Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by cannabinoid agonists.

Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aß(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging.

Leptin gene therapy attenuates neuronal damages evoked by amyloid-ß and rescues memory deficits in APP/PS1 mice.

There is growing evidence that leptin is able to ameliorate Alzheimer's disease (AD)-like pathologies, including brain amyloid-ß (Aß) burden. In order to improve the therapeutic potential for AD, we generated a lentivirus vector expressing leptin protein in a self-inactivating HIV-1 vector (HIV-leptin), and delivered this by intra-cerebroventricular administration to APP/PS1 transgenic model of AD. Three months after intra-cerebroventricular administration of HIV-leptin, brain Aß accumulation was reduced. By electron microscopy, we found that APP/PS1 mice exhibited deficits in synaptic density, which were partially rescued by HIV-leptin treatment. Synaptic deficits in APP/PS1 mice correlated with an enhancement of caspase-3 expression, and a reduction in synaptophysin levels in synaptosome preparations. Notably, HIV-leptin therapy reverted these dysfunctions. Moreover, leptin modulated neurite outgrowth in primary neuronal cultures, and rescued them from Aß42-induced toxicity. All the above changes suggest that leptin may affect multiple aspects of the synaptic status, and correlate with behavioral improvements. Our data suggest that leptin gene delivery has a therapeutic potential for Aß-targeted treatment of mouse model of AD.

Hipopituitarismo sintomático en paciente con síndrome de silla turca vacía / Symptomatic hypopituitarism in patients with empty sella syndrome

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Fracaso hepático agudo tras golpe de calor / Acute liver failure following heat stroke

La afectación hepática en el curso de un golpe de calor suele ser un proceso frecuente, necesitando en algunos casos muy graves y raros de la realización de trasplante hepático. Presentamos el caso de un paciente varón de 31 años, deportista amateur, que mientras participaba en una competición de maratón sufrió un golpe de calor con fracaso hepático agudo acompañado de rabdomiolisis, insuficiencia renal y coagulopatía. La elevada temperatura ambiental, la duración del ejercicio y la altura a la que se realizó pudieron contribuir a la aparición del cuadro. La evolución del paciente, tras la aplicación de medidas conservadoras, fue favorable recibiendo el alta hospitalaria en pocos días

Hepatic involvement during heat stroke appears frequently. In some severe and rare cases liver transplantation is needed. We report a case of a 31 years old man, amateur runner, who suffered heat stroke-related acute liver failure, rhabdomyolysis, renal failure and coagulation im-pairment during a marathon. High environmental temperature, exercise duration and height where race took place could be involved. Patient had a favourable course with conservative treatment being discharged in a few days

[Acute liver failure following heat stroke]. / Fracaso hepático agudo tras golpe de calor.

Hepatic involvement during heat stroke appears frequently. In some severe and rare cases liver transplantation is needed. We report a case of a 31 years old man, amateur runner, who suffered heat stroke-related acute liver failure, rhabdomyolysis, renal failure and coagulation im-pairment during a marathon. High environmental temperature, exercise duration and height where race took place could be involved. Patient had a favourable course with conservative treatment being discharged in a few days.

[Disseminated inflammatory pseudotumor of the lymph nodes]. / Seudotumor inflamatorio diseminado de los ganglios linfáticos.

Inflammatory pseudotumour of lymph nodes is a benign type of lymphadenopathy recently described as a peculiar nodal reaction, which displays distinctive clinical and histological features. The origin of the disease is unknown although an inflammatory etiology has been suggested. We study a new case of inflammatory pseudotumour of lymph nodes which had an unusual clinical presentation, with lymphadenopathy on both sides of the diaphragm and enlargement of liver and spleen. In addition, focal fibrinoid vascular necrosis was observed on histological examination, an unusual finding which makes difficult the differential diagnosis with other lesions, particularly vasculitis.