Altered fibroblast proliferation and apoptosis in diabetic gingival wounds.

Although it is known that diabetes impairs oral wound healing, relatively little is known about the cellular parameters affected, particularly in connective tissue. This study investigated the hypothesis that diabetes impairs connective tissue formation in healing gingiva, and that impaired healing is associated with factors that decrease fibroblast numbers. Full-thickness wounds were created in the palatal gingiva of type 1 and type 2 diabetic and normoglycemic mice.

FOXO1 plays an essential role in apoptosis of retinal pericytes.

Purpose: An early and significant event in diabetic retinopathy is the loss of retinal microvascular pericytes. Studies were performed to investigate pathways through which an advanced glycation endproduct and tumor necrosis factor (TNF)-alpha stimulate apoptosis in retinal pericytes through the activation of the pro-apoptotic transcription factor Forkhead box O1 (FOXO1).

Methods: Human retinal pericytes were stimulated by carboxymethyllysine (CML)-collagen, an advanced glycation endproduct, or TNF-alpha in vitro.

TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1.

To gain insight into the effect of diabetes on fracture healing, experiments were carried out focusing on chondrocyte apoptosis during the transition from cartilage to bone. Type 1 diabetes was induced in mice by multiple low-dose streptozotocin injections, and simple transverse fractures of the tibia or femur was carried out. Large-scale transcriptional profiling and gene set enrichment analysis were performed to examine apoptotic pathways on total RNA isolated from fracture calluses on days 12, 16, and 22, a period of endochondral bone formation when cartilage is resorbed and chondrocyte numbers decrease.

Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring.

Background: New intraparenchymal brain injury on magnetic resonance imaging is observed in 36% to 73% of neonates after cardiac surgery with cardiopulmonary bypass. Brain immaturity in this population is common. We performed brain magnetic resonance imaging before and after neonatal cardiac surgery, using a high-flow cardiopulmonary bypass protocol, hypothesizing that brain injury on magnetic resonance imaging would be associated with brain immaturity.

Impaired wound healing in mouse models of diabetes is mediated by TNF-alpha dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1).

Aims/hypothesis: The role of TNF-alpha in impaired wound healing in diabetes was examined by focusing on fibroblasts.

Methods: Small excisional wounds were created in the db/db mice model of type 2 diabetes and normoglycaemic littermates, and in a streptozotocin-induced type 1 diabetes mouse model and control mice. Fibroblast apoptosis was measured by the TUNEL assay, proliferation by detection of proliferating cell nuclear antigen, and forkhead box O1 (FOXO1) activity by DNA binding and nuclear translocation.

High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing.

Diabetes interferes with fracture repair; therefore, we investigated mechanisms of impaired fracture healing in a model of multiple low-dose streptozotocin-induced diabetes. Microarray and gene set enrichment analysis revealed an up-regulation of gene sets related to inflammation, including tumor necrosis factor (TNF) signaling in the diabetic group, when cartilage is being replaced by bone on day 16, but not on days 12 or 22. This change coincided with elevated osteoclast numbers and accelerated removal of cartilage in the diabetic group (P < 0.

Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro.

An aqueous extract of Ceylon cinnamon (C. zeylanicum) is found to inhibit tau aggregation and filament formation, hallmarks of Alzheimer's disease (AD). The extract can also promote complete disassembly of recombinant tau filaments and cause substantial alteration of the morphology of paired-helical filaments isolated from AD brain.

BMP2 is essential for post natal osteogenesis but not for recruitment of osteogenic stem cells.

The effects of BMP2 on bone marrow stromal cell differentiation and bone formation after bone marrow ablation were determined using C57 BL/6J (B6) mice. Inhibition of BMP2 expression with lentiviral BMP2 shRNA prevented both mineralized nodule formation in vitro and bone formation in vivo, and blocked the expression of Runx2 and osterix, transcriptional determinants of terminal osteogenic differentiation. No effect was observed on the expression of Sox9, a transcription factor, which is the one of the first transcriptional determinant to be expressed in committed chondroprogenitor and osteoprogenitor cells.

Outcome measures in spinal cord injury: recent assessments and recommendations for future directions.

Study Design: Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations.

Objectives: Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies.

Methods: a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI.

Interactions of actinomycin D with human telomeric G-quadruplex DNA.

The G-quadruplex structural motif of DNA has emerged as a novel and exciting target for anticancer drug discovery. The human telomeric G-quadruplex consists of a single strand repeat of d[AGGG(TTAGGG)(3)] that can fold into higher-order DNA structures. Small molecules that selectively target and stabilize the G-quadruplex structure(s) may serve as potential therapeutic agents and have garnered significant interest in recent years.

FOXO1 plays an important role in enhanced microvascular cell apoptosis and microvascular cell loss in type 1 and type 2 diabetic rats.

Objective: To investigate early events leading to microvascular cell loss in diabetic retinopathy.

Research Design And Methods: FOXO1 was tested in vivo by DNA binding activity and by nuclear translocation in microvascular cells in retinal trypsin digests. In vivo studies were undertaken in STZ-induced diabetic rats and Zucker diabetic fatty rats using the tumor necrosis factor (TNF)-specific blocker, pegsunercept, or by inhibiting FOXO1 with RNAi.

Activation of the acquired immune response reduces coupled bone formation in response to a periodontal pathogen.

Osteoimmunolgy involves the interaction of the immune system with skeletal elements. This interaction can lead to the formation of osseous lesions. To investigate how the acquired immune response could contribute to osteolytic lesions, we injected the periodontal pathogen Porphyromonas gingivalis adjacent to calvarial bone with or without prior immunization against the bacterium.

