P47 Creation of longer-lasting (substantive) oral care flavours

Mainstream oral care flavours are primarily designed to provide hedonic (taste) benefits and to promote breath freshness. In particular, a key criterion for a commercially successful toothpaste flavour is a long lasting reduction in the perception of mouth odour. Various additives can help deliver this benefit, in addition to flavours formulated according to patented guidelines. The residence time (substantivity) in the mouth of flavours and additives is clearly critical with respect to the longevity of the breath-freshening benefit, and little data are available in the literature to guide the selection of substantive components. The aim of this project was to investigate the dynamics of flavour loss from the buccal cavity following brushing using a mass spectrometer equipped with an atmospheric pressure headspace sampler which enabled real-time determination of flavour components in mouth air. A number of flavour ingredients found in peppermint- and spearmint-based oral care flavours were studied. The in vivo decay kinetics of flavour ingredient loss were quantified and found to be strongly related to the physicochemical properties of ingredients, except in the case of esters where a more complex dependence was observed arising from chemical transformation occurring in addition to physical transportation away from the mouth. Surprisingly, some materials were discovered to undergo rapid degradation with a half-life of minutes. Confirmatory studies of the decay kinetics of such materials were carried out in vitro, and structural features were identified which were associated with the observed hydrolytic vulnerability. This work has allowed the development of new guidelines to enable the creation of longer-lasting oral care flavours.     

Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging

A wide variety of neuroendocrine tumours express somatostatin receptors, and can be visualized by radiolabelled somatostatin analogue scintigraphy. To investigate the value of [111In]-octreotide scintigraphy (Octreoscan), 48 patients (37 with proven carcinoid, pancreatic endocrine and medullary carcinoma of thyroid tumours, 11 with neuroendocrine syndromes multiple endocrine neoplasia (MEN-I) and Zollinger-Ellison syndrome (ZES) were examined with 111In-DTPA-D-Phe1- octreotide. Scintigrams were obtained at 24 and 48 h, and the results were compared with CT and magnetic resonance imaging (MRI). Thirty-five of 48 patients had positive [111In]-octreotide scintigraphy (23/25 (92%) carcinoids, 8/9 (89%) PETs, 4/11 (36%) MEN-I & ZES). Of the 42 lesions located by conventional imaging techniques, 37 (88%) were also identified by Octreoscan. Unexpected lesions (40 sites), not detected by CT or MR imaging were found in 24/48 (50%) patients. [111In]- octreotide scintigraphy has a higher sensitivity for tumour detection, and is superior to MR imaging and CT scanning in the identification of previously unsuspected extraliver and lymph node metastases. It may also be helpful for the localization of clinically suspected tumours in patients with MEN-I and ZES.      

