Fabrication and characterization of poly(DL-lactic-co-glycolic acid)/zirconia-hybridized amorphous calcium phosphate composites

Several minerals, such as hydroxyapatite and β-tricalcium phosphate, have been incorporated into bioresorbable polyester bone scaffolds to increase the osteoconductivity both in vitro and in vivo. More soluble forms of calcium phosphate that release calcium and phosphate ions have been postulated as factors that increase osteoblast differentiation and mineralization. Recently, a zirconia-hybridized pyrophosphate-stabilized amorphous calcium phosphate (Zr-ACP) has been synthesized allowing controlled release of calcium and phosphate ions. When incorporated into bioresorbable scaffolds, Zr-ACP has the potential to induce osteoconductivity. In this study, 80–90% (w/v) porous poly(DL-lactic-co-glycolic acid) (PLGA) scaffolds were formed by thermal phase separation from dioxane while incorporating Zr-ACP. Scanning electron microscopy revealed a highly porous structure with a pore size ranging from a few μm to about 100 μm, smaller than we had hoped for. Zr-ACP particles were evenly dispersed in the composite structure and incorporated into the pore walls. The amorphous structure of the Zr-ACP was maintained during composite fabrication, as found by X-ray diffraction. Composite scaffolds had larger compressive yield strengths and moduli compared to pure polymer scaffolds. These initial efforts demonstrate that PLGA/Zr-ACP composites can be formed in ways that ultimately serve as promising bone scaffolds in tissue engineering.     

Effect of synthesis temperature of PEO-grafted PU/PS IPNs on surface morphology and in vitro blood compatibility

When hydrophilic/hydrophobic polymers have a microdomain structure, platelet adhesion and activation are effectively suppressed by prohibition of the excessive assembly of glycoproteins and adenosine triphosphate (ATP) consumption of the platelets on the surface. In this study, poly(ethylene oxide)-grafted hydrophilic polyurethane (PU)/hydrophobic polystyrene (PS) interpenetrating polymer networks (IPNs) were synthesized by varying the synthesis temperature to control the phase separation and the microdomain surface structure, and the effect of the degree of phase separation on the in vitro blood compatibility. The size of the dispersed PS-rich domains in the PU-rich matrix decreased, and the hydrophilicity also decreased as the synthesis temperature of the PS network during the IPN synthesis was decreased, as the phase separation was suppressed during the synthesis. The amount of the adsorbed bovine plasma fibrinogens (BPF) on the PEO-grafted PU/PS IPNs decreased as the synthesis temperature was decreased, and the in vitro adhesion of the platelets was also suppressed on the PEO-grafted PU/PS IPNs prepared at lower temperature. The microdomain structure on the surface affected the adhesion and the activation of the adhered platelets, and the suppression of the phase separation resulted in the decrease of the domain size, which also enhanced the blood compatibility of the PEO-grafted PU/PS IPNs.     

Effects of intragastric administration of predigested nutrients on food intake,body weight and taste acceptability: Potential relevance of the cephalic/neural phase of digestion

In this study we analyzed the effect of the intragastric administration of partially digested and natural nutrients on subsequent food intake, body weight and flavor acceptability in rats. The results showed that enterally administered natural nutrients reduced the subsequent ingestion of food to a greater degree compared with the same nutrients in partially digested form. This greater reduction does not appear to be due to a higher nutritional effect of the former, because the body weight of both groups of animals was similar. Animals intragastrically administered with partially digested nutrients developed an acceptance response to a previously paired flavored stimulus, in contrast to animals receiving natural nutrients under the same conditions. These results are interpreted in terms of the cephalic phase of digestion and may be relevant to the treatment of clinical symptoms associated with enteral feeding.     

Delirium in a Palliative Care Unit

Abstract

Intractable pain and other intolerable symptoms or the patients' wish to exercise self-determination can mandate palliative sedation. Yet, three bioethical principles must be balanced in comparable situations: one and two being beneficence (to do the best for our patient) and non-maleficence (do no harm) versus patient autonomy (the right for self-determination). Theoretically, palliative sedation incurs the potential risk of accelerating death, particularly in cases in which the disease is not advanced, because the consequences of sedation (perhaps no calorie or fluid uptake) would be likely to cause death (refusal to eat or drink sufficiently). If, however, the disease is far advanced (and the prognosticated life-span short) and the patient unwilling to eat and drink anyway, then initiated sedation might not be associated with accelerated death (and thus do harm to the patient, from an external viewpoint). Therefore, palliative sedation continues to be an area of discussion and a challenge as to when and how to implement it. Here, we introduce the case of a patient with advanced gastric cancer who asked for palliative sedation. We briefly describe his and the family's thoughts and follow the course of the disease until his death. With this report, we re-emphasize that, with precise sedation by continuous infusion of midazolam, it is possible to let the patient wake up for voiding and defecation and communicate with family members. By such individual approaches, it is possible to let the natural course of disease continue. Our patient had at no point in time asked for physician-assisted suicide.     

Synthesis, antihypertensive activity, and 3D-QSAR studies of some new p-hydroxybenzohydrazide derivatives

p-Hydroxybenzohydrazide 2 on treatment with aromatic/aliphatic aldehyde followed by cyclization with carbon disulphide afforded compounds 4a-4n. Also, compound 2 by treatment of substituted isothiocyanate followed by the treatment of chloroacetic acid yields the corresponding compounds 6a-6i. All the test compounds were assayed for antihypertensive activity by non-invasive blood pressure measurement and invasive blood pressure measurement methods. The test compounds showed significant antihypertensive activity. The intact compounds were subjected to 3D-QSAR studies. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r(2) = 0.98, q(2) = 0.74) was achieved. The 3D-QSAR plots illustrated insights into the structure-activity relationship of these compounds which may aid in the design of potent p-hydroxybenzohydrazide derivatives as antihypertensive agents.     

Circulating γδ T cells and the risk of acute‐phase response after zoledronic acid administration

The use of intravenous nitrogen‐containing bisphosphonates (N‐BPs) is associated with the appearance of an acute phase response (APR) in a proportion of the patients for reasons that are poorly understood. The APR was attributed to the indirect activation of γδ T cells with the release of interferon‐γ and tumor necrosis factor (TNF). Forty patients with postmenopausal or senile osteoporosis (age range = 53–91 years) never previously treated with intravenous (iv) bisphosphonate, received a single 5‐mg zoledronic acid (ZOL) iv infusion over 15 minutes. White blood cells were counted and analyzed with an automated hematology analyzer (ADVIA 2120i Siemens, New York, USA) and by flow cytometer (BD FACSCanto, Becton Dickinson). The occurrence of APR was defined by the occurrence of fever (>37 °C) during the next 2 days. Forty‐two percent of patients (17 of 40) receiving the infusion of ZOL experienced an APR. Compared with the others they were younger (69 ± 7 years versus 74 ± 8 years; p = 0.06), and both the proportion and absolute number of γδ T cells were significant higher (p = 0.02 and p = 0.013, respectively). Nonsignificant differences were found between the two groups for white blood cells and for the other circulating lymphocyte subpopulations. Age was inversely correlated with circulating γδ T cells (p = 0.003) but the difference between the two groups in circulating γδ T cells persisted for age‐adjusted values and vice versa. In conclusion, the results of this study indicate that the number of circulating γδ T cells, together with age, are important determinant of the occurrence of APR after intravenous infusion of ZOL and possibly of any other N‐BPs. © 2012 American Society for Bone and Mineral Research