In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.     

Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin's lymphoma: dose finding and identification of predictors of response

Previous phase I-II clinical trials have shown that recombinant human erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a randomized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo. A total of 146 patients who had hemoglobin (Hb) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial. Patients were randomized to receive 1,000 U (n = 31), 2,000 U (n = 29), 5,000 U (n = 31), or 10,000 U (n = 26) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the patients, 84 suffered from MM and 62 from low- to intermediate-grade NHL, including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median serum Epo level was 32 mU/mL, and endogenous Epo production was found to be defective in 77% of the patients, as judged by a value for the ratio of observed-to-predicted serum Epo levels (O/P ratio) of < or = 0.9. An intention-to-treat analysis was performed to evaluate treatment efficacy. The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P = .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1,000 U, 2,000 U, 5,000 U, and 10,000 U groups, respectively (P values versus control). The probability of response (delta Hb > or = 2 g/dL) increased steadily and, after 8 weeks, reached 31% (2,000 U), 61% (5,000 U), and 62% (10,000 U), respectively. Regression analysis using Cox's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo, whereas only one quarter of those with adequate Epo levels did so. Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production. From a practical point of view, we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels, whereas the choice of the initial dosage should be based on residual marrow function.     

X-ray Absorption Spectroscopy and Atomic Force Microscopy of Films Generated from Organosulfur Extreme-Pressure (EP) Oil Additives

This study examines the interaction of sulfur-based oil additives on steel. Sulfurized isobutylene, dialkyldithiocarbamate and sulfurized esters were the additives investigated in this report. For the first time, X-ray absorption near edge structure (XANES) spectroscopy has provided detailed insight into the chemistry of both the thermo-oxidative and tribochemical films generated from these additives. It was found that the chemical nature of these films was strongly dependent on the operating environment for the additives. The XANES revealed that thermally, all three S additives reacted very similarly with steel to form a film mainly comprised of iron sulfate at temperatures as low as 100 °C. The ample supply of diffused oxygen from the base oil along with oxide naturally present on the substrate allowed for the complete oxidation of the S from the decomposed additive to iron sulfate. Tribochemical films were comprised of different forms of sulfur than observed for the thermo-oxidative films. The moderate AW conditions yielded a mixture of both oxidized and reduced forms of sulfur, with pyrite, FeS₂, being the major constituent. Rubbing between the steel pin and the substrate partially depleted the oxide layer present, allowing the additive to interact intimately with the fresh substrate, yielding FeS₂. Under extreme-pressure conditions, complete removal of the oxide layer occurred with a drastic increase in the interfacial temperatures between the pin and v-block, allowing for the complete thermal decomposition of FeS₂ to FeS to occur. AFM imaging of the AW films revealed the presence of tiny smooth domains randomly oriented, which were completely different from the pad-like structures observed for AW films generated from a typical ashless thiophosphate additive. The inability of the sulfur-based additives to form large pad-like structures, which can ultimately support the load, resulted in poor AW protection to the metal.     

Study of interaction of EP and AW additives with dispersants using XANES

The chemical interaction of two kinds of dispersants (bis-succinimide dispersant and borated bis-succinimide dispersant) with four kinds of antiwear (AW) and extreme pressure (EP) additives (zinc dialkyldithiophosphate, dialkyldithiophosphate ester, diphenylphosphate ester and dialkyldithiocarbamate) has been investigated under different contact pressures. The chemical compositions of the tribofilms have been studied by B, N, P and S X-ray absorption near edge structure (XANES) spectroscopy. The N K-edge XANES analysis has been used to follow the reaction pathway of amine and imide functional groups in the dispersants and their interactions with EP and AW additives. It has been found that AW additives react with amine to form amine phosphate at low load. However, at high load, there is a good evidence for the formation of a nitrate phase in the tribofilms, the first direct observation of oxidative dispersant loss in the rubbing contact. On the other hand, EP additives behave differently and in general are less reactive. The B K-edge XANES has been employed to follow the interaction of borated dispersant with the EP and AW additive. In general, boron originally in the trigonal coordination, is converted to a tetrahedral coordination form in the process of tribofilm formation.     

The effect of vegetable and spice addition on the acrylamide content and antioxidant activity of innovative cereal products

The aim of the work was to assess the impact of vegetable and spice addition on the acrylamide content and antioxidant activity of extruded cereal crisps. The foods were based on grain ingredients, such as brown rice, whole grain flour, wheat bran, with different vegetables. Products from one group contained green vegetables, such as broccoli and zucchini; garlic was included as a flavour additive (0.75–1.50%). The second group of crisps consisted of similar cereal ingredients with pumpkin and cinnamon; additionally ginger was included as a flavour additive (0.75–1.50%). The results indicate that the production of a new, innovative product with appropriate nutritional value and acceptable quality is a complex process. The production process significantly changed the nutritional value of the product. The content of acrylamide in zucchini and broccoli crisps was relatively low; ranging from 78 to 86 μg/kg of product. The addition of garlic did not significantly affect the acrylamide content in the final product. For cereal–pumpkin crisps, the acrylamide content was 7 times higher in comparison with zucchini and broccoli products. The acrylamide content in pumpkin and ginger crisps exceeded the benchmark level. The antioxidant activity of the pumpkin product was significantly higher (p < 0.05) than for crisps with green vegetables.     

