Printable PICN Composite Mechanically Compatible with Human Teeth.

Polymer-infiltrated ceramic network (PICN) composites are mechanically compatible with human enamel, and are therefore promising dental restorative materials. Fabrication technology for PICN composites used in tooth restorative material has been established through computer-aided design/computer-aided manufacturing (CAD/CAM) milling, however, to date, has not been successfully developed using 3-dimensional (3D) printing. This study aimed to develop a 3D-printable PICN composite as a restorative material. The PICN composite was fabricated using a specific method based on 3D printing. A 3D-printable precursor slurry containing a high concentration of silica nanoparticles was produced and 3D-printed using stereolithography (SLA). The 3D-printed object was sintered to obtain a nano-porous object, and subsequently infiltrated and polymerized with resin monomer. Three different fabrication condition combinations were used to produce the 3D-printed PICN composites, which were characterized based on microstructure, mechanical properties, inorganic content, physicochemical properties, and overall shrinkage. The 3D-printed PICN composites were also compared to 2 commercially available CAD/CAM composite blocks, namely a PICN composite and a dispersed-filler composite. The 3D-printed PICN composites exhibited a nano-sized dual-network structure comprising a silica skeleton with infiltrated resin. The 3D-printed PICN composite exhibited a similar Vickers hardness to enamel, and a similar elastic modulus to dentin. The 3D-printed PICN composite exhibited comparable flexural strength (>100 MPa) to the CAD/CAM block, and acceptable water sorption and solubility for practical use. Further, the 3D-printed model-crown underwent isotropic shrinkage during sintering without fatal deformation. Overall, the potential of this 3D-printable PICN composite as a restorative material with similar mechanical properties to human teeth was successfully demonstrated.

Identification of V-type nerve agents in vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator and fluoridating conversion tube.

A field-portable gas chromatography-mass spectrometry (GC-MS) system (Hapsite ER) was evaluated for the detection of nonvolatile V-type nerve agents (VX and Russian VX (RVX)) in the vapor phase. The Hapsite ER system consists of a Tri-Bed concentrator gas sampler, a nonpolar low thermal-mass capillary GC column and a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump. The GC-MS system was attached to a VX-G fluoridating conversion tube containing silver nitrate and potassium fluoride. Sample vapors of VX and RVX were converted into O-ethyl methylphosphonofluoridate (EtGB) and O-isobutyl methylphosphonofluoridate (iBuGB), respectively. These fluoridated derivatives were detected within 10 min. No compounds were detected when the VX and RVX samples were analyzed without the conversion tube. A vapor sample of tabun (GA) was analyzed, in which GA and O-ethyl N,N-dimethylphosphoramidofluoridate were detected. The molar recovery percentages of EtGB and iBuGB from VX and RVX vapors varied from 0.3 to 17%, which was attributed to variations in the vaporization efficiency of the glass vapor container. The conversion efficiencies of the VX-G conversion tube for VX and RVX to their phosphonate derivatives were estimated to be 40%. VX and RVX vapors were detected at concentrations as low as 0.3 mg m-3 . Gasoline vapor was found to interfere with the analyses of VX and RVX. In the presence of 160 mg m-3 gasoline, the detection limits of VX and RVX vapor were increased to 20 mg m-3 . Copyright © 2017 John Wiley & Sons, Ltd.

Effects of the experimental diabetes on dopamine D1 receptor-mediated locomotor-enhancing activity in mice.

The effects of diabetes on the dopamine-related locomotor-enhancing activities were studied in mice. Although spontaneous locomotor activity in diabetic mice was significantly greater than that in nondiabetic mice, the locomotor-enhancing effects of methamphetamine (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.) and SKF82958 (1 mg/kg, s.c.), a selective dopamine D1-receptor agonist, in diabetic mice were significantly lower than those in nondiabetic mice. When dopamine level in the whole brain was reduced by pretreatment with 6-hydroxydopamine (6-OHDA), spontaneous locomotor activity was significantly reduced in both nondiabetic and diabetic mice. There was no significant difference in the total spontaneous locomotor activity counts within 3 h between 6-OHDA-treated nondiabetic and 6-OHDA-treated diabetic mice. Furthermore, the locomotor-enhancing effect of SKF82958 in 6-OHDA-treated diabetic mice was also significantly lower than that in 6-OHDA-treated nondiabetic mice. In a binding assay, the Bmax values of [3H]SCH23390 binding to whole-brain membranes of diabetic mice were significantly lower than those in nondiabetic mice. However, there was no significant difference in the Kd values between nondiabetic and diabetic mice. These results suggest that the decreased density of dopamine D1 receptors in diabetic mice may result in hyporesponsiveness to dopamine-related locomotor enhancement.

