Development and Mechanical Characterization of Bioadhesive Semi-Solid,Polymeric Systems Containing Tetracycline for the Treatment of Periodontal Diseases

Purpose. This study examined the mechanical characteristics and release of tetracycline from bioadhesive, semi-solid systems which were designed for the treatment of periodontal diseases. Methods. Tetracycline release into phosphate buffered saline (pH 6.8, 0.03 M) was examined using a Caleva 7ST dissolution apparatus at 37°C. The mechanical properties of each formulation (hardness, compressibility, adhesiveness, elasticity and cohesiveness) were determined using texture profile analysis. Syringeability was measured using the texture analyser in compression mode as the work of syringeability i.e. the force required to express the product from a periodontal syringe over a defined distance. Results. Tetracycline release from all formulations was zero-order for 24–54 h and ranged from 1.59 ± 0.20 to 15.80 ± 0.50 mg h^–1. Increased concentrations of hydroxyethylcellulose (HEC) decreased the rate of release of tetracycline, due to the concomitant increase in product viscosity and the subsequent decreased rate of penetration of dissolution fluid into the formulation. Conversely, an increased polyvinylpyrrolidone (PVP) concentration increased tetracycline release rates, due to an increased formulation porosity following dissolution of this polymer. Increased concentrations of HEC and PVP increased the hardness, compressibility and work of syringeability of the semi-solid formulations, due to increased product viscosity. An increase in formulation adhesiveness, a parameter related to bioadhesion, was observed as the concentrations of HEC and PVP were increased, illustrating the adhesive nature of these polymers. Increased concentrations of HEC and PVP enhanced the semi-solid nature of the product, resulting in decreased product elasticity and cohesiveness. Several statistically significant interactions between polymeric formulation components were observed within the factorial design, with respect to rate of release and all mechanical properties. These interactions arose because of variations in the physical states (dissolved or dispersed) of polymeric formulation components. Conclusions. The optimal choice of bioadhesive formulation for use in periodontal disease will involve a compromise between achieving the necessary release rate of tetracycline and the mechanical characteristics of the formulation, as these factors will affect clinical efficacy and the ease of product application into the periodontal pocket.     

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

Background  

Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment.     

Lymphocyte 5'-nucleotidase and aminopeptidase N activity in patients on maintenance hemodialysis treated with human recombinant erythropoietin and 1-alpha-D3

BACKGROUND: Patients with end-stage renal disease (ESKD) present an immunodeficiency state paradoxically exacerbated by hemodialysis (HD) and associated with signs of T-cell activation. B cells are also activated in uremia, and this activation could be altered by erythropoietin therapy in HD patients. In this study, the effects of human recombinant erythropoietin (rHu-EPO) and 1-alpha-D3 treatments on lymphocyte immunomodulatory enzymes, aminopeptidase N (APN), and 5'-nucleotidase activity in patients on HD were investigated in hemodialysis patients before and after two-month treatment with s.c. rHu-EPO (15 patients, 2000-3000 U three times weekly) or oral 1-alpha-D3 (14 patients, 2 microg three times weekly). RESULTS: A two-month EPO treatment of 15 HD patients produced a rise in hemoglobin from 6.51 +/- 0.18 to 9.69 +/- 0.14 g/dL. Basal lymphocyte APN activity in HD patients was not significantly different from the level in healthy controls. Treatment of patients with rHu-EPO increased unstimulated lymphocyte APN activity to values significantly higher than those before treatment (p<0.05). A two-month pulse oral 1-alpha-D3 treatment of 14 HD patients increased hematocrit by 21% and raised hemoglobin from 7.11 +/- 0.32 to 8.80 +/- 0.39 g/dL. Unstimulated and Con A-stimulated lymphocyte APN activity after pulse oral 1-alpha-D3 was significantly increased (p<0.01 and p<0.05, respectively) from the pretreatment levels. In HD patients lymphocyte basal, Con A-, and PMA-stimulated 5'-nucleotidase activity was significantly higher (p<0.05) than it was in healthy controls. The two-month treatment with rHu-EPO or pulse oral 1-alpha D3 did not change the level of lymphocyte 5'-nucleotidase in these patients. CONCLUSIONS: This study demonstrated that a two-month treatment of HD patients with rHu-EPO or pulse oral 1-alpha D3 significantly increases activity of lymphocyte APN, important for cleavage of peptides and small proteins, which accumulate in the blood of ESKD patients. In HD patients lymphocyte ecto-5'-nucleotidase activity was significantly higher than that in healthy controls and was not changed after a two-month treatment with rHu-EPO or pulse oral 1-alpha D3. We speculate that oxidative stress activates 5'-nucleotidase and production of adenosine by lymphocytes of HD patients.     

The role of sodium in hypertension is more complex than simply elevating arterial pressure

Excessive salt intake exacerbates hypertension and further increases left-ventricular mass in clinical essential and experimental hypertension. Additionally, a growing body of evidence strongly suggests that high dietary salt loading exerts detrimental cardiac effects independently of its hemodynamic load. The clinical evidence of cardiac structural and functional alterations associated with salt is, however, scarce. In order to explore the purported beliefs in humans, in this review we draw on our experimental studies in naturally occurring hypertension and discuss the clinical implications of the nonhemodynamic mechanisms underlying these salt-related changes.     

