Effectiveness of XP-Endo Finisher, Endoactivator, and PUI agitation in the penetration of intracanal medicaments into dentinal tubules: A confocal laser scanning microscope analysis.

Background: This investigation assessed the impact of irrigation activation systems on the depth of penetration of intracanal medicaments into dentinal tubules. Methods: Ninety-six mandibular premolar teeth were prepared using ProTaper Next up to size X3. The teeth were randomly divided into four groups based on the final irrigation activation systems (n=24): group 1: EndoActivator, group 2: XP-Endo Finisher, group 3: Passive ultrasonic irrigation (PUI), and group 4: control. After the final irrigation, all the samples were divided into two subgroups (n=12): subgroup A: calcium hydroxide (Ca(OH)2 ) and subgroup B: modified triple antibiotic paste (mTAP). Statistical analysis involved three-way analysis of variance (ANOVA). Results: EndoActivator, XP-Endo Finisher, and PUI activation methods significantly increased the penetration of intracanal medicaments compared to conventional needle irrigation (P<0.05). The XP-Endo Finisher group exhibited the highest penetration percentage and maximum penetration depth, showing a statistically significant difference from the EndoActivator group (P<0.001). No significant difference was observed between XP-Endo Finisher and PUI, nor between PUI and EndoActivator (P>0.05). mTAP showed a higher percentage of dentinal tubule penetration than Ca(OH)2, although no significant difference was found in maximum penetration depth. The coronal region demonstrated the highest penetration percentage and depth, while the apical region showed the lowest. Conclusion: This study showed the effectiveness of XP-Endo Finisher in improving the penetration of intracanal medicaments into dentinal tubules. The findings emphasize the importance of selecting appropriate irrigation activation systems to improve treatment outcomes in endodontics. By demonstrating the effectiveness of advanced systems like XP-Endo Finisher, this research supports their integration into routine clinical practice for better endodontic success.

[Risk analysis applied to the monitoring of immunosuppressor concentrations in lung transplant recipients]. / Analyse de risques appliquée au suivi des concentrations des immunosuppresseurs chez les patients transplantés pulmonaire.

Mastering and monitoring immunosuppressant concentrations is central to the care of lung transplant patients and involves multiple stakeholders. The objective is to conduct a risk analysis to evaluate the impact of various actions taken. The lung transplantation team was convened to carry out a failure mode effect analysis. The process was divided into stages where different risks were identified. The risk priority number (RPN) (severity, frequency, detectability) and risk level of criticality (frequency, severity) were established before implementation of actions (before 2009) and then after (in 2022) to classify risks according to four levels of criticality. The implemented actions included the establishment of a quality assurance process, computerization of monitoring, and double analysis by a physician/pharmacist pair. Thirty-two risks were identified during the four stages of the process: biological sampling (n=13), reception (n=3), analysis and treatment of levels (n=5), transmission of information/prescriptions to the patient (n=11). The total raw RPN (before 2009) was 839, with 12 major risks. The current total RPN (in 2022) was 452 (a decrease of 46.1%), with 7 major risks identified. The analysis enabled the objective evaluation of the effectiveness of the actions taken. The most secure stage of the process is the reception of residual level results. Efforts should focus on empowering and involving patients, as well as engaging local stakeholders in collaboration with the specialized transplantation team.

Analysis of tooth staining by endodontic medication in root canal therapy using spectrophotometry.

The assessment of the discoloration caused by calcium hydroxide, triple antibiotic paste, and chlorhexidine gel when used as intra-canal medicaments in teeth undergoing root canal treatment is of interest. The study measured the discoloration over seven and fourteen days using a spectrophotometer. After obtaining ethical clearance, ninety anterior teeth requiring root canal therapy were selected based on eligibility criteria. Using basic randomization, participants were split up into three groups, each consisting of thirty patients. The colorimeter was used to measure preoperative, one and two weeks following the medication's removal. All groups showed significant discoloration, with 2% chlorhexidine gel (p≤0.03) and triple antibiotic paste (p≤0.02) causing the highest discoloration in the central region of teeth. The discoloration was inversely correlated with the remaining dentin thickness. Thus, intracanal medicaments used for endodontic treatment cause tooth discolouration.

