Intranasal bilosomes in thermosensitive hydrogel: advancing desvenlafaxine succinate delivery for depression management.

Depression, the second biggest cause of disability worldwide, is widespread. Many antidepressant medications, including Desvenlafaxine Succinate (D.V.S.), function by elevating neurotransmitter levels at the synapse through the inhibition of reabsorption by neurons. However, the effectiveness of these treatments is often limited by their inability to reach the brain using conventional administration methods. Bilosome-stabilized nanovesicles containing bile salts have drawn much interest because of their adaptability and versatility in various applications. This study aimed to address this issue by formulating intranasal bilosomes incorporated into a mucoadhesive in situ gel to deliver D.V.S. directly to the brain for depression treatment. The desvenlafaxine-loaded bilosomes were developed using a thin film hydration method based on the l-optimal design. They were intended to provide a more convenient route of administration for antidepressants, enhancing bioavailability and brain targeting through intranasal delivery. The study assessed the optimized bilosomes for particle size (311.21 ± 0.42 nm), Zeta potential (-37.35 ± 0.43)and encapsulation efficiency (99.53 ± 0.41%) and further evaluated them in ex vivo and in vivo pharmacokinetics studies. Pharmacokinetic data reveal enhanced brain uptake compared to a free drug. A statistically optimized bilosome formulation was determined. The intranasal administration of mucoadhesive in situ gel containing desvenlafaxine succinate-loaded bilosomes facilitated direct nose-to-brain drug delivery, improving brain bioavailability.

Boron increases root elongation by reducing aluminum induced disorganized distribution of HG epitopes and alterations in subcellular cell wall structure of trifoliate orange roots.

Aluminum toxicity limits the plant growth by inducing inhibition of root elongation. Although several mechanisms have been proposed regarding the phytotoxic effects of aluminum on inhibition of root elongation; the primary causes of aluminum induced root inhibition and its mitigation by boron (B) are still elusive. The present study was carried out to explore the mechanisms of B induced mitigation of aluminum toxicity and to investigate the changes in well wall structure under aluminum toxicity coupled with the techniques of confocal laser microscope, lumogallion and transmission electron microscope. The results revealed that aluminum toxicity severely hampered the root elongation and plant biomass. Moreover, alteration in subcellular structure were observed under aluminum toxicity, however, such negative effects were further exacerbated with B deficiency. Aluminum toxicity indicated disorganized distribution of HG (homogalacturonan) epitopes with higher accumulation of apoplastic aluminum. Nevertheless, B supply improved root elongation, and reduced the aluminum uptake. Taken together, it is concluded that B application can reduce aluminum toxicity and improve root elongation by decreasing Al3+ accumulation to cell wall, alteration in the cell wall structure and reducing the distribution of HG epitopes in the roots of trifoliate (Poncirus trifoliate) orange.

Comparative Evaluation of Penetration of Various Nano-sized Intra-canal Medicaments: An In Vitro Confocal Laser Scanning Microscopic Study.

Background: To assess and contrast the depth of penetration of conventional calcium hydroxide, nanoparticle calcium hydroxide, silver nanoparticles, and combination of nanoparticle calcium hydroxide and silver nanoparticles into dentinal tubules using confocal laser scanning microscope. Materials and Methods: Eighty human single-rooted teeth were decoronated and instrumented up to Protaper Universal F3. Teeth were separated into four groups at random (n = 20) following chemomechanical preparation. Group 1: Control Conventional Calcium Hydroxide; Group 2: Nanoparticle Calcium Hydroxide; group 3: Silver Nanoparticles; group 4: Combination of Nanoparticle Calcium Hydroxide and Silver Nanoparticles. With the use of lentulo spirals, medications were injected into the canals, stirred up with ultrasound, and then kept at 37°C for 24 hours. A 1 mm thick slice was obtained at 5 mm from the root apex by sectioning the root perpendicular to the long axis of the tooth and then put on a glass slide to measure the depth of penetration using a confocal laser microscope. Statistical Analysis: To quantify the depth of penetration among the four groups, a one-way ANOVA was used and post hoc-Tukey's test was used to compare between groups. Results: All of the groups were statistically significant, with group 4 showing the greatest depth of penetration, followed by group 2 and group 3. In contrast, all other groups in the intergroup comparison were statistically significant (P value 0.05) aside from the comparison of group 2 to group 3. Conclusion: Silver nanoparticles and nanoparticle calcium hydroxide together demonstrated greater penetration than calcium hydroxide, silver nanoparticles, and nanoparticle calcium hydroxide alone.

Confocal Laser Scanner Evaluation of Bactericidal Effect of Chitosan Nanodroplets Loaded with Benzalkonium Chloride.

