Effects of Rinsing Water Temperature and Preheated Composites on Microleakage of Composite Restorations with Two Bonding Agents.

Objectives: The aim of this study was to evaluate the effects of rinsing water temperature and preheated composites on microleakage of class V restorations with two different bonding agents. Materials and Methods: Eighty class V cavities were prepared in the buccal and lingual surfaces of 40 molars. Single Bond and Prime and Bond NT bonding agents were used. The teeth were divided into four groups of 10. G1: After acid etching, cavities were rinsed with 23˚C water and filled with 23˚C composite resin. G2: Rinsing water and composite resin had 55˚C temperature. G3: Rinsing water had 55˚C and composite resin had 23˚C temperature. G4: Rinsing water had 23˚C and composite resin had 55˚C temperature. The specimens were immersed in 0.5% basic fuchsine dye. Microleakage scores were analysed with the Kruskal-Wallis, Mann-Whitney U, and Wilcoxon tests. Results: There were significant differences in microleakage of specimens prepared with Single Bond and Prime and Bond NT only in group 1 (P<0.05). There were no significant differences between the microleakage of groups rinsed with different water temperatures (P>0.05). There were significant differences between the unheated and preheated composite groups (P<0.05). Conclusion: Preheating of composite is a valuable method to increase its adaptability and decrease microleakage of composite restorations.

Opioid overdose, interventions, and challenges.

This short letter briefly reviews the significance of opioid overdose as well as the existing approaches to combat the epidemic. It also signifies the importance of naloxone, its commercially available dosage forms, and the unmet need for developing safe and effective naloxone dosage forms that can easily be administered in emergency settings.

In vitro evaluation of adhesion and mechanical properties of oral thin films.

Oral drug delivery is often challenged with enzymatic degradation of drug molecules in the gastrointestinal tract and high first-pass metabolism, resulting in low bioavailability. Delivery of drug molecules via the oral cavity mucosa is considered a viable option to enhance bioavailability. One of the relatively new dosage forms for transmucosal drug delivery is the oral thin film (OTF) with mucoadhesive properties that offers several advantages over conventional dosage forms, including faster dissolution, higher patient compliance, and extended oral retention by reduced salivary washout. Mucoadhesive OTFs should have sufficient muco-adhesiveness as well as suitable mechanical properties for their best performance, thus such characterization is critical in the successful design and development of OTFs. However, there is currently no FDA or USP-recommended analytical procedure or standard available for evaluating adhesiveness and mechanical properties of mucoadhesive OTFs. Therefore, we aimed to develop a fast and reliable in vitro method capable of differentiating various OTFs in terms of their adhesive strengths using a texture analyzer. We found that an in vitro gel substrate composed of 4% w/v gellan gum and 2% w/v glycerin could be used to discriminate between the adhesive features of the tested film samples. Also, our studies show that the adhesion test parameters of 0.96 N target force, probe speed of 0.1 mm/s, holding time of 15 s, and conditioning medium volume of 200 µL while using the said substrate could successfully differentiate between the adhesion strength of the OTF samples. We further examined the film samples for their physicomechanical properties to obtain a tangible and practical range of mechanical values for pharmaceutical OTFs using the puncture test and folding endurance test. We found a breaking factor above 34.5 N/mm, elongation to puncture less than 5.55% and folding endurance of at least 50 folds can be used as a starting point when designing and manufacturing OTFs.

Mucoadhesion and Mechanical Assessment of Oral Films.

Aligned with efforts to overcome shortcomings of conventional oral dosage forms, mucoadhesive oral thin films have been the focus of drug development. Transmucosal drug delivery through oral cavity is a popular alternative to deliver many drugs due to several advantages over conventional oral delivery including greater bioavailability due to bypassing the first-pass effect and avoiding enzymatic or acid-related degradation in the gastrointestinal tract, faster onset of action, and better patient compliance particularly in geriatric and pediatric patients. Furthermore, among solid transmucosal delivery platforms, buccal and sublingual strips or patches are more attractive due to their flexibility, ease of administration, high patient compliance, and fast dissolution. They are also more stable compared to oral gels making them a desirable candidate to deliver many small and large molecules locally or systemically. Mucoadhesion and mechanical properties of oral films are crucial in their performance, and therefore ways to measure these properties are also similarly important. Since they are relatively new to the pharmaceutical market, there are currently no FDA-recommended or USP standard methods available to characterize such dosage forms. This review intends to cover and discuss various methods cited in the literature to measure and evaluate mucoadhesive and mechanical properties of oral films.

Effect of intracerebroventricular injection of GABA receptors antagonists on morphine-induced changes in GABA and GLU transmission within the mPFC: an in vivo microdialysis study.

