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The recent re-emergence and the increasing popularity of nitazenes, a group of new synthetic opioids (NSO) that belong to the benzimidazole chemical class, has raised public health concerns. As a class of potential opioid analgesic agents whose development was discontinued in the 1960s due to their high potential for abuse, very little is known about their metabolism and physiologic disposition. In the current study, three nitazenes-butonitazene, isotonitazene and protonitaze were incubated in human liver microsomes (HLM), human S9 (HS9) fractions and recombinant cytochrome P450 enzymes. All three nitazenes were rapidly metabolized in both HLM and HS9 with over 95% depletion within 60 min. In HLM, butonitazene, isotonitazene and protonitazene had in vitro intrinsic clearance (CLint) (µL/min/mg protein) values of 309, 221 and 216 respectively compared to 150 of verapamil, the positive control. In HS9, CLint values were 217, 139, and 150 for butonitazene, isotonitazene and protonitazene respectively compared to only 35 for testosterone, the control probe substrate. Putative metabolite identified from this study include products of hydroxylation, desethylation, dealkylation, desethylation followed by dealkylation, and desethylation followed by hydroxylation. The metabolic phenotyping showed CYP2D6, CYP2B6 and CYP2C8 and the major hepatic enzymes responsible for the metabolism of nitazenes. Within 30 min of incubation, CYP2D6 depleted butonitazene (99%), isotonitazene (72%) and butonitazene (100%) significantly. The rapid metabolism of nitazenes may be an important factor in accurate and timely detections and quantitation of the unchanged drugs in human matrices following intoxication or in forensic analysis. The involvement of multiple polymorphic CYPs in their metabolism may play important roles in the susceptibility to intoxication and/or addiction, depending on the activity of the metabolites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jadhav and Fasinu.)

Trial Design: This is a prospective, block-randomized, blinded, multiple arm and parallel-group superiority clinical trial., Methods: Seventy-eight patients satisfying the recruitment standards, were randomly allocated into three groups as follows: Group I (n = 26) - Inferior alveolar nerve block (IANB) devoid of aromatherapy (AT); Group II (n = 26) - IANB with lavender AT and Group III - IANB with rose AT (n = 26) with the help of the ultrasonic aroma diffuser (with respective oils)for 20 min/2 h in operatories 1,2 and 3 respectively. For AT, 3-4 drops of lavender and rose-conditioned oils were added from a 100 ml solution containing 100 mg of these medicinal plants. The pre-operative (PRO) and access opening (AO) pain as well as the anxiety of patients were recorded using the Visual Analog Scale (VAS) and Modified Dental Anxiety Scale (MDAS) respectively. Data thus obtained was entered into the Excel sheet and subjected to statistical tests (analysis of variance and paired t -test). The p-value less than 0.05 was considered statistically significant., Results: Group I showed non-significant disparity between PRO and AO for both VAS as well as MDAS (p = 0.62, p = 0.71). However, group II (p = 0.04, p = 0.02) and group III (p = 0.03, p = 0.01) revealed significant differences between PO - AO VAS and MDAS. MDAS and VAS intergroup comparison revealed a significant difference among groups I and II (p = 0.03, p = 0.04), and groups I and III (p = 0.02, p = 0.03). However non-significant disparity was observed among groups II and III (p = 0.85, 0.34). Moreover, there was a statistically significant reduction in anxiety levels in females compared to males after rose AT (p = 0.02). Nevertheless, groups I and II did not show any gender predilection for anxiety as well as pain., Conclusion: Alleviation of dental anxiety as well as reduction in pain during AO of teeth with SIP can be achieved using Lavender and rose AT. In female patients, rose AT can be preferred over lavender AT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Self-assessment (SA) is an interactive course that endorses the accomplishment of learning objectives through learners' identification of insufficiencies in their didactic knowledge and pre-clinical skills. This study was planned to determine whether there is any improvement in the faculty assessment (FA) score following the implementation of SA in the Pre-clinical Conservative Dentistry Course., Methods: Fifty-four first-semester dental students were given an introductory lecture followed by a demonstration for Class I Cavity Preparation in typhodont mandibular first molar. At the end of the demonstration, the Scoring Rubric (SR) was explained point-wise in the prepared cavities. During the next session, all students performed Class I cavity preparation and they were given an assessment sheet to enter their scores (SA1). All teeth were evaluated by the Grading Faculties in a blinded manner (FA1). Each participant was explained the difference in their respective SA1 from FA1 and their queries were resolved individually. During the next sessions, Students and Grading Faculties followed the same protocol and scores were recorded as SA2, FA2, SA3 and FA3., Results: The mean score of SA1 was significantly higher than that of FA1 (p < 0.001). However, no significant difference was obtained between SA and FA in the second (p = 0.352) and third (p = 0.434) assessments. In contrast with first assessment, mean marks obtained in FA were higher compared to SA in both second and third assessments. There was a statistically significant improvement in mean marks obtained by the students over time (p < 0.001)., Conclusion: SA endorsed student-faculty communication and enhanced student's poise and technical skills in operative pre-clinical dentistry., (© 2024. The Author(s).)

