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Biomedical subjects

R Pujol

Publications and source records attributed to R Pujol.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea.

Efferent feedback systems provide a means for modulating the input to the central nervous system. The lateral olivocochlear efferents modulate auditory nerve activity via synapses with afferent dendrites below sensory inner hair cells. We examined the effects of dopamine, one of the lateral olivocochlear neurotransmitters, by recording compound and single unit activity from the auditory nerve in adult guinea pigs. Intracochlear application of dopamine reduced the compound action potential (CAP) of the auditory nerve, increased the thresholds and decreased the spontaneous and driven discharge rates of the single unit fibres without changing their frequency-tuning properties. Surprisingly, dopamine antagonists SCH-23390 and eticlopride decreased CAP amplitude as did dopamine. In some units, both SCH-23390 and eticlopride increased the basal activity of auditory nerve fibres leading to an improvement of threshold sensitivity and a decrease of the maximum driven discharge rates to sound. In other units, the increase in firing rate was immediately followed by a marked reduction to values below predrug rates. Because CAP reflects the summed activity of auditory nerve fibres discharging in synchrony, both the decrease in sound-driven discharge rate and the postexcitatory reduction account for the reduction in CAP. Ultrastructural examination of the cochleas perfused with eticlopride showed that some of the afferent dendrites were swollen, suggesting that the marked reduction in firing rate may reflect early signs of excitotoxicity. Results suggest that dopamine may exert a tonic inhibition of the auditory nerve activity. Removal of this tonic inhibition results in the development of early signs of excitotoxicity.

Acoustic Stimulation↗
PubMed2001

Prevalence of psoriasis in Spain (Epiderma Project: phase I).

BACKGROUND: Various national and international studies are under way to obtain reliable data on the epidemiological features of psoriasis. OBJECTIVES: The purpose of this study was to determine the prevalence of psoriasis in the general population in Spain as well as its variations according to sex, age and distribution in different geographical areas. MATERIAL AND METHODS: A random sample (12,938 subjects from 4027 households), representative of the general population, was the basis for a cross-sectional survey through telephone calls performed by trained non-medical interviewers using a specific questionnaire. RESULTS: The prevalence of psoriasis, similar in both sexes, was estimated to be 1.17-1.43%. The highest prevalence rates were shown among 20-50-year-old subjects. Distribution of psoriatic patients was not homogeneous throughout the country and prevalence was shown to be higher in the central dry region of the country. CONCLUSIONS: In a population of about 40 million inhabitants, 470,000-570,000 psoriatic subjects constitute an important target for health care issues and further epidemiological studies.

Adolescent↗
PubMed2001

Improvement in endothelial dysfunction in patients with hypoalphalipoproteinemia and coronary artery disease treated with bezafibrate.

Isolated low high-density lipoprotein cholesterol (HDLc) is a well-known risk factor for cardiovascular disease and is associated with arterial endothelium dysfunction. Several studies have shown that cholesterol lowering in patients with hypercholesterolemia improves endothelial function, but the effect of treating low HDLc levels remains unknown. We studied the effect of increasing HDLc on endothelial function in patients with coronary artery disease (CAD) and isolated low HDLc (HDLc) <0.91 mM, low-density lipoprotein cholesterol (LDLc) <4.1 mM, and triglycerides <2.8 mM. Flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperemia was measured by brachial ultrasound, before and after bezafibrate treatment (400 mg daily for 6 months) in 16 patients with CAD and impaired FMD (<10%). After bezafibrate therapy, HDLc increased from 0.79-1.0 mM (p = 0.0008) at the expense of both HDL2 and HDL3 subfractions, apolipoprotein A-I increased from 1.04-1.19 g/l (p = 0.0012), and fibrinogen decreased from 4.45-3.39 g/l (p = 0.0007). The impaired FMD increased after bezafibrate treatment from a median of 2.5-12.3% (p = 0.0004). Endothelial function was normalized in eight patients (50%), improved in four (25%), and did not change in four (25%). These observations indicate that in patients with isolated low HDLc and CAD, bezafibrate treatment improves endothelial function of brachial arteries, increases HDLc and apolipoprotein A-I, and lowers fibrinogen concentrations.

