Epidemiology of Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease in Taiwan.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic condition characterized by progressive, partially reversible airflow obstruction. Osteoporosis represents a significant comorbidity in individuals with COPD. However, the incidence and prevalence of osteoporosis among the COPD population remain unclear in Taiwan. Therefore, our objective is to investigate the incidence and prevalence of osteoporosis in patients with COPD. METHODS: In this cross-sectional study, we enrolled a COPD population retrieved from the Taiwan National Health Insurance Research Database (NHIRD) spanning the years 2003 to 2016. Osteoporosis patients were identified using diagnosis codes. The study included newly diagnosed COPD patients from 2003 to 2016. The case group comprised patients who developed osteoporosis or osteoporotic fractures after their COPD diagnosis. We calculated the prevalence and incidence of osteoporosis in individuals with COPD and conducted trend tests. RESULTS: A total of 1,297,579 COPD patients were identified during the period from 2003 to 2016, with 275,233 of them in the osteoporosis group. The average prevalence of osteoporosis among individuals with COPD was 21.21% from 2003 to 2016 in Taiwan. The number of osteoporosis cases increased from 6,727 in 2003 to 24,184 in 2016. The prevalence of osteoporosis among COPD patients increased from 3.62% in 2003 to 18.72% in 2016. The number of osteoporosis cases among individuals with COPD continued to rise over the years, reaching its highest point in 2016 with 24,184 new cases. The incidence of osteoporosis fluctuated during the study period but generally remained around 3,000 cases per 100,000 person-years. Notably, there was a significant upward trend in incidence from 2003 to 2006, after which the trend stabilized and remained relatively constant. CONCLUSIONS: Our study highlights an increase in both the prevalence and incidence of osteoporosis in individuals with COPD. Given the significant medical, economic, and social implications associated with osteoporosis, a comprehensive and robust assessment of its healthcare burden can offer valuable insights for healthcare system planning and policymaking.

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride.

BACKGROUND: Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects. AIM: This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers. OBJECTIVE: The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality. METHODS: Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels. RESULTS: FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone. CONCLUSION: The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

Metformin induces autophagy of cisplatin-resistant human gastric cancer cells in addition to apoptosis.

Metformin has been used to treat cases of type 2 diabetes mellitus, and mounting studies have shown that metformin can act alone or in synergy with other anticancer agents to achieve anti-cancer efficacies on various types of tumors. However, the role of metformin in either inducing autophagy and cisplatin-resistance of human gastric cancer (GC) cells has never been examined. The study has established a cisplatin-resistant GC cell line and investigated the effects of metformin on inducing autophagy on it. The results demonstrated that treatment with metformin can concentration-dependently suppress the cell viability and cell confluence of cisplatin-resistant GC cells, while having no effects on human primary stomach epithelial cells (HPSEC). For the first time, we found that metformin can significantly increase the acidic vesicular organelles (AVO) level and decrease the acridine orange (AO) level spontaneously in the cisplatin-resistant GC cells. Thus, we further checked the other markers, Atg5, Atg12 and LC3-II, which showed that metformin indeed induced autophagy in the cisplatin-resistant GC cells. In addition, treatment of 3-Methyladenine (3-MA) can significantly rescue the metformin-induced autophagy. At the same time, metformin can induce the alterations of apoptosis-associated signal molecules, such as caspase-3 and caspase-7 activities. Overall, the pilot study provided evidence for metformin induced autophagy in addition to apoptosis, making it as an effective anticancer drug for the therapy of cisplatin-resistant GC. Killing the cisplatin-resistant GC cells with non-toxic metformin via both autophagy and apoptosis might extend its usefulness in our fighting with chemo-resistance of gastric cancer cells.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker N',N'-methylene bisacrylamide. The prepared nanogels were subjected to sol-gel fraction, polymer volume fraction, swelling, drug loading, and drug release studies. A high gel fraction was seen with the increasing feed ratio of polymer, monomer, and crosslinker. Greater swelling and drug release were observed at pH 4.6 and 7.4 as compared to pH 1.2 due to the deprotonation and protonation of functional groups of alginate and 2-acrylamido-2-methylpropanesulfonic acid. An increase was observed in swelling, loading, and release of the drug with the incorporation of a high feed ratio of polymer and monomer, while a reduction was seen with the increase in crosslinker feed ratio. Similarly, an HET-CAM test was used to evaluate the safety of the prepared nanogels, which showed that the prepared nanogels have no toxic effect on the chorioallantoic membrane of fertilized chicken eggs. Similarly, different characterizations techniques such as FTIR, DSC, SEM, and particle size analysis were carried out to determine the development, thermal stability, surface morphology, and particle size of the synthesized nanogels, respectively. Thus, we can conclude that the prepared nanogels can be used as a suitable agent for the sustained release of caffeine.

