bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing the dynamics of neutrophil accumulation in vivo by reflectance confocal microscopy
Authors: Wolberink Eshter A.W. , Peppelman Malou , van de Kerkhof Peter C.M. , van Erp Piet E.J. , Gerritsen Marie‐Jeanne P.
Published: February 2014

Reflectance confocal microscopy (RCM) is an imaging tool, which visualizes the epidermal skin layers in vivo with a cellular resolution. Neutrophil accumulation is a characteristic feature in psoriasis and is thought to play a role in the pathophysiology of psoriasis. Until now, imaging of neutrophil accumulation in vivo is not performed. We evaluated the dynamics of neutrophil migration in active psoriatic lesions by non‐invasive RCM imaging. Additionally, we evaluated the time phasing and duration of neutrophil trafficking. We performed RCM imaging prior to the start of topical treatment and for seven consecutive days with a 24‐h time interval at the Radboud University Medical Center, Nijmegen, the Netherlands. Twelve psoriatic lesions in three patients with a severe exacerbation of psoriasis were included. The four most active lesions were selected in each patient based on the highest degree of redness, induration and expansion in the previous 2 weeks. In all lesions, a cyclic pattern of neutrophil migration was observed, consisting of squirting papillae, transepidermal migration, accumulation in the stratum spinosum, accumulation in the stratum corneum and degeneration of the abscesses. The time interval of a neutrophil‐trafficking cycle was 5–7 days and showed a synchronic time phasing. This study is the first to establish the dynamics and time phasing of neutrophil migration in vivo in psoriatic lesions. Previously reported theories were confirmed by these novel in vivo data. RCM might distinguish between active or chronic psoriatic areas, which might contribute to new insights into the pathogenesis of psoriasis.
Astaxanthin, a xanthophyll carotenoid, inhibits ultraviolet‐induced apoptosis in keratinocytes
Authors: Yoshihisa Yoko , Rehman Mati ur , Shimizu Tadamichi
Published: February 2014

Intra‐cellular reactive nitrogen/oxygen species and apoptosis play important roles in ultraviolet (UV)‐induced inflammatory responses in the skin. Astaxanthin (AST), a xanthophyll carotenoid, exhibits diverse clinical benefits. The protective effects of AST against UV‐induced apoptosis were investigated in the present study. Astaxanthin (5 μm) caused a significant decrease in the protein content and the mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase (COX)‐2, and decreased the release of prostaglandin E2 from HaCaT keratinocytes after UVB (20 mJ/cm2) or UVC (5 mJ/cm2) irradiation. No significant protective effects against UV‐induced reactive oxygen species (ROS) were observed in AST‐pretreated cells. Astaxanthin caused a significant inhibition of UV‐irradiation‐induced apoptosis, as evidence by a DNA fragmentation assay. Furthermore, we found that the treatment with AST caused a reduction in the UVB‐ or UVC‐induced protein and mRNA expression of macrophage migration inhibitory factor (MIF), IL‐1β and TNF‐α in HaCaT keratinocytes. These results suggest that AST effectively protects against UV‐induced inflammation by decreasing iNOS and COX‐2, and thereby inhibiting the apoptosis of keratinocytes.
Therapeutic potential of the anti‐diabetic agent metformin in targeting the skin cancer stem cell diaspora
Authors: Reddi Anand , Powers Matthew A. , Dellavalle Robert P.
Published: February 2014

Type II diabetes is associated with increased prevalence of cancer including both melanoma and squamous cell carcinoma (SCC) of the skin. Emerging evidence from epidemiological studies suggest that diabetic patients on metformin have a lower risk of cancer incidence and mortality in a broad range of neoplasms. In both melanoma and SCC, populations of cancer stem cells (CSC) contribute to tumor initiation and metastasis. We propose that metformin constitutes a new class of targeted therapy that acts on the skin CSC diaspora. We posit that metformin selectively and simultaneously targets CSCs of the primary tumor as well as in metastatic niches thereby disrupting the dynamic dispersal of circulating CSCs between the primary tumor and metastatic site. This hypothesis suggests a new concept in dermato‐oncology that treatment of type II diabetes and prevention of skin cancer are two sides of the same coin.
Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases
Authors: Kim Hye One , Kim Jin Hye , Chung Bo Young , Choi Min Gyu , Park Chun Wook
Published: February 2014

Polychlorinated biphenyls (PCBs) and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) are major environmental pollutants, and their effects on the human body critically depend on the aryl hydrocarbon receptor (AhR). The aim of this study was to evaluate the significance of the AhR and its ligands in chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Expression of AhR‐related mRNA was increased in lesional skin from patients with AD and psoriasis compared to those of normal skin from healthy controls. The AhR and aryl hydrocarbon receptor nuclear translocator were colocalized in the nuclei of keratinocytes at the lower epidermis of psoriatic lesions, which suggested activation of the AhR pathway. After treatment of normal human epidermal keratinocytes with TCDD or PCBs, IL‐6 and IL‐8 production were increased. The results of this study suggest that AhR is highly expressed in the acute lesional skin of patients with AD and psoriasis, and the AhR pathway is activated especially in psoriasis.
MAUPing Workplace Clusters
Authors: Nielsen Michael M. , Hennerdal Pontus
Published: February 2014

