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Biomedical subjects

J Valverde

Publications and source records attributed to J Valverde.

At least 37 records · Page 2Linked to original sources

Senescent erythrocytes: modification of rheologic properties, antigenic expression and interaction with monocytes.

Human erythrocytes have a well-defined lifespan of 120 days. Their eventual removal from circulation is a complex process affected by many cellular parameters, making them susceptible to sequestration in the spleen and other organs. The purpose of this study was to investigate putative changes in rheologic properties, antigenic expression and interaction with monocytes of senescent erythrocytes (SE). SE and young erythrocyte (YE) fractions were obtained by differential centrifugation from 20 healthy donor blood samples. Membrane rheomechanic properties (by diffractometric method), ABO and MN antigens reactivity and erythrophagocytosis by peripheral monocytes were investigated in each fractions. SE showed a little decrease in the deformability index and an increase of both membrane elastic modulus and surface viscosity. The studies performed indicate a decreased expression in the antigens of both blood group systems studied (p < 0.01) and an increased rate of erythrophagocytosis by monocytes in SE compared to YE (p < 0.01). The significant modifications in the biomechanic properties of senescent red blood cell membrane and the loss of antigenic expression could lead to physiological phagocytosis.

Antigens↗

[Blood preservation. Bacteriological, immunohematological, hematological and hemorrheological studies].

The knowledge of erythrocyte viability during blood bank storage period has been a major problem for transfusional practice. This problem must be considered by taking into account blood flowing properties which are directly related to the rheological properties of erythrocytes. The aim of this work was to perform an interdisciplinary study of the modifications induced in erythrocyte properties during 29 days storage of whole blood in a blood bank. Three samples of venous blood collected from healthy adults in plastic bags, anticoagulated with ACD (citric acid, citrate, dextrose) and stored at 4 degrees C were studied. Rheological properties (deformability, membrane elasticity and surface viscosity), immunohematological conditions (antigenicity) of erythrocytes, haematological index variation and bacteriological cultures of blood were weekly analysed. Rheological studies were performed using the Erythrodeformeter, a polymicroviscosimeter (paper filter) and erythrocyte filtration through polycarbonate membranes of 5 microns pore diameter. Impairment of membrane rheological properties, loss of antigenicity and decreases of Ht, Hb, MCHC and MHC were observed. Bacteriological cultures gave always negative results. The studies performed showed significant alterations of erythrocyte rheological parameters. It becomes evident that such modifications would influence the erythrocyte mechanical behavior in microcirculation and impair the in vivo viability of the transfused red cells.

Adult↗

Effect of complement on the rheological properties of the erythrocyte membrane.

The effect of complement (C) on the erythrocyte deformability was investigated. Sheep erythrocytes (E) were sensitized with specific antibodies (A) and treated with various doses of human C. Gravity filtration of unlysed EAC showed a C dose-dependent decrease in whole cell deformability, which was shown to be due to an impairment of the membrane rheological properties. As the fluidity of the lipid bilayer, sensed by a spin label, was not modified, the observed effects should be related to an interaction between C and the cytoskeleton. The influence of C3b and C3d in these processes seems unlikely, as similar hemagglutination titers were found, respectively, for anti-C3c and anti-C3d antisera against the varying EAC. The study of the degree of spontaneous hemolysis of EAC in buffers with solutes of different Stokes radii showed that differing-sized functional C lesions were produced, and that the formation of larger-sized lesions was favored by incubation with higher C doses. These results suggest that the insertion of proteins from the membrane attack complex, C5b-9 (MAC), into the erythrocyte membrane may be responsible for the effect of C on the rheological properties of the erythrocyte membrane.

Animals↗

[Diarrhea associated with Clostridium difficile. One-year retrospective study at a tertiary hospital].

BACKGROUND: Diarrhea associated with Clostridium difficile is a health care problem of growing importance in the last few years specially in the hospital environment. The epidemiologic data and factors associated with this disease have not, to date, been sufficiently studied in Spain. METHODS: The cases of diarrhea associated with C. difficile reported in 1996 in a tertiary hospital of 1,500 beds were retrospectively reviewed, collecting clinical and epidemiologic data. The technique used for the detection of the C. difficile toxin was EIA Premier. RESULTS: One hundred thirty-two patients were included in the study, 83.3% of whom were over the age of 65 years, who had had 148 episodes of diarrhea associated with C. difficile. Most had been admitted into internal medicine (36%) or in the geriatric department (25%) and the remaining in the surgical departments (16.4%) or others (22.6%). The most frequently prescribed antibiotics were third generation cephalosporins (28.6%), clindamycin (17%), quinolones (11.1%) and macrolides (9.1%). Most of the patients received from 2 to 4 antibiotics prior to presenting diarrhea. Thirteen percent of the episodes of diarrhea associated with C. difficile were exclusively treated with withdrawal of the prescribed antibiotic, while the remaining cases were also given specific treatment which in 68.6% of the cases was with metronidazole and 31.4% with vancomycin. No significant difference was observed in the evolution of the patients according to the antibiotic prescribed. CONCLUSIONS: Diarrhea associated with C. difficile should be taken into account as a frequent complication of wide spectrum antibiotic treatment, specially in the elderly, immunosuppressed or in patients with pluripathology. With this study the authors wish to underline the need for the judicious use of antibiotics in the hospital environment and aid in the rapid diagnosis of this entity.

