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Prospective validation of %p2PSA and the Prostate Health Index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml-1

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Asian Journal of Andrology 2017年第3期19卷 286-290页

作者： Lincoln GL tan Yung Khan tan Bee Choo Tai karen ml tan Vineet Gauhar Ho Yee Tiong Robert CW Hawkins Thomas P Thamboo Felicia SK Hong Edmund Chiong Department of Urology National University Hospital National University Health System Singapore Department of Urology Tan Tock Seng Hospital Singapore Saw Swee Hock School of Public Health National University of Singapore Singapore Department of Laboratory Medicine National University Hospital Singapore Department of Urology Alexandra Hospital Jurong Health Singapore Department of Laboratory Medicine Tan Teck Seng Hospital Singapore Department of Pathology National University Hospital Singapore.

Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng ml-1, False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index （PHI） in Asian men presenting with a total PSA between 4.0 and 10 ng m1-1. We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1, Thirty （19.1%） were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHh The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity （95% CI） of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 （49%） unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHi levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng *** its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic ＂gray zone＂ of 4-10 ng m1-1, False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index （PHI） in Asian men presenting with a total PSA betwe

关键词： biological markers prostate specific antigen prostatic neoplasms

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Importance of adapted digestion conditions to simulate in vitro lipid digestion of broilers in different life stages

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Animal Nutrition 2023年第1期12卷 151-158页

作者： Daphne Michels Sarah H.E.Verkempinck Agnese Panozzo karen Vermeulen Marc E.Hendrickx Liesbet Thijs Tara Grauwet Laboratory of Food Technology and Leuven Food Science and Nutrition Research Centre(LFoRCe) Department of Microbial and Molecular Systems(M2S)KU LeuvenLeuven3001Belgium Kemin Animal Nutrition and Health Kemin Europa N.V.Herentals2200Belgium

In vitro digestion studies demonstrate large potential to gain more and quicker insights into the underlying mechanisms of feed additives,allowing the optimization of feed ***,current in vitro digestion models relevant for broiler chickens lack sufficient description in terms of protocols and standardisation ***,no distinction is made between the different life phases of these animals(starter,grower,and finisher).Hence,our research aimed to establish adapted in vitro digestion conditions,corresponding to the 3 life phases in broilers,with specific focus on lipid *** effect of 3 different bile salt concentrations of 2,10,and 20 mM,and 3 different lipase activities of 5,20,and 100 U/ml,on in vitro lipid digestion kinetics were evaluated using a full factorial *** values were selected to represent starter,grower,and finisher birds,*** findings showed that the extent of lipid digestion was mainly influenced by lipase *** rate of lipid digestion was affected by an interplay between bile salt concentration and lipase activity,due to possible lipase inhibition at certain bile salt ***,this work resulted in 3 in vitro lipid digestion models representative for starter,grower,and finisher *** conclusion,this research showed the impact of adapted in vitro digestion conditions on lipid digestion kinetics and thus the need for these conditions relevant for each life phase of broilers.

关键词： Lipolysis Lipase activity Bile salt In vitro digestion Broiler chicken Emulsion

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Lactobacilli,bifi dobacteria and *** nissle induce pro-and anti-inflammatory cytokines in peripheral blood mononuclear cells

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World Journal of Gastroenterology 2006年第37期12卷 5978-5986页

作者： Ulf Helwig karen M Lammers Fernando Rizzello Patricia Brigidi Verena Rohleder Elisabetta Caramelli Paolo Giochetti Juergen Schrezenmeir Ulrich R Foelsch Stefan Schreiber Massimo Campieri University Hospital Schleswig-Holstein Campus Kiel 1~(st) Medical Department Schittenhelmstr.12 24105 Kiel Germany University of Bologna Department of Internal Medicine and Gastroenterology Policlinico S. Orsola Via Massarenti 9 40138 Bologna Italy University of Bologna Department of Internal Medicine and Gastroenterology Policlinico S. Orsola Via Massarenti 9 40138 Bologna Italy University of Bologna Institute for Microbiology Via Bellmeloro 9 40138 Bologna Italy University Hospital Schleswig-Holstein Campus Kiel 1~(st) Medical Department Schittenhelmstr.12 24105 Kiel Germany University of Bologna Histology and General Embryology and Pharmaceutical Science Via Bellmeloro 9 40138 Bologna Italy Federal Research Center for Nutrition and Food Location Kiel Institute for Physiology and Bioche- mistry of Nurtition Hermann-Weigmann-Str.1 24103 Kiel Germany