The modifiable areal unit problem (MAUP) is seldom accounted for in economic geography cluster studies. This issue is particularly problematic as clusters play such a central role in regional development policy. In this study, we tested for the appearance of the MAUP when examining workplace category clusters over three different administrative scales in Stockholm County, Sweden. The measures used were the standardised ratio, global autocorrelation, and local autocorrelation. We discovered not only that the appearance of clusters depended on the administrative unit scale but also that the location of the clusters, based on the local indicator of spatial association, fluctuated wildly over the various administrative scales. Thus, our conclusion was that the robustness and validity of workplace category clusters should always be challenged if the MAUP has not been taken into account, or at least tested for.
Does Federal Aid to States Aid the States?
Authors: Horváth Zachary , Moore Brian David , Rork Jonathan C.
Published: February 2014

Using data from 1977 to 2009, we explore whether the agency issuing federal aid to states influences the rate of state economic growth. We find that agencies' housing poverty alleviation programs, such as the Department of Health and Human Services and the Department of Labor, have negative effects. The Department of Commerce and the Department of Interior have consistent positive effects, although this last effect is due to inordinately disproportionate spending in the state of Wyoming. Overall growth effects are relatively modest, suggesting that potential future cuts to federal discretionary spending may not be as damaging as feared.
Public Sector Agglomeration in Developed Countries: The Role of Oversight
Authors: Turner Sidney C.
Published: February 2014

A small but growing body of empirical research underscores the relationship between a city's status as a political capital and its status within an urban hierarchy. Both theoretical and empirical work has attributed this to the agglomeration effects of government activity in the capital. The hypothesis of this paper is that this agglomeration is driven by distance‐based transaction costs of oversight. This hypothesis is tested using a sample of U.S. metropolitan statistical areas for the years 2001–2008. The results are consistent with the hypothesis. Specifically, the empirical results indicate that greater distance from the capital is related to lower levels of government employment and expenditure per government employee among noncapital metropolitan areas.
The scaffold protein JLP plays a key role in regulating ultraviolet B‐induced apoptosis in mice
Authors: Enkhtuya Radnaa , Sato Tokiharu , Wakasugi Mitsuo , Tuvshintugs Baljinnyam , Miyata Hirofumi , Sakurai Takeshi , Matsunaga Tsukasa , Yoshioka Katsuji
Published: February 2014

The ultraviolet B (UVB) component of sunlight can cause severe damage to skin cells and even induce skin cancer. Growing evidence indicates that the UVB‐induced signaling network is complex and involves diverse cellular processes. In this study, we investigated the role of c‐Jun NH2‐terminal kinase‐associated leucine zipper protein (JLP), a scaffold protein for mitogen‐activated protein kinase (MAPK) signaling cascades, in UVB‐induced apoptosis. We found that UVB‐induced skin epidermal apoptosis was prevented in Jlp knockout (KO) as well as in keratinocyte‐specific Jlp KO mice. Analysis of the repair of UVB‐induced DNA damage over time showed no evidence for the involvement of JLP in this process. In contrast, UVB‐stimulated p38 MAPK activation in the skin was impaired in both Jlp KO and keratinocyte‐specific Jlp KO mice. Moreover, topical treatment of UVB‐irradiated mouse skin with a p38 inhibitor significantly suppressed the epidermal apoptosis in wild‐type mice, but not in Jlp KO mice. Our findings suggest that JLP in skin basal keratinocytes plays an important role in UVB‐induced apoptosis by modulating p38 MAPK signaling pathways. This is the first study to show a critical role for JLP in an in vivo response to environmental stimulation.
Optimisation of vacuum pulse osmotic dehydration of blanched pumpkin
Authors: Corrêa Jefferson L. G. , Ernesto Dovel B. , Alves José G. L. F. , Andrade Raphael S.
Published: February 2014

Pulsed vacuum osmotic dehydration (PVOD) is an efficient process for obtaining semi‐dehydrated food. The effects of temperature (30–50°C), solute concentration (NaCl 0–15 kg per 100 kg solution, sucrose, 15–35 kg per 100 kg solution) and vacuum pulse application (50–150 mbar and 5–15 min) on water loss (WL), solid gain (SG), water activity (aw) and total colour difference (∆E) of previously blanched pumpkin slices were assessed through Plackett–Burman experimental design. Temperature was not statistically significant in the process. Later, with the aid of a central composite design (CCD), it was found that concentration of sucrose and NaCl was influent on the WL, SG, aw and ∆E, and the pressure and time of application of vacuum were influent on WL and SG. The optimal conditions of process were stabilised with the desirable function, and the simulated data were similar from the experimental ones.
n‐3 fatty acids in health and disease
Authors: NORDØY A. , DYERBERG J.
Published: February 2014

Not more than 10 years ago, most of us knew very little about n‐3 polyunsaturated fatty acids. The message to both the patient and the physician with regard to fatty acids and fats in the diet was based largely on over‐simplified information. For example, saturated fats were said to be ‘bad’. A high consumption of saturated fats increased both blood cholesterol and the risk of coronary heart disease (CHD). In contrast, the polyunsaturated fatty acids in the diet were thought to be basically ‘good’. They reduced serum cholesterol and may have delayed the development of atherosclerosis.

