Carboxymethyl cellulose-based rotigotine nanocrystals-loaded hydrogel for increased transdermal delivery with alleviated skin irritation.

Transdermal rotigotine (RTG) therapy is prescribed to manage Parkinson's disease (Neupro® patch). However, its use is suffered from application site reactions. Herein, drug nanocrystalline suspension (NS)-loaded hydrogel (NS-HG) employing polysaccharides simultaneously as suspending agent and hydrogel matrix was constructed for transdermal delivery, with alleviated skin irritation. RTG-loaded NS-HG was prepared using a bead-milling technique, employing sodium carboxylmethyl cellulose (Na.CMC) as nano-suspending agent (molecular weight 90,000 g/mol) and hydrogel matrix (700,000 g/mol), respectively. NS-HG was embodied as follows: drug loading: ≤100 mg/mL; shape: rectangular crystalline; crystal size: <286.7 nm; zeta potential: -61 mV; viscosity: <2.16 Pa·s; and dissolution rate: >90 % within 15 min. Nuclear magnetic resonance analysis revealed that the anionic polymers bind to RTG nanocrystals via charge interaction, affording uniform dispersion in the matrix. Rodent transdermal absorption of RTG from NS-HG was comparable to that from microemulsions, and proportional to drug loading. Moreover, NS-HG was skin-friendly; erythema and epidermal swelling were absent after repeated application. Further, NS-HG was chemically stable; >95 % of the drug was preserved up to 4 weeks under long term (25 °C/RH60%), accelerated (40 °C/RH75%), and stress (50 °C) storage conditions. Therefore, this novel cellulose derivative-based nanoformulation presents a promising approach for effective transdermal RTG delivery with improved tolerability.

Novel bioequivalent oral disintegrating tablet of aripiprazole prepared by direct compression technique with shortened disintegration time.

Herein, we aimed to formulate a novel oral disintegrating tablet (ODT) of aripiprazole (ARP) capable of rapid disintegration using a direct compression technique. Different ODTs were fabricated with directly compressible excipients, and their disintegration time, wettability (water absorption ratio and wetting time), and mechanical properties (hardness and friability) were evaluated. The optimized ODT comprised F-Melt® type C, Prosolv® SMCC HD90, and Na croscarmellose (10 mg of ARP in a 130 mg tablet). The ODT with 3.1-5.2 kp hardness exhibited rapid disintegration (14.1-17.2 sec), along with appropriate mechanical strength (friability < 0.24%). In a bioequivalent study in Korean healthy subjects (randomized, single-dose, two-period crossover design, n = 37), the novel ODT offered the equivalent pharmacokinetic profile to that of a conventional immediate release tablet (Otsuka, Abilify®, Japan), despite different disintegration and dissolution profiles. The 90% confidence intervals of the geometric mean test to reference ratios considering the area-under-the-curve and maximum plasma drug concentrations were 1.0306-11051 and 0.9448-1.1063, respectively, satisfying FDA regulatory criteria for bioequivalence. The novel ART ODT was physicochemically stable under the accelerated storage condition (40 °C, RH75%) for 24 weeks. Therefore, the novel ARP-loaded ODT is expected to be an alternative to oral ARP therapy, providing improved patient adherence.

Evaluation of eccentric tooth contact on a semi-adjustable articulator by using an occlusal analysis system.