AIM： To investigate whether the stimulation of peripheral blood mononuclear cells （PBMNC） with the cell debris and cell extraction of different probiotic strains is similar or species specific. METHODS： Three strains of bifidobacteria, 4 strains of lactobacilli, and E. coli nissle were sonicated and centrifuged in order to divide them into cell extract and cell debris. PBMNC were separated by density gradient and incubated for 36 h with either the cell debris or the cell extract of single strains of probiotic bacteria in doses from 10^2 to 10^8 CFU/ml. Cell supernatants were taken and interleukin （IL）-10, IL-1β, and tumor necosis factor （TNF）-α were determined by ELISA. RESULTS： Depending on the species super-family, the strains had different stimulation patterns. Except for both L. casei strains, the cell extract of bitTdobacteria and/actobacilli had less stimulating capacity than cell debris, whereas the cell extract of E. coli nissle had similar stimulating properties to that of the cell debris of the strain and significantly more stimulating capacity than that of bifidobacteria and lactobacilli. The cell debris of bifidobacteria stimulated more cytokine release than the cell debris of lactobacilli. The cell debris of lactobacilli did not have a stimulating capacity when lower concentrations were used. Neither cell extraction nor cell debris had an inhibitory effect on the production of the tested cytokines by stimulated PBMNC. CONCLUSION： The incubation of probiotic strains, which have been used in clinical trials for inflammatory diseases, with immunocompetent cells leads to different species specific reactions. High IL-10 response to cell debris of bifidobacteria and E. coli nissle can be found. This corresponds to positive effects of bihdobacteria and E. coli nissle in clinical trials for inflammatory bowel disease compared to negative outcomes obtained with lactobacilli.

关键词： Lactobacilli Bifidobacteria Probiotics Interleukin-l0 Tumor necrosis factor-α Interleukin-1β Peripheral blood mononuclear cells

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Drug-Seeking Behavior Is Significantly Attenuated in Nutritionally Supplemented Cocaine Withdrawn Sprague-Dawley Rats

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Journal of Behavioral and Brain Science 2021年第7期11卷 143-156页

作者： Lauriann Young Annice Webber-Waugh karen Thaxter Physiology Section Department of Basic Medical Sciences The University of the West Indies (UWI) Mona Jamaica

Aim: The effect of patented nutritional supplementation on drug-seeking behavior in cocaine addicted rats during acute drug withdrawal was investigated using a biased Conditioned Place Preference (CPP) paradigm. Method: Twenty-four (24) male Sprague-Dawley rats with pre-conditioned preference for the black chamber of the CPP box were randomly divided into Cocaine (COC) or Saline (SAL) treated groups. Rats (n = 12) treated with cocaine hydrochloride 20 mg/kg/ml, i.p. (COC group) were confined individually to the white chamber on days 1, 3, 5 and 7. On alternate days, they were given 1 ml saline vehicle, i.p. and confined to the black chamber. Control rats (SAL group, n = 12) received only vehicle on all 8 days and were confined on alternate days to the white or black chamber. Positive place preference was confirmed for COC rats, which subsequently received 6 increasing daily doses of cocaine. CPP performances of both COC and SAL rats were recorded following an acute 3-day withdrawal period. All animals were then randomly assigned to rats fed either chow reconstituted with the nutritional supplement (COC-S and SAL-S) or standard rat chow (COC-N and SAL-N) for 8 weeks, followed by final CPP performances. Results: Following supplementation, COC-S rats made significantly less entries and time spent in the white chamber (p Conclusion: Drug-seeking behavior that persisted during cocaine withdrawal was significantly diminished in the nutritionally supplemented.

关键词： Cocaine Conditioned Place Preference Nutritional Supplement Addiction Drug-Seeking Behavior

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CagA EPIYA polymorphisms in Colombian Helicobacter pylori strains and their influence on disease-associated cellular responses

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World Journal of Gastrointestinal Oncology 2013年第3期5卷 50-59页

作者： Carlos Alberto Fajardo Andrés Javier Quiroga Andrea Coronado karen Labrador Nicole Acosta Pilar Delgado Carlos Jaramillo María Mercedes Bravo Cancer and Infectious Agents Research Group National Cancer Institute Molecular Diagnostics and Bioinformatics Laboratory Biological Sciences Department Los Andes University