The lesson learnt from the Greenland Eskimos did not really change this concept, but has taught us more about some of the mechanisms involved [1, 2]. Today a common interest in regard to the potential benefit of n‐3 fatty acids is shared by almost everybody interested in the treatment and prevention of CHD. The diverse effects of twenty‐carbon fatty acids of the n‐6 and n‐3 families on platelet and vessel wall function, prostaglandin synthesis and lipoprotein metabolism, make them of special interest in relation to thrombosis and atherosclerosis [3].
Interactions between the metabolism of n‐3 and n‐6 fatty acids
Authors: SPRECHER H.
Published: February 2014

Abstract. Dietary n‐3 fatty acids modify the fatty acid composition of phospholipids of different cells and tissues from rats in diverse ways. Neutrophil and platelet phospholipids contain elevated amounts of 20: 5n‐3, but only relatively small changes occur in the levels of 22‐carbon n‐3 fatty acids. Conversely, dietary n‐3 acids result primarily in an increase in 22‐carbon n‐3 acids in heart, liver and kidney phospholipids. Platelets metabolize exogenous n‐6 and n‐3 fatty acids into a variety of different autocoids. However, it appears that only arachidonate and 20:5n‐3 are released from phospholipids upon agonist‐induced stimulation of phospholipases. Neutrophils metabolize arachidonate and 20: 5n‐3 in similar ways, both relative to phospholipid biosynthesis and the subsequent release of these acids for metabolism into leukotrienes.
n‐3 fatty acids as precursors for active metabolic substances: dissonance between expected and observed events
Authors: LANDS W. E. M.
Published: February 2014

Abstract. It may be hypothesized that many diseases are associated with an overproduction of eicosanoids from the n‐6 acid, arachidonic acid (20:4n‐6), and the formation and function of these n‐6 eicosanoids can be antagonized by dietary n‐3 fats. This hypothesis provides a basis for evaluating the benefits and risks of including various amounts of n‐3 and n‐6 fats in the diet. Understanding the impact of dietary polyunsaturated fats leads inevitably to a reappraisal of what is ‘normal’ in terms of what is typical and what is desirable for the fatty acid composition of tissue lipids, the magnitude of eicosanoid‐mediated responses, and the frequency and severity of certain diseases.
Fish oils in cardiovascular disease
Authors: FITZGERALD G. A. , BRADEN G. , FITZGERALD D. J. , KNAPP H. R.
Published: February 2014

Abstract. Although several studies have reported an inverse relationship between the dietary history of fish intake and the prospective incidence of death from coronary heart disease, it is unclear whether these results represent the effects of n‐3 fatty acids themselves or whether they merely reflect a more fundamental alteration in diet, such as a reduction in saturated fatty acids, n‐3 fatty acids alter platelet eicosanoid formation, replacing arachidonate derived thromboxane (Tx)A2 with the biologically inert TxA3. However, they are a relatively inefficient approach to platelet inhibition. This is evident from results obtained in a model of coronary thrombosis followed by thrombolysis with tissue plasminogen activator (tPA). By contrast, high doses of n‐3 fatty acids (15 g day−1) significantly reduced blood pressure in mild hypertensives in a double‐blind, controlled study characterized by a prolonged run‐in period and adequate follow‐up. Fish oils inhibit the vascular proliferative response to injury in a variety of animal models, apparently independently of their effects on lipoprotein metabolism. Recent results imply that they may selectively interfere with the vascular expression of mitogenic peptides.
Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention
Authors: RENAUD S. , DE LORGERIL M.
Published: February 2014

Abstract. From the Seven Countries Study and recent statistics from WHO and the OECD, it is clear that saturated fats, mainly dairy fats, are closely associated with the mortality rate from ischaemic heart disease (IHD). Consumption of alcohol, especially wine, but not polyunsaturated fats, seem to offer protection. Racial and other environmental factors do not seem to be confounding factors for that relationship as evaluated by studies in migrants, Japanese to USA, Southern Europeans to Australia, and in vegetarians in California. By contrast, very few trials using dietary polyunsaturated/saturated (P/S) ratios from 1.5‐2.5 vs 0.4‐0.7 have really prevented coronary death by diet modification. The only successful trial had a P/S ratio of 0.7. High P/S ratio increases platelet reactivity. Recent studies indicate that thrombosis and platelets play a more prominent role in IHD than expected. To decrease platelet activity and prevent IHD, a P/S ratio of 0.4‐0.7 should be preferred.
n‐3 fatty acids and coronary heart disease: epidemiology from Eskimos to Western populations
Authors: KROMHOUT D.
Published: February 2014