STATEMENT OF PROBLEM: Duplicating mandibular movement with a semi-adjustable articulator has been reported to lack accuracy. However, although previous studies have analyzed articulator movement, few have compared excursive tooth contact on the articulator with tooth contact during actual mandibular movement. PURPOSE: The purpose of this clinical study was to evaluate the concordance of semi-adjustable articulator contacts with intraoral contacts during eccentric movements by using a T-scan occlusal analysis system. MATERIAL AND METHODS: Forty-two participants with normal occlusion and without signs of temporomandibular disorder were analyzed for the reproducibility of eccentric tooth contact on a semi-adjustable articulator. Maxillary casts made from irreversible hydrocolloid impressions were mounted on a semi-adjustable articulator with the facebow. The condylar inclination of the articulator was set by using interocclusal records. Three recordings of right and left excursive mandibular movement and protrusive mandibular movement were made in the supine position by using the T-scan v9.1. The same procedure was then performed with the articulator. The results of complete mandibular movement from T-scan measurements were divided into 4 time points for analysis: T0, T1, T2, and T3. The concordance of intraoral and articulator occlusal contacts was evaluated at each point, and the occlusal force for each tooth was compared. Overall concordance and concordance of the working and nonworking sides were also calculated. Repeated measures analysis of variance was used to analyze differences between the concordance of intraoral and articulator contacts according to mandibular movement direction, time, and working and nonworking sides (α=.01). RESULTS: For all teeth, concordance between the intraoral and articulator occlusal contacts during excursive mandibular movement was greatest at T0, decreasing at T1 and T2, and increasing at T3. No significant differences were found in the concordance among the right lateral, left lateral, and protrusive excursion (P>.01). The concordance of working side occlusal contacts during lateral excursion was significantly lower at T3 than that at T0 (P<.01). CONCLUSIONS: When comparing intraoral and articulator contacts during lateral eccentric mandibular movement, concordance was affected by time and working or nonworking side. Reproducibility of initial eccentric tooth contact on a semi-adjustable articulator appeared to be reliable. However, occlusal adjustment of the working side might be required after prosthesis delivery.

Effect of particle size on in vivo performances of long-acting injectable drug suspension.

Herein, entecavir-3-palmitate (EV-P), an ester prodrug of entecavir (EV), was employed as a model drug, and the effect of drug particle size on in vivo pharmacokinetic profiles and local inflammatory responses, and those associations were evaluated following intramuscular (IM) injection. EV-P crystals with different median diameters (0.8, 2.3, 6.3, 15.3 and 22.6 µm) were prepared using the anti-solvent crystallization method, with analogous surface charges (-10.7 ~ -4.7 mV), and crystallinity (melting point, 160-170 °C). EV-P particles showed size-dependent in vitro dissolution profiles under sink conditions, exhibiting a high correlation between the median diameter and Hixon-Crowell's release rate constant (r2 = 0.94). Following IM injection in rats (1.44 mg/kg as EV), the pharmacokinetic profile of EV exhibited marked size-dependency; 0.8 µm-sized EV-P particles about 1.6-, 3.6-, and 5.6-folds higher systemic exposure, compared to 6.3, 15.3, and 22.6 µm-sized particles, respectively. This pharmacokinetic pattern, depending on particle size, was also highly associated with histopathological responses in the injected tissue. The smaller EV-P particles (0.8 or 2.3 µm) imparted the larger inflammatory lesion after 3 days, lower infiltration of inflammatory cells, and thinner fibroblastic bands around depots after 4 weeks. Conversely, severe fibrous isolation with increasing particle size augmented the drug remaining at injection site over 4 weeks, impeding the dissolution and systemic exposure. These findings regarding the effects of formulation variable on the in vivo behaviors of long-acting injectable suspension, provide constructive knowledge toward the improved design in poorly water-soluble compounds.

High-Payload Nanosuspension of Centella asiatica Extract for Improved Skin Delivery with No Irritation.

