bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of omega‐3 fatty acids across the blood–brain barrier after dietary supplementation with a docosahexaenoic acid‐rich omega‐3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study
Authors: Freund Levi Y. , Vedin I. , Cederholm T. , Basun H. , Faxén Irving G. , Eriksdotter M. , Hjorth E. , Schultzberg M. , Vessby B. , Wahlund L.‐O. , Salem N. , Palmblad J. 
Published: November 2013

AbstractObjectiveLittle is known about the transfer of essential fatty acids (FAs) across the human blood–brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega‐3 (n‐3) FAs would change the FA profile of the cerebrospinal fluid (CSF).MethodsA total of 33 patients (18 receiving the n‐3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double‐blind, placebo‐controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n‐3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation.ResultsAt 6 months, the n‐3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n‐3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n‐3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin‐1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers.ConclusionsOral supplementation with n‐3 FAs conferred changes in the n‐3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.
Expression and Activity of Collagenases in the Digital Laminae of Horses with Carbohydrate Overload‐Induced Acute Laminitis
Authors: Wang L. , Pawlak E.A. , Johnson P.J. , Belknap J.K. , Alfandari D. , Black S.J. 
Published: November 2013

BackgroundMatrix metalloproteinases (MMP) are hypothesized to degrade structurally important components of the laminar extracellular matrix (ECM) in horses with laminitis.ObjectiveTo compare levels of expression of stromelysin‐1 (MMP‐3), collagenases (MMP‐1, ‐13), and membrane type‐MMPs (MMP‐14, ‐15, ‐16), and the distribution of theirECMsubstrates, in laminae of healthy horses and horses with carbohydrate overload laminitis.AnimalsTwenty‐five adult horses.MethodsGene and protein expression were determined in extracts of laminae using real‐time quantitative polymerase chain reaction and Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis. Distribution of MMP‐13 andECMcomponents was determined using indirect immunofluorescent microscopy of nonfixed frozen sections.ECMmorphology was assessed by hematoxylin and eosin staining.ResultsOf the genes studied, only those encoding MMP‐1 and ‐13 were upregulated inCHO‐induced laminitis; MMP‐1 at Obel grade (OG)1 lameness and MMP‐13 at OG3 lameness. Laminar MMP‐1 was present as 52 kDa proenzyme only. MMP‐13 was present as pro‐ (61 kDa) and processed (48 kDa) enzyme. MMP‐13 localized to the basal epithelium of the secondary epidermal laminae and its increased expression were accompanied by the appearance in secondary dermal laminae (SDL) of multiple foci that were devoid of collagen I, fibronectin, chondroitin and keratan sulfate glycosaminoglycans, and eosin‐staining material.Conclusions and Clinical RelevanceMMP‐13 is upregulated in laminae of horses withCHO‐inducedOG3 lameness and, by degrading components of theECM, may contribute to the formation ofECM‐free lesions (gaps or tears) that appear in theSDLwithOG3 lameness.
Iron Status in Blood Donor Dogs
Authors: Zaldívar‐López S. , Iazbik M.C. , Marín L.M. , Couto C.G. 
Published: November 2013

BackgroundDespite the popularity of canine blood donor (BD) programs, there is scarce scientific information regarding iron status in this canine population of dogs.ObjectiveTo assess iron status in dogs used in a blood donor program.AnimalsA total of 130 healthy dogs (75 BD, 55 controls [C]) were included. A subset of dogs (n = 12) were used to evaluate the effects of repetitive donations by having a second and more recent sample analyzed.MethodsSerum iron concentration (SI), unsaturated iron‐binding capacity (UIBC), total iron‐binding capacity (TIBC), and percentage transferrin saturation (%SAT) were obtained. Values were compared using a 2‐way ANOVA (factors: BD status, breed). For the subset of BD, the first sample (less frequent donors ‐LD‐, after a mean of 3.8 donations) was compared to a second sample (experienced donors ‐ED‐, mean 13.6 donations) using a paired t‐test.ResultsSI (183.7 ± 55.3 μg/dL) and %SAT (55.7 ± 17.4%) were higher and UIBC (152.6 ± 73.3 μg/dL) was lower in BD dogs than in C (153.9 ± 51.7 μg/dL, 43.8 ± 17.8%, and 224.1 ± 120.6 μg/dL, respectively). Also, UIBC and TIBC were lower, and %SAT higher in Greyhounds when compared with non‐Greyhounds. ED had decreased %SAT and increased UIBC and TIBC when compared with LD.Conclusions and Clinical ImportanceOur canine BD population did not have iron deficiency and had higher SI concentration than C. However, ED (~14 consecutive blood donations every ~8 weeks) developed a mild iron deficiency, although values were still within canine reference intervals. Greyhounds have higher %SAT than non‐Greyhounds, which might be a breed‐specific peculiarity.
Effects of Pioglitazone on Insulin Sensitivity and Serum Lipids in Obese Cats
Authors: Clark M. , Thomaseth K. , Dirikolu L. , Ferguson D. C. , Hoenig M. 
Published: November 2013

