Decreased neural damage after spinal cord injury in tPA-deficient mice

Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin. It plays an important role in the nervous system, including the processes of neuronal migration, neurite outgrowth, and neuronal plasticity. tPA has also been suggested to have a role in several neuropathological conditions, such as cerebral ischemia, seizures, and demyelinating diseases. To investigate the role of tPA in spinal cord injury, wild-type mice and mice with homozygous tPA deficiency (tPA(-/-) mice) were subjected to spinal cord contusion and the differences of hindlimb function, electrophysiological changes, and histopathological changes were assessed for 6 weeks. Functional recovery was greater in tPA(-/-) mice than in wild-type mice throughout the observation period. The time course of myoelectric motor-evoked potentials supported the hindlimb functional findings. Histological examination showed that injured areas were smaller in tPA(-/-) mice than wild-type mice on Luxol fast blue staining or myelin basic protein and neurofilament protein immunostaining at 6 weeks after contusion. Electron microscopy showed that the white matter was better preserved in tPA(-/-) mice than in wild-type mice. The expression of tPA protein was widespread on the first day after contusion and this expression was detected for at least a week. Activation of microglia/macrophages and apoptotic cell death were significantly reduced in tPA(-/-) mice after contusion. This study shows that neural damage is decreased in tPA(-/-) mice after spinal cord injury. Suppression of tPA production may help to decrease secondary injury after spinal cord contusion.     

The office hysteroscopic evaluation of postmenopausal patients

Objective The objective was to characterize postmenopausal women with endometrial polyps and to evaluate their significance.Methods The study population included all consecutive postmenopausal patients with a diagnosis of endometrial polyps. Demographic, medical and gynecological data were assessed with regard to the endometrial histologic findings.Results Of the 181 eligible patients, 34 had endometrial hyperplasia (4 cases of them had endometrial carcinoma). The 144 patients using hormone replacement therapy had significantly higher rate of endometrial hyperplasia than non-hormone users (p<0.006). No differences were observed among the endometrial histological categories for any of the presenting symptoms and signs, ultrasonographic findings, or medical histories.Conclusion Postmenopausal endometrial polyps is a common, mostly benign entity. However, the relatively high rate of concomitant endometrial hyperplasia, especially in patients receiving hormone replacement therapy, dictates a thorough histological evaluation in all cases.     

Living related donor liver transplantation for primary sclerosing cholangitis with hepatocellular carcinoma and Crohn's disease: a case report

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a premalignant condition associated with a risk of developing cholangiocarcinoma in 10% to 20% of patients. However, the prevalence of hepatocellular carcinoma (HCC) in patients with PSC is estimated to be only 2%. In addition, PSC often occurs in association with inflammatory bowel disease. Ulcerative colitis occurs in 60% of PSC patients and Crohn's disease occurs in about 10%. We diagnosed a patient as having PSC with HCC and concomitant Crohn's disease prior to living related donor liver transplantation (LRDLT). PATIENTS AND METHODS: A 63-year-old woman was diagnosed as having PSC with solitary HCC. Preoperative liver condition was Child-Pugh grade C. Colonoscopic findings showed an active longitudinal ulcer in the terminal ileum and clinically diagnosed Crohn's disease. The medical treatment was 5'-aminosalicylates. She received a left lobe graft from her daughter. The immunosuppressants were tacrolimus and azathioprine, which was changed to predonisolone because of leukopenia and moderate acute cellular rejection, after which the postoperative course was uneventful. Colonoscopic findings revealed disappearance of the longitudinal ulcer in the terminal ileum at 15 months after LRDLT. There was no evidence of PSC or HCC recurrence. CONCLUSIONS: Generally, PSC with HCC is rare with a poor prognosis; however, LRDLT may be a treatments option although the patient with PSC had a combined HCC. Moreover, aminosalicylates together with the immunosuppressants may be effective for the clinical management of concomitant Crohn's disease.     

IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis

PURPOSE: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. EXPERIMENTAL DESIGN: Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. RESULTS: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. CONCLUSION: Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.     

Effect of linear alkylbenzene sulphonate (LAS) on non-specific defence mechanisms in rainbow trout (Oncorhynchus mykiss)

Linear alkylbenzene sulphonate (LAS) is among the most widely disseminated xenobiotics to enter waste streams and the aquatic environment. In the present investigation, we present a novel approach to evaluate in toxicity of LAS. The effects of sublethal levels (0.2 and 0.4 mg/l) of LAS on non-specific immune system, phagocytosis, respiratory burst and lyzosyme activity, and specific growth rate in the rainbow trout, Oncorhynchus mykiss, during a 54-day exposure were examined by a static bioassay test procedure. The phagocytic activity of leukocytes from fish exposed to 0.4 mg/l LAS statistically decreased compared with the control fish values. No significant reductions were observed in the extra-intracellular respiratory burst and lysozyme activities after exposure to LAS at any of the concentrations tested. The final body weight in fish groups exposed to the LAS were found to be significantly lower than in the control. The specific growth rate results also supported the result above. The results of this study showed sublethal doses (0.2-0.4 mg/l) of LAS caused to statistically insignificant suppression of non-specific immune system mechanisms excluding phagocytosis in fish at laboratory conditions. These doses of LAS may produce potential synergism on immune system when presented with other environmental pollutants.