Intraventricular insulin reduces the antinociceptive effect of [D-Ala2, NMePhe4, Gly-ol5]enkephalin in mice.

The effects of pretreatment with insulin on the antinociception induced by intracerebroventricular (i.c.v.) administration of the mu-opioid receptor agonist [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO) were studied in mice. Intracerebroventricular pretreatment with insulin (1 and 3 mU) for 60 min dose dependently attenuated the antinociception induced by i.c.v. DAMGO (5.6 ng) in mice. Intracerebroventricular pretreatment with a highly selective tyrosine kinase inhibitor, lavendustin A, at doses of 100 and 300 ng for 10 min, dose dependently reversed the antinociceptive effect of DAMGO (5.6 ng) in insulin-treated mice. The antinociceptive effect of DAMGO (5.6 ng, i.c.v.) was significantly reduced in C57BL/KsJ-db/db diabetic mice compared with that in age-matched control (C57BL/KsJ-db/ + + ) mice. When C57BL/KsJ-db/db diabetic mice were pretreated with lavendustin A (300 ng), the antinociceptive effect of DAMGO was significantly increased. These results indicate that tyrosine kinase may be involved in the reduction of DAMGO-induced antinociception by insulin in mice. Furthermore, the attenuation of DAMGO-induced antinociception in C57BL/KsJ-db/db diabetic mice may be due in part to increased tyrosine kinase activity as a result of hyperinsulinemia.

Modulation by serum glucose levels on morphine-induced antinociceptive effect in C57BL/KsJ-db/db mice.

The role of serum glucose levels on the sensitivity to the antinociceptive effect of morphine in streptozotocin-induced diabetic mice and C57BL/KsJ db/db mice were examined. The sensitivity to the antinociceptive effect of morphine was significantly reduced in streptozotocin-induced diabetic mice as compared with age-matched nondiabetic mice. Pretreatment with insulin (3 U/kg, s.c.) significantly reduced the serum glucose levels of streptozotocin-induced diabetic mice as compared with those of untreated diabetic mice. However, post-drug (morphine) tail-flick latency was not affected by pretreatment with insulin. The antinociceptive effect of morphine was also significantly reduced in C57BL/KsJ-db/db mice as compared with age-matched control mice. When CS-045 was administered to C57BL/KsJ-db/db mice, the serum glucose levels were significantly reduced. There was no significant difference in the antinociceptive effect of morphine between CS-045-treated C57BL/KsJ-db/db mice and C57BL/KsJ-db/++ mice. Adoptive transfer of supernatant of the spleen cell homogenate from C57BL/KsJ-db/db mice to naive ICR mice had no significant effect on the recipients' antinociceptive sensitivities to s.c. morphine. These findings support the our previous suggestion that some factor(s) derived from spleen mononuclear cells is the prime factor involving the insulin-insensitive mechanisms for the reduction of mu-opioid agonist-induced antinociception during the severe stages of diabetes.

Antinociceptive effect of buprenorphine in mu1-opioid receptor deficient CXBK mice.

The antinociceptive effect of buprenorphine was examined in mu1-opioid receptor-deficient CXBK mice. I.p. administration of buprenorphine at a dose of 3 mg/kg produced marked antinociception in the tail-flick test in C57BL/6 mice, a progenitor strain of CXBK mice. The antinociceptive effect of buprenorphine in C57BL/6 mice was antagonized by pretreatment with either beta-funaltrexamine (beta-FNA), a mu-opioid receptor antagonist, or naloxonazine (NXZ), a selective mu1-opioid receptor antagonist. The antinociceptive effect of buprenorphine (3 mg/kg, i.p.) in CXBK mice was significantly less than that in C57BL/6 mice. Neither beta-FNA nor NXZ reduced the antinociceptive effect of buprenorphine in CXBK mice. There was no significant difference between the buprenorphine-induced antinociceptive effect in CXBK mice and NXZ-treated C57BL/6 mice. Furthermore, neither naltrindole, a selective delta-opioid receptor antagonist, nor norbinaltorphimine, a selective kappa-opioid receptor antagonist, had a significant effect on the antinociceptive effects of buprenorphine in both CXBK and C57BL/6 mice. These results support our previous hypothesis that mu1- rather than mu2-, delta- or kappa-opioid receptors are involved in the antinociceptive effects of buprenorphine.