AIM: To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori ) strains from Colombia on the host cell biology. METHODS: Eighty-four H. pylori-cagA positive strains with different Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs patterns, isolated from patients with gastritis (n=17), atrophic gastritis (n=17), duodenal ulcer (n=16), intestinal metaplasia (n=16) and gastric cancer (n=18), were included. To determine the integrity of the cag pathogenicity island (cag PAI) we evaluated the presence of cagA, cagT, cagE, and cag10 genes by polymerase chain reaction. AGS gastric epithelial cellswere infected with each strain and assayed for translo-cation and tyrosine phosphorylation of CagA by western blot, secretion of interleukin-8 (IL-8) by enzyme-linked immuno sorbent assay after taking supernatants from cocultures and cell elongation induction. For cell elongation quantification, coculture photographs were taken and the proportion of "hummingbird" cells (>15 μm) was determined. RESULTS: Overall 72% (60/84) of the strains were found to harbor a functional cag PAI. Levels of phos-phorylated CagA were significantly higher for isolates from duodenal ulcer than the ones in strains from gas-tritis, atrophic gastritis, intestinal metaplasia and gastric cancer (49.1% ± 23.1% vs 21.1% ± 19.5%, P ml and from 8.8 to 1442 pg/ml at 6 h and 30 h post-infection, respectively. cagPAI-defective strains did not induce detectable levels of IL-8 at 6 h post-infection. At 30 h post-infection all strains induced IL-8 expression in AGS cells, although cagPAI-defective strains induced significantly lower levels of IL-8 than strains with a functional cagPAI (57.1 ± 56.6 pg/ml vs 513.6 ± 338.6 pg/ml,P < 0.0001). We did not observe differences in the extent of cell

关键词： Helicobacter pylori cagA 3’region CagA protein Interleukin 8 Cell elongation Glu-Pro-Ile-Tyr-Ala

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Virgin Coconut Oil Improved Discriminative Learning and Working Memory in Aging Cycling and Non-Cycling Female Sprague-Dawley Rats Supporting Its Beneficial Effect in Retarding Age-Related Cognitive Decline

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Advances in Aging Research 2021年第5期10卷 97-112页

作者： Lauriann Young Brittany Smith Annice Webber-Waugh karen Thaxter Physiology Section Department of Basic Medical Sciences The University of the West Indies (UWI) Mona Jamaica

Aim: Beneficial effects of virgin coconut oil (VCO) consumption to improve cognition in menopausal females remain inconclusive. This study examined the effect of VCO supplementation in aging cycling and non-cycling rodents to assess its impact on cognition. Methods: Sprague-Dawley rats (10 - 18 months) were randomly assigned to a supplemented VCO group (SVCO) that received oral doses of 1.42 mL/kg/day VCO (n = 10) and a non-supplemented (NVCO) group (n = 10). Their performance in a biased Y-maze discriminative learning paradigm was assessed over a 16-week period. Rats were initially allowed 3 minutes to explore the maze (habituated) and subsequently pre-trained in the non-preferred, white chamber to associate the presentation of a tone with a treat (reward). Training

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Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

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World Journal of Hepatology 2016年第17期8卷 726-730页

作者： karen Louise Thomsen Holger Jon Moller Jonas Heilskov Graversen Nils E Magnusson Soren K Moestrup Hendrik Vilstrup Henning Gronbaek Department of Hepatology and Gastroenterology Aarhus University Hospital Department of Clinical Biochemistry Aarhus University Hospital Affinicon Aps Incuba Science Park Institute of Molecular Medicine University of Southern Denmark Department of Clinical Medicine Faculty of HealthMedical Research LaboratoryAarhus University Department of Biomedicine University of Aarhus

AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid ***: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P ml vs 389 ± 67 μg/ml, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/ml vs 21583 ± 7117 pg/ml, P = 0.03) and IL-6(15685 ± 3779 pg/ml vs 25715 ± 4036 pg/ml, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other ***: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.

关键词： Acute phase response Dexamethasone Endotoxin Hemoglobin scavenger receptor CD163 Cytokines Inflammation Rats

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手性液相色谱法直接定量乳粉中RRR-α-生育酚

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食品安全质量检测学报 2021年第12期12卷 4923-4928页

作者：王枚博 karen J.Schimpf 宋畅雅培贸易(上海)有限公司上海200233 Abbott Nutrition Analytical Research and DevelopmentColumbus OH 43219

目的建立手性液相色谱法直接测定乳粉中RRR-α-生育酚的检测方法。方法样品经氢氧化钾皂化,石油醚-异丙醚萃取。经小粒径纤维素衍生物型手性柱Daicel Chiralcel OD-3 (2.1 mm×150 mm, 3μm)直接分离,采用无水乙醇-正己烷(5:995, V:V)(A... 详细信息