Abstract. The original cross‐cultural comparisons between Greenland Eskimos and Danes and between Japan and Western countries suggested that a high fish intake was associated with low mortality rates from coronary heart disease. More comprehensive cross‐cultural studies, e.g. the Seven Countries Study showed that the saturated fat content of the diet is more important than the amount of fish in explaining differences in coronary heart disease mortality between countries. Cohort studies carried out in cultures with a low level of fish consumption showed that persons who eat fish once or twice a week had lower mortality rates from coronary heart disease than persons who did not eat fish. The results of the epidemiological studies carried out so far suggest that a diet low in saturated fat in combination with a low level of fish consumption may be of importance for coronary heart disease prevention.
Influence of dietary fish oil on arterial thrombosis and atherosclerosis in animal models and in man
Authors: HORNSTRA G.
Published: February 2014

Abstract. In animal models of arterial thrombosis, fish‐oil‐enriched diets have been shown to have an antithrombotic effect. There is strong evidence, however, that this only holds if the fish‐oil consumption is associated with a reduction of the saturated fat intake. In animal models of atherosclerosis the effect of a marine diet is not consistent. Although in some studies with cod‐liver oil (which is relatively low in saturated fatty acids) a beneficial effect is observed, studies with other, more saturated fish oils do not confirm this. The influence of fish‐oil consumption on some thrombotic complications of human atherosclerosis is not well documented. So far, the few results reported are not very promising, but it should remembered that this mainly concerns short‐term studies. Studies with respect to human fibrinolysis are equivocal. Evidence has been obtained that fish consumption may even have an adverse effect on certain aspects of the fibrinolytic process. The studies performed so far do not provide conclusive evidence as to the importance of fish‐ and fish‐oil‐enriched food for prevention and therapy of ischaemic cardiovascular disease. Further research is needed, especially with long‐term, high‐quality animal models. Moreover, long‐term, well‐controlled, prospective human intervention studies are required to investigate the effect of feasible fish(oil)‐enriched diets on morbidity and mortality of ischaemic cardiac and vascular diseases.
Effects of moderate freshwater fish diet on lipid metabolism of Finnish students
Authors: HÄNNINEN O. , ÅGREN J. J.
Published: February 2014

Abstract. The effect of moderate freshwater fish intake on the lipid metabolism was studied in healthy students using a public catering system. In the first trial, male students ate an average of 3.7 fish meals per week (about 1 g of n‐3 fatty acids daily) for 15 weeks. The n‐3 fatty acids increased in the erythrocyte and platelet membranes at the expense of n‐6 fatty acids. Serum triglyceride, apolipoprotein A1 and B levels and platelet thromboxane B2 production decreased. In the dose response study, four groups had been eating fish for 12 weeks. Similar findings were made with the highest dose as in the previous study. In addition, new measurements showed a decrease in the platelet and erythrocyte aggregability. With two lower doses (1.5 and 2.3 diet meals eaten per week), only a tendency to decreased triglyceride level and aggregability was noticed. The results obtained show that already moderate freshwater fish intake modifies, in a long‐term, lipid metabolism, supporting the hypothesis of protective effect against cardiovascular diseases.
Hypolipidaemic effects of n‐3 fatty acids in primary hyperlipoproteinaemia
Authors: ILLINGWORTH D. R. , CONNOR W. E. , HATCHER L. F. , HARRIS W. S.
Published: February 2014

Abstract. The influence of fish oils rich in n‐3 fatty acids on plasma lipid and lipoprotein concentrations in patients with primary hyperlipoproteinaemia is reviewed. When used as a dietary supplement, n‐3 fatty acids exert their greatest effect on the concentrations of triglyceride‐rich lipoproteins and these effects are dose dependent. Low doses of n‐3 fatty acids reduce plasma triglyceride concentrations in patients with phenotypic type IV, type V and type IIB hyperlipoproteinaemia, but concurrently result in modest increases in the plasma concentrations of low density lipoprotein (LDL). With very high doses plasma concentrations of LDL cholesterol decrease in patients with the type IIB phenotype. At low doses n‐3 fatty acids do not significantly lower concentrations of LDL cholesterol in patients with primary hypercholesterolaemia whereas at higher doses a modest LDL lowering effect is achieved. The results indicate that the therapeutic potential of n‐3 fatty acids as hypolipidaemic agents is greatest in patients with hypertriglyceridaemia.
Epidemiological and intervention studies on the effect of marine polyunsaturated fatty acids on blood pressure
Authors: BØNAA K.
Published: February 2014

Abstract.Evidence of a blood‐pressure‐lowering effect of marine polyunsaturated fatty acids was examined in epidemiological and intervention studies. Data from observational studies suggest that in populations consuming diets rich in sea food, the prevalence of elevated blood pressure is low compared with Western societies. These observations were supported by results from intervention studies with fish oil supplementation to Western diets. At present dietary supplementation with fish oil concentrates should be considered experimental.
Dietary fish oil and ischaemic arrhythmias
Authors: RIEMERSMA R. A. , SARGENT C. A.
Published: February 2014

