Optical properties of pb(Zr,Ti)O(3) films prepared by aerosol deposition.

The optical properties and related band structure of ferroelectric lead zirconate titanate [PZT, Pb(Zr0(0.6)Ti0(0.4))O(3)] films prepared on glass substrates at room temperature by aerosol deposition were investigated. The reflectance and transmittance of the PZT films were measured in the wavelength range from UV to nearinfrared. The measured optical spectra were analyzed using dielectric function models that describe optical transitions in the band gap region. Optical absorption of the as-deposited PZT films was found to be larger than that of the annealed PZT films in the near-infrared wavelength range. The analyzed results indicated that post-deposition annealing increased the band gap energy of the PZT films, corresponding to a decrease in optical absorption.

Potential application of human interferon-alpha in microbial infections of the oral cavity.

We have been evaluating the potential use of interferon-alpha (IFN-alpha) against fungal infections of the oral cavity. IFN-alpha has been reported to enhance the antifungal activity of neutrophils. This cytokine is also known to synergize with interleukin-1 in enhancing a number of immunomodulatory responses. To study cytokine involvement in oral defense mechanisms against microbial infection, we first demonstrated the presence of antimicrobial interleukins (IL)-1 alpha, IL-1 beta, and IL-8 in the saliva, which can all augment the microbicidal activity of neutrophils, and the presence of epithelial cells and neutrophils in oral lavage fluid from healthy volunteers. Immunostaining for cytokines produced by these cells showed that the candidate producers of both IL-1 alpha and IL-8 are epithelial cells, but those of IL-1 beta remained inconclusive. We next found that IFN-alpha enhanced IL-1 alpha-augmented neutrophil-mediated anticandidal action while marginally enhancing IL-8- and IL-1 beta-mediated reactions. These results suggest that IFN-alpha is a potential agent for treating oral mycosis by cooperating with endogenous cytokine(s) in the saliva, in addition to its intrinsic antiviral action.

Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6.

Gas6, a ligand of receptor tyrosine kinases Axl, Sky, and Mer, potentiates cell proliferation and prevents cell death. It also contains g-carboxylglutamic acid residues that mediate the interaction of some blood coagulation factors with negatively charged phospholipids. In our previous study, we demonstrated that Gas6 specifically binds to phosphatidylserine (PS) and links Axl-expressing cells to the PS-coated surface. In this study, to further understand the biological role of the interaction of Gas6 with PS, we examined the effect of Gas6 on the uptake of PS liposomes by macrophages. In vitro phagocytosis studies showed that Gas6 enhanced the uptake of PS liposomes approximately threefold and that the interaction of Gas6 with the surface of macrophages was essential for this enhancement. Analyses of the mechanism of the uptake of PS liposome suggested that Gas6 interacts with PS liposome via its N-terminal Gla domain and with macrophages via its C-terminal domain. Like that of PS liposomes, the uptake of apoptotic cells by macrophages was also enhanced, approximately twofold, in the presence of Gas6. These findings suggest that Gas6 may help phagocytic cells recognize cells with PS exposed on their surfaces, which is considered to be one of the mechanisms for clearing away dying cells. Thus, Gas6 may play a critical role in homeostasis by facilitating the clearance of PS-expressing cells.

Diurnal effect on caffeine clearance.

Caffeine (300 mg) was given orally to nine healthy subjects at 10:00 AM (day trial) or at 10:00 PM (night trial) using a crossover design. Saliva was obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of caffeine. Urine was collected for 8 hours after caffeine dosing. Caffeine clearances in saliva during the day trial were not different from those in the night trial. No significant difference was observed in urinary molar ratios of metabolites (AFMU + 1X + 1U/17U) between the two trials. These data suggest that caffeine clearances in saliva do not vary with its administration time. Since caffeine clearances in plasma are reflected in the urinary ratios of caffeine metabolites, its clearance in plasma might also not be altered by the time of dosing.

