Health information-seeking behavior in patients with coronary artery disease: Activating methods.

INTRODUCTION: Coronary artery disease (CAD) has a high mortality rate worldwide, and continuous health behavior practice and careful management are required owing to risks such as rapid changes in symptoms and emergency hospitalization. The utilization of health-related information is an important factor for long-term disease management in patients with CAD. For this purpose, an understanding of health information-seeking behavior is needed first. METHODS: This study analyzed data from the 2021 Korea Medical Panel Survey, and logistic regression analysis was conducted to confirm the factors influencing the health information-seeking behavior of patients with CAD. RESULTS: The health information-seeking behavior of patients with CAD differed according to demographic characteristics, and differences in preferred information use were confirmed. Finally, it was identified that insufficient levels of health literacy were a major reason for CAD patients not engaging in health information-seeking behaviors (OR, 0.17; 95% CI, 0.09-0.33; p < 0.001). CONCLUSION: This study suggests that to improve health information-seeking behaviors, the application of education and intervention programs to increase the level of health literacy is necessary.

A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan.

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl2, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables-DMPC (X1, 70.58 mol%), cholesterol (X2, 22.54 mol%), and DCP (X3, 6.88 mol%)-and three response variables: encapsulation efficiency (Y1, 76.92%), released amount of free fatty acid at 2 h (Y2, 39.82%), and released amount of RVP at 6 h (Y3, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells.

Krukovine (KV) is an alkaloid isolated from the bark of Abuta grandifolia (Mart.) Sandw. (Menispermaceae) with anticancer potential in some cancers with KRAS mutations. In this study, we explored the anticancer efficacy and mechanism of KV in oxaliplatin-resistant pancreatic cancer cells and patient-derived pancreatic cancer organoids (PDPCOs) with KRAS mutation. After treatment with KV, mRNA and protein levels were determined by RNA-seq and Western blotting, respectively. Cell proliferation, migration, and invasion were measured by MTT, scratch wound healing assay, and transwell analysis, respectively. Patient-derived pancreatic cancer organoids (PDPCOs) with KRAS mutations were treated with KV, oxaliplatin (OXA), and a combination of KV and OXA. KV suppresses tumor progression via the downregulation of the Erk-RPS6K-TMEM139 and PI3K-Akt-mTOR pathways in oxaliplatin-resistant AsPC-1 cells. Furthermore, KV showed an antiproliferative effect in PDPCOs, and the combination of OXA and KV inhibited PDPCO growth more effectively than either drug alone.

Enhanced oral absorption of insulin: hydrophobic ion pairing and a self-microemulsifying drug delivery system using a D-optimal mixture design.

The lipophilicity of a peptide drug can be considerably increased by hydrophobic ion pairing with amphiphilic counterions for successful incorporation into lipid-based formulations. Herein, to enhance the oral absorption of insulin (INS), a self-microemulsifying drug delivery system (SMEDDS) formulation was developed. Prior to optimization, INS was complexed with sodium n-octadecyl sulfate (SOS) to increase the loading into the SMEDDS. The INS-SOS complex was characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and its dissociation behavior. The SMEDDS was optimized using a D-optimal mixture design with three independent variables including Capmul MCM (X1, 9.31%), Labrasol (X2, 49.77%), and Tetraglycol (X3, 40.92%) and three response variables including droplet size (Y1, 115.2 nm), INS stability (Y2, 46.75%), and INS leakage (Y3, 17.67%). The desirability function was 0.766, indicating excellent agreement between the predicted and experimental values. The stability of INS-SOS against gastrointestinal enzymes was noticeably improved in the SMEDDS, and the majority of INS remained in oil droplets during release. Following oral administration in diabetic rats, the optimized SMEDDS resulted in pharmacological availabilities of 3.23% (50 IU/kg) and 2.13% (100 IU/kg). Thus, the optimized SMEDDS is a good candidate for the practical development of oral delivery of peptide drugs such as INS.

Enhanced dissolution and bioavailability of revaprazan using self-nanoemulsifying drug delivery system.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the dissolution and oral bioavailability (BA) of revaprazan (RVP). Various SNEDDSs containing 200 mg of RVP were formulated using Capmul MCM, Tween 80, and Brij L4, and they were characterized according to their size, polydispersity index, and dissolution behavior. Dissolution rates of all SNEDDS formulations significantly (p < 0.05) improved with the formation of nanoemulsion with monodispersity. Formulation D resulted in RVP dissolution exceeding 70% at 2 h. Compared to raw RVP, SNEDDS exhibited a 4.8- to 7.4-fold improved effective permeability coefficient (Peff) throughout the intestine in the in situ single pass intestinal permeability study and a 5.1-fold increased oral BA in the in vivo oral absorption assessment in rats. To evaluate the degree of lymphatic uptake, cycloheximide (CYC), a chylomicron flowing blocker, was pretreated prior to the experiment. This pretreatment barely affected the absorption of raw RVP; however, it greatly influenced the absorption of SNEDDS, resulting in an approximately 40% reduction in both the Peff value and oral BA representing lymphatic transport. Thus, we suggest that the SNEDDS formulation is a good candidate for improving oral absorption of RVP through enhanced lymphatic uptake.

