ABSTRACT
OBJECTIVE: Cerebral dyschromatopsia is sometimes associated with acquired prosopagnosia. Given the variability in structural lesions that cause acquired prosopagnosia, this study aimed to investigate the structural correlates of prosopagnosia-associated dyschromatopsia, and to determine if such colour processing deficits could also accompany developmental prosopagnosia. In addition, we studied whether cerebral dyschromatopsia is typified by a consistent pattern of hue impairments. METHODS: We investigated hue discrimination in a cohort of 12 subjects with acquired prosopagnosia and 9 with developmental prosopagnosia, along with 42 matched controls, using the Farnsworth-Munsell 100-hue test. RESULTS: We found impaired hue discrimination in six subjects with acquired prosopagnosia, five with bilateral and one with a unilateral occipitotemporal lesion. Structural MRI analysis showed maximum overlap of lesions in the right and left lingual and fusiform gyri. Fourier analysis of their error scores showed tritanopic-like deficits and blue-green impairments, similar to tendencies displayed by the healthy controls. Three subjects also showed a novel fourth Fourier component, indicating additional peak deficits in purple and green-yellow regions. No subject with developmental prosopagnosia had impaired hue discrimination. CONCLUSIONS: In our subjects with prosopagnosia, dyschromatopsia occurred in those with acquired lesions of the fusiform gyri, usually bilateral but sometimes unilateral. The dyschromatopsic deficit shows mainly an accentuation of normal tritatanopic-like tendencies. These are sometimes accompanied by additional deficits, although these could represent artifacts of the testing procedure.
Subject(s)
Color Perception/physiology , Color Vision Defects , Discrimination, Psychological/physiology , Prosopagnosia , Temporal Lobe/diagnostic imaging , Adolescent , Adult , Aged , Case-Control Studies , Cohort Studies , Color Vision Defects/complications , Color Vision Defects/diagnostic imaging , Color Vision Defects/pathology , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Photic Stimulation , Prosopagnosia/complications , Prosopagnosia/diagnostic imaging , Prosopagnosia/pathology , Young AdultABSTRACT
We previously showed that genetic inactivation of malonyl-CoA decarboxylase (MCD), which regulates fatty acid oxidation, protects mice against high-fat diet-induced insulin resistance. Development of insulin resistance has been associated with activation of the inflammatory response. Therefore, we hypothesized that the protective effect of MCD inhibition might be caused by a favorable effect on the inflammatory response. We examined if pharmacological inhibition of MCD protects neonatal cardiomyocytes and peritoneal macrophages against inflammatory-induced metabolic perturbations. Cardiomyocytes and macrophages were treated with LPS to induce an inflammatory response, in the presence or absence of an MCD inhibitor (CBM-301106, 10 µM). Inhibition of MCD attenuated the LPS-induced inflammatory response in cardiomyocytes and macrophages. MCD inhibition also prevented LPS impairment of insulin-stimulated glucose uptake in cardiomyocytes and increased phosphorylation of Akt. Additionally, inhibition of MCD strongly diminished LPS-induced activation of palmitate oxidation. We also found that treatment with an MCD inhibitor prevented LPS-induced collapse of total cellular antioxidant capacity. Interestingly, treatment with LPS or an MCD inhibitor did not alter intracellular triacylglycerol content. Furthermore, inhibition of MCD prevented LPS-induced increases in the level of ceramide in cardiomyocytes and macrophages while also ameliorating LPS-initiated decreases in PPAR binding. This suggests that the anti-inflammatory effect of MCD inhibition is mediated via accumulation of long-chain acyl-CoA, which in turn stimulates PPAR binding. Our results also demonstrate that pharmacological inhibition of MCD is a novel and promising approach to treat insulin resistance and its associated metabolic complications.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carboxy-Lyases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Insulin Resistance , Macrophage Activation/drug effects , Macrophages, Peritoneal/drug effects , Myocytes, Cardiac/drug effects , Animals , Animals, Newborn , Biological Transport/drug effects , Carboxy-Lyases/metabolism , Cardiotonic Agents/pharmacology , Cells, Cultured , Ceramides/metabolism , Glucose/metabolism , Lipid Metabolism/drug effects , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Mice , Myocytes, Cardiac/cytology , Myocytes, Cardiac/immunology , Myocytes, Cardiac/metabolism , Phenylurea Compounds/pharmacology , Phosphorylation/drug effects , Protein Processing, Post-Translational/drug effects , Proto-Oncogene Proteins c-akt/metabolism , RatsABSTRACT
Spasticity, resulting in involuntary and sustained contractions of muscles, may evolve in patients with stroke, cerebral palsy, multiple sclerosis, brain injury, and spinal cord injury (SCI). The authors critically review the neural mechanisms that may contribute to spasticity after SCI and assess their likely degree of involvement and relative significance to its pathophysiology. Experimental data from patients and animal models of spasticity as well as computer simulations are evaluated. The current clinical methods used for the management of spasticity and the pharmacological actions of drugs are discussed in relation to their effects on spinal mechanisms. Critical assessment of experimental findings indicates that increased excitability of both motoneurons and interneurons plays a crucial role in pathophysiology of spasticity. New interventions, including forms of spinal electrical stimulation to suppress increased neuronal excitability, may reduce the severity of spasticity and its complications.
Subject(s)
Muscle Spasticity/etiology , Muscle Spasticity/therapy , Spinal Cord Injuries/complications , Spinal Cord Injuries/therapy , Animals , Humans , Models, Neurological , Muscle Spasticity/physiopathology , Spinal Cord Injuries/physiopathologyABSTRACT
BACKGROUND: Acetylsalicylic acid (ASA) is used in the treatment of acute myocardial infarction (AMI) but is also a risk factor for peptic ulcer disease (PUD) bleeding. OBJECTIVE: To determine the factors associated with continued ASA use in patients with AMI who develop PUD bleeding. METHODS: AMI patients who developed PUD bleeding during the same hospitalization at two tertiary care hospitals in Edmonton, Alberta, between January 1999 and December 2006, were evaluated retrospectively. Multivariate analysis was used to determine predictors of the primary outcome of continued ASA use during PUD bleeding. RESULTS: A total of 102 patients were analyzed. Thirty-eight patients (37%) were continued on ASA, while 64 (63%) had ASA discontinued during their hospitalization. On multivariate regression analysis, significant predictors of continued ASA use included lowrisk ulcer stigmata on endoscopy (OR 3.7; 95% CI 1.4 to 10.2; P=0.01) and AMI requiring coronary intervention (OR 8.2; 95% CI 2.1 to 32.1; P=0.002). The mean (+/- SD) blood transfusion requirement was 3.9+/-3.6 units. The 30-day rebleeding and mortality rates were 14% and 14%, respectively. CONCLUSIONS: The continued use of ASA during AMI and PUD bleeding was variable. However, patients with low-risk ulcers and those who received coronary intervention were more likely to have ASA continued during PUD bleeding. Further studies evaluating the gastrointestinal risk of immediate ASA use in AMI with acute PUD bleeding are required.