Abstract. Ventricular fibrillation (VF), a serious arrhythmia, is an important cause of death from ischaemic heart disease. There is substantial evidence that experimental diets with a high polyunsaturated (linoleic acid) to saturated fatty acid ratio offer protection against VF. In this article the effects of large amounts of dietary fish oil (up to 30%cal) are reviewed. It is concluded that in all recently published studies marked increases in the incorporation of n‐3 fatty acids in membranes was achieved. Two studies were too small, however, to demonstrate any statistically significant difference in VF. The results from a third, a long term feeding study, show a reduction in VF when compared with a highly saturated fat diet, but not when compared to a polyunsaturated fatty acid (n‐6) rich diet. Using a more realistic fish oil supplement (0.4%cal) for 8 weeks, we observed a small but nonsignificant reduction in the incidence of VF during acute myocardial ischaemia in the isolated perfused rat heart. The need for further work on the effect of dose, dietary period and confounding influences of saturated fatty acids and linoleic acid are discussed.
n‐3 fatty acids and leucocytes
Authors: SCHMIDT E. B. , DYERBERG J.
Published: February 2014

Abstract. The evidence presented here favours the view that dietary supplementation with n‐3 fatty acids results in attenuated activity of pro‐inflammatory leukotrienes formed through the 5‐lipoxygenase pathway in leucocytes. Neutrophil and monocyte Chemotaxis seem to decrease, although this may depend on the patient groups studied, n‐3 fatty acids increase the proliferative responses of lymphocytes. It is less clear, whether n‐3 fatty acids affect other parts of leucocyte function. The possible value of n‐3 PUFAs in inflammatory diseases in humans needs to be documented in carefully conducted clinical trials, which also should look carefully for possible side effects. However, the results obtained so far have been promising. The modulating effect of n‐3 fatty acids on leucocyte activity—together with their other effects—could be favourable in atherosclerosis and coronary disease.
n‐6 and n‐3 fatty acids during early human development
Authors: CRAWFORD M. A. , DOYLE W. , DRURY P. , LENNON A. , COSTELOE K. , LEIGHFIELD M.
Published: February 2014

Abstract. The food intakes of pregnant women were analysed from two contrasting socio‐economic areas in London. There were significant differences in mean calorie and EFA intakes. Analysis of maternal and cord blood essential fatty acids (EFAs) in relation to birth weight, placental weight and head circumference were consistent with the dietary data. To assess the EFA tissue status of the low birth weight babies, the umbilical arteries from 14 separate babies of different birth weights were studied. Surprisingly high levels of the Mead acid (20:3 n‐9) were found, with the highest appearing in the artery from the baby with the lowest birth weight. This data may not necessarily imply an EFA deficiency, but at the least it probably indicates a remarkable thirst for long chain n‐6 and n‐3 fatty acids for fetal brain development.
Dietary n‐3 fatty acids and children with hyperlipidaemia
Authors: OSE L. , GRØNN M. , LEVORSEN A. , TRYGSTAD O. , LUND H. , WIIG I.
Published: February 2014

Abstract. A review of the literature shows that no studies on children with primary genetic lipid disorders have been published. Case reports are presented indicating that hyperlipidaemias presenting in children—both familial hypercholestrolaemia and disorders with secondary hyperlipidaemia (triglycerides) may benefit of the intake of n‐3 fatty acids.
Pregnancy duration and the ratio of long‐chain n‐3 fatty acids to arachidonic acid in erythrocytes from Faroese women
Authors: OLSEN S. F. , HANSEN H. S. , JENSEN B. , SØRENSEN T. I. A.
Published: February 2014

Abstract. Dietary long‐chain n‐3 fatty acids (FA) may prolong gestation by inhibiting formation of prostaglandins from arachidonic acid. FA were quantified in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipids (TL) of red cells sampled during pregnancy from 29 Faroese women. The ratio of long‐chain n‐3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient 0.50, P = 0.035), but not with the (3/6) ratio in PE (correlation coefficient 0.21, P = 0.40) or TL (correlation coefficient 0.29, P = 0.26). The association with the (3/6) ratio in PC could not be attributed to confounding by maternal age, weight, marital status or smoking.
n‐3 fatty acids and blood glucose control in diabetes mellitus
Authors: VESSBY B.
Published: February 2014

Abstract. Our knowledge of the effects of n‐3 fatty acids on the glucose homeostasis in diabetes mellitus is at present incomplete. The results are in certain respects conflicting. Several studies have shown that addition of n‐3 fatty acids, especially in type‐2 diabetes, may increase blood glucose concentrations without a concomitant increase of insulin or C‐peptide concentrations. The glucose/insulin ratio is increased in fasting as well as after meals. On the other hand, some data indicate that, in spite of increased or unchanged glucose concentrations, there may be an improved peripheral insulin sensitivity. The stimulated insulin response may be reduced after mixed meals, although there are no indications of significant impairments of the response to intravenous glucose. The reasons for the observed changes are still obscure. More controlled studies, during prolonged periods of time, are needed. At present it would seem important to closely follow diabetic patients with respect to glucose and lipid metabolism if treated with n‐3 fatty acids. As for now, diabetic patients are recommended to increase their intake of fish in the diet. The use of pharmacological doses of n‐3 fatty acids remains investigational.
Dietary marine lipids suppress murine autoimmune disease
Authors: ROBINSON D. R. , TATENO S. , KNOELL C. , OLESIAK W. , XU L. , HIRAI A. , GUO M. , COLVIN R. B.
Published: February 2014

