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At least 811 records · Page 45Linked to original sources
PubMed2003

Effects of fructose-1,6-bisphosphate on morphological and functional neuronal integrity in rat hippocampal slices during energy deprivation.

D-fructose-1,6-bisphosphate, a high energy glycolytic intermediate, attenuates ischemic damage in a variety of tissues, including brain. To determine whether D-fructose-1,6-bisphosphate serves as an alternate energy substrate in the CNS, rat hippocampal slices were treated with D-fructose-1,6-bisphosphate during glucose deprivation. Unlike pyruvate, an endproduct of glycolysis, 10 mM D-fructose-1,6-bisphosphate did not preserve synaptic transmission or morphological integrity of CA1 pyramidal neurons during glucose deprivation. Moreover, during glucose deprivation, 10-mM D-fructose-1,6-bisphosphate failed to maintain adenosine triphosphate levels in slices. D-fructose-1,6-bisphosphate, however, attenuated acute neuronal degeneration produced by 200 microM iodoacetate, an inhibitor of glycolysis downstream of D-fructose-1,6-bisphosphate. Because (5S, 10R)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine, an antagonist of N-methyl-D-aspartate receptors, exhibited similar protection against iodoacetate damage, we examined whether (5S, 10R)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine and D-fructose-1,6-bisphosphate share a common neuroprotective mechanism. Indeed, D-fructose-1,6-bisphosphate diminished N-methyl-D-aspartate receptor-mediated synaptic responses and partially attenuated neuronal degeneration induced by 100-microM N-methyl-D-aspartate. Taken together, these results indicate that D-fructose-1,6-bisphosphate is unlikely to serve as an energy substrate in the hippocampus, and that neuroprotective effects of D-fructose-1,6-bisphosphate are mediated by mechanisms other than anaerobic energy supply.

Adenosine Triphosphate↗
PubMed2005

Integrating cognitive function screening and assessment into the routine care of multiple sclerosis patients.

Cognitive dysfunction, a common feature of multiple sclerosis (MS), frequently leads to impaired activities of daily living, social skills deficits, diminished social support, and unemployment. There is growing evidence indicating that cognitive impairment is amenable to the effects of medication and behavioral counseling. Unfortunately, routine neuropsychological testing is rare in MS clinics because screening is ineffective and testing strategies are often too cumbersome or expensive. Recent research supports the reliability of a brief screening test called the Multiple Sclerosis Neuropsychological Screening Questionnaire as well as a minimal neuropsychological battery called the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Data indicate that the Multiple Sclerosis Neuropsychological Screening Questionnaire has excellent split-half and test-retest reliability, and that it predicts neuropsychological deficiency with good sensitivity and specificity. Recently acquired data also show that the Minimal Assessment of Cognitive Function in Multiple Sclerosis tests have good test-retest reliability, discriminate MS patients from normal controls, and predict unemployment in MS patients. Thus, these or similar methods should be employed for the routine monitoring of cognitive functioning of MS patients.

Adult↗
PubMed2004

Assessment of left ventricular volume and function by integration of simplified 3D echocardiography, tissue harmonic imaging and automated extraction of endocardial borders.

BACKGROUND: Quantitative three-dimensional echocardiography (3DEcho) of left ventricle (LV) is still limited because of the need for manually tracing endocardial borders: this can increase observer variability depending on the quality of fundamental (FUND) 2D images. We tested the combination of a simplified 3DEcho technique for LV reconstruction with automated endocardial border detection (Digital Echo Quantification, DEQ) and tissue harmonic imaging (THI) for enhancement of endocardium-cavity interface. METHODS: Twenty-five consecutive patients with ischaemic heart disease and dilated or distorted LV underwent 3DEcho and gated-SPECT nuclear examinations evaluating: (a) end-diastolic and end-systolic volumes (EDV, ESV); (b) ejection fraction (EF); (c) volume/time curve (VTC). Thereafter, 3DEcho was applied to 47 patients with acute myocardial infarction (AMI) at pre-discharge and 6 months to evaluate remodelling. RESULTS: Integrated 3DEcho values in THI modality were obtained in 84% of patients and correlated well with nuclear data for EDV (r = 0.95, mean difference = -2.2 +/- 15.8 ml), ESV (r = 0.98, mean difference = -3.5 +/- 10.2 ml), and EF (r = 0.82, mean difference = 0.6 +/- 6.4%; all mean differences NS vs. 0), with an interobserver variability of 4.9, 5.7 and 8.2% for EDV, ESV and EF respectively. Automated VTC by 3DEcho in THI modality reproduced well that obtained by nuclear technique (r = 0.96) and allowed recognition of LV remodelling in 36% of patients at 6 months. Integrated 3DEcho values in FUND modality were obtained only in 52% of patients and showed much higher errors and interobserver variability. CONCLUSIONS: THI permits accurate 3D reconstruction of LV borders detected by DEQ, allowing automated VTC throughout the cardiac cycle as well as study of LV remodelling.