Preparation of oligozoospermic and/or asthenozoospermic semen for intrauterine insemination using the SpermPrep semen filtration column.

OBJECTIVE: To improve the quality of oligozoospermic and/or asthenozoospermic semen by the SpermPrep (Fertility Technologies Inc., Natick, MA) semen filtration column. DESIGN: The SpermPrep column was applied for semen manipulation in oligozoospermia and/or asthenozoospermia (sperm count less than 20 x 10(6)/mL, sperm motility less than 40%). After concentration of motile sperm using a 40% Percoll density gradient centrifugation, the sperm suspension was filtered through the SpermPrep column. The percentage yield of motile sperm by the SpermPrep method was compared with those by a two-layer Percoll density gradient (Pharmacia, Uppsala, Sweden) centrifugation and a swim-up method. Infertile couples with poor quality semen were treated with intrauterine insemination (IUI) with motile sperm by the three preparations through three cycles. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital. PATIENTS: Twenty-one couples with long-standing infertility because of poor quality semen. MAIN OUTCOME MEASURE: Recovery of motile sperm, sperm motility, and outcome of IUI were evaluated among three semen preparations. RESULTS: Motility was improved by the SpermPrep method in 32 of 33 cases of oligozoospermia and/or asthenozoospermia. Percentage yield of motile sperm by the SpermPrep method was significantly greater than those by the two-layer Percoll density gradient and swim-up methods (42.7 +/- 4.6 versus 22.1 +/- 3.1 and 13.8 +/- 3.5), but there is no significant difference in the sperm motility among three semen preparations. After one treatment cycle for each preparation, 2 of 21 women conceived after IUI with motile sperm separated in the SpermPrep method. CONCLUSIONS: The SpermPrep method is an improved semen manipulation method for oligozoospermia and/or asthenozoospermia.

Adhesion and reliability of interfaces in cemented total joint arthroplasties.

Debonding of the prosthetic/polymethylmethacrylate interface has been implicated in the initial failure process of cemented total hip arthroplasties. However, little quantitative understanding of the debonding process, as well as of the optimum interface morphology for enhanced resistance to debonding, exists. Accordingly, a fracture-mechanics approach has been used in which adhesion at the interface is characterized in terms of the interface fracture energy, G (J/m2), and shown to be a strong function of the morphology, debonding length, and loading mode of the interface. Double-cantilever-beam and four-point-flexure fracture-mechanics samples containing four clinically relevant prosthetic surface preparations were prepared to survey a range of interface roughness and loading modes. Adhesion at the interface could not be characterized with a single-valued material property but was found to exhibit resistance-curve behavior in which resistance to debonding increased with both the initial debond extension and the roughness of the interface. Values of debonding initiation, Go, were relatively insensitive to the roughness of the surface and the loading mode, whereas steady-state fracture resistance of the interface, Gss, increased significantly with the roughness and shear loading of the interface. These quantitative results suggest that debonding of the prosthetic/polymethylmethacrylate interface may be primarily attributed to surface interactions such as interlocking and the pullout of rough asperities that occur behind the debond tip. A simple mechanics analysis of such interactions was performed and revealed increases in the fracture resistance of the interface that were consistent with experimentally measured values.

Different immunosuppressive effects of liposomal FK506 in liver and kidney transplantation.

The efficacy of liposomal FK506 was compared between a canine liver transplantation model and a canine kidney transplantation model. The present study revealed that liposomal FK506 increased immunosuppressive efficacy of FK506 in liver transplantation but decreased in kidney transplantation. Because liposomal FK506 increased FK506 levels in the liver and spleen, and decreased FK506 levels in the kidney, it was suggested that enhanced immunosuppressive efficacy in liver transplantation should be attributed to the local immunosuppressive effects in the hepatic allograft rather than effective suppression of splenocyte activity.

Technical evaluation of newly-developed inorganic membranes for plasma fractionation.