Objective: Incisal composite build-up shows a high failure susceptibility. The incorporation of fiber-reinforced composite (FRC) during composite restoration could improve its strength. Hence the study was planned to compare the effect of various positions of FRC on the strength of composite resin incisal build-ups., Methods: In maxillary incisors (n = 90), 3 mm of the incisal edge was cut and teeth were categorized into three groups based on the location and number of fibers used during incisal composite build-up - Group I: composite resin; Group II: composite resin and a single fiber palatally and Group III: composite resin along with two fibers palatally., Results: The data showed that group II had the maximum load-bearing values followed by group I and group III., Conclusion: Within the confines of our study, it can be concluded that the addition of FRC to the conventional incisal composite build-up increased the overall strength restoration. Such composite restoration reinforced with a single fiber on the palatal side showed the highest load-bearing capacity compared to two fibers reinforced and unreinforced composites. The common mode of failure in group I was in composite resin, in two fibers reinforced at fibers-composite junction, and in one fiber reinforced composite was in the remaining part of the tooth., (© 2023. The Author(s).)

Background: Dental education is considered as a complex, challenging and often stressful educational procedure. Acquisition of psychomotor skills by undergraduate students is an important step in many health professions to become a successful professional. During under graduation, class II cavity preparation exercise is of utmost important in dentistry., Objective: To compare class II cavities prepared by students after hands-on live demonstration and pre-recorded video demonstration using well-organised evaluation rubrics., Method: Preclinical dental students (n= 50) were divided into two groups. The students in group I (n= 25) attended a hands-on live demonstration performed by one faculty while students in group II (n= 25) watched a 15-minute pre-recorded procedural video on the projector. Both groups were appealed to prepare class II cavity for amalgam involving disto-occlusal surface of mandibular second molar articulated on jaw model (TRU LON study model, Jayna industries, Ghaziabad U.P., India). Following completion of the preparations, all teeth were collected, and labelled grades of prepared cavities were given according to prespecified rubrics. The data of scores were presented as means and standard deviation. Statistical analysis of data was executed using SPSS software. A paired t-test was used to compare scores between groups., Results: The study shows that the video-supported demonstration of a cavity preparation was better than the live hands-on demonstration. A higher mean response for the procedural video group was found compared to the live demonstration group (p= 0.000133)., Conclusion: Pre-recorded video-supported demonstration along with guidance by a tutor may be a viable alternative to hands-on live demonstration in cavity preparation procedures during undergraduate dental training. Moreover, rubric methods can be implemented in the teaching of various preclinical exercises for conservative dentistry and endodontics.