OBJECTIVES: Many studies have focused on ventral tegmental area than of other mesocorticolimbic areas, and implicated a key role for the medial prefrontal cortex (mPFC) in the development of addictive behaviors. So far, the role of gamma-aminobutyric acid (GABA) receptors in the discriminative properties of morphine has received little attention and few studies evaluated the role of these receptors in drug dependence. Hence, we investigated the role of this receptor on morphine- induced GABA/ glutamate (GLU) changes in the mPFC following morphine administration using in vivo microdialysis. MATERIALS AND METHODS: In this study, 60 rats weighing 270-300 g were divided into six groups. First, microdialysis probe was inserted into the mPFC and was perfused with artificial cerebrospinal fluid and collected the baseline samples in all groups. In saline and morphine groups, the saline, in phaclophen and (phaclofen+morphine) groups, phaclofen (100 nmol), and in bicuculline and (bicuculline+morphine) groups, bicuculline (20 nmol) was injected intracerebroventricular. In saline, phaclofen and bicuculline groups 20 min later, animals received saline (0.2 ml, IP) and others groups received morphine (20 mg/kg, IP). RESULTS: Our results showed that morphine increased the average concentration of GABA and decreased the concentration of GLU within mPFC. Pretreatment with phaclofen and bicuculline 20 min before morphine administration had no effect on GABA and GLU release for 100 min. CONCLUSION: The present study indicated that morphine influence the GABA and GLU transmission in mPFC. Therefore evaluation of neurochemistry changes of this neural circuitry may provide further insight into the mechanisms underlying drug dependence.

Safety and performance of current abuse-deterrent formulations.

INTRODUCTION: Prescription opioid abuse is now an epidemic that has forced the government and industries to take initiatives. These include developing abuse-deterrent formulations (ADFs), issuing regulatory guidances and allocating massive budgets to ensure the safety and effectiveness of these medications. Areas covered: This review covers the regulatory guidance on evaluation and labeling of the branded and generic ADFs. It also includes the relevant patents and technologies, the in-vitro, in-vivo, the post-marketing data, the FDA reviews, and the products' labeling of the FDA-approved products with abuse-deterrent features. Expert opinion: Despite the development of a dozen products with abuse-deterrent features, most of these technologies rely on the same deterrent agent, making it easier for abusers to focus their manipulation efforts and share their experience to defeat the technology. Further advancement in the field requires developing more robust, more diverse, safer, and affordable deterrent technologies for the extended- and immediate-release opioid products. Moreover, advances in the reporting of the post-market results, issuance of policies in support of the ADFs, and concurrent monitoring of the illicit opioid market are other considerations that can further help in confronting the epidemic.

Clinical and radiological evaluation of implants placed with osteotome sinus lift technique: 19-month follow-up.

AIMS: Implant placement in the posterior region of the maxilla might be problematic due to poor regional bone quality. The aim of this study was to clinically and radiologically evaluate implants which were placed in the posterior region of the maxilla (with insufficient bone height) with osteotome sinus lift technique after 19-month follow-up. MATERIALS AND METHODS: Twenty-four patients with posterior maxillary alveolar height ranging from 5 to 8 mm were chosen for this prospective study. After breaking of the cortical bony sinus floor, sufficient bone substitute was placed, and sinus floor was elevated. In this way, a new sinus floor was created, which was designated for further implants placement. Fifty implants were placed immediately after osteotomy sinus lift technique. The mean clinical and radiological follow-up period was 19 months (with a range of 14-24 months). Success factors such as the absence of mobility, pain, infection, and the amount of crestal bone loss were determined in this study. For data analyzing, Kruskal-Wallis and Mann-Whitney tests were used. RESULTS: After 19 months, results showed 96% success rate. Two out of fifty implants failed due to mobility. The mean depth of implants in sinus, mean height of residual crestal bone before surgery, and the mean rate of crestal bone loss were 3.8, 7.9, and 0.71 mm, respectively. CONCLUSION: Osteotome sinus lift technique is a noninvasive surgical method for enhancing a desired length. Furthermore, implants insertion was successful after osteotome sinus lift technique in cases with insufficient bone height.

The Role of GABAB Receptors in Morphine Self-Administration.

BACKGROUND: There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration. METHODS: THIS STUDY WAS PERFORMED IN FOUR GROUPS OF RATS: (1) Saline group, which received saline in the self-administration session. (2) Morphine group, which received morphine in saline solution in the self-administration session. (3) Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. (4) Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded. RESULTS: Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test. CONCLUSION: Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates.

Comparison of microleakage of composite restorations using fifth and sixth generation dentin bonding agent: an in vivo study.

INTRODUCTION: The success of bonded restorations depends on effective bonding between restorative materials and tooth structure, and it prevents microleakage. New dentin bonding systems have been introduced which promotes this concept. The aim of this study was to compare the amount of microleakage between 'single bond' vs 'Prompt L-Pop' during different time periods. MATERIALS AND METHODS: In this clinical trial study, 60 nonretentive class five cavities were prepared on buccal surfaces of human premolars which were scheduled to be removed for orthodontic purposes. The cavities were restored using two different bonding agents; fifth generation (Single Bond) and sixth generation (Prompt L-Pop) and then filled with resin composite (Filtek Z-250). The samples in both groups were extracted after placing the restoration in three periods of time: Immediately, 1 week and 6 months postplacement. Specimens were sealed with two layers of nail varnish except for 1 mm around restoration and immersed in a silver nitrate solution for 24 hours. The teeth were then sectioned longitudinally and the degree of microleakage was determined by stereomicroscope based on standard usual criteria. RESULTS: Single bond showed more leakage at dentin margin than enamel margin in all three extraction periods and differences were significant among three groups (p < 0.05). In samples which were restored with Prompt L-Pop only in groups of 6 months there were significant differences between enamel and dentin margins. At enamel margin there were no significant differences between microleakage of groups according to the passage of time (p > 0.05). CONCLUSION: The results of this study using two different bonding systems, indicate that adhesion to enamel was more valuable than dentin and perhaps systems that include self-etching primers are less sensitive to remaining moisture on dentin and they are less affected during different time periods.