Diabetes causes the accelerated loss of cartilage during fracture repair which is reversed by insulin treatment.

Fracture healing in diabetic individuals and in animal models of diabetes is impaired. To investigate mechanisms by which diabetes may affect fracture healing we focused on the transition from cartilage to bone, a midpoint in the fracture healing process. Femoral fractures were induced in mice rendered diabetic by multiple low dose streptozotocin treatment and compared to matching normoglycemic mice.

International standards to document remaining autonomic function after spinal cord injury.

Study Design: Experts opinions consensus.

Objective: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI).

Background And Rationale: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI.

Toll-like receptor 9 mediates CpG oligonucleotide-induced cellular invasion.

Toll-like receptor 9 (TLR9) belongs to the innate immune system and recognizes microbial and vertebrate DNA. We showed previously that treatment with the TLR9-agonistic ODN M362 (a CpG sequence containing oligonucleotide) induces matrix metalloproteinase-13-mediated invasion in TLR9-expressing human cancer cell lines. Here, we further characterized the role of the TLR9 pathway in this process.

Cytokines that promote periodontal tissue destruction.

Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone, key features of the disease process. An intermediate mechanism that lies between bacterial stimulation and tissue destruction is the production of cytokines, which stimulates inflammatory events that activate effector mechanisms. These cytokines can be organized as chemokines, innate immune cytokines, and acquired immune cytokines.

Pelvic ischemia is measurable and symptomatic in patients with coronary artery disease: a novel application of dynamic contrast-enhanced magnetic resonance imaging.

Introduction: Pelvic ischemia can manifest as vascular-mediated erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), and is associated with cardiac ischemia.

Aims: We aimed to develop a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique to measure pelvic perfusion in benign tissue.

Methods: Nine men with coronary artery disease (CAD) were compared with nine without.

The transcription factor ST18 regulates proapoptotic and proinflammatory gene expression in fibroblasts.

Suppression of tumorigenicity 18 (ST18) and the homologues neural zinc-finger protein-3 (NZF3) and myelin transcription factor 3 (Myt3) are transcription factors with unknown function. Previous studies have established that they repress transcription of a synthetic reporter construct consisting of the consensus sequence AAAGTTT linked to the thymidine kinase promoter. In addition, ST18 exhibits significantly reduced expression in breast cancer and breast cancer cell lines.

Comparison of POCT and central laboratory blood glucose results using arterial, capillary, and venous samples from MICU patients on a tight glycemic protocol.

Background: Point of care (POC) glucose meters are routinely used to monitor glucose levels for patients on tight glycemic control therapy. We determined if glucose values were different for a POC glucose meter as compared to the main clinical laboratory for medical intensive care unit patients on a tight glycemic protocol and whether the site of blood sampling had a significant impact on glucose values.

Methods: Eighty-four patients (114 paired samples) who were on a tight glycemic protocol in the period November 2005 through August 2006 were enrolled.

P. gingivalis and E. coli lipopolysaccharides exhibit different systemic but similar local induction of inflammatory markers.

Background: Porphyromonas gingivalis is a Gram-negative bacterium that is an important etiologic agent of human adult periodontitis. The goal of the study was to test the hypothesis that two isoforms of P. gingivalis lipopolysaccharide (PgLPS), PgLPS(1435)(/1449) and PgLPS(1690), exhibit differences in their capacity to stimulate systemic versus local responses compared to Escherichia coli lipopolysaccharide (LPS).

Improving the efficiency of screening for major depression in people with spinal cord injury.

Background/objective: To investigate the metric properties, relative efficiency, sensitivity and specificity, and positive predictive value of a short form of the Patient Health Questionnaire-9 (PHQ-9) that may be used as a screening test for depression.

Methods: Data from the National Spinal Cord Injury Statistical Center Database containing 3,652 records with complete data for the PHQ-9 were analyzed using Confirmatory Factor Analysis, Item Response Theory Graded Response Model analysis, and sensitivity and specificity analysis of classification.

Results: A scale comprised of items 1, 2, and 6 from the PHQ-9 has a relative efficiency of 0.

Towards guidelines for evaluation of measures: an introduction with application to spinal cord injury.

Background: Both clinical practice and research in spinal cord injury (SCI) continue to struggle with issues of the quality and utility of outcome measures employed. Despite widespread deference to dicta on "reliability and validity," systematic means of grading the level of evidence for measures are lacking.

Objectives: This paper explains the methods and principles for use in systematic reviews of measures in SCI.

Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy.

Retinal microvascular cell loss plays a critical role in the pathogenesis of diabetic retinopathy. To examine this further, type 1 streptozotocin-induced diabetic rats and type 2 Zucker diabetic fatty rats were treated by intravitreal injection of the tumor necrosis factor-specific inhibitor pegsunercept, and the impact was measured by analysis of retinal trypsin digests. For type 2 diabetic rats, the number of endothelial cells and pericytes positive for diabetes-enhanced activated caspase-3 decreased by 81% and 86%, respectively, when treated with pegsunercept (P < 0.

Substituents on etoposide that interact with human topoisomerase IIalpha in the binary enzyme-drug complex: contributions to etoposide binding and activity.

Etoposide is a widely prescribed anticancer agent that stabilizes topoisomerase II-mediated DNA strand breaks. The drug contains a polycyclic ring system (rings A-D), a glycosidic moiety at C4, and a pendant ring (E-ring) at C1. A recent study that focused on yeast topoisomerase II demonstrated that the H15 geminal protons of the etoposide A-ring, the H5 and H8 protons of the B-ring, and the H2', H6', 3'-methoxyl, and 5'-methoxyl protons of the E-ring contact topoisomerase II in the binary enzyme-drug complex [ Wilstermann et al.