Algorithms↗
PubMed2006

Mechanical tension and integrin alpha 2 beta 1 regulate fibroblast functions.

The extracellular matrix (ECM) environment in connective tissues provides fibroblasts with a structural scaffold and modulates cell shape, but it also profoundly influences the fibroblast phenotype. Here we studied fibroblasts cultured in a three-dimensional network of native collagen, which was either mechanically stressed or relaxed. Mechanical load induces fibroblasts that synthesize abundant ECM and a characteristic array of cytokines/chemokines. This phenotype is reminiscent of late granulation tissue or scleroderma fibroblasts. By contrast, relaxed fibroblasts are characterized by induction of proteases and a subset of cytokines that does not overlap with that of mechanically stimulated cells. Thus, the biochemical composition and physical nature of the ECM exert powerful control over the phenotypes of fibroblasts, ranging from "synthetic" to "inflammatory" phenotypes. Interactions between fibroblasts and collagen fibrils are mostly mediated by a subset of beta 1 integrin receptors. Fibroblasts utilize alpha 1 beta 1, alpha 2 beta 1, and alpha 11 beta 1 integrins for establishing collagen contacts and transducing signals. In vitro assays and mouse genetics have demonstrated individual tasks served by each receptor, but also functional redundancy. Unraveling the integrated functions of fibroblasts, collagen integrin receptors, collagen fibrils, and mechanical tension will be important to understand the molecular mechanisms underlying tissue repair and fibrosis.

Animals↗
PubMed1987

Temporal aspects of the pathophysiology of human ulcer disease.

In this paper, a peptic ulcer is considered from the perspective that it is representative of a heterogeneous group of multifactorial determined or influenced disorders having a common pathomorphologic expression. This heterogeneity involves pathophysiological attributes, including both functional (including secretory and motility events and their respective driving mechanisms) and morphologic alterations that relate to mucosal resistance. Patients with duodenal ulcer (DU) have been observed to exhibit alterations, in comparison to normal subjects, in the circadian rhythm characteristics of several gastrointestinal functions. Prominent among these are altered amplitudes of several circadian-organized gastric variables, such as intragastric pH, gastrin, pepsinogen and gastric mitotic index. With respect to any given variable, a reduced group amplitude (a measure of one-half the peak-trough difference of a 24-hr rhythm) could signify an increased dispersion of acrophases (the location of the peak of a circadian rhythm along the 24-hr time scale) reflecting interindividual variation in synchronization schedules, sleep-wake patterns, or chronobiologic alterations. A reduced interindividual amplitude further supports the concept of the heterogeneity of peptic disease. A decrease in the intraindividual amplitude of certain gastric rhythms implies an altered temporal pattern over the 24 hr. This is consistent with the hypothesis of a decrease in the amount of time available for recovery of a given function or set of integrated functions, and hence, increased susceptibility to mucosal injury. Normal high-amplitude variation in gastrointestinal functioning over the 24 hr appears to be required for natural restoration of the gut.

Circadian Rhythm↗
PubMed2004

Effect of perineurial window size on nerve regeneration, blood-nerve barrier integrity, and functional recovery.

End-to-side neurorrhaphy is used clinically to reconstruct nerve injuries when the lack of a suitable proximal nerve stump precludes conventional approaches to microsurgical repair. In end-to-side neurorrhaphy, the distal stump of a transected nerve is sutured to the side of an intact nerve that serves as an axon donor. Prior studies suggest that this perineurial window is a prerequisite for effective nerve regeneration into the recipient nerve. However, the optimal size for this perineurial window remains uncertain. This study evaluated the effect of perineurial window size on collateral axonal sprouting, blood-nerve barrier architecture, and functional impairment of the donor nerve. One hundred twenty Lewis rats were randomized to 1 and 5 mm perineurial window groups and examined at serial time points. The 5 mm perineurial window group exhibited significantly greater fiber counts at the repair zone than the 1mm group within 4 weeks (p < 0.005). Marked breakdown of the blood-nerve barrier was present 2 week postoperatively and resolved by 4 weeks regardless of 1 versus 5 mm perineurial window size. Tibial function indices in both groups normalized between 4 and 6 weeks postoperatively. A large (5 mm) perineurial window induced greater collateral sprouting or regenerative response than a small (1 mm) perineurial window without increasing cross sectional nerve injury or delaying functional recovery.

Animals↗
PubMed2003

Isolevuglandins, a novel class of isoprostenoid derivatives, function as integrated sensors of oxidant stress and are generated by myeloperoxidase in vivo.

