Development of Polyvinyl Alcohol (PVA) Nanofibers Containing Cationic Lipid/siRNA Complexes via Electrospinning: The Impact of PVA Characterization.

This study aimed to develop polyvinyl alcohol (PVA) nanofibers encapsulating 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/siRNA complexes via electrospinning for the delivery of nucleic acid-based drugs. It also focused on the influence of the intrinsic properties of PVA on the efficacy of the system. PVA nanofibers, with diameters of 300-400 nm, were obtained, within which the siRNA remained intact and the DOTAP/siRNA complexes were uniformly dispersed. By incorporating DOTAP/siRNA complexes into the PVA nanofibers and assessing the impact of their RNA interference (RNAi) activity in A549-Luc cells, a stable inhibition of luciferase expression was observed. An examination of the nanofiber preparation process revealed that even when DOTAP or siRNA were added separately to the PVA solution without forming complexes, the RNAi effect was retained. The DOTAP/siRNA complexes released from the PVA nanofibers were internalized by the cells, with some PVA residues remaining on their surfaces. The significance of the degree of hydrolysis and polymerization of PVA on the performance of nanofibers was highlighted. Notably, PVA with a low degree of hydrolysis substantially enhanced RNAi effects, with luciferase expression inhibition reaching 91.5 ± 0.7%. Nanofibers made of PVA grades with anionic or cationic modifications were also evaluated, suggesting that they affect the efficacy of siRNA delivery. The insights obtained suggest avenues for future research to optimize drug delivery systems further.

Controlled Release of Lysozyme Using Polyvinyl Alcohol-Based Polymeric Nanofibers Generated by Electrospinning.

Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics. LZM-loaded PVA monolithic nanofibers having 50% drug content exhibit efficient entrapment, wherein rapid dissolution is achieved within 30 min. The initial burst of LZM from the nanofiber was reduced as the LZM content was lowered. The initial dissolution is greatly influenced by the choice of PVA grade used; fully hydrolyzed PVA nanofibers demonstrate controlled release due to the reduced water solubility of PVA. Furthermore, coaxial electrospinning, which creates core-shell nanofibers with polycaprolactone as a controlled release layer, enables sustained LZM release over an extended period. This study confirms a correlation between PVA characteristics and controlled drug release and provides valuable insights into tailoring nanofiber properties for pharmaceutical applications.

Comparison of intravenous sedation using midazolam versus dexmedetomidine in elderly patients with dementia: a randomized cross-over trial.

Differences between the effects of intravenous sedation with midazolam (MID) and dexmedetomidine (DEX) on the cerebral function of elderly patients with severe dementia are unclear. This study aimed to compare the effects of intravenous sedation with MID or DEX on parameters such as brain waves and cerebral blood flow (CBF). This cross-over study analyzed 12 patients with severe dementia, with each patient receiving both drug treatments. Each drug was administered until a Modified Observer's Assessment of Alertness/Sedation (OAA/S) score of 2 was reached. Bispectral index (BIS) and normalized tissue hemoglobin index (nTHI), which reflects CBF using near-infrared spectroscopy, were measured. Mann-Whitney U, Wilcoxon signed-rank, and Friedman tests, and multiple regression analysis were performed. While a similar decline in BIS values was observed in both groups (P < 0.030), there was a significant decrease in nTHI up to 11% in the MID group (P = 0.005). In the DEX group, nTHI values did not differ from baseline. When an OAA/S score of 2 was just achieved, CBF in the MID group (- 5%) was significantly lower than in the DEX group (± 0%). In dementia patients, sedation with MID resulted in a decrease in CBF, while the CBF value was maintained during sedation with DEX.

A new device for fiducial registration of image-guided navigation system for liver RFA.

