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.     

Intermediate-conductance calcium-activated potassium channels participate in neurovascular coupling

BACKGROUND AND PURPOSE

Controlling vascular tone involves K⁺ efflux through endothelial cell small- and intermediate-conductance calcium-activated potassium channels (K_Ca2.3 and K_Ca3.1, respectively). We investigated the expression of these channels in astrocytes and the possibility that, by a similar mechanism, they might contribute to neurovascular coupling.

EXPERIMENTAL APPROACH

Transgenic mice expressing enhanced green fluorescent protein (eGFP) in astrocytes were used to assess K_Ca2.3 and K_Ca3.1 expression by immunohistochemistry and RT-PCR. K_Ca currents in eGFP-positive astrocytes were determined in situ using whole-cell patch clamp electrophysiology. The contribution of K_Ca3.1 to neurovascular coupling was investigated in pharmacological experiments using electrical field stimulation (EFS) to evoke parenchymal arteriole dilatation in FVB/NJ mouse brain slices and whisker stimulation to evoke changes in cerebral blood flow in vivo, measured by laser Doppler flowmetry.

KEY RESULTS

K_Ca3.1 immunoreactivity was restricted to astrocyte processes and endfeet and RT-PCR confirmed astrocytic K_Ca2.3 and K_Ca3.1 mRNA expression. With 200 nM [Ca²⁺]_i, the K_Ca2.1-2.3/K_Ca3.1 opener NS309 increased whole-cell currents. CyPPA, a K_Ca2.2/K_Ca2.3 opener, was without effect. With 1 µM [Ca²⁺]_i, the K_Ca3.1 inhibitor TRAM-34 reduced currents whereas apamin (K_Ca2.1-2.3 blocker) had no effect. CyPPA also inhibited currents evoked by NS309 in HEK293 cells expressing K_Ca3.1. EFS-evoked Fluo-4 fluorescence confirmed astrocyte endfoot recruitment into neurovascular coupling. TRAM-34 inhibited EFS-evoked arteriolar dilatation by 50% whereas charybdotoxin, a blocker of K_Ca3.1 and the large-conductance K_Ca channel, K_Ca1.1, inhibited dilatation by 82%. TRAM-34 reduced the cortical hyperaemic response to whisker stimulation by 40%.

CONCLUSION AND IMPLICATIONS

Astrocytes express functional K_Ca3.1 channels, and these contribute to neurovascular coupling.

LINKED ARTICLES

This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-3     

Acute kidney injury among medical and surgical in-patients in the Cape Coast Teaching Hospital,Cape Coast,Ghana: a prospective cross-sectional study

BackgroundAcute kidney injury (AKI) is a syndrome associated with high morbidity, mortality and high hospital costs. Despite its adverse clinical and economic effects, only a few studies have reported reliable estimates on the incidence of AKI in sub-Sahara Africa. We assessed the incidence and associated factors of AKI among medical and surgical patients admitted to a tertiary hospital in Ghana.MethodsA prospective cross-sectional study was conducted among one hundred and forty-five (145) consecutive patients admitted to the medical and the surgical wards at the Cape Coast Teaching Hospital (CCTH), Cape Coast, Ghana from April 2017 to April 2018. Socio-demographic and clinical information were collected using structured questionnaires. AKI was diagnosed and staged with the KDIGO guideline, using admission serum creatinine as baseline kidney function.ResultsThe mean age of the study participants was 46.6±17.7 years, whilst the male:female ratio was 68:77. The overall incidence of AKI among the participants was 15.9% (95% CI: 10.33 – 22.84%). Stage 1 AKI occurred in 56.5% of the participants, whilst stages 2 and 3 AKI respectively occurred among 4.1% and 2.8% of respondents. About 20% of the participants in the medical ward developed AKI (n= 15) whilst 12% of those in surgical ward developed AKI (n= 8). Among the participants admitted to the medical ward, 60.0%, 26.7% and 13.3% had stages 1, 2 and 3 AKI respectively. Whilst 50.0%, 25.0% and 25.0% respectively developed stages 1, 2 and 3 AKI in the surgical ward. Medical patients with AKI had hypertension (40%), followed by liver disease (33.3%); 37.5% of surgical inpatients had gastrointestinal (GI) disorders.ConclusionThe incidence of AKI is high among medical and surgical patients in-patients in the CCTH, Ghana, with hypertension and liver disease as major comorbidities.     

A molecular basis for hemoglobin-H disease in American blacks

We have applied gene counting and restriction endonuclease mapping techniques to the study of two American black families in which there were one or more cases of HbH disease. We found deletions of three of the four normal alpha-globin genes in individuals with HbH disease. In two of these individuals, the chromosome containing the single alpha gene could have originated by crossing over between mispaired alpha genes, resulting in a deletion of about 4.2 kilobases (kb).     

Duodenal mucosal histology and histochemistry in active, treated and healed duodenal ulcer: Correlation with duodenal prostaglandin E2 production

We investigated whether impaired duodenal mucosal prostaglandin E₂ (PGE₂) production previously observed in duodenal ulcer (DU) was a primary pathophysiological abnormality or secondary to mucosal architectural changes that accompany ulceration. One hundred patients were studied: at endoscopy, paired duodenal biopsies were taken in patients with normal endoscopies and from the ulcer edge or scar and background mucosa in active or healed DU. One of the pair of biopsies was used to estimate PGE₂ synthesis ability, the other was processed for histology and histochemistry. The following features graded: goblet cell numbers and staining with Periodic acid-Schiff reagent (PAS), epithelial staining with PAS, villous atrophy, columnar cell height, inflammatory cell infiltrate and micro-erosions and gastric metaplasia taken as a whole. Patients were found to have normal endoscopy (n= 31), active untreated DU (n= 20), active DU on treatment with either cimetidine or ranitidine (n= 13), healed DU on maintenance treatment (n= 27) and healed DU off treatment (n= 9). Active duodenal ulceration was found to be associated with decreased numbers of goblet cells, loss and blunting of villi, increased columnar cell height, increased epithelial cell PAS staining and with gastric metaplasia. After healing, only villous blunting remained. These changes were present, but less marked, at sites removed from the ulcer and were not apparent in the patient groups with healed ulcers. A strong correlation between overall gastric metaplasia and epithelial cell PAS staining and the reduced ability to synthesize PGE₂ (P < 0.001) was only apparent when biopsies from all patients were grouped together, but not within individual patient subgroups. There was no consistent correlation between PGE₂ generation and individual parameters of pathological change in the duodenum. We conclude that, although inflammatory and mucosal changes may contribute, the evidence suggests that the impaired PGE₂ generation in DU disease is, to a large extent, independent of histological and histochemical features.