Background: In dentistry, nosocomial infection poses a great challenge to clinicians. The microbial contamination of water in dental unit waterlines (DUWLs) is ubiquitous. Such infected DUWLs can transmit oral microbes in the form of aerosols. Previous studies have suggested treating DUWLs with various disinfectants to reduce cross-contamination. The literature lacks a comparative evaluation of the effect of the use of 0.2% chlorhexidine (CHX) and 0.1% sodium hypochlorite (NaOCl) in DUWLs on aerosolized bacteria generated during dental procedures., Objective: To compare the effect of NaOCl and CHX in DUWLs on aerosolized bacteria generated during restorative and endodontic procedures., Materials and Methods: A total of 132 patients were equally divided into three groups (n = 44 in each group) according to the content of DUWL as follows. Group I-0.1% NaOCl Group II-0.2% CHX Group III-distilled water (Positive control) One-way ANOVA was performed and the Kruskal-Wallis test was used for intergroup comparison., Results: For the restorative procedure, inter-group comparison of mean colony-forming units (CFU) scores showed a statistically significant difference between the groups (p - .001) with the score of group 3 higher than group 2 followed by group 1. For the endodontics, an inter-group comparison of CFU scores showed a statistically significant difference between the groups (p - .003) with the mean score in group 1 being the lowest and group 3 being the highest., Conclusion: The addition of NaOCl or CHX in DUWLs shows an effective reduction in aerosolized bacteria compared to distilled water., (© 2023. The Author(s).)

Objective: This study compared the potential for apical extrusion of sodium hypochlorite (NaOCl) when using needle irrigation (NI), passive ultrasonic irrigation (PUI), passive subsonic irrigation (PSI), and negative pressure system (NP)., Materials and Methods: One hundred freshly extracted human permanent anterior teeth with complete root formation were embedded rigidly in agarose gel-containing cresol purple. Teeth were randomly allocated to six groups: G1-NI; G2-PUI; G3-PSI; G4-NP; G5-positive control; and G6-negative control. The chemomechanical preparation was completed and 12 ml of 3% NaOCl was delivered for 180 s in all groups. Dye diffusion was standardized by doing gel photography after the NaOCl final irrigation the Chi-square test and Kruskal-Wallis one-way analysis of variance test were used for the data analysis., Results: G1 had statistically significant apical extrusion compared to G2 ( P = 0.001), G3 ( P = 0.001), and G4 ( P = 0.001) groups. G4 showed the least amount of apical extrusion., Conclusions: pH-sensitive gel model is useful in evaluating NaOCl extrusion. NP produced least NaOCl extrusion as compared to the other three systems. Due consideration should be given to the potential for apical extrusion of the irrigant before the selection of an irrigation system., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Conservative Dentistry and Endodontics.)

Background: The aim of this study was to compare dentinal crack formation in root canal walls following 3 single file systems with continuous rotation under a scanning electron microscope (SEM)., Materials and Methods: In this SEM study, seventy mandibular premolars were randomly divided into 5 groups. 3 experimental groups ( n = 20) and 2 control groups ( n = 5) as follows: Group I: Neolix NiTi file system, Group II: OneShape systems, Group III: OneCurve file system, positive control: conventional Hand File system, negative control: unprepared. After root canal preparations, the roots were sectioned at 3, 6, and 9 mm from the apex with water irrigation. The sections were inspected in all directions under SEM at × 100 magnification to determine the presence of cracks. The Chi-square test was used to analyze the data. There is a statistically significant difference in the crack formation between the apical third ( P = 0.012) and coronal third ( P = 0.002) when comparing all the 5 groups. No significant difference is found in the middle third ( P = 0.46). P < 0.05 is considered statistically significant., Results: Maximum cracks in the apical third were seen with One Shape file 11 (55%) and in the coronal third with Neolix NiTi 14 (70%). There is a statistically significant difference in the crack formation only in OneCurve when comparing the apical, middle, and coronal third for the individual group ( P = 0.042)., Conclusion: There was a significant difference in crack formation in apical and coronal third. OneCurve caused the least incidence of cracks when compared to other file systems. OneCurve file system can be a choice for canal preparation over Neolix Niti and OneShape., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article., (Copyright: © 2021 Dental Research Journal.)

