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Inhibitor development is one of the major adverse events associated with increased morbidity and mortality in patients with congenital hemophilia. Recent treatment for them is immune tolerance induction (ITI), which involves the administration of high doses of factor concentrates over a prolonged period, sometimes combined with immunosuppressive agents. We report a case of inhibitor elimination with Rituximab, and high-dose factor VIII concentrates in a 5-year-old boy with hemophilia A. The patient improved clinically, with fewer bleeding episodes. However, he continued to have low immunoglobulin levels, which led to recurrent infections. After an infusion of intravenous immunoglobulin, inhibitor titers increased rapidly and his ITI was deemed a failure. In conclusion, even though it failed in the present study, Rituximab may be an alternative adjuvant therapy to eliminate the inhibitor in patients with hemophilia. The appropriate schedule and long-term side effects need further investigation.
Sparstolonin B (SsnB) exists in the tubers of Scirpus yagara and Sparganium stoloniferum, and it is known to modulate inflammatory mediators. Here, we investigated whether SsnB could reduce the renal functional damage in a cecal ligation and puncture (CLP)-induced septic mice. The effect of SsnB was measured via assessment of blood urea nitrogen (BUN), serum creatinine, total glutathione, lipid peroxidation, catalase activity, glutathione peroxidase activity, and superoxide dismutase activity. Our findings showed that SsnB treatment in mice with CLP-induced renal damage elevated the BUN and creatinine levels in plasma and protein levels in the urine. In contrast, the excessive production of nitric acid and induction of nitric oxide synthase were decreased. Moreover, SsnB inhibited the activation of nuclear factor-kappa B, reduced the plasma levels of tumor necrosis factor-α and interleukin-6, and thus reduced lethality. SsnB also increased lipid peroxidation and restored the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues, thereby enhancing the antioxidant defense system. Conclusively, our results indicate that SsnB can protect mice from sepsis-induced renal injury.
Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report preclinical studies for Ad-stTRAIL carried out using rats. We delivered Ad-stTRAIL intracranially and determined its pharmacokinetics and biodistribution. Most Ad-stTRAIL remained in the delivered site and the relatively low number of viral genomes was detected in the opposite site of brain and cerebrospinal fluid. Similarly, only small portion of the viral particles injected was found in the blood plasma and major organs and tissues, probably due to the brain-blood barrier. Multiple administrations did not lead to accumulation of Ad-stTRAIL at the injection site and organs. Repeated delivery of Ad-stTRAIL did not show any serious side effects. Our data indicate that intracranially delivered Ad-stTRAIL is a safe approach, demonstrating the potential as a novel therapy for treating gliomas.
Seed zones were constructed using temperature and precipitation data for the Korean Peninsula and were described as 65 zones. Seed zones for South Korea were reclassified, and they were classified into 34 districts. This study was conducted to define the spread of 5 native seed species (Pinus densiflora, Quercus acutissima, Quercus variabilis, Acer pictum, Carpinus tschonoskii) by linking the seed zones with MaxEnt. The emergence point of native seeds was acquired through the 1:5,000 Forest Type Map and the 4th national natural environment survey data. Based on the MaxEnt result, regions with a habitat probability of 0.5 or more were extracted and overlapped with seed zones to identify the native seed habitat. After analyzing the climate regions with high habitat density, regions with high habitat density of native seeds for each administrative district were identified. In the case of Pinus densiflora, Quercus acutissima, and Quercus variabilis, the Winter minimum temperature(WMT) -9.4~-6.6℃, Annual Heat:Moisture(AH:M) 19~24℃/m was 37%, 43%, and 34%, respectively. occupied the largest area. In Acer pictum, WMT -6.6~-3.8℃ and AH:M 16~19℃/m accounted for 42% of the area, and Carpinus tschonoskii had WMT -3.8~-1.1℃, AH:M <16℃/m Districts accounted for the largest area at 33%. The regions with high density of Pinus densiflora, Quercus acutissima, and Quercus variabilis by administrative district were distributed in high density in Seoul, Southern Gyeonggi-do, Chungcheong-do, and Gyeongsangbuk-do. Acer pictum was distributed in high density in Jeolla-do and Gyeongsang-do, and Carpinus tschonoskii in Jeju, Jeollanam-do and Gyeongsangnam-do. Through this study, seed zones for each of the 5 native seeds were established, and it is expected to provide basic data for the management of native seeds.