Zingiberis Siccatum Rhizoma, the active component of the Kampo formula Daikenchuto, induces anti-inflammatory actions through α7 nicotinic acetylcholine receptor activation.

BACKGROUND: We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti-inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti-inflammatory action. METHODS: The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation (IM) was carried out on the distal ileum. The anti-inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules. KEY RESULTS: Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) antagonists, such as HC-030031, significantly inhibited the amelioration of macrophage infiltration by ZSR. The inhibition of macrophage infiltration by ZSR was abolished in both α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT4 R) knockout mice. CONCLUSIONS & INFERENCES: Daikenchuto-induced anti-inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI, is dependent on the effects of ZSR. Zingiberis Siccatum Rhizoma activates TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT4 R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI.

New bone formation induced by surface strontium-modified ceramic bone graft substitute.

OBJECTIVES: This study assessed the effect of surface strontium ion (Sr) modification on the osteogenic activity of an osteoconductive ceramic bone graft substitute with the hope of using the bone healing effect of Sr for potential application in periodontal and maxillofacial regenerative surgery. MATERIALS AND METHODS: A simple wet chemical treatment was employed to deliver Sr to the surface of particulate porcine bone graft. The osteogenic activity of surface Sr-modified bone substitute was compared in vitro and in vivo with that of unmodified ceramic bone, other clinically available synthetic bone or osteoinductive allograft bone. RESULTS: The resultant bone substitute showed the formation of Sr-containing microstructured surface layer along with the formation of additional nanostructures and displayed sustained Sr release. Sr modification promoted the osteogenic differentiation of bipotential ST2 stem cells. Sr-modified bone substitute increased the amount of newly formed bone at early healing period in calvarial defect of rabbits. CONCLUSIONS: These results suggest that the surface Sr modification by wet chemical treatment is a promising approach to enhance the early bone healing capacity of osteoconductive ceramic bone substitutes.

Hydrocarbon Deposition Attenuates Osteoblast Activity on Titanium.

Although the reported percentage of bone-implant contact is far lower than 100%, the cause of such low levels of bone formation has rarely been investigated. This study tested the negative biological effect of hydrocarbon deposition onto titanium surfaces, which has been reported to be inevitable. Osteogenic MC3T3-E1 cells were cultured on titanium disks on which the carbon concentration was experimentally regulated to achieve carbon/titanium (C/Ti) ratios of 0.3, 0.7, and 1.0. Initial cellular activities such as cell attachment and cell spreading were concentration-dependently suppressed by the amount of carbon on the titanium surface. The osteoblastic functions of alkaline phosphatase activity and calcium mineralization were also reduced by more than 40% on the C/Ti (1.0) surface. These results indicate that osteoblast activity is influenced by the degree of hydrocarbon contamination on titanium implants and suggest that hydrocarbon decomposition before implant placement may increase the biocompatibility of titanium.

Nano-indentation testing of new and fractured nickel-titanium endodontic instruments.

AIM: To investigate the effect of cyclic fatigue on nickel-titanium (NiTi) endodontic instruments using a nano-indentation test. METHODOLOGY: Eight ProFile NiTi rotary instruments (size 30, taper 0.06; Dentsply Maillefer, Ballaigues, Switzerland) were tested using a cyclic fatigue set-up until fracture. The fractured instruments and eight new NiTi instruments of the same size and taper were used for a nano-indentation test on the internal surfaces of a NiTi instruments in the region just adjacent to their fractured edge (group I) and in the same region of the new group (group II), and the cutting part beside the shaft for both instruments [group III (fractured) and group IV (new)]. Data were statistically analyzed using one-way analysis of variance and Games-Howell post hoc test. The alpha-type error was set at 0.05. RESULTS: Significant differences in terms of hardness and elastic modulus for each group (P < 0.05) were found, with group I having the lowest mean values followed by group III. Additionally, standard deviations increased remarkably after failure, as represented by groups I and III. CONCLUSION: The nano-indentation technique can be applied to determine the performance and the failure mechanism of NiTi instruments. The fatigue process revealed a significant decrease in the hardness and elastic modulus of the NiTi instrument. As indicated by the low hardness, the fatigue process did not result in work hardening but rather work softening.