Isolevuglandins (isoLGs) are a family of reactive gamma-ketoaldehydes generated by free radical oxidation of arachidonate-containing lipids through the isoprostane pathway. Elevated plasma levels of isoLG protein adducts are observed in subjects with atherosclerosis compared with age/gender-matched controls. However, mechanisms for the generation of isoLGs in vivo are not established. Here we show that free radical-induced peroxidation promoted by the myeloperoxidase (MPO)/H2O2 system of leukocytes serves as one mechanism for the generation of isoLGs in vivo. Using a Candida sepsis model of inflammation, we demonstrate 3.5- and 2.7-fold increases in iso[4]LGE2 and isoLGE2 adducts of plasma proteins after pathogen exposure in wild-type mice. Plasma levels of F2 isoprostanes were not significantly increased after pathogen challenge in this model. MPO knockout mice demonstrated significant reductions (34%, P=0.003) in plasma levels of iso[4]LGE2 protein adducts after pathogen challenge compared with wild-type mice. Mass spectrometry and immunochemical methods demonstrate MPO-dependent formation of iso[4]LGE2 and isoLGE2 phospholipids and their corresponding isoLG protein adducts in model systems. The present studies thus identify MPO as one pathway for generation of isoLGs in vivo. They also suggest that long-lived protein isoLG adducts may serve as an alternative integrated sensor of oxidant stress in vivo.

Animals↗
PubMed2000

Low-flow desflurane and sevoflurane anesthesia minimally affect hepatic integrity and function in elderly patients.

UNLABELLED: Hepatic blood flow is reduced in a dose-related manner by all inhaled anesthetics now in use. We assessed hepatic function in elderly patients anesthetized with desflurane or sevoflurane. We measured the cytosolic liver enzyme alpha glutathione S-transferase (alpha GST), the formation of the lidocaine metabolite monoethylglycinexylidide (MEGX), and gastric mucosal tonometry-derived variables as sensitive markers of hepatic function and splanchnic perfusion. Thirty patients, 70 to 90 yr old, were allocated randomly to receive desflurane or sevoflurane anesthesia. Anesthetic exposure ranged from 2.1-4.5 minimum alveolar concentration hours. No significant changes in standard liver enzyme markers were seen throughout the study. In both anesthetic groups, tonometric measurements showed a significant decrease from baseline in regional PCO(2), regional to arterial difference in PCO(2), and intramucosal pH at 90 min after skin incision. alpha GST concentrations increased significantly in both groups (desflurane: median peak concentrations 5.8 microg/L [25th, 75th percentile 5.3 microg/L, 7.2 microg/L]; sevoflurane: 7.0 microg/L [5.8 microg/L, 7.3 microg/L]) without showing differences between both anesthetic groups. A return to baseline values in tonometric values and alpha GST levels was seen 24 h postoperatively. MEGX formation did not change significantly after surgery. Median MEGX concentrations postoperatively were 70.0 ng/mL (56.2 ng/mL, 102.0 ng/mL) and 70.0 ng/mL (60.0 ng/mL, 94.2 ng/mL) in the desflurane and sevoflurane groups, respectively. We conclude that, overall, liver function in elderly patients is well preserved during desflurane and sevoflurane anesthesia. Increased serum levels of alpha GST and changes of gastric tonometry-derived variables imply a reduction in splanchnic perfusion, leading to a temporary impairment of hepatocyte oxygenation. IMPLICATIONS: We measured the lidocaine metabolite monoethylglycinexylidide, the cytosolic liver enzyme, alpha glutathione S-transferase, and gastric mucosal tonometry-derived variables to evaluate the effects of desflurane and sevoflurane on hepatic function in elderly patients. Liver function was well preserved, whereas increased alpha glutathione S-transferase levels and changes in tonometry-derived variables indicated a reduction in splanchnic blood flow and a temporary impairment of hepatocyte oxygenation for both anesthetics.

Aged↗
PubMedDate not supplied

Trauma registrar training: integrating registry functions into the trauma program--Part I.

The University of Pennsylvania Health System Trauma Network views the registry staff as key members of the trauma team and the registry as a vital component to the overall success of our programs. Trauma Registry databases are increasingly complex and require highly skilled and knowledgeable personnel to perform the functions of the job. Although the background and experience level of each registry staff member may differ, this orientation and training process provides a consistent educational experience for all. This guideline ensures that all registry functions are being performed in a standardized and consistent manner. It sets the stage for validation of not only the data, but also an individual's performance relative to abstraction and computer entry. Providing the proper learning environment for registry staff has proven to be most beneficial for our network as we strive to develop and maintain trauma registry databases which have a strong foundation and provide valid, useful and current information.

Abstracting and Indexing↗
PubMedDate not supplied

Trauma registrar training: integrating registry functions into the trauma program--Part 2.

Effective health-information management is heavily reliant upon the data-collection process of the health care program. This is also true in trauma-care systems, where healthcare providers have come to rely on timely access to complete and accurate information to support many critical functions of a trauma program. The process by which data are collected and analyzed deserves constant attention and reassessment. Data obtained in reports and analyses are only as accurate as the data abstraction and validation processes allow. The University of Pennsylvania Health System Trauma Network recognizes this, and as a result, developed this training and orientation guideline. This guideline supports the importance of the registry role in the overall trauma program, but most importantly, it fosters and supports a team approach to data collection, which in our experience has allowed us to develop and maintain trauma registry databases which provides valid, useful and current information for all.

Curriculum↗