The effects of photobiomodulation and/or azithromycin treatment on bone resorption biomarkers in gingival crevicular fluid from patients with stage III-IV grade C periodontitis.

OBJECTIVES: This study aims to investigate the impact of photobiomodulation (PBM) and/or azithromycin (AZM) therapy in combination with full-mouth subgingival instrumentation (FSI) on receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) levels and RANKL/OPG ratios in gingival crevicular fluid (GCF) on patients with stage III-IV grade C periodontitis. MATERIALS AND METHODS: The study was conducted on 77 stage III-IV grade C periodontitis patients and 20 periodontally healthy controls. Patients with stage III-IV grade C periodontitis were categorized into four treatment groups: 1) only FSI (FSI) group; 2) FSI+AZM (AZM) group; 3)FSI+PBM (PBM) group and 4) FSI+PBM+AZM (AZM+PBM) group. Clinical periodontalparameters and RANKL and OPG levels and RANKL/OPG ratios in GCF were measured at thebaseline and month 3rd of the therapy. RESULTS: Compared with the periodontally healthy controls,all the baseline clinical parameters were higher in the Stage III-IV grade C periodontitis groups (P< 0.05); however, there were no statistically significant differences between the Stage III-IV gradeC periodontitis groups (P>0.05). In month 3rd, the lowest values in all clinical parameters weregenerally observed in the antibiotics groups whereas the highest values were observed in the FSIgroup. Furthermore, the highest RANKL and OPG values in antibiotic groups and the highestRANKL/OPG ratio in PBM group were observed in the third months. RANKL/OPG ratios did notchange in the FSI and antibiotics groups after the treatment, but it increased significantly in thePBM group. CONCLUSION: While PBM treatment combined with FSI increases the RANKL levels,AZM increases OPG levels. Also, PBM+AZM treatment shows additional clinical andimmunological beneficial efficacy.

Design of in-situ implant for the brain-targeted drug delivery using cross-linked gellan gum polymer through response surface methodology.

The analysis aimed to prepare an in-situ implant (ISFI) formulation holding dimethyl fumarate as (a model drug) using cross-linked gellan gum by homogenization method. Cross-linking of gellan gum was done with L-cysteine to improve its gelation properties. Fourier transform infrared spectroscopy (FTIR) and (DSC) Differential scanning calorimetry were used to test the compatibility of the drug-polymer. The diverse formulations were prepared and tested using Design Expert® ver 8.0.1 software to optimize the experiment technique and employ the response surface. The tissue compatibility of the test verified the existence of non-irritants in the established formulation. All preparations contained the drug content from approximately 97.98 to 99.88%. Viscosities are ideal for injection in the optimized formulation (1,55 percent w/w in water). The optimized formula was monitored, and up to 156hours, it was found to be 95.7%. The result was that ISFI can effectively monitor and control the delivery of several powerful drug products.

Evaluating the Depth of Penetration of Calcium Hydroxide Mixed With Three Different Herbal Essential Oils Using a Confocal Laser Scanning Microscope.