Phase transformation behaviour and bending property of twisted nickel-titanium endodontic instruments.

AIM: To investigate the relationship between phase transformation behaviour and bending property of nickel-titanium endodontic instruments manufactured by a twisting process. METHODOLOGY: The phase transformation behaviour and bending property of Twisted Files (TF; SybronEndo, Orange, CA, USA) and K3 (SybronEndo) with.06 taper and size 30 tip were investigated. K3 was used as control group. Phase transformation behaviour was estimated by differential scanning calorimetry (DSC). Transformation temperatures were calculated from the DSC curve. Bending load of the instruments was measured by cantilever-bending test at 37°C. Data were analysed by Student's t-test and Mann-Whitney U-test. RESULTS: The phase transformation temperatures of TF were significantly higher (P<0.05) than those of K3. The bending load values were significantly lower for TF than that of K3 (P<0.05), both in the elastic and super-elastic ranges. CONCLUSIONS: The new method of manufacturing NiTi instruments by twisting coupled with heat treatment might contribute to the increased phase transformation temperatures and superior flexibility.

Antidepressant-like Effect of l-perillaldehyde in Stress-induced Depression-like Model Mice through Regulation of the Olfactory Nervous System.

Perillae Herba (a leaf of Perilla frutescens) has been prescribed as one of the component herbs in certain Kampo (Japanese herbal) medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animal's duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days) significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function.

Cathodic alkaline treatment of zirconium to give the ability to form calcium phosphate.

The cathodic polarization technique to form an alkaline environment on a zirconium (Zr) surface, discussed in the present study, is unique, and gives the ability to form calcium phosphate in a simulated body fluid to Zr; on the other hand, many previous studies have been conducted using immersion in alkaline solutions. In this study, two discrete techniques were investigated. Zr was cathodically polarized in an electrolyte without calcium and phosphate ions, and Zr was cathodically polarized in another electrolyte containing calcium and phosphate ions, Hanks' solution, to directly form a calcium phosphate layer. The surface was characterized using X-ray photoelectron spectroscopy, and the performance of the material was evaluated by immersion in Hanks' solution. As a result, the ability to form calcium phosphate in Hanks' solution was given by cathodic polarization in the Na(2)SO(4) solution containing H(2)O(2). In addition, a cathodic potential under -1.5 V(SCE) is required to form hydroxyapatite directly in Hanks' solution. This research clearly reveals useful surface modification techniques giving the ability to form calcium phosphate in a simulated body fluid by cathodic polarization.

Effect of heat treatment on transformation temperatures and bending properties of nickel-titanium endodontic instruments.

AIM: To investigate the effect of heat treatment on the bending properties of nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Nickel-titanium super-elastic alloy wire (1.00 mm Ø) was processed into a conical shape with a 0.30 mm diameter tip and 0.06 taper. The heat treatment temperature was set at 440 or 500 degrees C for a period of 10 or 30 min. Nonheat-treated specimens were used as controls. The phase transformation behaviour was examined using differential scanning calorimetry. A cantilever-bending test was used to evaluate the bending properties of the specimens. Data were analyzed by ANOVA and the Tukey-Kramer test (P = 0.05). RESULTS: The transformation temperature was higher for each heat treatment condition compared with the control. Two clear thermal peaks were observed for the heat treatment at 440 degrees C. The specimen heated at 440 degrees C for 30 min exhibited the highest temperatures for M(s) and A(f), with subsequently lower temperatures observed for specimens heated at 440 degrees C for 10 min, 500 degrees C for 30 min, 500 degrees C for 10 min, and control specimens. The sample heated at 440 degrees C for 30 min had the lowest bending load values (P < 0.05), both in the elastic range (0.5 mm deflection) and in the super-elastic range (2.0 mm deflection). The influence of heat treatment time was less than that of heat treatment temperature. CONCLUSIONS: Change in the transformation behaviour by heat treatment may be effective in increasing the flexibility of nickel-titanium endodontic instruments.

