Cryomilled electrospun nanofiber mats containing d-mannitol exhibit suitable for aerosol delivery of proteins.

Dry powder inhalers (DPIs) are the first choice for inhalation drug development. However, some conventional DPI formulation processes require heating, which may damage high molecular weight drugs such as proteins and nucleic acids. In this study, we propose a novel DPI preparation process that avoids the use of heat. Dry powders were prepared by cryomilling nanofiber mats composed of polyvinyl alcohol, D(-)-mannitol (Man), and α-chymotrypsin (α-Chy) as the model drug using the electrospinning method. The addition of Man conferred high dispersibility and excellent in vitro aerosol performance to the nanofiber mat powder in a very short milling time (less than 0.5 min) as assessed using the Andersen cascade impactor. Powders were classified according to the degree of friability, and among these, nanofiber mats containing 15 % Man and milled for 0.25 min exhibited the highest aerosol performance. Nanofiber mats containing Man milled for less than 0.5 min also exhibited greater α-Chy enzymatic activity than a nebulized α-Chy solution. Furthermore, single inhalation induced no significant lung tissue damage as evidenced by lactate dehydrogenase activity assays of mouse bronchoalveolar lavage fluid. This novel DPI formulation process may facilitate the safe and efficient inhalational delivery of therapeutic proteins.

Improvement of the setting properties of mineral trioxide aggregate cements using cellulose nanofibrils.

Cellulose nanofibrils (CNFs) exhibit excellent mechanical properties and are used to reinforce various composites. The effects of incorporating CNFs into commercial mineral trioxide aggregate (MTA) cements (NEX MTA (NEX) and ProRoot® MTA (PR)) on the underwater setting properties, compressive strength, and flowability were estimated in this study. NEX mixed without CNFs disintegrated after water immersion. NEX mixed with CNF-suspended solutions showed good setting properties under water immersion and a similar compressive strength, which was kept in air (100% relative humidity). PR did not degrade after water immersion, regardless of the presence of CNFs, and no significant difference in the compressive strength caused by CNFs incorporation was detected. The relative flowability of the NEX mixture decreased with increasing CNFs content up to 1.0 w/v%. The application of CNF-incorporated MTA in various dental cases is promising because CNFs prevent the water-immersion-dependent collapse of some MTA cements immediately after mixing.

Direct sac puncture embolization for a left subclavian aneurysm with Marfan syndrome: A case report.

Subclavian artery aneurysms, occasionally related to connective tissue diseases, including Marfan syndrome, are rare and conventionally managed with surgery or endovascular treatment. However, in some cases, both interventions are challenging because of the inability to reach an aneurysm through a safe route or postoperative adhesion. This report describes the case of a 43-year-old patient with a left subclavian artery aneurysm and Marfan syndrome. In this case, the patient's 5 previous surgeries related to Marfan syndrome made surgery and endovascular treatment difficult. Therefore, an alternative was researched, and we decided to perform a method of percutaneous embolization with coils and N-butyl cyanoacrylate using the direct puncture technique, which succeeded in eliminating the blood flow in the left subclavian artery aneurysm. No severe complications were associated with the procedure. The patient was free from the risk of an aneurysm rupture post-treatment, and the left back pain improved. Follow-up computed tomography 2 years postsurgery revealed the aneurysm being under control without re-enlarging. Our method is considered an effective and safe therapeutic option for cases in which surgical approach and transarterial access routes are limited.

Clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy with cisplatin in combination with oral S-1 on stage III and IV oral cancer.

OBJECTIVE: The aim of this study was to examine the clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy (IACRT) using cisplatin in combination with oral S-1 (tegafur/gimeracil/oteracil potassium) on stage III and IV oral squamous cell carcinoma. STUDY DESIGN: Thirty patients received infusions of superselective intra-arterial cisplatin 60 mg/m2 by the Seldinger method and conventional external beam radiotherapy (total 40 Gy) combined with oral S-1 on the day of irradiation. Curative surgery and neck dissection were performed 4 to 6 weeks after IACRT. The clinical response of the primary lesion was evaluated approximately 4 weeks after IACRT. The surgically resected specimens were examined for histologic features according to the grading system for histologic evaluation and for residual tumor grade (RGrades). RESULTS: Histopathologic evaluation of the therapeutic effect was grade 2 in 10 patients and grade 3 in 16 patients. According to the distribution of RGrades, the remaining tumor cells were mostly in the central area of the primary lesion, as seen in 24 patients. CONCLUSIONS: These findings indicate that neoadjuvant IACRT with cisplatin and oral S-1 was an effective treatment, suggesting the possibility of reducing the extent of curative surgery based on RGrades.

Stiff coils enhance shape retention and pressure resistance in an aneurysm model even at low volume.