Introduction The goal of endodontic therapy is to completely eliminate the infection and stop microbes from infecting or reinfecting the root canal and the periradicular tissues. Amongst the primary microorganisms, Enterococcus faecalis (E. faecalis), a Gram-positive anaerobe, is the main cause of pulpal and periapical inflammation causing root canal failure. Literature evidence shows that the gold-standard calcium hydroxide is ineffective against E. faecalis due to its resistance to the alkaline pH and proton pump mechanism. Herbal essential oils such as oregano, basil, and thyme are known to possess antimicrobial properties against E. faecalis. However, their combination with calcium hydroxide as an intracanal medicament and the depth of penetration is still unknown. Aim To evaluate the depth of penetration of calcium hydroxide mixed with three different herbal essential oils using a confocal laser scanning microscope. Material and methods Fifty single-rooted premolars were decoronated and randomly divided into five groups. Group 1 - Oregano oil with calcium hydroxide, Group 2 - Basil oil with Calcium hydroxide, Group 3 - Thyme oil with calcium hydroxide, Group 4 - Calcium hydroxide with saline, Group 5 - Negative control. The teeth were instrumented and inoculated with E. faecalis and incubated for 21 days. Calcium hydroxide mixed with respective oils or saline and 0.1% rhodamine B dye was placed in the canals and again incubated for 7 days. Two sections each of 1 mm were horizontally cut at 3 mm and 5 mm from the apex and later subjected to a confocal laser scanning microscope to evaluate the depth of penetration. One-way ANOVA, post-hoc Tukey test, and student t-test were performed. Results At the middle third, basil oil had the maximum depth of penetration (1377.47±14.1 µm) followed by oregano oil (1345.4±26.5 µm) and thyme oil (1160.4±24.6 µm). At apical third, basil oil (1152.4±31.6 µm) showed maximum depth of penetration, followed by thyme (988.3±26.2 µm) and oregano oils (419.5±19.8 µm). The depth of penetration of these oils was greater at the middle third than at the apical third. Conclusion Basil, oregano, and thyme oil have good penetration depth into the dentinal tubules and can be successfully used in root canal procedures as intracanal medicaments.

The Effect of Intracanal Medicaments on the Healing of Apical Periodontitis.

BACKGROUND: Apical periodontitis is a prevalent inflammatory condition affecting the tissues surrounding the root apex of a tooth. The selection of appropriate intracanal medicaments for its management remains a topic of ongoing research. This study aimed to investigate the effect of calcium hydroxide and triple antibiotic paste on the healing of apical periodontitis. METHODS: A total of 304 teeth from 215 patients with apical periodontitis were included in this observational study. Patients were randomly assigned to three groups: Group A (calcium hydroxide), Group B (triple antibiotic paste), and Group C (control). Baseline characteristics were recorded, and follow-up assessments were conducted at three, six, and 12 months. Parameters such as reduction in apical radiolucency, presence of periapical healing, bleeding on probing (BOP) percentage, clinical attachment level (CAL), and periodontal depth were evaluated. RESULTS: At baseline, the three groups exhibited similar distributions of apical periodontitis parameters. Over the 12-month follow-up, Group A and Group B demonstrated a significant reduction in apical radiolucency compared to Group C (p < 0.05). The presence of periapical healing was more frequent in Group A (85%) and Group B (80%) compared to Group C (60%). Group A showed the lowest mean BOP percentage (15.2 ± 3.5), followed by Group B (18.6 ± 4.2) and Group C (22.1 ± 4.8). Similarly, Group A demonstrated the highest mean CAL (5.8 ± 0.9 mm) and the lowest mean periodontal depth (3.2 ± 0.6 mm). Group B exhibited intermediate values for CAL (5.2 ± 1.1 mm) and periodontal depth (3.6 ± 0.8 mm). CONCLUSION: In this study, both calcium hydroxide and triple antibiotic paste demonstrated potential therapeutic effects in promoting healing and reducing apical radiolucency compared to the control group. Calcium hydroxide exhibited the most favorable outcomes, with a higher presence of periapical healing, lower BOP percentage, and superior CAL and periodontal depth measurements. These findings contribute to the understanding of intracanal medicaments' effectiveness in apical periodontitis management.

Development and characterization of palbociclib-loaded PLGA nanobubbles for targeted cancer therapy.

