Effect of the Particle Size and Layer Thickness of GNP Fillers on the Dielectric Properties and Actuated Strain of GNP-PDMS Composites.

Dielectric elastomer actuators (DEAs), a type of electroactive polymers (EAPs), are smart materials that are used in various fields such as artificial muscles and biomimetic robots. In this study, graphene nanoplatelets (GNPs), which are conductive carbon fillers, were added to a widely used DEA, namely, polydimethylsiloxane (PDMS), to improve its low actuated strain. Four grades of GNPs were used: H5, H25, M5, and M25 (here, the number following the letter indicates the average particle size of the GNPs in µm). The average layer thickness of the H grade is 13−14 nm and that of the M grade is 5−7 nm. PDMS composites were prepared by adding 0.5, 1, 2, and 3 wt% of each GNP, following which the mechanical properties, dielectric properties, and actuated strain of the composites were measured. The mechanical properties were found to increase as the particle size increased. Regarding the dielectric characteristics, it was found that the higher the aspect ratio of the filler, the easier the formation of a micro-capacitor network in the composite­this led to an increase in the dielectric constant. In addition, the higher amounts of GNPs in the composites also led to an increase in the dielectric constant. For the actuated strain analysis, the electromechanical sensitivity was calculated using the ratio of the dielectric constant to the Young's modulus, which is proportional to the strain. However, it was found that when the loss tangent was high, the performance of the actuated strain decreased owing to the conversion of electric energy into thermal energy and leakage current loss. As a result, the highest actuated strain was exhibited by the M25 composite, with an actuated strain value of 3.01% measured at a low electric field (<4 kV/mm). In conclusion, we proved that the GNP−PDMS composites with a thin layer and large particle size exhibited high deformation.

Textile-Based Wearable Sensor for Skin Hydration Monitoring.

This research describes a wearable skin hydration sensor based on cotton textile to determine the state of hydration within the skin via impedance analysis. The sensor structure comprises a textile substrate, thermoplastic over-layer, conductive patterns, and encapsulant, designed for stable and reliable monitoring of the skin's impedance change in relation to hydration level. The porcine skin with different hydration levels was prepared as a model system of the skin, and the textile-based sensor carefully investigated the porcine skin samples' impedance characteristics. The impedance study reveals that (1) the total impedance of skin decreases as its hydration level increases, and (2) the impedance of the stratum corneum and epidermis layers are more dominantly affected by the hydration level of the skin than the dermis layer. Even after repetitive bending cycles, the impedance data of skin measured by the sensor exhibit a reliable dependence on the skin hydration level, which validates the flexibility and durability of the sensor. Finally, it is shown that the textile-based skin hydration sensor can detect various body parts' different hydration levels of human skin while maintaining a stable conformal contact with the skin. The resulting data are well-matched with the readings from a commercial skin hydration sensor.

Clinical outcomes of palliative self-expandable metal stent placement in right- and left-sided malignant colon obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

Idiopathic Retroperitoneal Hematoma with Spontaneous Resolution.

A 54-year-old man was transferred from another hospital due to a hematoma in the third portion of the duodenum on abdomen CT. He had been admitted for 2 weeks due to vomiting at another hospital. He had abdominal discomfort and nausea without abdominal pain when he visited the Gwangyang Sarang Hospital. Other than a distended abdomen and mild general abdominal tenderness, the results of physical examination were unremarkable. Abdominal CT revealed an approximately 9 cm thick walled hematoma at the anteroinferior site of the duodenal third portion. Upper endoscopy revealed stenosis of the third portion of the duodenum without mucosal lesions. The endoscope was not advanced through the narrowed duodenal lumen. A retroperitoneal hematoma was diagnosed, and his state was classified as subacute rather than acute based on the duration. The surgeon did not recommend surgical treatment. Urgent treatment was unnecessary; he was managed conservatively. The size of the hematoma decreased from 9.0 cm to 5.8 cm on the following CT. He could begin to eat food on the 26th admission day, and he was discharged on the 31st admission day. The hematoma disappeared entirely on the following CT. This paper describes a rare case of idiopathic retroperitoneal hematoma with a spontaneous resolution.