Poly(epsilon-caprolactone) and poly(epsilon-caprolactone)-polyvinylpyrrolidone-iodine blends as ureteral biomaterials: characterisation of mechanical and surface properties,degradation and resistance to encrustation in vitro

This study describes the physicochemical properties and in vitro resistance to encrustation of solvent cast films composed of either poly(epsilon-caprolactone) (PCL), prepared using different ratios of high (50,000) to low (4000) (molecular weight) m.wt., or blends of PCL and the polymeric antimicrobial complex, poly(vinylpyrrolidone)-iodine (PVP-I). The incorporation of PVP-I offered antimicrobial activity to the biomaterials. Films were characterised in terms of mechanical (tensile analysis, dynamic mechanical thermal analysis) and surface properties (dynamic contact angle analysis, scanning electron microscopy), whereas degradation (at 37 degrees C in PBS at pH 7.4) was determined gravimetrically. The resistance of the films to encrustation was evaluated using an in vitro encrustation model. Reductions in the ratio of high:low-m.wt. PCL significantly reduced the ultimate tensile strength, % elongation at break and the advancing contact angle of the films. These effects were attributed to alterations in the amorphous content and the more hydrophilic nature of the films. Conversely, there were no alterations in Young's modulus, the viscoelastic properties and glass-transition temperature. Incorporation of PVP-I did not affect the mechanical or rheological properties of the films, indicative of a limited interaction between the two polymers in the solid state. Manipulation of the high:low m.wt. ratio of PCL significantly altered the degradation of the films, most notably following longer immersion periods, and resistance to encrustation. Accordingly, maximum degradation and resistance to encrustation was observed with the biomaterial composed of 40:60 high:low m.wt. ratios of PCL; however, the mechanical properties of this system were considered inappropriate for clinical application. Films composed of either 50:50 or 60:40 ratio of high:low m.wt. PCL offered an appropriate compromise between physicochemical properties and resistance to encrustation. This study has highlighted the important usefulness of degradable polymer systems as ureteral biomaterials.     

Agenesis of the corpus callosum

This paper presents a case of a sixteen-year-old female patient with agenesis of corpus callosum which was accidentally discovered during etiological investigation of the consciousness disorder. Agenesis of corpus callosum, a rare congenital defect, might be associated with macrocephalia and various degrees of mental impairment, optic defects, and seizures. Apart from patients with these pathologic states, there are individuals with agenesis of corpus callosum, but without any clinical disturbances.     

Eating patterns and meal frequency of elite Australian athletes

We undertook a dietary survey of 167 Australian Olympic team athletes (80 females and 87 males) competing in endurance sports (n = 41), team sports (n = 31), sprint- or skill-based sports (n = 67), and sports in which athletes are weight-conscious (n = 28). Analysis of their 7-day food diaries provided mean energy intakes, nutrient intakes, and eating patterns. Higher energy intakes relative to body mass were reported by male athletes compared with females, and by endurance athletes compared with other athletes. Endurance athletes reported substantially higher intakes of carbohydrate (CHO) than other athletes, and were among the athletes most likely to consume CHO during and after training sessions. Athletes undertaking weight-conscious sports reported relatively low energy intakes and were least likely to consume CHO during a training session or in the first hour of recovery. On average, athletes reported eating on approximately 5 separate occasions each day, with a moderate relationship between the number of daily eating occasions and total energy intake. Snacks, defined as food or drink consumed between main meals, provided 23% of daily energy intake and were chosen from sources higher in CHO and lower in fat and protein than foods chosen at meals. The dietary behaviors of these elite athletes were generally consistent with guidelines for sports nutrition, but intakes during and after training sessions were often sub-optimal. Although it is of interest to study the periodicity of fluid and food intake by athletes, it is difficult to compare across studies due to a lack of standardized terminology.     

Melatonin-loaded lecithin/chitosan nanoparticles: Physicochemical characterisation and permeability through Caco-2 cell monolayers

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as a mucoadhesive colloidal nanosystem for transmucosal delivery of melatonin was investigated. The size, zeta potential and melatonin loading of the lecithin/chitosan NPs were investigated as a function of lecithin type (Lipoid S45, S75 and S100) and chitosan content in the preparation. The NPs were characterised by mean diameter and zeta potential ranging between 121.6 and 347.5 nm, and 7.5 and 32.7 mV, respectively, and increasing with lecithin-negative charge and chitosan content in the preparation. Melatonin loadings were up to 7.1%. All NPs were characterised by prolonged release profiles with an initial burst (approximately 25%), followed by a slow release phase. Approximately 60–70% of melatonin was released in 4 h. The permeability of melatonin was investigated using Caco-2 cells as an in vitro model of the epithelial barrier. Melatonin permeability from an NP suspension prepared with Lipoid S45 lecithin and a lecithin-to-chitosan weight ratio (L/C) of 20:1 (sample C2) was significantly improved compared to the permeability of melatonin from the solution (P < 0.001) and from all other NPs investigated (P < 0.05). The results obtained by the cell viability studies (MTT and LDH leakage assays) showed that C2 NP suspension did not induce plasma membrane damage or decrease cell viability and could be safely applied to Caco-2 cells in the concentration range tested (<400 μg/ml).     

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone‐sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT ) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C‐cells. Fifteen‐month‐old Wistar rats were either bilaterally orchidectomized (Orx) or sham‐operated (SO ). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg^?1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C‐cells by immunohistochemical staining for thyroglobulin and CT . Thyroid follicular epithelium, interstitium, colloid and CT ‐immunopositive C‐cells were examined morphometrically. Serum concentrations of osteocalcin (OC ), triiodothyronine (T₃), thyroxine (T₄) and CT were determined as well as urinary calcium (Ca²⁺) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P  < 0.05), but trabecular separation (Tb.Sp) was decreased (P  < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P  < 0.05) compared with Orx, whereas Vv of the colloid was lower (P  < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC , T₃, T₄ and urinary Ca²⁺ concentrations (P  < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.