Aged↗
PubMed2001

Lipid and lipoprotein levels in premenopausal systemic lupus erythematosus patients.

The purpose of this study was to assess the prevalence of dyslipoproteinemia and to analyze the clinical variables that are associated with it in a sample of premenopausal systemic lupus erythematosus (SLE) patients. We studied 53 premenopausal (34.5 y) SLE outpatients and 45 controls. Clinical variables studied included patient age, weight, height, body mass index (BMI), age at disease onset, disease duration, clinical activity of SLE, renal involvement and drug therapy. Total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides were measured using standard enzymatic techniques. Apolipoproteins (apo) A-I and B were determined by radial immunodiffusion. Twenty-nine patients (55%) and 14 controls (30%) had dyslipoproteinemia. An increase in TC, triglycerides, HDL3-C, apo A-I and apo B, and a decrease in HDL2-C and HDL-C/TC index was found in SLE patients in comparison with controls. TC (P = 0.007), apo B (P = 0.02), LDL-C (P = 0.03) and triglycerides (P = 0.0001) were significantly correlated with proteinuria. Patients on prednisone therapy had higher triglycerides levels (P = 0.03) than untreated patients. TC (P = 0.01), LDL-C (P = 0.006) and triglycerides (P = 0.04) were also correlated with the dose of prednisone. Dyslipoproteinemia is a common feature in adult SLE premenopausal patients which is characterized by an increase in TC, triglycerides and apo B, and an abnormal distribution of HDL subclasses. Corticosteroid therapy and proteinuria are the best predictors of dyslipoproteinemia in these patients.

Adult↗
PubMed2000

The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea.

The role of AMPA receptors in cochlear synaptic transmission and excitotoxicity was investigated by comparing the actions of a selective AMPA antagonist GYKI 53784 (LY303070) with additional AMPA/kainate antagonists, GYKI 52466 and DNQX, and the NMDA antagonist, D-AP5, in several electrophysiological, neurotoxicological and histochemical tests. GYKI 53784 had the same potency as DNQX and was 10 times more potent than GYKI 52466 in reducing auditory nerve activity. The NMDA antagonist D-AP5 had no effect on auditory nerve activity. When single-fiber activity was blocked with GYKI 53784, the effects of AMPA or kainate were also antagonized. GYKI 53784 completely blocked excitotoxicity (i.e. destruction of the afferent nerve endings) induced by AMPA and kainate. The histochemical detection of Co(2+) uptake was used to study Ca(2+) influx within the primary auditory nerve cells. Application of AMPA induced no significant Co(2+) uptake into the cells, suggesting that these receptors normally have a very low permeability to Ca(2+). Application of kainate induced significant Co(2+) uptake that was blocked by the AMPA receptor antagonist GYKI 53784 suggesting that kainate stimulated Ca(2+) entry through AMPA receptor channels. Results suggest that AMPA-preferring receptors are functionally located at the sensory cell-afferent synapse whereas NMDA and kainate receptors are not.

Action Potentials↗
PubMed2000

Influence of serum amyloid A on the decrease of high density lipoprotein-cholesterol in active sarcoidosis.