I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation.

A decrease in orexin-A (OX-A) levels has been reported to be associated with depression. It is also well known that stress and depression can disrupt neurogenesis in the dentate gyrus of the hippocampus; however, it is unclear how OX-A is involved in depression and/or neurogenesis. In the present study, we investigated the effect of i.c.v. administration of OX-A on the forced swimming test (FST), an accepted behavioral screen of antidepressant-like activity, and on the cell proliferation with bromodeoxyuridine (BrdU) in the dentate gyrus at 4 days after i.c.v. administration of OX-A. OX-A administration (140 pmol/mouse) led to a significant reduction in animal immobility in the FST, without affecting spontaneous locomotor activities or serum corticosterone levels. In addition, the number of BrdU-positive cells in the dentate gyrus was significantly increased in OX-A-treated mice in vivo; however, OX-A did not affect the percentage of doublecortin-positive cells in the dentate gyrus. The proliferation of neural progenitor cells derived from rat fetal brain was not affected by OX-A treatment in vitro, and the orexin receptor 1 (OXR1) protein was not expressed in these cells. Treatment with the OXR1 antagonist SB-334867 (30 mg/kg, i.p.) blocked both the OX-A-induced decrease in the immobility of FST and increase in BrdU-positive. Moreover, the OX-A-induced increase in neuropeptide Y (NPY)-positive cells in the hilus of the dentate gyrus was blocked by SB-334867. These results suggest that OX-A induces an antidepressive-like effect, at least in part, via the enhancement of cell proliferation in the dentate gyrus. These effects of OX-A also may be partly relevant to the regulation of the NPY system in the hilus of the dentate gyrus.

Analysis of pharmacological effect and molecular mechanisms of a traditional herbal medicine by global gene expression analysis: an exploratory study.

BACKGROUND AND OBJECTIVES: Although traditional herbal medicines have been used for more than 2000 years, there are few studies on their molecular mechanisms of action. We examined the pharmacological effect and mechanism of action of a traditional herbal medicine (Kososan) with global gene expression analysis using a DNA chip. METHODS: Fourteen healthy subjects were given the herbal medicine (Kososan) for 2 weeks and interviewed. Peripheral blood was collected before and after 2-week medication. Based on the outcomes of the interview, the subjects were divided into responders and non-responders. We analysed the blood samples from responder and non-responder groups, respectively, using a DNA chip. RESULTS: In the Kososan responder group, 70 genes were over-expressed (2-fold or more), and their over-expression was normalized by Kososan (0.5-fold or less), whereas 24 genes were under-expressed (0.5-fold or less), and the under-expression was normalized by Kososan (2-fold or more). CONCLUSION: This exploratory study suggests that gene expression profiling is a possible approach for studying the effects of complex herbal remedies. Some of the genes studied seem to have functions related to the pharmacological effects of Kososan, which have been known for a long time.

Phase transformation behaviour and bending properties of hybrid nickel-titanium rotary endodontic instruments.

AIM: To investigate the bending properties of hybrid rotary nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Four types of nickel-titanium rotary endodontic instruments with different cross-sectional shapes (triangular-based and rectangular-based) and different heat treatment conditions (super-elastic type and hybrid type with shape memory effect) were selected to investigate bending properties and phase transformation behaviour. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 3.0 mm. A commercial rotary instrument, ProFile (PF; Dentsply Maillefer, Ballaigues, Switzerland) was used as a reference for the bending test. Phase transformation temperatures were calculated from the diagrams obtained from differential scanning calorimetry. Data were analysed by anova and Scheffe's test. RESULTS: The bending load values of the hybrid type that had undergone additional heat treatment at the tip were significantly lower (P < 0.05) than those of the super-elastic type with no additional heat treatment. The bending load values of rectangular-based cross-sectional shaped instruments were significantly lower (P < 0.05) than those of triangular-based cross-sectional shaped instruments. Phase transformation temperatures (M(s) and A(f) points) of the hybrid type were significantly higher (P < 0.05) than the super-elastic type. The M(f) and A(s) points of the tip part were significantly higher (P < 0.05) than those of the whole part of the hybrid instrument. CONCLUSIONS: Additional heat treatment of hybrid nickel-titanium instruments may be effective in increasing the flexibility of nickel-titanium rotary instruments.

