Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD.

The posterior cingulate cortex (PCC) is the brain region displaying the earliest sign of energy hypometabolism in patients with amnestic mild cognitive impairment (MCI) who develop Alzheimer's disease (AD). In particular, the activity of the mitochondrial respiratory enzyme cytochrome oxidase (C.O.) is selectively inhibited within the PCC in AD. The present study is the first experimental analysis designed to model in animals the localized cortical C.O. inhibition found as the earliest metabolic sign of early-stage AD in human neuroimaging studies. Rats were used to model local inhibition of C.O. by direct injection of the C.O. inhibitor sodium azide into the PCC. Learning and memory were examined in a spatial holeboard task and brains were analyzed using quantitative histochemical, morphological and biochemical techniques. Behavioral results showed that sodium azide-treated rats were impaired in their memory of the baited pattern in probe trials as compared to their training scores before treatment, without non-specific behavioral differences. Brain analyses showed that C.O. inhibition was specific to the PCC, and sodium azide increased lipid peroxidation, gliosis and neuron loss, and lead to a network functional disconnection between the PCC and interconnected hippocampal regions. It was concluded that impaired memory by local C.O. inhibition in the PCC may serve to model in animals a metabolic lesion similar to that found in patients with amnestic MCI and early-stage AD. This model may be useful as an in vivo testing platform to investigate neuroprotective strategies to prevent or reduce the amnestic effects produced by posterior cingulate energy hypometabolism.

Probing the local structure and mechanical response of nanostructures using force modulation and nanofabrication.

Nanostructures of self-assembled monolayers (SAMs) are designed and produced using coadsorption and nanografting techniques. Because the structures of these artificially engineered domains are predesigned and well-characterized, a systematic investigation is possible to study the mechanical responses to force modulation under atomic force microscope tips. Force modulation imaging reveals characteristic contrast sensitivity to changes in molecular-level packing, molecule chain lengths, domain boundaries, and surface chemical functionalities in SAMs. By means of actively tuning the driving frequency, the resonances at the tip-surface contact are selectively activated. Therefore, specific surface features, such as the edges of the domains and nanostructures or desired chemical functionalities, can be selectively enhanced in the amplitude images. These observations provide a new and active approach in materials characterization and the study of nanotribology using atomic force microscopy.

Force Measurements between Semifluorinated Thiolate Self-Assembled Monolayers: Long-Range Hydrophobic Interactions and Surface Charge.

Long-range interactions between self-assembled monolayers (SAMs) of semifluorinated alkanethiols have been studied by direct force measurements in water and aqueous NaCl solutions. SAMs prepared from three different thiols, with identical fluorinated head groups but varying hydrocarbon spacer lengths, were investigated: CF(3)(CF(2))(9)(CH(2))(x)SH, where x=2, 11, or 17. Force measurements show that the interactions in water and electrolyte solutions are composed of both double-layer interactions emerging from what appears to be charges adsorbed onto the surfaces and long-range "hydrophobic" attractions, in excess of the expected van der Waals forces. The three investigated thiols produce similar results in force measurements, though the contact angles with water are slightly different. The "hydrophobic" attraction has the form of step-like attractive discontinuities in the force profiles at separations ranging from 20 to 40 nm, caused by bridging of microscopic bubbles residing at the surfaces. The shape or range of these discontinuities are not significantly affected by replacement of the water with either 1 mM or 1 M NaCl solutions. The origin of the charges causing the electrostatic double-layer interaction is unclear, but some possible causes are discussed. Copyright 2001 Academic Press.

[Sodium diphenylhydantoin as a probable cause of pancreatitis]. / Difenilhidantoinato sódico como probable causa de pancreatitis.

INTRODUCTION: Drug-induced pancreatitis is much more common in children than in adults. Many drug have been implicated in its pathogenesis. Among the neuropsychiatric drugs only valproic acid, carbamazepine, clozapine and ergotamine have been reported. Phenytoin is commonly used for the treatment of epilepsy. It has been associated to pancreatitis only in two previous reports. CASE REPORT: Male adolescent who initiated with cerebellar hemorrhage due to an arteriovenous malformation. During his evolution he presented the following complications: pneumonia, two urinary tract infection, gastrointestinal bleeding and arterial hypertension. Eighteen days after admission he developed seizures and was treated with phenytoin. The next day he presented pancreatic symptoms and pancreatitis was confirmed by elevated enzymes and a CAT scan with pancreatic edema. Other etiologies were discarded. Pancreatic enzymes persisted high until phenytoin was stopped and have been within normal values after 18 months of follow-up. CONCLUSIONS: In this case three of the four Miller criteria have been fulfilled. We consider that the antiepileptic treatment was the direct cause of the pancreatitis because there was a clear temporal association of the symptoms with the initiation and suspension of the drug.