The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing's sarcoma models., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: This prospective, block randomized clinical trial was conducted to evaluate the effect of aromatherapy on the success rate of inferior alveolar nerve block (IANB) in teeth with irreversible pulpitis., Method and Materials: In this clinical trial, 46 patients fulfilling the inclusion criteria were randomly divided into two equal groups: group I (n = 22) received IANB in a closed operatory without any fragrance, whereas group II (n = 24) received IANB in a separate closed operatory saturated with lavender fragrance using a candle warmer. The modified dental anxiety scale (MDAS) for anxiety and visual analog scale (VAS) for pain were recorded preoperatively as well as during access cavity preparation. For MDAS, a total score of more than 18 was considered as tremendously anxious or dental phobic. No or mild pain on VAS was considered as success. Data were analyzed using paired t test and independent sample t test. P < .05 was considered as statistically significant., Results: Difference in mean VAS (P = .749) and MDAS (P = 1.000) between both the groups was statistically nonsignificant. However there was a statistically significant difference in mean VAS (P = .000) and MDAS (P = .001) during access opening., Conclusion: Lavender aromatherapy can be used successfully to alleviate dental anxiety as well as to increase the anesthetic success rate of IANB in teeth with irreversible pulpitis.

A series of quinoxaline-2-hydroxyphenylbenzothiazole scaffolds were synthesized and characterized using NMR, UV, fluorescence spectroscopy and LCMS. These newly synthesized compounds were found to be cytotoxic in human epithelioid cervix carcinoma (HeLa) and human colon cancer cell lines (Caco-2). Selectivity of the compounds 7e and 7g are more than 9 fold higher in Caco-2 cells with respect to the normal cell line HEK-293. The most fluorescent compound 7e has displayed high cytoselectivity, significant cellular uptake in HeLa cells and strong binding efficacy with DNA and BSA. The most potent compound 7g has primarily classified as BCS class 4 and BDDCS class 4., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Accurate working length (WL) determination is necessary in achieving optimal healing by non-surgical root canal therapy in teeth with inflammatory apical root resorption. Electronic apex locators (EALs) are one of the mainstays in determination of WL of teeth., Aim: This study evaluated the accuracy of three EALs [RootZX (third generation), iPex (fourth generation) and Raypex 6 (modification of a fifth generation)] in determining the WL of teeth with simulated apical root resorption in permanent teeth., Materials and Methods: Forty freshly extracted maxillary anterior teeth were collected and a 45° oblique cut was made at the root apex with a disc to simulate apical root resorption. Actual working length (AWL) was determined by direct visual method and was used as a control. Electronic working length (EWL) values were measured by three different apex locators that are RootZX (Group I), iPex (Group II) and Raypex 6 (Group III) at apex, 0.5 mm and 1 mm from apex. All values obtained were tabulated and statistical evaluation was carried out., Results: At apex, EWL obtained using iPex (p=0.05) showed a statistically significant difference from AWL. At 0.5 mm and 1.0 mm tolerance, iPex showed non-acceptability for WL measurement in 67.5% and 17.5% of samples compared to Root ZX (12.5% and 2.5%) and Raypex (7.5% and none) respectively., Conclusion: Within the limitation of this study, it can be concluded that Raypex 6 and RootZX show statistically significant accuracy in WL measurement compared with iPex in teeth with apical root resorption.

Adenosine is known as an endogenous purine nucleoside and it modulates a wide variety of physiological responses by interacting with adenosine receptors. Among the four adenosine receptor subtypes, the A 3 receptor is of major interest in this study as it is overexpressed in some cancer cell lines. Herein, we have highlighted the strategy of designing the h A 3 receptor targeted novel benzothiazolylquinoline scaffolds. The radioligand binding data of the reported compounds are rationalized with the molecular docking results. Compound 6a showed best potency and selectivity at h A 3 among other adenosine receptors., Competing Interests: We have no competing interests.