Constant transmembrane pressure experiments were made by crossflow filtration to clarify sieving characteristics of microporous glass membranes for plasma fractionation. The distribution of pore diameters is more limited in the microporous glass membranes than in currently utilized synthetic polymer membranes. The filtration resistance of the concentration polarization layer is the dominant factor in plasma fractionation. Proteins are separated more sharply with a higher wall shear rate because of destruction of the concentration polarization layer formed on membrane surfaces. Plasma fractionation using a microporous glass membrane with a pore diameter of 15 nm may allow separation of albumin and IgG at higher wall shear rates. Cascade filtration techniques using microporous glass membranes with various pore diameters may be suitable for plasma fractionation.

[Clinical effects of oxybutynin hydrochloride (Pollakis)--especially in the treatment of pollakisuria, urgency and urinary incontinence].

The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.

[Phase I study of YM881 (zinostatin stimalamer) suspension by hepatic arterial infusion. Research Group for Intra-arterial Infusion Therapy with YM881].

A phase I study of YM-881 (zinostatin stimalamer), neocarzinostatin combined with butylesterified styrene maleate, suspended in iodized poppy oil ethyl ester, was conducted in patients with hepatocellular carcinoma by giving single intra-arterial infusions via catheters inserted by Seldinger's method. Four dose levels, 2, 4, 6, and 8 mg, were tested. Major adverse reactions were fever, anorexia, nausea, vomiting, and abnormal hepatic function. Both the incidence and severity of adverse reactions tended to increase with the 8 mg dose. Tumor regression of 50% or more occurred in one receiving 2 mg and one receiving 4 mg. The results of the study suggest that doses of 6 mg or less may be appropriate for the phase II studies.

[Phase II study of YM881 (zinostatin stimalamer) suspension injected into the hepatic artery. Research Group for Intra-arterial Injection Therapy with YM881].

A phase II study of YM 881 (zinostatin stimalamer) to determine the response and safety was conducted in patients with hepatocellular carcinoma by injecting a suspension of the drug into the hepatic artery. Repeated doses of 4 to 6 mg of the drug were given every 4 weeks so that the tumor tissues were filled with the suspension. Of the 195 registered patients, 15 were ineligible for the study, 8 dropped out, and data were missing for 5. A total of 167 patients completed the study. Response was assessed in the 167 patients who completed the study. CR was found in one, PR in 59, MR in 25, NC in 67, and PD in 15, with a response rate of 35.9. The safety of the drug was assessed in 177, excluding ineligible patients and 3 who dropped out because of the concurrent use of other drugs. Adverse reactions were found in 93.2% of the patients, and abnormal values in clinical laboratory tests in 60.5%. Major unwanted symptoms included fever, nausea, vomiting, and anorexia. Major abnormal changes in laboratory tests were elevated total bilirubin and LDH and abnormal hepatic function. About half the patients had malaise and pain related to the intra-arterial infusion therapy. The one year survival rate was 56.9%, and the duration of survival of 50% of the patients was 407 days.

[A perspective study on blood flow of the gastrointestinal anastomosis with special reference to the influence on blood flow at the anastomotic region by the suture material and it's size and the suturing interval].

To investigate the change of blood flow of the gastrointestinal anastomotic site by the material of the suture, the size of suture, the suture interval, blood flow, microangiography and histology of the anastomosis including tissue reaction were examined. Results are as follows. 1. When the colonic anastomosis was devascularized, the anastomotic blood flow was significantly lower and the avascular area in microangiography was significantly larger in the case of the silk and the 2mm suturing interval group compared to those of the polyglycolic acid (PGA) and the 4mm group. Concerning the size, the 4-0 group and the 6-0 group did not show any difference. 2. The necrotic change of the tissue surrounded by the suture was observed in 42.9% in the 4mm interval group and in 75.0% in the 2mm group. 3. The areas of the extension of tissue reaction to the suture were wider in the silk group than those of the PGA group. In conclusion, blood circulation of the anastomosis is affected by the material of the suture as well as by the suture interval, and under an insufficient blood flow, the use of the suture with lesser tissue reaction is preferable, and the suture interval should be kept at 4mm.

