Pathways involved in the generation of reactive oxygen and nitrogen species during glucose deprivation and its role on the death of cultured hippocampal neurons.

Oxidative stress has been suggested as a mechanism contributing to neuronal death induced by hypoglycemia, and an early production of reactive species (RS) during the hypoglycemic episode has been observed. However, the sources of reactive oxygen (ROS) and nitrogen (RNS) species have not been fully identified. In the present study we have examined the contribution of various enzymatic pathways to RS production and neuronal death induced by glucose deprivation (GD) in hippocampal cultures. We have observed a rapid increase in RS during GD, which depends on the activation of NMDA and non-NMDA receptors and on the influx of calcium from the extracellular space. Accordingly, intracellular calcium concentration [Ca(2+)](i) progressively increases more than 30-fold during the GD period. It was observed that superoxide production through the activation of the calcium-dependent enzymes, phospholipase A(2) (cPLA(2)) and xanthine oxidase (XaO), contributes to neuronal damage, while nitric oxide synthase (NOS) is apparently not involved. Inhibition of cPLA(2) decreased RS at early times of GD whereas inhibition of XaO diminished RS at more delayed times. The antioxidants trolox and ebselen also showed a protective effect against neuronal death and diminished RS generation. Inhibition of NADPH oxidase also contributed to the early generation of superoxide. Taking together, the present results suggest that the early activation of calcium-dependent ROS producing pathways is involved in neuronal death associated with glucose deprivation.

Actualización del tratamiento médico de la hemorragiauterina disfuncional / An update of the medical management of dysfunctional uterine bleeding

La hemorragia uterina disfuncional es un transtorno frecuente ginecológico. Es un diagnóstico de exclusión, y el clínico debe proceder a una evaluación lógica y escalonada de todas las causas de sangrado anormal. La menorragia en la mayoría de los casos se asocia con anovulación. El tratamiento médico debería ser la primera opción terapéutica y puede ser dividido en terapia no hormonal y hormonal. Los dos principales tratamientos para la menorragia asociada a ciclos ovulatorios son no hormonales, mediante un antifibrinolítico como el ácido tranexámico y antiinflamatorios. Tradicionalmente la terapia hormonal para la menorragia ha estado constituida por los progestágenos y los anticonceptivos orales. El sistema intrauterino de liberación de levonorgestrel ofrece un nuevo concepto terapéutico que combina una eficaz contracepción con una reducción del sangrado menstrual. Es una buena alternativa conservadora a la resección endometrial y parece ser una importante alternativa a la medicación oral. En el manejo de la pérdida menstrual excesiva hay una evidencia demostrada de que muchos médicos no prescriben los tratamientos más adecuados. El incremento en la utilización de tratamientos efectivos mejoraría las expectativas de las pacientes y supondría una alternativa a la cirugía (AU)

Estudio de tolerancia a cefpodoxima proxetil en pacientes con hipersensibilidad a betalactámicos / Study of tolerance to cefpodoxime proxetil in patients allergic to beta-lactam antibiotics

Objetivos: Se seleccionó de forma aleatoria a un grupo de 30 pacientes (< 65 años) diagnosticados de hipersensibilidad a betalactámicos mediante pruebas cutáneas o provocación controlada para estudiar su tolerancia a cefpodoxima proxetil, una cefalosporina de tercera generación que se administra por vía oral. Material y metodos: Se realizaron pruebas cutáneas con penicilina G, amoxicilina, ampicilina, cefpodoxima proxetil, cefalexina, ceftazidima y cefotaxima; simultáneamente se extrajo sangre para la realización de una prueba de liberación de histamina con penicilina G, amoxicilina, ampicilina y cefpodoxima. Se realizó una prueba de tolerancia oral con dosis terapéuticas (200 mg) de cefpodoxima proxetil (Otreon) a simple ciego a 26 pacientes.Se volvió a administrar el fármaco 15 días después. Se solicitó consentimiento informado por escrito a todos los pacientes. Se utilizaron como controles 36 pacientes que habían tolerado betalactámicos en los 6 meses previos. Resultados: Todos los pacientes toleraron con normalidad la administración de dosis terapéuticas de cefpodoxima proxetil. En el estudio se analizan los resultados de las distintas pruebas realizadas tanto in vivo como in vitro. Conclusiones: La tolerancia a cefpodoxima proxetil, una cefalosporina de tercera generación que se administra por vía oral, ha sido buena en pacientes con hipersensibilidad a betalactámicos. Con nuestro estudio apoyamos los datos existentes en la actualidad de que la reactividad cruzada clínica con cefalosporinas en pacientes con hipersensibilidad constatada a betalactámicos es muy escasa. Antes de recomendar su uso es necesario realizar más estudios (AU)

Paracetamol (acetaminophen) hypersensitivity.

BACKGROUND: Acetaminophen (paracetamol) is an analgesic antipyretic drug with no antiinflammatory effects and is widely used worldwide. Earlier clinical studies reported IgE-mediated adverse reactions to acetaminophen, but in vivo and in vitro tests have been inconclusive. OBJECTIVE: We propose to demonstrate an IgE-mediated mechanism in four patients with adverse reactions to acetaminophen (paracetamol). Tolerance to aspirin and other nonsteroidal antiinflammatory drugs are present in all patients. METHODS: We studied four patients with anaphylactic reactions to acetaminophen who tolerated aspirin and other nonsteroidal antiinflammatory drugs. Skin tests, oral challenges and immunoassay for allergen-specific IgE antibodies with acetaminophen were performed in all patients. RESULTS: All patients tolerated the aspirin oral challenge without adverse effects. In contrast, the oral challenge with acetaminophen produced adverse effects in all patients. Skin tests with acetaminophen were positive in two patients (3-mm wheal and flare) and IgE antibodies acetaminophen were detected in serum from two patients. CONCLUSION: We describe four patients with adverse reactions to acetaminophen but with tolerance to aspirin and other nonsteroidal antiinflammatory drugs. Skin tests, oral challenges, and serum IgE results with acetaminophen suggest that an IgE-mediated mechanism is responsible for these reactions.

Venom immunotherapy: tolerance to a 3-day protocol of rush-immunotherapy.

In the last 10 years in the Ramón y Cajal Hospital, in Madrid, we have treated 78 patients who had presented anaphylactic reactions after hymenoptera stings, by means of a rush immunotherapy protocol. Fifty patients received wasp venom and 30 received honeybee venom (2 patients were treated with both venom types). Venom immunotherapy is given to out-patients, at the hospital, in the morning. The interval between injections administered on the same day is 30 minutes and the patient stays for 2 hours under observation after the last daily dose. The schedule we use is as follows: Day 1 (0.05-1-5-10 micrograms of venom), Day 2 (20-40 micrograms), Day 3 (40-60 micrograms), Day 5 (100 micrograms). Afterwards, they receive 100 micrograms after 2 weeks and, finally, monthly. In order to achieve a better tolerance, patients are protected with antihistamines on the days they are administered the immunotherapy (mequitazine 5 mg every 12 hours) and also, doses equal or over 40 micrograms are given fractionally, injecting half dose in each arm. The percentage of systemic reactions (mild or moderate) is 13.3% for patients treated with honeybee venom and 2% for patients treated with wasp venom. These percentages are lower than those obtained with conventional protocols in which it takes several weeks to reach the maintenance dose. The speed and convenience of this protocol and also its appropriate safety have led us to use it as a routine treatment for patients who require venom immunotherapy after suffering anaphylactic reactions due to hymenoptera stings.