ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health concern, closely associated with the rising prevalence of type 2 diabetes mellitus (T2DM) and obesity. This systematic review and meta-analysis aim to comprehensively evaluate the prevalence of NAFLD in DM patients in Saudi Arabia, a country undergoing rapid socioeconomic changes. Our multifaceted search strategy identified four high-quality studies conducted between 2003 and 2022, covering hospital and community settings. The aggregate prevalence rate of NAFLD in DM patients was notably high, ranging from 47.8% to 72.8%. However, substantial heterogeneity (I² = 90.6%) was observed, indicating variability attributed to diverse study characteristics. The uniform application of ultrasound for diagnosis was noteworthy but raised concerns regarding sensitivity. This analysis underscores the urgency of public health measures for early detection and management of NAFLD in DM-prone populations in Saudi Arabia.
ABSTRACT
To improve the relationships between commonly conducted in vitro studies for locally-acting nasal spray drug products with in vivo regional deposition, this study developed a set of in vitro adult nasal geometries that captured the range of nasal drug delivery to the region posterior to internal nasal valve (INV), also known as posterior delivery (PD), and evaluated their performance with existing in vivo data. The PD of fluticasone propionate (FP) and fluticasone furoate (FF) in 40 nasal cavities was statistically analyzed to identify three airway models representing the low, mean, and high PD in adults. The models were also externally validated by comparing the in vitro nasal deposition from a different drug product (mometasone furoate (MF)) with the relevant in vivo data. The three selected geometries represented the low, mean, and high PD with multiple nasal sprays. They were verified in terms of reproducibility of in vitro data and validated by showing a reasonable agreement with preexisting in vivo MF PD despite differences in administration and defining the regions. The three models are envisioned to potentially facilitate the development of locally-acting nasal sprays and provide a better understanding of how in vitro metrics relate to in vivo regional nasal deposition.
Subject(s)
Nasal Sprays , Nose , Administration, Intranasal , Fluticasone , Mometasone Furoate , Reproducibility of ResultsABSTRACT
Nasal sprays, which produce relatively large pharmaceutical droplets and have high momentum, are primarily used to deliver locally acting drugs to the nasal mucosa. Depending on spray pump administration conditions and insertion angles, nasal sprays may interact with the nasal surface in ways that creates complex droplet-wall interactions followed by significant liquid motion after initial wall contact. Additionally, liquid motion can occur after deposition as the spray liquid moves in bulk along the nasal surface. It is difficult or impossible to capture these conditions with commonly used computational fluid dynamics (CFD) models of spray droplet transport that typically employ a deposit-on-touch boundary condition. Hence, an updated CFD framework with a new spray-wall interaction (SWI) model in tandem with a post-deposition liquid motion (PDLM) model was developed and applied to evaluate nasal spray delivery for Flonase and Flonase Sensimist products. For both nasal spray products, CFD revealed significant effects of the spray momentum on surface liquid motion, as well as motion of the surface film due to airflow generated shear stress and gravity. With Flonase, these factors substantially influenced the final resting place of the liquid. For Flonase Sensimist, anterior and posterior liquid movements were approximately balanced over time. As a result, comparisons with concurrent in vitro experimental results were substantially improved for Flonase compared with the traditional deposit-on-touch boundary condition. The new SWI-PDLM model highlights the dynamicenvironment that occurs when a nasal spray interacts with a nasal wall surface and can be used to better understand the delivery of current nasal spray products as well as to develop new nasal drug delivery strategies with improved regional targeting.
ABSTRACT
INTRODUCTION: One of the challenges that clinicians encounter in the dental office is treating occlusal discrepancies. Malocclusion has been classified into three main classes that were further classified by researchers into more detailed subclasses later on. Pseudo-class III malocclusion has been called apparent or positional class III malocclusion, and its treatment usually consists of different modalities depending on how early the case is treated. When early orthodontic intervention was not possible, the restorative treatment becomes an excellent alternative especially when the teeth require restorative rehabilitation. Treatment. In this case report, the patient was suffering from dental wear, multiple failed old restorations, and edge-to-edge occlusal relationship which could be classified as pseudo-class III malocclusion. The patient's esthetic complaint was addressed with full-coverage lithium disilicate and monolithic zirconia restorations that were successful in reestablishing the patient's occlusal relationship and were able to eliminate the biological manifestations of dental caries. CONCLUSION: We were able to provide an alternative to orthodontic treatment where esthetic and functional needs of the patient were met after careful diagnosis and proper management. This clinical approach will give chance to treat patients suffering from minor occlusal discrepancies that require restorative intervention without the need to go through orthodontic therapy.
ABSTRACT
Quantifying drug delivery to the site of action using locally-acting nasal suspension sprays is a challenging but important step toward understanding bioequivalence (BE) between test and reference products. The main objective of this study was to investigate the in vitro deposition pattern of two common but different locally-acting nasal suspension sprays using multiple nasal cavities. Twenty anatomically accurate nasal replicas were developed from high-resolution sinonasal computed tomography scans of adults with healthy nasal airways. The airways were segmented into two regions of anterior and posterior to the internal nasal valve. Both sides of the septum were considered separately; hence, 40 nasal cavities were studied. The positioning of the spray nozzle in all 40 cavities was characterized by the head angle, coronal angle, and the insertion depth. Despite using a controlled protocol to minimize the anterior losses, a wide range of variability in posterior drug delivery was observed. The observed intersubject variability using this in vitro method may have important implications for understanding BE of locally-acting nasal suspension sprays.
