Analysis of soot formation in a rapeseed oil-fueled diffusion flame: focusing on the importance of soot in Nara sumi.

Nara sumi is a traditional Japanese craft that has been handed down in Nara since ancient times, and now plays a major role as a regional resource. Soot is considered to be one of the most important materials for its quality. However, the making process has been supported solely by the rule of thumb for craftsmen for many years, and there is very little scientific understanding of that. Therefore, we are focusing on the soot formation process in this study. Soot was collected from different heights in a rapeseed oil-fueled diffusion flame and analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. As a result, it was confirmed that the formation of the soot shape completes at the bottom of the outside of the flame and that the shape does not change thereafter. It was also confirmed that the oxidation of soot occurs at the bottom of the outside of the flame. These results are expected to contribute to the further scientific understanding of the soot formation process.

Continuous infusion of substance P inhibits acute, but not subacute, inflammatory pain induced by complete Freund's adjuvant.

Previous studies have reported that continuous infusion with substance P (SP) into rat dorsal striatum ameliorated both mechanical allodynia in both formalin-evoked transient inflammatory pain and neuropathic pain models. However, a role of striatal SP in persistent inflammatory pain has not been demonstrated. The current study examined the effect of continuous infusion of SP into the rat dorsal striatum by reverse microdialysis on persistent inflammatory pain induced by complete Freund's adjuvant (CFA). Intraplantar injection of CFA evoked both mechanical allodynia and paw edema 3 and 7 days post-injection. The continuous infusion of SP ameliorated the CFA-evoked mechanical allodynia, but not paw edema, 3 days after the CFA injection. This antinociceptive effect of SP was partially inhibited by co-infusion with the neurokinin-1 (NK1) receptor antagonist CP96345. Conversely, at 7 days both CFA-evoked mechanical allodynia and paw edema were not affected by SP treatment. To clarify why the effect of SP treatment on CFA-induced pain changed, we evaluated NK1 receptor protein levels at both time points. The NK1 receptor protein level was decreased at 7, but not 3, days post CFA injection. These data suggest that persistent inflammatory pain can downregulate the striatal NK1 receptor. The current study demonstrates that striatal SP-NK1 receptor pathway can exert antinociceptive effect only on the third days of inflammatory pain phase defined as an acute but not the 7 days defined as a subacute.

Continuous infusion of substance P into rat striatum relieves mechanical hypersensitivity caused by a partial sciatic nerve ligation via activation of striatal muscarinic receptors.

Previous studies have demonstrated that continuous substance P (SP) infusion into the rat striatum attenuated hind paw formalin-induced nociceptive behaviors and mechanical hypersensitivity via a neurokinin-1 (NK1) receptor dependent mechanism. However, whether there is a role of striatal infusion of SP on chronic, neuropathic pain has yet to be demonstrated. The present study investigated the effect of continuous SP infusion into the rat striatum using a reverse microdialysis method is antinociceptive in a rat model of chronic, mononeuropathic pain. Two weeks after partial sciatic nerve injury, the ipsilateral hind paw demonstrated mechanical hypersensitivity. Infusion of SP (0.2, 0.4, or 0.8 µg/mL, 1 µL/min) for 120 min into the contralateral striatum dose-dependently relieved mechanical hypersensitivity. The antinociceptive effect of SP infusion was inhibited by co-infusion with the NK1 receptor antagonist CP96345 (10 µM). Neither ipsilateral continuous infusion nor acute microinjection of SP (10 ng) into the contralateral striatum was antinociceptive. A role of striatal muscarinic cholinergic neurons is suggested since co-infusion of SP with atropine (10 µM), but not the nicotinic receptor mecamylamine (10 µM), blocked antinociception. The current study suggests that activation of striatal muscarinic receptors through NK1 receptors could be a novel approach to managing chronic pain.

Reaction of thymidine and ascorbic acid induced by UV in the presence of salicylic acid.

