Background and Purpose
Vasopressin V1B receptor antagonists may be effective for the treatment of depression and anxiety and the objective of this study was to characterize the pharmacological ...profiles of two newly synthesized arginine vasopressin receptor 1B (V1B receptor) antagonists, TASP0233278 and TASP0390325.
Experimental Approach
We investigated the in vitro profiles of TASP0233278 and TASP0390325. In addition, the effect of TASP0390325 on the increase in plasma adrenocorticotropic hormone (ACTH) levels induced by corticotropin‐releasing factor (CRF)/desmopressin (dDAVP) was investigated. We also investigated the antidepressant and anxiolytic profiles of TASP0233278 and TASP0390325 in animal models.
Key Results
Both TASP0233278 and TASP0390325 showed a high affinity and potent antagonist activity for V1B receptors. Oral administration of TASP0390325 antagonized the increase in plasma ACTH levels induced by CRF/dDAVP in rats, indicating that TASP0390325 blocks the anterior pituitary V1B receptor in vivo. Oral administration of TASP0233278 or TASP0390325 also exerted antidepressant effects in two models of depression (a forced swimming test and an olfactory bulbectomy model). Moreover, TASP0233278 improved depressive‐like behaviour induced by repeated treatment with corticosterone, a model that has been shown to be resistant to treatment with currently prescribed antidepressants. In addition to depression models, TASP0233278 or TASP0390325 exerted anxiolytic effects in several anxiety models (social interaction, elevated plus‐maze, stress‐induced hyperthermia, separation‐induced ultrasonic vocalization and sodium lactate‐induced panic‐like responses in panic‐prone rats).
Conclusion
TASP0233278 and TASP0390325 are potent and orally active V1B receptor antagonists with antidepressant and anxiolytic activities in rodents.
Background
Revisional bariatric procedures are on the rise. The higher complexity of these procedures has been reported to lead to increased risk of complications. The objective of our study was to ...compare the perioperative risk profile of revisional bariatric surgery with primary bariatric surgery in our experience.
Methods
A prospectively maintained database of all patients undergoing bariatric surgery by three fellowship-trained bariatric surgeons from June 2005 to January 2013 at a center of excellence was reviewed. Patient demographics, type of initial and revisional operation, number of prior gastric surgeries, indications for revision, postoperative morbidity and mortality, length of stay, 30-day readmissions, and reoperations were recorded. These outcomes were compared between revisional and primary procedures by the Mann–Whitney or Chi square tests.
Results
Of 1,556 patients undergoing bariatric surgery, 102 patients (6.5 %) underwent revisional procedures during the study period. Indications for revisions included inadequate weight loss in 67, failed fundoplications with recurrent gastroesophageal reflux disease in 29, and other in 6 cases. Revisional bariatric procedures belonged into four categories: band to sleeve gastrectomy (
n
= 23), band to Roux-en-Y gastric bypass (
n
= 25), fundoplication to bypass (
n
= 29), and other (
n
= 25). Revisional procedures were associated with higher rates of readmissions and overall morbidity but no differences in leak rates and mortality compared with primary procedures. Band revisions had similar length of stay with primary procedures and had fewer complications compared with other revisions. Patients undergoing fundoplication to bypass revisions were older, had a higher number of prior gastric procedures, and the highest morbidity (40 %) and reoperation (20 %) rates.
Conclusions
In experienced hands, many revisional bariatric procedures can be accomplished safely, with excellent perioperative outcomes that are similar to primary procedures. As the complexity of the revisional procedure and number of prior surgeries increases, however, so does the perioperative morbidity, with fundoplication revisions to gastric bypass representing the highest risk group.