BACKGROUND: The titrated extract of Centella asiatica (CA) has received much attention as a cosmeceutical ingredient owing to its anti-wrinkle effect. However, due to the low solubility and high molecular weight of pharmacologically active constituents, including asiatic acid (AA), madecassic acid (MA), and asiaticoside (AS), it is challenging to fabricate high-payload topical preparations of CA with satisfactory skin absorption profiles. PURPOSE: This study aimed to design a high-payload topical preparation of CA using nanocrystallization technique and to evaluate its skin absorption profile and local tolerability. METHODS: High-payload nanocrystal suspensions (NSs) were prepared using lab-scale bead-milling technology, by adjusting the type and amount of suspending agent, CA content, type of vehicle, and milling speed. CA-loaded NSs were characterized in terms of morphology, particle size, crystallinity, and in vitro dissolution pattern. Skin absorption of CA nanocrystals was evaluated using a vertical Franz diffusion cell mounted with porcine skin. In vivo skin irritation following topical application of high-payload NS was assessed in normal rats. RESULTS: The optimized NS system, composed of 10% (w/v) CA, 0.5% polyvinylpyrrolidone (PVP) K30 as steric stabilizer, and 89.5% of distilled water, was characterized as follows: spherical or elliptical in shape, 200 nm in size, with low crystallinity. The in vitro dissolution of AA or MA from NSs was markedly faster compared to raw material, under sink condition. Penetration of AA, MA, and AS in the porcine skin was markedly elevated using the high-payload NS formula, providing 5-, 4-, and 4.5-fold higher accumulation in skin layer, compared to that of the marketed cream formula (CA 1%, Madeca cream). Moreover, topical application of high-payload NS was tolerable, showing neither erythema nor oedema in normal rats. CONCLUSION: The novel NS system is expected to be a virtuous approach for offering a better skin absorption of CA, without using an excess quantity of solubilizers.

Laparoscopic Liver Resection Enhanced by an Intervention-Guided Fluorescence Imaging Technique Using Sodium Fluorescein.

BACKGROUND AND OBJECTIVES: In laparoscopic liver resections, tumor localization is a critical aspect of ensuring clear resection margins and preserving the hepatic parenchyma. In this study, we designed a fluorescence imaging technique using a new fluorophore for tumor localization. MATERIALS AND METHODS: Immediately before laparoscopic or transthoracic liver resection, microcatheter was inserted through the hepatic artery and used to engrave the segment containing the tumor in the intervention room. Under blue light, the fluorescence of the lesion was visually confirmed, and the location was determined through intraoperative sonography. After tumor localization, liver resection was performed. RESULTS: From February 2017 to March 2020, 24 patients underwent laparoscopic liver resection (LLR) or video-assisted transthoracic liver resection (VTLR) using intervention-guided fluorescence imaging technique (IFIT). CONCLUSIONS: IFIT can provide some advantages in the field of LLR. In addition, in cases of VTLR for hepatocellular carcinoma in the superior posterior segment in patients with marginal liver function, IFIT is considered useful.

Comparison of two computerized occlusal analysis systems for indicating occlusal contacts.

PURPOSE: The purpose of this study was to compare the performance of Accura to that of the T-scan for indicating occlusal contacts. MATERIALS AND METHODS: Twenty-four subjects were selected. Their maxillary dental casts were scanned with a model scanner. The Stereolithography files of the casts were positioned to align with the occlusal plane. Occlusal surfaces of every tooth were divided into three to six anatomic regions. T-scan and Accura recordings were made during two masticatory cycles. The T-scan and Accura images were captured at the maximum bite force and overlapped to the cast. Photographs of interocclusal records were used as the reference during overlap. The occlusal contacts were counted to compare the T-scan and Accura. McNemar's test was used for statistical significance and the corresponding P-values were calculated from a chi-square distribution with one degree of freedom. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Accura were calculated relative to the T-scan values as a control. RESULTS: No statistical differences (P>.05) were found between the T-scan and Accura methods. The accuracy of Accura was 75.8%, sensitivity was 82.1%, specificity was 60.1%, PPV was 82.9%, and NPV was 60.1%. CONCLUSION: Accura could be another possible option as a computerized occlusal analysis system for indicating occlusal contacts at maximum intercuspation.

Development of a Breastfeeding Effectiveness Scale (BES).

