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Biomedical subjects

J M Ferrer

Publications and source records attributed to J M Ferrer.

At least 19 recordsLinked to original sources

The binding of benzopyranes to human serum albumin. A structure-affinity study.

The binding of several benzopyranes to serum albumin was studied by equilibrium dialysis at pH 7.4 in a 67 mM sodium phosphate buffer at 37 degrees C. The equilibrium data were analyzed using a computer program for curve fitting. The binding isotherm for warfarin, 4-hydroxycoumarin, 4-chromanol, coumarin, 3-acetylcoumarin, and benzoic acid can be described by two stoichiometric dissociation constants. Elimination of the 4-hydroxyl group in the coumarin chemical structures decreases the binding affinity of the compounds on the primary binding site of serum albumin, with 4-chromanol the smallest ligand which binds to seroalbumin with high affinity. Thus, the affinity of 4-benzopyranol and the 4-hydroxybenzopyranones greater than that of benzopyranones. On the other hand, elimination of the 2-oxo group in the benzopyranone chemical structures decreases affinity for the secondary binding site.

Binding Sites

Electrophysiological and neurochemical study of the rat geniculo-cortical pathway. Evidence for glutamatergic neurotransmission.

The projection from the dorsal lateral geniculate nucleus to the primary visual cortex of the rat was studied electrophysiologically. Electrical stimulation of the dorsal lateral geniculate nucleus and the optic tract produced three types of responses on neurons of area 17: excitation followed by inhibition, excitation and inhibition. These results extend and confirm, in adult rats, previous studies done in rat geniculate-visual cortex cocultures preparations in vitro. The role of glutamate in the neurotransmission of the rat geniculo-cortical pathway was also investigated. In a first set of experiments, the effects of kynurenate, an antagonist of glutamate receptors, on visual cortex neurons with a monosynaptic excitatory response to dorsal lateral geniculate nucleus stimulation were studied. Microiontophoresis of kynurenate in area 17 neurons selectively suppressed the excitatory response to dorsal lateral geniculate nucleus and optic tract stimulation. In a second set of experiments, the effects of electrical stimulation of the dorsal lateral geniculate nucleus and the optic tract on the release of amino acids in the rat visual cortex in vivo were studied. Using the push-pull method, we perfused a discrete region of the visual cortex with artificial cerebrospinal fluid (CSF), and the amino acid content of the perfusates was analysed by high performance liquid chromatography (HPLC). Stimulation of either the dorsal lateral geniculate nucleus or the optic tract significantly increased glutamate release in area 17. The rest of the amino acids studied did not show significant changes. The results provide evidence for the participation of glutamate in the neurotransmission of the geniculo-cortical pathway in the rat.

Animals

[Image processing in the primary visual cortex].

INTRODUCTION: Area 17 or the primary visual area forms the first link in the chain of cerebral analysis of a visual image. The neurones forming the primary visual cortex are characterized by the extreme precision of their connections, functional specialization and hierarchic organization. The spatial precision of the connections within the system for vision permit retinotopic representation in the visual cortex, so that each point of the retina is projected into a specific area of the cortex. The cortical neurones which analyze the characteristics of the image situated in a precise zone of the visual field are themselves organized into a basic functional unit known as a hypercolumn. Within each hypercolumn there are various columnar cell systems with receptive fields having similar characteristics. Thus, each hypercolumn is made up of multiple orientation columns, two ocular dominance columns and 'blob' regions. All these systems permit the analysis of different aspects of the image. The neurones belonging to the orientation columns are sensitive to the orientation, spatial frequency and movement of a visual stimulus; those of the 'blob' regions to colour, and the binocular neurones of the ocular dominance columns to depth. Within each column, the hierarchical pattern of neurone interconnections determines the successive appearance of cells with receptive fields having new properties.

Geniculate Bodies

[Transitory episode of laughter as the initial symptom of an ischemic stroke].