Tumor necrosis factor-alpha inhibits in vivo collagen synthesis.

In this study we sought to determine the in vivo role of tumor necrosis factor-alpha (TNF-alpha) at the wound-healing site. In vivo abrogation of endogenous TNF-alpha activity in experimental wounds by administration of anti-murine TNF-alpha rabbit serum resulted in a significant 77.5% increase in wound collagen deposition, as assessed by wound sponge granuloma hydroxyproline content. Administration of pharmacologic doses of recombinant murine TNF-alpha into subcutaneously inserted polyvinyl alcohol sponges resulted in an increase in collagen deposition (1594 +/- 117 vs 1014 +/- 49 and 1588 +/- 135 vs 1014 +/- 49 micrograms/100 mg sponge, for TNF-alpha in situ administration at a dose of 0.05 and 0.5 micrograms, respectively). This effect could be abolished by the simultaneous systemic treatment of the animals with the antiinflammatory drug indomethacin. The data suggest that the enhanced collagen deposition after TNF-alpha administration is a consequence of a nonspecific inflammatory activity that indirectly promotes collagen synthesis. The data also support the hypothesis that endogenous wound TNF-alpha down-regulates collagen synthesis during normal wound healing.

Sepsis impairs gut amino acid absorption.

Sepsis has been shown to adversely affect the barrier and metabolic functions of the small intestine as well as to reduce mesenteric blood flow and cause histologic damage. However, the effect of sepsis on gut absorptive function has been largely ignored. In this study, intestinal absorption of arginine and an amino acid analogue, aminoisobutyric acid, was studied using in vivo and in vitro techniques in an experimental model of sepsis. In vivo studies showed a significant impairment in the absorption of both amino acids from the intestinal lumen 24 and 72 hours after cecal ligation and puncture. Uptake of these amino acids by everted gut sacs prepared from septic animals was also significantly reduced. This reduction in absorptive capacity of the gut may limit the ability of enteral feeding alone to supply nutritional requirements during sepsis and may also contribute to the associated morbidity and mortality.

The effect of hemorrhagic shock on intestinal amino acid absorption in vivo.

Hemorrhagic shock causes a disproportionate decrease in portal blood flow which may adversely affect the barrier and absorptive functions of the intestine. The absorptive capacity of the small intestine was studied during shock induced by mild and severe hemorrhage in the rat by measurement of the uptake of a radiolabelled amino acid analog (aminoisobutyric acid: AIB). Hemorrhage resulted in a significant reduction in systemic blood pressure, portal blood flow, and the absorption of AIB from the small intestine. Resuscitation restored both blood pressure and portal blood flow. But a significant reduction in absorption of AIB persisted. This suggests that hemorrhage results in an inhibition of amino acid intestinal active transport which is not dependent on the mesenteric circulation. The reduced intestinal absorptive function has important implications for the route of administration of nutrition following hemorrhage and trauma.

Arginine enhances T-cell responses in athymic nude mice.

Supplemental L-arginine has been shown to enhance thymic and T-cell responses in rodents. We examined the ability of supplemental dietary L-arginine to induce T-cell function in athymic nude mice that lack a normally developed T-cell system. Groups of male nude (nu/nu) mice (Balb/c background) 7 to 8 weeks old were given for 2 weeks 1.2% arginine hydrochloride solution for drinking, whereas controls received acidified tap water. All mice ingested a standard laboratory chow. In the first experiment, the arginine-supplemented animals had significantly greater number of T cells in the spleen (assessed by the number of Thy 1.2-positive lymphocytes) and these cells had enhanced mitogenic responses to mitogenic stimulation (phytohemagglutinin and concanavalin A). In vivo delayed-type hypersensitivity responses to 2,4-dinitro-1-difluorobenzene were also significantly increased after the 2 weeks of arginine supplementation. In a second experiment, mice maintained under the same conditions were skin grafted with rat tail skin. Animals were observed for 100 days for rejection but no significant difference was noted in skin graft survival. We conclude that dietary arginine can increase extrathymic T-cell maturation and function, but cannot induce in vivo allogeneic graft recognition in athymic nude mice.