Optimization of a floating poloxamer 407-based hydrogel using the Box-Behnken design: in vitro characterization and in vivo buoyancy evaluation for intravesical instillation.

Intravesical instillation of a poloxamer 407 (PLX)-based hydrogel offers advantages such as thermo-sensitivity and sol-to-gel transition, but its utility is limited by urinary obstruction and insufficient bladder residence time. To overcome these obstacles, a floating PLX-hydrogel (FPH) was developed using sodium bicarbonate (BC) as a floating agent and hyaluronic acid (HA) as a gel strength modulator. The FPH composition was optimized using the Box-Behnken design with three independent variables: X1 [PLX concentration, 23.91%], X2 [BC concentration, 5.15%], and X3 [HA concentration, 3.49%]. The quadratic model was the best fit (desirability function, 0.623), resulting in response parameters of Y1 [floating time, 53.7 s], Y2 [gelation temperature gap, 20.3°C], and Y3 [duration time of gel, 396.7 min]. Rheological observations revealed the mechanical rigidity (storage modulus > loss modulus at elevated temperature) of the optimized FPH (phase transition temperature, 15.08°C). Gel erosion and drug release studies were performed using the gravimetric method; the remaining FPH fraction decreased exponentially with time, and gemcitabine release was biphasic and surface erosion-controlled. In vivo buoyancy was evaluated in rats using ultrasonography; these results were similar to those of the in vitro floating behavior. Thus, optimized FPH for intravesical instillation is a prospective option for bladder cancer treatment.

Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design.

PURPOSE: To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed. METHODS: Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X1) and the amounts of Florite PS-10 (FLO; X2) and Vivapur 105 (VP105; X3), and three response variables, ie, dissolution efficiency at 30 min (Y1), dissolution enhancing capacity (Y2), and Carr's index (Y3). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex®, solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study. RESULTS: G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2-333.0 µg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X1 (-0.41), X2 (0.31), and X3 (-0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y1 (40.3%), Y2 (0.008), and Y3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex®, and solid micelle, respectively. CONCLUSION: The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.

Surgical Outcomes of Subtotal Parathyroidectomy for Renal Hyperparathyroidism.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of subtotal parathyroidectomy for patients with renal hyperparathyroidism. METHODS: We studied 25 patients with renal hyperparathyroidism who underwent subtotal parathyroidectomy from October 2002 to October 2017. We analyzed serum intact parathyroid hormone (iPTH), calcium, and inorganic phosphorus levels before and at multiple time points following surgery, and evaluated the surgical outcomes and complications. RESULTS: Of the 25 patients, 13 (52%) were male and 12 (48%) were female, and the mean age was 53.4±9.3 years. The mean duration of dialysis before parathyroidectomy was 156.8±79.5 months. Mean preoperative serum iPTH and calcium levels were 1,199.0±571.3 pg/mL and 10.5±1.0 mg/dL, respectively. At 6 months postoperatively, the mean iPTH and calcium levels decreased to 49.2±47.6 pg/mL (P<0.01) and 8.0±1.0 mg/dL (P<0.01), respectively. Recurrent hyperparathyroidism occurred in two patients: one subsequently underwent kidney transplantation and the other continued hemodialysis and maintained normal calcium levels. One patient developed postoperative permanent hypoparathyroidism. CONCLUSION: Subtotal parathyroidectomy is a safe and effective surgical treatment for renal hyperparathyroidism.

Quantitative analysis of nasal transcripts reveals potential biomarkers for Parkinson's disease.

Patients with Parkinson's disease (PD) oftentimes develop olfactory dysfunction in their early stages, converting the nasal environment into a useful source of potential biomarkers. Here we determined the possible application of nasal fluid cells for PD biomarker identification. Thirty PD patients and 13 age-matched healthy controls were enrolled in this study. Messenger RNA levels of selected PD-related genes were monitored through real-time quantitative PCR. Target gene transcripts can be efficiently amplified from the cDNA library from human nasal fluid cell pellets. And subsequent analysis showed both a marked downregulation of parkin transcripts and an upregulation of AIMP2 in PD patients when compared to controls (cutoff value = 1.753 for with 84.2% sensitivity and 84.6% specificity; 0.359 for parkin with 76.7% sensitivity and 76.9 specificity). Moreover, alteration pattern of parkin and AIMP2 in PD was distinct from another neurodegenerative disease, multiple system atrophy. Analysis in both the early and late stages of PD cases reported that parkin levels inversely correlated with PD stages. Our results validate the practical value of easily accessible nasal fluid cells and the utility of both AIMP2 and parkin as potential biomarkers for PD diagnosis.