Enhancement of in vitro antibacterial activity and bioactivity of iodine-loaded titanium by micro-scale regulation using mixed-acid treatment.

Postoperative infection and subsequent device loss are serious complications in the use of titanium dental implants and plates for jawbone reconstruction. We have previously reported that NaOH-CaCl2 -thermal-ICl3 -treated titanium (NaCaThIo) has a nano-scale surface and exhibits antibacterial activity against Staphylococcus aureus. The present study examined the surface properties of mixed-acid treated and then iodine-treated titanium (MA-NaCaThIo), and evaluated oral antibacterial activity and cytotoxicity compared with the results obtained with NaCaThIo. MA-NaCaThIo formed a surface layer with a nano-scale network structure having microscale irregularities, and both the thickness of the surface layer (1.49 ± 0.16 µm) and the average surface roughness (0.35 ± 0.03 µm) were significantly higher than those of NaCaThIo. Furthermore, MA-NaCaThIo maintained high hydrophilicity with a contact angle of 7.5 ± 1.7° even after 4 weeks, as well as improved apatite formation, iodine ion release, and antibacterial activity against Prevotella intermedia compared to NaCaThIo. Cell culture test revealed that MA-NaCaThIo exhibited no cytotoxicity against MG-63 and Vero cells, while increased cell proliferation, ALP activity and mineralization of MG-63 compared to NaCaThIo. This treated titanium is expected to be useful for the development of next-generation titanium devices having both bone-bonding and antibacterial properties.

Clinical Study of 14 Cases of Bone Augmentation with Selective Laser Melting Titanium Mesh Plates.

Additive manufacturing techniques are being used in the medical field. Orthopedic hip prostheses and denture bases are designed and fabricated based on the patient's computer-aided design (CAD) data. We attempted to incorporate this technique into dental implant bone augmentation. Surgical simulation was performed using patient data. Fourteen patients underwent bone augmentation using a selective laser melting (SLM) titanium mesh plate. The results showed no evidence of infection in any of the 14 patients. In 12 patients, only one fixation screw was used, and good results were obtained. The SLM titanium mesh plate was good adaptation in all cases, with bone occupancy greater than 90%. The average bone resorption of the marginal alveolar bone from the time of dental implant placement to the time of the superstructure placement was 0.69 ± 0.25 mm. Implant superstructures were placed in all cases, and bone augmentation with SLM titanium mesh plates was considered a useful technique.

Radiosensitizing effect of 5-aminolevulinic acid in colorectal cancer in vitro and in vivo.

The radiosensitizing effect of 5-aminolevulinic acid (5-ALA) has been demonstrated in glioma and melanoma in a number of studies. Enhancing the radiosensitivity of colorectal cancer may improve survival rates and lessen adverse effects. The present study assessed the radiosensitizing effect of 5-ALA in colorectal cancer using the human colon cancer cell line HT29 in vitro and in vivo. In vitro, cells were pretreated with 5-ALA and exposed to ionizing radiation. Cells pretreated with or without 5-ALA were compared using a colony formation assay. In vivo, HT29 cells were implanted into mice subcutaneously and subsequently exposed to ionizing radiation. 5-ALA was administrated by intraperitoneal injection. Subcutaneous tumors treated with or without 5-ALA were compared. Single-dose and multi-dose irradiations were applied both in vitro and in vivo. Cells exposed to multi-dose irradiation and pretreated with 5-ALA in vitro had a significantly lower surviving fraction compared with cells without 5-ALA pretreatment. Following multi-dose irradiation in vivo, the volume of the subcutaneous tumors treated with 5-ALA was significantly lower compared with that of tumors without treatment. These results suggest that radiotherapy with 5-ALA may enhance the therapeutic effect in colon cancer.

[A Case Report of Gastric Carcinoma with Lymphoid Stroma Differentially Diagnosed from Malignant Lymphoma].

A 49-year-old man was referred to our hospital for close examination of a submucosal tumor with ulceration located in the upper gastric body. PET-CT showed FDG uptake both in the gastric tumor and an enlarged lymph node. Although routine biopsies and EUS-FNA of this tumor did not demonstrate any malignant findings, he underwent excisional biopsy of the enlarged lymph nodes to rule out malignant lymphoma. Histopathological examination revealed that the excised specimens were metastatic nodes of poorly differentiated carcinoma probably from the known gastric tumor. Subsequently, he underwent total gastrectomy with D2, and histopathological findings confirmed the final diagnosis of gastric carcinoma with lymphoid stroma(GCLS). We report a case of GCLS that was difficult to diagnose.

Intravenous infusion of amino acids in dogs attenuates hypothermia during anaesthesia and stimulates insulin secretion.