BackgroundPioglitazone is a thiazolidinedione (TZD) insulin sensitizer approved for use in human type 2 diabetes mellitus. Therapeutic options for diabetes in cats are limited.ObjectiveTo evaluate the effects of pioglitazone in obese cats, which are predisposed to insulin resistance, to assess its potential for future use in feline diabetes mellitus.AnimalsA total of 12 obese purpose‐bred research cats (6 neutered males and 6 spayed females, 5–7 years of age, weighing 5.4–9.8 kg).MethodsRandomized, placebo‐controlled 3‐way crossover study. Oral placebo or pioglitazone (Actos™; 1 or 3 mg/kg) was administered daily for 7‐week periods, with IV glucose tolerance testing before and after each period.ResultsThree mg/kg pioglitazone significantly improved insulin sensitivity (geometric mean [95% CI] 0.90 [0.64–1.28] to 2.03 [1.49–2.78] min−1pmol−1L;P = .0014 versus change with placebo), reduced insulin area under the curve during IVGTT (geometric mean [range] 27 [9–64] to 18 [6–54] min∙nmol/L;P = .0031 versus change with placebo), and lowered serum triglyceride (geometric mean [range] 71 [29–271] to 48 [27–75] mg/dL;P = .047 versus change with placebo) and cholesterol (geometric mean [range] 187 [133–294] to 162 [107–249] mg/dL;P = .0042 versus change with placebo) concentrations in the obese cats. No adverse effects attributable to pioglitazone were evident in the otherwise healthy obese cats at this dosage and duration.Conclusions and Clinical ImportanceResults of this study support a positive effect of pioglitazone on insulin sensitivity and lipid metabolism in obese cats, and suggest that further evaluation of the drug in cats with diabetes mellitus or other metabolic disorders might be warranted.
Molecular and biochemical modifications of liver glutamine synthetase elicited by daytime restricted feeding
Authors: Vázquez‐Martínez Olivia , De Ita‐Pérez Dalia , Valdés‐Fuentes Marlen , Flores‐Vidrio Alejandra , Vera‐Rivera Gabriela , Miranda María I. , Méndez Isabel , Díaz‐Muñoz Mauricio 
Published: November 2013

AbstractBackground & AimsThe circadian clock system in the liver plays important roles in regulating metabolism and energy homeostasis. Restricted feeding schedules (RFS) become an entraining stimulus that promotes adaptations that form part of an alternative circadian clock known as the food entrained oscillator (FEO). The aim of this study was to evaluate the daily variations of glutamine synthetase (GS) in liver under a daytime RFS.MethodsHepatic GS properties were analysed at 3‐h intervals over a 24‐h period in adult male Wistar rats maintained in a 12:12 h light–dark cycle. RFS group: food access for 2‐h in light phase, during 3 weeks. AL group: feeding ad libitum. Fa group: acute fast (21 h). Fa–Re group: acute fast followed by refed 2 h. mRNA expression was measured by RT‐qPCR, protein presence by Western‐blot and immunohistochemistry, enzyme activity by a spectrophotometric assay, and glutamine by high pressure liquid chromatography.Results and ConclusionsRestricted feeding schedule induced circadian rhythmicity in mRNA levels of GS and the loss of the rhythmic pattern in mitochondrial GS activity. GS activity in liver homogenates displayed a robust rhythmic pattern in AL that was not modified by RFS. The presence of GS and its zonal distribution did not show rhythmic pattern in both groups. However, acute Fa and Fa–Re diminished GS protein and activity in liver homogenates. Hepatic glutamine concentrations showed a 24‐h rhythmic pattern in both groups, in an antiphasic pattern. In conclusion, daytime RFS influences the liver GS system at different levels, that could be part of rheostatic adaptations associated to the FEO, and highlight the plasticity of this system.
Histological features of chronic hepatitis C in haemodialysis patients
Authors: Sakellariou Stratigoula , Boletis John N. , Sypsa Vana , Psichogiou Mina , Tiniakos Dina , Delladetsima Ioanna 
Published: November 2013