Designing and In Vitro Characterization of pH-Sensitive Aspartic Acid-Graft-Poly(Acrylic Acid) Hydrogels as Controlled Drug Carriers.

Acetaminophen is an odorless and white crystalline powder drug, used in the management of fever, pain, and headache. The half-life of acetaminophen is very short; thus, multiple intakes of acetaminophen are needed in a day to maintain a constant pharmacological action for an extended period of time. Certain severe adverse effects are produced due to the frequent intake of acetaminophen, especially hepatotoxicity and skin rashes. Therefore, a drug carrier system is needed which not only prolongs the release of acetaminophen, but also enhances the patient compliance. Therefore, the authors prepared novel aspartic acid-graft-poly(acrylic acid) hydrogels for the controlled release of acetaminophen. The novelty of the prepared hydrogels is based on the incorporation of pH-sensitive monomer acrylic acid with polymer aspartic acid in the presence of ethylene glycol dimethacrylate. Due to the pH-sensitive nature, the release of acetaminophen was prolonged for an extended period of time by the developed hydrogels. Hence, a series of studies was carried out for the formulated hydrogels including sol-gel fraction, FTIR, dynamic swelling, polymer volume analysis, thermal analysis, percent porosity, SEM, in vitro drug release studies, and PXRD analysis. FTIR analysis confirmed the grafting of acrylic acid onto the backbone of aspartic acid and revealed the development of hydrogels. The thermal studies revealed the high thermal stability of the fabricated hydrogels as compared to pure aspartic acid. An irregular surface with a few pores was indicated by SEM. PXRD revealed the amorphous state of the developed hydrogels and confirmed the reduction in the crystallinity of the unreacted aspartic acid by the formulated hydrogels. An increase in gel fraction was observed with the increasing concentration of aspartic acid, acrylic acid, and ethylene glycol dimethacrylate due to the availability of a high amount of free radicals. The porosity study was influenced by the various compositions of developed hydrogels. Porosity was increased due to the enhancement in the concentrations of aspartic acid and acrylic acid, whereas it decreased with the increase in ethylene glycol dimethacrylate concentration. Similarly, the pH-responsive properties of hydrogels were evaluated by dynamic swelling and in vitro drug release studies at two different pH levels (1.2 and 7.4), and a greater dynamic swelling and acetaminophen release were exhibited at pH 7.4 as compared to pH 1.2. An increase in swelling, drug loading, and drug release was seen with the increased incorporation of aspartic acid and acrylic acid, whereas a decrease was detected with the increase in the concentration of ethylene glycol dimethacrylate. Conclusively, the formulated aspartic acid-based hydrogels could be employed as a suitable nonactive pharmaceutical ingredient for the controlled delivery of acetaminophen.

Enhancement of the Topical Bioavailability and Skin Whitening Effect of Genistein by Using Microemulsions as Drug Delivery Carriers.

