P2X7 receptor antagonist delivery vehicle based on photocrosslinked amphiphilic hybrid gels

We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist. P2X7R has been reported as a key mediator in inflammatory processes and controlled delivery of this molecule would be critical for the treatment of inflammatory arthritis. The hybrid gel designed here for the sustained delivery of P2X7R antagonists is based on crosslinked hydrophobic styrene-butadiene-styrene (SBS) polymer as a continuous network, where hydrogel particles prepared with hydrophilic poly(ethylene glycol) (PEG) were embedded into this system. PEG hydrogel particle-incorporated SBS gels were characterized through electron microscopy, water contact angle observations, and strong mechanical properties were confirmed through nanoindentation measurements. The release of P2X7R antagonist from these hybrid hydrogel-elastomer system demonstrated a sustained drug release profile up to 28 days at physiological pH, which was not observed in earlier reports. We obtained drug release percentages ranging from 49.72% to 93.04% which indicated the tunability of release through SBS crosslinking and hydrophilic/hydrophobic nature of SBS. This tunability is significant to achieve simultaneous improvements in drug efficacy with reduced side effects. CellTiter-Glo luminescence measurements using human kidney cells revealed that these networks are non-toxic and highly biocompatible with percent cell viabilities of higher than 85%. The approach presented here with crosslinked, amphiphilic and elastic SBS gel systems is not only promising for extended release of P2X7R antagonist but could also allow for incorporation of different molecules so that simultaneous/sequential and extended release profiles for therapeutic molecules could be achieved.

We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist.     

IgG4-related disease and ANCA positive vasculitis in childhood: a case-based review

Clinical Rheumatology - Autoimmune pancreatitis (AIP) type 1 is an IgG4-related disease (IgG4-RD), characterized by inflammatory pseudotumors and histologically by dense lymphoplasmacytic...     

Acetyl salicylic acid improves somatosensory evoked potentials in streptozotocin-diabetic rats

Microalbuminuria and retinopathy was studied in a non-proteinuric diabetic population of Cameroon. Patients were enrolled on a consecutive basis in two referral hospitals in Yaoundé. Retinopathy was evaluated by direct ophthalmoscopy and biomicroscopy, and controlled by mydriatic fundus photography. Detection of microalbuminuria was carried out on an overnight urine sample using Micral II test (Boehringer Mannheim). Anthropometric and blood pressure measurements were done using validated methods. In 64 non-proteinuric diabetic patients (9 IDDM and 55 NIDDM) aged 19-70 years with known duration of diabetes of 1-23 years, the prevalence of retinopathy was 37.5%. Microalbuminuria was detected in 53.1% of patients. Microalbuminuria correlated with duration of diabetes, and blood pressure, retinopathy was positively correlated with age, and blood pressure. Retinopathy was not significantly associated with the known duration of diabetes. Retinopathy was found to be independently associated with microalbuminuria (P < 0.001) and microalbuminuria appeared to be a sensitive marker of retinopathy. The prevalence of retinopathy and microalbuminuria in this population was high. Microalbuminuria and non-proliferative retinopathy are independently associated, and are both associated with increased blood pressure levels in the study population. As shown in previous studies microalbuminuria may also be a sensitive marker of early diabetic retinopathy in African diabetic patients.     

Mood and metabolic consequences of sleep deprivation as a potential endophenotype’ in bipolar disorder

It has been commonly recognized that circadian rhythm and sleep/wake cycle are causally involved in bipolar disorder. There has been a paucity of systematic research considering the relations between sleep and mood states in bipolar disorder. The current study examines the possible influences of sleep deprivation on mood states and endocrine functions among first-degree relatives of patients with bipolar disorder and healthy controls. Blood samples were taken at two time points in the consecutive mornings at predeprivation and postdeprivation periods. Participants simultaneously completed the Profiles of Mood States at two time points after giving blood samples. Plasma T3 and TSH levels increased after total sleep deprivation in both groups. Sleep deprivation induced TSH levels were reversely associated with depression–dejection among healthy controls. A paradoxical effect was detected for only the first-degree relatives of the patients that changes in plasma cortisol levels negatively linked to depression–dejection and anger–hostility scores after total sleep deprivation. Plasma DHEA levels became correlated with vigor-activity scores after sleep deprivation among first-degree relatives of bipolar patients. On the contrary, significant associations of depression–dejection, anger–hostility, and confusion–bewilderment with the baseline plasma DHEA levels became statistically trivial in the postdeprivation period. Findings suggested that first-degree relatives of patients with bipolar disorder had completely distinct characteristics with respect to sleep deprivation induced responses in terms of associations between endocrine functions and mood states as compared to individuals whose relatives had no psychiatric problems. Considering the relationships between endocrine functions and mood states among relatives of the patients, it appears like sleep deprivation changes the receptor sensitivity which probably plays a pivotal role on mood outcomes among the first-degree relatives of patients with bipolar disorder.     

Evaluation of polymerization shrinkage of bulk-fill resin composites using microcomputed tomography

This study evaluated the influence of cavity depth on polymerization shrinkage of bulk-fill resin composites with and without adhesive resin. Standardized     

Effects of 2-Hydroxypropyl-Beta-Cyclodextrin on Cardiovascular Signs of Amitriptyline Poisoning in a Rat Model

The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4.19 mg/kg/min), or high-dose HPBCD (16.76 mg/kg/min) was infused, and MAP, heart rate (HR), and electrocardiogram were recorded for 60 min. Hearts were examined for tissue damage and apoptosis. HPBCD infusion alone did not yield significant difference for MAP, HR, QRS duration, QT interval, and cardiac tissue damage when compared to dextrose (p > 0.05). In the poisoning model, MAP and HR decreased, while QRS duration and QT interval prolonged significantly following amitriptyline infusion (p < 0.0167). Dextrose, low-dose HPBCD, and high-dose HPBCD infusion similarly corrected MAP, HR, QRS duration, and QT interval values at the end-experiment time point (p > 0.05). Histological scores for tissue damage and apoptosis showed no significant difference between the groups (p > 0.05). Based on our results, HPBCD did not show cardiovascular toxicity, while it was not more effective than dextrose for the treatment of amitriptyline poisoning. Further antidotal studies of cyclodextrins with higher doses and/or binding affinities are needed for poisonings.