AbstractBackground & AimsHCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV‐infected HD patients within the context of a comparative analysis including non‐uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined.MethodsSixty‐one consecutive liver biopsies from HD patients and 326 from non‐uraemic patients with chronic HCV infection were comparatively evaluated.ResultsHaemodialysis patients with CHC were older than control subjects (P = 0.031), showing a similar HCV genotype distribution (P = 0.328) and lower viral load (P = 0.001). CHC in HD patients was significantly milder according to stage (P = 0.033), grade and its parameters (periportal activity, portal inflammation and lobular activity) (P < 0.001). The frequency of lymphoid aggregates (10.2% vs 50%, P < 0.001), bile duct lesions (1.7% vs 22.1%, P < 0.001) and extent of steatosis (P = 0.022) in HD group was significantly reduced. Multivariate analysis showed that non‐uraemic patients had 2.3 times higher risk of developing steatosis independently of genotype distribution and age. In HD group, genotype 3, longer HD duration and age at infection were significantly associated with steatosis, while older age at infection correlated with advanced fibrosis.ConclusionsChronic hepatitis C in HD patients is usually very mild, losing its diagnostic histological features while patient's age and age at infection retain their prognostic significance. The weak inflammatory response, probably because of immunocompromised status and low viral load, may present a beneficial factor in the natural course of the disease.
Induction of systemic oxidative stress leads to brain oedema in portacaval shunted rats
Authors: Bosoi Cristina R. , Tremblay Mélanie , Rose Christopher F. 
Published: November 2013

AbstractBackground & AimsThe pathogenesis of hepatic encephalopathy (HE) is multifactorial and often associated with the development of brain oedema. In addition to ammonia playing a central role, systemic oxidative stress is believed to aggravate the neuropsychological effects of ammonia in patients with chronic liver disease (CLD). The aim of this study was to (i) induce systemic oxidative stress in hyperammonaemic portacaval anastomosed (PCA) rats by inhibiting the antioxidant glutathione using Dimethyl maleate (DEM) and (ii) investigate whether a synergistic relationship between ammonia and oxidative stress contributes to the pathogenesis of brain oedema in CLD.MethodsFour‐week PCA and sham‐operated rats received DEM (0.4–4 mg/kg/day) for the last 10 days before sacrifice when oxidative stress markers [reactive oxygen species (ROS) and malondialdehyde (MDA)] were assessed in blood and frontal cortex. Brain water content was measured using a specific gravimetric technique.ResultsDimethyl maleate induced an increase in ROS and MDA in the blood, but not in the brain, of the PCA rats, compared with non‐treated PCA rats. This was accompanied with an increase in brain water content (PCA+DEM: 78.45 ± 0.13% vs. PCA: 77.38 ± 0.11%, P < 0.001). Higher doses of DEM induced systemic oxidative stress in sham‐operated controls, but brain oedema did not develop.ConclusionsDimethyl maleate provoked systemic, not central, oxidative stress in PCA rats, resulting in the development of brain oedema. Independently, hyperammonaemia and systemic oxidative stress do not precipitate brain oedema; therefore, our findings sustain that a synergistic effect between hyperammonaemia and systemic oxidative stress is responsible for the development of brain oedema in HE.
Pegylated interferon α‐2a plus ribavirin for decompensated hepatitis C virus‐related cirrhosis: relationship between efficacy and cumulative dose
Authors: Xu Yan , Qi Wenqian , Wang Xu , Zhao Ping , Zhang Yonggui , Zhang Qian , Qin Shaoyou , Wang Jiangbin 
Published: November 2013

