Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease

Kim, H.&#x2010,S.,Kang, J.&#x2010,H.,Jeung, E.&#x2010,B.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2016 Journal of veterinary internal medicine Vol.30 No.5

<P><B>Background</B></P><P>The concentrations of circulating adipokines in dogs with myxomatous mitral valve disease (MMVD) have not been investigated in detail.</P><P><B>Objectives</B></P><P>To determine whether serum concentrations of adipokines differ between healthy dogs and dogs with MMVD and whether circulating concentrations depend on the severity of heart failure resulting from MMVD.</P><P><B>Animals</B></P><P>In the preliminary study, 30 healthy dogs and 17 client‐owned dogs with MMVD, and in the subsequent study, 30 healthy dogs and 46 client‐owned dogs with MMVD.</P><P><B>Methods</B></P><P>Prospective case‐controlled observational study. In the preliminary study, serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor‐α were measured. In the subsequent study, MMVD dogs were divided into three groups according to the International Small Animal Cardiac Health Council (ISACHC) classification, and serum concentrations of leptin and adiponectin were measured.</P><P><B>Results</B></P><P>In the preliminary study, serum leptin and adiponectin concentrations differed significantly between dogs with MMVD and healthy dogs. Serum leptin (<I>P</I> = .0013) concentrations were significantly higher in dogs with MMVD than in healthy dogs, whereas adiponectin (<I>P</I> = .0009) concentrations were significantly lower in dogs with MMVD. However, we observed no significant differences in the other variables. In the subsequent study, dogs classified as ISACHC class 3 had higher serum concentrations of leptin (<I>P</I> = .0022) than healthy dogs but ISACHC class 1 or 2 dogs did not. Serum adiponectin concentrations were significantly lower in ISACHC class 1 (<I>P</I> < .0001) dogs than in healthy dogs, whereas adiponectin concentrations in ISACHC class 3 dogs were significantly higher than in ISACHC class 1 dogs (<I>P</I> = .0081).</P><P><B>Conclusions and Clinical Importance</B></P><P>Circulating concentrations of leptin and adiponectin might be altered in dogs with MMVD.</P>

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Cho, K.&#x2010,D.,Paek, J.,Kang, J.&#x2010,H.,Chang, D.,Na, K.&#x2010,J.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.2

<P><B>Background</B></P><P>An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.</P><P><B>Objectives</B></P><P>To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).</P><P><B>Animals</B></P><P>Thirty healthy dogs and 15 client‐owned dogs with PDH.</P><P><B>Methods</B></P><P>Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.</P><P><B>Results</B></P><P>The serum leptin (<I>P</I> < .0001) and insulin (<I>P</I> < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (<I>P</I> = .0039) and insulin (<I>P</I> = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.</P><P><B>Conclusions and Clinical Importance</B></P><P>Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.</P>

Serum Adipokine Concentrations in Dogs with Acute Pancreatitis

Paek, J.,Kang, J.&#x2010,H.,Kim, H.&#x2010,S.,Lee, I.,Seo, K.W.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.6

<P><B>Background</B></P><P>Limited information is available about the role of adipokines in the development and progression of acute pancreatitis (AP) in dogs.</P><P><B>Objectives</B></P><P>To determine whether the circulating concentrations of adipokines differed between healthy dogs and dogs with AP, and whether the circulating concentrations differed between AP survivors and AP nonsurvivors.</P><P><B>Animals</B></P><P>Twenty‐eight healthy dogs and 25 client‐owned dogs with AP.</P><P><B>Methods</B></P><P>Prospective observational cohort study of 25 client‐owned dogs with newly diagnosed AP and 28 otherwise healthy dogs with similar body condition scores. The serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured.</P><P><B>Results</B></P><P>The serum concentrations of leptin (<I>P </I>=<I> </I>.0021), resistin (<I>P </I>=<I> </I>.0010), visfatin (<I>P </I><<I> </I>.0001), IL‐1β (<I>P </I><<I> </I>.0001), IL‐6 (<I>P </I>=<I> </I>.0002), IL‐10 (<I>P </I><<I> </I>.0001), and IL‐18 (<I>P </I><<I> </I>.0001) were significantly higher in dogs with AP than healthy dogs, whereas the adiponectin concentration (<I>P </I>=<I> </I>.0011) was significantly lower. There were significant differences in the serum concentrations of leptin (<I>P </I>=<I> </I>.028) and adiponectin (<I>P </I>=<I> </I>.046) in survivors and nonsurvivors. After the disappearance of clinical signs, the concentrations of resistin (<I>P </I>=<I> </I>.037) and IL‐1β (<I>P </I>=<I> </I>.027) decreased significantly, whereas the serum concentrations of leptin (<I>P </I>><I> </I>.999), adiponectin (<I>P </I>=<I> </I>.11), visfatin (<I>P </I>=<I> </I>.83), IL‐6 (<I>P </I>=<I> </I>.82), IL‐10 (<I>P </I>=<I> </I>.82), IL‐18 (<I>P </I>=<I> </I>.56), and TNF‐α (<I>P </I>=<I> </I>.94) did not differ significantly.</P><P><B>Conclusion and Clinical Importance</B></P><P>This study showed that dysregulation of adipokines might be involved in the pathogenesis of AP. In addition, leptin and adiponectin are likely to be associated with mortality rate in AP.</P>

