Down-regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis

BACKGROUND: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l-arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis. METHODS: We conducted histological studies on 18 kidneys of six-week-old-rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor-beta1 (TGF-beta1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting. RESULTS: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF-beta1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 +/- 52.60 vs. 221.19 +/- 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 +/- 0.42 vs. 0.14 +/- 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 +/- 0.78 vs. 14.00 +/- 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF-beta1 level and tubular cell apoptosis. CONCLUSION: Our study confirmed the down-regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.     

Modulation of carcinogenicity in 1,2,3,4-tetrahydro-7,12- dimethylbenz[a]anthracene (THDMBA) by fluorine substitution: crystal structures of the 5- and 6-fluoro regioisomers.

1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) is an animal carcinogen which lacks an aromatic bay-region and shows promise as a model to investigate non-classical mechanisms of carcinogenesis. The fluorine-substituted derivatives at positions 5 and 6 on the B-ring exhibit a striking range of oncogenic potential wherein the 6F-THDMBA is twice as potent as the parent carcinogen, but the 5F-THDMBA is virtually inactive. To study structure-reactivity relationships for these fluorine regioisomers, we have determined the three-dimensional structures of the compounds by single-crystal X-ray diffraction. These crystal structures are the first such to be reported for any monofluoro anthracene (or pyrene) derivative. The partially-reduced A-ring exists in both enantiomeric half-chair conformers in the crystalline state, and the compounds have quasi-planar anthracene ring systems which exhibit a right-handed twist in the 'beta'-conformer, with the expected opposite twist in the other. A complete analysis of bond lengths, bond angles and torsion angles is presented. Preliminary electrostatic potentials have been derived from the X-ray data sets, and the results indicate significant differences in potential between 5F- and 6F-THDMBA at positions near the partially reduced bay region. Such results are likely to be of importance in the understanding of metabolic activation to reactive intermediates capable of bonding covalently to DNA.     

Magnetic resonance in the staging of multiple myeloma]

The authors retrospectively reviewed the MR examinations of 46 patients with clinical and laboratory findings of monoclonal gammopathies (MG). All cases had been submitted to radiographic examination which had shown skeletal involvement in 22 cases and osteoporosis in 11, with rupture of the vertebral body in 3 patients. Scintigraphy had been performed on all patients and CT on 12; 36 patients were subsequently submitted to follow-up (at 6, 12 and 24 months). MR examinations were performed with dedicated coils and standard sequences for the subjects with skeletal localizations on X-ray images. The extant cases, with no radiographic evidence of skeletal involvement, were submitted to MRI of the spine, skull and pelvis. In agreement with clinical and laboratory findings and with follow-up results (in 36 patients), MRI diagnosed MG with no skeletal involvement in 13 cases, osteoporosis in 8 (with rupture of the vertebral body in 2), asymptomatic non-progressive myeloma in 4, solitary myeloma in 3, and multiple myeloma in 18 cases. The good identification of bone marrow and its multiplanarity make MRI the method of choice in the study of patients with suspected or known gammopathies. If compared with other modalities, MRI is more sensitive and accurate in depicting the tumor, its size and relationship to periskeletal tissues, and its possible multifocality. Moreover, the technique has proven to be a valid tool during the follow-up, showing tumor response to therapy.     

Lumbar disk herniation: MR imaging assessment of natural history in patients treated without surgery.

The aim of this study was to evaluate the evolution of lumbar disk herniation in patients treated without surgery. Sixty-nine patients with a lumbar disk herniation proved at magnetic resonance (MR) imaging underwent a follow-up MR imaging study. The disk herniations evaluated during both MR imaging examinations were measured and classified into four categories according to the change in size that occurred. The patients were also divided into three clinical classes on the basis of the clinical outcome. Sixty-three percent of the patients showed a reduction of disk herniation of more than 30% (48% had a reduction of more than 70%), while only 8% demonstrated worsening of the clinical picture. These findings suggest that lumbar disk herniation may be primarily a medical (nonsurgical) disease and that MR imaging could play an important role in management of and research into the disorder.     

Recurrent cerebral venous infarcts and superior vena cava obstruction: case report

Abstract We report a patient with repeated venous infarcts in the occipital lobe and occlusion of the superior vena cava. The pathogenetic relationships between the superior vena cava occlusion and the brain infarcts are discussed. High pressure in the superior venous territory and incomplete patency of the transverse sinus are probably responsible for the venous infarcts. Received: 12 July 1996 Accepted: 27 August 1996     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Magnetic resonance in the evaluation of intracranial aneurysms

Eighteen patients affected by intra-cranial aneurysms, with size ranging from 3 to 30 mm, were studied by means of MRI, CT, and angiography. MRI was performed using Spin-Echo (SE) sequences with different Repetition Times (TR) and Echo Times (TE), which allowed the characterization of the lesions in relation to the relaxation times. MRI could identify all the aneurysms. In 13 subjects the parent vessels could be seen. In 5 patients the aneurysms could be recognized only after angiography, due to their dimension (less than 4 mm). The "flow effects" and the presence of methemoglobin and hemosiderin in the thrombosed portion of the lumen allowed both the detection of flow abnormalities and the characterization of laminate intra-aneurysmal thrombosis. In conclusion, MRI appears to be a sensitive methodology in the detection of intracranial aneurysms, even more sensitive than CT and Angiography in characterizing this kind of lesions.     

人骨髓间质干细胞体外扩增和向内皮细胞定向诱导分化的研究

目的：体外分离、扩增成人骨髓间质干细胞（MSCs）和向内皮细胞（ECs）定向诱导分化，开辟心血管组织工程种子细胞的新来源。 方法： 采用Percoll(1 073 g/L)从正常成人骨髓中分离出MSCs，纯化和扩增后流式细胞仪鉴定其纯度；用血管内皮生长因子(VEGF)诱导MSCs向ECs分化，Ⅷ因子(vWF)免疫组化和透射电镜(TEM)鉴定细胞性质。 结果： 5.0×105个MSCs在体外扩增15代后，获得8.0×1012个MSCs，扩增了约1.6×107倍；MSCs在加入VEGF诱导培养大约14-21 d，80%-90%的诱导细胞对Ⅷ因子相关抗原呈阳性反应；TEM可观察到胞浆内有Weible-palade小体，证实为ECs。 结论： 成人骨髓MSCs在体外具有定向诱导分化为ECs的潜能，这为心脏组织工程瓣体外构建, 尤其是在小儿先天性心脏病组织工程研究中种子细胞的来源提供了可能性。     

Direct ultrastructural evidence of target-directed polarization by cytotoxic lymphocytes in lesions of human graft-vs-host disease

Cytotoxic lymphocytes are thought to kill target cells by means of potent cytotoxic granules that congregate near the microtubular organizing center and the Golgi apparatus at one pole of the killer cell. We searched for evidence of this type of polarization in 12 lip biopsy specimens from patients with acute and/or chronic graft-vs-host disease (GVHD) compared with two lip specimens from normal individuals. Lymphocytes with such polarization were found in contact with epithelial cells of the squamous mucosa in all 12 cases of GVHD, and cells of the cuboidal minor salivary duct epithelium were found in two of 11 evaluable cases. The data add support to the hypothesis that cytolytic lymphocytes attack epithelial cells in GVHD.