INTRODUCTION: Pathological laughter occurs in pseudobulbar paralysis, in psychiatric disorders and as a sign of convulsions (gelastic crisis). An extremely rare form is the "fou rire prodromique' a pathological episode of laughter preceding a stroke. The pathogenesis is unknown and classically differentiated from gelastic crises. "Fou rire prodromique' has been described in subcortical ischaemic or haemorrhagic strokes, not in cortical strokes. CLINICAL CASE: We describe a patient with an ischaemic cerebrovascular accident due to embolism of the left Sylvian artery. The clinical picture started with a short episode of pathological laughter which preceded sensitive aphasia and weakness of the right limbs. CONCLUSIONS: We suggest that in the case described it is impossible to differentiate between the "fou rire prodromique' and a gelastic crisis as a first sign of an embolic cerebrovascular accident.

Aged

Peptidase inhibitors potentiate the effects of neurotensin and neuromedin N on self-stimulation of the medial prefrontal cortex.

The purpose of this study was to examine the possible role of endogenous peptidases in the inhibition of intracranial self-stimulation (ICSS) produced by injections of neurotensin (NT) and neuromedin N (NN) into the medial prefrontal cortex (MPC) of the rat. We studied the effects on ICSS of the MPC of the administration of thiorphan and bestatin, two specific inhibitors of the peptidases that inactivate NT and NN respectively. Microinjections into MPC of thiorphan (10 micrograms) and bestatin (25 micrograms) potentiated in inhibition of ICSS produced by the intracortical administration of NT (10 nmol) and NN (20 nmol) respectively. This potentiation affected both the amplitude and the duration of the inhibition of ICSS produced by the neuropeptides. Our data indicate that endogenous peptidases are involved in the inactivation of NT and NN in the prefrontal cortex.

Animals

Estimates of the convergence of association projections from area 17 to rostral area 18 in the cat depend on injection site size.

To estimate the degree of convergence of corticocortical projections from area 17 to the rostral part of area 18 in the cat, we injected the retrograde tracer diamidino yellow either at single or multiple adjacent sites in area 18. We measured the diameters of the individual or larger composite injections and the diameters of the labelled regions in area 17; from these values we estimated convergence factors. Small injections led to underestimates of the overall convergence of this pathway. A maximal value for convergence (about 3 mm) was obtained with larger composite injections (above about 3 mm in diameter). These results indicate that some area 17-to-18 projections may arborize widely in area 18. Their detection may require that injected tracer covers a large portion of their arbors.

Amidines

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital.

1. A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). the proportion of suspected ADRs related to hospital admissions was 4.3%. 2. The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3. The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4. There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37-2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72-5.42). 5. The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group.

Child, Preschool

Mediation by neurotensin-receptors of effects of neurotensin on self-stimulation of the medial prefrontal cortex.

1 Intracortical microinjections of neurotensin (NT) selectively decreased intracranial self-stimulation (ICSS) of the medial prefrontal cortex in the rat. 2 To elucidate whether this effect is mediated by NT receptors or by the formation of NT-dopamine complexes, we investigated the effects on ICSS of intracortical microinjections of neurotensin (1-11), an NT fragment that forms extracellular complexes with dopamine but does not bind to NT receptors. 3 We also studied the effects of the peripheral administration of SR 48692, a selective antagonist of NT receptors, on the inhibition of ICSS produced by the intracortical administration of NT. 4 Unilateral microinjections of neurotensin (1-11) at doses of 10, 20 and 40 nmol into the medial prefrontal cortex did not change the basal ICSS rate of this area. 5 The intraperitoneal administration of SR 48692 at doses of 0.08 and 0.16 mg kg-1 30 min before microinjection of 10 nmol of NT into the medial prefrontal cortex, antagonized the inhibition of ICSS produced by the neuropeptide. 6 These results demonstrate that the inhibitory effect of NT on ICSS is mediated by NT receptors.

Animals

Binding of coumarins to site I of human serum albumin. Effect of the fatty acids.

It is known that binding site I on human serum albumin (HSA) consists of a zone of two overlapping regions: the specific binding region represented by warfarin binding and the specific binding region represented by azapropazone and phenylbutazone binding. In this paper binding parameters to defatted HSA and to HSA with fatty acids (molar ratio of fatty acid/HSA = 4) were compared. High-affinity binding sites for warfarin, 4-chromanol, 4-hydroxycoumarin, coumarin, 3-acetylcoumarin and phenylbutazone (759,549 M-1 > Ka > 67,024 M-1) constitute binding site I on HSA. In this binding area defatted HSA can bind two molecules of warfarin, but the presence of fatty acids diminish the binding capacity of warfarin to HSA (2 > n > 1).

