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Volume 221 (2010)
- Issue 4 Pages 257-
- Issue 3 Pages 175-
- Issue 2 Pages 87-
- Issue 1 Pages 1-
Volume 221, Issue 4
August
Displaying 1-8 of 8 articles from this issue
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Michiko Yokosawa, Yukihiko Sonoda, Shin-Ichiro Sugiyama, Ryuta Saito, ...2010 Volume 221 Issue 4 Pages 257-264
Published: 2010
Released on J-STAGE: July 07, 2010
JOURNAL FREE ACCESSPrognosis for the patients with glioblastoma, the most common malignant brain tumor, remains dismal. A major barrier to progress in treatment of glioblastoma is the relative inaccessibility of tumors to chemotherapeutic agents. Convection-enhanced delivery (CED) is a direct intracranial drug infusion technique to deliver chemotherapeutic agents to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED can provide wider distribution of infused agents compared to simple diffusion. We have reported that CED of a polymeric micelle carrier system could yield a clinically relevant distribution of encapsulated agents in the rat brain. Our aim was to evaluate the efficacy of CED of polymeric micellar Am80, a synthetic agonist with high affinity to nuclear retinoic acid receptor, in a rat model of glioblastoma xenografts. We also used systemic administration of temozolomide, a DNA-alkylating agent, which has been established as the standard of care for newly diagnosed malignant glioma. U87MG human glioma cells were injected into the cerebral hemisphere of nude rats. Rats bearing U87MG xenografts were treated with CED of micellar Am80 (2.4 mg/m2) on day 7 after tumor implantation. Temozolomide (200 mg/m2/day) was intraperitoneally administered daily for 5 days, starting on day 7 after tumor implantation. CED of micellar Am80 provided significantly longer survival than the control. The combination of CED of micellar Am80 and systemic administration of temozolomide provided significantly longer survival than single treatment. In conclusion, temozolomide combined with CED of micellar Am80 may be a promising method for the treatment of malignant gliomas.View full abstractDownload PDF (904K) -
Xiangwei Kong, Meng Cao, Ruidong Ye, Yin Ding2010 Volume 221 Issue 4 Pages 265-270
Published: 2010
Released on J-STAGE: July 08, 2010
JOURNAL FREE ACCESSMalocclusion, the improper positioning of the teeth and jaws, is among the most important global oral health burdens. People with malocclusion may require orthodontic treatment to correct the problem. Orthodontic treatment is a way of straightening or moving teeth, to improve the appearance of the teeth and how they work. It is generally best carried out in children aged 9 to 12 years, whose teeth are mainly young permanent teeth with incomplete root formation. However, the relationship between orthodontic force and tooth development has not been fully understood. In this study, we sought to investigate the effects of orthodontic force on dentine formation and mineralization during the development of young permanent teeth. Standardized orthodontic tooth movement was performed with the orthodontic appliance in five-week-old rats. To obtain longitudinal assessment of dentine formation, tetracycline was administered on the operation day and 1, 3, 7, 14 or 21 days afterward. We found that the distance between two tetracycline stripes, which indicates the amount of dentine formation during orthodontic treatment, increased with time. Importantly, no significant difference was detected in dentine formation between treated and control rats. In contrast, immunohistochemical analysis showed that the expression of dentin sialoprotein, a marker of odontoblast differentiation and mineral apposition, was significantly elevated in crown and root dentine after orthodontic treatment. In conclusion, orthodontic treatment does not affect the dentine formation of young permanent teeth, but it promotes the activation of odontoblasts and accelerates the dentine mineralization. These results suggest the safety of early orthodontic treatment.View full abstractDownload PDF (1856K) -
Francisco Urrea, Blanca Ortiz-Quintero, Francisco Javier Sanchez-Garci ...2010 Volume 221 Issue 4 Pages 271-279
Published: 2010
Released on J-STAGE: July 13, 2010
JOURNAL FREE ACCESSActivation of CD4+ T cells plays a main role in adaptive immune response by regulating cellular and humoral immunity via processes associated with changes in cell surface oligosaccharide receptors. Lectins are glycoproteins that specifically recognize oligosaccharides and have been used to characterize changes in oligosaccharides present on T cell surface and their effects on activation. A lectin from Amaranthus leucocarpus seeds (ALL) is specific for glycoprotein structures containing galactose-N-acetylgalactosamine and is able to bind to human and murine CD4+ T cells, however, its effect on activation remains unclear. We examined the effect of ALL on the activation of peripheral blood human CD4+ T cells and analyzed cell proliferation, expression of the activation-associated molecule CD25, secretion of the activation-dependent cytokine interleukin (IL)-2 and