Predictors of clinical outcomes of self-expandable metal stent treatment for malignant colorectal obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

ABSTRACT: There has been increased use of self-expandable metal stents (SEMS) in treating malignant colorectal obstruction (MCO). The aim of this study was to investigate factors that are associated with the outcomes of SEMS placement for MCO.Clinical data from patients who underwent SEMS placement for MCO at 6 hospitals in Honam province of South Korea between 2009 and 2018 were reviewed retrospectively. Eight hundred two patients were identified and their data were analyzed. Technical success, clinical success, complications, and predictors of outcome were included as main outcome measures.Technical and clinical success rates were 98.8% (792/802) and 90.1% (723/802), respectively. Complications including stent migration, stent occlusion due to tumor ingrowth and outgrowth, perforation, bacteremia/fever, and bleeding occurred in 123 (15.3%) patients. In multivariate regression analyses, procedure time was significantly associated with the technical success of SEMS placement (P = .001). Longer length of obstruction, the use of covered stent, and longer procedure time were significant independent predictive factors for the clinical success of SEMS placement (odds ratio [OR] 0.974 (95% confidence interval [CI] 0.950-0.990); P = .043, OR 0.255 (95% CI 0.138-0.471); P < .001, and OR 0.957 (95% CI 0.931-0.984); P = .002, respectively). Stage IV colorectal cancer and the use of covered stent were significant independent predictive factors for the development of complications after SEMS placement (OR 2.428 (95% CI 1.407-4.188); P = .001 and OR 3.329 (95% CI 2.060-5.378); P < .001, respectively).Longer length of obstruction, the use of covered stent, and longer procedure time were associated with lower clinical success rates. Having stage IV colorectal cancer and the use of covered stents were associated with an increased risk of complications.

Properties of Conductive Polyacrylonitrile Fibers Prepared by Using Benzoxazine Modified Carbon Black.

Composites of carbon black (CB) and polymers are attractive for producing conductive fibers. Herein, to achieve improved interactions with polymers, the surface of CB was modified to form 4-aminobenzoyl-functionalized carbon black (ABCB), benzoxazine-functionalized carbon black (BZCB), and Ag-anchored carbon black (Ag-ABCB). The surface-modified CBs were characterized by Fourier transform infrared spectroscopy and thermogravimetric analysis, and X-ray photoelectron spectroscopy was utilized to confirm the presence of Ag in Ag-ABCB. Conductive polyacrylonitrile (PAN) fibers were wet-spun with conductive fillers (CB, ABCB, Ag-ABCB, and BZCB) to investigate the effects of various functional groups on the electrical and mechanical properties. After annealing the conductive PAN fibers, the conductivity and tensile strength greatly increased, whereas the diameter decreased. Notably, the fiber with a BZCB/PAN weight ratio of 12/88 possessed a conductivity of 8.9 × 10-4 S/cm, and strength of 110.4 MPa, and thus the highest conductivity and best mechanical properties in the conductive PAN fiber. These results indicate that the annealed BZCB/PAN fibers have potential applications in the manufacturing of antistatic fabrics.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

New monoclonal antibody-based test for Helicobacter pylori urease in gastric tissue.

BACKGROUND/AIMS: To evaluate a new monoclonal antibody for Helicobacter pylori urease in gastric tissue. METHODS: A total of 107 volunteers were enrolled. All subjects underwent a (13)C-urea breath test and esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia. Six biopsy specimens in the gastric antrum and body were obtained for a rapid urease test and histology. The new monoclonal antibody-based H. pylori urease test (HPU) was performed to rapidly and qualitatively detect urease in two biopsy specimens. RESULTS: H. pylori infection was diagnosed in 73 subjects. The sensitivity and specificity of the HPU was 89% and 74%, respectively. The subjects were divided into two groups: one with true-positive and true-negative HPU results (n = 90) and the other with false-positive and false-negative HPU results (n = 17). Across all subjects, ammonia levels were 900.5 ± 646.7 and 604.3 ± 594.3 µmol/L (p > 0.05), and pH was 3.37 ± 1.64 and 2.82 ± 1.51 (p > 0.05). Sensitivity was higher in the presence of atrophic gastritis or intestinal metaplasia. CONCLUSIONS: HPU detected H. pylori in approximately 10 min. Gastric aspirate ammonia and pH levels did not affect the test results. Sensitivity was good in the presence of atrophic gastritis or intestinal metaplasia.

Cadmium induces urokinase-type plasminogen activator receptor expression and the cell invasiveness of human gastric cancer cells via the ERK-1/2, NF-κB, and AP-1 signaling pathways.

