Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of Dermatophagoides mix-based immunotherapy.

BACKGROUND: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farinae (Dermatophagoides mix) adsorbed on aluminum hydroxide. OBJECTIVE: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. MATERIAL AND METHODS: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15000 SQ+) were administered at weekly intervals with 1 maintenance injection (15000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. RESULTS: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. CONCLUSION: This new updosing phase of Dermatophagoides mix-based immunotherapy had a good tolerability profile and induced a significant immunological effect.

Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of dermatophagoides mix–based immunotherapy

Background: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farina ( Dermatophagoides mix) adsorbed on aluminum hydroxide. Objective: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. Material and Methods: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15 000 SQ+) were administered at weekly intervals with 1 maintenance injection (15 000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. Results: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. Conclusion: This new updosing phase of Dermatophagoides mix–based immunotherapy had a good tolerability profile and induced a significant immunological effect (AU)

Antecedentes: Se ha desarrollado una mejorada vacuna de inmunoterapia específica (SCIT) adsorbida en hidróxido de aluminio y administración subcutánea con una fase de incremento de dosis más rápida y simplificada que contiene D. pteronyssinus y D. farinae (HDM; Dermatophagoides mezcla) a partes iguales. Objectivo: Evaluar la tolerabilidad de la fase de incremento de dosis de esta nueva formulación de extracto alergénico en SCIT y su impacto inmunológico. Material y Métodos: Ensayo clínico multicéntrico, abierto, de un brazo, fase II/III. Los sujetos que se podían incluir eran pacientes con una historia clínica de rinitis/conjuntivitis a ácaros de polvo doméstico (con/sin asma) y que presentaran sensibilización a HDM (IgE específica y prueba cutánea positiva). Se administraron cinco dosis semanales de Dermatophagoides mezcla en la fase de inicio (300, 600, 3000, 6000 y 15.000 SQ+) y una inyección de mantenimiento (15.000 SQ+) dos semanas tras la última inyección de la fase de incremento de dosis. Dos días tras cada visita se contactó con los pacientes por teléfono para seguir cualquier acontecimiento adverso (AE). Además, se evaluaron la IgG4, factor bloqueante de IgE y la respuesta cutánea inmediata. Resultados: Se incluyeron 102 sujetos en el ensayo (52,9% varones) con una edad media de 29,3±7,7 años. Se notificaron 117 reacciones adversas (RA) relacionadas con el medicamento en investigación: 101 locales, con independencia del tamaño de la reacción, en 48 (47,1%) pacientes y 7 sistémicas, todas grado I, en 5 (4,9%) pacientes. Todas las RA fueron de intensidad leve, excepto una, de intensidad moderada. Tras seis semanas de tratamiento, se obtuvieron incrementos estadísticamente significativos en el factor bloqueante de IgE y en IgG4, así como en la reducción de la respuesta cutánea inmediata. Conclusión: Esta nueva fase de incremento de dosis con inmunoterapia con Dermatophagoides mezcla presenta un buen perfil de tolerabilidad e induce una respuesta inmunológica significativa (AU)

Omalgia pruriginosa / Pruriginous omodynia

La notalgia parestésica es una mononeuropatía sensitiva producida por atrapamiento de los ramos dorsales de las raíces espinales de D2 a D6, debido a que estos nervios se angulan 90° al pasar por la musculatura paraespinal. Se desconoce su causa, pero se ha visto relacionada con alteraciones en la estática de la columna a ese nivel (artrosis, escoliosis). Parestesias, prurito y quemazón son los síntomas más frecuentes y, junto con el hallazgo de una placa hiperpigmentada en dicha localización, constituyen los pilares de su diagnóstico. La electroneurografía muestra signos de denervación en las raíces afectadas. Únicamente la capsaicina tópica ha demostrado eficacia en ensayos clínicos. Otras terapias descritas en la literatura son la acupuntura, el bloqueo anestésico paravertebral local, la fisioterapia y la oxcarbazepina (AU)

Notalgia paresthetica is a sensory mononeuropathy producedby the dorsal spinal nerve root branch entrapmentfrom D2 to D6 because these nerves are angles 90° when passingthrough the paraspinal musculature. Its cause is unknownbut it has been observed to be related with alterationsin the spinal cord statics at this level (arthritis, scoliosis). Paresthesias,pruritus and burning sensation are the most frequentsymptoms. Together with the finding of a hyperpigmentedplaque at that location, they are the mainstay of itsdiagnosis. The electroneurography shows signs of denervationin the affected roots. Only topical capsaicin has beenshown to be effective in clinical trials. Other therapies describedin the literature are acupunture, local paravertebralblock anesthesia, physical therapy and oxcarbazepine (AU)

Dengue virus in Mexican bats.