intracellular calcium influx changes using flow cytometry. CD4+ T cells were stimulated with anti-CD3 antibodies that provided the first activation signal in the presence or absence of ALL. ALL alone did not induce CD4+ T cell activation but when also stimulated with anti-CD3 antibodies, ALL up-regulated CD25 expression, cell proliferation, IL-2 secretion and an intracellular calcium influx in a dose-dependent manner. In addition, ALL recognized CD4+ T cells expressing the CD69 and Ki67 molecules expressed only by activated T cells and induced production of the TH1-type cytokine interferon-γ. Our findings indicate that ALL binds to human activated CD4+ T cells and enhances the degree of activation of CD4+ T cells that are stimulated with anti-CD3 antibodies. ALL provides a new tool for analyzing T cell activation mechanisms.View full abstractDownload PDF (1132K) -
Yi-Chun Chen, Yu-Chun Chen, Li-Fang Chou, Tzeng-Ji Chen, Shinn-Jang Hw ...2010 Volume 221 Issue 4 Pages 281-285
Published: 2010
Released on J-STAGE: July 13, 2010
JOURNAL FREE ACCESSAdrenal insufficiency (AI), a life-threatening disorder, usually starts with variable nonspecific symptoms and signs of poor appetite, fatigue, fever, and gastrointestinal discomfort, and may progress to adrenal crisis with complications of electrolyte imbalance, change of consciousness or even shock. Epidemiological data about AI in the elderly population are limited. Based on nationwide hospitalization datasets in Taiwan, we retrospectively analyzed the annual incidence of AI among the elderly population (≥ 60 years old), as well as co-morbidities. The prevalence of AI increased from 6.5/105 (n = 1,293) in 1996 to 20.8/105 (n = 4,681) in 2007. In 2006, AI was newly diagnosed in 3,494 patients (1,701 women and 1,793 men), which represented an incidence of 15.5/105 in the whole population. Nearly four fifths (1,349 women and 1,429 men) of the patients were 60 years old and over, corresponding to an incidence of 92.4/105 in the elderly population. The most common co-morbidities were pneumonia (8.6%, n = 238) and urinary tract infections (6.9%, n = 193). Within the one-year observation after discharge, pneumonia was also the most frequent diagnosis in subsequent hospitalizations; besides, 178 (6.5%) patients died in the hospital and the common causes of death were respiratory failure (n = 34), septicemia (n = 23), pneumonia (n = 16), and chronic obstructive pulmonary disease (n = 9). In conclusion, the majority of the elderly have co-morbidities when AI was initially diagnosed. Infectious and pulmonary diseases as the most common co-morbidities also play a major role in subsequent hospitalizations and in-hospital deaths.View full abstractDownload PDF (169K) -
Shizuko Akiyama, Hidenobu Ohta, Shimpei Watanabe, Takahiro Moriya, Aya ...2010 Volume 221 Issue 4 Pages 287-298
Published: 2010
Released on J-STAGE: July 16, 2010
JOURNAL FREE ACCESSMaternal circadian information has been reported to play an important role in fetal physiology and development. Hormones and nutrition have been mainly investigated as circadian cues from mother to fetus. However, the influences of circadian properties of the pregnant reproductive organs on fetuses have not been fully investigated. To gain an insight on the circadian functions of the reproductive organs, we examined molecular clocks in the pregnant rat uterus and placenta. By using a Period1-luciferase (Per1-luc) rat, whose tissues express luciferase corresponding to activation of Period1, a “key clock gene”, we examined the uterus clock during non-pregnancy, on embryonic day 12 (E12), and on E22 (the end of pregnancy) in a light-dark (LD) cycle and constant darkness (DD). By in situ hybridization we further explored Per1 mRNA rhythms in the placenta on E12 and E22. The uterus in vitro showed clear circadian Per1-luc rhythms both in and out of pregnancy, having peaks at around the time corresponding to dusk in LD. Likewise, in DD, the uterus in vitro had the same Per1-luc rhythms. The decidua in LD showed circadian Per1 mRNA rhythms, peaking during night 6 h after dusk, while the decidua in DD showed the same Per1 mRNA rhythms only on E22. In contrast, the labyrinth showed no circadian Per1 mRNA rhythms in LD or DD during pregnancy. These results suggest that the uterus and decidua, a maternally-originated tissue of the placenta, but not the labyrinth, a fetus-originated tissue of the placenta, can provide the fetus with circadian information.View full abstractDownload PDF (4481K) -
Yang Ho Kang, Jung Sook Jin, Dong Won Yi, Seok Man Son2010 Volume 221 Issue 4 Pages 299-307
Published: 2010
Released on J-STAGE: July 16, 2010