OBJECTIVE: We have previously observed low levels of high density lipoprotein (HDL) cholesterol in active sarcoidosis. The aim of this study was to analyze the role of serum amyloid A (SAA) on this lipid disorder. METHODS: Eighty five untreated sarcoid patients, 40 with active disease and 45 with inactive disease, were recruited. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL(2)-cholesterol, HDL(3)-cholesterol, apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and triglyceride concentrations. Serum amyloid A protein and lecithin-cholesterol acyltransferase (LCAT) activity were measured. RESULTS: In active sarcoidosis we found significantly reduced levels of HDL-cholesterol (1.17+/-0.36 vs. 1. 44+/-0.39 mmol/l, P=0.002), HDL(3)-cholesterol (0.78+/-0.23 vs. 1. 02+/-0.21 mmol/l, P<0.0001), and apo A-I (1.36+/-0.29 vs. 1.61+/-0. 27 g/l, P<0.0001) and significantly increased levels of triglyceride (1.51+/-0.64 vs. 1.03+/-0.46 mmol/l, P<0.0001), and apo B (1.14+/-0. 25 vs. 0.99+/-0.27 g/l, P=0.012) versus inactive sarcoidosis. Serum amyloid A concentrations were significantly increased in the patients with active disease (155.45+/-154.01 mg/ml) compared to the inactive sarcoid patients (89.70+/-65.36 mg/ml) (P=0.011). There were no significant differences in cholesterol, LDL-cholesterol, HDL(2)-cholesterol or LCAT values between groups. Multivariate logistic regression analysis showed that HDL-cholesterol (regression coefficient b=-1.96; S.E.=0.87; P=0.02) and SAA (regression coefficient b=0.01; S.E.=0.004; P=0.01) were the two variables independently associated with disease activity. Moreover, a significant negative correlation was observed between SAA levels and both HDL-cholesterol (r=-0.39; P=0.01) and apo A-I (r=-0.35; P=0.03) levels, in the active sarcoid group. Conversely, no correlation was found in the inactive sarcoid group. CONCLUSION: The low HDL-cholesterol and apo A-I concentrations seen in active sarcoid patients are associated with a significant increase of SAA levels. We suggest that the displacement of apo A-I by SAA on HDL accounts for the lower level of HDL-cholesterol seen in active sarcoidosis.

Adult↗
PubMed2000

[Seroepidemiological study of brucellosis in a rural endemic area].

BACKGROUND: This study investigated the prevalence of Brucella spp. antibodies in the general population in the Health Area of Tremp (Region of Pallars Jussà, Lleida). It also identified the risk factors with the presence of these. PATIENTS AND METHODS: A total of 346 (191 men and 155 women) were studied. Information about the sex, age, location, the personal and familiar antecedents of brucellosis, occupational risk, contact with the animals and the consumption of non-hygienic dairy products was recorded. The estimation of the seroprevalence was carried out by the ELISA IgG test. The association of independent variables with the presence of antibodies was assessed by the Coombs to Brucella and the ELISA IgG tests. It was assessed by using the calculation of the analysis variance. RESULTS: The personal antecedents, the contact with the animals and the occupational risk all showed a statistically significant relation (p < 0.05) with the Coombs and ELISA IgG tests. The familiar antecedents showed a significant relation with the ELISA IgG. The consumption of dairy products and the location showed no statistically significant relation. A seroprevalence was obtained among the researched population of 11.9%, the maximum occurred in Isona surgery (25.6%) and the minimum in Tremp (9.8%). CONCLUSIONS: The seroprevalence is high and the epidemiological profile associated with the fact of being seropositive is associated with the profession of the study subject and it coincides with de infection mechanisms present in the area.

Adolescent↗
PubMed2000

[Regenerative potential in the organ of Corti after otic intoxication].

The auditory sensory cells are sensitive to a variety of influences such as noise, ototoxic drugs and aging. In the cochlea of mammals, the destroyed sensory cells are not replaced by new sensory cells. That leads to cochlear deafness, a frequent disease in human. Unfortunately, such auditory impairment is out of reach of treatment. The development of new therapeutic strategies in this field requires a precise knowledge of the mechanisms involved in auditory sensory cells disappearance and in organ of Corti's degeneration. The aim of our study was to characterize cellular and molecular changes in the cochlea of rats which had been intoxicated with the ototoxic antibiotic amikacin. The animals were sacrificed at different survival times during and after the antibiotic treatment and their cochleas were investigated using transmission and scanning electron microscopy and using confocal microscopy after tissue labellings with different fluorescent probes. The results revealed the existence of three periods. The first one corresponds to the disappearance of the sensory cells which die by apoptosis. During the second period, the organ of Corti undergoes a scarring process; concomitantly, a contingent of nonsensory supporting cells attempts to transdifferentiate directly into sensory cells. This process however fails, and the supporting cells never reach the status of hair cells. A general process of dedifferentiation of all the epithelial cells of the organ of Corti followed by a massive apoptosis of numerous epithelial cells and of most ganglion cells occurs during the third period. After that, the organ of Corti is definitely reduced to a simple monolayered epithelium. On the basis of these data, experimental strategies aimed i) to protect the sensory cells against apoptosis and ii) to promote sensory cell regeneration are now under study. They might have important implications in human therapy.

