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Biomedical subjects

M D Jiménez

Publications and source records attributed to M D Jiménez.

At least 19 recordsLinked to original sources

Role of L-arginine in ibuprofen-induced oxidative stress and neutrophil infiltration in gastric mucosa.

It has been proposed that neutrophil and oxygen dependent microvascular injuries may be important prime events in gastrointestinal (GI) toxicity of non-steroidal antiinflammatory drugs (NSAIDs). L-arginine (L-ARG) is an essential amino acid which participates in many important biochemical reactions associated to the normal physiology of the organism. In these experimentations, we studied the role of L-ARG, aminoacid precursor of NO synthesis, on ibuprofen (IB) induced gastric lesions, and also on the inflammatory and oxidative mechanisms related to mucosal damage. Oral administration of IB (100 mg kg(-1)), produced severe damage on gastric mucosa, which was more important after 6 h test-period, and was accompanied by a significant increment in myeloperoxidase (MPO) activity, as index of neutrophil activation, as well as lipid peroxidation (LP) levels and xanthine oxidase (XO) activity. However, no changes were observed in total mucosal glutathione (tGSH), nor glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. Simultaneous treatment with equimolar doses of L-ARG (oral and i.p.), considerably reduced the number and intensity of lesions, and at the same time (6 h) the maximum protection was also observed. In addition, L-ARG inhibited the IB-induced LP and XO enhancement, but did not produce changes in leukocyte infiltration, tGSH, GSH-Px and SOD activity. These findings suggest that (1) L-ARG protective effect on gastric mucosa against IB-induced mucosal lesions could be explained by a local effect and also might be due to the systemic action of the aminoacid; (2) the active oxygen species, derived both from XO and activated neutrophils, could play a role in the pathogenesis of gastric injury induced by IB, (3) L-ARG exhibit a protective effect against IB-induced mucosal damage, probably through the inhibition of oxidative stress derived via xanthine-XO, but it does not block the oxygen free radical production through polymorphe nuclear leukocytes.

Animals↗

Topiramate for patients with refractory migraine: an observational, multicenter study in Spain.

INTRODUCTION: The efficacy of current preventive migraine treatments is limited. In addition, tolerability problems are not infrequent. OBJECTIVES: To check our experience with topiramate in the treatment of patients with refractory migraine. PATIENTS AND METHODS: We offered treatment with topiramate to patients with the diagnosis of International Headache Society (IHS) migraine who had not responded to or tolerated beta-blockers, amitriptyline, flunarizine and/or valproate. This series is made up of 115 patients (88 women), between 16 and 81 years. Most of them (n=79) fulfilled the Silberstein et al. criteria for transformed migraine. The parameters analyzed were "response" (reduction in migraine frequency>50%), excellent response (>75%) and tolerability. RESULTS: After 3 months, the maintenance doses of topiramate ranged from 25 to 400 mg, though most patients took 100 mg. Twenty-four (21%) patients withdrew due to adverse events, mostly cognitive difficulties, that had already occurred with doses as low as 25-50 mg, while 26 (23%) found topiramate ineffective. The remaining 65 (56%) patients responded, 34 with excellent response. Sixteen patients (10 obese) lost weight (3-13 kg). CONCLUSIONS: Topiramate seems to be a good therapeutic option for about half of the patients with refractory migraine. In these patients response is usually excellent. Intolerance due to adverse events appears in one-fifth of the cases early and at low doses.

Adolescent↗

[Service portfolio in neurology].

The specialist health assistance service book (SB) is the development of a clinical health product directed to the general population. The main objectives are: the offer of a clinical health product or to look for new offers, the evaluation or accreditation of neurological departments, the management of neurological departments, the SB presentation to main skateholder (patients, doctors, managers) and finally to inform patients of the neurological products through health resources map, that allowed them to use it. The SB includes emergency, inpatient and outpatient neurological services, and also specific diagnostic and treatment neurological procedures. In a few departments there will be also clinical units directed to specific neurological diseases or processes. It is important to develop the neurological SB in every department because it can satisfy the patients needs, and allow us to adapt quickly to our changing health reality.

Hospital Departments↗

New issues about nitric oxide and its effects on the gastrointestinal tract.