目的建立手性液相色谱法直接测定乳粉中RRR-α-生育酚的检测方法。方法样品经氢氧化钾皂化,石油醚-异丙醚萃取。经小粒径纤维素衍生物型手性柱Daicel Chiralcel OD-3 (2.1 mm×150 mm, 3μm)直接分离,采用无水乙醇-正己烷(5:995, V:V)(A)和三乙胺-正己烷(5:995, V:V)(B)(A:B=10:90)作为流动相进行等度洗脱,流速为0.2 ml/min,柱温30℃,检测波长为294 nm,外标法定量。结果 RRR-α-生育酚和其他α-生育酚异构体的分离度大于1.2。在0.5~50μg/ml范围内线性关系良好,相关系数大于0.999,检出限为0.20 mg/100 g,定量限为0.60 mg/100 g,加标回收率为95.0%~109.4%,相对标准偏差为2.7%。结论该方法快速、准确、灵敏,适合测定乳粉中RRR-α-生育酚的含量。

关键词： RRR-α-生育酚维生素E 手性液相色谱法乳粉

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Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats

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World Journal of Gastroenterology 2016年第25期22卷 5761-5768页

作者： Juliana Fernandes Matos Madileine Francely Americo Yuri karen Sinzato Gustavo Tadeu Volpato Luciana Aparecida Corá Marcos Felipe Freitas Calabresi Ricardo Brandt Oliveira Debora Cristina Damasceno Jose Ricardo Arruda Miranda Sao Paulo State University BotucatuSP 18618-970Brazil Instituto de Ciencias Biologicas e da Saude Federal University of Mato GrossoBarra do GarcasMT 78600-000Brazil Universidade Estadual de Ciencias da Saude de Alagoas MaceioAL 57010-300Brazil Sao Paulo University Ribeirao PretoSP 14049-900Brazil

AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant(estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats(n = 23) were randomly divided into(1) non-pregnant,(contractility, n =6; transit, n = 6); and(2) pregnant(contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry(ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions(3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying(168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control(54.23 ± 15.14 ng/m L and 129.96 ± 30.52 ng/ml vs 13.25 ± 6.31 ng/ml). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0(44.3 ± 15.18 pg/ml vs 24.96 ± 5.96 pg/ml). CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.

关键词： Reproductive physiological process Sex hormones Gastrointestinal motility Magnetic fields Gastric emptying

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Δ<sup>9</sup>-Tetrahydrocannabinol Produced Positive Place Preference in Mice without Significant <i>Ex-Vivo</i>Effect on Hepatic Arylamine N-Acetyltransferase Activity: Implications for Its Addictive Liability and Absence of Effect on Xenobiotic Metabolism

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Journal of Behavioral and Brain Science 2021年第8期11卷 179-192页

作者： Lauriann Young karen Thaxter Danielle Campbell Sheena Francis Nicola Laurieri Rupika Delgoda Physiology Section Department of Basic Medical Sciences The University of the West Indies (UWI) Mona Campus Kingston Jamaica Natural Products Institute The University of the West Indies (UWI) Mona Campus Kingston Jamaica Department of Pharmacology Oxford University Oxford England UK

Aim: Δ9-Tetrahydrocannabinol (Δ9-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ9-THC in mice and whether Δ9-THC had any impact ex-vivo and in-vitro on NAT activity. Methods: Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. Mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ9-THC (0.10, 0.50 or 2.0 mg/kg/ml, ip) or amphetamine (AMP, 5.0 mg/kg/ml, ip);while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the white, drug-paired chamber during a 15-min post-conditioning exploration of the CPP apparatus were compared with the pre-conditioning exploratory scores. Livers from Δ9-THC treated and untreated mice were excised and NAT enzyme activity determined ex-vivo using a spectrophotometric assay with p-anisidine as substrate. The impact of varying concentrations of Δ9-THC (0.00 - 162 μM) on the activities of NAT from untreated mice livers were also investigated in-vitro. Results: Δ9-THC treated mice entered and spent significantly more time in the drug-paired CPP chamber (p ≤ 0.05) at post-conditioning vs pre-conditioning (F = 11.22). Mice treated with 2.0 mg/kg Δ9-THC made significantly more entries into the drug-paired chamber (p ≤ 0.05) as compared with their vehicle controls. AMP-treated mice displayed significant (p In-vitro NAT evaluations revealed a dose-dependent inhibitory impact of Δ9-THC on NAT

关键词： Cannabis Marijuana Conditioned Place Preference Addiction Drug Reward

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