OBJECTIVE: To evaluate the effect of intravenous infusion of amino acids on the prevention of hypothermia during anaesthesia in dogs. STUDY DESIGN: Randomized experimental trial. ANIMALS: Seven healthy Beagle dogs. METHODS: Four concentrations of amino acids were prepared with a 10% amino acid solution and an acetated Ringer's solution, and dogs were infused with each of the solutions at 1 week intervals. Dogs were infused with amino acid solution at 12 mL kg(-1)  hour(-1) for 60 minutes before and for 60 minutes after induction of anaesthesia. Acetated Ringer's solution was infused at the same rate for the remaining 60 minutes of anaesthesia. The infusion treatments were: 1) A0, nutrient-free acetated Ringer's solution; 2) A6, 0.6 g kg(-1)  hour(-1) ; 3) A9, 0.9 g kg(-1)  hour(-1) ; and 4) A12, 1.2 g kg(-1) hour(-1) . Rectal temperature (RT), heart rate (HR), mean arterial pressure (MAP), blood insulin, glucose, urea nitrogen (BUN) and creatinine concentrations, and time to extubation were measured. RESULTS: Before anaesthesia, RT was not affected by amino acid infusion. RT decreased progressively during anaesthesia and the absolute values of RT from 30 to 120 minutes were significantly higher in A12 than in A0 (p < 0.05). Reductions in HR and MAP during anaesthesia were attenuated by amino acid infusion in a dose-dependent manner. Plasma insulin concentration was significantly higher in A12 than in A0 during amino acid infusion and the increase in insulin concentration was greater during than before anaesthesia. BUN increased during amino acid infusion in a dose- and time-dependent fashion. Time until extubation was shorter in A12 than in A0. CONCLUSIONS AND CLINICAL RELEVANCE: Amino acids infused at 1.2 g kg(-1)  hour(-1) in dogs attenuated the decrease in RT, HR, and MAP during anaesthesia, and induced a significant increase in plasma insulin concentration.

Structure-based optimization of cyclopropyl urea derivatives as potent soluble epoxide hydrolase inhibitors for potential decrease of renal injury without hypotensive action.

Epoxyeicosatrienoic acids (EETs) are known to have beneficial pharmacological effects on various cardiovascular events. However, EETs are biologically metabolized by soluble epoxide hydrolase (sEH) to less active metabolites. In our search for potent sEH inhibitors, we optimized a series of cyclopropyl urea derivatives and identified compound 38 as a potent sEH inhibitor with minimal CYP inhibition and good oral absorption in rats. Administration of 38 to DOCA-salt rats suppressed urinary albumin and MCP-1 excretion without affecting systolic blood pressure.

Fabrication of cultured oral gingiva by tissue engineering techniques without materials of animal origin.

BACKGROUND: Cultured gingival substitute has been found to be a useful graft material for treatment of gingival recession. However, such substitutes include xenograft derivative materials that involve concomitant risk of viral contamination. To eliminate this risk, we designed new gingival substitutes made of recombinant human collagen types I and III sponges and cultured these substitutes in animal-free media (HFDM-1). METHODS: Gingival fibroblasts were seeded onto sponges of type I or III recombinant collagen. These sponges were cultured in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS), HFDM-1 with 2% human serum (HS), or HFDM-1. Fibroblast proliferation in these samples was compared using the cell-counting kit assay. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) released into the cultured media were examined by enzyme-linked immunosorbent assay. RESULTS: The fibroblasts proliferated significantly in all six combinations of collagen and medium types. The fibroblast growth rate after 9 days of culture was equal between HFDM-1 with 2% HS and DMEM with 10% FBS. The type III collagen sponge showed a higher fibroblast growth rate than the type I sponge. VEGF concentrations in HFDM-1 with 2% HS were higher than those in other media. The highest HGF levels were detected in DMEM with 10% FBS. CONCLUSIONS: The new cultured gingival substitute containing no animal-derived materials produced good cell proliferation and VEGF release. The results suggested that the substitute may provide a new tool for the treatment of gingival recession.

Reduction of myocardial infarct size by SM-197378, a novel Na+/H+ exchange inhibitor, in rabbits.

The effects of SM-197378, 2-[[[amino(imino)methyl]amino]carbonyl]-1-methyl-4-trifluoromethyl-1H-indol-7-yl=hydrogen=sulfate monohydrate, a novel potent Na+/H+exchange inhibitor, on heart injury were studied using a rabbit model involving 30 min of myocardial ischemia and 5 h of reperfusion. Intravenous administration of SM-197378 before ischemia reduced the infarct size by approximately 30-50% in a dose-dependent manner. This anti-necrotic effect was achieved without significant hemodynamic changes. Moreover, administration of SM-197378 before reperfusion also resulted in a significant, approximately 30-40%, reduction in the infarct size. The anti-necrotic effect of pre-ischemic bolus treatment with SM-197378 was compared with that of nicorandil, a K+channel opener with nitrate-like activity, and ischemic preconditioning. With 30 and 60 min of ischemia, the anti-necrotic effects of SM-197378 and ischemic preconditioning were similar and superior to that of nicorandil. With 90 min of ischemia, the anti-necrotic effect of SM-197378 was superior to that of ischemic preconditioning.