Genistein, the most abundant isoflavone of the soy-derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase, which can inhibit UVB-induced skin carcinogenesis in hairless mice and UVB-induced erythema on human skin. In current study, genistein-loaded microemulsions were developed by using the various compositions of oil, surfactants, and co-surfactants and used as a drug delivery carrier to improve the solubility, peremability, skin whitening, and bioavailbility of genistein. The mean droplet size and polydispersity index of all formulations was less than 100 nm and 0.26 and demonstrated the formation of microemulsions. Similarly, various studies, such as permeation, drug skin deposition, pharmacokinetics, skin whitening test, skin irritation, and stability, were also conducted. The permeability of genistein was significantly affected by the composition of microemulsion formulation, particular surfactnat, and cosurfactant. In-vitro permeation study revealed that both permeation rate and deposition amount in skin were significantly increased from 0.27 µg/cm2·h up to 20.00 µg/cm2·h and 4.90 up to 53.52 µg/cm2, respectively. In in-vivo whitening test, the change in luminosity index (ΔL*), tended to decrease after topical application of genistein-loaded microemulsion. The bioavailability was increased 10-fold by topical administration of drug-loaded microemulsion. Conclusively, the prepared microemulsion has been enhanced the bioavailability of genistein and could be used for clinical purposes.

Improved skin permeability and whitening effect of catechin-loaded transfersomes through topical delivery.

The aim of the study was to prepare catechin-loaded transfersomes to enhance drug permeability through topical administration for the skin protection against ultraviolet radiation induced photo-damage. The results showed that the catechin-loaded transfersomes were monodispersed with polydispersity index (PDI) < 0.2, <200 nm in particle size and with high encapsulation efficiency (E.E.%) greater than 85%. The in vitro skin permeation test indicated that the catechin-loaded transfersomes enhanced the skin permeability by 85% compared to the catechin aqueous solution. Similarly, the in-vivo skin whitening study demonstrated that F5 transfersome formulation was effective in tyrosinase inhibition and had good biocompatibility to the guinea pig skin. Finally, the stability study showed that both physicochemical properties and E.E.% of the F5 transferosome formulation were fairly stable after 3 months storage. Therefore, topical administration of catechin-loaded transfersomes could be considered as a potential strategy for the treatment of UV-induced oxidative damage to the skin.

Fabrication and In Vitro Evaluation of pH-Sensitive Polymeric Hydrogels as Controlled Release Carriers.

The purpose of the current investigation was to develop chondroitin sulfate/carbopol-co-poly(acrylic acid) (CS/CBP-co-PAA) hydrogels for controlled delivery of diclofenac sodium (DS). Different concentrations of polymers chondroitin sulfate (CS), carbopol 934 (CBP), and monomer acrylic acid (AA) were cross-linked by ethylene glycol dimethylacrylate (EGDMA) in the presence of ammonium peroxodisulfate (APS) (initiator). The fabricated hydrogels were characterized for further experiments. Characterizations such as Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR) were conducted to understand the surface morphology, thermodynamic stability, crystallinity of the drug, ingredients, and developed hydrogels. The swelling and drug release studies were conducted at two different pH mediums (pH 1.2 and 7.4), and pH-dependent swelling and drug release was shown due to the presence of functional groups of both polymers and monomers; hence, greater swelling and drug release was observed at the higher pH (pH 7.4). The percent drug release of the developed system and commercially available product cataflam was compared and high controlled release of the drug from the developed system was observed at both low and high pH. The mechanism of drug release from the hydrogels followed Korsmeyer-Peppas model. Conclusively, the current research work demonstrated that the prepared hydrogel could be considered as a suitable candidate for controlled delivery of diclofenac sodium.

Preparation and Evaluation of Azelaic Acid Topical Microemulsion Formulation: In Vitro and In Vivo Study.