When a neutral solution of thymidine and ascorbic acid was irradiated with UV light of wavelength longer than 300 nm in the presence of salicylic acid as a photosensitizer, six product peaks appeared in an HPLC chromatogram in addition to small amounts of thymidine dimers. The six products were identified as three pairs of diastereomers of 5-(2-deoxy-2-l-ascorbyl)-5,6-dihydrothymidine, 5-(2-l-ascorbyl)-5,6-dihydrothymidine, and 5,6-dihydrothymidine. These results suggest that novel DNA damage may be generated by ascorbic acid with salicylic acid induced by sunlight.

Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury-model mice via suppression of TNF-α expression in the spinal cord.

BACKGROUND: Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism of the analgesic effect of GJG in a chronic constriction injury model. RESULTS: GJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p<0.0001; cold-plate test, p<0.0001; hot-plate test p»0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-a in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-a was co-expressed in Iba1-positive cells at day 3 post-operation. GJG decreased the phosphorylation of p38 in the ipsilateral dorsal horn. Moreover, intrathecal injection of tumor necrosis factor-a opposed the anti-allodynic effect of GJG in the cold-plate test. CONCLUSIONS: Our data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-a expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation.

Go-sha-jinki-Gan (GJG), a traditional Japanese herbal medicine, protects against sarcopenia in senescence-accelerated mice.

Sarcopenia is characterized by age-associated skeletal muscle atrophy and reduced muscle strength; currently, no pharmaceutical treatment is available. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine that is used to alleviate various age-related symptoms, especially motor disorders. Here, we investigated the effect of GJG on aging-associated skeletal muscle atrophy by using senescence-accelerated mice (SAMP8). Immunohistochemical and western blotting analyses clearly showed that GJG significantly reduced the loss of skeletal muscle mass and ameliorated the increase in slow skeletal muscle fibers in SAMP8 mice compared to control mice. The expression levels of Akt and GSK-3ß, the phosphorylation of FoxO4, and the phosphorylations of AMPK and mitochondrial-related transcription factors such as PGC-1α were suppressed, while the expression of MuRF1 increased in SAMP8 mice, but approximated that in senescence-accelerated aging-resistant (SAMR1) mice after GJG treatment. We demonstrate for the first time that GJG has a therapeutic effect against sarcopenia.

Efficacy of traditional Japanese herbal medicines-Keishikajutsubuto (TJ-18) and Bushi-matsu (TJ-3022)-against postherpetic neuralgia aggravated by self-reported cold stimulation: a case series.

OBJECTIVES: It has been reported that postherpetic neuralgia (PHN) in patients over 60 years of age is aggravated under cold stimulation and is often difficult to treat. Keishikajutsubuto (TJ-18) and Bushi-matsu (TJ-3022) are traditional Japanese herbal medicines and have long been used to treat neuralgia and arthralgia, which are aggravated following cold stimulation. This study was designed to evaluate the effectiveness of combined TJ-18 and TJ-3022 therapy in cases of PHN aggravated by self-reported cold stimulation. DESIGN: Fifteen (15) PHN patients aged 60 years and over were examined. Patients were aware of the persistent pain despite other treatments; pain was generally aggravated following exposure to cold stimulation. First, TJ-18 (7.5 g/day) was administered to patients, and then TJ-3022 (1.0 g/day) was also administered and progressively increased by 0.5-1.0 g increments every 2-4 weeks, until stable improvement was achieved, which was rated using the visual analogue scale (VAS). Analgesic effects were evaluated using the VAS during each patient visit. OUTCOME MEASURES: Background variables, responses to treatment (time course of VAS rating, VAS improvement rate), the amount of additional TJ-3022 administered, and adverse reactions were analyzed. RESULTS: Twelve (12) of the 15 patients completed the entire trial. Patient ages were 61-85 years, the male-to-female ratio was 4:8, and length of time after onset of herpes zoster was 2-92 months. In 3 patients, oral TJ-18 treatment was not possible due to hot flash or gastric discomfort. The VAS improvement rate for patients being orally administered both TJ-18 and TJ-3022 was 76.5±27.7% (mean±standard deviation). The additional TJ-3022 dose was 1.0-5.0 g/day. Twelve (12) patients have been treated without serious adverse reactions. CONCLUSIONS: TJ-18 and TJ-3022 combination treatment is a promising means of treating intractable PHN, which has a self-reported tendency to aggravate pain under cold stimulation.

Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB.

Nuclear factor (NF)-κB has been shown to be associated with cancer resistance to radiotherapy (RT), and is constitutively active in the murine osteosarcoma cell line, LM8. Parthenolide has been reported to show antitumor activity through inhibition of the NF-κB pathway. In this study, we investigated the radio-sensitizing activity of parthenolide. We established Luc-LM8, a stable transfectant reporter construct of NF-κB transcriptional activity into LM8. Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were cultured with or without parthenolide treatment, irradiated, and subjected to cell viability and apoptosis assays. In vivo, to investigate whether parthenolide enhances radio-sensitivity of tumors, a tumor growth assay was conducted. Parthenolide enhanced the growth inhibitory effect of RT and induced the apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was significantly suppressed in the mice treated with parthenolide and RT. The present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation. Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing drug for use in cancer RT.

Parthenolide, a natural inhibitor of Nuclear Factor-kappaB, inhibits lung colonization of murine osteosarcoma cells.

PURPOSE: The transcription factor nuclear factor-kappaB (NF-kappaB) regulates the expression of several genes important for tumor metastasis and is constitutively active in the highly metastatic murine osteosarcoma cell line LM8. Parthenolide, a sesquiterpene lactone, was reported to inhibit the DNA binding of NF-kappaB. The purpose of this study is to investigate the usefulness of parthenolide as target for antimetastatic therapies. EXPERIMENTAL DESIGN: We examined the effect of parthenolide on metastasis-associated phenotypes in vitro and in murine experimental lung metastasis models by s.c. and i.v. inoculation of LM8 cells. RESULTS: We found that parthenolide strongly induced apoptosis and inhibited cell proliferation and the expression of vascular endothelial growth factor in vitro. In the in vivo metastasis models, parthenolide treatment suppressed lung metastasis when treatment was initiated concurrently with s.c. or i.v. inoculation of tumor cells, whereas lung metastasis was not reduced when parthenolide was given after the homing of tumor cells. The growth of s.c. tumors that developed at the inoculation site was not suppressed by parthenolide. We also found that the genetic inhibition of NF-kappaB activity by expressing mutant IkappaBalpha suppressed lung metastasis in vivo but not s.c. tumor growth. This supports our notion that the metastasis-preventing effect of parthenolide is mediated at least in part by inhibition of NF-kappaB activity. CONCLUSIONS: These findings suggested that NF-kappaB is a potential molecular target for designing specific prophylactic interventions against distant metastasis and that parthenolide is a hopeful candidate for an antimetastatic drug.

Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification.

Leptin has been suggested to mediate a variety of actions, including bone development, via its ubiquitously expressed receptor (Ob-Rb). In this study, we investigated the role of leptin in endochondral ossification at the growth plate. The growth plates of wild-type and ob/ob mice were analyzed. Effects of leptin on chondrocyte gene expression, cell cycle, apoptosis and matrix mineralization were assessed using primary chondrocyte culture and the ATDC5 cell differentiation culture system. Immunohistochemistry and in situ hybridization showed that leptin was localized in prehypertrophic chondrocytes in normal mice and that Ob-Rb was localized in hypertrophic chondrocytes in normal and ob/ob mice. Growth plates of ob/ob mice were more fragile than those of wild-type mice in a mechanical test and were broken easily at the chondro-osseous junction. The growth plates of ob/ob mice showed disturbed columnar structure, decreased type X collagen expression, less organized collagen fibril arrangement, increased apoptosis and premature mineralization. Leptin administration in ob/ob mice led to an increase in femoral and humeral lengths and decrease in the proportional length of the calcified hypertrophic zone to the whole hypertrophic zone. In primary chondrocyte culture, the matrix mineralization in ob/ob chondrocytes was stronger than that of wild-type mice; this mineralization in both types of mice was abolished by the addition of exogenous leptin (10 ng/ml). During ATDC5 cell differentiation culture, exogenous leptin at a concentration of 1-10 ng/ml (equivalent to the normal serum concentration of leptin) altered type X collagen mRNA expression and suppressed apoptosis, cell growth and matrix calcification. In conclusion, we demonstrated that leptin modulates several events associated with terminal differentiation of chondrocytes. Our finding that the growth plates of ob/ob mice were fragile implies a disturbance in the differentiation/maturation process of growth plates due to depletion of leptin signaling in ob/ob mice. These findings suggest that peripheral leptin signaling plays an essential role in endochondral ossification at the growth plate.

