Decreased NAA in gray matter is correlated with decreased availability of acetate in white matter in postmortem multiple sclerosis cortex.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids.

High resolution stereoscopic volume visualization of the mouse arginine vasopressin system.

New imaging technologies have increased our capabilities to resolve three-dimensional structures from microscopic samples. Laser-scanning confocal microscopy is particularly amenable to this task because it allows the researcher to optically section biological samples, creating three-dimensional image volumes. However, a number of problems arise when studying neural tissue samples. These include data set size, physical scanning restrictions, volume registration and display. To deal with these issues, we undertook large-scale confocal scanning microscopy in order to visualize neural networks spanning multiple tissue sections. We demonstrate a technique to create and visualize a three-dimensional digital reconstruction of the hypothalamic arginine vasopressin neuroendocrine system in the male mouse. The generated three-dimensional data included a volume of tissue that measures 4.35 mm x 2.6 mm x 1.4mm with a voxel resolution of 1.2 microm. The dataset matrix included 3508 x 2072 x 700 pixels and was a composite of 19,600 optical sections. Once reconstructed into a single volume, the data is suitable for interactive stereoscopic projection. Stereoscopic imaging provides greater insight and understanding of spatial relationships in neural tissues' inherently three-dimensional structure. This technique provides a model approach for the development of data sets that can provide new and informative volume rendered views of brain structures. This study affirms the value of stereoscopic volume-based visualization in neuroscience research and education, and the feasibility of creating large-scale high resolution interactive three-dimensional reconstructions of neural tissue from microscopic imagery.

Critical decisions in the management of endoscopic perforations of the colon.

The ideal management of suspected colon perforation following colonoscopy remains elusive because the incidence is only 0.1 to 2.0 per cent. The patient with obvious perforation deserves immediate exploration, but the patient with equivocal findings poses a diagnostic dilemma. We propose an algorithm based on the results of water-soluble contrast enema that allows for rapid, definitive surgical decision-making. If perforation is confirmed, early operation allows for primary repair without resection or colostomy, or if no perforation is identified, medical management can be undertaken with confidence. This algorithm should ensure that the surgical management of this potentially lethal complication is not unnecessarily delayed.

Clostridium perfringens sepsis with intravascular hemolysis following laparoscopic cholecystectomy: a newly reported complication.

Clostridium perfringens sepsis with hemolysis following cholecystectomy is a rare complication that has a very high mortality. The best chance for survival is ensured by early diagnosis, prompt initiation of antibiotics, and hyperbaric oxygen therapy if readily available. To our knowledge, this is the first reported case following laparoscopic cholecystectomy.

New therapies for the chronic complications of older diabetic patients.

Recently, four biochemical mechanisms have been implicated in the pathogenesis of certain late complications of diabetes mellitus. All of these mechanisms (altered polyol pathway activity, disrupted myo-inositol metabolism, increased vascular permeability, and increased nonenzymatic glycosylation of proteins) are activated by exposure of tissues to hyperglycemia. There is evidence to suggest that the development of retinopathy, nephropathy, and neuropathy is directly related to the level of glycemia in patients with diabetes mellitus. Whether strict glycemic control will prevent or reverse diabetic complications is the subject of the Diabetes Control and Complications Trial. Until the results of that study are reported, and until euglycemia can be achieved in all diabetic patients, the search will continue for other pharmacologic agents that might prevent the development of complications. Therapies that are currently under investigation include administration of aldose reductase inhibitors and supplementation of dietary myo-inositol. It is too early to conclude whether such therapies will prove useful in the prevention or reversal of diabetic complications.