Vaccine therapy update for pregnant, immunocompromised, and chronic diseases patients.

The use of vaccines in pregnant, immunocompromised or chronic diseases patients has been widely discussed in the literature recently. Vaccines continue to be a safe and effective method to induce or recall immune response to several infective agents or even induce an effective response in chronically infected patients. The general presumption of adverse events, lack of response and unwanted tolerance seem to be responsible for the decreased vaccination rate in these patients. In the present review, the use of rational vaccination schemes, new patents of use, along as new approaches and patents have been discussed with the scope to diminish the high morbidity and mortality often encountered in these patients.

Metabolic syndrome and asthma.

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

Sensibilización al maní en pacientes venezolanos con enfermedades atópicas y/o urticaria / Sensitization to peanut in Venezuelan patients with atopic diseases and / or uticaria

La sensibilización y las manifestaciones alérgicas al maní se han incrementado últimamente a nivel mundial, constituyendo el mismo la causa principal de anafilaxia por alimentos. Como la prevalencia de alergia al maní varía de acuerdo a las regiones nos propusimos evaluar, en una etapa preliminar, la sensibilización al maní por pruebas cutáneas (“skin prick test”) en pacientes venezolanos atópicos y/o con urticarias que acudieron a la Consulta ambulatoria de Alergía del Instituto de Inmunología. El 5,4 % de los pacientes manifestó algún tipo de manifestación cutánea o respiratoria al ingerir maní. Se demostró sensibilización al maní por pruebas cutánea en el 6,5 % de los pacientes. Sin embargo, un porcentaje pequeño (2 %) de ellos mostró, en conjunto, pruebas cutáneas positivas y síntomas a la ingesta del maní. Ningún paciente refirió síntomas severos tras la ingestión de maní. La mayoría de los pacientes con pruebas positivas al maní, también mostraron pruebas positivas a otros alimentos. Estos resultados concuerdan con la percepción de los médicos venezolanos de una baja frecuencia de reacciones adversas, especialmente graves, a la ingesta de maní en nuestro país

Peanut allergy and sensitization incidence has increased world wide to become the first cause of food anaphylaxis. Since the prevalence of peanut allergy changes according to geographical areas, the aim of the study was to assess, in a preliminary report, peanut allergy incidence by skin prick test in atopic Venezuelan patients with atopy and or urticaria from the outpatient allergy clinic of the Institute of Immunology. Cutaneous or respiratory manifestations after peanut ingestion was observed in 5.4 % of the patients studied. Cutaneous test was positive in 6.5 % of patients. In the other hand, a small group (2 %), showed positive skin test along with symptoms after peanut ingestion. None of the patients had severe reactions. Most of the patients with peanut positive skin test were positive to other food allergens. These results are in accordance with the general clinical perception of small frequency of adverse reaction, specially the most serious ones, to peanut ingestion in our country

Perspectives of new therapies for endometriosis.

Endometriosis is an inflammatory disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease affects: ovarian function, oocyte quality, embryo development and implantation, and uterine function resulting in infertility or spontaneous pregnancy loss. Even though the world's prevalence is above 10 %, an effective treatment has not yet been found. New pharmacological approaches have been designed and patented that could serve as future therapies for this disease.

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.

Total and biologically active CD154 in patients with SLE.

CD154, a member of the tumor necrosis factor receptor family, is involved in several biological responses. In the sera of systemic lupus erythematosus (SLE) patients, the levels of sCD154 have been shown to be increased, however, few reports have dealt with the biologically active tetramer. Here, we assessed the biological activity of the serum CD154 tetramer using bioassays for BC activation and production nitrite or peroxide. The patients showed a markedly increased total sCD154 serum concentration (12.5 +/- 8.2 vs. 3.9 +/- 1.2 ng/ml; p < 0.001). ba-sCD154 was significantly increased in non-treated patients (7.4 +/- 3.4 ng/ml, n = 22; p < 0.001) and patients with the highest SLE disease activity index (SLEDAI) scores (5.3 +/- 2.9 ng/ml, n = 8), but not in stable patients (1.3 +/- 1.2 ng/ml, n = 30) whose values were similar to normal healthy donors (NHD; 0.8 +/- 0.2 ng/ml). Patients with SLEDAI above 8 that recovered after successful treatment displayed significantly decreased levels of ba-sCD154. We conclude that the bioassay is a useful tool discriminating active and stable SLE, as well as non-treated patients.

Serum adipokine levels in patients with systemic lupus erythematosus.

In patients with systemic lupus erythematosus (SLE) metabolic alterations are often observed, which may be due to either the disease, the genetic background or the treatment. We studied the serum levels of the adipokines leptin, adiponectin, resistin, visfatin and ghrelin in patients with SLE and controls. Leptin levels were lower and adiponectin, ghrelin and visfatin levels were higher in the patients. No significant differences were encountered for resistin. The values of adipokines were independent of treatment, even after correction for body mass index. Inverse correlations were found among leptin and adiponectin, ghrelin and visfatin. We conclude that adipokines are involved in the metabolic imbalance of patients with SLE.