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K&#x2010,H.,Hong, K&#x2010,S.,Lee, B&#x2010,C.,Oh, M&#x2010,S.,Cho, Y&#x2010,J.,Koo, J&#x2010,S.,Park, J&#x2010,M.,Bae, H&#x2010,J.,Han, M&#x2010,K.,Ju, Y&#x2010,S.,Kang, D&#x2010,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

Biocompatible Poly(2‐hydroxyethyl methacrylate)‐<i>b</i>‐poly(<small>L</small>‐histidine) Hybrid Materials for pH‐Sensitive Intracellular Anticancer Drug Delivery

Johnson, Renjith P.,Jeong, Young&#x2010,Il,Choi, Eunji,Chung, Chung&#x2010,Wook,Kang, Dae Hwan,Oh, Sae&#x2010,Ock,Suh, Hongsuk,Kim, Il WILEY‐VCH Verlag 2012 Advanced Functional Materials Vol.22 No.5

<P><B>Abstract</B></P><P>A series of synthetic polymer bioconjugate hybrid materials consisting of poly(2‐hydroxyethyl methacrylate) (p(HEMA)) and poly(<SMALL>l‐</SMALL>histidine) (p(His)) are synthesized by combining atom transfer radical polymerization of HEMA with ring opening polymerization of benzyl‐<I>N</I>‐carboxy‐<SMALL>L</SMALL>‐histidine anhydride. The resulting biocompatible and membranolytic p(HEMA)<SUB>25</SUB>‐<I>b</I>‐p(His)<SUB><I>n</I></SUB> (<I>n</I> = 15, 25, 35, and 45) polymers are investigated for their use as pH‐sensitive drug‐carrier for tumor targeting. Doxorubicin (Dox) is encapsulated in nanosized micelles fabricated by a self‐assembly process and delivered under different pH conditions. Micelle size is characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) observations. Dox release is investigated according to pH, demonstrating the release is sensitive to pH. Antitumor activity of the released Dox is assessed using the HCT 116 human colon carcinoma cell line. Dox released from the p(HEMA)‐<I>b</I>‐p(His) micelles remains biologically active and has the dose‐dependent capability to kill cancer cells at acidic pH. The p(HEMA)‐<I>b</I>‐p(His) hybrid materials are capable of self‐assembling into nanomicelles and effectively encapsulating the chemotherapeutic agent Dox, which allows them to serve as suitable carriers of drug molecules for tumor targeting.</P>

<i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms

Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. &#x2010,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. &#x2010,K.,Yoon, Y. &#x2010,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4

<P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.&#x2010,S.,Choi, K.&#x2010,M.,Choi, M.&#x2010,H.,Ji, S.&#x2010,Y.,Lee, S.,Sin, D.&#x2010,M.,Oh, K.&#x2010,W.,Lee, Y.&#x2010,M.,Hong, J.&#x2010,T.,Yun, Y.&#x2010,P.,Yoo, H.&#x2010,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes

Illeperuma, Rasika P.,Kim, Do Kyeong,Park, Young Jin,Son, Hwa Kyung,Kim, Jue Young,Kim, Jinmi,Lee, Doo Young,Kim, Ki&#x2010,Yeol,Jung, Da&#x2010,Woon,Tilakaratne, Wanninayake M.,Kim, Jin Alan R. Liss, Inc 2015 International journal of cancer Vol.137 No.11