OBJECTIVE: The objective of this study was to develop and optimize palbociclib-loaded nanobubbles for targeted breast cancer therapy. MATERIALS AND METHODS: Biocompatible poly(DL-lactide-co-glycolide) was used to create nanobubbles loaded with palbociclib. The formulation process was meticulously crafted using a three-level Box-Behnken design and a double emulsion solvent evaporation method to precisely tailor the nanobubbles' properties. RESULTS: The Derringer's desirability method optimized variables by transforming responses into a desirability scale, resulting in a global desirability value. Optimal settings, A: 526.97mg, B: 250mg,C: 2.0% w/v, D: 6101rpm, achieved a D value of 0.949. Palbociclib nanobubbles demonstrated a smaller particle size (31.78±2.12) than plain nanobubbles (38.56±3.56). PDI values indicated a uniform size distribution. The zeta potential remained consistent, with values of -31.34±3.36 for plain and -31.56±3.12 for drug-loaded nanobubbles. Encapsulation efficiency was 70.12%, highlighting effective drug encapsulation. Palbociclib release was significantly higher from nanobubbles in pH 7.4, especially with ultrasound, releasing almost 99.34% of the drug. Hemolytic activity assays confirmed safety for injection. Fluorescent intensity analysis revealed a two-fold increase in cellular uptake of palbociclib facilitated by ultrasound. The MTT assay demonstrated enhanced cytotoxicity of palbociclib-loaded nanobubbles, especially with ultrasound, emphasizing their potential for improved therapeutic efficacy. The IC50 values for palbociclib, without ultrasound, and with ultrasound were 98.3µM, 72.34µM, and 61.34µM, respectively. CONCLUSION: The significant findings of this study emphasize the potential of palbociclib-loaded nanobubbles as a promising therapeutic system for improved breast cancer treatment.

[Training pharmacy students to conduct targeted interviews on oral anticoagulants: Development and evaluation of training using healthcare simulation]. / Formation des étudiants en pharmacie conduisant des entretiens ciblés sur les anticoagulants oraux : élaboration et évaluation d'une formation par la simulation en santé.

OBJECTIVES: Pharmaceutical care for patients receiving oral anticoagulants (OACs) should be performed by trained healthcare professionals to prevent adverse effects and improve patient adherence. Before meeting patients, all pharmacy students in our department (in a one-year hospital internship program) experienced a theoretical training for several years. It was decided to add a practical component based on simulation training. The study reports the simulation program conception and the assessment of the simulation-based training for pharmacy students involved in conducting interviews with patients receiving ACOs. METHODS: Organization and content of the training course were defined by two hospital pharmacists and one pharmacy resident. Skills' assessment was measured in pharmacy students in 3 steps: (1) initial assessment by individual interview, (2) group training by simulation, (3) final assessment by individual interview. Student satisfaction was also assessed at the end of the training. RESULTS: Four scenarios and one assessment form were developed and 16 pharmacy students experienced the training. An improvement in skills after the simulations courses was observed in all parts of the process: the pre-interview (mean +15%), the interview itself (+16%) and the post-interview (+18%). All students felt more comfortable and motivated to conduct interviews and recommended that this training be continued. CONCLUSIONS: The study underlines the impact of the simulation training on students' skills and their satisfaction with the overall training program. The simulation training is now fully added to the program. Further studies should explore the skills improvement in real life during the first patient interview.

In vivo pharmacokinetic study of carmustine in rats after giving single-dose of carmustine API solution, flexible liposomes, in situ nasal gel, optimized flexible liposomes embedded in situ nasal gel, and marketed formulation.

BACKGROUND: Carmustine is used in the treatment of glioblastoma (GBM). GBM is a well-known life-threatening type of cancerous tumor. GBM covers 60.00% among all primary brain tumors, with an occurrence of 74,000 cases across the globe. Management for GBM is still very difficult because most of the medicines are unable to cross the blood-brain barrier (BBB). The present work observed that flexible liposomes embedded in situ nasal gel of carmustine is the best brain-targeted medicine delivery system for the management of GBM through the nasal route. AIM: To evaluate in vivo pharmacokinetic parameters of carmustine formulations administered through nasal routes in Wistar rats. METHODS: In this work, different pharmacokinetic parameters were determined for carmustine formulations viz. carmustine API (Active Pharmaceutical Ingredient) solution, flexible liposomes, in situ thermoreversible intranasal gel, optimized flexible liposomes embedded in situ thermoreversible intranasal gel via intranasal administration in rats, and compared with marketed intravenous injection of carmustine administered through intravenous route. Carmustine was estimated with the help of a validated high-performance liquid chromatography (HPLC) approach. Three to four-months-old normal Wistar rats of either sex, having a weight of 200-250 grams were used in this study. RESULTS: Intranasal administration of optimized flexible liposomes embedded in situ nasal gel showed greater Cmax (∼two-fold), AUC0→t (∼three-fold), AUC0→∞ (∼six-fold), and decreased Tmax (1h) data in the brain, than commercial intravenous injection of carmustine. The plasma concentration of carmustine administered through nasal route was found to be comparatively lower than intravenous administration, indicating lower systemic exposure to carmustine via the nasal route. CONCLUSION: In vivo pharmacokinetics results revealed that the optimized flexible liposomes embedded in situ nasal gel of carmustine can effectively deliver carmustine to brain by nasal drug delivery system in Wistar rats.

