Neurocysticercosis in Persons with Epilepsy in Medellín,Colombia

Summary: Purpose: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellin, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. Methods: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. Results: Prevalence of neurocys@ercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellin. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. Conclusions: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.     

A statewide targeted burn prevention program

The statewide Burn Prevention Program has demonstrated a significant improvement in testable knowledge of burn prevention and fire safety among children and senior citizens as a result of an effective educational program. Formal evaluation using written examinations was done with the children. The statistical significance of the results of these evaluations was analyzed using chi square tests and two sample t tests. Significant improvements were seen in both mean test scores and the percentage of children answering all the test questions correctly. A much less formal type of evaluation was done with the elderly group. Senior citizens were assisted with a pre-program questionnaire. The results of this questionnaire were compared to the results of "BURN-GO" (copyright 1986), a bingotype game, played immediately after the educational session. Again, the post-implementation results of the program were significantly higher than those achieved prior to the intervention.     

Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1-3 mM DL-2-amino-5-phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss produced by N-methyl-D-aspartate (NMDA), with relatively little effect on that produced by either kainate or quisqualate. As expected, this selective NMDA receptor blockade only partially reduced the neuroexcitation or acute neuronal swelling produced by the broad-spectrum agonist glutamate; surprisingly, however, this blockade was sufficient to reduce glutamate-induced neuronal cell loss markedly. Lower concentrations of APV or D-APV had much less protective effect, suggesting that the blockade of a large number of NMDA receptors was required to acutely antagonize glutamate neurotoxicity. This requirement may be caused by the amplification of small amounts of acute glutamate-induced injury by subsequent release of endogenous NMDA agonists from injured neurons, as the "late" addition of 10-1000 microM APV or D-APV (after termination of glutamate exposure) also reduced resultant neuronal damage. If APV or D-APV were present both during and after glutamate exposure, a summation dose-protection relationship was obtained, showing substantial protective efficacy at low micromolar antagonist concentrations. Screening of several other excitatory amino acid antagonists confirmed that the ability to antagonize glutamate neurotoxicity might correlate with ability to block NMDA-induced neuroexcitation: The reported NMDA antagonists ketamine and DL-2-amino-7-phosphono-heptanoate, as well as the broad-spectrum antagonist kynurenate, were all found to attenuate glutamate neurotoxicity substantially; whereas gamma-D-glutamylaminomethyl sulfonate and L-glutamate diethyl ester, compounds reported to block predominantly quisqualate or kainate receptors, did not affect glutamate neurotoxicity. The present study suggests that glutamate neurotoxicity may be predominantly mediated by the activation of the NMDA subclass of glutamate receptors--occurring both directly, during exposure to exogenous compound, and indirectly, due to the subsequent release of endogenous NMDA agonists. Given other studies linking NMDA receptors to channels with unusually high calcium permeability, this suggestion is consistent with previous data showing that glutamate neurotoxicity depends heavily on extracellular calcium.     

The α1β1 and α2β1 Integrins Provide Critical Support for Vascular Endothelial Growth Factor Signaling, Endothelial Cell Migration, and Tumor Angiogenesis

Angiogenesis is a complex process, involving functional cooperativity between cytokines and endothelial cell (EC) surface integrins. In this study, we investigated the mechanisms through which the alpha(1)beta(1) and alpha(2)beta(1) integrins support angiogenesis driven by vascular endothelial growth factor (VEGF). Dermal microvascular EC attachment through either alpha(1)beta(1) or alpha(2)beta(1) supported robust VEGF activation of the Erk1/Erk2 (p44/42) mitogen-activated protein kinase signal transduction pathway that drives EC proliferation. Haptotactic EC migration toward collagen I was dependent on alpha(1)beta(1) and alpha(2)beta(1) as was VEGF-stimulated chemotaxis of ECs in a uniform collagen matrix. Consistent with the functions of alpha(1)beta(1) and alpha(2)beta(1) in supporting signal transduction and EC migration, antibody antagonism of either integrin resulted in potent inhibition of VEGF-driven angiogenesis in mouse skin. Moreover, combined antagonism of alpha(1)beta(1) and alpha(2)beta(1) substantially reduced tumor growth and angiogenesis of human squamous cell carcinoma xenografts. Collectively, these studies identify critical collaborative functions for the alpha(1)beta(1) and alpha(2)beta(1) integrins in supporting VEGF signal transduction, EC migration, and tumor angiogenesis.     

