain tissues.

The effect of sex, age (range = 41-84 years), postmortem delay (range = 1-71 h) and freezing storage time (FST) (range = 8-75 months) at -25 degrees C on the density of muscarinic receptors (MR) was examined in tissue sections of several representative areas of 41 postmortem brains from adult patients who had died from non-neurological disorders using [3H]N-methylscopolamine as a ligand. Neither age, sex nor postmortem delay determined significant changes in the density of MR in frontal and entorhinal cortex, hippocampus and striatum. By contrast, FST significantly decreased the densities of MR in frontal and entorhinal cortex, pyramidal layer of CA1 and CA3 fields at the hippocampus and over caudate nucleus. This reduction in MR densities did not reach statistical significance, for any region, when FST was less than 39 months. Although there was a tendency towards a decrease, no significant changes were observed in putamen and over hippocampal dentate gyrus. FST (range = 11-78 months) also significantly decreased the densities of MR in the same regions of postmortem brains from 18 patients who had died with a clinico-pathological diagnosis of Alzheimer's disease (AD). Even though there was a general tendency towards a decrease (between 7% in the caudate and 30% in the dentate gyrus at the hippocampus), no significant differences could be seen in MR densities between control and AD cases, except in the hilus in the dentate gyrus (P < 0.022), when brains were matched for FST. From the present results it is clear that control and diseased brains must also be matched for FST as well as for other factors such as sex, age and postmortem delay. It is possible that differences in FST could in part account for the variability of the reported results measuring MR in control and AD brains. At least for MR, FST shorter than three years would seem to be acceptable when performing this kind of studies.

Adult↗
PubMed1996

The spectrin repeat folds into a three-helix bundle in solution.

Spectrin, a major component of the membrane skeleton, is mainly composed of tandemly repeated segments of approx. 106 amino acids. We have undertaken the determination of the three-dimensional structure of a chicken brain alpha-spectrin repeat by heteronuclear multidimensional NMR. Sedimentation equilibrium demonstrates that this repeat is monomeric at the concentration used for NMR (1 mM). Its secondary structure was identified using a collection of sequential and medium range NOEs, chemical shifts, HN-Halpha coupling constants, and relaxation measurements. These data unequivocally demonstrate the presence of three long helices connected by two loops. A set of interhelical NOEs indicates that the helices assemble into a triple helical structure. Our results provide experimental evidence supporting the triple-helical bundle proposed by modelling.

Amino Acid Sequence↗
PubMed1996

[3H]Sumatriptan binding sites in human brain: regional-dependent labelling of 5-HT1D and 5-HT1F receptors.

The general properties of [3H]sumatriptan binding sites in postmortem human brain tissue sections are described. High concentrations of autoradiographic grains were seen in globus pallidus = substantia nigra > cortex > putamen > hippocampus. While 5-HT (5-hydroxytryptamine) displaced in all regions more than 90% of [3H]sumatriptan binding, the level of binding inhibited by 5-CT (5-carboxamidotryptamine) varied in each region. Although the binding inhibited by 5-CT in some regions such as globus pallidus and substantia nigra was equivalent to that obtained with 5-HT, in cortical areas, such as frontal cortex and hippocampus, a substantial level of binding insensitive to 5-CT was seen. In addition, in membrane binding assays, 10 nM metergoline displaced most [3H]sumatriptan specific binding in striatum and only 16% in frontal cortex. In the human brain sumatriptan binds to at least two 5-HT1 receptors, 5-HT1D and 5-HT1F.

Adult↗
PubMed1996

Stereoselective metabolic pathways of ketoprofen in the rat: incorporation into triacylglycerols and enantiomeric inversion.

The enantiomeric bioinversion of ketoprofen (KP) enantiomers and their incorporation into triacylglycerols were investigated in the rat (1) in vitro, using liver homogenates, subcellular fractions, and hepatocytes, and (2) in vivo, in different tissue samples after oral administration of the radiolabelled compounds. In liver homogenates or subcellular fractions, the enantiomer (S)-ketoprofen (S-KP) was recovered unchanged, whereas (R)-ketoprofen (R-KP) was partially converted into its Coenzyme A (CoA) thioester and inverted to S-KP. Both processes occurred mainly in the mitochondrial fraction. This supports the mechanism of inversion via stereoselective formation of CoA thioester of R-KP, already described for other non-steroidal anti-inflammatory drugs. Incorporation into triacylglycerols was detected after incubation with intact hepatocytes in the presence of added glycerol. The process was stereoselective for R-KP vs. S-KP (covalently bound radioactivity 26,742 +/- 4,665 dpm/10(6) cells vs. 6,644 +/- 3,179 dpm/10(6) cells, respectively). However, no incorporation was found in liver samples after oral administration of either R-KP or S-KP. On the contrary, in adipose tissue samples a significant and stereoselective formation of hybrid triacylglycerols was observed: 11,076 +/- 2,790 dpm.g-1 for R-KP vs. 660 +/- 268 dpm.g-1 for S-KP. The incorporated R/S ratio, higher in adipose tissue (R/S = 17) than in hepatocytes (R/S = 4), indicates that fat may be the main tissue store for the xenobiotic R-KP in rats.