Adult↗

Treatment of chronic hepatitis C with interferon-alpha. Clinical histological and virological implications.

OBJECTIVE: to identify pretreatment predictive factors of long-term biochemical and virological response to interferon-alpha in chronic hepatitis C and to determine the effects of a second course of interferon-alpha in patients who responded but relapsed after interferon withdrawal. DESIGN: retrospective analysis. SETTING: outpatient liver clinic of a tertiary hospital in Spain. PATIENTS: 112 patients with chronic hepatitis C were treated with recombinant interferon-alpha (3 MU three times a week for 6 months). Twenty-four patients who responded but relapsed after interferon withdrawal were treated with a second course of interferon (3 MU three times a week for 12 months). RESULTS: seventy-two patients were non-responders (64%), 11 patients had a sustained response (10%) and 29 patients responded but relapsed after interferon withdrawal (26%). Five (25%) of the 24 patients who relapsed and were treated with a second course of interferon experienced a sustained response (mean follow-up: 10 months). By multivariate analysis, four pretreatment variables were found to be predictive of a complete response: age < 40 years (p = 0.0004), history of IVDA (p = 0.001), low serum levels (p = 0.013), and genotype 3 (p = 0.01). Two variables were found to be predictive of a sustained response: short duration of HCV infection (p = 0.09) and genotype 3 (p = 0.01). Sustained responders appeared to have lower HCV-RNA levels than those with complete response who relapsed and non-responders. HCV viremia levels were not associated with the severity of liver histology, duration of disease or the source of hepatitis. CONCLUSIONS: in the present study a low sustained response rate was observed using a standard interferon-alpha regimen (3 MU three times a week for 6 months). The sustained response rate increased slightly with a second course of interferon-alpha (3 MU three times a week for 12 months) in patients with a complete response who relapsed after interferon withdrawal. Sustained response is related to viral genotype and duration of HCV infection.

Adolescent↗

[Osteonecrosis in systemic lupus erythematosus. Report of 3 cases].

We present three cases of patients with systemic lupus erythematosus (SLE) and osteonecrosis or avascular necrosis (AV). Although, the pathogenesis of osteonecrosis is controversial and multifactorial, the glucocorticoids therapy is the most important factor contributing to the lesion. We report the clinical presentation of the three patients. We comment the characteristics of AV, the diagnosis and the treatment of this uncommon complication in SLE patients.

Adult↗

Regulated release and polarized localization of brain-derived neurotrophic factor in hippocampal neurons.

The site and regulation of neurotrophic factor release from neurons is poorly understood. We used a combination of model cell lines and primary culture systems to study the polarity of BDNF sorting and the regulation of its release from hippocampal neurons. Transfection and expression of a human BDNF cDNA in a mouse pituitary cell line, AtT20, resulted in the colocalization of BDNF with the secretory granule marker, chromogranin A. Furthermore, stimulation of these cells with 56 mM KCl or with 5 mM 8-bromo-cAMP increased the release of BDNF approximately 10-to 15-fold within 30 min. To study BDNF release from primary cultures of hippocampal neurons, cells were infected with a defective Herpes Simplex Viral (HSV) vector expressing human BDNF. Depolarizing conditions increased the release of BDNF 5-fold from these cells, further verifying that secretion is regulated. Immunocytochemical analysis using highly specific antibodies determined that endogenous BDNF was predominantly localized to the somatodentritic domain of hippocampal neurons. These findings support the view that BDNF functions as a target-derived signal for afferents to hippocampal pyramidal cells and that it may serve as a regulator of hippocampal plasticity.

Animals↗

GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis.

To test whether glial cell line-derived neurotrophic factor (GDNF) regulates the development of nigral dopaminergic neurons in vivo, neonatal rats received bilateral injections of GDNF into the striatum. Injections at postnatal day 2 induced a unique transient behavioral pattern characterized by forelimb hyperflexure, clawed toes of all limbs, and a kinked tail. Parallel to the behavioral changes, the levels of striatal and ventral mesencephalic dopamine and serotonin were increased from 60% to 100% with a proportional increase of principal metabolite levels. GDNF increased tyrosine hydroxylase activity in the ventral mesencephalon, but did not affect striatal activity of choline acetyltransferase and GABA uptake. GDNF failed to induce sprouting of dopaminergic neurites. Our findings suggest that during development striatal GDNF regulates the capacity of dopaminergic and of serotonergic neurons for neurotransmitter production and release.