AbstractBackground & AimsA combination of pegylated interferon alpha‐2a (Peg‐IFNα‐2a) and ribavirin (RBV) achieves a sustained virological response (SVR) in 40–50% of patients infected with genotype 1 hepatitis C virus (HCV), but efficacy rates are significantly lower in patients with decompensated HCV‐induced cirrhosis. The efficacy and tolerability of Peg‐IFNα‐2a and RBV, the cumulative dose effect, time to achieve planned cumulative dose and role of HCV phenotype on treatment response were determined in patients with decompensated HCV‐induced cirrhosis.MethodsIn this case‐controlled study, 257 patients with decompensated HCV‐induced cirrhosis were enrolled, including patients treated with partial splenic embolization for leukopaenia. Of patients with sufficient blood cell counts, 130 patients opted for antiviral therapy (treatment group) consisting of 180 μg/kg Peg‐IFNα‐2a for 48 weeks with 800–1200 mg/day RBV; the remaining 127 were considered the control group. Primary endpoints were SVR and absence of relapse; the secondary end point was assessment of disease progression.ResultsSustained virological response was highest and relapse rates were lowest when cumulative doses of Peg‐IFNα‐2a and RBV were both ≥80% of the prescribed dose. Patients achieving ≥80% of the planned cumulative doses in 48 weeks had a significantly higher SVR compared with patients achieving this in 72 weeks. Patients with HCV genotype 1 had significantly lower SVR compared with patients with HCV genotype 2 (19.7% vs. 42.9%, respectively; P = 0.008). Treatment group patients had a significantly lower rate of SVR‐independent liver disease‐related mortality.ConclusionsOur findings provide additional evidence to support the use of Peg‐IFNα‐2a and RBV therapy for decompensated HCV‐induced cirrhosis.
Geographical and environmental gradients shape phenotypic trait variation and genetic structure in Populus trichocarpa
Authors: McKown Athena D. , Guy Robert D. , Klápště Jaroslav , Geraldes Armando , Friedmann Michael , Cronk Quentin C. B. , El‐Kassaby Yousry A. , Mansfield Shawn D. , Douglas Carl J. 
Published: November 2013

Summary

Populus trichocarpa is widespread across western North America spanning extensive variation in photoperiod, growing season and climate. We investigated trait variation in P. trichocarpa using over 2000 trees from a common garden at Vancouver, Canada, representing replicate plantings of 461 genotypes originating from 136 provenance localities.

We measured 40 traits encompassing phenological events, biomass accumulation, growth rates, and leaf, isotope and gas exchange‐based ecophysiology traits. With replicated plantings and 29 354 single nucleotide polymorphisms (SNPs) from 3518 genes, we estimated both broad‐sense trait heritability (H2) and overall population genetic structure from principal component analysis.

Populus trichocarpa had high phenotypic variation and moderate/high H2 for many traits. H2 ranged from 0.3 to 0.9 in phenology, 0.3 to 0.8 in biomass and 0.1 to 0.8 in ecophysiology traits. Most traits correlated strongly with latitude, maximum daylength and temperature of tree origin, but not necessarily with elevation, precipitation or heat : moisture indices. Trait H2 values reflected trait correlation strength with geoclimate variables. The population genetic structure had one significant principal component (PC1) which correlated with daylength and showed enrichment for genes relating to circadian rhythm and photoperiod.

Robust relationships between traits, population structure and geoclimate in P. trichocarpa reflect patterns which suggest that range‐wide geographical and environment gradients have shaped its genotypic and phenotypic variability.
Functional diversification of duplicated chalcone synthase genes in anthocyanin biosynthesis of Gerbera hybrida
Authors: Deng Xianbao , Bashandy Hany , Ainasoja Miia , Kontturi Juha , Pietiäinen Milla , Laitinen Roosa A. E. , Albert Victor A. , Valkonen Jari P. T. , Elomaa Paula , Teeri Teemu H. 
Published: November 2013

Summary

Chalcone synthase (CHS) is the key enzyme in the first committed step of the flavonoid biosynthetic pathway and catalyzes the stepwise condensation of 4‐coumaroyl‐CoA and malonyl‐CoA to naringenin chalcone. In plants, CHS is often encoded by a small family of genes that are temporally and spatially regulated. Our earlier studies have shown that GCHS4 is highly activated by ectopic expression of an MYB‐type regulator GMYB10 in gerbera (Gerbera hybrida).

The tissue‐ and development‐specific expression patterns of three gerbera CHS genes were examined. Virus‐induced gene silencing (VIGS) was used to knock down GCHS1 and GCHS4 separately in gerbera inflorescences.

Our data show that GCHS4 is the only CHS encoding gene that is expressed in the cyanidin‐pigmented vegetative tissues of gerbera cv Terraregina. GCHS3 expression is pronounced in the pappus bristles of the flowers. Expression of both GCHS1 and GCHS4 is high in the epidermal cells of gerbera petals, but only GCHS1 is contributing to flavonoid biosynthesis.