Abstract. Dietary marine lipids reduce both mortality and the severity of glomerulonephritis in inbred murine strains which develop spontaneous autoimmune disease. The protective effects of marine lipids appear to be accounted for by the major n‐3 fatty acids in these preparations, 20:5 and 22:6. The n‐3 fatty acids in dietary fish oil are extensively incorporated into several lipid classes in the spleen of autoimmune mice, including phosphatidylinositol, phosphatidylethanolamine, plasmalogens and saturated ether‐linked phospholipids as well as diacylphosphoglycerides. The effects of dietary marine lipids on autoimmune disease in experimental models are highly specific. Careful controlled trials will be required to establish the role of dietary marine lipids in the therapy of human autoimmune disease.
Effect of n‐3 fatty acid supplement to patients with atopic dermatitis
Authors: BJØRNEBOE A. , SØYLAND E. , BJØRNEBOE G‐E A. , RAJKA G. , DREVON C. A.
Published: February 2014

Abstract. The effects of dietary supplement with n‐3 fatty acids to patients with atopic dermatitis were investigated in a 12‐week, prospective, double‐blind study. The experimental group received daily 10 g of fish oil, containing 3 g n‐3 fatty acids, of which eicosapentaenoic acid represented about 1.8 g. The controls received an isoenergetic placebo supplement containing olive oil. Compliance was monitored by gas chromatographic analysis of fatty acid pattern in serum phospholipids. Results favoured the experimental group with regard to scale (P < 0.05), itch (P < 0.05) and overall subjective severity (P < 0.02) as compared to the controls.
HCl secretion and [Ca2+]i in cultured parietal cells
Authors: CHEW C. S. , LJUNGSTRÖM M.
Published: February 2014

Abstract. Gastric parietal cells in primary culture have been tested to determine their utility as a model for the study of the role of intracellular calcium ([Ca2+]i) in the control of HCl secretion. Changes in [Ca2+]i were measured in single cells on a microscope stage using the cell‐permeant form of the fluorescent calcium probe, fura‐2. Simultaneous images of cell fluorescence and morphology were acquired using a digitized video image analysis system and two video cameras, one for low‐light level fluorescence detection and one for high resolution DIC/transmitted light images. Both histamine and carbachol, which are known stimulants of HCl secretion, increased [Ca2+]i and stimulated dramatic changes in morphology in these cultured cells. Changes in morphology were accompanied by an increased uptake of the weak base, [14C]‐aminopyrine (AP), and a shift from green to red fluorescence of another weak base, acridine orange. These results indicate that cultured parietal cells, maintained under controlled conditions on a microscope stage, retain viability and secretagogue responsiveness. Thus, this cellular model appears to be suitable for correlation of changes in [Ca2+]i and activation of HCl secretion.
Role of polarization of gastric EMFs in evaluation of contemporary HCl models
Authors: REHM W. S. , CARRASQUER G. , SCHWARTZ M.
Published: February 2014

Abstract. The neutral proton pump (NP) model postulates a neutral exchange of K+ for H+ across the secretory membrane and the electrogenic proton pump (EP) model an electrogenic proton pump. Previous evidence is briefly reviewed and polarization of EMFs by transmucosal voltage clamping (VC) is presented. During VC, open circuit potential difference (PD) (VOC) is obtained by breaking the circuit for 2 s (after dielectric capacitors have discharged). The magnitude of polarization in Cl− media is less than in Cl−‐free media, presumably due to the high conductance of Cl− paths. The magnitude in Cl−‐free media is from 35 to 50 mV for a VC of 100 mV (nutrient side positive). The Na+/K+‐ATPase is not essential because with choline sulphate media polarization is typical. With Cl−‐free media, VOC versus IH (H+ rate) is exponential but (VC ‐ VOC) versus IH is linear. Polarization on the basis of the NP model would be due to changes in K+ diffusion potentials. However, with 80 mM K+ on both sides (Cl−‐free media) polarization is typical. We conclude that polarization cannot be due to a change in K+ diffusion potentials but to polarization of the EP model. The problem remains of how to incorporate the important finding of the H+/K+‐ATPase into a model for the intact tissue.
Acid transport by intracellular vesicles
Authors: VAN DYKE R. W.
Published: February 2014

Abstract. Many intracellular organelles contain a unique primary, electrogenic proton pump termed the vacuolar H+‐ATPase. This pump, found in many endocytic, secretory, and storage vesicles in fungal, plant and animal cells, functions, in conjunction with a chloride conductance, to acidify the vesicle interior. Although remotely related to the mitochondrial ATP synthase, the vacuolar H+‐ATPase is a distinct pump which differs in inhibitor sensitivity, subunit composition and function. The vacuolar H+‐ATPase transports only protons, and permeable anions (chloride) are required for optimal vesicle acidification. Allosteric and regulatory effects are not yet fully understood. Vesicle acidification appears to be essential for receptor‐mediated endocytosis, protein synthesis, and secretion and storage of small solutes such as neurotransmitters. A similar plasma membrane‐located H+‐ATPase may contribute to urinary acidification and cell pH regulation.
The occurrence of auto‐antibodies in patients with gastro‐duodenal lesions
Authors: MÅRDH S. , SONG Y.‐H.
Published: February 2014