Postoperative recurrence of hepatocellular carcinoma.

Sixty-nine patients with hepatocellular carcinoma underwent curative hepatic resections as primary cases from 1981 to 1986. Seven patients died in the hospital after operation. The other 62 patients left the hospital and were closely followed for 25 to 78 months. Recurrence of carcinoma became obvious in 41 (66%) of 62 patients. The clinical and pathologic features of these 41 patients were not significantly different from those of the other patients. Recurrent tumors were found in the residual liver in 38 patients (93%), in the bone in 2 (5%), and in the lung in 1 (2%). Recurrence was diagnosed within 1 year, between 1 and 2 years, and more than 2 years after the operation in 22 (56%), 10 (26%), and 7 (18%) patients, respectively. It was difficult to determine the exact time of recurrence in two patients. There was a significant negative correlation between the size of primary tumor and time until recurrence; the larger the primary tumor, the shorter the time until recurrence. Among the 29 patients who underwent local excisions for their primary tumors, 19 recurrences were observed. Eighteen were found in the residual liver, in the same segment as the primary tumor, or in one near it. Larger hepatic resection for primary tumors is thus advocated to prevent recurrence.

[Acute respiratory failure after hepatic resection in canine biliary obstruction model].

Acute respiratory failure after hepatic resection, especially in case of concomitant liver dysfunction, is the most troublesome postoperative complication. In order to clarify the pathophysiological mechanism of acute respiratory failure, EVLW (extravascular lung water) was measured by double indicator dilution method in canine model. Mongrel dogs underwent laparotomy and the common bile duct was ligated and divided. After 6 weeks, EVLW was significantly elevated compared with that of normal dogs (p less than 0.05). From 4 hours after 70% hepatic resection dextran-40 was loaded to increase PWP (pulmonary wedge pressure). EVLW was increased accompanying the elevation of PWP in all groups, but in the group with biliary obstruction EVLW was significantly increased for the same elevation of PWP. These results suggest that permeability of pulmonary capillary was highly increased after hepatic resection in biliary obstruction group. Pulmonary edema in this canine model seems to resemble ARDS in human and the pathophysiological mechanism was thought to be related with depression of RES phagocytic function, activation of complement system and pulmonary vascular plugging by aggregates of degenerating granulocytes and endothelial injury. Gabexate mesilate blocked the increase of the lung vascular permeability and was thought to be effective to protect the lung from postoperative acute respiratory failure.

The effect of nifedipine, a calcium channel blocker, on liver ischemia in dogs.

This study was undertaken in order to determine whether the administration of nifedipine, a calcium channel blocker, could protect the liver from ischemic damage and to investigate its effect on the hepatic cellular energy status and cardio-vascular system after 60 minutes of hepatic ischemia in dogs. The ischemia was induced by temporarily clamping the portal vein and hepatic artery. One group of animals (n = 17) received nifedipine (5 micrograms/kg body weight) intravenously 15 minutes before the induction of liver ischemia, which was continued at a dose of 0.2 microgram/kg body weight/min throughout the ischemic period, and for an additional 30 minutes afterwards. Control dogs (n = 16) were not given nifedipine and survival was observed over seven days. The survival rate was 83 per cent in the nifedipine treated animals and 0 per cent in the control animals. Serum glutamic oxaloacetic transaminase levels were greatly increased following ischemia, and they were significantly lowered with the nifedipine treatment. The hepatic energy charge decreased remarkably during the hepatic ischemia, however it increased gradually after declamping but did not returned to its preoperative value in either group until one hour later and then it was higher in the nifedipine treated animals than in the control animals. Cardiac index and portal venous blood flow ratio remained higher in the nifedipine treated animals than in the control animals, after the ischemic period. These results suggest that nifedipine may have a powerful cytoprotective effect and that the period of warm hepatic ischemia could be prolonged with its use.