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.

Immunophenotype characteristics of peripheral blood mononuclear leukocytes of chronic idiopathic urticaria patients.

The pathogenesis of chronic idiopathic urticaria (CIU) is not completely understood although autoimmunity has been proposed. The aim of the study was to assess the expression of different leukocyte antigens, by flow cytometry, assaying total blood of 29 patients with CIU and of 20 sex and age matched controls. Moreover, we assessed soluble CD154 a marker of immune cell activation, predominantly memory T cells. When patients were divided depending an their response to the autologous serum skin test (ASST), three different groups were encountered: group 1 (n=11): with negative ASST-, group 2 (n=11): positive ASST (ASST+) with normal lymphocyte counts and group 3 (n=7): ASST+ with low lymphocyte counts (< 1500 cells/mm3). A significant increase in CD19+ percentage and not in the absolute count (P < 0.05) was observed in group 1 as compared to controls and to the other groups. In contrast, CD30+, CD45RO+ and CD4+/CD45RO+ percentages and biologically active soluble CD154 levels were significantly higher (P < 0.05) in group 3 as compared to group 1 or to controls. In ASST positive groups, CD45RO+ and CD4+/CD45RO+ positiveness correlates with wheal diameter. In conclusion, memory cells may play a role in these different types of patients and in understanding CIU pathogenesis.

Immunophenotype characteristics of peripheral blood mononuclear leukocytes of chronic idiopathic urticaria patients

La patogénesis de la urticaria crónica idiopática (CIU) no se conoce completamente; sin embargo, la autoinmunidad juega un papel importante en un subgrupo de pacientes. El objetivo de este estudio fue la determinación de antígenos leucocitarios en sangre total, utilizando citometría de flujo, de 29 pacientes con CIU y 20 controles de similar edad y sexo. Adicionalmente, se determinó el CD154 soluble como marcador de activación de células inmunes, predominantemente linfocitos T de memoria. Se describieron 3 grupos de pacientes de acuerdo al resultado de la prueba de suero antólogo (ASST): grupo 1: negativo (n = 11), grupo 2: prueba positiva y contaje linfocitario normal (n = 11) y grupo 3 prueba positiva y contaje linfocitario bajo (< 1500 células/mm3) (n = 7). En el grupo 1, se observó un aumento significativo (P < 0,05) en el porcentaje de células CD19+ aunque no en su número absoluto cuando se comparó con los controles y los pacientes con ASST +. En contrapartida, el porcentaje de células positivas para CD30, CD45RO y CD4/CD45RO y los niveles de CD154 soluble biológicamente activo fueron significativamente mayores (P < 0,05) en el grupo 3, en comparación con los controles y el grupo 1. Además, en los grupos con ASST positiva, los porcentajes de células CD45RO+ y CD4/CD45RO+ se correlacionan con el tamaño del habón a la ASST. En conclusión, las células de memoria pudieran jugar un papel importante en la patogénesis de la CIU.

New frontiers in the therapeutic management of transplant rejection.

Understanding of the mechanisms of transplant and xenotransplant rejection represents one of the most important aspects of both basic and clinical immunology. This review discusses the roles of 1) immune response and 2) the influence of various products of arachidonic acid metabolism on immune response in graft survival. The review also includes an overview of novel therapeutic approaches developed to prevent, or at least delay, graft rejection. New discoveries in basic and clinical immunology have generated new areas of research in pharmacology that may prevent rejection more efficiently, a key issue in modern medicine.

Total and biologically active serum-soluble CD154 in patients with chronic idiopathic urticaria.

The pathogenesis of chronic idiopathic urticaria (CIU) is not understood completely; however, autoimmunity has been implicated. Because membrane and soluble forms of CD154 have been reported to be increased, in several autoimmune diseases, we have quantified the soluble CD154 (sCD154) molecule by a sandwich enzyme-linked immunosorbent assay in serum samples of 32 patients with CIU (aged 32 +/- 12 years) and compared them with 32 age- and sex-matched nonallergic controls. A marked increase was observed in patients with CIU as compared with controls (4.8 +/- 2.6 ng/mL versus 2.9 +/- 0.9 ng/mL; p < 0.0005). No significant differences were found between groups of patients with positive or negative autologous serum skin test. A biological assay to determine sCD154 showed that patients with positive autologous serum skin test have the highest levels (4.9 +/- 1.2 ng/mL) of biologically active sCD154 as compared with their negative counterparts (2.2 +/- 1.3 ng/mL; p < .001) and controls (0.6 +/- 0.3 ng/mL; p < 0.001). Active sCD154 can be derived from mast cell activation or other leukocytes. It is concluded that active sCD154 may be involved in the immune activation observed in patients with CIU.