Abstract. The occurrence of auto‐antibodies in patients with the autoimmune disease pernicious anaemia and in patients with active duodenal ulcers was investigated. In order to characterize antigenic structures, various cellular and subcellular fractions were prepared from pig gastric mucosa and from a homogenate of duodenal mucosa. By means of an enzyme‐linked immunosorbent assay and immunoblotting, both the H+,K+‐ATPase and pepsinogen/pepsin were shown to constitute the major antigens. All of the seven pernicious‐anaemia sera that were tested contained auto‐antibodies against both antigens, and the epitopes of the H+,K+‐ATPase were shown to be localized on its cytoplasmic face. In 75% (18/24) of the sera from patients with duodenal ulcers, auto‐antibodies were detected when using purified antigens. Six sera reacted with H+,K+‐ATPase and twelve reacted with pepsinogen, one reacted with both antigens, and four sera reacted with the duodenal mucosal antigen. The occurrence of auto‐antibodies indicates that there is a mucosal lesion and that immunological factors may be involved in the pathogenesis of the disease in some patients.
Identification of agonists of duodenal alkaline secretion
Authors: GARNER A. , HEYLINGS J. R. , HAMPSON S. E. , STANIER A. M.
Published: February 2014

Abstract. This report describes approaches for accurate determination of the comparative activities of stimulants of duodenal alkaline secretion. We screened about 200 standard pharmacological agents using a bullfrog‐isolated mucosal preparation in order to characterize fully the mechanisms of duodenal alkaline secretion. A variety of eicosanoids, phosphodiesterase (PDE) inhibitors, adrenoreceptor agonists and benzodiazepines, together with forskolin, 6‐hydroxydopamine, 2‐chloroadenosine, dipyridamole, dihydropyridazinone and testosterone, caused a reproducible increase in the metabolism‐dependent component of duodenal alkaline secretion. Prostaglandin E2 (ED50 of 0.02 μg ml−1 in vitro) was the most potent and efficacious stimulant in the isolated mucosa and in the perfused cat duodenum in vivo. In the isolated duodenum, the predominant mechanism for stimulating alkaline secretion appears to be via elevation of intracellular cAMP levels, but in vivo indirect effects, for example on mucosal blood flow, may determine the overall influence of agents on duodenal alkalinization.
Pathophysiology of gastrointestinal mucosal permeability
Authors: CRISSINGER K. D. , KVIETYS P. R. , GRANGER D. N.
Published: February 2014

Abstract. The intestinal mucosa is composed of multiple barriers to the lumen‐to‐blood transport of solutes, including the unstirred water and mucous layers, the apical and basolateral cell membranes of the epithelial cell, the paracellular junctions, the interstitial matrix, and the capillary and lymphatic endothelia. The epithelial barrier appears effectively to restrict the movement of solutes with a radius as low as 3 Å, yet it also permits limited permeation by molecules as large as albumin (36 Å radius). There is evidence to suggest that the restrictive properties of the gastrointestinal mucosa are significantly altered under various physiological and pathological conditions, and measurement of plasma (or luminal) clearances of water‐soluble molecules has proved to be a popular method for studying intestinal permeability. The aim of this review is to discuss the concept of the plasma clearance method, methodological aspects of the technique, factors that influence plasma‐to‐lumen clearance measurements (e.g. solute size, blood flow, and permeability of the epithelial cell barrier), and advantages and disadvantages of the clearance method. Finally, application of the clearance technique to the study of ischaemia/reperfusion‐, ethanol‐, and FMLP‐induced mucosal injury will be described.
A Large Cohort Study Evaluating Risk Factors Associated With Uncontrolled Hypertension
Authors: Elperin Dina T. , Pelter Mitchell A. , Deamer Robert L. , Burchette Raoul J.
Published: February 2014

Hypertension is the most common primary diagnosis in the United States. Risks for long‐term consequences such as myocardial infarction, heart failure, stroke, and kidney disease continue to significantly increase as long as hypertension remains uncontrolled. This retrospective cohort study of 661,075 patients identified with uncontrolled hypertension, defined as systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg, from a large integrated healthcare organization was conducted to examine multiple patient characteristics to determine their association with uncontrolled hypertension. Multivariate analysis revealed that compared with Caucasians, African Americans (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.16–1.20) were significantly associated with uncontrolled hypertension, as were unpartnered populations (OR, 1.15; 95% CI, 1.14–1.17), number of antihypertensive medications prescribed (OR, 1.37; 95% CI, 1.33–1.41), and adherence to most antihypertensive medications. A secondary analysis found an association between uncontrolled blood pressure and Patient Health Questionnaire‐9 (PHQ‐9) score (OR, 1.21; 95% CI, 1.16–1.26). Our findings suggest that the presence of these identified risk factors recommends a commitment to a more aggressive hypertension management program to prevent cardiovascular disease caused by uncontrolled hypertension.
Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1
Authors: Albrecht Björn , Brandeis Daniel , von Sandersleben Henrik Uebel‐ , Valko Lilian , Heinrich Hartmut , Xu Xiaohui , Drechsler Renate , Heise Alexander , Kuntsi Jonna , Müller Ueli C. , Asherson Philip , Steinhausen Hans‐Christoph , Rothenberger Aribert , Banaschewski Tobias
Published: February 2014