Over the last years the important role of nitric oxide (NO) as endogenous modulator of numerous physiological functions has been shown. NO is involved in the regulation of blood flow, maintenance of vascular tone, control of platelet aggregation, and modulation of the activity of the mastocytes. It also plays a key role as neurotransmitter in the central and peripheric nervous system (non adrenergic non colinergic, NANC, neurons), in the nervous control of the cerebral blood flow and in the neuroendocrine regulation or synaptic plasticity. However, NO shows a dual behavior: at physiological concentrations, released through the constitutive synthase (cNOS), it regulates house-keeping functions, whereas its overproduction by the inducible isoenzyme (iNOS) exhibits cytotoxic activity because interacting with reactive species producing peroxinitrites (ONOO) and other compounds, which are highly damaging for the tissues. In the gastrointestinal tract (GIT) NO participates in the modulation of the smooth musculature tone, such as the regulation of intestinal peristaltism, gastric emptying and antral motor activity. It also regulates acid and gastric mucus secretion, alkaline production, and is involved in the maintenance of mucosal blood flow. In physiological conditions, NO acts as an endogenous mediator modulating both, the repairing and integrity of the tissues, and exhibits gastroprotective properties against different types of aggressive agents. However, high concentrations of NO are related to numerous pathological processes of GIT including peptic ulcer, chronic gastritis, gastrointestinal cancer, bacterial gastroenteritis, celiac or chronic inflammatory bowel diseases. Recently, this hypothesis that cNOS is always beneficial and iNOS is always deleterious, has been questioned, since that a series of data suggest that the increase of cNOS activity could be responsible for the derived pathological changes and, by contrast, NO liberated by the inducible isoenzyme might play a repairing effect in certain pathological disorders. The pharmaceutical industry is really interested in proving the clinical benefits of the mediator. Numerous NO-donor drugs, nitrate derivatives, have been frequently used in the cardiovascular diseases due to their vasodilating properties, which allow an enhancement of coronary blood flow. More recently, the protective effect of NO against non steroidal antiinflammatory drugs (NSAID)-gastroenteropathy has been shown, because its vasodilating and antioxidant properties render it a potentially useful agent. Different NSAID, including acetyl salicylic acid, diclofenac or naproxen, have been formulated by attaching a NO releasing-moiety. These NO-NSAID, antiinflammatories combined with precursors of the mediator, or with inhibitors of the inducible synthase, are currently being evaluated. However, although the pharmacotherapeutical possibilities of NO are considerable, it is necessary to elucidate the exact mechanisms derived from stimulation/inhibition of the isoenzymes in order to determine the clinical utility of NO-donors.

Animals↗

[Simplified method for the processing of sputum in the diagnosis of tuberculosis].

OBJECTIVE: We evaluated a simplified method for processing three serial sputum samples as a single sample, and compare the results with those obtained when processing three samples individually. MATERIAL AND METHODS: During a 32-week period, we studied 867 sputum samples from 289 patients with pulmonary tuberculosis suspicious. Samples from 148 patients (n = 444) were processed by simplified method, and samples from 141 patients (n = 423) were processed by individually method. All cultures were processed by ESP Culture System II (Difco Laboratories, USA). RESULTS: Seven mycobacterium's strains were isolated by individually method. Simplified method detected another seven strains. In both cases, four strains were identified as Mycobacterium tuberculosis. Mean time to detection mycobacteria were 21.5 and 24 days for simplified and individually method, respectively. Cultures from 21 patients were contaminated (11 patients by simplified method and 10 patients by individually method). Mean time to detection contaminated cultures were 8 days and 7.5 days for simplified and individually method, respectively. CONCLUSION: Simplified method may be a useful alternative in laboratories that must handle increasing numbers of samples, without decline in diagnostic performance.

Bacteriological Techniques↗

Autosomal dominant nocturnal frontal lobe epilepsy in a Spanish family with a Ser252Phe mutation in the CHRNA4 gene.

BACKGROUND: A large family with autosomal dominant nocturnal frontal lobe epilepsy from the south of Spain was studied. The clinical appearance of the disease in this family, which included 28 members, of whom 11 were affected and 2 were obligate carriers, was identical to that previously described in an Australian family and a Norwegian family, in which mutations in exon 5 of the CHRNA4 gene were found. METHODS: Following DNA extraction, the family was genotyped with 4 fluorescent markers flanking the locus to the CHRNA4 gene on chromosome 20q13.3, and lod score computations were performed. The exon 5 of the CHRNA4 gene was amplified between nucleotides 535 and 825 and polymerase chain reaction products were purified and sequenced directly. RESULTS: The same missense mutation as that found in the Australian family, C-->T, which causes the replacement of a serine with phenylalanine in amino acid 252 in exon 5, was detected. This mutation segregated with the disorder in all 11 affected members, in the 2 obligate carriers, and in 1 asymptomatic sibling, and was not found in 1 spouse and 1 daughter. Neither of the 2 polymorphisms found in a series of families with epilepsy were found in our sample [corrected]. CONCLUSIONS: These data confirm the clinical homogeneity in the phenotypic expression of autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in the CHRNA4 gene, and the pathogenic role of the Ser252Phe mutation in this disorder.

Adult↗

Prenatal diagnosis of fragile X syndrome: (CGG)n expansion and methylation of chorionic villus samples.

Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)n trinucleotide repeat in the FMR-1 gene and hypermethylation of its 5' upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR-1 gene. In the ten 'at-risk' CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not 'at risk' for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR-1 gene in chorionic villus tissues.

Blotting, Southern↗

Accuracy of teleradiology in skeletal disorders: solitary bone lesions and fractures.

To evaluate the diagnostic accuracy of digitized film radiography and digital teleradiology for detecting bone fractures and for studying solitary bone lesions, we examined 633 single radiographs from 373 patients (159 with solitary bone lesions, 123 with fractures and 91 without pathology). Radiographs were digitized using a commercial teleradiology workstation and transmitted to a local hospital over a standard telephone line. Images were reviewed by two groups of three experienced radiologists. Receiver operating characteristic (ROC) curves were analysed for conventional films, digitized images and transmitted teleradiology images. No significant differences were found among readers for the evaluation of bone fractures and solitary bone lesions. Teleradiology systems permit remote expert consultation, and telediagnosis therefore is a powerful tool in telemedicine.

Bone Diseases↗