Biological Transport

Alterations in interleukin secretion (IL-2 and IL-4) by CD4 and CD4 CD45RO cells from common variable immunodeficiency (CVI) patients.

The failure of B cells from CVI patients to secrete normal amounts of antibodies has been attributed either to an intrinsic B cell defect or to a lack of cooperation from T cells. In an attempt to improve the definition of the origin of this defect in one of the main cellular compartments, we studied the ability of helper CD4 cells and their CD4 CD45RO subpopulation from CVI patients to secrete interleukins (IL-2 and IL-4) in response to mitogen stimulation. We found that CD4 and CD4 CD45RO cells from some patients secrete abnormal amounts of interleukins (in general low levels of IL-2 and high levels of IL-4) upon stimulation with pokeweed mitogen (PWM). These irregularities may contribute to the defective differentiation of B cells in these patients.

Adolescent

Differential reactivity of structural components of eosinophil leucocyte granules as revealed by ethanolic phosphotungstic acid.

After glutaraldehyde fixation and ethanolic phosphotungstic acid (E-PTA) treatment before embedding, thin sections of rat bone marrow and large intestine showed a characteristic pattern of electron opacity in eosinophil leucocyte granules. In both mature eosinophils and precursor cells, the matrix appeared highly contrasted while the crystalline core revealed no electron density. Additional treatment of sections with uranyl acetate did not modify the contrasting pattern of eosinophil granules. The absence of electron dense reaction in the crystalline core after E-PTA treatment seems to originate from removal of core components. The selective reactivity of the matrix toward E-PTA could be a valuable ultrastructural marker for studies on the differentiation of specific granules along the maturation of eosinophil leucocytes.

Animals

[Adverse reactions from angiotensin-converting enzyme inhibitor drugs reported by the yellow card].

BACKGROUND: The aim of the present study was to analyze the adverse reactions (AR) to captopril (CP) and enalapril (EN) reported by voluntary notification by the yellow card (YC) over the first five years of the foundation of the Drug Surveillance Center of the Valencian Community. METHODS: The AR described were classified by organs and systems, evaluating the age and the sex of the patient, the indication for the drug, dosage used, and the level of health care assistance received since notification. Previous knowledge of the reported AR was analyzed, as was the possible relation of causality with the drug and severity of the same. The rates of notification were calculated with respect to the consumption of both drugs, expressed in daily dosage defined (DDD). RESULTS: Two hundred one YC were evaluated, 111 for CP and 90 for EN referring 160 and 133 clinical manifestations, respectively. The rate of notification was 2.51 YC/million DDD for CP and 5.57 for EN. The AR in the respiratory tract were the most frequently reported with cases of dry cough representing 33.7% of the total YC for CP and 33.8% for EN. Cutaneous AR followed for both drugs. Angioedema was reported in 0.09 AR/million DDD for CP and 0.56 for EN. Reactions were most frequently observed in patients over the age of 50 with a predominance of the female sex, being usually slight and with 80% having been notified from primary health care centers. CONCLUSIONS: The high number of reports of cough demonstrate that this is the most frequently observed adverse reaction. The distribution of reactions and the characteristics of the patients with the same coincide with other studies. The low number of yellow cards reporting severe adverse reactions may support the favorable safety profile of this pharmacologic group, or, to the contrary, be a consequence of the under-reporting of adverse reactions.

Adult

Functional organization of corticocortical projections from area 17 to area 18 in the cat's visual cortex.