Cadmium exposure has been linked to human cancers, including stomach cancer. In this study, the effects of cadmium on urokinase-type plasminogen activator receptor (uPAR) expression in human gastric cancer cells and the underlying signal transduction pathways were investigated. Cadmium induced uPAR expression in a time- and concentration-dependent manner. Cadmium also induced uPAR promoter activity. Additionally, cadmium induced the activation of extracellular signal regulated kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and the activation of c-Jun amino terminal kinase (JNK). A specific inhibitor of MEK-1 (PD98059) inhibited cadmium-induced uPAR expression, while JNK and p38 MAPK inhibitors did not. Expression vectors encoding dominant-negative MEK-1 (pMCL-K97M) also prevented cadmium-induced uPAR promoter activity. Site-directed mutagenesis and electrophoretic mobility shift studies showed that sites for the transcription factors nuclear factor (NF)-κB and activator protein-1 (AP-1) were involved in cadmium-induced uPAR transcription. Suppression of the cadmium-induced uPAR promoter activity by a mutated-type NF-κB-inducing kinase and I-κB and an AP-1 decoy oligonucleotide confirmed that the activation of NF-κB and AP-1 are essential for cadmium-induced uPAR upregulation. Cells pretreated with cadmium showed markedly enhanced invasiveness and this effect was partially abrogated by uPAR-neutralizing antibodies and by inhibitors of ERK-1/2, NF-κB, and AP-1. These results suggest that cadmium induces uPAR expression via ERK-1/2, NF-κB, and AP-1 signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS cells.

Detection of Helicobacter pylori in Gastric Aspirates Using a Monoclonal Antibody-Based Test.

BACKGROUND/AIMS: The objective of this study was to evaluate a monoclonal antibody-based test to detect Helicobacter pylori-specific antigen in gastric aspirates from humans. METHODS: Sixty-one volunteers were enrolled in the study. All of the subjects underwent a (13)C-urea breath test (UBT) before esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia and used for polymerase chain reaction (PCR), culture, and monoclonal antibody-based detection of H. pylori. Multiple biopsies of the gastric antrum and body were obtained for a rapid urease test (RUT) and histological evaluation. RESULTS: Thirty-six subjects were H. pylori-positive and 25 were H. pylori-negative according to the UBT results. Compared with the H. pylori-negative subjects, H. pylori-positive subjects had a higher pH (4.77±1.77 vs 3.49±1.30, p<0.05) and ammonia level (1,130.9±767.4 vs 184.2±126.3, p<0.0001). The sensitivities and specificities of the PCR test, RUT, culture test, and monoclonal antibody-based test were 100% and 72%, 89% and 100%, 47% and 100%, and 78% and 100%, respectively. CONCLUSIONS: The monoclonal antibody-based test for diagnosing H. pylori infection in gastric aspirates has increased sensitivity compared with the culture test and specificity as high as that of the RUT. The test may be useful as an additive test for examining gastric aspirates.

Production of biohydrogen by aqueous phase reforming of polyols over platinum catalysts supported on three-dimensionally bimodal mesoporous carbon.

Now in 3D! Three-dimensionally bimodal carbons (3D-BMC) with mesopores of tunable size (controlled through the polymerization of the carbon precursor) are synthesized. After loading with platinum, the catalysts are used in aqueous phase reforming of polyols, and show superior performance in terms of carbon conversion, hydrogen yield, selectivity, and hydrogen production rate compared to platinum catalysts supported on activated carbon or two-dimensional CMK-3.

[Culture and polymerase chain reaction of Helicobacter pylori from rectal and terminal ileal fluid after polyethylene glycol (colyte) ingestion in healthy adults with positive urea breath test].

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) transmission route is not yet clearly understood. Isolating H. pylori from stool, saliva, and vomitus is very difficult. However, H. pylori could be cultured from feces in the setting of rapid gastrointestinal tract transit. The aim of this study was to isolate H. pylori by culture and PCR in the rectum and terminal ileum during colonoscopy. METHODS: Twenty subjects with positive UBT (urea breath test) were included. We performed polymerase chain reaction (PCR) test and culture of H. pylori with the rectal fluid and terminal ileal fluid during colonoscopy. RESULTS: H. pylori was cultured with rectal fluid from 9 (45.0%) of 20 subjects and with ileal fluid from 11 (55.0%) of 20 subjects. H. pylori was a little more frequently cultured from the terminal ileal fluid than the rectal fluid without statistical significance (p>0.05). PCR test detected flaA (16/20, 80.0% and 17/20, 85.0%), 16S rRNA gene (16/20, 80.0% and 17/20, 85.0%), cagA (10/20, 50.0% and 12/20, 60.0%), and ureC (9/20, 45% and 11/20, 54.5%) from the rectal fluid and the terminal ileal fluid, respectively. The specificity and sensitivity of ureC were 100%. CONCLUSIONS: H. pylori could be cultured from the rectal fluid and terminal ileal fluid in the setting of rapid gastrointestinal tract transit. These results suggest of fecal-oral transmission of H. pylori.