Bioceramics are materials which include Alumina, Zirconia, Bioactive glass, Glass ceramics, Hydroxyapatite, resorbable Calcium phosphates, among others. They have been used in dentistry for filling up bony defects, root repair materials, apical fill materials, perforation sealing, as endodontic sealers and as aids in regeneration. They have certain advantages like biocompatibility, non toxicity, dimensional stability and most importantly in endodontic applications, being bio-inert. They have a similarity to Hydroxyapatite, an intrinsic osteo conductive activity and have an ability to induce regenerative responses in the human body. In Endodontics, they can be broadly classified into Calcium Phosphate/ Tricalcium/ Hydroxyapatite based, Calcium Silicate based or mixtures of Calcium Silicate and Phosphates. This review focuses on an overview of Bioceramics, classification and their advantages. It also gives a detailed insight into individual bioceramic materials currently used in the fields of Endodontics along with their properties and applications., Competing Interests: Conflict of interest: None declared.

Context and Aims: The purpose of this study was to compare and evaluate the shaping ability of ProTaper (PT) and Self-Adjusting File (SAF) system using cone-beam computed tomography (CBCT) to assess their performance in oval-shaped root canals., Materials and Methods: Sixty-two mandibular premolars with single oval canals were divided into two experimental groups ( n = 31) according to the systems used: Group I - PT and Group II - SAF. Canals were evaluated before and after instrumentation using CBCT to assess centering ratio and canal transportation at three levels. Data were statistically analyzed using one-way analysis of variance, post hoc Tukey's test, and t -test., Results: The SAF showed better centering ability and lesser canal transportation than the PT only in the buccolingual plane at 6 and 9 mm levels. The shaping ability of the PT was best in the apical third in both the planes. The SAF had statistically significant better centering and lesser canal transportation in the buccolingual as compared to the mesiodistal plane at the middle and coronal levels., Conclusions: The SAF produced significantly less transportation and remained centered than the PT at the middle and coronal levels in the buccolingual plane of oval canals. In the mesiodistal plane, the performance of both the systems was parallel., Competing Interests: There are no conflicts of interest.

Background: The purpose of this study was to evaluate the canal cleaning ability of three novel endodontic rotary instruments and compare with ProTaper files as a control in apical third of root canals under scanning electron microscopy (SEM)., Materials and Methods: Eighty freshly extracted mandibular premolars were selected according to inclusion criteria. Buccal cusp tips were ground to ensure having a flat coronal reference point with a total tooth length of 16 mm for all samples. Teeth were divided equally into four groups: Group I (ProTaper group), Group II (ProTaper next group), Group III (variable taper group), and Group IV (self-adjusting file [SAF] group). Using SEM, the dentinal surfaces were observed and rated at apical thirds with a magnification of ×1000 for the presence/absence of smear layer and debris. Descriptive analysis was performed, and analysis of variance with Bonferroni post hoc test was carried out for comparison between the groups, at a significance level of 0.05., Results: There was statistically significant difference between Group II and Group IV for debris ( P = 0.047) and smear layer ( P = 0.037)., Conclusion: In apical third of root canal, SAF showed statistically significant canal cleaning ability due to combined effect of continuous streaming irrigation with effectively replacing the irrigant from the apical portion of the root canal, irrigants activation through the creation of turbulence, and its self-adapting design to root canal anatomy with a scrubbing motion on the canal walls., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article.