Lipoteichoic Acid from Lacticaseibacillus rhamnosus GG as a Novel Intracanal Medicament Targeting Enterococcus faecalis Biofilm Formation.

The demand for safe and effective endodontic medicaments to control Enterococcus faecalis biofilms, a contributor to apical periodontitis, is increasing. Recently, lipoteichoic acid (LTA) of family Lactobacillaceae has been shown to have anti-biofilm effects against various oral pathogens. Preliminary experiments showed that LTA purified from Lacticaseibacillus rhamnosus GG (Lgg.LTA) was the most effective against E. faecalis biofilms among LTAs from three Lactobacillaceae including L. rhamnosus GG, Lacticaseibacillus casei, and Lactobacillus acidophilus. Therefore, in this study, we investigated the potential of Lgg.LTA as an intracanal medicament in human root canals infected with E. faecalis. Twenty eight dentinal cylinders were prepared from extracted human teeth, where two-week-old E. faecalis biofilms were formed followed by intracanal treatment with sterile distilled water (SDW), N-2 methyl pyrrolidone (NMP), calcium hydroxide (CH), or Lgg.LTA. Bacteria and biofilms that formed in the root canals were analyzed by scanning electron microscopy and confocal laser scanning microscopy. The remaining E. faecalis cells in the root canals after intracanal medicament treatment were enumerated by culturing and counting. When applied to intracanal biofilms, Lgg.LTA effectively inhibited E. faecalis biofilm formation as much as CH, while SDW and NMP had little effect. Furthermore, Lgg.LTA reduced both live and dead bacteria within the dentinal tubules, indicating the possibility of minimal re-infection in the root canals. Collectively, intracanal application of Lgg.LTA effectively inhibited E. faecalis biofilm formation, implying that Lgg.LTA can be used as a novel endodontic medicament.

Current perspectives on calcium silicate-based intracanal medicaments: A scoping review of clinical and laboratory evidence.

OBJECTIVE: Intracanal medicaments, primarily calcium hydroxide, play a significant role in optimizing root canal disinfection. Recently, calcium silicate-based intracanal medicaments have emerged as potential alternatives. This scoping review sought to map the available evidence concerning the clinical and laboratory properties of these bioceramic medicaments. DATA: The study protocol was registered a priori (https://osf.io/rnyuv/) and a systematic search strategy using relevant MeSH terms was employed. SOURCES: The search was conducted across databases including the Cochrane Library, EMBASE, PubMed/MEDLINE, SciVerse Scopus, and Web of Science. STUDY SELECTION: Studies that investigated the clinical and laboratory properties of calcium silicate-based intracanal medicaments were included. CONCLUSIONS: Out of 1008 potentially relevant articles, 15 met the inclusion criteria. The majority of the studies came from Brazil, primarily focusing on Bio-C Temp (Angelus). The studies revealed acceptable biocompatibility, alkaline pH, and high calcium ion release. However, they showed reduced antibacterial activity compared to conventional calcium hydroxide formulations. Tooth discoloration beyond clinically acceptable thresholds was also a significant concern. A single clinical case report exhibited potential for periapical healing and root development, though this evidence is very limited. While current evidence is preliminary, high-quality clinical trials are essential to determine their clinical efficacy and safety in endodontic treatments. CLINICAL RELEVANCE: Calcium silicate-based intracanal medicaments have lower antibacterial activity and potential for tooth discoloration compared to conventional calcium hydroxide-based medicaments. Given the available evidence, they cannot be recommended for routine clinical practice.

