Antibiotic eluting clay mineral (Laponite®) for wound healing application: an in vitro study.

Different materials in form of sponge, hydrogel and film have been developed and formulated for treating and dressing burn wounds. In this study, the potential of Laponite, a gel forming clay, in combination with an antimicrobial agent (mafenide), as a wound dressing material was tested in vitro. Laponite/mafenide (Lap/Maf) hydrogel was formulated in three different ratios of Lap/Maf 1:1, 1:2, 1:3. Laponite/mafenide/alginate (Lap/Maf/Alg) film was also formulated by combining Lap/Maf gel (1:1) with alginate. Intercalation rate of mafenide into the layers of Laponite nanoparticles and physico-chemical properties, including wound dressing characteristics of materials were studied using various analytical methods. Furthermore, the degradation of materials and the release profile of mafenide were investigated in simulated wound exudates fluid and antibacterial effectiveness of the eluted mafenide was tested on a range of bacterial species. The cytotoxicity of materials was also evaluated in skin fibroblast culture. The results showed that mafenide molecules were intercalated between the nano-sized layers of Laponite. The eluted mafenide showed active antibacterial effects against all three tested bacteria. All intercalated mafenide released from Lap/Maf 1:1 and 1:2 gel formulations and nearly 80% release from 1:3 formulation during test period. No significant difference was observed in release profile of mafenide between Lap/Maf/Alg film and Lap/Maf formulations. Wound dressing tests on Lap/Maf/Alg film showed it is a breathable dressing and has capacity to absorb wound exudates. The study showed that prepared Lap/Maf composite has the potential to be used as an antibiotic eluting gel or film for wound healing application. Additionally, Laponite has shown benefits in wound healing processes by releasing Mg(2+) ions and thereby reducing the cytotoxic effect of mafenide on fibroblast cells.

Biointerface: protein enhanced stem cells binding to implant surface.

The number of metallic implantable devices placed every year is estimated at 3.7 million. This number has been steadily increasing over last decades at a rate of around 8 %. In spite of the many successes of the devices the implantation of biomaterial into tissues almost universally leads to the development of an avascular sac, which consists of fibrous tissue around the device and walls off the implant from the body. This reaction can be detrimental to the function of implant, reduces its lifetime, and necessitates repeated surgery. Clearly, to reduce the number of revision surgeries and improve long-term implant function it is necessary to enhance device integration by modulating cell adhesion and function. In this paper we have demonstrated that it is possible to enhance stem cell attachment using engineered biointerfaces. To create this functional interface, samples were coated with polymer (as a precursor) and then ion implanted to create a reactive interface that aids the binding of biomolecules--fibronectin. Both AFM and XPS analyses confirmed the presence of protein layers on the samples. The amount of protein was significant greater for the ion implanted surfaces and was not disrupted upon washing with detergent, hence the formation of strong bonds with the interface was confirmed. While, for non ion implanted surfaces, a decrease of protein was observed after washing with detergent. Finally, the number of stem cells attached to the surface was enhanced for ion implanted surfaces. The studies presented confirm that the developed bionterface with immobilised fibronectin is an effective means to modulate stem cell attachment.

Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR.

The efficacy, safety and tolerability of bupropion XR and venlafaxine XR was assessed and compared with placebo in adult outpatients with major depressive disorder (MDD). Adults meeting DSM-IV criteria for MDD with a minimum Hamilton Depression Rating Scale (HAMD) 17-Item total score of > or =18 were randomized to eight weeks of double-blind treatment with either bupropion XR (150 mg/day), venlafaxine XR (75 mg/day) or placebo. At the end of the fourth week of treatment, a dosage increase to bupropion XR 300 mg/day or venlafaxine XR 150 mg/day was allowed if, in the opinion of the investigator, response was inadequate. The primary efficacy endpoint was mean change from baseline at week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last observation carried forward (LOCF). Mean changes from baseline at week 8 (LOCF) in MADRS total score were statistically significant for bupropion XR and venlafaxine XR patients compared to the placebo group: -16.0 for bupropion XR (P = 0.006 vs placebo), -17.1 for venlafaxine XR (P < 0.001 vs placebo) and -13.5 for placebo. Secondary outcomes (including CGI-S, HAM-A, MEI, Q-LES-Q-SF, responder and remitter analyses) also improved significantly for both active treatment groups compared with placebo. The most frequently reported adverse events were dry mouth and insomnia for bupropion XR, and nausea, hyperhidrosis, fatigue, and insomnia for venlafaxine XR. In this double-blind, placebo-controlled trial, bupropion XR at doses up to 300 mg/day and venlafaxine XR at doses up to 150 mg/day demonstrated comparable antidepressant efficacy.

Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine - a new paradigm for tissue repair.

Tissue regeneration by stem cells is driven by the paracrine activity of shedding vesicles and exosomes, which deliver specific cargoes to the recipient cells. Proteins, RNA, cytokines and subsequent gene expression, orchestrate the regeneration process by improving the microenvironment to promote cell survival, controlling inflammation, repairing injury and enhancing the healing process. The action of microRNA is widely accepted as an essential driver of the regenerative process through its impact on multiple downstream biological pathways, and its ability to regulate the host immune response. Here, we present an overview of the recent potential uses of exosomes for regenerative medicine and tissue engineering. We also highlight the differences in composition between shedding vesicles and exosomes that depend on the various types of stem cells from which they are derived. The conditions that affect the production of exosomes in different cell types are deliberated. This review also presents the current status of candidate exosomal microRNAs for potential therapeutic use in regenerative medicine, and in applications involving widely studied organs and tissues such as heart, lung, cartilage and bone.

Orientation and conformation of anti-CD34 antibody immobilised on untreated and plasma treated polycarbonate.

The conformation and orientation of proteins immobilised on synthetic materials determine their ability to bind their antigens and thereby the sensitivity of the microarrays and biosensors employing them. Plasma immersion ion implantation (PIII) of polymers significantly increases both their wettability and protein binding capacity. This paper addresses the hypothesis that a PIII treated polymer surface modifies the native protein conformation less significantly than a more hydrophobic untreated surface and that the differences in surface properties also affect the protein orientation. To prove this, the orientation and conformation of rat anti-mouse CD34 antibody immobilized on untreated and PIII treated polycarbonate (PC) were investigated using ToF-SIMS and FTIR-ATR spectroscopy. Analysis of the primary structure of anti-CD34 antibody and principal component analysis of ToF-SIMS data were applied to detect the difference in the orientation of the antibody attached to untreated and PIII treated PC. The difference in the antibody conformation was analysed using deconvolution of the Amide I peak (in FTIR-ATR spectra) and curve-fitting. It was found that compared to the PIII treated sample, the antibody immobilized on the untreated PC sample has a secondary structure with a lower fraction of ß-sheets and a higher fraction of α-helices and disordered fragments. Also, it was found that anti-CD34 antibody has a higher tendency to occur in the inactive 'tail-up' orientation when immobilized on an untreated PC surface than on a PIII treated surface. These findings confirm the above hypothesis.

Vitreoretinal surgery in diabetic patients on hemodialysis.

The present paper reports our first results after pars plana vitrectomy in patients with diabetic retinopathy and hemodialysis with a follow-up of 6 to 24 months. Between January 1992 and October 1994 we performed vitreoretinal surgery with silicone oil tamponade in nine eyes of seven patients with diabetic nephropathy on hemodialysis. All patients had had type I diabetes for 19-32 years. Over the observation period the retina was completely attached in eight eyes. Final visual acuity of 0.1-0.7 was attained in four eyes, 0.06 two, hand movements in one eye. Two eyes had no useful final visual acuity because of redetachment of the retina or secondary glaucoma with rubeosis iridis. The small number of complications shows that pars plana vitrectomy can be done in diabetic patients with nephropathy on hemodialysis. This significantly improves their quality of life.

[Results of two year use of dipyridamole and metindol in patients with primary focal and (or) segmental glomerulosclerosis]. / Wyniki dwuletniego stosowania dipirydamolu i metindolu w leczeniu chorych na pierwotne, ogniskowe i (albo) segmentalne szkliwiejace klebkowe zapalenie nerek.

Primary focal or segmental glomerulosclerosis is neuropathy diagnosed in 10% of children and 20% of adult patients with nephrotic syndrome. Immunosuppressive therapy was applied during two years period. The very good clinical results were obtained in 20% and good results in 40% of patients after indomethacin and dipyridamole therapy.

A mini-review on novel intraperiodontal pocket drug delivery materials for the treatment of periodontal diseases.

Periodontal disease is defined as chronic inflammatory condition characterized by the destruction of the periodontal tissues causing loss of connective tissue attachment, loss of alveolar bone, and the formation of pathological pockets around the diseased teeth. The use of systemic antibiotics has been advocated for its treatment, but concerns emerged with respect to adverse drug reactions and its contribution to bacterial resistance. Thus local drug delivery devices have been developed that aim to deliver a high concentration of antimicrobial drugs directly to the affected site, while minimizing drug's systemic exposure. A burst release of antimicrobial agent from carrier, resulting in a short and inadequate exposure of bacteria residing in periodontal pocket to the agent, remains the main challenge of current local delivery systems for the treatment of periodontal disease. This review aims to investigate and compare different local antimicrobial delivery systems with regard to the treatment of periodontal disease.

Surface characteristics and microbial adherence ability of modified polymethylmethacrylate by fluoridated glass fillers.

BACKGROUND: The current study objectives were to evaluate the influence of fluoridated glass fillers loading on the surface roughness, wettability, and adherence of candida and bacteria with and without saliva presence to a polymethylmethacrylate (PMMA) denture base material surface. METHODS: Four concentrations of fluoridated glass fillers were added to PMMA: 1%, 2.5%, 5% and 10% by weight pre-polymerization and 0% was the control. Discs of each concentration were fabricated (n = 5 for each variable). Surface roughness (Ra ) was measured using atomic force microscopy (AFM). Wettability was assessed by measuring the contact angle of a sessile drop of water. Specimens were incubated with Candida albicans, or Streptococcus mutans with and without saliva coating. Adherence was presented as a percentage of the colonized surface area, counted using an optical microscope at x100 magnification. RESULTS: The 10% group showed significantly greater roughness than the control and 1% groups; however, no significant differences in contact angle values were detected. The microbial adhesion was inversely proportional to the fluoridated glass fillers concentration where 10% concentration significantly decreased candidal and bacterial adhesion compared to others. Saliva coating significantly decreased microbial adhesion. CONCLUSIONS: It was concluded that fluoridated glass fillers could decrease microbial adhesion to acrylic denture base without adversely affecting surface properties.

Biocompatible, smooth, plasma-treated nickel-titanium surface--an adequate platform for cell growth.

High nickel content is believed to reduce the number of biomedical applications of nickel-titanium alloy due to the reported toxicity of nickel. The reduction in nickel release and minimized exposure of the cell to nickel can optimize the biocompatibility of the alloy and increase its use in the application where its shape memory effects and pseudoelasticity are particularly useful, e.g., spinal implants. Many treatments have been tried to improve the biocompatibility of Ni-Ti, and results suggest that a native, smooth surface could provide sufficient tolerance, biologically. We hypothesized that the native surface of nickel-titanium supports cell differentiation and insures good biocompatibility. Three types of surface modifications were investigated: thermal oxidation, alkali treatment, and plasma sputtering, and compared with smooth, ground surface. Thermal oxidation caused a drop in surface nickel content, while negligible chemistry changes were observed for plasma-modified samples when compared with control ground samples. In contrast, alkali treatment caused significant increase in surface nickel concentration and accelerated nickel release. Nickel release was also accelerated in thermally oxidized samples at 600 °C, while in other samples it remained at low level. Both thermal oxidation and alkali treatment increased the roughness of the surface, but mean roughness R(a) was significantly greater for the alkali-treated ones. Ground and plasma-modified samples had 'smooth' surfaces with R(a)=4 nm. Deformability tests showed that the adhesion of the surface layers on samples oxidized at 600 °C and alkali treatment samples was not sufficient; the layer delaminated upon deformation. It was observed that the cell cytoskeletons on the samples with a high nickel content or release were less developed, suggesting some negative effects of nickel on cell growth. These effects were observed primarily during initial cell contact with the surface. The most favorable cell responses were observed for ground and plasma-sputtered surfaces. These studies indicated that smooth, plasma-modified surfaces provide sufficient properties for cells to grow.

Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.

Major depressive disorder in the elderly is associated with increased morbidity and reduced quality of life. This 10 week, placebo-controlled study investigated the efficacy and tolerability of extended-release bupropion (150-300 mg once daily) in depressed patients aged 65 years or older. The statistical assumptions necessary for the validity of the protocol-specified analysis of covariance were not met for the analysis of the primary outcome variable (Montgomery-Asberg Depression Rating Scale total score at Week 10, last observation carried forward). Alternative statistical methods used for the analysis of this variable demonstrated statistical significance. Statistically significant improvements were observed on the majority of secondary end points when compared with placebo, including the health outcome measures for motivation and energy, and life satisfaction and contentment. Adverse events were generally mild to moderate and similar between treatment groups. This study demonstrated that the extended-release bupropion is an effective, well-tolerated treatment for major depression in the elderly.