<▼1><P>Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate model for studying the role of fibroblasts during early stage carcinogenesis. In this sense, this study aims at investigating whether areca nut (AN)‐exposed fibroblasts cause DNA damage of epithelial cells. For this study, immortalized hNOF (hTERT‐hNOF) was used. We found that the levels of GRO‐α, IL‐6 and IL‐8 increased in AN‐exposed fibroblasts. Cytokine secretion was reduced by antioxidants in AN‐exposed fibroblasts. Increase in DNA double strand breaks (DSB) and 8‐oxoG FITC‐conjugate was observed in immortalized human oral keratinocytes (IHOK) after the treatment of cytokines or a conditioned medium derived from AN‐exposed fibroblasts. Cytokine expression and DNA damage were also detected in OSF tissues. The DNA damage was reduced by neutralizing cytokines or antioxidant treatment. Generation of reactive oxygen species (ROS) and DNA damage response, triggered by cytokines, were abolished when NADPH oxidase (NOX) 1 and 4 were silenced in IHOK, indicating that cytokine‐triggered DNA damage was caused by ROS generation through NOX1 and NOX4. Taken together, this study provided strong evidence that blocking ROS generation might be a rewarding approach for cancer prevention and intervention in OSF.</P></▼1><▼2><P><B>What's new?</B></P><P>Fibroblasts in the tumor microenvironment influence tumor initiation and growth and are of particular interest in oral submucous fibrosis (OSF), a progressive fibrotic disease of malignant potential. This study shows that the release of tumor‐promoting cytokines by fibroblasts exposed to areca nut, the primary cause of OSF, induce DNA damage in oral keratinocytes. The findings suggest that fibroblasts indirectly promote epithelial transformation in OSF by secreting cytokines, whereby DNA damage of epithelial cells is inflicted by reactive oxygen species generated <I>via</I> NADPH oxidases. These insights could inform the development of new therapeutic approaches for OSF.</P></▼2>

MicroRNA signatures associated with immortalization of EBV‐transformed lymphoblastoid cell lines and their clinical traits

Lee, J.&#x2010,E.,Hong, E.&#x2010,J.,Nam, H.&#x2010,Y.,Kim, J.&#x2010,W.,Han, B.&#x2010,G.,Jeon, J.&#x2010,P. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.1

<P><B>Abstract</B></P><P><B>Objective: </B> MicroRNAs (miRNAs) are negative regulators of gene expression that play important roles in cell processes such as proliferation, development and differentiation. Recently, it has been reported that miRNAs are related to development of carcinogenesis. The aim of this study was to identify miRNAs associated with terminal immortalization of Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell line (LCL) and associated clinical traits.</P><P><B>Material and Methods: </B> Hence, we performed miRNA microarray approach with early‐ (p6) and late‐passage (p161) LCLs.</P><P><B>Results and Conclusion: </B> Microarray data showed that nine miRNAs (miR‐20b*, miR‐28‐5p, miR‐99a, miR‐125b, miR‐151‐3p, miR‐151:9.1, miR‐216a, miR‐223* and miR‐1296) were differentially expressed in most LCLs during long‐term culture. In particular, miR‐125b was up‐regulated in all the tested late‐passage LCLs. miR‐99a, miR‐125b, miR‐216a and miR‐1296 were putative negative regulators of <I>RASGRP3</I>, <I>GPR160</I>, <I>PRKCH</I> and <I>XAF1</I>, respectively, which were found to be differentially expressed in LCLs during long‐term culture in a previous study. Linear regression analysis showed that miR‐200a and miR‐296‐3p correlated with triglyceride and HbA1C levels, respectively, suggesting that miRNA signatures of LCLs could provide information on the donor’s health. In conclusion, our study suggests that expression changes of specific miRNAs may be required for terminal immortalization of LCLs. Thus, differentially expressed miRNAs would be a potential marker for completion of cell immortalization during EBV‐mediated tumorigenesis.</P>

Distinctive hematological abnormalities in East Asian neonates and children with down syndrome

KIM, D.&#x2010,W.,KIM, H.&#x2010,R.,SHIN, M.&#x2010,G.,BAEK, H.&#x2010,J.,KOOK, H.,HWANG, T.&#x2010,J.,SHIN, J.&#x2010,H.,SUH, S.&#x2010,P.,RYANG, D.&#x2010,W. Blackwell Publishing Ltd 2011 International journal of laboratory hematology Vol.33 No.4

<P><B>Summary</B></P><P><B>Introduction: </B> Neonates with Down syndrome (DS) are predisposed to developing transient abnormal myelopoiesis (TAM) and acute myeloid leukemia (AML) associated with DS. However, there is a paucity of data on hematological aberrations and <I>GATA1</I> mutations in neonates with DS in East Asian populations.</P><P><B>Methods: </B> Total 109 patients with DS who had one or more CBCs obtained were enrolled. The molecular analysis of the <I>GATA1</I> gene performed in 10 patients (three TAM, three AML associated with DS at diagnosis, one remission case of AML associated with DS and three DS without TAM or AML).</P><P><B>Results: </B> East Asian DS neonates showed low frequency of thrombocytopenia, uncommon neutrophilia and higher prevalence rate of TAM compared to previous reports from western countries. <I>GATA1</I> mutations were identified in almost all TAM and AML associated with DS samples, but were not detected in the samples from DS without TAM or AML associated with DS.</P><P><B>Conclusion: </B> East Asian DS neonates and children showed distinctive spectrum of hematological abnormalities.</P>