Enhancement of Antigen-specific functional responses by neutrophils from allergic patients.

It has been demonstrated that neutrophils from healthy donors or from patients with inflammatory disorders can bind immunoglobulin (Ig) E proteins through binding to Mac-2/epsilon bp. Functional responses to allergens were assessed by measuring the respiratory burst and intracellular Ca2+ levels, and binding of allergens to neutrophils was assessed by flow cytometry analysis and fluorescence microscopy. In this article, we demonstrate that neutrophils sensitized to specific allergens (from allergic patients), but not from healthy donors, are sensitive to allergens of the same type as those that produce clinical allergic symptoms. The activation of neutrophils was analyzed by the induction of a respiratory burst that was detected with luminol-dependent chemiluminescence. Intracellular Ca2+ levels increased parallel to those of the inducing allergens. In addition, the specific binding of allergens on the cell surface was revealed by flow cytometry and allergen-FITC-labeled staining analyses. The present data suggest a restricted recognition of allergen by sensitive neutrophils, probably associated with the specific binding of the allergen to its corresponding IgE molecule, which is bound to the Mac-2/epsilon bp structure. These findings demonstrate a functional role of allergen-associated neutrophils during the allergic state.

[Clinical experience in the treatment of motor fluctuations in Parkinson's disease. Delphi consensus of a group of experts in movement disorders]. / Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.

INTRODUCTION: Motor fluctuations are one of the most common complications of Parkinson's disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT: Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION: The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations.

TITLE: Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.Introducción. Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. Desarrollo. Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. Conclusión. El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motoras.

Neuronal loss and neuronal atrophy. Computer simulation in connection with Alzheimer's disease.

A decrease in the number of neuronal profiles in the isocortex of man may be observed on microscopic sections in aging and in degenerative diseases such as Alzheimer's disease. It can be the consequence of a loss of neurons per unit volume or of a reduction of the neuronal volume (i.e. pseudo-loss). This latter possibility has been tested by simulating neuronal atrophy, with sections of various thicknesses. An unfolding algorithm was used for the simulation. The data published in the current literature concerning Alzheimer's disease were treated with the unfolding algorithm. The neocortical pseudo-loss did not exceed a few percentage points, probably much less than the measurement error. New methods of cell counting have been recently proposed to discriminate real from pseudo-loss. They should be used when the risk of dealing with pseudo-loss is high. A chart to assess the percentage of pseudo-loss as a function of perikaryal atrophy is proposed: it relies on the evaluation of the size of the cell relative to the section thickness (relative caliper diameter). This chart may be used to correct cell counts of homogeneous cell populations.

Arsenic-cadmium interaction in rats.

Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone.

Plasma kallikrein amidolytic activity in patients with urticaria.

We have studied the plasma kallikrein amidolytic activity in healthy control subjects (inactive), patients with chronic urticaria (active) and patients with acute urticaria (active) from their admission to the emergency room (active) to the time after which their clinical symptomatology had disappeared (inactive). We found statistically significant differences (p < 0.01) in the active groups of urticaria patients. This leads us to believe that kallikrein participates in the development of symptomatology in these patients.

Production of soluble CD23 from peripheral blood lymphocytes of asthmatic patients.

The low-affinity receptor IgE (Fc epsilon RII) as shown to be identical to CD23 several years ago. The presence of the CD23 was demonstrated on a variety of human cells, such as T cells, monocytes, eosinophils, platelets, lymphocytes B, etc., and it can be cleaved in soluble fragments. We studied the in vitro production of soluble CD23 (sCD23) in PBMC of patients with bronchial asthma and in healthy donor cells. If we stimulate production with a polyclonal activator [Phytohemagglutinin (PHA) at a concentration of 10 micrograms/ml], it can be seen that the greatest amounts of sCD23 are produced on the fourth day and that production is greater in asthmatic patients than in control group (p < 0.01). When stimulated additionally by an antigen, the production of sCD23: Is greater when stimulated with PHA. Is released in quantities greater than in healthy group cells, when the PBMC are stimulated with the antigen to which the patients are sensitive (olive pollen). The quantity released depends on the concentration of the antigen added to the culture. Is not released in greater quantities by healthy groups cells in the presence of the antigen than in healthy group cells without the antigen. Is not released in greater quantities by cells of asthmatics in the presence of an antigen to which they are not sensitive (D. pteronyssinus). This leads us to conclude that the release of sCD23 in these patients could play a role in the physiopathology of extrinsic bronchial asthma.

Relationship of blood EG2+ eosinophils in patients with bronchial asthma.

The presence of eosinophils in peripheral blood has been previously associated with different degrees of activity in the evolution of disease in asthmatics. The eosinophil cationic protein is a mediator released by the eosinophils when they are activated due to various stimuli. The monoclonal antibody EG2 binds to human ECP, the epitopes which EG2 recognizes is only present in the secreted form of ECP, hence it only stains eosinophils which are undergoing activation and/or secretion. Flow cytometry was used to measure the level of eosinophils stained by the monoclonal antibody EG2 (eosinophil EG2+) in the peripheral blood of subjects with unstable extrinsic bronchial asthma, stable extrinsic bronchial asthma and healthy control group. A statistically significant higher level of eosinophil EG2+ was found in the group with unstable asthma than in either the group with stable asthma or the group of healthy subjects (p < 0.0002). No difference was found between the patients with stable asthma and the control group. The level of eosinophil EG2+ in peripheral blood, measured by flow cytometry, could be used as an indicator of inflammatory activity in patients suffering from bronchial asthma.