PURPOSE: Radiofrequency ablation for liver tumors (liver RFA) is widely performed under ultrasound guidance. However, discriminating between the tumor and the needle is often difficult because of cavitation caused by RFA-induced coagulation. An unclear ultrasound image can lead to complications and tumor residue. Therefore, image-guided navigation systems based on fiducial registration have been developed. Fiducial points are usually set on a patient's skin. But the use of internal fiducial points can improve the accuracy of navigation. In this study, a new device is introduced to use internal fiducial points using 2D US. METHODS: 3D Slicer as the navigation software, Polaris Vicra as the position sensor, and two target tumors in a 3D abdominal phantom as puncture targets were used. Also, a new device that makes it possible to obtain tracking coordinates in the body was invented. First, two-dimensional reslice images from the CT images using 3D Slicer were built. A virtual needle was displayed on the two-dimensional reslice image, reflecting the movement of the actual needle after fiducial registration. A phantom experiment using three sets of fiducial point configurations: one conventional case using only surface points, and two cases in which the center of the target tumor was selected as a fiducial point was performed. For each configuration, one surgeon punctured each target tumor ten times under guidance from the 3D Slicer display. Finally, a statistical analysis examining the puncture error was performed. RESULTS: The puncture error for each target tumor decreased significantly when the center of the target tumor was included as one of the fiducial points, compared with when only surface points were used. CONCLUSION: This study introduces a new device to use internal fiducial points and suggests that the accuracy of image-guided navigation systems for liver RFA can be improved by using the new device.

Long-term results and management of ureteral transitional cell carcinoma using the holmium: YAG laser via rigid-ureteroscopy.

The standard operative procedure for ureteral transitional cell carcinoma is nephrouterectomy with partial cystectomy at the affected ureteral orifice. However, nephron-sparing surgery and endoscopic surgery and management have become common practice for low-grade and low-stage cases. We investigated the follow-up results of patients who underwent endoscopic surgery using the holmium:YAG laser, and evaluated its treatment effect. The patients were 4 men and 3 women aged from 68 to 87 years (mean: 74.7 years). Two were imperative cases and 5 were elective cases. The tumor size ranged from 8 to 25 mm (mean: 15.4 mm). Hydronephrosis was not found in any case, and urinary cytology was negative in all cases. Biopsy revealed 5 cases of grade 1, and 2 of grade 2. A Versa Pulse Select 80 laser generator, a 365-microm slim line laser fiber, and a rigid ureteroscope with 8F-point diameter were used. A 6F double J catheter was placed postoperatively for 3 weeks. Pulse energy was set at 0.5-1.0 J (mean: 0.8 J) with a frequency of 10 Hz. The total amount of energy was 0.9-11.22 KJ (mean: 2.89 KJ) and the operation time including ureteral stent placement was 20-97 min (mean: 66 min). Neither urinary tract perforation nor ureteral stricture associated with laser irradiation was observed. The postoperative follow-up period ranged from 23-88 months (mean: 67.8 months). Patients underwent urinary cytological examination once a month, and cystoscopy, retrograde pyelography and urethroscopy once every 3 months for 2 years, then once every 6 months thereafter. One patient developed tumor recurrence 23 months after surgery and received another laser treatment, but no recurrence has been observed in the other 6 patients (85.7%). Transurethral endoscopic surgery and management using the holmium:YAG laser is safe and effective nephron-sparing surgery for ureteral transitional cell carcinoma, and good long-term treatment results can be expected even in elective cases if the indications are carefully selected.

Cyclooxygenase-2 expression in invasive transitional cell carcinoma of the urinary bladder.

Cyclooxygenase-2 (COX-2) activity is reported to increase apoptosis, inhibit angiogenesis and reduce metastasis. We analyzed COX-2 expression in patients with invasive bladder cancer to evaluate the feasibility of selective COX-2 inhibitor treatment targeting COX-2. Forty patients with pathologically diagnosed invasive transitional cell carcinoma of the urinary bladder (pT2-pT4) were evaluated. Immunohistochemical staining was used to evaluate COX-2 expression, and cases with staining of ≥10% of tumor cells were defined as positive. In 2 patients, 0% of the primary tumors stained for COX-2, while 1-5% was stained in 16 patients, 5-10% in 3 patients and ≥10% in 19 patients (19/40, 47.5%). In terms of grade, 2 patients with grade 2 (2/3, 66.6%) and 17 patients with grade 3 (17/37, 45.4%) were COX-2 positive. When categorized by stage, 11 patients with pT2 (11/22, 50.0%), 6 with pT3 (6/13, 46.1%) and 2 with pT4 (2/5, 40.0%) were positive. Lymph node metastasis was observed in 10 patients; 2 of them, with pN2, were COX-2 positive. Those with COX-2-positive metastatic lymph nodes had grade 3 primary tumors, which were also COX-2 positive. In addition, COX-2-negative metastatic lymph node patients also had negative primary tumors. The results of this study suggest that 47.5% of patients with invasive bladder cancer may benefit from treatment with selective COX-2 inhibitors targeting COX-2, and that treatment efficacy can be expected in patients with lymph node metastasis when their primary tumors are COX-2 positive.