TNF-α, nitric oxide and IFN-γ are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii

We previously reported that genetic susceptibility of mice to peroral infection with T. gondii is associated with CD4+ T cell-dependent, interferon (IFN)-gamma-mediated necrosis of their small intestine. We examined the role of tumour necrosis factor (TNF)-alpha and nitric oxide (NO), in addition to IFN-gamma. At 7 days after infection, a marked increase in CD4+ T cells was observed in lamina propria mononuclear cells (LPC) of the small intestine as compared with normal mice, and significantly greater amounts of mRNA for IFN-gamma, TNF-alpha, and inducible NO synthase (iNOS) were detected in LPC of the small intestine of infected than uninfected animals. Treatment of infected mice with anti-TNF-alpha monoclonal antibody (mAb) or the iNOS inhibitor, aminoguanidine, prevented necrosis and prolonged time to death. Infected iNOS-targeted mutant mice did not develop the disease whereas infected, control mice did. Treatment with anti-TNF-alpha mAb did not affect the expression of IFN-gamma in the LPC but inhibited expression of iNOS in the infected mice, indicating the role of TNF-alpha in the induction of iNOS. These results suggest that NO induced by a combination of IFN-gamma and TNF-alpha through activation of iNOS is a critical mediator of intestinal pathology and contributes to early mortality in genetically susceptible mice.     

Granular Cell Myoblastoma of the Gallbladder

A case of granular cell myoblastoma of the gallbladder in a 39-year old Japanese female is presented. Granular cell myoblastomas arising in the biliary tract are a rare occurrence. This tumor has not yet been reported in the gallbladder.     

胰岛素作用相关的蛋白酪氨酸磷酸酶及其抑制剂

胰岛素作用相关的蛋白酪氨酸磷酸酶及其抑制剂尹义存邹大进综述胰岛素受体（ＩＮＳＲ）是受胰岛素（ＩＮＳ）调节的酪氨酸蛋白激酶（ＰＴＫａｓｅ）。该受体与ＩＮＳ结合后发生自身磷酸化。受体调节区的某些位点的磷酸化最终可导致内在的酪氨酸（Ｔｙｒ）磷酸转移酶的激...     

Three-Dimensional Echocardiographic Evaluation of Aortic and Mitral Valve Stenosis

Dynamic volume rendered three-dimensional echocardiography allows the spatial recognition of anatomy and function of the aortic and mitral valves with acceptable image quality. The aortic valve can be best visualized in a view from the ascending aorta down to the valve level, thus allowing an overview of the aortic aspect of the valve in a surgeon's perspective in ∼ 80% of patients. Planimetric measurement of the aortic valve area was possible in 88% of patients, and there is no systematic overestimation or underestimation of aortic valve area compared with two-dimensional echocardiography and catheterization. The entire valvular circumference of the mitral valve can be assessed from both a left atrial and a left ventricular perspective. Advantages of the three-dimensional transesophageal echocardiography mitral valve area determination compared with transthoracic two-dimensional planimetry and Doppler-derived pressure half-time method are present in patients with severely calcified mitral valves and in those with combined aortic regurgitation.     

Evaluation of In-vivo Transdermal Absorption of Cyclosporin with Absorption Enhancer Using Intradermal Microdialysis in Rats

The purpose of this study was to evaluate the effect of absorption enhancer on in-vivo transdermal absorption of cyclosporin using intradermal microdialysis in rats. Cyclosporin oily solutions (0.5, 2, 8% w/v) were prepared from Sandimmun (10% w/v oily oral preparation of cyclosporin) by diluting with olive oil. 1-[2-(Decylthio)ethyl]azacyclopentan-2-one (HPE-101) and glycerin were added to the cyclosporin formulation as an absorption enhancer at various concentrations between 1 and 20%. These formulations were applied to the shaved abdomen of rats treated with intradermal microdialysis at a flow rate of 2.5 μL min^?1 for 6 h. Cyclosporin was immediately detected and attained a plateau in the dermal dialysate after topical application of cyclosporin oily solution alone. Cyclosporin levels in the dialysate increased with increasing cyclosporin concentrations in the formulation from 0.5 to 8% (w/v). HPE-101 did not influence cyclosporin absorption at concentrations less than 6% (w/v). Addition of 10% (w/v) HPE-101 significantly enhanced an apparent absorption rate of cyclosporin by 4.9 times. However, 20% (w/v) HPE-101 did not show the enhancing activity. On the other hand, addition of glycerin at concentrations of 6, 10, and 20% (v/v) significantly enhanced an apparent absorption rate of cyclosporin by 3.0, 64, and 6.9 times, respectively. The time lag for cyclosporin absorption was less than 0.21 h in all tested cases. This microdialysis study shows that glycerin is a suitable enhancer for improving the in-vivo cyclosporin absorption from the skin.