Endoscopic submucosal resection of rectal carcinoid tumors with a ligation device

BACKGROUND: Local endoscopic mucosal resection of rectal carcinoid tumors is often associated with margin involvement that requires further intervention. The efficacy of resection of these tumors with endoscopic submucosal resection with a ligation device (ESMR-L) was evaluated. METHODS: Fourteen rectal carcinoid tumors were treated by ESMR-L between 1999 and 2002. ESMR-L was performed with a conventional colonoscope with an attached band-ligator device. For comparison, 14 rectal carcinoid tumors, treated by either endoscopic mucosal resection or polypectomy between 1990 and 1997, were evaluated as historical controls. All tumors were estimated to be 1 cm or less in diameter. OBSERVATIONS: There were no differences between the 2 groups in terms of age, gender, or tumor size. For 6 (43%) patients in the control group, there was tumor involvement at the margin of the resection specimen, whereas all tumors removed by ESMR-L had histopathologically proven negative margins (p < 0.05). The mean vertical resection margin also was significantly deeper in the ESMR-L group (p < 0.05). There was no complication of any procedure. CONCLUSIONS: ESMR-L is technically simple, minimally invasive, and safe for treatment of small rectal carcinoid tumors contained within the submucosa. ESMR-L provides a deeper resection margin compared with that obtained with conventional endoscopic mucosal resection or polypectomy.     

Pharmacokinetics and drug interactions of antidepressive agents

Tricyclic antidepressive agents(TCAs) are conventional antidepressant. Cytochrome P450(CYP) 2D6 is involved in the hydroxylation of TCAs, while N-demethylation of TCAs is mediated by other such as CYP2C19, 3A4 and 1A2. The elimination of TCAs is impaired by CYP2D6 inhibitors such as quinidine. Newer antidepressants, selective serotonin uptake inhibitors(SSRIs), are also metabolized in the liver. Fluvoxamine, an SSRI, is a potent inhibitors for CYP1A2 and CYP2C19, moderate for CYP3A4 and weak for CYP 2D6. Paroxetine, another SSRI, causes substantial inhibition of CYP2D6 activity. Milnacipran, a serotonin and noradrenaline reuptake inhibitor, is mainly excreted unchanged in urine and some part as its glucronide conjugate. In contrast to many SSRIs, milnacipran is devoid of metabolic inhibition.     

Origins and pathways of fluid entering sublobular lymphatic vessels in cat livers

The liver, which produces a large volume of lymph, has a lymphatic system which can be classified into three categories: portal, sublobular, and superficial lymphatic vessels. As little is known about the origin and pathways of sublobular lymph, this study demonstrates pathways of interstitial fluid flowing into sublobular lymphatic vessels. Livers from cats whose thoracic ducts were either ligated or non-ligated were examined by light-, transmission electron- and scanning electron-microscopy (SEM). Complete ligation of the thoracic duct caused significant dilation of the hepatic sinusoids, the space of Disse, and channels passing through the limiting plate. Sublobular interstitial space and sublobular lymphatic vessels were also expanded. The channels between hepatocytes forming the limiting plate contained collagen fibers, and connected the space of Disse with a sublobular interstitial space. The alkali-water maceration/SEM confirmed that collagen fibers traversing the layer of the limiting plate independently of blood vessels connected collagen fibers in the space of Disse with those in the sublobular space. Complete ligation of the thoracic duct also showed an accumulation of mast cells and plasma cells in the sublobular interstitial space. Our data suggest that fluid in the space of Disse flows along collagen fibers in channels traversing the limiting plate as well as those along the sinusoids and central veins that drain into sublobular veins, and enters the sublobular interstitial space to finally lead into sublobular lymphatic vessels. Our study has also shown that hepatic lymphostasis causes the accumulation of mast cells and plasma cells in the sublobular interstitial space, which may be involved in lymphangiogenesis and fibrogenesis.     

Effect of a thin HA coating on the stress/strain distribution in bone around dental implants using three-dimensional finite element analysis

Three-dimensional finite element analysis was performed for thin hydroxyapatite (HA) coated and titanium dental implants to study the effects on stress/strain distribution in the mandible with application of axial and oblique loads. The implants were of screw and cylinder types. With an axial load, the maximum equivalent bone stresses in the titanium implants were 21.5 and 29.0 MPa for the cylinder and screw types respectively, and the stress and strain distributions differed. For the cylinder type, the highest stress was located at the implant base, and for the screw type, it was located at the top edge of the first thread within the cortical bone. For the HA-coated cylinder and screw implants, the maximum equivalent bone stresses were 7.1 and 7.2 MPa respectively. The stress and strain distributions were similar, and the highest stress was located on the upper side of the cortical bone around the implant neck for both implants. Of the implants examined, the screw type HA-coated implant had the most uniform stress distribution in bone.     

The importance of parent artery geometry in intra-aneurysmal hemodynamics

We show the importance of arterial geometry in intra-aneurysmal hemodynamics. Using a new geometric parameterized saccular aneurysm model including parameters for parent artery shape and the configuration of the aneurysm in the parent artery, we performed a parametric computational fluid dynamics study. We examined lateral saccular aneurysm models with different aneurysm shapes (i.e., the ratio of aneurysm height to aneurysm neck diameter) and different configurations (i.e., the torsion angle of the aneurysm to the upstream part of the parent artery). The aneurysm lateral to the curve of the parent artery had significantly higher wall shear stress than the aneurysm inside or outside the curve of the artery, even with the same shape of the aneurysm. Our findings suggest the important role played by the configuration of the aneurysm relative to the parent artery in intra-aneurysmal hemodynamics.     

Recombinant thrombomodulin ameliorates experimental autoimmune encephalomyelitis by suppressing high mobility group box 1 and inflammatory cytokines

Recombinant thrombomodulin (rTM) has pleiotrophic properties, including anti‐coagulation and anti‐inflammation; however, its effectiveness as a treatment for multiple sclerosis (MS) has not been evaluated fully. High mobility group box 1 (HMGB1) and proinflammatory cytokines, working as inflammatory mediators, are reportedly involved in the inflammatory pathogenesis of MS. The aim of this study was to determine whether rTM can be a potential therapeutic agent for experimental autoimmune encephalomyelitis (EAE). EAE mice received rTM treatment (1 mg or 0·1 mg/kg/day) from days 11 to 15 after immunization. The clinical variables, plasma levels of inflammatory cytokines and HMGB1 and pathological findings in EAE were evaluated. rTM administration ameliorated the clinical and pathological severity of EAE. An immunohistochemical study of the spinal cord showed weaker cytoplasmic HMGB1 staining in the rTM‐treated EAE mice than in the untreated EAE mice. Plasma levels of inflammatory cytokines and HMGB1 were suppressed by rTM treatment. In conclusion, rTM down‐regulated inflammatory mediators in the peripheral circulation and prevented HMGB1 release from nuclei in the central nervous system, suppressing EAE‐related inflammation. rTM could have a novel therapeutic potential for patients with MS.     

Measurement of Individual Red Blood Cell Motions Under High Hematocrit Conditions Using a Confocal Micro-PTV System

Developments in optical experimental techniques have helped in elucidating how blood flows through microvessels. Although initial developments were encouraging, studies on the flow properties of blood in microcirculation have been limited by several technical factors, such as poor spatial resolution and difficulty obtaining quantitative detailed measurements at such small scales. Recent advances in computing, microscopy, and digital image processing techniques have made it possible to combine a particle tracking velocimetry (PTV) system with a confocal microscope. We document the development of a confocal micro-PTV measurement system for capturing the dynamic flow behavior of red blood cells (RBCs) in concentrated suspensions. Measurements were performed at several depths through 100-μm glass capillaries. The confocal micro-PTV system was able to detect both translational and rotational motions of individual RBCs flowing in concentrated suspensions. Our results provide evidence that RBCs in dilute suspensions (3% hematocrit) tended to follow approximately linear trajectories, whereas RBCs in concentrated suspensions (20% hematocrit) exhibited transversal displacements of about 2% from the original path. Direct and quantitative measurements indicated that the plasma layer appeared to enhance the fluctuations in RBC trajectories owing to decreased obstruction in transversal movements caused by other RBCs. Using optical sectioning and subsequent image contrast and resolution enhancement, the system provides previously unobtainable information on the motion of RBCs, including the trajectories of two or more RBCs interacting in the same focal plane and RBC dispersion coefficients in different focal planes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Glucocorticoids Induce Cardiac Fibrosis via Mineralocorticoid Receptor in Oxidative Stress: Contribution of Elongation Factor Eleven-Nineteen Lysine-Rich Leukemia (ELL)

Background

Cardiac fibrosis is considered to be a crucial factor in the development of heart failure. Blockade of the mineralocorticoid receptor (MR) attenuated cardiac fibrosis and improved the prognosis of patients with chronic heart failure but the ligand for MR and the regulatory mechanism of MR pathway in the diseased heart are unclear. Here, we investigated whether glucocorticoids can promote cardiac fibrosis through MR in oxidative stress and the involvement of elongation factor eleven-nineteen lysine-rich leukemia (ELL), a co-activator of MR, in this pathway.

Methods and Results

The MR antagonist eplerenone attenuated corticosterone-induced collagen synthesis assessed by [³H]proline incorporation in rat neonatal cultured cardiac fibroblasts in the presence of H₂O₂, as an oxidative stress but not in the absence of H₂O₂. H₂O₂ increased the ELL expression levels and MR-bound ELL. ELL expression levels and MR-bound ELL were also increased in the left ventricle of heart failure model rats with significant fibrosis and enhanced oxidative stress. Eplerenone did not attenuate corticosterone-induced increase of [³H]proline incorporation in the presence of H₂O₂ after knockdown of ELL expression using small interfering RNA in cardiac fibroblasts.

Conclusion

Glucocorticoids can promote cardiac fibrosis via MR in oxidative stress, and oxidative stress modulates MR response to glucocorticoids through the interaction with ELL. Preventing cardiac fibrosis by modulating glucocorticoid-MR-ELL pathway may become a new therapeutic strategy for heart failure.