PURPOSE: To elucidate the characteristics of 3 D frame coils and identify the optimal coil for visceral aneurysms. MATERIAL AND METHODS: Using a vascular model, we compared the postembolization coil distribution and repulsive force of three coils: Guglielmi detachable coil (GDC; stock wire diameter, 0.004 in; primary diameter, 0.015 in), Target XL (0.003, 0.014), and Target XXL (0.003, 0.017). Additionally, the coil area, roundness, and center of gravity were quantitatively compared. The coil repulsive force was measured by compressing the postembolization vessel model with a digital force gauge. RESULTS: There were no significant differences in the coil area and roundness among the three coil types. Compared with the Target coils, the GDC deployed evenly along the vessel wall, its center of gravity was less displaced, and although it had the lowest embolic density, its repulsive force was greater regardless of the number of coils used. CONCLUSIONS: GDC coils with a larger stock wire diameter and a smaller primary diameter unfolded evenly along the wall and had a greater repulsive force. Coil stiffness contributes to coil stability and shape retention, indicating the possibility of preventing recurrence by selecting a frame coil with a focus on coil stiffness.

Delayed retroperitoneal hemorrhage during veno-venous extracorporeal membrane oxygenation: a case report.

CASE: There are several reports of retroperitoneal hemorrhage induced by percutaneous femoral cannulation for extracorporeal membrane oxygenation (ECMO). However, there are no reports of delayed retroperitoneal hemorrhage, which develops a few days after ECMO initiation and is unrelated to the ECMO cannulation. Herein, we report a rare case of delayed retroperitoneal hemorrhage during veno-venous extracorporeal membrane oxygenation (VV-ECMO). OUTCOME: A 54-year-old man was referred to our hospital because of severe acute respiratory distress syndrome. We initiated VV-ECMO. The patient had severe delirium and was confined to a long-term supine position to maintain circuit safety. On day 13, computed tomography unexpectedly revealed a large retroperitoneal hemorrhage spreading around the psoas muscle. CONCLUSION: Delayed retroperitoneal hemorrhage can develop during VV-ECMO management a few days after its initiation. Anticoagulant use and forceful muscular strain could be risk factors of delayed retroperitoneal hemorrhage.

Histopathological differences of experimental aneurysms treated with bare platinum, fibered, and bioactive coils.

PURPOSE: To evaluate the histopathological features of experimental aneurysms embolized with bare platinum, fibered, and bioactive coils. MATERIAL AND METHODS: Twelve experimental aneurysms were constructed in three swine. The aneurysms were divided into four groups and were embolized using a bare platinum coil alone (P group, n = 2), a bioactive coil alone (B group, n = 2), a combination of fibered and bare platinum coils (F/P group, n = 4) and a combination of fibered and bioactive coils (F/B group, n = 4). Histopathological data for all aneurysms recorded at 63 days were analyzed in terms of neointima formation, fibrosis, foreign-body giant-cell infiltration, and organization. RESULTS: Fibrosis was significantly greater in group B compared with that in group F/P (p = .02).　 Inflammation with foreign-body giant-cell infiltration was significantly greater in groups F/P and F/B compared with that in groups P and B (p = .007). CONCLUSION: The present study revealed that the embolic effect of fibered coils was not a thrombus but instead was a foreign-body response in the chronic phase.

Antitubercular activity of triterpenoids from Asteraceae flowers.

Twenty-eight 3-hydroxy triterpenoids of taraxastane- (1-7), oleanane- (8-12), ursane- (13-15), lupane- (16,18,19), taraxane- (20), cycloartane- (21-25), tirucallane- (26-28), and dammarane-types (29) isolated from the non-saponifiable lipid fraction of the flower extract of chrysanthemum (Chrysanthemum morifolium) and one lupane-type 3alpha-hydroxy triterpenoid (17) derived from 16 were tested for their antitubercular activity against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay (MABA). Fifteen compounds showed a minimum inhibitory concentration (MIC) in the range of 4-64 microg/ml, among which maniladiol (9; MIC 4 microg/ml), 3-epilupeol (17; 4 microg/ml), and 4,5alpha-epoxyhelianol (27; 6 microg/ml) exhibited the highest activity. Cytotoxicity of compound 17 against Vero cells gave an IC50 value of over 62.5 microg/ml, suggesting some degree of selectivity for M. tuberculosis.

Isolation, structural elucidation, and inhibitory effects of terpenoid and lipid constituents from sunflower pollen on Epstein-Barr virus early antigen induced by tumor promoter, TPA.

Eight fatty acid esters of triterpene alcohols (1-8), four free triterpene alcohols (9, 12, 17, and 18), four diterpene acids (19-22), two tocopherol-related compounds (23 and 24), four estolides (25-28), three syn-alkane-4,6-diols (29-31), one 1,3-dioxoalkanoic acid (32), and one aliphatic ketone (33), along with the mixture of free fatty acids, were isolated from the diethyl ether extract of the pollen grains of sunflower (Helianthus annuus). Among these compounds, 14 (2-8, 12, 23, 25-28, and 33) were new naturally occurring compounds, and their structures were determined on the basis of spectroscopic methods. Twenty-four terpenoids and lipids (1-4, 6-9, 12, and 19-33) and six free triterpene triols (10, 11, and 13-16), derived from their fatty acid esters (2, 3, and 5-8) by alkaline hydrolysis, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells, which is known to be a primary screening test for antitumor promoters. Among the 30 compounds tested, 21 compounds possessing a di- or a polycyclic ring system in the molecule (1-4, 6-16, and 19-24) showed potent inhibitory effects on EBV-EA induction (91-100% inhibition at 1 x 10(3) mol ratio/TPA).