Comparison of the biomechanical effect of posterior condylar offset and kinematics between posterior cruciate-retaining and posterior-stabilized total knee arthroplasty

Background

The effect of the changes in the femoral posterior condylar offset (PCO) on anterior–posterior (AP) translation and internal–external (IE) rotation in cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) remains unknown. The purpose of this study was to compare the kinematics in CR and PS TKA with respect to the difference in prosthetic design and PCO change through a computational simulation.

Control of Mammalian Cell and Bacteria Adhesion on Substrates Micropatterned with Poly(ethylene glycol) Hydrogels

A simple method for controlling the spatial positioning of mammalian cells and bacteria on substrates using patterned poly(ethylene glycol) (PEG) hydrogel microstructures is described. These microstructures were fabricated using photolithography on silicon, glass or poly (dimethylsiloxane) (PDMS) surfaces modified with a 3-(trichlorosilyl) propyl methacrylate (TPM) monolayer. During the photogelation reaction, the resulting hydrogel microstructures were covalently bound to the substrate via the TPM monolayer and did not detached from the substrate upon hydration. For mammalian cell patterning, microwell arrays of different dimensions were fabricated. These microwells were composed of hydrophilic PEG hydrogel walls surrounding hydrophobic TPM floors inside the microwells. Murine 3T3 fibroblasts and transformed hepatocytes were shown to selectively adhere to the TPM monolayer inside the microwells, maintaining their viability, while adherent cells were not present on the hydrogel walls. The number of cells inside one microwell could be controled by changing the lateral dimension of the microwells, thus allowing only a single cell per microwell if desired. In the case of 30×30 m microwells, as many as 400 microwells were fabricated in 1 mm². In addition, PEG hydrogel microstructures were also shown to effectively resist the adhesion of bacteria such as Escherichia coli.     

Contribution of CsrR-regulated virulence factors to the progress and outcome of murine skin infections by Streptococcus pyogenes

Streptococcus pyogenes with null mutations in the csrRS regulatory locus are highly virulent in mice due to derepression of hyaluronic acid capsule synthesis and exotoxins, e.g., streptolysin S (SLS) and pyrogenic exotoxin B (SpeB). We generated derivatives of a DeltacsrRS strain that also carry deletions in hasAB (leading to an acapsular phenotype) or in sagA (phenotypically SLS-) or an interruption of speB (SpeB-) to test the relative contributions of these factors to the development of necrotic skin lesions. Inoculation of 2 x 10(6) to 4 x 10(6) CFU of either acapsular or SLS- strains into hairless mice resulted in lesions approximately 70% smaller than those of the DeltacsrRS parent strain. Elimination of SLS also reduced lethality from 100% to 0% at this inoculum (P < 10(-7); Fisher exact test). In contrast, SLS+ SpeB- mutants yielded lesions that were only 41% smaller than the parent strain (t = 2.2; P = 0.04), but only 3 the 17 lesions had dermal sloughing (P = 10(-5)). The nonulcerative lesions associated with SpeB- strains appeared pale with surrounding erythema. We conclude that capsule and SLS contribute to the subcutaneous spread of S. pyogenes and to a fatal outcome of infection. SpeB facilitates early dermal ulceration but has minor influence on lesion size and mortality. Large ulcerative lesions are observed only when both toxins are present.     

An efficient SNP system for mouse genome scanning and elucidating strain relationships

A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average ~1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608±136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies.