Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor,masitinib

The host foreign body response (FBR) adversely effects the performance of numerous implanted biomaterials especially biosensors, including clinically popular glucose-monitoring sensors. Reactive formation of a fibrous capsule around implanted sensors hinders the transport of essential analytes to the sensor from the surrounding tissue, resulting in loss of glucose response sensitivity and eventual sensor failure. Several strategies have sought to mitigate the foreign body response's effects on CGM sensors through the use of local delivery of pharmaceuticals and biomolecules with limited success. This study describes release of a tyrosine kinase inhibitor – masitinib – from the sensor implant to target tissue resident mast cells as key mediators of the FBR. Model implants are coated with a composite polymer hydrophilic matrix that rapidly dissolves upon tissue implantation to deposit slower-degrading polymer microparticles containing masitinib. Matrix dissolution limits coating interference with sensor function while establishing a local controlled-release delivery depot formulation to alter implant tissue pharmacology and addressing the FBR. Drug efficacy was evaluated in a murine subcutaneous pocket implant model. Drug release extends to more than 30 days in vitro. The resulting FBR in vivo, evaluated by implant capsule thickness and inflammatory cell densities at 14, 21, and 28 days, displays statistically significant reduction in capsule thickness around masitinib-releasing implant sites compared to control implant sites.     

Periodontal findings in patients with oral submucous fibrosis and comet assay of affected gingival epithelial cells

Background: Oral submucous fibrosis (OSF) involves large sections of population and is related to certain chewing practices that involve direct exposure of the gingiva to noxious chemicals and additives. The impact of such practices, although studied extensively in relation to the cheek mucosa, is not elucidated as far as gingival tissues are concerned. The possible DNA damage on affected gingiva is also one of the objectives of the present study. Methods: One hundred cases of individuals with OSF and 89 without OSF were examined for periodontal parameters and compared. Biopsies of gingival tissue from both categories were examined with conventional hematoxylin and eosin staining for epithelial, connective tissue, and inflammatory changes. Comet assay of epithelial cells obtained from scraping the gingival surface of both patients with OSF and control individuals was performed . Results: Patients with OSF had poorer oral hygiene and greater loss of attachment, probing depth, and recession compared with controls. Significant histopathologic changes in the form of loss of rete ridges with gingival epithelium reduced to a flattened surface was observed. All the patients with OSF showed comet cells in larger numbers. The controls also showed comet cells but in fewer numbers, and the number of individuals showing comet cells was significantly less. Conclusion: OSF showed significant changes in affected gingiva, and the presence of comet cells in all the patients with OSF is a significant indicator of possible pathognomonic developments.     

Periodontal findings in a patient with Mauriac syndrome: a case report

Mauriac syndrome is a rare condition that affects people with uncontrolled diabetes. The case history of a 17-year-old female patient diagnosed with Mauriac syndrome and concurrently suffering from type 1 diabetes mellitus (T1DM), stunted growth, hepatomegaly, and severe periodontal disease is described. Non-surgical periodontal therapy was the treatment provided. Severe periodontal destruction was seen in conjunction with the unique features of this syndrome, such as hepatomegaly, dwarfism, moon-shaped face, cushingoid fat deposition, delayed puberty, and brittle diabetes. Treatment resulted in decreased plaque and gingival scores. A bi-directional relationship has been established between diabetes mellitus and periodontal disease and there is an increasing emphasis on perio-systemic interrelationships. Given the effect that such systemic disorders have on periodontal health, periodontists should be involved in the early diagnosis and treatment of such patients.     