The aim was to evaluate the antibacterial efficacy and penetration depth into dentinal tubules of a solution of chitosan nanodroplets (NDs) loaded with Benzalkonium Chloride (BAK). Seventy-two human single-root teeth with fully formed apex were used. Cylindrical root dentin blocks were longitudinally sectioned and enlarged to a size of a Gates Glidden drill #4. After sterilization, root canals were infected with Enterococcus faecalis ATCC 29212 and further incubated for three weeks. Specimens were assigned to three experimental groups (n = 20), plus positive (n = 6) and negative (n = 6) controls. In the first group, irrigation was achieved with 2 mL of NDs solution loaded with BAK (NDs-BAK), in the second with 2 mL of 5% sodium hypochlorite (NaOCl) and in the last with 2 mL of 2% chlorhexidine (CHX). Specimens were rinsed and vertically fractured. Confocal laser scanning microscopy (CLSM) and viability staining were used to analyze the proportions of dead and live bacteria quantitatively. The volume ratio of red fluorescence (dead) was calculated in 3D reconstructions. Data were analyzed by one-way ANOVA and post hoc Bonferroni tests (p < 0.05). The ratio of red fluorescence over the whole green/red fluorescence resulted in a significant comparison of NDs-BAK with NaOCl (p < 0.01) and NaOCl with CHX (p < 0.01). No differences were found between NDs-BAK and CHX (p > 0.05). The mean depth of efficacy was, respectively: NDs-BAK 325.25 µm, NaOCl 273.36 µm and CHX 246.78 µm with no statistical differences between groups. The NaOCl solution showed the highest antimicrobial efficacy, but nanodroplets with BAK seemed to have the same effect as CHX with a high depth of efficacy.

Modeling of corona virus and its application in confocal microscopy.

Background: The proposal of spiky apertures showed resolution improvement compared with the circular apertures. Three models of corona virus are given. The 1st model consists of uniform circular aperture provided with 8 spikes while the 2nd model has 16 spikes for the same uniform circular aperture. The 3rd model has circular linear distribution with 8 spikes. Results: The Normalized Point Spread Function (PSF) or the impulse response is computed for the three models using fast Fourier transform technique. In addition, the autocorrelation function corresponding to these apertures is calculated and compared with that corresponding to the ordinary circular and conic apertures. Coronavirus image is used as an object in the formation of images using confocal scanning laser microscope provided with suggested models. The fabricated MATLAB code is used to compute and plot all images and line plots. Conclusions: The PSF plots are computed from Eqs. (8) and (12) using MATLAB code showing narrower cutoff in the PSF for spiky aperture compared with that corresponding to the uniform circular aperture and modulated linear and quadratic apertures. Hence, I reached resolution improvement in the case of spiky aperture.

Tailoring Terpesomes and Leciplex for the Effective Ocular Conveyance of Moxifloxacin Hydrochloride (Comparative Assessment): In-vitro, Ex-vivo, and In-vivo Evaluation.

AIM: To compare the ability of both terpesomes (TPs) and leciplex (LPs) loaded moxifloxacin hydrochloride (MOX) for enhancing ocular drug conveyance. METHODS: Two separate 21.31 full-factorial trials were established to determine the influence of multiple variables upon nanovesicles properties and select the optimized formulae using Design Expert® software. The thin-film hydration method was used to formulate TPs, while the single-step procedure was used for LPs. All formulae were characterized for their entrapment efficiency percent (EE%), particle size distribution (PS), polydispersity index (PDI), and zeta potential (ZP). Then, the optimized formulae were selected, evaluated, and compared for additional assessments. RESULTS: The optimized formulae TP4 and LP1 showed EE% of 84.14±0.21 and 78.47±0.17%, PS of 578.65±5.65 and 102.41±3.39 nm, PDI of 0.56±0.04 and 0.28±0.01, ZP of -12.50±0.30 and 32.50±0.50 mV, respectively. Further, LP1 showed enhanced corneal permeation across cow cornea compared to MOX solution and TP4. Besides, confocal laser scanning microscopy assessment viewed valuable infiltration from the fluoro-labeled LP through corneal layers compared to TP. LP1 showed spherical morphology and, its ability to adhere to mucus membranes was justified. Further, LP1 showed superiority over MOX solution in biofilm inhibition and eradication in addition to the treatment of infected mice with methicillin-resistant Staphylococcus aureus without any inflammatory response. Finally, the histopathological study verified the harmlessness and biocompatibility of the assembled LPs. CONCLUSION: The gained outcomes confirmed the capability of utilizing LPs as a successful nanovesicle for the ocular conveyance of MOX over TPs and MOX solution.

Microleakage Assessment of Two Different Pit and Fissure Sealants: A Comparative Confocal Laser Scanning Microscopy Study.