Application progress of nanomaterials in the treatment of prostate cancer.

Prostate cancer is one of the most common malignant tumors in men, which seriously threatens the survival and quality of life of patients. At present, there are serious limitations in the treatment of prostate cancer, such as drug tolerance, drug resistance and easy recurrence. Sonodynamic therapy and chemodynamic therapy are two emerging tumor treatment methods, which activate specific drugs or sonosensitizers through sound waves or chemicals to produce reactive oxygen species and kill tumor cells. Nanomaterials are a kind of nanoscale materials with many excellent physical properties such as high targeting, drug release regulation and therapeutic monitoring. Sonodynamic therapy and chemodynamic therapy combined with the application of nanomaterials can improve the therapeutic effect of prostate cancer, reduce side effects and enhance tumor immune response. This article reviews the application progress of nanomaterials in the treatment of prostate cancer, especially the mechanism, advantages and challenges of nanomaterials in sonodynamic therapy and chemodynamic therapy, which provides new ideas and prospects for research in this field.

[Evaluation of medication self-administration feasibility in a university hospital: Clinical audits and recommendations]. / Évaluation de la faisabilité du dispositif d'auto-administration des médicaments par le patient dans un centre hospitalier universitaire : audits de pratique et recommandations pour une mise en œuvre sûre.

The French Health Authority recently published guidelines about patient self-administration of medications for voluntary hospitalized patients under medical supervision. This study aimed to assess medication management practices in our hospital and provide recommendations for self-administration medication. A prospective monocentric study was performed from January to June 2023, involving patient and nurse surveys based on the guidelines from the French Health Authority. A total of 207 patients participated in the survey, with a mean age of 59.6years. Among them, 56% were inclined to self-manage treatments initiated during hospitalization. Among patients with regular treatments, 62% were inclined to self-manage them in the hospital. In weekday hospitalization units, 92% of patients were inclined to self-manage their regular treatments, and 75% of those initiated during hospitalization. Among the 26 surveyed nurses, 71% reported patient autonomy for taking drugs in narrative transmissions, and 88% verified medication intake through self-administration, while 96% digitally traced it. The concept of self-administration of medication appears promising, especially within weekday hospitalization units, particularly for patients with a good understanding of their treatment. Nurses currently assess patient autonomy without specific monitoring tools. Collaborative efforts among healthcare professionals, with pharmacists playing a central role, are essential for the success of this innovative approach.

Comparative Evaluation of Antimicrobial Efficacy of Triple Antibiotic Paste Herbal Combination and Camphorated Monochlorophenol as Intracanal Medicaments against Enterococcus faecalis in Deciduous Molars: An In Vivo Study.