Production of islet cell sheets using cryopreserved islet cells.

BACKGROUND: To establish novel islet-based therapies, our group has recently developed technologies to create a contiguous, monolayered sheet made from freshly dispersed islet cells. Islet cell sheets generated from freshly isolated cells are easily transplantable for engraftment into subcutaneous sites in rodents. The use of a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), grafted culture dishes with laminin-5 coating is an important feature of this process. To expand the utility of this protocol, the present study was performed to assess whether sheets generated using cryopreserved islet cells maintained viability and normal cellular phenotypes. METHODS: Dispersed islet cells obtained from Lewis rats were, cryopreserved using University of Wisconsin solution and 10% dimethyl sulfoxide. Specially coated plastic dishes were prepared by covalently immobilizing PIPAAm onto the culture plastic, followed by a coating of rat laminin-5. After 1 month of cryopreservation, the thawed cells were plated onto the PIPAAm-coated dishes. RESULTS: Viability of the thawed islet cells as assessed by trypan blue exclusion test was 86% ± 5%. Thawed dispersed islet cells favorably attached to PIPAAm dishes could be harvested as a contiguous cell sheet using a simple change in culture temperature conditions. Electron microscopy showed the harvested islet cell sheet to retain cell-cell connections and numerous secretion granules. CONCLUSIONS: The present data indicated that dispersed islet cells, which were appropriately frozen and thawed, represent another viable cells source to create functional islet sheets for tissue engineering and potential clinical applications.

In vivo engineering of metabolically active hepatic tissues in a neovascularized subcutaneous cavity.

Recent success in clinical hepatocyte transplantation therapy has encouraged further investigation into bioengineering hepatic tissues in vivo. Engineering tissues in the subcutaneous space is an attractive method; however, hepatocyte survival has been transient due to insufficient vascular network formation. To establish a vascularized cavity, we created a polyethylene terephthalate mesh device coated with poly(vinylalcohol) that allowed for the gradual release of basic fibroblast growth factor (bFGF), a potent angiogenic factor. The efficacy of the bFGF-releasing device in inducing vascular network formation in the subcutaneous space was observed in mouse and rat studies. Isolated mouse hepatocytes transplanted into newly vascularized subcutaneous cavities allowed for persistent survival up to 120 days. In the absence of a vascularized compartment, the survival of the transplanted hepatocytes was markedly diminished. Functional maintenance of the engineered hepatic tissues was confirmed by high expression of liver-specific mRNAs and proteins. These engineered hepatic tissues have the ability to take up inoculated compounds and express strong induction of drug-metabolizing enzymes, demonstrating functional relevance as a metabolic tissue. In conclusion, we have created a novel technology to engineer functionally active hepatic tissues in the subcutaneous space, which will likely facilitate hepatocyte-based therapies.

Effects of fatigue loading and PMMA precoating on the adhesion and subcritical debonding of prosthetic-PMMA interfaces.

Debonding of clinically relevant CoCrMo-polymethylmethacrylate (PMMA) interfaces is shown to occur subcritically under fatigue loading, implying that debonding may occur at loads much lower than those required for catastrophic failure. Interface fracture mechanics samples containing precoated and uncoated grit-blasted CoCrMo substrates and a PMMA layer were constructed and quantitatively evaluated in terms of their critical interface adhesion and subcritical debond behavior. The precoat surfaces had markedly enhanced adhesion and fatigue resistance in both air and simulated physiological environmental conditions compared to the uncoated samples. Constraint of the PMMA layer does not significantly affect the debond process for thickness between 2- and 5-mm. In addition, wear particles were collected and shown to be consistent with particle sizes reported in vivo and are on the scale of the metal surface roughness. Life prediction methods using the subcritical debond-growth data are discussed.