INTRODUCTION: Pit and fissures of permanent dentition are considered to be highly vulnerable to the adhesion of cariogenic microorganisms and consequently result in caries formation. The main problem associated with sealant failure will be microleakage. Therefore, sealants can be considered to be an effective preventive procedure for dental caries, only if it strongly bonds to the tooth, and protect the pit and fissures from the oral bacterial environment. AIM AND OBJECTIVE: To compare and assess the microleakage of two different pit and fissure sealants on permanent molars. MATERIALS AND METHODS: A total of 20 extracted third molars were randomly divided into two groups where group I is conventional sealant and group II is hydrophilic sealant. Occlusal surfaces of permanent molars were treated with 37% orthophosphoric acid before sealant placement. Tooth samples were subjected to 0.1% rhodamine dye immersion, thermocycling, and tooth samples were sectioned and evaluated under a confocal laser microscope for dye penetration. A non-parametric test (Mann-Whitney U) was performed to compare the mean microleakage score difference between the groups. RESULTS: Group II (hydrophilic sealant) showed a minimum level of the microleakage score when compared to group I (conventional sealant) and was found to be statistically significant using the Mann-Whitney U test with a p value <0.05. CONCLUSION: The less the microleakage, the better will be the retention of the sealant for a longer duration and cariostatic action. HOW TO CITE THIS ARTICLE: Prabakar J, Indiran MA, Kumar P, et al. Microleakage Assessment of Two Different Pit and Fissure Sealants: A Comparative Confocal Laser Scanning Microscopy Study. Int J Clin Pediatr Dent 2020;13(S-1):S29-S33.

Influence of sodium hypochlorite/etidronic acid combination and SmearOFF on push-out bond strength of fiber posts to root dentin.

The aim was to evaluate the effects of different irrigation protocols on the bonding ability of fiber posts on root canal dentin through push-out test and the dentin tubule penetration of luting cement by confocal laser scanning microscope (CLSM). Forty-eight single-rooted premolars were divided into six groups (n=8) based on post space irrigation protocols: Saline 0.85%; Etidronate 18% (HEBP); EDTA 17%; NaOCl 5.25%+EDTA 17%; NaOCl 2.5%/HEBP 9% combination; SmearOFF. Two specimens per group were assessed with CLSM. The push-out test and the failure analysis were performed. Whilst EDTA had the highest bond strength at the coronal and middle thirds, it was not statistically significant compared to saline, HEBP, and NaOCl/HEBP at the middle third (p>0.05). Cement/dentin adhesive failures were predominant (41.9%) and the intratubular fluorescence intensity was significant among the groups (p<0.05). EDTA resulted in highest bond strength values and dentinal penetration.

Estudio de la sensibilidad y especificidad diagnóstica del microscopio confocal de reflectancia (MCR) en lesiones tumorales de la piel / Diagnostic sensitivity and specificity of the Reflectance Confocal Laser Microscope (RCLM) in tumors of the skin

Introducción: El Microscopio Láser Confocal de Reflectancia (MCR) es una técnica no invasiva, con resolución cuasi histológica, que permite la visualización de células y estructuras de la piel. Esta tecnología es especialmente útil en el diagnóstico de lesiones tumorales. Material y métodos: Se trata de un estudio retrospectivo que busca medir la sensibilidad y especificidad del MCR en el diagnóstico de lesiones tumorales de la piel. Luego de obtener imágenes con el MCR de las lesiones, éstas se resecaron y se enviaron a estudio histopatológico, observando la correlación entre ambas técnicas. Resultados: Encontramos un 98 por ciento de concordancia entre el diagnóstico por MCR y el diagnóstico histopatológico para el total de tumores. El MCR mostró una sensibilidad y especificidad de 100 por ciento paramelanomas y sensibilidad de 93 por ciento y especificidad de 100 por ciento para carcinoma basocelular. En el caso de nevus atípico, la sensibilidad fue de 100 por ciento y la especificidad de 97 por ciento. Sólo dos lesiones que en la histopatología demostraron ser carcinomas basocelulares superficial y nodular fueron confundidas conqueratosis liquenoide y nevus atípico respectivamente. Discusión: Este estudio demostró una alta concordancia entre el MCR y la histopatología en tumores malignos. Sin duda que el MCR es y seguirá siendo un pilar fundamental en el diagnóstico de las lesiones tumorales de la piel, así como en la investigación y seguimiento in vivo de diversas lesiones de la piel.

Introduction: The Reflectance Confocal Laser Microscope (RCLM) is a new non-invasive technology, with quasi-histological resolution, which allows visualization of cells and skin structures and is particularly useful in the diagnosis of skin tumors. Material and methods: This is a retrospective study aimed to determine the diagnostic sensitivity and specificity of the RCLM in tumors of the skin using conventional histology as the gold standard for diagnosis. The images were obtained from patients with tumors of the skin using the RCLM, which were subsequently excised and sent to histopathological analysis. Results: We found a 98 percent concordance between the previous diagnosis by RCLM and pathology results. Diagnosis by confocal microscopy showed a sensitivity and specificity of 100 percent for melanomas, 93 percent sensitivity and 100 percent specificity for basal cell carcinoma and a sensitivity of 100 percent and specificity of 97 percent for atypical nevi. Only 2 lesions on histopathology proved to be superficial and nodular basal cell carcinomas were confused with lichenoid keratosis and atypical nevi, respectively. Discussion: We believe that RCLM is and will remain a really useful tool in the diagnosis of tumours of the skin as well as in research and in vivo monitoring of various types of skin lesion.