Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients.

BACKGROUND: One of the gene polymorphisms often studied in asthmatic patients is the ß2 adrenergic receptor (ADRß2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRß2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRß2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. METHODS: Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. RESULTS: Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. CONCLUSION: The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.

Role of beta2 agonists in respiratory medicine with particular attention to novel patents and effects on endocrine system and immune response.

Beta adrenergic receptors are very important in respiratory medicine. Traditionally, the stimulation of beta adrenergic receptors by beta2-agonists is commonly used for giving bronchodilation in chronic airflow obstruction However; the wide distribution of these receptors in cells and tissues other than airway smooth muscle suggests that beta agonists should offer other beneficial effects in respiratory disease. Recent studies have shown the importance of these receptors in the modulation of endocrine and immune system that affect respiratory function and may decrease therapy effectiveness in asthma and chronic obstructive pulmonary disease. New patented compound and uses have provided new insights in future therapeutics of respiratory diseases in which genetic, endocrine and immune response should be considered.

Inhibitors of phosphoinositol 3 kinase and NFκB for the treatment of chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. In the present article, we review the new patents on phosphoinositide 3 kinase and NFκb inhibitors for future therapies.

New pharmacological treatments for patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lung to noxious particles or gasses. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. METHODS AND RESULTS: A literature search using PubMed, Science Direct, EBSCO and free patents on line for the years 2000-2010. CONCLUSIONS: Recent discoveries in the physiology and pathology of airways diseases have served to generate potential new drugs for the treatment of COPD patients. Several substances that block or activate specific pathways and receptors the aim of which is to decrease inflammation and increase airway obstruction reversibility are being used in different clinical protocols and hopefully will be available for patients in the near future.

Estudio piloto de marcadores inflamatorios en el sindrome de apnea obstructiva del sueño / Pilot study of inflammatory markers in the syndrome of obstructive sleep apnea

El síndrome de Apnea Obstructiva del Sueño (SAOS), consiste en la aparición repetida de episodios de obstrucción faríngea durante el sueño como consecuencia de un colapso de la vía respiratoria. La respuesta fisiológica a la hipoxia intermitente crónica es la generación de una respuesta inflamatoria local y sistémica. Se han evidenciado cambios importantes a nivel cardiovascular en pacientes con SAOS; sin embargo, se desconocen cuáles marcadores séricos y genéticos pudieran ser de utilidad. En el presente estudio, se presentan 15 marcadores séricos y 3 genéticos (IL-6, IL-1β y TNF-α) en un grupo de cinco pacientes para determinar cuáles pueden ser los marcadores de interés en la aparición y en el desarrollo de esta patología respiratoria. Se proponen como marcadores los niveles séricos: proteína C reactiva, TNFα, IL-6, el receptor soluble de TNF I, sCD62, sCD154, nitrotirosina y anti-oxLDL. Los niveles de IL-1 β, el receptor de TNF soluble II, sCD25, sCD54, nitritos y nitratos no parecieran ser buenos marcadores en SAOS. Los estudios genéticos no fueron concluyentes.

Obstructive sleep apnea syndrome (OSAS) is a repeated sequences of pharynx obstruction during sleep as a consequence of airway collapse. The physiological response to the desaturation is the generation of a local and systemic inflammatory immune response. Important changes at cardiovascular levels in patients with OSAS have been observed; however, it is not know which serum or genetic parameters could be useful. In the present study, we present 15 serum and 3 genetic (IL-6, IL-1β y TNF-α) markers in a group of five patients in order to determine which marker could be useful to study the genesis and progression of this respiratory pathology. The proposed serum markers are C reactive proteín, TNFα, IL-6, soluble de TNF receptor I, sCD62, sCD154, nitrotirosine and anti-oxLDL. The levels of IL-1 β, soluble TNF receptor II, sCD25, sCD54, nitrite y nitrate do not seem to be good markers for OSAS. The genetic studies were not conclusive.

Pharmacological modulation of Th17.

Recently, a third subset of Th17 cells has been described. This T helper subset induces the release of chemokines and growth factors and causes neutrophil accumulation in several mammalian organs. Pharmacological intervention blocking Th17 generation as well as IL-17 signaling might prove useful in a variety of diseases including asthma, chronic obstructive pulmonary disease, Crohn's disease, cystic fibrosis, multiple sclerosis, psoriatic disease and rheumatoid arthritis. Here, we describe the patents that address a potential pharmacological use of promoting or targeting IL-17.

Presencia de agentes antígenos extractables del núcleo en niños con hepatitis autoinmune / Presence of extractable antigens of the nucleus in children with autoimmune hepatitis

La hepatitis autoinmune (HAI) es una enfermedad inflamatoria del hígado, con autoanticuerpos tisulares, altos niveles de inmunoglobulina IgG, ausencia de etiología conocida y con respuesta a la terapia inmunosupresora. Los anticuerpos han sido intensamente evaluados y conducen a la clasificación de HAI en tres grupos serológicos. El 20 por ciento de niños con HAI muestran antígenos extractables del núcleo (anti Sm, anti SSA y anti SSB) sin que estos pacientes muestren criterios para otras enfermedades autoinmunes. Se reporta un caso de un adolescente masculino de 12 años de edad quién presentó clínica de esplenomegalia, insuficiencia renal aguda secundaria a nefritis intersticial, elevación transaminasas, hipergammaglobulinemia, hipocomplementemia, ANA y anti DNA positivos, anti Sm y anti SSA positivos, anticardiolipinas IgM e IgG positivas, SMA positivo y biopsia hapática con hallazgos histopatológicos compatibles con hepatitis autoinmune. A pesar de presentar anticuerpos altamente específicos para otras enfermedades autoinmunes (Ejm. LES) el paciente no cumple los criterios mínimos establecidos

Pseudotumor cerebral como complicación de traumatismo craneoencefálico: presentación de un caso clínico / Brain pseusotumor as complication of cranio cerebral trauma: a clinical case presentation

El pseudotumor cerebral es un síndrome clínico por hipertensión intracraneal, con citoquímico y cultivos de líquido cefalorraquídeo normales, sin ninguna malformación anatómica ni funcional de los ventrículos cerebrales. Son múltiples las causas de pseudotumor cerebral incluyendo las metabólicas, infecciosas, farmacológicas, hematológicas, traumatismos craneoencefálicos e idiopáticas siendo éstas las más frecuentes. Aunque es una entidad benigna con pronóstico excelente, la pérdida visual permanente es la complicación más grave, por lo que requiere un diagnóstico y tratamiento precoz. Se describe el caso clínico de preescolar masculino de 5 años, quien posterior a traumatismo craneoncefálico presentó clínica de pérdida visual transitoria, náuseas, vómitos, cefalea, irritabilidad, parálisis del sexto par craneal, fotofobia, diplopía y visión borrosa, cuya evaluación oftalmológica reportó papiledema bilateral, la punción lumbar con manometría practicada en dos oportunidades evidenció elevación de la presión intracraneal siendo este procedimiento diagnóstico y terapéutico; el análisis citoquímico y cultivo del LCR fue normal. La TAC de cráneo reveló el hallazgo de un quiste aracnoideo congénito. Se indicó un fármaco de elección acetazolamida con mejoría de los signos de hipertensión intracraneal y la parálisis del sexto par craneal. Sólo permaneció un discreto papiledema con campimetría normal dos meses posterior al egreso sin ricidiva