Drug recovery following buccal absorption of propranolol.

1 Buccal absorption of propranolol in two volunteers was followed by repeated rinsing of the mouth with buffer solutions for twelve 2 min periods. Values for absorption, recovery and asymptotic recovery were calculated. 2 Large amounts of propranolol were recoverable from the buccal mucosa; recovery was biexponential and the amount recovered depended on the time allowed for absorption and on the pH of buffers used for recovery. 3 In the case of the drug studied, the buccal absorption test was not an adequate model of passive drug transfer through lipid membranes, and more clearly reflected partitioning into the buccal mucosa. 4 It does not follow from disappearance of drug from the buccal cavity that it has entered the circulation. Unabsorbed drug clearly cannot enter the circulation, but other conclusions about systemic absorption cannot be drawn with certainty from the buccal absorption model. 5 Partitioning back into the saliva after absorption also needs to be taken into account for a true model of systemic absorption of orally administered drugs, and a revised schematic representation of the kinetics of oral drug absorption is presented.

Effects of an adhesion promoter on the debond resistance of a metal-polymethylmethacrylate interface.

Debonding and premature failure of prostheticpolymethylmethacrylate interfaces have been shown to be exacerbated by exposure to physiological environment. In efforts to counteract these hydrolytic degradation effects, two clinically relevant Co-Cr-Mo surface morphologies were treated with an organosilane adhesion promoter (gamma-methacyloxypropyltrimethoxy) before interface bonding. Samples were quantitatively characterized in terms of the adhesion (fracture) and subcritical debond growth-rate (fatigue) behavior of the interface. The steady-state interface debond resistance, Gss (J/m2), was shown to increase with application of the silane pretreatment both in air (20 degrees C, 45% relative humidity) and simulated physiological environment (37 degrees C, Ringer's). Similarly, positive shifts in the subcritical debond threshold, deltaG(TH), values are observed for silane pretreated interfaces. A shift in the debond path from primarily adhesive failure in untreated surfaces to cohesive failure between the silane layer and bulk polymethylmethacrylate for silane treated surfaces was observed. Silane pretreatment of Co-Cr-Mo surfaces was shown to effectively limit the degree of the environmental degradation. General insights to the effects of surface roughness, chemical enhancement, and the environmental effects on the thermodynamics at the interface and resulting debond behavior are discussed.

Occlusal hypofunction causes changes of proteoglycan content in the rat periodontal ligament.

The biological functions of proteoglycans and glycosaminoglycans are closely associated with mechanical stress on the tissue. In order to reveal the relationship between proteoglycans in the periodontal ligament and mechanical stress such as occlusal stimuli, occlusal hypofunction of rat unilateral mandibular molars was induced by extraction of the opposing first, second and third maxillary molars. Immunohistochemical analyses were performed using antibodies for chondroitin sulfate, decorin, biglycan, heparan sulfate and keratan sulfate, and hyaluronic acid-binding protein. Chondroitin sulfate, observed more strongly in the cervical side than in the apical side of the periodontal ligament of the unextracted sides of mandible, and uniformly present in the extracellular matrix of the periodontal ligament, decreased significantly from 1 wk post-extraction of the antagonists, with a decrease in thickness and disarrangement in fibrous components. Decorin core protein, uniformly present in the periodontal ligament of the unextracted sides, decreased as early on as 2 d post-extraction. Heparan sulfate, mainly localized on the cell surface of vascular endothelial cells and osteoclastic cells as well as in the extracellular matrix of the unextracted sides, decreased significantly in association with the decreased number of blood vessels and osteoclastic cells as early on as 2 d post-extraction. Biglycan, keratan sulfate and hyaluronic acid, uniformly distributed in the periodontal ligament of the unextracted sides, showed little change after the extraction. These results demonstrate that occlusal hypofunction causes tissue remodeling of the periodontal ligament, with a significant decrease of chondroitin sulfate, decorin and heparan sulfate.