Lithocholic acid upregulates uPAR and cell invasiveness via MAPK and AP-1 signaling in colon cancer cells.

The secondary bile acid lithocholic acid (LCA) induced expression of urokinase-type plasminogen activator receptor (uPAR) and enhanced cell invasiveness in colon cancer cells. A dominant negative mutant or a specific inhibitor of MEK-1 suppressed LCA-induced uPAR expression. Deletions and site-directed mutagenesis revealed that the AP-1 site was required for LCA-induced uPAR transcription. LCA-mediated enhanced cell invasiveness was partially abrogated by uPAR neutralizing antibody and inhibitors of both Erk-1/2 and AP-1. These results suggest that LCA induces uPAR expression via Erk-1/2 and AP-1 pathway and, in turn, stimulate invasiveness of human colon cancer cells.

[A case of macroscopically unvisualized mucin-hypersecreting biliary papillomatosis diagnosed by microscopy].

The mucin-hypersecreting biliary papillomatosis is a premalignant neoplasm characterized by intraductal papillary proliferation involving extensive areas of the intrahepatic and/or extrahepatic bile duct. We report a case of mucin-hypersecreting biliary papillomatosis manifested as obstructive jaundice and diagnosed only by microscopy, with a review of literatures. A 74-year-old female, who had a past history of cholecystectomy about 13 years ago, was admitted to our hospital with jaundice. A CT scan showed marked dilatation of intrahepatic and extrahepatic bile duct without intraductal filling defect or extrabiliary mass. During endoscopic retrograde cholangiopancreatography, mucin extrusion from the duodenal major papilla and dilated common bile duct with amorphous filling defects was noted. Percutaneous transhepatic biliary drainage for cholangioscopy was failed. In the operation field, there was a lot of mucin but was no visible mass at the common bile duct with bare eyes and cholangioscopy. However, papilloma was detected at the random biopsy specimen by microscopy. The patient underwent partial resection of common bile duct and choledocho-jejunal anastomosis.

A processing circuit for overlapped pulse signals for a thermal neutron coincidence counter.

We have developed a processing circuit for overlapped pulse signals. The overlapped pulse signals are generated when the pulse signals of a He-3 detector, by using a neutron coincidence counter, are connected to shift register coincidence electronics by an OR gate device. The developed circuit detects the overlapped pulse signals from among four input signals and produces new 50 ns pulse wide signals. We considered a case where two pulse signals are simultaneously overlapped among four signals. This circuit was tested with an ACP safeguards neutron counter (ASNC) for an advanced spent fuel conditioning process (ACP) and a (252)Cf neutron source at high rates. The loss rate of the output signal was reduced by 1.27% for singles and 4.75% for doubles when compared with the OR gate device. Also the variation for the triples was much bigger.

P2Y receptors mediate Ca2+ signaling in duodenocytes and contribute to duodenal mucosal bicarbonate secretion.

Since little is known about the role of P2Y receptors (purinoceptors) in duodenal mucosal bicarbonate secretion (DMBS), we sought to investigate the expression and function of these receptors in duodenal epithelium. Expression of P2Y(2) receptors was detected by RT-PCR in mouse duodenal epithelium and SCBN cells, a duodenal epithelial cell line. UTP, a P2Y(2)-receptor agonist, but not ADP (10 microM), significantly induced murine duodenal short-circuit current and DMBS in vitro; these responses were abolished by suramin (300 microM), a P2Y-receptor antagonist, or 2-aminoethoxydiphenyl borate (2-APB; 100 microM), a store-operated channel blocker. Mucosal or serosal addition of UTP induced a comparable DMBS in wild-type mice, but markedly impaired response occurred in P2Y(2) knockout mice. Acid-stimulated DMBS in vivo was significantly inhibited by suramin (1 mM) or PPADS (30 microM). Both ATP and UTP, but not ADP (1 microM), raised cytoplasmic-free Ca(2+) concentrations ([Ca(2+)](cyt)) with similar potencies in SCBN cells. ATP-induced [Ca(2+)](cyt) was attenuated by U-73122 (10 microM), La(3+) (30 microM), or 2-APB (10 microM), but was not significantly affected by nifedipine (10 microM). UTP (1 microM) induced a [Ca(2+)](cyt) transient in Ca(2+)-free solutions, and restoration of external Ca(2+) (2 mM) raised [Ca(2+)](cyt) due to capacitative Ca(2+) entry. La(3+) (30 microM), SK&F96365 (30 microM), and 2-APB (10 microM) inhibited UTP-induced Ca(2+) entry by 92, 87, and 94%, respectively. Taken together, our results imply that activation of P2Y(2) receptors enhances DMBS via elevation of [Ca(2+)](cyt) that likely results from an initial increase in intracellular Ca(2+) release followed by extracellular Ca(2+) entry via store-operated channel.