Variations of the cellular antigens CD4 and CD8 in pollinic patients during the spring.

In order to study the possible variations of CD4 and CD8 antigens in pollinic patients, we have studied 25 individuals (11 rhinoconjunctivitis and 14 rhinoconjunctivitis-asthma) before (T0), in the middle (T1) and after the spring (T2). The number of receptors per cell of CD4 start from values in T0, decrease in T1 and increase at the end of the spring (p < 0.00001), which could represent a mechanism to limit the clonal response to an antigen. An increase in the CD4/CD8 bright ratio could be indicate a higher helper mechanism in T1 with respect to T0 and T2 (p < 0.01). The opposite meaning is to given to the increase of CD8bright receptors in the asthmatic patients, and not only in those who suffer only from a rhinopathy (the only difference between the two groups of patients) during T2 over the T1 (p < 0.00001). The greater number of lymphocytes CD8 dim + during T1 with respect to T2 (p < 0.009) and the increase in the number of receptors of such cells during T1 with respect to T2 (p < 0.00001) suggests a possible intervention of these cells in the regulation of the response of the B and T lymphocytes. Of the two soluble factors CD4 (sCD4) and CD8 (sCD8), only the sCD4 increases during T1 (p < 0.0001) in an inverse manner as occurs with CD4 cell receptors, while the sCD8 remains unchanged during the three periods.(ABSTRACT TRUNCATED AT 250 WORDS)

The study cellular subpopulations in peripheral blood from a normal reference group population (blood donors).

The spectacular development of monoclonal antibodies against cellular antigens an technology such as flow cytometry allow the investigation of cellular subpopulations that until now have been unknown. At the same time, the functional study of these subpopulations becomes of maximal interest, as this information could have future applications for pathological processes. Due ti this basic need for information, we have studied diverse lymphocytic subpopulations in a normal population that serves as a reference group, using the following antigens: CD3, CD4, CD8, CD20, CD45RA, CD25, LAM1, CD29, CD11b and CD23. Some of these subpopulations had not been previously studied in a normal reference group.

Peripheral blood T lymphocytes in seasonal bronchial asthma.

Variations in T lymphocytes in asthmatic patients are related to disease severity. However, the effects of natural exposure to pollens on peripheral blood T lymphocytes have not been clarified. In this paper, the effects on peripheral blood CD4 and CD8 lymphocytes from pollen-sensitive subjects and from nonatopic donors were studied during and outside the pollen season. In patients who suffer from seasonal asthma, we found an increase in the CD4/CD8 bright ratio and a decrease in the mean number of CD4 receptors per cell during the pollen season. No variation was observed in healthy subjects. These results suggest that CD4 lymphocytes may be causally linked to the pathogenesis of seasonal bronchial asthma.

Fulminant herpes hepatitis in a healthy adult: a treatable disorder?

Hepatitis due to herpes simplex virus (HSV) is a potentially fatal disorder that is often not considered in the differential diagnosis of acute hepatitis. This disease occurs most often in patients with impaired immunity and is very uncommon in healthy patients. HSV hepatitis presents with a wide clinical spectrum, and the clinical diagnosis is difficult. We describe a case of disseminated herpes virus infection with fulminant hepatitis mimicking an acute human immunodeficiency virus infection in a 33-year-old healthy man. Preliminary studies suggest that early treatment of HSV hepatitis with acyclovir may be beneficial in these patients. A high index of suspicion and the availability of early diagnostic tools, such as HSV DNA detection, may dramatically improve the clinical outcome of severe HSV hepatitis.

IgE-mediated downregulation of L-selectin (CD62L) on lymphocytes from asthmatic patients.

BACKGROUND: L-selectin (CD62L) mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in leukocyte attachment to the endothelium at sites of inflammation. Although it has been demonstrated that L-selectin is shed after lymphocyte activation, it is unknown whether the expression of L-selectin on the surface of lymphocytes can be modulated by an IgE-dependent mechanism or whether immunotherapy (IT) might affect this mechanism. METHODS: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood lymphocytes from both groups of asthmatic patients in vitro with an anti-IgE antibody (Ab). Expression of L-selectin on the lymphocyte surface was analyzed by flow cytometry, and the levels of soluble L-selectin (sL-selectin) on culture supernatant by ELISA. RESULTS: L-selectin was downregulated from the surface of lymphocytes in a time- and anti-IgE antibody dose-dependent manner (with a concomitant upregulation of shed L-selectin in the supernatant). When lymphocytes from non-IT asthmatic patients were cultivated with anti-IgE Ab, a statistically significantly greater CD62L downmodulation on the lymphocyte surface was observed compared with lymphocytes from the healthy group (P<0.002) and from the IT-asthmatic group (P<0.001). When lymphocytes from non-IT asthmatic patients were cultivated with anti-IgE Ab, a significantly greater sL-selectin level in the culture supernatant was observed compared with lymphocytes from the healthy group (P<0.001) and with lymphocytes from IT-asthmatic group (P<0.001). CONCLUSIONS: We present evidence that the expression of L-selectin on the surface of lymphocytes can be modulated by an IgE-dependent mechanism. This mechanism can be affected by IT.

[Immunotherapy with an oral Alternaria extract in childhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro parameters]. / Inmunoterapia con un extracto oral de Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusiones sobre parámetros in vivo e in vitro.

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.

Parkinsonismo farmacológico frente a demencia con cuerpos de Lewy / Pharmacological Parkinsonismo opposite to dementia with Lewy's bodies

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