Subject(s)
Nasal Sprays , Nose , Administration, Intranasal , Adult , Aerosols , Humans , Nasal Cavity/diagnostic imaging , Research SubjectsABSTRACT
Every year, complications during pregnancy affect more than 26 million women. Some of those diseases are associated with significant morbidity and mortality, as is the case of preeclampsia, the main cause of maternal deaths globally. The ability to improve the delivery of drugs to the placenta upon administration to the mother may offer new opportunities in the treatment of diseases of pregnancy. The objective of this study was to develop megalin-targeting liposome nanocarriers for placental drug delivery. Megalin is a transmembrane protein involved in clathrin-mediated endocytic processes, and is expressed in the syncytiotrophoblast (SynT), an epithelial layer at maternal-fetal interface. Targeting megalin thus offers an opportunity for the liposomes to hitchhike into the SynT, thus enriching the concentration of any associated therapeutic cargo in the placental tissue. PEGylated (2 KDa) lipids were modified with gentamicin (GM), a substrate to megalin receptors as we have shown in earlier studies, and used to prepare placental-targeting liposomes. The ability of the targeting liposomes to enhance accumulation of a fluorescence probe was assessed in an in vivo placental model - timed-pregnant Balb/c mice at gestational day (GD) 18.5. The targeting liposomes containing 10 mol% GM-modified lipids increased the accumulation of the conjugated fluorescence probe in the placenta with a total accumulation of 2.8% of the initial dose, which corresponds to a 94 fold increase in accumulation compared to the free probe (p < .0001), and 2-4 fold accumulation compared to the non-targeting control liposomes (p < .0001), as measured by both tissue extraction assay and ex vivo imaging. Furthermore, confocal images of placental SynT cross-sections show a 3-fold increase of the targeting liposomes compared with the non-targeting liposomes. The rate and extent of uptake of a fluorescent probe encapsulated within targeting liposomes was also probed in an in vitro model of the human placental barrier (polarized BeWo monolayers) using flow cytometry. Targeting liposomes containing 5 mol% GM-modified lipids enhanced the uptake of the probe by 1.5 fold compared to the non-targeting control. An increase to 10 mol% of the modified lipid resulted in further enhancement in uptake, which was 2 fold greater compared to control. In a competition assay, inhibition of the megalin receptors resulted in a significant reduction in uptake of the fluorescence probe encapsulated in GM-modified liposomes compared to the uptake without free inhibitor (p < .0001), implicating the involvement of megalin receptor in the internalization of the liposomes. Taken together, these results demonstrate that megalin-targeted liposomes may offer an opportunity to enhance the delivery of therapeutics to the placenta for the treatment of diseases of pregnancy.
Subject(s)
Liposomes , Low Density Lipoprotein Receptor-Related Protein-2 , Animals , Drug Delivery Systems , Female , Gentamicins , Placenta , PregnancyABSTRACT
This paper describes the synthesis of two amino acid-based monomer and their graft copolymerization onto starch and utilization of the prepared graft copolymers as drug carriers. The two monomers were synthesized and reacted with acryloyl chloride to get the corresponding acryloylamino acid, which were further grafted onto starch using the microwave-assisted grafting technique. All factors affecting the efficiency of the grafting reaction were studied and the prepared graft copolymers were fully characterized. Atenolol, as a model drug in the form of salt was immobilized onto the graft copolymers by ionic bonds and the loading was confirmed by use of FT-IR, TGA and NMR. The drug release was studied in both acidic and alkaline media and it was found that the release takes place in alkaline medium rather than in acidic medium and this indicates that these polymers can be used as carriers for drugs whose target is the colon.
Subject(s)
Alanine/analogs & derivatives , Biopolymers/chemistry , Microwaves , Phenylalanine/analogs & derivatives , Starch/chemistry , Alanine/chemical synthesis , Alanine/chemistry , Atenolol/administration & dosage , Delayed-Action Preparations , Drug Carriers , Drug Stability , Hot Temperature , Hydrogen-Ion Concentration , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phenylalanine/chemical synthesis , Phenylalanine/chemistry , Polymerization , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , ThermogravimetryABSTRACT
ß-Cyclodextrin was grafted onto cotton fabric through crosslinking with butane tetracarboxylic acid in presence of sodium hypophosphite monohydrate as a catalyst. This finished cotton fabric was loaded with the antimicrobial agent octenidine dihydrochloride. ß-Cyclodextrin-grafted cotton fabrics, both after loading with octenidine dihydrochloride or before loading (control) were characterized for their antimicrobial activity against two types of bacteria (Gram positive and Gram negative) and two types of fungi, using the Diffusion Disk Method. The antimicrobial cotton fabric was subjected to several washing cycles and the antimicrobial activity was measured after each washing cycle to examine the durability of this antimicrobial finishing against repeated washing. The measurements showed that the finished cotton fabrics retain reasonable deal of their antimicrobial activity, even after 20 washing cycles. This long-lasting antimicrobial activity is attributed to the hosting ability of the cavities present in cyclodextrin moieties, which host the antimicrobial agent molecules and release them gradually.