Aim: Compare the efficacy of triple antibiotic paste (TAP), herbal extracts, and camphorated monochlorophenol (CMCP) as intracanal medicaments against Enterococcus faecalis (E. faecalis) in deciduous molars. Materials and methods: A total of 60 samples were collected from canals of first and second molars of 4-10-year-old children, with more than two-thirds root length, and fitting the inclusion criteria. Samples were collected at three intervals-S1 was collected just after access opening, S2 was collected after biomechanical preparation (BMP) and irrigation, and just before placement of medicament. Randomization was done to place the medicaments into three groups: group I-CMCP, group II-TAP, and group III-herbal combination. Sample S3 was taken 48 hours after removal of medicament from the canals. The collected samples were transported via Amies media to the laboratory, where they were anaerobically incubated for 24 hours. Growth of E. Faecalis was observed, and manual counting of the colony-forming unit (CFU) was done. The change in CFU in all samples was calculated, and the results were statistically analyzed. Results: The results show that there is a change from S1 (TAP = 118.67 ± 122.48, herbal = 109.07 ± 106.43; CMCP = 110.73 ± 120.53) to S2 (TAP = 34.13 ± 63.47; herbal = 27.67 ± 39.39; CMCP = 16.40 ± 26.32) and S3 (TAP = 12.33 ± 24.82; herbal = 4.73 ± 12.78; CMCP = 3.40 ± 7.12). It is seen that there is a significant difference seen from S1 to S2 in all three groups (p ≤ 0.05) using repeated measure analysis of variance (ANOVA) test. This shows that all three medicaments were effective in reducing bacterial counts of E. Faecalis from sample S1 (pre) to S3 (post) significantly after exposure to root canal bacterial flora for 48 hours (2 days). The pairwise comparison of the change in CFU within each group, S1-S3, also shows significant changes. There is a significant decrease in CFU seen from S1 to S2 and S1 to S3 but not from S2 to S3 for all three groups, which was evaluated using the post hoc Bonferroni test. It was also observed that in between the canals, although there was a change from S1 to S3 in terms of the CFU, there was no significant difference in the decrease in the bacterial count when intercanal comparison was made. There was, however, a change that was seen to be significant when values from each canal were compared from S1 to S3. Conclusion: All three medicaments have successfully shown a decrease in the numbers of E. faecalis, which the study aimed at checking. Although the effect varied intergroups, it was mild, so herbal alternatives could be used instead of antibiotics and CMCP. Also, because the local application is effective in controlling interappointment flare-ups, the medicaments can be successfully given without having to prescribe systemic antibiotics. How to cite this article: Tawde MM, Lakade L, Patil S, et al. Comparative Evaluation of Antimicrobial Efficacy of Triple Antibiotic Paste Herbal Combination and Camphorated Monochlorophenol as Intracanal Medicaments against Enterococcus faecalis in Deciduous Molars: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(3):243-254.

A Comparative Evaluation of Herbal Extracts and Triple Antibiotic Paste as Intracanal Medicament against Enterococcus faecalis: A Microbiological Study.

Purpose: The purpose of the study is to compare and evaluate the efficacy of herbal extracts over modified triple antibiotic paste (MTAP) as intracanal medicaments against Enterococcus faecalis (E. faecalis). Ginger, turmeric, and nutmeg extract were checked for antibacterial activity by agar disk diffusion method at 100, 50, 25, and 12.5% concentration. Combination groups were prepared, and the combination group showing the best zone of inhibition was further evaluated. Materials and methods: A total of 103 samples were taken and divided into five groups: group I-MTAP, group II-ginger, group III-turmeric, group IV-nutmeg, and group V-saline. Based on different concentrations, the groups were again subdivided into subgroups at 100, 50, 25, and 12.5%. Combination groups of ginger + nutmeg, ginger + turmeric, and turmeric + nutmeg were made and evaluated. The combination group showing the best zone of inhibition was again divided into 100, 50, 25, and 12.5% and further evaluated. Results: Modified triple antibiotic was effective in the elimination of E. faecalis. Herbal extracts showed a reduction in the number of E. faecalis. Nutmeg showed a reduction in E. faecalis, followed by ginger, followed by turmeric. Conclusion: This study shows that the combination of ginger + nutmeg at 12.5% concentration (35 mm) showed the highest zone of inhibition among all the herbal combinations, which is almost equal to that of MTAP. How to cite this article: Golla S, Gambhir N, Gupta N, et al. A Comparative Evaluation of Herbal Extracts and Triple Antibiotic Paste as Intracanal Medicament against Enterococcus faecalis: A Microbiological Study. Int J Clin Pediatr Dent 2024;17(3):285-290.

Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms.

Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.

[Low-dose methotrexate: Indications and side effects, particularly in cases of diffuse interstitial pneumonia]. / Méthotrexate à faible dose : indications et effets secondaires, en particulier en cas de pneumopathie interstitielle diffuse.

INTRODUCTION: Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use. STATE OF THE ART: In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD). PERSPECTIVES AND CONCLUSIONS: Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment.