We used anatomical and physiological methods to study the functional organization of the association projection from area 17 to area 18 in the cat's visual cortex. Neurons in area 17 projecting to area 18 (revealed by retrograde transport of fluorescent tracer) tend to be clustered over regions of layer 4 receiving input from the ipsilateral eye (visualized by anterograde transneuronal tracing). Since the contralateral input overlaps these ipsilateral patches, the association cells lie preferentially in regions that are likely to be binocularly innervated. Indeed, almost all cells recorded electrophysiologically within the association clusters were strongly binocular, whereas between the clusters, many neurons were dominated by the contralateral eye. There is sufficient jitter in the retinotopic organization of area 17 for the discontinuous distribution of association cells to provide a continuous representation of the visual field. Cells in each association cluster in the rostral part of area 17 project divergently to innervate a zone extending up to 3 mm wide, anteroposteriorly, in the superficial layers of area 18. The receptive fields of cells at any point in area 18 are larger than for the corresponding point in area 17. Neurons recorded at two points in area 18, separated by a distance equal to the limit of anatomical divergence of the projection from area 17, have receptive fields that overlap by an amount similar to the region of visual field covered by the receptive fields of cells in a single association cluster in area 17 at a similar retinotopic position. Thus, area 18 receives a full and strongly binocular representation of the visual field not only from the lateral geniculate nucleus but also from area 17. The divergence of the area 17 to 18 projection compensates for the difference in receptive field size by ensuring that the receptive fields of each cluster of projecting neurons overlap fairly precisely those of the recipient neurons in area 18.

Amidines

Postnatal development and plasticity of corticocortical projections from area 17 to area 18 in the cat's visual cortex.

We used retrogradely transported fluorescent tracers to study the development of projections from area 17 to area 18 in normal and monocularly deprived kittens. In newborn animals, cells in area 17 that were labeled from small, discrete injections in area 18 were concentrated around the retinotopically corresponding zone, but distributed with lower density over a very wide surrounding area. Hence, the total convergence and divergence of the projection were initially enormous, but they decreased dramatically, mainly during the first postnatal month, through elimination of the sparse, widespread distribution of projections. Injections of two different tracers close together in area 18 produced very few double-labeled cells in area 17 at any age, implying that most individual axons arborize over very small territories even at birth. In normal kittens the peak density of association cells in the upper layers, corrected for the overall expansion of the cortex, doubled over the first postnatal month and then declined gradually over the following several months, presumably because of continuing selection and elimination. As shown in previous work (Price and Blakemore, 1985a), area 17 to 18 cells in newborn kittens were distributed in two continuous bands in supragranular and infragranular layers. During normal maturation, elimination of projections results in the formation of distinct clusters; these lie preferentially in the upper layers above patches of ipsilateral eye input to layer 4 (Price et al., 1994). Monocular deprivation, which causes the terminal patches representing the deprived eye to become much smaller than normal, did not stop the normal decrease in overall convergence/divergence or the appearance of clusters of association cells, but the clusters were distinctly larger than normal in both hemispheres. Monocular deprivation also prevented the normal reduction in density of association cells within clusters after 1 month of age. Comparison with results from binocularly deprived animals, where clusters also form but association cell density is low, suggests that the size of clusters and the density of association cells retained depend on the overall level of cortical activity.

Aging

SCH 23390 decreases self-stimulation of the medial prefrontal cortex in the rat.

We studied the effects of peripheral and central administration of SCH 23390, a selective antagonist of dopamine D1 receptors, on intracranial self-stimulation of the medial prefrontal cortex of the rat. Intraperitoneal injections of SCH 23390 produced a dose-related decrease in self-stimulation. Unilateral microinjections of SCH 23390 into the medial prefrontal cortex also produced a dose-related decrease in self-stimulation in the ipsilateral medial prefrontal cortex. However, self-stimulation of the contralateral, noninjected prefrontal cortex, used as control, was not affected. Together with previous data, the present results suggest that the dopamine neurotransmission involved in self-stimulation of the prefrontal cortex of the rat is mediated by dopamine D1 receptors.

Animals

Effects of neonatal ablation of area 18 on corticocortical projections from area 17 to extrastriate visual areas in cats.

Using retrogradely transported fluorescent dyes, we investigated the distributions of corticocortical neurones in area 17 projecting to area 19 and to the lateral suprasylvian visual area in a normal cat and two cats in which area 18 had been ablated at 4 days old. Cells projecting to area 19 were distributed in a much more continuous manner in the lesioned cats than in the normal one, whereas those projecting to the lateral suprasylvian cortex were located in discrete patches in all three cats. Neonatal ablation of area 18 can thus prevent the normally occurring developmental removal of neurones or their axons projecting from area 17 to area 19, but not the removal occurring in the projection from area 17 to the lateral suprasylvian cortex.

Animals