Reduction of myocardial infarct size by SM-198110, a novel Na+/H+ exchange inhibitor, in rabbits.

The effects of 3-[2-({[amino(imino)methyl]amino}carbonyl)-4-chloro-1H-indol-1-yl]-1-propanesulphonic acid monohydrate (SM-198110), a novel potent Na+/H+ exchange inhibitor, and cariporide (Hoe642), another Na+/H+ exchange inhibitor, were studied in a myocardial ischaemia and reperfusion injury model. Anaesthetized rabbits were subjected to occlusion of the coronary artery for 30 min followed by reperfusion for 5 h. SM-198110 or cariporide was administered before ischaemia and before reperfusion. We also assessed the anti-necrotic effect of SM-198110 when given before reperfusion, both alone and together with glibenclamide, a K(ATP) channel blocker, 5-hydroxydecanoate (5-HD), a mitochondrial K(ATP) channel-selective blocker and 8-(p-sulphophenyl)-theophylline (8-SPT), an adenosine receptor blocker. The infarct size was reduced dose-dependently by i.v. administration of SM-198110 before ischaemia, with a significant reduction in serum creatine phosphokinase activity. Infarct sizes, normalized to the size of the area-at-risk (means+/-SE) were: vehicle 56.6+/-3.7%; low-dose SM-198110 39.2+/-6.3%; mid-dose 32.8+/-7.4% (P < 0.05); high-dose 22.1+/-6.7% (P < 0.01). This anti-necrotic effect of SM-198110 was achieved without significant haemodynamic changes. Cariporide given before ischaemia also reduced infarct size significantly and dose-dependently. SM-198110 administered before reperfusion also resulted in a dose-dependent reduction in the infarct size. Infarct sizes were: vehicle 56.6+/-3.7%; low-dose SM-198110 44.5+/-5.7%; mid-dose 36.3+/-6.6% (P < 0.01); high-dose 34.7+/-3.8% (P < 0.01). In contrast, cariporide given before reperfusion did not reduce infarct sizes significantly. The anti-necrotic effect of SM-198110 was observed even when given 10 min after the beginning of reperfusion. Glibenclamide and 5-HD abolished the anti-necrotic effect of treatment before reperfusion with SM-198110. However, the co-administration of 8-SPT with SM-198110 did not affect infarct size. These results suggest that, in addition to Na+/H+ exchange inhibition, mitochondrial and/or sarcolemmal K(ATP) channels contribute to the anti-necrotic effect of SM-198110 when the latter is given before reperfusion.

Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts.

The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.

Synthesis and release of activin and noggin by cultured human amniotic epithelial cells.

Recent studies suggest that extra-embryonic tissues may be essential sources of early organizing signals for the mouse embryo. In vitro studies of human amniotic epithelial cells (HAEC) have shown that the amnion can produce various biologically active substances. In this study, the synthesis and release of activin A and noggin, and the activin signaling pathway, was investigated in HAEC. Conditioned medium from cultured HAEC contained activin A which was functionally active in Xenopus laevis animal cap assays. Immunohistochemistry, western blotting and reverse transcription-polymerase chain reaction confirmed that HAEC also synthesize and release noggin. Noggin transcripts were induced by the addition of recombinant activin A, and activin A was inhibited by activin antibody except in the presence of cycloheximide (CHX). These data demonstrate that noggin mRNA expression is induced directly by activin A without new protein synthesis, indicating that noggin is a primary response gene. The results suggest that there is an activin signaling pathway in HAEC, and that the human amnion might therefore be involved in neural formation during early development.

Effects of SM-20550, a new Na(+)/H(+) exchange inhibitor, on survival and infarct size in rat myocardial infarction.

The effect of a novel potent Na(+)/H(+) exchange inhibitor, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid], on survival after myocardial infarction was studied. Anesthetized rats underwent occlusion of the coronary artery (30 min) followed by reperfusion (14 days). SM-20550 was administered intravenously before ischemia (1-day treatment group) or before ischemia and on the 2 days following (3-day treatment group). The infarct size was significantly reduced on the 14th day after surgery by approximately 17 and 20% in 1- and 3-day treatment groups, respectively. The survival rate on day 14 was significantly enhanced in both treatment groups (96%) compared with the vehicle-treated control group (70%). These results suggest that SM-20550 improved survival after myocardial infarction, at least due to its antinecrotic effect.