JOURNAL FREE ACCESSVascular calcification refers to the deposition of calcium phosphate in cardiovascular tissues, including arteries and myocardium. Vascular calcification is frequently associated with cardiovascular disease. Recently, bone morphgenetic protein-7 (BMP-7) has been proposed to play an inhibitory role in vascular calcification, but its inhibitory effect has not been fully elucidated. We therefore tested the hypothesis that BMP-7 inhibits vascular calcification by using two conditions, high levels of vitamin D and phosphate, each of which could enhance vascular calcification. C57BL/6 mice were treated for 3 days with high vitamin D (500,000 IU/kg/day) in the presence or absence of recombinant human BMP-7 (rhBMP-7). Expression levels of osteopontin and osteocalcin, markers of the osteoblastic phenotype, were assessed by immunohistochemical staining or Western blotting analysis. Vitamin D increased calcium staining in thoracic aortas and hearts and the expression levels of osteopontin and osteocalcin in mice. Importantly, pretreatment for 7 days and subsequent treatment for 3 days with rhBMP-7 (10 μg/kg/day) abolished the vitamin D-mediated increases in the above parameters. In addition, human aortic smooth muscle cells (HASMCs) were cultured with high β-glycerophosphate, a phosphate donor, for 2 weeks in the presence or absence of rhBMP-7. High β-glycerophosphate increased expression levels of osteopontin and osteocalcin as well as calcium staining in HASMCs, but these changes were attenuated by treatment with BMP-7. Thus, BMP-7 inhibits vascular calcification associated with high levels of vitamin D or phosphate. We propose that BMP-7 treatment may be helpful in reducing the risks of cardiovascular disease related to vascular calcification.View full abstractDownload PDF (2629K) -
Yoko Nakajima, Tetsuya Ito, Yasuhiro Maeda, Sayaka Ichiki, Naruji Sugi ...2010 Volume 221 Issue 4 Pages 309-313
Published: 2010
Released on J-STAGE: July 21, 2010
JOURNAL FREE ACCESSSome oral antibiotics contain a pivalate ester, because molecules with a pivalate entity show enhanced absorption in the intestine. Upon absorption, such a “prodrug” is broken down into the active form of a given antibiotic and a pivalate molecule, the latter of which is converted to pivaloylcarnitine through pivaloyl-CoA and is excreted in the urine. Long-term administration of drugs containing pivalate decreases blood carnitine level and causes defects in fatty acid oxidation. Here, we used liquid chromatography tandem mass spectrometry to measure carnitine and pivaloylcarnitine levels in two patients (Patient 1: 16-month-old boy and Patient 2: 18-month-old boy) with secondary carnitine deficiency and hypoglycemic convulsions caused by pivalate-containing antibiotics. Both patients were administered excessive doses of pivalate for the long-term treatment of recurrent infection, and consequently, the serum free carnitine levels were very low (Patient 1: 1.0 μmol/L and Patient 2: 0.4 μmol/L), compared to normal range of 33.3-43.0 μmol/l, while the serum pivaloylcarnitine levels were elevated from normally undetectable level (Patient 1: 3.7 μmol/L and Patient 2: 1.6 μmol/L). Patient 1 recovered immediately after the glucose infusion, whereas Patient 2 remained symptomatic even after blood glucose level was normalized and fully recovered after carnitine supplementation. The urine pivaloylcarnitine level in Patient 2 was increased during carnitine supplementation (from 821.4 to 12,200 μmol/g creatinine) even after discontinuing the antibiotics, indicating that a considerable amount of pivalate was accumulated in the tissues. In conclusion, long-term administration of pivalate-containing antibiotics should be avoided particularly in children.View full abstractDownload PDF (481K) -
Mariko Takayama, Yoko Kuramoto, Ryuhei Okuyama, Kenshi Yamasaki, Setsu ...2010 Volume 221 Issue 4 Pages 315-319
Published: 2010
Released on J-STAGE: July 24, 2010
JOURNAL FREE ACCESSPressure ulcers (PUs) are chronic wounds that occur as areas of tissue necrosis that results from external physical compression, shear forces, and friction. Recently, the efficacy of polyvinylidene film dressing (PVFD) for PUs without any agents promoting wound healing has been reported, suggesting that PUs have their own mechanism of spontaneous healing achieved by vascularization, synthesis of extracellular matrix, and re-epithelization. Since vascular endothelial growth factor (VEGF) 165 and fibroblast growth factor 2 (FGF-2) are released at traumatic or surgical wound sites and play major roles in vascularization and wound healing, we measured the concentrations of VEGF165 and FGF-2 in the exudate and fibrinous sloughs of PUs after PVFD. We collected 10 exudate samples and 3 samples of fibrinous sloughs from 10 PUs of 9 patients immediately after PVFD for 8 h and measured VEGF165 and FGF-2 by ELISA. All 10 exudate samples contained substantial amounts of VEGF165, from 2.79 to 13.27 μg g-1, irrespective of the severity of the PUs. In contrast, we detected FGF-2 (0.21 and 2.03 μg g-1) in only two exudate samples. Similarly, we detected VEGF165 (from 3.14 to 5.93 μg g-1) and FGF-2 (less than 0.31 μg g-1) in fibrinous sloughs of 3 PUs. These results demonstrate that the exudate and fibrinous sloughs of PUs contain considerable amounts of VEGF, which would contribute to the spontaneous healing of PUs by PVFD. The presence of VEGF165 in the exudate of PUs inspires us to reconsider the treatment strategy of PUs that enhances the spontaneous healing.View full abstractDownload PDF (349K)
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