Introduction: In teeth with irreversible pulpitis, successful local anesthesia is hard to achieve irrespective of the amount of local anesthesia and technique used. Such cases can be managed by concoction of pre-medications like anxiolytics, analgesics and effective local anesthesia. This double-blind, placebo-controlled study was planned to evaluate the effect of oral administration of alprazolam and diclofenac potassium on the success rate of inferior alveolar nerve block (IANB), Gow-Gates (GG) and Vazirani-Akinosi (VA) techniques for the root canal treatment of mandibular molars with irreversible pulpitis., Method: 198 emergency patients with symptomatic irreversible pulpitis were randomly divided into three groups as - A, B and C receiving IANB, GG or V-A respectively using 2% lidocaine with 1: 100,000 epinephrine. These groups were sub-divided into sub-groups I and II as control and pre-medication groups. Patients who did not react to the stimulus made by an explorer between the canine and first premolar and showing subjective lip and tongue numbness were included in the study., Result: All sub-groups showed statistically significant reduction in VAS score. However sub-groups V and VI (that is GG with and without pre-medication respectively) showed best improvement in initial severe pain in mandibular molars with irreversible pulpitis. Moreover, all pre-medication sub-groups showed better pain control compared to respective control groups., Conclusion: It was concluded that use of pre-medications in the form of combination of anxiolytics and analgesics improves the success rate of local anesthesia in teeth with irreversible pulpitis. Use of anxiolytics eases the patient in endodontic emergencies. Also use of GG along with pre-medication is the best method for effective pain management of acute pain in irreversible pulpitis.

Dens invaginatus (DI) is a developmental anomaly seen infrequently in maxillary canines. This article describes cone-beam computed tomography-guided nonsurgical management of type III (subtype B) DI in a permanent maxillary canine associated with a sinus tract and peri-invagination periodontitis in a 17-year-old female. After gaining access to the root canal, thorough chemo-mechanical preparation was performed and usage of intracanal medicament of calcium hydroxide was prescribed for 3 weeks, during which the sinus tract healed completely. Obturation was completed by a technique of down-packing master-cone gutta-percha, followed by backfilling with thermoplasticized gutta-percha. At 12-months follow-up, the patient was asymptomatic with complete resolution of the sinus tract and radiographic evidence of healing of periapical pathology.

A novel three components approach for the synthesis of bioactive Ru-arene pyridinylmethylene complexes has been developed using pyridine carboxaldehyde, amino pyridine and dichloro (p-cymene) ruthenium(II) dimer as starting materials. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human Epitheloid Cervix Carcinoma (HeLa) cell line. It was established that compounds [(η(6)-pcymene)RuCl(κ(2)-N,N-(3,5-dinitro-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4o), [(η(6)-pcymene)RuCl(κ(2)-N,N-N-(3,5-dibromo-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4c), [(η(6)-pcymene)RuCl(κ(2)-N,N-(3,5-dibromo-6-methylpyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4j) and [(η(6)-pcymene)RuCl(κ(2)-N,N-3(3-bromo-5-methyl-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4b) were significantly active against both the cell lines., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Longitudinal tooth fracture can be classified as craze lines, fractured cusp, cracked tooth, split tooth and vertical root fracture based on extent and severity of the fracture line. The most common type of longitudinal tooth fracture is fractured cusp that poses the treatment dilemma. Retention of the fractured cusp segment temporarily with matrix band followed by permanent bonded restoration and finally removal of tooth fragment during crown preparation is a novel technique. This paper throws light on a matricing and holding technique for the management of supra-crestally fractured palatal cusp of maxillary first premolar in a 29-year-old Asian male.

Introduction: Clinicians use various anaesthesia techniques like Posterior Superior Alveolar (PSA) nerve block, buccal infiltration with or without supplemental anaesthesia like palatal and intraligamentary infiltrations for root canal treatment in maxillary molars. However there is no general consensus regarding which technique is enough for performing endodontic treatment in maxillary molars., Aim: The aim of this questionnaire-based survey is to compare and evaluate the various techniques used to anaesthetize the maxillary molars and its effect on postoperative pain., Materials and Methods: The data were obtained from 290 dental practitioners using a specially prepared questionnaire survey conducted anonymously. The questionnaire contained questions covering data such as years in dentistry, acquired specialty, techniques used for anaesthetizing maxillary molars, success of anaesthesia, and postoperative pain, etc., Results: Buccal infilteration with supplemental anaesthesia in the form of palatal (82%) and intra-ligamentary infilteration (88%) show higher success rate compared to only buccal infilteration (69%). However, intra-ligamentary infilteration group showed highest rate (75%) of postoperative pain. General practitioners (62% of clinicians) prefer to give both buccal and palatal infilterations and specialists opt for only buccal infilteration (66-74% of specialists)., Conclusion: Only buccal infilteration is sufficient during root canal treatment of maxillary molars. Routine use of supplemental anaesthesia in the form of palatal and intra-ligamentary infilteration is not necessary unless patient experiences discomfort during endodontic treatment. However, intra-ligamentary infilteration may lead to postoperative discomfort in the form of pain.