Gerbera contains a family of three CHS encoding genes showing different spatial and temporal regulation. GCHS4 expression in gerbera petals is regulated post‐transcriptionally, at the level of either translation elongation or protein stability.
Correlations of seed traits with tofu texture in 48 soybean cultivars and breeding lines
Authors: Huang Mao , Kaletunc Gonul , St. Martin Steve , Feller Marcia , McHale Leah K. 
Published: November 2013

AbstractFood‐grade soybeans [Glycine max (L.) Merr] used to produce tofu have specific seed composition, shape, size and colour requirements. Seed qualities, such as protein content, have been correlated with tofu texture. The objective of this study was to determine the relationships between textural qualities of tofu and seed characters, including shape, size, density, weight, protein content and oil content. Tofu was produced from the seed of 48 high‐protein or food‐grade soybean lines grown at two locations in 2010. Four tofu textural traits were assessed including work to failure, deformability, stiffness and hardness. Seed protein and oil content were significantly correlated with stiffness and hardness, and protein was additionally correlated with work to failure. Pearson's correlation coefficients ranged from 0.45 to 0.60 (adjusted P‐values < 0.002) for protein and −0.49 to −0.35 for oil (adjusted P‐values < 0.016). No significant correlations between tofu texture and seed volume or shape were detected. Seed protein content can be assessed for indirect selection for tofu firmness, whereas this study reveals no evidence that seed size affects tofu texture.
IFN‐γ inhibits basal and α‐MSH‐induced melanogenesis
Authors: Son Jinyoung , Kim Misun , Jou Ilo , Park Kyoung Chan , Kang Hee Young 
Published: November 2013

SummaryInflammatory cytokines are closely related to pigmentary changes. In this study, the effects of IFN‐γ on melanogenesis were investigated. IFN‐γ inhibits basal and α‐MSH‐induced melanogenesis in B16 melanoma cells and normal human melanocytes. MITF mRNA and protein expressions were significantly inhibited in response to IFN‐γ. IFN‐γ inhibited CREB binding to the MITF promoter but did not affect CREB phosphorylation. Instead, IFN‐γ inhibited the association of CBP and CREB through the increased association between CREB binding protein (CBP) and STAT1. These findings suggest that IFN‐γ inhibits both basal and α‐MSH‐induced melanogenesis by inhibiting MITF expression. The inhibitory action of IFN‐γ in α‐MSH‐induced melanogenesis is likely to be associated with the sequestration of CBP via the association between CBP and STAT1. These data suggest that IFN‐γ plays a role in controlling inflammation‐ or UV‐induced pigmentary changes.
Oral Glycopyrrolate for Refractory Pediatric and Adolescent Hyperhidrosis
Authors: Kumar Monique G. , Foreman Rebecca S. , Berk David R. , Bayliss Susan J. 
Published: November 2013

AbstractPrimary hyperhidrosis is a common disorder affecting children and adolescents, and it can have a significant negative psychosocial effect. Treatment for pediatric hyperhidrosis tends to be limited by low efficacy, low adherence, and poor tolerance. Oral glycopyrrolate is emerging as a potential second‐line treatment option, but experience with safety, efficacy, and dosing is especially limited in children. We present an institutional review of 12 children with severe, refractory hyperhidrosis treated with oral glycopyrrolate; 11 (92%) noted improvement and 9 (75%) would recommend oral glycopyrrolate to their friends. No significant side effects were noted. Our retrospective analysis suggests that oral glycopyrrolate is safe and effective in children with hyperhidrosis.
Why is Rose Bengal More Phototoxic to Fibroblasts In Vitro Than In Vivo?
Authors: Yao Min , Gu Chuan , Doyle Francis J. , Zhu Hong , Redmond Robert W. , Kochevar Irene E. 
Published: November 2013

AbstractPhotosensitized protein cross‐linking has been recently developed to seal wounds and strengthen tissue. Although the photosensitizing dye, Rose Bengal (RB), is phototoxic to cultured cells, cytotoxicity does not accompany RB‐photosensitized tissue repair in vivo. We investigated whether the environment surrounding cells in tissue or the high irradiances used for photo–cross‐linking inhibited RB phototoxicity. Fibroblasts (FB) grown within collagen gels to mimic a tissue environment and monolayer cultured FB were treated with RB (0.01–1 mm) and the high 532 nm laser irradiances used in vivo for tissue repair (0.10–0.50 W cm−2). Monolayer FB were substantially more sensitive to RB photosensitization: the LD50 was >200‐fold lower than that in collagen gels. Collagen gel protection was associated with increased Akt phosphorylation, a prosurvival pathway. RB phototoxicity in collagen gels was 25‐fold greater at low (0.030 W cm−2) that at high (0.50 W cm−2) irradiances. Oxygen depletion at high irradiance only partially accounted for the irradiance dependence of phototoxicity as replacing air with nitrogen only increased the LD50 by four‐fold in monolayers. These results indicate that the lack of RB phototoxicity during in vivo tissue repair results from upregulation of prosurvival pathways in tissue cells, oxygen depletion and irradiance‐dependent RB photochemistry.