Animals↗

Achalasia-like syndrome as the first manifestation in a patient with CREST syndrome.

We report a case of oesophageal disease as the first manifestation in a patient with CREST syndrome. A 46-year-old man with achalasia-like syndrome developed CREST syndrome 4 years later. A pneumatic dilatation of the cardia was performed. After pneumatic dilatation the dysphagia and regurgitation disappeared but the patient developed reflux oesophagitis. Four years after diagnosis of oesophageal disease he presented with a clinical picture of CREST syndrome. An acute ileus and constipation developed later. After receiving medical therapy with omeprazole and cisapride the patient is free of oesophageal symptoms and bowel movements are normal. Oesophageal disease is common in patients with limited and diffuse scleroderma, but to our knowledge achalasia-like syndrome has not been previously described as the first manifestation of the systemic disease.

Anti-Ulcer Agents↗

Periarticular ankle sarcoidosis: a variant of Löfgren's syndrome.

OBJECTIVE: To focus more attention on the syndrome characterized by periarticular ankle inflammation associated with bilateral hilar adenopathy--some authors regard it as a variant of the Löfgren syndrome, while other suggest it is a distinct clinical entity-- we present a series of 33 cases of periarticular ankle sarcoidosis. METHODS: Sarcoidosis was diagnosed in 330 patients at Bellvitge Hospital over a 20 year period. The medical charts of patients who presented with periarticular ankle inflammation (swelling of both ankles with acute inflammatory signs and preserved articular motion) were reviewed. RESULTS: 33 patients (10%) were identified. Periarticular ankle inflammation began during the spring in more than one-half (54.5%). The mean age was 33 years and patients were predominantly women (66.6%). Most cases (78.8%) were stage I on chest radiograph. All patients had thoracic gallium scans showing increased hilar/mediastinal uptake. Increased characteristic parotid, lacrimal, and/or submandibular uptake was found in 11 of 13 patients who had head scans. Four of 6 whose scans included the legs had bilateral ankle uptake. Erythema nodosum was present concomitantly in 36.3% of patients. No granulomas were found in 4 biopsies of periarticular ankle tissue. All 24 patients who were followed had inactive disease one year after diagnosis. CONCLUSION: The association of periarticular ankle inflammation with bilateral hilar adenopathy is an acute form of sarcoidosis that follows a benign course to total remission. It should be regarded as a variant of the Löfgren syndrome.

Adult↗

Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.

Glial-cell-line-derived neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra. These neurons participate in the control of motor activity, emotional status and cognition, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

Animals↗

Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons.

Homozygous Igf1-/- mice at 2 months of age had reduced brain weights, with reductions evenly affecting all major brain areas. The gross morphology of the CNS was normal, but the size of white matter structures in brain and spinal cord was strongly reduced, owing to decreased numbers of axons and oligodendrocytes. Myelinated axons were more strongly reduced in number than unmyelinated axons. The volume of the dentate gyrus granule cell layer was reduced in excess of the decrease in brain weight. Among populations of calcium-binding protein-containing neurons, there was a selective reduction in the number of striatal parvalbumin-containing cells. Numbers of mesencephalic dopaminergic neurons, striatal and basal forebrain cholinergic neurons, and spinal cord motoneurons were unaffected. Cerebellar morphology was unaltered. Our findings suggest cell type- and region-specific functions for IGF-I and emphasize prominent roles in axon growth and maturation in CNS myelination.

Animals↗

Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation.

REK7 is an Eph-related tyrosine kinase receptor expressed exclusively in the nervous system, predominantly in hippocampus and cortex. A soluble REK7-IgG fusion protein, produced to analyze the biological role of REK7, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. Using REK7-IgG as an affinity reagent, we purified and cloned a novel REK7 ligand called AL-1, a GPI-linked protein homologous to other members of an emerging ligand family. Membrane attachment of AL-1 appears necessary for receptor activation, since REK7 on cortical neurons is efficiently activated by transfected cells expressing GPI-linked AL-1, but not by soluble AL-1. Consistent with this, soluble AL-1 blocks axon bundling. Our findings, together with the observation that both molecules are expressed in the brain, suggest a role in the formation of neuronal pathways, a crucial feature of nervous system development and regeneration.

Amino Acid Sequence↗

[Methotrexate treatment of amyloidosis secondary to rheumatoid arthritis].

Amyloidosis secondary to rheumatoid arthritis is a complication with a poor prognosis and as yet an undefined medical therapy. In the last decades the use of different cytostatics has been advocated to avoid renal function deterioration. The clinical characteristics and course in eight patients with amyloidosis secondary to rheumatoid arthritis are here reported after therapy with low dosage methotrexate. In twelve patients who followed a 12-month therapy a clinical improvement was observed, with a marked decrease in proteinuria; in one of them proteinuria disappeared. These results suggest that methotrexate at low doses might be an alternative in the early treatment of amyloidosis secondary to rheumatoid arthritis in patients with preserved renal function.

Amyloidosis↗