Adipose Tissue↗
PubMed1996

Intramedullary tuberculoma of the spinal cord with syringomyelia.

We describe a patient with a presumed intramedullary tuberculoma treated only with antituberculous therapy. MRI showed a ring-enhancing annular lesion in the thoracic spinal cord with a distant syringomyelic cavity, which improved after therapy. MRI in this case allowed us not only to achieve a presumptive diagnosis but also to assess the therapeutic response, making surgical exploration unnecessary.

Adult↗
PubMed1996

Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group.

There are very limited data on overall epidemiology of ARF. It is crucial to know the incidence, etiology and clinical feature of ARF to promote prevention strategies and to implement adequate resources for the management of this entity. During a nine month period, a collaborative prospective protocol with 98 variables was developed to assess all ARF episodes encountered in the 13 tertiary-care hospitals in Madrid, Spain (covering 4.2 million people of over 14 years of age). ARF was considered when a sudden rise in serum creatinine concentration (SCr) to more than 177 mumol/liter was found in patients with normal renal function, or when the sudden rise (50% or more) was observed in patients with previous mild-to-moderate chronic renal failure (SCr < 264 mumol/liter). Of the 748 cases of ARF studied, 665 episodes presented in inhabitants from the Madrid area. This gives an overall incidence of ARF of 209 cases per million population (p.m.p.; 95% CJ 195 to 223). The incidence of acute tubular necrosis (ATN) was 88 cases p.m.p. (95% CI 79 to 97), prerenal ARF 46 p.m.p (95% CI 40 to 52), acute-onset chronic ARF 29 p.m.p. (95% CI 24 to 34), and obstructive ARF 23 p.m.p. (95% CI 19 to 27). The mean age was 63 +/- 17 years. The most frequent causes of ARF were ATN (45%), prerenal (21%), acute-onset chronic renal failure (12.7%) and obstructive ARF (10%). Renal function was normal at admission in 48% of patients who later developed ARF. Mortality (45%) was much higher than that of the other patients admitted (5.4%, P < 0.001). This real outcome correlated extremely well with the expected outcome calculated through out the severity index of ARF (SI) 0.433 +/- 0.246 (mean +/- SD). In 187 cases, mortality was attributed to underlying disease, thus corrected mortality due to ARF was 26.7%. Dialysis was required in 36% of patients, and was associated with a significantly higher SI of ARF (0.57 +/- 0.23 vs. 0.35 +/- 0.19, P < 0.001) and mortality (65.9 vs. 33.2%, P < 0.001). Mortality in patients hemodialyzed with biocompatible synthetic membranes (N = 50) was similar to that observed with cellulosic ones (N = 84; 66% vs. 59.5%, NS). Mortality was higher in patients with coma, assisted respiration, hypotension, jaundice (all P < 0.001) and oliguria (P < 0.02). This study gives, for the first time, the incidence of all forms of ARF in a developed country. ARF is iatrogenically induced at a high rate by modern medicine. Prevention strategies, particularly in the perioperative period, are needed to decrease its impact.

Acute Kidney Injury↗
PubMed1996

Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem human brain.

The anatomical distribution of [3H]sumatriptan-binding sites was analysed in brain tissue sections from 11 subjects. Relevant concentrations of [3H]sumatriptan-binding sites were seen in areas such as visual cortex > locus niger > globus pallidus > layers IV-V of the frontal cortex > subiculum > entorhinal cortex > nucleus tractus solitarius > nucleus trigeminalis caudalis. This distribution of [3H]sumatriptan-binding sites in the human brain shows some differences when compared with that of 5HT1D receptors, confirming that, besides 5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences are evident between the distribution of [3H]sumatriptan-binding sites in the human brain and that reported for guinea-pig and rat brains, emphasizing that caution is needed in extrapolating experimental data from animals to humans. Furthermore, these data help to explain some of the therapeutic actions of sumatriptan. The remarkable levels of binding found in areas as nucleus tractus solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks sumatriptan could exert its specific anti-emetic effects and, partly at least, induce analgesia by directly acting over these brain nuclei.

Adult↗
PubMed1996

Ontogenetic development of 5-HT1D receptors in human brain: an autoradiographic study.

The pattern of pre- and postnatal appearance of 5-HT1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [125I]GTI (serotonin O-carboxymethyl-glycyl-[125I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [125I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period.

Adult↗