Background

Difficulties with performance and brain activity related to attentional orienting (Cue‐P3), cognitive or response preparation (Cue‐CNV) and inhibitory response control (Nogo‐P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.

Methods

Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7‐repeat allele and the DAT1 10‐6 haplotype.

Results

Children with ADHD showed diminished performance and lower Cue‐P3, CNV and Nogo‐P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue‐P3 and CNV, but Nogo‐P3 was not reduced. Children with the DAT1 10‐6 haplotype had no difficulties with performance or Cue‐P3 and CNV, but contrary to expectations increased Nogo‐P3. There were no Genotype by ADHD interactions.

Conclusions

This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10‐6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.
Centres and Peripheries: Research Styles and Publication Patterns in ‘Top’USJournals and theirEuropean Alternatives, 1960–2010
Authors: Üsdiken Behlül
Published: February 2014

In view of recent literature, suggesting a growing international ascendancy ofUS‐style scholarship but also a decreasingUSdominance in journal publications,Iask two questions with regard to management and organization studies: (1) whether there has been an increasing convergence towardsUS‐style research; and (2) whether the purported decline in the relative amount ofUSpublications has been uniform across leading journals based in theUSAandEurope. In addressing these questions,Itake a historical perspective and draw upon the centre–periphery model of international scholarship, arguing that convergence or fragmentation in styles of research and variations in publication patterns have evolved through the interplay between processes of influence by the centre (i.e., theUSA) and imitative or competitive responses by the periphery. Empirically, the study spans the period 1960–2010 and is confined to ‘top’US‐based journals and their mainEuropean alternatives. The findings answer the first question with a ‘no, other than a greater tendency towards theUS‐style when educational or collaborative ties to theUSAare involved and by the recently emerging parts of the periphery’. The second question again is answered with a ‘no, the decline has been much less in “top”USjournals relative to the ones based inEurope’.
Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy
Authors: Zeng R. , Coates J.R. , Johnson G.C. , Hansen L. , Awano T. , Kolicheski A. , Ivansson E. , Perloski M. , Lindblad‐Toh K. , O'Brien D.P. , Guo J. , Katz M.L. , Johnson G.S.
Published: February 2014

Background

Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported.

Objective

To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds.

Animals

DNA from 33,747 dogs was genotyped at SOD1:c.118, SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined.

Methods

Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias.

Results

The SOD1:c.118A allele was found in cross‐bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes.

Conclusions and Clinical Importance

We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy.
A New Look at the Public Wage Premium in Italy: The Role of Schooling Endogeneity
Authors: Ghinetti Paolo
Published: February 2014

This paper uses a sample of male workers to estimate public and private wage structures and the public wage premium for Italy. Results from a model with endogenous sector and schooling suggest that public employees have on average lower unobserved wage potentials in both sectors than private employees, but work in the sector where they benefit from a comparative wage advantage. Schooling is positively correlated with wages in both sectors, and controlling for that is crucial to get more reliable estimates and predictions. The associated average unconditional public wage premium is 12 per cent. The net premium is 9 per cent, but not statistically significant.
L2 Reading Comprehension and Its Correlates: A Meta‐Analysis
Authors: Jeon Eun Hee , Yamashita Junko
Published: February 2014

The present meta‐analysis examined the overall average correlation (weighted for sample size and corrected for measurement error) between passage‐level second language (L2) reading comprehension and 10 key reading component variables investigated in the research domain. Four high‐evidence correlates (with 18 or more accumulated effect sizes: L2 decoding, L2 vocabulary knowledge, L2 grammar knowledge, first language [L1] reading comprehension), and six low‐evidence correlates (L2 phonological awareness, L2 orthographic knowledge, L2 morphological knowledge, L2 listening comprehension, working memory, metacognition) were included in the study. For the four high‐evidence correlates, a series of moderator analyses were also carried out to examine the effects of age, L2 proficiency, L1–L2 script and language distance, and measurement characteristics. The results showed that L2 grammar knowledge (r = .85), L2 vocabulary knowledge (r = .79), and L2 decoding (r = .56) were the three strongest correlates of L2 reading comprehension. The six low‐evidence correlates had moderate‐to‐strong mean correlations, with L2 listening comprehension being the strongest correlate (r = .77) and metacognition (r = .32) being the weakest correlate. Age, some measurement characteristics, and L1–L2 language distance were found to be significant moderators for some reading components.