An in-line ionization chamber has been developed for the real-time measurement of the absolute intensity of the pulsed parametric X-ray (PXR) beam during irradiation experiments. The ...quasi-monochromatic PXR generating system was developed at the Laboratory for Electron Beam Research and Application (LEBRA) in Nihon University. In contrast to typical narrow X-ray beams in synchrotron radiation facilities, the PXR beam profile is as large as approximately 100 mm in diameter with rather uniform flux distribution at the X-ray output port in the experimental hall. The energy of the PXR beam ranges from 5 to 34 keV, which is specified by the PXR target crystal plane and its geometrical condition. The ionization chamber is of a plane parallel type employing 6-μm thick double-sided aluminum vapor-deposited polyester films for the plane electrodes through which the X-ray beam passes. The plane bias electrode has been placed at an equal distance of 25 mm from the two plane earth electrodes that act as the beam windows with an aperture diameter of 120 mm. Due to the pulsed property of the PXR beam and the geometrical configuration of the ionization chamber, the charge-sensitive preamplifier output pulse height represents an integral of the fast electron current, corresponding to a half of the total ionization charge produced by the beam. The intensity of the PXR beam has been measured for various X-ray energies by using nitrogen and argon, respectively, as the filling gas.
Status of the parametric X-ray generator at LEBRA, Nihon University Hayakawa, Y.; Sato, I.; Hayakawa, K. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
November 2006, 2006-11-00, Letnik:
252, Številka:
1
Journal Article
Recenzirano
A parametric X-ray radiation (PXR) generator system was constructed in 2001 in a dedicated beamline connected to the 125MeV electron linac of the Laboratory for Electron Beam Research and Application ...at Nihon University. This generator system consists of two perfect-silicon-crystal plates mounted on precisely moving mechanical setup to achieve a wide tunability. The experimental operation of the PXR generator started early in 2004; X-rays were first observed through this device in April 2004. Application studies using the PXR beam from a 100MeV electron beam have been conducted since July 2004. Preliminary results suggest the possibility of applying the PXR to advanced X-ray imaging and to the measurement of X-ray absorption fine structure.
Although mesh use is important for effective herniorrhaphy in adults, prosthetic infections can cause serious morbidity. Bacterial adherence to the mesh is a known precursor to prosthetic infection. ...We compared the ability of common mesh prosthetics to resist bacterial adherence. The meshes studied included polypropylene (Marlex, expanded polytetrafluoroethylene (PTFE) with and without silver chlorhexidine coating (DualMesh Plus and Dualmesh) composite meshes (Composix E/X, Proceed, and Parietex Composite) and lightweight polypropylene meshes (TiMesh, Ultrapro, and Vypro). Fifteen samples of each mesh type were individually inoculated with a suspension of 10(8 )methicillin-resistant Staphylococcus aureus (MRSA) in tryptic soy broth. After incubation at 37 degrees C for 1 h, the mesh pieces were then removed and serially washed. The colony-forming units (CFU) of MRSA present in the initial inoculum, at the end of the 1-h warm-water bath (broth count), and the pooled washes (wash count), were determined using serial dilutions and spot plating. The bacteria not accounted for in the broth or wash counts were considered adhered to the mesh. Samples of each mesh type were also analyzed using scanning electron microscopy (SEM). Data are presented as the mean percentage adherence with ANOVA and Tukey's test used to determine significance (P<0.05). The DualMesh Plus mesh had no detectable MRSA in the broth or the pooled wash samples. Dualmesh had less adherence compared with Marlex, Proceed, and Vypro (P<0.05). Conversely, Vypro had a statistically higher adherence (96%, P<0.05) as compared to TiMesh, Ultrapro, Composix E/X, and Parietex Composite. SEM confirmed bacterial adherence to all the mesh types except DualMesh Plus. The ability of a biomaterial to resist infection has an important clinical significance. DualMesh Plus, due to its antimicrobial coating, is the only mesh type of the nine tested that demonstrated a bactericidal property. Standard PTFE (Dualmesh) also had less bacterial adherence. Vypro demonstrated an increase in bacterial adherence; this was possibly due to the multifilament polyglactin 910 weaved within the prolene component of the mesh.
Abstract
Background
There is no established diagnostic biomarker for ulcerative colitis (UC). Although we recently reported an anti-αvβ6 integrin antibody to diagnose UC, there is no large-scale ...validation study on this antibody to diagnose UC. This study aimed to validate the diagnostic value of anti-αvβ6 integrin antibody for UC in a nation-wide, multicenter cohort (UCV6-Dx Study).
