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.

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.

[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.

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.

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.

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.

[Balancing drug regulation and health democracy: The role of patient and healthcare professional advisors at the ANSM]. / Concilier régulation du médicament et démocratie sanitaire : rôle des conseillers patient ou professionnel de santé à l'ANSM.

The French National Agency for Health Products (ANSM) is a regulatory and public health agency. Its regulatory, health policing and public health protection activities require a perfect fit with the field and the various people involved in the use of health products. Since 2019, the ANSM has adapted its organisation, procedures and processes to encourage and improve interaction with its stakeholders, as part of its policy of openness towards civil society. To accompany this ambitious change and to support its staff, the Agency has recruited advisors corresponding to the main users of health products: prescribers (doctor's hospital and outpatient), pharmacists and patients. Working as a group or individually, they provide a "lived" user perspective on health products at each stage of the evaluation process. They may be involved in the assessment of dossiers, signals or applications received by the Agency, in the internal validation of reports or in discussions with stakeholders. They are particularly involved when the analysis requires expertise that goes beyond the technical, scientific or regulatory aspects. They may also work with ANSM staff to explain certain processes and difficulties in the field. Advisors help to ensure that regulatory and/or scientific expertise is clear and consistent with user experience. In addition to their scientific and therapeutic aspects, medicines are also economic, social and political issues. Their regulation is therefore particularly affected by the need for health democracy. This requires the active participation of health professionals, patients and, more broadly, civil society in the decision-making process. Civil society is a space occupied by a wide range of actors who exert pressure from different ideological positions to influence the regulation of health products. In this context, taking into account a plurality of viewpoints in the regulation of health products is necessary and complex, but its operation can be facilitated by the collective efforts of the actors and the adaptation of organisations, such as the integration of advisors.

[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.

[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.

Comparative Analysis of the Cytotoxic Effects of Modified Triple Antibiotic Hydrogel: Insights From Experimental Models.

INTRODUCTION:  The effectiveness of intracanal medicaments (ICMs) in root canal therapy is critical for successful dental treatments, yet their cytotoxic effects pose significant challenges. This research uses zebrafish embryos and dental pulp stem cells (DPSCs) to identify the optimal concentration that balances antibacterial efficacy with minimal toxicity. AIM:  This study aims to address the need for effective ICMs in dentistry by formulating and assessing the embryotoxicity and cytocompatibility of a novel carrageenan-based modified triple antibiotic paste (MTAP) hydrogel at different concentrations (1, 5, and 10 mg/mL) using a zebrafish model and cell culture assay. MATERIALS AND METHODS:  The hydrogel was formulated by combining antibiotic solutions (ciprofloxacin, metronidazole, and amoxicillin) with carrageenan and xanthan gum. Zebrafish embryos were exposed to varying concentrations of MTAP hydrogel, chlorhexidine (CHX), calcium hydroxide (CaOH2), and plain carrageenan to assess developmental toxicity, survival rate, heart rate, hatching rate, and macrophage migration. The cytotoxicity against DPSCs was examined within a timeframe of 6, 24, and 72 hours with the use of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. RESULTS:  The analysis revealed developmental toxicity with malformations observed at higher concentrations of MTAP hydrogel, CaOH2, and CHX medicaments, indicating potential toxicity. Significant impacts on survival, heart rate, and hatching rate were noted in the CaOH2 and CHX groups, as well as at higher MTAP hydrogel concentrations, emphasizing the importance of dosage considerations. The neutral red assay confirmed toxicity, with macrophage migration observed in CaOH2, CHX, and higher MTAP hydrogel concentrations. Lower concentrations, particularly at 1 mg/mL, showed no adverse effects on zebrafish embryos and larvae. These findings align with cell viability investigations, which demonstrated that higher antibiotic concentrations resulted in decreased cell proliferation and viability over time. Conversely, at a lower concentration of 1 mg/mL, cell proliferation notably increased after 72 hours. Plain MTAP and CHX exhibited the highest toxicity levels in the MTT assay. CONCLUSION:  The study concludes that while higher concentrations of MTAP hydrogel exhibit toxic effects, the hydrogel at 1 mg/mL demonstrates no adverse impact on zebrafish embryos, larvae, and DPSCs. These findings underscore the necessity of optimizing ICM concentrations to balance antibacterial efficacy and minimal cytotoxicity.

Chitosan-Gelatin Scaffolds Loaded with Different Antibiotic Formulations for Regenerative Endodontic Procedures Promote Biocompatibility and Antibacterial Activity.

BACKGROUND: This study investigated the biocompatibility and antibacterial efficacy of chitosan-gelatin (CH-G) scaffolds loaded with slow-releasing antibiotic formulations used in regeneration endodontic procedures (REPs). METHODS: Scaffolds were fabricated using freeze drying and loaded with varying concentrations of augmentin or modified triple antibiotic paste (mTAP). High-resolution scanning electron microscopy (SEM) was used to characterize the scaffold, while drug release was monitored via UV-Vis spectrophotometry. Immortalized human mesenchymal stem cells (hMSCs) were cultured on CH-G scaffolds alone (control), either 0.1 mg/mL or 1 mg/mL of augmentin or mTAP, and 10 mg/mL calcium hydroxide (Ca(OH)2). Cell viability and proliferation were assessed using the Alamar Blue assay and SEM, respectively, and live/dead staining further corroborated cell viability. Antibacterial activity against Enterococcus faecalis was evaluated using the MTT assay and confocal laser scanning microscopy (CLSM). RESULTS: Augmentin at 0.1 mg/mL appeared to promote better cell growth and attachment within the scaffolds than all other formulations, exhibiting acceptable viability. SEM revealed improved cell attachment in augmentin and mTAP groups compared to the Ca(OH)2 group. Augmentin at 1 mg/mL and mTAP groups significantly reduced viable bacteria compared to controls. Augmentin groups and mTAP at 1 mg/mL were highly effective in eliminating E. faecalis biofilms, with mTAP potentially causing more cell death within the remaining biofilm structures. CONCLUSIONS: This study suggests that CH-G scaffolds loaded with augmentin and mTAP, particularly at a concentration of 1 mg/mL, offer promising advantages for REPs due to their biocompatibility, antibacterial efficacy, and ability to promote cell attachment. Further research may explore the long-term effects in clinical settings.