体外培养脂肪组织来源干细胞与胶原/壳聚糖复合支架的亲和性

目的：制备适合脂肪组织来源的干细胞生长的支架,观察复合支架各组成的体积比率与细胞培养的亲和性. 方法：实验于2006-09/2007-01在大连理工大学干细胞与组织工程研发中心完成.①实验方法：将3.55 g/L Ⅰ型胶原和20 g/L壳聚糖分别以9∶1,7∶3,5∶5,3∶7,1∶9的体积比混合冻干,碳化二亚胺/N-羟基琥珀酰亚胺交联后再次冻干并进行分析.②实验评估：扫描电镜观察不同材料交联前后的微观结构;IPP软件分析计算支架的平均孔径;测量支架的吸水性和孔隙率;通过胶原酶检测支架的体外生物可降解性;扫描电镜和苏木精-伊红染色观察脂肪组织来源的干细胞在复合支架上的生长情况. 结果：①交联前后的微观结构：冻干后的各种支架材料呈白色,表面粗糙,材料内部呈海绵状多孔隙结构,其中以胶原/壳聚糖体积比为9∶1的复合支架最为疏松,1∶9的支架最致密.扫描电镜下支架的胶原含量越高,支架内的胶原丝越多,支架的孔与孔之间相互连通构成了通孔.交联前后支架的形态结构无明显改变.②支架的平均孔径∶交联后体积比为9∶1,7∶3和5∶5的复合支架孔径50～200 μm,可用于细胞的三维培养.③支架的吸水性和孔隙率∶体积比为5∶5的复合支架的吸水性和含水量最高,而7∶3次之;多孔支架在水中未发生明显的溶胀现象;支架的孔隙率均在90%以上.④支架的体外生物可降解性：未交联的支架随着胶原含量的减少,支架的降解速率增加.而交联后随着胶原含量的减少,降解速率减慢,交联后的复合支架降解速度较未交联慢.⑤脂肪组织来源的干细胞在复合支架上的生长情况：脂肪组织来源的干细胞在支架上培养5 d后扫描电镜观察细胞在7∶3的支架上爬行生长并融合成片,苏木精-伊红染色观察支架孔内及表面出现大量的细胞团,并融合成片状,而5∶5支架上黏附生长的细胞较少. 结论：结合支架的孔径、吸水性、孔隙率、体外生物可降解性和细胞与支架的生物相容性,可知体积比为7∶3的复合支架对脂肪组织来源的干细胞的亲和性较好,适于脂肪组织来源的干细胞的三维培养.     

PDLA/PLLA and PDLA/PCL nanofibers with a chitosan‐based hydrogel in composite scaffolds for tissue engineered cartilage

Osteoarthritis (OA) is the most prevalent musculoskeletal disease in humans, causing pain, loss of joint motility and function, and severely reducing the standard of living of patients. Cartilage tissue engineering attempts to repair the damaged tissue of individuals suffering from OA by providing mechanical support to the joint as new tissue regenerates. The aim of this study was to create composite three dimensional scaffolds comprised of electrospun poly(D,L‐lactide)/poly(L‐lactide) (PDLA/PLLA) or poly(D,L‐lactide)/polycaprolactone (PDLA/PCL) with salt leached pores and an embedded chitosan hydrogel to determine the potential of these scaffolds for cartilage tissue engineering. PDLA/PLLA‐hydrogel scaffolds displayed the largest compressive moduli followed by PDLA/PCL‐hydrogel scaffolds. Dynamic mechanical tests showed that the PDLA/PLLA scaffolds had no appreciable recovery while PDLA/PCL scaffolds did exhibit some recovery. Primary canine chondrocytes produced both collagen type II and proteoglycans (primary components of extracellular matrix in cartilage) while being cultured on scaffolds composed of electrospun PDLA/PCL. As a result, a composite electrospun embedded hydrogel scaffold shows promise for treating individuals suffering from OA. Copyright © 2012 John Wiley & Sons, Ltd.     

The Pim protein kinases regulate energy metabolism and cell growth

The serine/threonine Pim kinases are overexpressed in solid cancers and hematologic malignancies and promote cell growth and survival. Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the rapamycin-sensitive mammalian target of rapamycin (mTORC1) activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK). Mouse embryonic fibroblasts (MEFs) deficient for all three Pim kinases [triple knockout (TKO) MEFs] demonstrated activated AMPK driven by elevated ratios of AMPATP relative to wild-type MEFs. Consistent with these findings, TKO MEFs were found to grow slowly in culture and have decreased rates of protein synthesis secondary to a diminished amount of 5'-cap-dependent translation. Pim-3 expression alone in TKO MEFs was sufficient to reverse AMPK activation, increase protein synthesis, and drive MEF growth similar to wild type. Pim-3 expression was found to markedly increase the protein levels of both c-Myc and the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), enzymes capable of regulating glycolysis and mitochondrial biogenesis, which were diminished in TKO MEFs. Overexpression of PGC-1α in TKO MEFs elevated ATP levels and inhibited the activation of AMPK. These results demonstrate the Pim kinase-mediated control of energy metabolism and thus regulation of AMPK activity. We identify an important role for Pim-3 in modulating c-Myc and PGC-1α protein levels and cell growth.     

Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity

Alloimmune feto-maternal destruction of blood cells is thought to be mediated by binding of alloantibodies to Fc receptors on effector cells. Blocking the antigen using inert antibodies might prolong cell survival. We have performed a "proof of principle" study in volunteers to measure the intravascular survival of autologous red cells coated with human recombinant IgG antibody containing a novel constant region, G1Deltanab, devoid of in vitro cytotoxic activity. RhD-positive red blood cells (RBCs), labeled with chromium-51 or technetium-99m, were separately coated to equal levels with wild-type IgG1 or G1Deltanab anti-D antibody (Fog-1). After re-injection, there was complete, irreversible clearance of IgG1-coated RBCs by 200 minutes, concomitant with appearance of radiolabel in plasma. Gamma camera imaging revealed accumulation in spleen and, at higher coating levels, in liver. In contrast, clearance of G1Deltanab-coated cells was slower, incomplete, and transient, with whole blood counts falling to 7% to 38% injected dose by about 200 minutes before increasing to 12% to 67% thereafter. There was no appearance of plasma radiolabel and no hepatic accumulation. These findings suggest that G1Deltanab-coated RBCs were not hemolysed but temporarily sequestered in the spleen and that our approach merits investigation in larger studies.     

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

Numerous genetic alterations have been identified during prostate cancer progression. The influence of environmental factors, particularly the diet, on the acceleration of tumor progression is largely unknown. Expression levels and/or activity of Src kinase are highly elevated in numerous cancers including advanced stages of prostate cancer. In this study, we demonstrate that high-fat diets (HFDs) promoted pathological transformation mediated by the synergy of Src and androgen receptor in vivo. Additionally, a diet high in saturated fat significantly enhanced proliferation of Src-mediated xenograft tumors in comparison with a diet high in unsaturated fat. The saturated fatty acid palmitate, a major constituent in a HFD, significantly upregulated the biosynthesis of palmitoyl-CoA in cancer cells in vitro and in xenograft tumors in vivo. The exogenous palmitate enhanced Src-dependent mitochondrial β-oxidation. Additionally, it elevated the amount of C16-ceramide and total saturated ceramides, increased the level of Src kinase localized in the cell membrane, and Src-mediated downstream signaling, such as the activation of mitogen-activated protein kinase and focal adhesion kinase. Our results uncover how the metabolism of dietary palmitate cooperates with elevated Src kinase in the acceleration of prostate tumor progression.     

Predictive Factors of Swallowing Disorders and Bronchopneumonia in Acute Ischemic Stroke

Background: In stroke patients, early complications such as swallowing disorders (SD) and bronchopneumonia (BP) are frequent and may worsen outcome. The aim of this study was to evaluate the prevalence of SD in acute ischemic stroke (AIS) and the risk of BP, as well as to identify factors associated with these conditions. Methods: We retrospectively studied all AISs over a 12-month period in a single-center registry. We determined the frequency of SD in the first 7 days and of BP over the entire hospital stay. Associations of SD and BP with patient characteristics, stroke features, dental status, and presence of a feeding tube were analyzed in multivariate analyses. Results: In the 340 consecutive patients, the overall frequency of SD and BP was 23.8% and 11.5%, respectively. The multivariate analyses showed significant associations of SD with NIHSS scores >4, involvement of the medulla oblongata and wearing a dental prosthesis (area under the receiver-operator curve (AUC) of 76%). BP was significantly associated with NIHSS scores >4, male sex, bilateral cerebral lesions, the presence of SD, and the use of an enteral feeding tube (AUC 84%). In unadjusted analysis, unfavorable 12-month outcome and mortality were increased in the presence of SD. Conclusion: In AIS, SD and BP are associated with stroke severity and localization and wearing a dental prosthesis increases the risk of SD. Given that patients with SD have an increased risk of poor outcome and mortality, high-risk patients warrant early interventions, including more randomized trials.