PURPOSE: The purpose of this study was to develop and evaluate breastfeeding effectiveness scale to measure effectiveness of breastfeeding for mothers in the early postpartum period. METHODS: A conceptual framework was constructed from properties of effective breastfeeding (Yang and Seo, 2011), and item construction was derived from literature review and analysis of the data along with interviews with breastfeeding mothers. Content validity was tested by experts. Each item was scored on a five-point Likert scale. The preliminary questionnaire was administered to 248 breastfeeding mothers. Data were analyzed using item analysis, factor analysis, Pearson correlation coefficients, and Cronbach's α. RESULTS: From the factor analysis, 20 items in seven factors were derived. The factors were identified as mother's satisfaction, suckling, assurance of milk quantity, infant's satisfaction, latching on, infant's feeding desire, and breastfeeding positioning. The seven factors explained 65.1% of total variance, Cronbach's α of the total items was .83 and the factors ranged from .44 to .75. CONCLUSION: Results of this study suggest that breastfeeding effectiveness scale is a reliable and valid instrument to measure breastfeeding effectiveness of mothers in the early postpartum period.

Usefulness of thermography in diagnosis of complex regional pain syndrome type I after transradial coronary intervention.

Complex regional pain syndrome (CRPS) is a very rare complication of transradial coronary intervention (TRI). We present the case of a 51-year-old man who suffered severe pain of the right forearm after TRI and progressed to type I CRPS. The patient had effort angina and underwent successful coronary artery stent deployment on the right coronary artery. After removing the hemostatic device, the patient had swelling and severe pain that was not relieved by analgesics. Continued pain progressed to allodynia, hyperalgesia, and hyperesthesia, which met the diagnostic criteria for CRPS. Electromyography showed no abnormalities in nerve conduction and thermography of the forearm showed temperature discrepancy between both forearms, which confirmed the diagnosis of CRPS. We treated the patient with sympathetic nerve block, but he still suffers from minor pain in the right forearm. This case demonstrates that unalleviated pain after TRI can progress to CRPS, and that thermography is a useful method to diagnose CRPS.

Application of the Modified Clavien Classification System to 120W Greenlight High-Performance System Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia: Is It Useful for Less-Invasive Procedures?

PURPOSE: To evaluate the accuracy and applicability of the modified Clavien classification system (CCS) in evaluating complications following photoselective vaporization of the prostate by use of the 120W GreenLight high-performance system (HPS-PVP). MATERIALS AND METHODS: The medical records of 342 men who underwent HPS-PVP were retrospectively analyzed. Patients were older than 40 years and had a prostate volume >30 mL and an International Prostate Symptom Score (IPSS) ≥8. Patients with prostatic malignancy, neurogenic bladder, urethral stricture, large postvoid residual volume (>250 mL), previous prostatic surgery, or urinary tract infection were excluded. All operations were done by a single surgeon, and patients were followed up for uroflowmetry and IPSS postoperatively. All complications were recorded and classified according to the modified CCS, and methods of management were also recorded. RESULTS: The patients' mean age was 71.6±7.3 years; mean prostate volume was 50.0±17.0 mL, and 95 cases (27.7%) had volumes greater than 70 mL. The mean total IPSS was 21.7±7.9 preoperatively and 12.3±8.1 at the first month postoperatively. A total of 59 patients (17.3%) experienced postoperative complications until the first month after the surgery. Among them, 49 patients (14.3%) showed grade I complications, 9 patients (2.6%) showed grade II complications, and 1 patient (0.3%) showed a grade IIIb complication. No patients had complications graded higher than IIIb. CONCLUSIONS: Although the modified CCS is a useful tool for communication among clinicians in allowing comparison of surgical outcomes, this classification should be revised to gain higher accuracy and applicability in the evaluation of postoperative complications of HPS-PVP.

Diffusion-weighted magnetic resonance imaging findings in a patient with trigeminal ganglioneuroma.