Calcium phosphate formation on titanium by low-voltage electrolytic treatments.

Electrochemical treatments are expected to be effective for the coating of calcium phosphate ceramics to a titanium substrate. In the present study, two types of chronoamperometry with a step potential and a cyclic wave potential at low voltage (up to 2.0 V) and low current density were performed in Hanks' solution to modify the surface characteristics of titanium. Titanium oxide film formed by self-passivation, that formed as reconstructed film during electrochemical treatments, and a calcium phosphate layer precipitated through treatments were characterised by X-ray photoelectron spectroscopy. The thickness and compositions of the surface films and layers were quantified from the XPS results. Calcium phosphate formation during immersion in Hanks' solution for 1.0 Ms was evaluated by scanning electron microscopy with energy-dispersive X-ray spectrometry. The results confirmed that the electrolytic treatments in this study were effective to accelerate calcium phosphate formation on titanium in Hanks' solution in spite of their lower voltage than conventional methods. The results also suggested that the hydroxyl group in the surface oxide film might contribute to the formation of calcium phosphate. This technique is a promising process for the treatment of thin titanium materials.

[Torsion of the right upper lobe due to primary lung cancer with pulmonary hypertrophic osteoarthropathy; report of a case].

A 61-year-old woman was admitted due to severe coughing. Chest X-ray revealed a mass in the right lower lung field at standing position and in the right upper lung field at supine position. A position of the mass changed with change in her posture because of lobar torsion. Bronchoscopic biopsy of the polypoid tumor obstructing the right upper bronchus revealed adenocarcinoma. She had hypertrophic osteoarthropathy simultaneously. Right pneumonectomy was performed. Postoperative course has been uneventful for 3 years.

Stimulating effect of Japanese herbal (kampo) medicine, hochuekkito on upper respiratory mucosal immune system.

Japanese herbal (Kampo) medicine, Hochuekkito (Bu-Zhong-Yi-Qi-Tang in Chinese, TJ-41) and Juzentaihoto (Shi-Quan-Da-Bu-Tang in Chinese, TJ-48) are well-known Kampo formulas used as tonic. Although these medicines have separately been applied to the patients clinically depending on their symptoms, the differences of the pharmacological activities for these medicines have not been fully understood. TJ-48 and TJ-41 were compared for their effects on antibody response in upper respiratory mucosal immune system in vivo. Oral administration of TJ-41 (100 mg kg(-1) per day) to early aged BALB/c mice, which were nasally sensitized with influenza hemagglutinin vaccine, significantly enhanced influenza virus-specific IgA and IgG antibody titers in nasal cavity and sera, respectively. However, oral administration of TJ-48 (100 mg kg(-1) per day) failed to show the enhancing activity. TJ-41 increased not only influenza virus-specific IgA antibody titer but also total IgA antibody titer in nasal cavity. The stimulating activity of TJ-41 disappeared after treatment with methotrexate. The present study strongly suggests that TJ-41 can stimulate the mucosal immune system of upper respiratory tract, and results in enhancement of antigen-specific antibody response in upper respiratory mucosal and systemic immune systems.

Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.

Koso-san (Xiang-Su-San in Chinese), a Kampo (Japanese herbal) medicine, is used clinically in East Asia for the treatment of depression-like symptoms associated with the initial stage of the common cold, allergic urticaria due to food ingestion, irritable bowel syndrome, chronic fatigue syndrome, insomnia, and autonomic imbalance. However, the antidepressant-like activity of Koso-san has never been evaluated scientifically. In this study, ddY mice subjected to a combination of forced swimming and chronic mild stresses were termed depression-like model mice. The degree of the depression-like state was measured by the animal's duration of immobility using the forced swimming test (FST). Oral administration of Koso-san (1.0 g/kg/body wt./day, 9 days) significantly shortened the duration of immobility of the depression-like model mice in the FST; however, locomotor activity was not affected. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of depression. Levels of corticotropin-releasing hormone mRNA expression in the hypothalamus and proopiomelanocortin mRNA expression in the pituitary were significantly increased, and glucocorticoid receptor protein expression in the hypothalamus paraventricular nucleus was downregulated in the depression-like model mice. However, Koso-san ameliorated these alterations to the normal conditions. The results of this study suggest that Koso-san shows the antidepressant-like effect through suppressing the hyperactivity of the HPA axis in depression-like model mice.