Amikacin↗
PubMed1999

Excitotoxicity, synaptic repair, and functional recovery in the mammalian cochlea: a review of recent findings.

Besides its fast excitatory properties, glutamate is known to have neurotoxic properties when released in large amounts or when incompletely recycled. This so-called excitotoxicity is involved in a number of acute and/or degenerative forms of neuropathology such as epilepsy, Alzheimer's, Parkinson's, stroke, and retinal ischemia. In the cochlea, excitotoxicity may occur in two pathological conditions: anoxia and noise trauma. It is characterized by a two-step mechanism: (1) An acute swelling, which primarily depends on the AMPA/kainate type of receptors, together with a disruption of the postsynaptic structures (type I afferent dendrites) resulting in a loss of function. Within the next 5 days, synaptic repair may be observed with a full or a partial (acoustic trauma) recovery of cochlear potentials. (2) The second phase of excitotoxicity, which may develop after strong and/or repetitive injury, consists of a cascade of metabolic events triggered by the entry of Ca2+, which leads to neuronal death in the spiral ganglion. Ongoing experiments in animals, tracking the molecular basis of both these processes, presages the development of new pharmacological strategies to help neurites to regrow and reconnect properly to the IHCs, and to prevent or delay neuronal death in the spiral ganglion. Human applications should follow, and a local (transtympanic) strategy against cochlear excitotoxicity may, in the near future, prove to be helpful in ischemic- or noise-induced sudden deafness, as well as in the related tinnitus.

Animals↗
PubMed1999

AMPA-preferring glutamate receptors in cochlear physiology of adult guinea-pig.

1. The present study was designed to determine which glutamate (Glu) receptors are involved in excitatory neurotransmission at the first auditory synapse between the inner hair cells and the spiral ganglion neurons. 2. The Glu receptors present at the membrane level were investigated on isolated spiral ganglion neuron somata from guinea-pigs by whole-cell voltage-clamp measurements. Glu and AMPA induced a fast onset inward current that was rapidly desensitized, while kainate induced only a non-desensitizing, steady-state current. NMDA induced no detectable current. 3. To further discriminate between the AMPA and kainate receptors present, we used the receptor-specific desensitization blockers, cyclothiazide and concanavalin A. While no effect was observed with concanavalin A, cyclothiazide greatly enhanced the Glu-, AMPA- and kainate-induced steady-state currents and potentiated Glu-induced membrane depolarization. 4. To extrapolate the results obtained from the somata to the events occurring in situ at the dendrites, the effects of these drugs were evaluated in vivo. Cyclothiazide reversibly increased spontaneous activity of single auditory nerve fibres, while concanavalin A had no effect, suggesting that the functional Glu receptors on the somata may be the same as those at the dendrites. 5. The combination of a moderate-level sound together with cyclothiazide increased and subsequently abolished the spontaneous and the sound-evoked activity of the auditory nerve fibres. Histological examination revealed destruction of the dendrites, suggesting that cyclothiazide potentiates sound-induced Glu excitotoxicity via AMPA receptors. 6. Our results reveal that fast synaptic transmission in the cochlea is mainly mediated by desensitizing AMPA receptors.

Animals↗
PubMed1999

Sequential changes in anti-GAL-1 staining of the rat organ of Corti following amikacin exposure.

Hair cell loss and a non-functional epithelial reorganization appeared in the organ of Corti after acoustic or toxic damage. Moreover, in the drug damaged organ of Corti, transient atypical cells were recently described with characteristics of both immature hair cells and/or non-sensory epithelial cells. The phenotype of these atypical cells has been now investigated by using the galectine 1 (GAL-1) antibody. In the normal organ of Corti, this antibody recognizes all the epithelial cells except the sensory hair cells and their supporting cells. At PD 21, transient atypical cells were not stained by GAL-1 antibody, suggesting that they were originated from hair cells or their supporting cells. Later, the organ of Corti was substituted by an epithelial scare, GAL-1 stained. This study also emphasizes the particular resistance of the cochlear apex to degeneration after antibiotic intoxication.

Amikacin↗