[Three sporadic cases of acute hepatitis E].

Acute hepatitis E is an endemic disease, commonly reported in Indian subcontinent, China, Africa, Central America, and so forth. It is a self-limiting disease like other acute hepatitis except in pregnant patient. Although sporadic hepatitis E is noted all over the world, most of them are associated with travel history to HEV-endemic area. In Korea, Hepatitis E is rarely reported. Moreover, sporadic acute hepatitis E without travel history to HEV-endemic area is very rare. We experienced three sporadic cases of acute hepatitis E, without travel history. All of them presented acute hepatitis symptoms, elevated aminotransferase, and positive IgM HEV Ab. Symptoms and aminotransferase levels were normalized during hospitalization and IgM HEV Ab converted negative after 4-8 months. We report three sporadic cases of onset-acute hepatitis E without travel history to HEV-endemic area.

[Telomerase expression in colorectal tubular adenoma determined by immunohistochemical staining].

BACKGROUND/AIMS: Telomeres are simple repeat elements located at each chromosome end of eukaryotic cells. The main function of telomeres is to cap the chromosome end and protect it from enzymatic attack. Telomerase that facilitates the synthesis of telomere has been detected in not only cancer but also precancerous lesion. In this study, we compared the telomerase expression between low grade and high grade colorectal tubular adenoma. METHODS: Among tissues from forty eight patients with colorectal tubular adenoma (23 low grade and 25 high grade colorectal dysplasia), telomerase expressions were evaluated by immunohistochemical staining. RESULTS: We classified 48 patients into two groups by the extent of nuclei staining pattern. High telomerase expression was a group which showed staining nucleus pattern above 50% in tubular adenoma. Low telomerase expression was a group which showed staining pattern nucleus below 50%. Twelve in 25 high grade colorectal dysplasia showed high telomerase expression (48%). Only one in 23 low grade colorectal dysplasia showed high telomerase expression (4%). Telomerase expression was much higher in the tissues from the patients with high grade than in those with low grade colorectal dysplasia (p<0.05). CONCLUSIONS: Activation of telomerase may be related to the malignant potential in colorectal epithelial cells. Further studies are needed to define the role of telomerase in colorectal tumorigenesis.

Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol.

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, menthol did the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2mg/ml was administered easily to the anus and to remain at the administered site without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquid suppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhance the rectal bioavailability of ibuprofen.

Benzoxazine oligomers: evidence for a helical structure from solid-state NMR spectroscopy and DFT-based dynamics and chemical shift calculations.

A combination of molecular modeling, DFT calculations, and advanced solid-state NMR experiments is used to elucidate the supramolecular structure of a series of benzoxazine oligomers. Intramolecular hydrogen bonds are characterized and identified as the driving forces for ring-shape and helical conformations of trimeric and tetrameric units. In fast MAS (1)H NMR spectra, the resonances of the protons forming the hydrogen bonds can be assigned and used for validating and refining the structure by means of DFT-based geometry optimizations and (1)H chemical-shift calculations. Also supporting these proposed structures are homonuclear (1)H[bond](1)H double-quantum NMR spectra, which identify the local proton-proton proximities in each material. Additionally, quantitative (15)N[bond](1)H distance measurements obtained by analysis of dipolar spinning sideband patterns confirm the optimized geometry of the tetramer. These results clearly support the predicted helical geometry of the benzoxazine polymer. This geometry, in which the N...H...O and O...H...O hydrogen bonds are protected on the inside of the helix, can account for many of the exemplary chemical properties of the polybenzoxazine materials. The combination of advanced experimental solid-state NMR spectroscopy with computational geometry optimizations, total energy, and NMR spectra calculations is a powerful tool for structural analysis. Its results provide significantly more confidence than the individual measurements or calculations alone, in particular, because the microscopic structure of many disordered systems cannot be elucidated by means of conventional methods due to lack of long-range order.