Three-dimensional, nano-structured PLGA scaffolds for bladder tissue replacement applications

In total, approximately 400 million people worldwide suffer from urinary bladder cancer (Nat Biotechnol 17 (1999) 149). When radical cysectomy is required as treatment, a replacement material is clearly necessitated. For this purpose, three-dimensional poly(lactic-co-glycolic acid) (PLGA) scaffolds were constructed using solvent casting and salt leaching processes. These scaffolds were manipulated to possess nano-dimensional surface features by soaking in sodium hydroxide at select concentrations and for various periods of time. Human bladder smooth muscle cells were then seeded onto these nano-dimensional scaffolds; adhesion and longer-term cell growth experiments were performed for either 4 h, or 1, 3, and 5 days, respectively. Additionally, collagen and elastin production was quantified following each experiment. In all cases, control cells were placed in an incubator and subjected to normal atmospheric pressure, while experimental cells were placed in a pressure chamber and subjected to a sustained pressure of 10 cm H(2)O. Results of this study provided evidence that porous, nano-dimensional polymeric scaffolds enhanced cell adhesion and growth, while also promoting increased elastin and collagen production. Moreover, in general, exposure to pressure did not alter cellular adhesion, growth, or extracellular matrix protein production, which suggests that the scaffolds and their resident cells will fair well in the complex mechanical environment of the bladder wall. In combination, these results provide evidence that the nano-dimensional PLGA scaffolds created in this research are promising as the next generation of bladder wall replacement materials.     

Accelerated chondrocyte functions on NaOH-treated PLGA scaffolds

Compared to conventional poly(lactic-co-glycolic acid) (PLGA), previous studies have shown that NaOH-treated PLGA two-dimensional substrates enhanced functions of osteoblasts (bone-forming cells), vascular and bladder smooth muscle cells, and chondrocytes (cartilage-synthesizing cells). In this same spirit, the purpose of this in vitro study was to fabricate three-dimensional NaOH-treated PLGA scaffolds and determine their efficacy toward articular cartilage applications. To improve functions of chondrocytes including their adhesion, growth, differentiation, and extracellular matrix synthesis, PLGA scaffolds were modified via chemical etching techniques using 1N NaOH for 10 min. Results demonstrated that NaOH-treated PLGA three-dimensional scaffolds enhanced chondrocyte functions compared to non-treated scaffolds. Specifically, chondrocyte numbers, total intracellular protein content, and the amount of extracellular matrix components (such as glycosaminoglycans and collagens) were significantly greater on NaOH-treated than on non-treated PLGA scaffolds. Underlying material properties that may have enhanced chondrocyte functions include a more hydrophilic surface (due to hydrolytic degradation of PLGA by NaOH), increased surface area, altered porosity (both percent and diameter of individual pores), and a greater degree of nanometer roughness. For these reasons, this study adds a novel tissue-engineering scaffold to the cartilage biomaterial community: NaOH-treated PLGA. Clearly, such modifications to PLGA may ultimately enhance the efficacy of tissue-engineering scaffolds for articular cartilage repair.     

Increased osteoblast functions on theta + delta nanofiber alumina

Nanophase materials, or materials with grain sizes less than 100 nm in at least one direction, are promising materials for various implant applications since our tissues are composed of nanometer components (i.e., proteins and/or inorganics). Specifically, bone is comprised of nanostructured hydroxyapatite and collagen fibers which continuously provide an extracellular matrix surface to bone-forming cells (osteoblasts) with a high degree of nanometer roughness. Despite this fact, materials currently utilized for orthopedic implants, whether metallic or ceramic, have constituent grain sizes in the non-biologically inspired micron regime. For this reason, the objective of the present in vitro study was to determine osteoblast functions on one classification of nanomaterials for orthopedic applications: nanofiber alumina. Various crystalline forms of nanofiber alumina were tested in this study. To obtained different crystalline structured nanofiber alumina, boehmite nanofiber alumina was sintered at either 400 degrees C, 600 degrees C, 800 degrees C, 1000 degrees C, or 1200 degrees C for 2 h in air. X-ray diffraction results provided evidence that boehmite nanofiber alumina remained boehmite when sintered at 400 degrees C but changed crystalline phases to gamma, gamma + delta, theta + delta, and alpha when sintered at 600 degrees C, 800 degrees C, 1000 degrees C, and 1200 degrees C, respectively. Moreover, compared to any other alumina formulation tested in this study, osteoblast functions (as measured by alkaline phosphatase activity and calcium deposition) were the greatest on theta + delta crystalline phase nanofiber alumina after 14 days of culture. Boehmite had the next greatest amount of calcium deposition by osteoblasts followed by gamma + delta. Gamma crystalline phase then followed and was greater than alpha crystalline phase nanofiber alumina which promoted osteoblast functions the least of all the compacts with the exception of borosilicate glass (reference substrate). For this reason, this study suggests that theta+delta nanofiber alumina should be further investigated in orthopedic applications.     

Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice

BACKGROUND. Control of highly pathogenic avian H5N1 influenza viruses is a major public-health concern. Antiviral drugs could be the only option early in the pandemic.METHODS. BALB/c mice were given oseltamivir (0.1, 1, or 10 mg/kg/day) twice daily by oral gavage; the first dose was given 4 h before inoculation with H5N1 A/Vietnam/1203/04 (VN1203/04) virus. Five- and 8-day regimens were evaluated.RESULTS. Oseltamivir produced a dose-dependent antiviral effect against VN1203/04 in vivo (P<.01). The 5-day regimen at 10 mg/kg/day protected 50% of mice; deaths in this treatment group were delayed and indicated the replication of residual virus after the completion of treatment. Eight-day regimens improved oseltamivir efficacy, and dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively (P<.05). Overall, the efficacy of the 5- and 8-day regimens differed significantly (death hazard ratio, 2.658; P<.01). The new H5N1 antigenic variant VN1203/04 was more pathogenic in mice than was A/HK/156/97 virus, and a prolonged and higher-dose oseltamivir regimen may be required for the most beneficial antiviral effect.CONCLUSIONS. Oseltamivir prophylaxis is efficacious against lethal challenge with VN1203/04 virus in mice. Viral virulence may affect the antiviral treatment schedule.     

Rapid assessment of microbial hazards in metalworking fluids

Industries that use metalworking fluids require a test method that can rapidly estimate the total number of bacteria. Such a test method would improve the ability to manage the metal working fluid by allowing near real-time decision making. The ability to manage the fluid more consistently and make critical decisions as they arise would reduce occupational exposures to contaminated metalworking fluid and likely result in fewer worker complaints and/or work stoppages. In this study, a filtration-based rapid adenosine triphosphate bioluminescence assay, which takes less than 10 min to perform, was evaluated as a test method for estimating total bacteria populations in metalworking fluid. This evaluation used two types of metalworking fluid (soluble and semisynthetic) that were inoculated using Pseudomonas aeruginosa and spoiled metalworking fluid. Daily parallel testing was completed on metalworking fluid samples using the rapid adenosine triphosphate assay and the standard plate count methods. Daily test results were evaluated by calculating r2 values using statistical correlation and regression procedures for each fluid type. Study results indicate the rapid adenosine triphosphate assay is strongly correlated to the standard plate count method for soluble and semisynthetic fluids, producing results of r2 = 0.74 and r2 = 0.89, respectively.     

Will periodic intravenous injections of conditioned bone marrow cells effectively reduce atherosclerosis?

Maintenance of healthy arteries requires a balance between injuries to the arterial wall and processes of intrinsic arterial repair. Such repair requires the availability of progenitor cells that are local to the wall itself. Progenitor cells from distant reservoirs like the bone marrow may also contribute to repair. Arterial repair seems to degrade over a lifetime, particularly with risk factors such as smoking and diabetes. Hence, a potential preventive/therapeutic strategy for atherosclerosis could be transfusion of competent bone marrow cells (BMCs) to restore effective repair in the face of arterial injury and depleted endogenous repair reservoirs. The challenge with this strategy has been the reliable collection and/or generation of BMCs that support arterial repair. In this study, we describe a set of experiments to elucidate a method of culturing BMCs that robustly retards atherosclerosis development in apolipoprotein E knockout mice. Identifying such a method would represent an important step in developing cell-based treatments for patients with proclivity for developing atherosclerosis.     

Retinal dysfunction and high myopia in association with 48,XXYY syndrome

Purpose

48,XXYY syndrome was first described in 1964 and approximately 100 cases have been reported in the literature. We report a case of 48,XXYY syndrome associated with high myopia and retinal dysfunction.

Methods

Case report.

Results

A 28-year-old man was referred with progressive deterioration of visual acuity (VA) bilaterally during the previous 4–5 years. Physical examination revealed tall stature, large feet and irregular teeth. Refraction revealed high myopia with VA 6/60 bilaterally. Fundoscopy revealed a normal vitreous, lightly pigmented retinal pigment epithelium and choroid but no bone spicules or overt signs of retinal degeneration. His visual fields were constricted. Electrodiagnostic testing revealed bilateral generalised retinal dysfunction with severe macular involvement. During follow-up, his ophthalmic examination did not exhibit significant changes while VA was gradually deteriorating. Eight years after presentation, VA was 3/60 bilaterally; electrophysiological testing showed no further change. At that stage, his parents consented for DNA analysis in order to determine the cause of retinal dysfunction. Chromosomal analysis revealed an abnormal male karyotype with two X chromosomes and two Y chromosomes consistent with 48,XXYY syndrome.

Conclusions

The present report is the first to describe retinal dysfunction and high myopia with 48,XXYY syndrome. The severe macular and generalised retinal dysfunction in this case are not those associated with myopia and are in keeping with a primary retinal dysfunction. A coincidental finding cannot be excluded, but ERGs have not previously been reported in 48,XXYY syndrome, and retinal dystrophy may be a previously undiagnosed component of this syndrome.     

Small bowel perforation secondary to accidental dental plate ingestion

The majority of ingested foreign bodies will pass through the gastrointestinal tract without incident, with less than 1% of cases resulting in complications. Herein we present a case of small bowel perforation secondary to the accidental ingestion of a dental plate. A diagnosis of perforation was made by CT imaging, but the exact cause could only be determined after resection of the affected bowel and histo-pathological examination. We re-iterate the importance of accurate and thorough history taking in patients with possible foreign body ingestion.