Individuals belonging to five families, 12 genera, and 19 different species of bats from dengue endemic areas in the Gulf and Pacific coasts of Mexico were examined by ELISA, RT-PCR, and for the presence of dengue virus (DV) NS1 protein. Nine individuals from four species were seropositive by ELISA: three insectivorous, Myotis nigricans (four positives/12 examined), Pteronotus parnellii (3/19), and Natalus stramineus (1/4), and one frugivorous Artibeus jamaicensis (1/35) (12.86% seroprevalence in positive species). DV serotype 2 was detected by RT-PCR in four samples from three species (all from the Gulf coast - rainy season): two frugivorous, A. jamaicensis (2/9), and Carollia brevicauda (1/2), and one insectivorous, M. nigricans (1/11). The latter was simultaneously positive for NS1 protein. DV RT-PCR positive animals were all antibody seronegative. M. nigricans showed positive individuals for all three tests. This is the first evidence suggesting the presence of DV in bats from Mexico.

Antagonistas del calcio / Calcium antagonists

Las antagonistas del calcio constituyen un grupo heterogéneo de fármacos. Todos ellos comparten un mismo mecanismo de acción, pero presentan diferencias en cuanto a su perfil famacocinético y farmacodinámico, en sus efectos secundarios y, por tanto en sus aplicaciones terapéuticas. Pueden clasificarse en selectivos 8verapamilo, diltizaem, nifedipino, etc) y no selectivos (flunaricina y cinaricina) según sea el tipo de bloqueo de la entrada de calcio a la célula a través de los canales tipo L (de inactivación lenta), que se encuentran en músculo estriado cardiaco y músculo liso vascular. Sus características farmacocinéticas (metabolismo por citocromo P450) y farmacodinámicas 8efectos inotrópicos y cronotrópicos) son las responsables de sus efectos adversos (cefalea, además, rubor facial, bradicardia, bloqueo auriculoventricular, hipotensión, disnea e insuficiencia cardiaca) e interacciones 8inductores enzimáticos, antiarrítmicos). Entre sus principales aplicaciones terapéuticas, cabe destacar su uso en hipertensión arterial, diabetes mellitus, angina de pecho, infarto agudo de miocardio, arritmias caridacas, miocardiopatía hipertrófica, hemorragia subaracnoidea, hipertensión pulmonar primaria, migraña, parto prematuro, demencia, fisura anal y fenómeno de Raynaud. Otros indicaciones más controvertidas podrían ser el espasmo esofágico difuso y la acalasia, dismenorrea, incontinencia urinaria/enureis nocturna e hiperplasia benigna de próstata (AU)

Calcium antagonists are a heterogeneous group of drugs. They all have the same mechanism of action, but present differences in terms of their pharmacokinetic and pharmacodynamics profiles, their secondary effects and, thus, their therapeutic applications. They can be classified as selective (verapamil, diltiazem, nifedipine, etc) and nonselective (flunarizine and cinnarizine) depending on their manner of blocking the entrance of calcium into the cell through the L-type channels (slow inactivation) located in the cardiac strated muscle and vascular smooth muscle. Their pharmacokinetic features (cytochrome P450 dependent metabolism) and pharmacodynamics characteristics (inotropic and chronotropic effects9 are responsible for their adverse effects (headache, edemas, facial flushing bradycardia, atrioventricular block, hypotension, dyspnea and heart failure) and interactions (enzyme inducers, antiarrhythmic agents). Among their main therapeutic applications are their use in hypertension, diabetes mellitus, angina pectoris, myocardial infarction, cardiac arrhythmias, hyperthorphic cardiomyopathy, subarachnoid hemorrhage, primary pulmonary hypertension, migraine, premature delivery in pregnancy, dementia, anal fissure and Raynaud´s phenomenon). Other more controversial indications would be diffuse esophageal spasm and achalasia, dysmenorrhea, nocturnal urinary incontinence/enuresis and benign prostatic hyperplasia (AU)

Hipomagnesemia e insuficiencia cardíaca / Hypomagnesemia and cardiac failure

No disponible

The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen.