Formulation Development,Optimization, and In Vitro–In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications

The present study aimed at formulating and optimizing natamycin (NT)-loaded polyethylene glycosylated nano-lipid carriers (NT-PEG-NLCs) using Box-Behnken design and investigating their potential in ocular applications. Response surface methodology computations and plots for optimization were performed using Design-Expert^® software to obtain optimum values for response variables based on the criteria of desirability. Optimized NT-PEG-NLCs had predicted values for the dependent variables which are not significantly different from the experimental values. NT-PEG-NLCs were characterized for their physicochemical parameters; NT's rate of permeation and flux across rabbit cornea was evaluated, in vitro, and ocular tissue distribution was assessed in rabbits, in vivo. NT-PEG-NLCs were found to have optimum particle size (<300 nm), narrow polydispersity index, and high NT entrapment and NT content. In vitro transcorneal permeability and flux of NT from NT-PEG-NLCs was significantly higher than that of Natacyn^®. NT-PEG-NLC (0.3%) showed improved delivery of NT across the intact cornea and provided concentrations statistically similar to the marketed suspension (5%) in inner ocular tissues, in vivo, indicating that it could be a potential alternative to the conventional suspension during the course of fungal keratitis therapy.     

Prevalence of facet joint pain in chronic low back pain in postsurgical patients by controlled comparative local anesthetic blocks

OBJECTIVE: To evaluate the prevalence of facet joint pain in patients with chronic low back pain (CLBP) after surgical intervention(s). DESIGN: A prospective, nonrandomized, consecutive study. SETTING: An ambulatory interventional pain management setting. PARTICIPANTS: The prevalence of facet joint pain was evaluated in patients with CLBP after various surgical intervention(s) referred to an interventional pain management practice. The sample was derived from 282 patients with persistent CLBP after various surgical intervention(s). Of these, 242 patients consented to undergo interventional techniques. A total of 117 consecutive patients with chronic, nonspecific low back pain, after lumbar surgical intervention(s) were evaluated with controlled, comparative local anesthetic blocks. INTERVENTIONS: Controlled, comparative local anesthetic blocks (1% lidocaine or 1% lidocaine followed by .25% bupivacaine) under fluoroscopic visualization using 0.5mL to block each facet joint nerve. MAIN OUTCOME MEASURES: A positive response was defined as at least 80% reduction of pain with ability to perform previously painful movements. A positive response was considered to be pain relief from the lidocaine block lasting at least 1 hour or at least 2 hours or greater than duration of relief with lidocaine when bupivacaine was used. Controlled, comparative local anesthetic blocks were used to eliminate false-positive results. Valid information is only obtained by performing controlled blocks in the form of comparative local anesthetic blocks, in which, on 2 separate occasions, the same joint is anesthetized by using local anesthetics with different durations of action. If patients obtained appropriate response with both blocks, they were considered a positive. If they obtained appropriate response with lidocaine but not with bupivacaine, they were considered false-positive, whereas if the response was negative with lidocaine, they were considered negative. RESULTS: The prevalence of lumbar facet joint pain in patients with recurrent pain after various surgical intervention(s) was 16% (95% confidence interval, 9%-23%). The false-positive rate with a single block with lidocaine was 49%. CONCLUSIONS: Facet joints are clinically important pain generators in a small but significant proportion of patients with recurrent CLBP after various surgical intervention(s).     

Cervical zygapophysial (facet) joint pain: effectiveness of interventional management strategies

Diagnostic facet joint nerve blocks have been utilized in the diagnosis of cervical facet joint pain in patients without disk herniation or radicular pain due to a lack of reliable noninvasive diagnostic measures. Therapeutic interventions include intra-articular injections, facet joint nerve blocks and radiofrequency neurotomy. The diagnostic accuracy and effectiveness of facet joint interventions have been assessed in multiple diagnostic accuracy studies, randomized controlled trials (RCTs), and systematic reviews in managing chronic neck pain.

This assessment shows there is Level II evidence based on a total of 11 controlled diagnostic accuracy studies for diagnosing cervical facet joint pain in patients without disk herniation or radicular pain utilizing controlled diagnostic blocks. Due to significant variability and internal inconsistency regarding prevalence in a heterogenous population; despite 11 studies, evidence is determined as Level II. Prevalence ranged from 36% to 67% with at least 80% pain relief as the criterion standard with a false-positive rate ranging from 27% to 63%.

The evidence is Level II for the long-term effectiveness of radiofrequency neurotomy and facet joint nerve blocks in managing cervical facet joint pain. There is Level III evidence for cervical intra-articular injections.