Noscapine (Nos), an antitussive benzylisoquinoline opium alkaloid, is a non-toxic tubulin-binding agent currently in Phase II clinical trials for cancer chemotherapy. While preclinical studies have established its tumor-inhibitory properties in various cancers, poor absorptivity and rapid first-pass metabolism producing several uncharacterized metabolites for efficacy, present an impediment in translating its efficacy in humans. Here we report novel formulations of Nos in combination with dietary agents like capsaicin (Cap), piperine (Pip), eugenol (Eu) and curcumin (Cur) known for modulating Phase I and II drug metabolizing enzymes. In vivo pharmacokinetic (PK), organ toxicity evaluation of combinations, microsomal stability and in vitro cytochrome P450 (CYP) inhibition effects of Nos, Cap and Pip using human liver microsomes were performed. Single-dose PK screening of combinations revealed that the relative exposure of Nos (2 μg h/mL) was enhanced by 2-fold (4 μg h/mL) by Cap and Pip and their plasma concentration-time profiles showed multiple peaking phenomena for Nos indicating enterohepatic recirculation or differential absorption from intestine. CYP inhibition studies confirmed that Nos, Cap and Pip are not potent CYP inhibitors (IC50>1 μM). Repeated oral dosing of Nos, Nos+Cap and Nos+Pip showed lower exposure (Cmax and AUClast) of Nos on day 7 compared to day 1. Nos Cmax decreased from 3087 ng/mL to 684 ng/mL and AUClast from 1024 ng h/mL to 508 ng h/mL. In presence of Cap and Pip, the decrease in Cmax and AUClast of Nos was similar. This may be due to potential enzyme induction leading to rapid clearance of Nos as the trend was observed in Nos alone group also. The lack of effect on intrinsic clearance of Nos suggests that the potential drug biotransformation modulators employed in this study did not contribute toward increased exposure of Nos on repeated dosing. We envision that Nos-induced enzyme induction could alter the therapeutic efficacy of co-administered drugs, hence emphasizing the need for strategic evaluation of the metabolism of Nos to reap its maximum efficacy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural "milieu" confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8 G), 10-gingerol (10 G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYP-specific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE's inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10 G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an in-depth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens.

The present case report is the first of its kind that documents the successful outcome of "revascularization," a regeneration-based treatment protocol in a mature adult patient. It belies the myth that "revascularization" should only be done in children and young, adolescent patients. The misconception that stem cells number as well as viability in older age group patients will not allow revascularization to be successful is also contradicted by this case. The paper highlights all the mechanisms that come into play and the enhancing of regenerative response by supplementation with platelet-rich plasma (PRP).

In the present study, a series of novel 2-[4-(1H-[1,2,4]-triazol-1-yl)phenyl]-1-substituted-4,6-difluoro-1H-benzo[d]imidazole derivatives are synthesized by the alkylation of 2-[4-(1H-[1,2,4]-triazol-1-yl)phenyl]-4,6-difluoro-1H-benzo[d]imidazole with substituted alkyl and aryl halides. The compounds were evaluated for their preliminary in-vitro antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhosa and then were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. The antibacterial data suggested that the analogs with electronegative substituents emerged as promising antimicrobials. It was also observed that the promising antimicrobials have proved to be better antimycobacterials. Few of selected analogs are under further evaluation for secondary antitubercular screening, as they have shown better activity compared to rifampin.