Methods
We enrolled 1241 UC patients, 798 Crohn’s disease (CD) patients, and 207 other gastrointestinal disease patients from 28 Japanese high-volume referral centers. Anti-Integrin αvβ6 ELISA Kit (MEDICAL & BIOLOGICAL LABORATORIES CO., LTD., Tokyo, Japan) was used to measure the titer of anti-αvβ6 integrin antibody. The cut-off value was 1.64 U/mL (the mean +3SD of 83 serum samples from healthy volunteers determined by the manufacturer). The primary outcome was the diagnostic value of the anti-αvβ6 integrin antibody. Secondary outcomes were factors associated with false negative results in UC patients, factors associated with false positive results in non-UC patients, and the optimal cut-off values using receiver operating characteristic (ROC) analysis.
Results
The diagnostic sensitivity of the anti-αvβ6 integrin antibody in UC was 87.7% and the specificities were 82.0% in CD and 87.4% in other gastrointestinal diseases. Multivariate logistic regression analysis showed that false negative results in UC patients were associated with age at the time of sample collection odds ratio (OR) 1.0242, p=0.034, 95% confidence interval (CI) 1.0018-1.0470, smoker (OR 2.5504, p=0.002, 95% CI 1.4216-4.5755), partial Mayo score (OR 0.8623, p=0.038, 95% CI 0.7495-0.9921), and advanced therapies (OR 0.5875, p=0.019, 95% CI 0.3765-0.9167) and false positive results in CD patients with disease location L2 (OR 2.6858, p=0.013, 95% CI 1.2323-5.8533). No factor was associated with false positive results in patients with other intestinal diseases. ROC analysis revealed that the optimal cut-off values estimated by the Youden method were 2.07 U/mL area under the curve (AUC) 0.9003, sensitivity 85%, specificity 87%, and 1.78 U/mL (AUC 0.9206, sensitivity 87%, specificity 89%) for discriminating UC from CD and other gastrointestinal diseases, respectively.
Conclusion
The usefulness of anti-αvβ6 integrin antibody for diagnosing UC was validated in the Japanese large-scale, nation-wide multicenter study.
The total syntheses of β-carboline alkaloids, (R)-(−)-pyridindolols (1, 5, and 6) are described. The two key steps involved are (1) a thermal electrocyclic reaction of the 3-alkenylindole-2-aldoxime ...10 and (2) a thermal cyclization of 3-alkynylindole-2-aldoxime 11 to construct the β-carboline N-oxides 8, which upon heating with acetic anhydride and sequential treatment with trifluoromethanesulfonic anhydride gave the triflates 18. The Stille coupling reaction of 18 with vinylstannane, followed by cleavage of MOM ether, afforded the 1-ethenyl-3-hydroxymethyl-β-carboline (7a). Subsequent acetylation of 7a yielded the acetate 7b, which was subjected to the Sharpless asymmetric 1,2-dihydroxylation by AD-mix-β to produce (R)-(−)-pyridindolol K2 (6). Selective acetylation of 6 was effected by Ac2O and collidine to form (R)-(−)-pyridindolol K1 (5). By contrast, hydrolysis of 6 provided (R)-(−)-pyridindolol (1).
The purpose of this study was to determine whether magnetic resonance imaging findings are accurate and can be confirmed surgically.
Surgical correlation of preoperative magnetic resonance imaging ...findings of trauma to tendons and ligaments of the foot and ankle were retrospectively studied in 28 patients who had undergone surgical repair for tears of the Achilles tendon, posterior tibial tendon, peroneal tendons, collateral ligaments, and other pathology.
This study corroborates that magnetic resonance imaging findings are confirmed surgically 83% of the time for tears of tendons and ligaments of the foot and ankle. Larger tendons (Achilles, posterior tibial tendon) have a 94% sensitivity and 6% specificity, respectively. Collateral ligament and high ankle sprains have a 73% sensitivity. There is a lower sensitivity of 57% for peroneus brevis and longus ruptures.
This study revealed that peroneal trauma can be an isolated event and in some cases can occur with other traumatic pathology such as collateral ligament tears.
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