Many works have dealt with the study of the allergenic relevance of profilin from allergenic extracts, mainly derived from pollens and vegetable foods. Olive pollen extracts also contain a profilin allergen (Ole e 2). This protein has been characterized in detail, so the amino-acid sequence of three isoforms and the structural model of one of them are already known. The prevalence of Ole e 2 for olive allergenic patients has been evaluated by different in vivo and in vitro methods, and the results compared with those obtained for another pollen profilins.

[Obesity in the 21st century. Progress in etiopathogenesis and treatment]. / La obesidad en el siglo XXI. Avances en la etiopatogenia y tratamiento.

Obesity is complex in its etiology and treatment. Its global incidence is increasing significantly. Favoring weight-loss can only bring beneficial effects. Obesity is a chronic condition with multifactorial origin. The discovery of the ob gene and its product, the OB protein or Leptin, neuropeptide Y, and the alterations of the metabolism of lipogenic tissues that inhibit appetite are significant advances in the understanding of its etiopathogenesis and treatment. This new knowledge will change the philosophy of the management of obesity. Obesity responds poorly to nonsurgical therapies. Its treatment must be long-term in spite of the considerable social and biological pressure that favor the regaining of weight. Treatment of the obese patient must be performed by a multidisciplinary team, and should include a hypoenergetic diet, exercise program, behavioral modifications, and in some instances, family therapy. The treatment of obesity should be tailored for each individual. Drug use in the treatment of obesity is not a substitute for modifying the individual's diet and physical activity. Bariatric surgery is indicated only when the BMI is greater than 30 kg/m2. Physicians and patients must interact closely and assess possible risks that are involved in its treatment against real benefits. A good relation between practitioner and patient is essential.

Oestrogens regulate pituitary alpha2,3-sialyltransferase messenger ribonucleic acid levels in the female rat.

Follicle-stimulating hormone (FSH) is synthesized by the anterior pituitary gland in multiple molecular forms. Increased acidic/sialylated FSH charge isoforms are associated with conditions characterized by a low oestrogen output. In the present study, we analysed the dynamics of the changes in mRNA levels of the enzyme Galbeta1,3[4]GlcNAc alpha2,3-sialyltransferase (2,3-STase) (one of the enzymes that incorporate sialic acid residues into the FSH molecule) in intact and ovariectomized rats. The anterior pituitaries of 4-day regularly cyclic adult female Wistar rats were obtained at 1000 h on the days of pro-oestrus (P), oestrus (O), dioestrus 1 (D1) and dioestrus 2 (D2), at 0200 h, 1400 h, 1800 h and 2200 h on D1, at 1800 h on day of O and at 1000 h after 7, 14, 21, 28 and 45 days of oophorectomy performed on the morning of P. Total RNA was isolated from each gland and the 2,3-STase levels were measured by Northern blot hybridization analysis employing a 346-base pair cDNA probe encoding for a non-conserved amino acid sequence of the catalytic domain of the enzyme. Maximal levels of the enzyme mRNA were detected at 1000 h on D1; thereafter, they progressively decreased by 60% during the ensuing 24 h, reaching the lowest concentration values (26% of the maximally observed level on D1) at 1000 h on day of P and remaining unchanged during the morning of O. Administration of the potent oestradiol receptor antagonist ICI 182,780 at 1000 h on D1 completely reverted the time-dependent decrease in 2,3-STase mRNA levels observed during the afternoon of D1, whereas oestradiol benzoate administered at 1000 h on day of O significantly reduced the enzyme mRNA levels (to 21% of the levels detected in vehicle-treated controls). In ovariectomized rats, the alpha2,3-STase mRNA progressively increased from day 21 to day 45 post castration. Administration of oestradiol benzoate on day 28 after oophorectomy significantly reduced the 2,3-STase mRNA levels (to 36% of the levels detected in vehicle-injected controls); ICI 182,780 partially counteracted this oestradiol-mediated effect. The dynamics of these changes in 2,3-STase mRNA levels partially correlated with changes in the relative abundance of the FSH charge isoforms separated by preparative chromatofocusing of anterior pituitary extracts, particularly in glands obtained during the morning of P and O. These data demonstrate for the first time that pituitary 2,3-STase is a hormonally-regulated enzyme and that the changes in transcription and/or stability of its mRNA may be involved, in part, in the post-translational processing of the FSH molecule during certain physiological conditions.