A case of intracranial ganglioneuroma arising from the trigeminal nerve in the pontine and cerebellopontine angle cistern, in a 44-year-old female, is presented with an emphasis on diffusion-weighted imaging findings. We will discuss on how the tumor in the very unusual location should be differentiated particularly focused on diffusion-weighted imaging findings.

Laparoscopic pyelolithotomy: comparison of surgical outcomes in relation to stone distribution within the kidney.

UNLABELLED: Abstract Purpose: To evaluate surgical outcomes of laparoscopic pyelolithotomy (LP) in relation to stone distribution within the kidney. METHODS: Between August 2008 and February 2012, 77 patients underwent LP as first-line treatment for renal stone(s). Cases were classified into four groups, depending on stone location: Group I (located in only renal pelvis), Group II (located only in renal calyx), Group III (located in renal pelvis and in one calyx), and Group IV (located in renal pelvis and in multiple calyces). Patient and stone characteristics, surgical outcomes, and complications were evaluated. RESULTS: Sixty-seven (81.8%) cases were stone-free after LP for large renal stones. Stone-free rates in a single session significantly decreased with greater stone dispersion (p<0.001). Mean hospital stay in group IV was significantly longer than in other groups (p=0.038). However, there were no significant differences in mean operation times (p=0.214), mean change in serum hemoglobin (p=0.709), postoperative analgesics usages (p=0.153), and number of analgesics used on an as-needed basis (p=0.079). There were no complications of grade IIIb or of greater severity. One patient in group II received blood transfusion, and 1 in group III required percutaneous drainage due to perirenal urine collection. CONCLUSIONS: LP is an effective and safe modality for managing renal stones diseases. Distribution of stone burden, and total stone burden, is an important predictor of surgical outcome of LP in renal stone diseases.

120W GreenLight High Performance System laser for benign prostate hyperplasia: 68 patients with 3-year follow-up and analysis of predictors of response.

OBJECTIVE: To investigate 3-year postoperative results of photoselective vaporization of the prostate using the 120W GreenLight High Performance System photoselective vaporization of the prostate (HPS-PVP) for treating benign prostate hyperplasia (BPH) >30 mL. METHODS: Records of 68 of 85 men who underwent HPS-PVP and were followed up for 3 years were analyzed retrospectively. Patients were older than 50 years with prostate volume >30 mL, International Prostate Symptom Score (IPSS) ≥8, maximum flow rate (Q(max.)) <15 mL/s, and bladder outlet obstruction (BOO) index ≥20. Parameters, including IPSS and Q(max.), were measured at baseline and 6, 12, 24, and 36 months postoperatively. Patients who improved by at least 30% from baseline IPSS scores were considered responders, and logistic regression analysis was done to determine predictors of response. RESULTS: Mean age, prostate volume, IPSS, Q(max.), and operative time were 71.6 ± 7.3 years, 50.0 ± 17.0 mL, 21.7 ± 7.9, 8.7 ± 3.1 mL/s, and 60.6 ± 31.9 minutes, respectively. Six months postoperatively, 50 (73.5%) patients responded with respect to IPSS score, and 40 (58.8%) maintained improvements at 3 years postoperatively. Analysis at 3-year follow-up showed that for IPSS ≥19, the higher the IPSS the greater the functional bladder capacity (FBC) and the lower the frequency of nocturia; and for BOO index ≥40, the higher the BOO index the better the response. CONCLUSION: HPS-PVP is a safe and effective procedure for treating BPH, having demonstrated that 60% of patients maintained efficacy at 3 years postoperatively. Baseline IPSS, FBC, nocturia, BOO index, and bladder contractility index were valuable for predicting response to surgery.

Diffuse ependymal dysembryoplastic neuroepithelial tumor causing spinal drop metastases: a case report.

Dysembryoplastic neuroepithelial tumors (DNETs) arise mostly in the supratentorial cerebral cortex. A very rare case of intraventricular DNET with diffuse ependymal involvement, which causes spinal drop metastasis, is presented.