[Protein induced proximity and targeted degradations by new degraders: concepts, developments, challenges for clinical applications]. / Induction de proximité et dégradation de cibles thérapeutiques par les nouveaux dégradeurs : quels concepts, quels développements, quel futur ?

The review is focused on recent drug discovery advances based on targeted protein degradation strategies. This new area of research has exploded leading to the development of potential drugs useful in a large variety of human diseases. They first target disease relevant proteins difficult to counteract with other classical strategies and extend now to aggregates, organelles, nucleic acids or lipidic droplets. These degraders engaged either the ubiquitin-proteasome system for PROTACs and molecular glues (first generation), or the lysosomal system via endosome-lysosome degradation (LYTACs) and autophagy-lysosome degradation (ATTEC, AUTAC, AUTOTAC) (following generations of degraders). PROTACs have expanded from the orthodox heterobifunctional ones to new derivatives such as homo-PROTACs, pro-PROTACs, CLIPTACs, HaloPROTACs, PHOTOTACs, Bac-PROTACs, AbTACs, ARN-PROTACs. The small molecular-weight molecular glues induce the formation of new ternary complexes which implicate the targeted protein and an ubiquitin ligase E3 allowing the protein ubiquinitation followed by its proteasomal degradation. Lysosomal degraders (LYTAC, ATTEC, AUTAC, AUTOTAC) specifically recognize extracellular and membrane proteins or dysfunctional organelles and transport them into lysosomes where they are degraded. They overcome the limitations observed with proteasomal degradations induced by PROTAC and molecular glues and demonstrate their potential to treat human diseases, especially neurodegenerative ones. Pharmaceutical companies are engaged at the world level to develop these new potential drugs targeting cancers, immuno-inflammatory and neurodegenerative diseases as well as a variety of other ones. Efficiency and risks for these novel therapeutic strategies are discussed.

Title: Induction de proximité et dégradation de cibles thérapeutiques par les nouveaux dégradeurs : quels concepts, quels développements, quel futur ? Abstract: La recherche dans le domaine de la dégradation ciblée des protéines s'est considérablement développée conduisant à l'élaboration de nouveaux outils chimiques à visée thérapeutique, les dégradeurs, potentiellement utiles dans diverses pathologies. Une grande variété d'objets à dégrader appartenant à divers compartiments intra- ou extracellulaires (protéines, complexes ou agrégats, organelles, acides nucléiques, gouttelettes lipidiques) a été ciblée à l'aide de ligands déjà existants, d'autres restent à découvrir. Les molécules de première génération, PROTAC et colles moléculaires, utilisent le système ubiquitine-protéasome pour détruire spécifiquement des protéines pathogéniques, certaines considérées jusqu'à présent comme inaccessibles en tant que cibles thérapeutiques. Au cours des cinq dernières années, ont été développés de nouveaux types de PROTAC hétéro-bifonctionnels comme les homo-PROTAC, pro-PROTAC, CLIPTAC, HaloPROTAC, PHOTOTAC, Bac-PROTAC, mais aussi des PROTAC macromoléculaires comme les AbTAC et ARN-PROTAC. Du fait de la grande diversité des substrats dégradés par les lysosomes, de nouveaux dégradeurs impliquant deux voies distinctes ont été ensuite produits : les chimères LYTAC pour la voie endosome-lysosome et les chimères ATTEC, AUTAC et AUTOTAC pour la voie autophagie-lysosome, augmentant ainsi considérablement le champ d'action des dégradeurs. Ces nouvelles molécules reconnaissent spécifiquement des protéines et/ou des organelles et permettent leur transport dans les lysosomes où ils sont dégradés. Les succès obtenus, que ce soit par dégradation protéasomale ou lysosomale pour plusieurs dizaines de dégradeurs (preuves de concepts et études cliniques en cours), expliquent l'intérêt quasi mondial des industries pharmaceutiques pour ces nouvelles molécules. Les challenges posés par leur développement et leur utilisation en clinique sont discutés.