Prokinetic effect of a Kampo medicine, Hange-koboku-to (Banxia-houpo-tang), on patients with functional dyspepsia.

Limited evidence is available as to whether Kampo medicine modifies gastrointestinal function in humans. We investigated the effect of a Kampo medicine, Hange-koboku-to (Banxia-houpo-tang, HKT), on patients with functional dyspepsia (FD) and on healthy volunteers with regard to gastric motility. The gastric emptying rate (GER) in FD patients was significantly lower than in the healthy subjects. GER in FD patients and in healthy volunteers showed a significant increase after 2 weeks of medication with HKT. Furthermore, gastrointestinal symptoms improved significantly in the FD patients after the administration of HKT. These results suggest that HKT improves delayed gastric emptying and acts as a prokinetic agent.

Lung herniation as an anatomic consequence of pneumonectomy.

BACKGROUND: Pneumonectomy causes an overdistention of the remaining lung as an adaptive response. Excessive lung herniation occasionally causes serious lung dysfunction. METHODS: Twenty-seven patients were selected from 152 patients who underwent pneumonectomy for lung cancer between 1990 and 1998. Complete resections were accomplished; no recurrence was observed for 3 years in these 27 patients. To evaluate the extent of herniation, the Lung Herniation Index (LHI) was developed and defined as the sum of proportions of the maximal transverse length of the remaining lung divided by the transverse length of the thoracic cavity, measured at the level of the aortic arch and the inferior pulmonary vein on chest computed tomography. Sequential changes in LHI were compared between groups. RESULTS: Changes in LHI did not differ between groups delineated on the basis of an FEV1 of 70 % (p = 0.45) and RV/TLC of 40 % (p = 0.99). Patients with a low body mass index (BMI) (< 20 kg/m(2)), however, showed a significantly greater degree of lung herniation than those with a high BMI (> or = 20 kg/m(2)) (p < 0.05). CONCLUSIONS: Concomitant COPD has no effect on lung herniation. Some preventive procedure should be considered for patients with low BMI.

Effect of the antiulcer polysaccharide fraction from Bupleurum falcatum L. on the healing of gastric ulcer induced by acetic acid in rats.

An antiulcer polysaccharide fraction (BR-2) from Bupleurum falcatum L. was examined for its effect on the healing of chronic ulcers induced by acetic acid in rats. When BR-2 was administered orally to the rats, it was shown to be effective in the healing of acetic acid-induced chronic ulcer. This result suggests that the use of herbal prescriptions containing B. falcatum L. may prove useful for the treatment of peptic ulcers.

Causes of titanium release from plate and screws implanted in rabbits.

To investigate the mechanism behind the release of metal from titanium implants in vivo, bone-plate-screw sets consisting of pure titanium were implanted into the legs of rabbits for 48 weeks. Four groups of experiments containing control were conducted: (1) The tibia cut artificially was fixed by one set of bone plate and screws, (2) the same set was implanted separately into muscles in the leg, (3) the set was fixed on the tibia and immediately retrieved, and (4) no implantation was performed. The amounts of titanium in all tissues from knee to ankle were quantified using atomic adsorption spectrometry. The ratio of amounts of titanium detected in the groups (1), (2), and (3) was 100 : 10 : 43. No titanium was detected in the group (4). Causes of the release of titanium in the group (1) include that in the groups (2) and (3). Major causes of titanium release were surgical handling in implantation and wear and/or fretting during experimental-term for 48 weeks. Titanium was also released in the absence of wear. No morphological abnormality was observed around tissue of the implant by biopsy at post-operation week 48.