Mechanical characterization of collagen fibers and scaffolds for tissue engineering

Engineered tissues must utilize scaffolding biomaterials that support desired cellular functions and possess or can develop appropriate mechanical characteristics. This study assessed properties of collagen as a scaffolding biomaterial for ligament replacements. Mechanical properties of extruded bovine achilles tendon collagen fibers were significantly affected by fiber diameter, with smaller fibers displaying higher tangent moduli and peak stresses. Mechanical properties of 125 micrometer-diameter extruded fibers (tangent modulus of 359.6+/-28.4MPa; peak stress of 36.0+/-5.4MPa) were similar to properties reported for human ligaments. Scaffolds of extruded fibers did not exhibit viscoelastic creep properties similar to natural ligaments. Collagen fibers from rat tail tendon (a well-studied comparison material) displayed characteristic strain-softening behavior, and scaffolds of rat tail fibers demonstrated a non-intuitive relationship between tangent modulus and specimen length. Composite scaffolds (extruded collagen fibers cast within a gel of Type I rat tail tendon collagen) were maintained with and without fibroblasts under standard culture conditions for 25 days; cell-incorporated scaffolds displayed significantly higher tangent moduli and peak stresses than those without cells. Because tissue-engineered products must possess appropriate mechanical as well as biological/chemical properties, data from this study should help enable the development of improved tissue analogues.     

A clinical, demographic and microbiologic study of ANUG patients in an urban dental school

35 ANUG patients were examined and compared clinically and demographically. Plaque removed from ulcerated sites in 20 patients was cultured using quantitative anaerobic procedures and examined by electron and darkfield microscopy. Patients were classified as having ANUG when presenting with ulceration and necrosis of interproximal papillae, pain and bleeding. The clinical symptoms of fetid odor, pseudomembrane formation, lymphadenopathy and elevated body temperature were present in 97%, 85%, 61% and 39% of the ANUG patients, respectively. 83% of the patients were smokers. The ANUG patients demonstrated a lower average age (24 years) than the general clinic population (32 years). There was a slightly higher % of male (54%) than female (46%) and the % of Caucasian (51%) and black (49%) ANUG patients were almost equal. Cultural studies revealed that gram-negative rods were the predominant cultivable micro-organisms present in the plaque, representing 78.2% of the total recoverable count. Of these, nearly half were strict anaerobes with Bacteroides gingivalis and Fusobacterium nucleatum accounting for 7.8% and 3.4%, respectively. Anaerobic and facultative gram-positive cocci (15.5%), gram-negative cocci (3.5%) and gram-positive rods (2.8%) were also isolated. Microscopic analysis of the morphologic composition of plaque revealed that rods (43%) constituted the greatest % of the total microorganisms observed followed by spirochetes (30%) and cocci (27%). 8 distinct types of spirochetal periplasmic flagellar arrangement were observed by electron microscopy, the "2-4-2" periplasmic flagellar arrangement being most numerous.     

Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.     

Care processes and clinical outcomes of continuous outpatient support with inotropes (COSI) in patients with refractory endstage heart failure

BACKGROUND: This study describes the process and outcomes of continuous outpatient support with inotropes (COSI) in patients with Stage D heart failure (HF). Although Stage D HF has recently been defined as end-stage disease requiring special interventions for survival such as COSI or ventricular assist devices, concern has been raised regarding the safety, efficacy, mortality outcomes, and ethics of COSI. METHODS AND RESULTS: Inotrope dependence was defined as worsening of the patient's clinical status with attempted inotrope withdrawal such that the patient was deemed unlikely to survive to permit hospital discharge. A care process for COSI was designed; baseline and outcome variables were evaluated. COSI was administered to 36 inotrope-dependent patients (age 55.4 +/- 9.5 years, 24 males). Baseline characteristics (mean +/- SD) were consistent with Stage D HF: left ventricular ejection fraction 19.9 +/- 8.5, left ventricular end-diastolic dimension (LVEDD) 70 +/- 10 mm, systolic blood pressure 97.4 +/- 13.4 mm Hg, serum creatinine 1.5 +/- 0.6, serum sodium 131.7 +/- 5.3; 69 HF hospitalizations (mean 1.9 +/- 1.8) 6 months before COSI initiation. Symptomatic hypotension, increasing dyspnea, renal dysfunction, and hypoperfusion most commonly prevented inotrope withdrawal. Despite Stage D HF, patients were discharged with COSI ambulatory, oriented, and pain free. Rehospitalizations were 46; 6 subjects accounted for 24 hospitalizations; 23 had 0 or 1 rehospitalization. Median survival was 3.4 months (range 0.2-26.3 months); and 3-, 6-, and 12-month Kaplan Meier survival was 51%, 26%, and 6%, respectively. The majority of patients died at home and chose to not undergo resuscitation attempts. CONCLUSION: COSI may be an acceptable treatment option for Stage D HF.     

Association of G-174C Polymorphism of the Interleukin-6 Gene Promoter with Graves' Ophthalmopathy

Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves' ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6 gene promoter polymorphism, at position -174 (G→C, termed as G-174C), which may affect IL-6 production, with the development of GO. The G-174C polymorphism was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and 186 healthy Polish adults. In patients with GD, the frequencies of the C allele (45 vs 42%; P=0.35) and C/C genotype (20 vs 15%; P=0.13) were not significantly different compared to controls. Subdividing patients with GD for the presence of eye disease revealed that the C allele (44 vs 45%; P=0.76) and C/C genotype (20 vs 20%; P=0.92) were equally distributed in patients with or without ophthalmopathy. There was also no association between the G-174C polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not associated with laboratory findings (thyroid volume, serum IL-6 and thyroid autoantibodies levels) in patients with GD at diagnosis. Our results suggest that G-174C polymorphism of the IL-6 gene does not contribute to the development and severity of GO.     

Size-dependent magnetic and magnetothermal properties of gadolinium silicide nanoparticles

Gadolinium silicide (Gd₅Si₄) nanoparticles are an interesting class of materials due to their high magnetization, low Curie temperature, low toxicity in biological environments and their multifunctional properties. We report the magnetic and magnetothermal properties of gadolinium silicide (Gd₅Si₄) nanoparticles prepared by surfactant-assisted ball milling of arc melted bulk ingots of the compound. Using different milling times and speeds, a wide range of crystallite sizes (13–43 nm) could be produced and a reduction in Curie temperature (T_C) from 340 K to 317 K was achieved, making these nanoparticles suitable for self-controlled magnetic hyperthermia applications. The magnetothermal effect was measured in applied AC magnetic fields of amplitude 164–239 Oe and frequencies 163–519 kHz. All particles showed magnetic heating with a strong dependence of the specific absorption rate (SAR) on the average crystallite size. The highest SAR of 3.7 W g⁻¹ was measured for 43 nm sized nanoparticles of Gd₅Si₄. The high SAR and low T_C, (within the therapeutic range for magnetothermal therapy) makes the Gd₅Si₄ behave like self-regulating heat switches that would be suitable for self-controlled magnetic hyperthermia applications after biocompatibility and cytotoxicity tests.

Gadolinium silicide (Gd₅Si₄) nanoparticles prepared by surfactant-assisted ball milling exhibit a size-dependent reduction in magnetic ordering temperature and a high magnetothermal effect making them suitable for magnetic hyperthermia applications.