The aim of this study was to design oil in water (O/W) microemulsion formulations for the topical administration of azelaic acid. The permeability of azelaic acid through rat skin and the anti-inflammatory activities of the formulations were conducted to examine the efficacy of the designed formulations. Skin irritation and stability tests were also performed. The permeability of azelaic acid was significantly increased by using O/W microemulsions as carriers. The edema index of ear swelling percentage was significantly recovered by the 5% drug-loaded formulation and a 20% commercial product, demonstrating that the experimental formulation possessed comparable effect with the commercial product on the improvement of inflammation. The experimental formulation did not cause significant skin irritation compared to the negative control group. Moreover, the drug-loaded formulation also showed thermodynamic stability and chemical stability after storage for 30 days. In conclusion, the O/W microemulsion was a potential drug delivery carrier for azelaic acid topical application.

Preparation, Characterization, Swelling Potential, and In-Vitro Evaluation of Sodium Poly(Styrene Sulfonate)-Based Hydrogels for Controlled Delivery of Ketorolac Tromethamine.

The objective of the current study work was to fabricate sodium poly(styrene sulfonate-co-poly acrylic acid) (SPSPAA) hydrogels by using a free radical co-polymerization method for controlled delivery of ketorolac tromethamine (KT). Polymer (sodium poly(styrene sulfonate) (SPS) polymerized with monomer acrylic acid (AA) in the presence of initiator ammonium peroxodisulfate (APS) and cross-linker N',N'-Methylene bisacrylamide (MBA). Different combinations of polymer, cross-linker and monomer, were employed for development of polymeric hydrogels. Various studies such as sol-gel, drug loading, dynamic swelling, and drug release studies were carried out to know the sol and gel portion of SPSPAA, swelling behavior of hydrogels at different pH media (1.2 and 7.4), quantification of drug loaded by fabricated hydrogels, and amount release of KT at pH 1.2 and 7.4. Higher dynamic swelling was found at pH 7.4 compared to pH 1.2, and as a result, greater percent release of drug was perceived at pH 7.4. Thermal stability, crystallinity, confirmation of functional groups and development of a new polymeric system, and surface morphology were evaluated via Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) respectively. The results showed that the present work could be used as a potential candidate for controlled delivery of KT.

Prescribing patterns of coronary artery aneurysm in Taiwan.

BACKGROUND: Coronary artery aneurysm (CAA) is a rare disease, and there are limited data on prescribing patterns for CAA. The aim of our study was to investigate prescribing patterns for CAA in Taiwan via the National Health Insurance Research Database (NHIRD). METHODS: We included all CAA patients in Taiwan from 2005 to 2011. Data from 1 year before and after the CAA diagnosis were used to analyze examinations, comorbidities and prescribing patterns. RESULTS: A total of 1397 patients diagnosed with CAA were enrolled in our study. Most pediatric patients with CAA were diagnosed with Kawasaki disease (95.7%). In pediatric CAA patients, the utilization rates of aspirin and gamma globulins were 82.9 and 53.6%, respectively, after CAA diagnosis. Among the antithrombotic agents, aspirin was used most commonly, followed by dipyridamole (16.9%), heparin (5.8%) and warfarin (4.6%). In adult CAA patients, common comorbidities included hypertension (63.4%), hyperlipidemia (39.6%), and diabetes mellitus (26.1%). Coronary atherosclerosis was identified in 72.5% of adult patients after CAA diagnosis. Antithrombotic agents, particularly aspirin, clopidogrel and heparin, were prescribed more frequently after CAA diagnosis. Among the prescribed medications, aspirin (75.8%), ß-blockers (48.3%), statins (47.6%), metformin (14.4%), sulfonylureas (14.4%) and isosorbide mononitrate (32.9%) were frequently observed in each category. CONCLUSIONS: Kawasaki disease was the main cause of CAA in pediatric patients, and coronary artery disease was the most common comorbidity in adult CAA patients. The most commonly used antithrombic agent after CAA diagnosis was aspirin in both adult and pediatric patients.