Issues of death and dying: the perspective of critical care nurses

A major shift in the care of terminally ill people, due to advances in technology, and the development of legislation regarding patient self-determination and autonomy, has occurred over recent years. Critical care nurses (CCNs) are involved daily in issues of death and dying and are very aware of the needs, fears and psychosocial issues of patients and their families. Professional associations see a legitimate role for nurses in assisting the dying to achieve a dignified death. For legislation, policies and guidelines surrounding end-of-life issues to be effective, and to assist nursing staff with these sensitive, often difficult concerns, it is important that data on the opinions and perspectives of CCNs be objectively obtained. In a study by the Department of Social and Preventive Medicine at the University of Queensland, questionnaires were sent to 1100 randomly sampled community members and almost 1200 health professionals (nurses, general practitioners and specialists), including 299 CCNs. The response rate of CCNs to a 30-page postal questionnaire was 79 per cent (n = 231), indicating those nurses' high levels of interest in and/or concern regarding this area. CCNs supported the use of advance directives, the appointment of proxies and the need for doctors and nurses to give sufficient medication to relieve pain, even if this hastened the death of the patient. In addition, CCNs, more than any other professional group, supported the right of the terminally ill patient to physician-assisted suicide or euthanasia, their responses being very similar to those of community members. CCNs clearly face issues which, from legal, medical and ethical viewpoints, cause them concern. In sharing their personal experiences, CCNs stressed the need for more communication between doctors and patients, as well as between doctors and nurses. In addition, CCNs saw a clear role for themselves as advocates for patients/families in the decision-making process.     

Continuous Well-Composedness Implies Digital Well-Composedness in n-D

Journal of Mathematical Imaging and Vision - In this paper, we prove that when a n-D cubical set is continuously well-composed (CWC), that is, when the boundary of its continuous analog is a...     

Comparative control of the bioactivity of some frequently consumed vegetables subjected to different processing conditions

The main aim of this investigation was to find processing conditions and to control them, which maximally preserve bioactive compounds and antioxidant activity of garlic and onions. Garlic, white and red onions were subjected to bleaching and boiling. The contents of polyphenols, flavonoids, flavanols, tannins, corresponding antioxidant activities and their correlation coefficients were determined in various methanol and acetone extracts. The antioxidant activity was determined by 2, 2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric-reducing/antioxidant power (FRAP) and Cupric reducing antioxidant capacity (CUPRAC) antioxidant assays. It was found that bleaching for 90″ most fully preserves polyphenols (8.25, 9.75 and 11.98 vs. 9.00, 10.52 and 15.87 mg GAE/g DW and the level of antioxidant activity – 8.82, 22.50 and 23.90 vs. 9.00, 23.05 and 24.30 μM TE/g DW of DPPH in extracts of treated samples with 100% of methanol vs. raw garlic, white and red onions, respectively. In conclusion, comparative control shows that bleaching for 90″ of all studied vegetables most fully preserves contents of bioactive compounds and the level of antioxidant activity. Extraction of bioactive compounds with 100% methanol was more effective than with 50% methanol and 100% acetone.     

Thymosin beta4, inhibitor for normal hematopoietic progenitor cells

Thymosin beta4 (Tbeta4), isolated from the calf thymus fraction 5, has a ubiquitous localization and plays a pleiotropic role in both the immune and nonimmune systems. Because it contains at its N-terminal end the sequence of a known inhibitor of hematopoiesis, the acetylated tetrapeptide Ac-N-Ser-Asp-Lys-Pro (AcSDKP, Goralatide), we have assayed Tbeta4 on human hematopoietic cells. We demonstrate that it inhibits normal bone marrow progenitor cell growth; indeed, it decreased the growth of both granulo-macrophagic and erythroid progenitors and reduces their percentage in S phase. Furthermore, we show that Tbeta4 reduces both the clonogenicity and the cell proliferation of purified CD34+ cells induced by a combination of seven growth factors. Although Tbeta4's inhibitory effect is very similar to that of AcSDKP, we demonstrate, using neutralizing antibodies and a truncated form of Tbeta4 devoid of the AcSDKP sequence, that the inhibitory effect of Tbeta4 is not mediated by the sequence AcSDKP. These data indicate that Tbeta4 is a novel inhibitor for human normal hematopoietic progenitors.