Measurement of lesion area and volume by three-dimensional spoiled gradient-echo MR imaging in osteonecrosis of the femoral head.

The purpose of this investigation is to evaluate the diagnostic ability of three-dimensional spoiled gradient-echo (3D SPGR) magnetic resonance (MR) imaging in cases of osteonecrosis of the femoral head (ONFH), and to determine the accuracy of 3D SPGR imaging in area and volume measurement of ONFH. T1-weighted spin-echo (SE) and 3D SPGR imaging were performed on 20 femoral heads obtained from patients with ONFH. After MR imaging, the femoral heads were cut parallel to the imaging plane and were evaluated histologically. Areas and volumes of necrotic lesions were measured with a computer program and the deviation between MR images and anatomical measurements was evaluated. A low signal intensity band on 3D SPGR MR images was observed in all femoral heads and corresponded histologically to repaired marrow with viable fibrous mesenchymal tissue. The area proximate to the low band area coincided with the necrotic region. Both area and volume measurements by T1-weighted SE and 3D SPGR images showed a strong correlation to histological measurements. The discrepancies between histological and imaging results were minimal in 3D SPGR imaging, especially at the anterior and posterior portions of the femoral head. Three-dimensional SPGR imaging provides more accurate measurements of the area and volume of a necrotic lesion than T1-weighted SE imaging.

Scintigraphic image patterns in dysplastic coxarthrosis: evaluation with reference to radiographic findings in 210 hips.

Little is known about scintigraphic image patterns in the various stages of coxarthrosis. We assessed bone scintigraphy in 159 patients (210 hips) with dysplastic arthrosis of the hip. Scintigraphic images were divided into 5 types related to the radiographic stages of the disease. The scintigraphic images showed little, if any, uptake in the stage of prearthrosis. In the early stage, we found an increase in uptake in the weight bearing area in 30% of cases. In the advanced stage, more than half of the cases had an increase in uptake in the medial side of the joint and in the weight bearing area. In the terminal stage, a marked increase in uptake in the weight bearing area was commonest. Since the osteoblastic reaction intensified, a marked increase in uptake was seen not only in the weight bearing area, but also throughout the entire joint. These types of scintigraphic patterns, which change with the stage of coxarthrosis, seem to reflect the natural course of the disease. All hips with rapid progression of the disease showed a marked increase in uptake of radionuclide the entire joint at earlier stages.

Stem fracture of the cementless spongy metal Lübeck hip prosthesis.

We performed 204 cementless total hip arthroplasties using a fully porous stem made of a cast cobalt-chrome-molybdenum alloy. Five stems fractured at the middle part. Champagne-fluted canals (P<.0001) and low canal fillings 1 cm below the lesser trochanter (P =.02) significantly correlated with stem fractures. Subsequent surgery revealed that all of the proximal parts were surrounded by fibrous tissue, and the distal parts showed bone ingrowth. Numerous voids were present close to the surface of the implant body. The core diameters of the fractured stems were 4 to 5 mm. The fractures may be attributed to the combination of the lack of proximal support, a champagne-fluted canal, the fully porous stem made of a cast cobalt-chrome-molybdenum alloy, and the narrow dimension of the stem core.