[EMERGINCaRE, the horizon scanning system for anticancer drugs of the French National Cancer Institute]. / EMERGINCaRE, le dispositif d'horizon scanning dédié aux médicaments anticancéreux développé par l'Institut national du cancer.

INTRODUCTION: In a context of intensive clinical development and innovation in oncology, the French National Cancer Institute has developed a horizon scanning focused on emerging anticancer drugs since 2019. This tool aims to provide further insight to national authorities responsible of the access to medicines and policymakers. METHODS: EMERGINCaRE is based on an annual cycle initiated by the identification of clinical developments of interest from a database, one to three years prior European marketing authorization. Clinical developments are ranked and prioritized using a scoring approach. Scores are based on public information about developments collected by the Institute and on the evaluation carried out by clinicians who were asked to analyse and identify the most impacting drugs. A national steering committee prioritizes several high-score developments each year. RESULTS: Seventy-five developments were analysed during the 2023 cycle. Among these developments, 50 are related to drugs for solid tumors and 25 for hematological malignancies. At the end of this cycle, six developments, including two concerning Advanced Therapy Medicinal Products, were prioritized. Half of these prioritized developments evaluate a drug for a poor prognosis cancer. DISCUSSION: Among the developments evaluated with a high clinical impact score, some drugs were finally approved for the clinical situation concerned. As first public Horizon Scanning in France, the methodology of EMERGINCaRE has been refined and deadlines have been optimized to provide annually the information generated by this system to interested public institutions.

Currently Available Treatment Modalities for Uterine Fibroids.

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. OBJECTIVES: In this review we present all currently available treatment modalities for uterine fibroids. METHODS: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. REVIEW: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient's age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. CONCLUSIONS: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient's desire for definitive treatment or fertility preservation.

The brown algae: Sargassum binderi sonder bears potential nephroprotective activity in in-vivo experimental model.

OBJECTIVES: This study aimed to investigate the protective activity of brown seaweed, the ethanolic and water extracts of Sargassum binderi (S. binderi) were examined. Anticancer drug, cisplatin is normally used for the treatment of solid tumors that cause acute kidney damage after assemblage in the renal tubules. MATERIAL AND METHODS: It was an acute nephrotoxicity study, animals were divided into several groups randomly, cisplatin (7mg/kg i.p.) and normal saline were used as positive and negative control respectively. The S. bindari ethanolic and water extract were given orally in a dose of 200mg/kg for 5days. Various biomarkers were assessed to observe the nephroprotective potential, while antioxidant activities were investigated using reduced glutathione, catalase and malondialdehyde as oxidative stress. GCMS was performed to validate the presence of important therapeutic moieties. RESULTS: The current result justified that pretreatment with S. binderi inhibited the elevation of antioxidant parameters and also showed protection against lipid peroxidation, induced by cisplatin challenge. The overall impact was the nephroprotection, which has been revealed from the results. GCMS evaluation of hexanes fraction revealed the presence of therapeutically important compounds including heptasiloxane, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, hexadecamethyl, cyclooctasiloxane, and hexadecamethyl. These compounds have been reported for their antioxidant, antibacterial, anticancer, and antifungal activities. CONCLUSION: S. binderi showed reno-protective effect by checking their well-known biochemical parameters probably due to the antioxidant activity as confirmed by the presence of compounds.

Effect of canal medicaments triple antibiotic paste, Bio-C Temp, and Nano-silver gel activated by visible blue light on canal dentin microhardness and extrusion bond strength of AH plus sealer: A SEM and EDX analysis.

AIM: Assessment of contemporary canal medicaments (Triple antibiotic paste (TAP), Bio-C Temp, and Nano silver gel activated by visible blue light on the dentin microhardness (MH) and push-out bond strength (PBS) of AH plus endodontic sealer. METHOD: Sixty extracted premolars were obtained and decontaminated. Canal cleaning and shaping were performed. The samples were randomly allocated into four groups based on the intracanal medicaments. Group 1= CH paste, Group 2= TAP, Group 3= Bio-C Temp, and Group 4= Nano-silver gel activated by visible blue light. MH assessment was performed using a Vickers Microhardness tester. Forty specimens, ten from each group underwent root canal obturation. PBS and failure mode evaluation were performed. ANOVA and Post Hoc Tukey test were utilized to conduct intra and inter-group comparisons. RESULTS: The maximum outcome of surface hardness was presented by Group-3 (Bio-C Temp®) specimens. However, minimum scores of MH were displayed by Group 1 (CH) treated teeth. The highest outcomes of EBS were exhibited by the cervical third of Group 3 (Bio-C Temp®) samples. The apical section of Group 4 Teeth with Nano Silver gel activated by visible blue light revealed the lowest scores of bond integrity. CONCLUSION: Bio-C Temp and TAP proved to be better intracanal medicament than other tested groups in terms of the push-out bond strength of the sealer. TAP displayed lower microhardness as compared to the Bio-C Temp.