Institute of Preventive Medicine

Institute of Preventive Medicine

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Lu C.-H.,Tri Service General Hospital | Hung Y.-J.,Tri Service General Hospital | Hsieh P.-S.,NDMC | Hsieh P.-S.,Institute of Preventive Medicine
European Journal of Pharmacology | Year: 2016

We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats. Male Sprague-Dawley rats were fed with either regular or HF diet for 8 weeks. Rats fed with regular diet were treated with vehicle for further 4 weeks. HF fed rats were divided into 6 groups, namely, vehicle, celecoxib (30 mg/kg/day), metformin (300 mg/kg/day), metformin (150 mg/kg/day), metformin (300 mg/kg/day) with celecoxib (30 mg/kg/day), and metformin (150 mg/kg/day) with celecoxib (15 mg/kg/day) for additional 4 weeks. Increased body weight in HF fed rats was significantly reduced by metformin alone and metformin combined with celecoxib. The increases in the HOMA-IR value and the area under the curve of glucose following an oral glucose tolerance test, systolic blood pressure, and adipocyte size were significantly diminished in treated rats, especially rats undergoing combined treatment. Treatments with either celecoxib or in combination with metformin resulted in a reduction in AT macrophage infiltration and decreases in levels of adipose tissue TNF-α, MCP-1, and leptin levels in high-fat (HF) fed rats. Furthermore, the elevated hepatic triglycerides content was significantly decreased in the combined treatment group compared to that of groups of celecoxib or metformin alone. Celecoxib exerts a synergistic beneficial effect with metformin on and obesity-associated metabolic and cardiovascular disorders in high-fat fed rats. © 2016 Elsevier B.V.

Chang H.,National Chiayi University | Yeh M.-K.,Institute of Preventive Medicine
International Journal of Nanomedicine | Year: 2012

Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized. © 2012 Chang and Yeh.

Kitahara C.M.,U.S. National Cancer Institute | Gamborg M.,Bispebjerg and Frederiksberg Hospitals | De Gonzalez A.B.,U.S. National Cancer Institute | Sorensen T.I.A.,Bispebjerg and Frederiksberg Hospitals | And 4 more authors.
Cancer Research | Year: 2014

Taller stature and obesity in adulthood have been consistently associated with an increased risk of thyroid cancer, but few studies have investigated the role of childhood body size. Using data from a large prospective cohort, we examined associations for height and body mass index (BMI) at ages 7 to 13 years with risk of thyroid cancer in later life. The study population included 321,085 children from the Copenhagen School Health Records Register, born between 1930 and 1989 in Copenhagen, Denmark, with measurements of height and weight from 7 to 13 years of age. These data were linked with the Danish Cancer Registry to identify incident thyroid cancer cases (1968-2010). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for age- and sex-specific height and BMI SD scores (SDS) using proportional hazards models stratified by birth cohort and sex. During follow-up (median 1/4 38.6 years), 171 women and 64 men were diagnosed with thyroid cancer. Both height and BMI were positively associated with thyroid cancer risk, and these associations were similar by age at measurement. Using age 10 as an example, HRs per 1 unit increase in SDS for height (~6-7 cm) and BMI (~1.5-2 kg/m2) were 1.22 (95% CI, 1.07-1.40) and 1.15 (95% CI, 1.00-1.34), respectively. These results, together with the relatively young ages at which thyroid cancers are diagnosed compared with other malignancies, suggest a potential link between early-life factors related to growth and body weight and thyroid carcinogenesis. © 2014 American Association for Cancer Research.

Vamosi M.,University of Southern Denmark | Heitmann B.L.,Institute of Preventive Medicine | Kyvik K.O.,University of Southern Denmark
Obesity Reviews | Year: 2010

The prevalence of obesity is on a global-wide increase, but still the aetiology of adult obesity is poorly understood. It has been shown that overweight children suffer from adverse psychological events, but less is known about the potential effects of adverse psychological factors among normal weight children for later development of obesity. The purpose of this study was to systematically review current literature on associations between psychological factors in childhood and development of obesity in adulthood. A systematic search was conducted in three electronic databases MEDLINE (silverplatter 1977-2008), PsycINFO (1972-2008) and PsycINFO Weekly (week 1 January 2007-week 3 July 2008) to identify studies of interest. Six prospective and two retrospective studies were identified. Psychosocial factors related to adult obesity were lack of childhood care, abuse and childhood anxiety disorders. In addition, depression in adolescence tended to be related to adult obesity but among young girls only. Learning difficulties and scholastic proficiencies below average were also risk factors. The current literature suggests that specific psychosocial factors in childhood may act as determinants for developing obesity in adulthood. © 2009 International Association for the Study of Obesity.

Chen M.-C.,Graduate Institute of Medical science | Lee C.-F.,Institute of Preventive Medicine | Huang W.-H.,National Defense Medical Center | Chou T.-C.,National Defense Medical Center
Biochemical Pharmacology | Year: 2013

The hypoxic environment in tumors is an important factor causing tumor angiogenesis by activating the key transcription factor, hypoxia-inducible factors-1α (HIF-1α). Magnolol isolated from Magnolia officinalis has been reported to exhibit an anticancer activity via elevation of apoptosis. However, whether magnolol inhibits tumor angiogenesis remains unknown. In the present study, we demonstrated that magnolol significantly inhibited angiogenesis in vitro and in vivo evidenced by the attenuation of hypoxia and vascular endothelial growth factor (VEGF)-induced tube formation of human umbilical vascular endothelial cells, vasculature generation in chicken chorioallantoic membrane and Matrigel plug. In hypoxic human bladder cancer cells (T24), treatment with magnolol inhibited hypoxia-stimulated H 2O2 formation, HIF-1α induction including mRNA, protein expression, and transcriptional activity as well as VEGF secretion. Additionally, the enhanced degradation of HIF-1α protein via enhancing prolyl hydroxylase activity and the decreased newly-synthesized HIF-1α protein in hypoxic T24 cells may involve the reduction of HIF-1α protein accumulation by magnolol. Interestingly, magnolol also acts as a VEGFR2 antagonist, and subsequently attenuates the down-stream AKT/mTOR/p70S6K/4E-BP-1 kinase activation both in hypoxic T24 cells and tumor tissues. As expected, administration of magnolol greatly attenuated tumor growth, angiogenesis and the protein expression of HIF-1α, VEGF, CD31, a marker of endothelial cells, and carbonic anhydrase IX, an endogenous marker for hypoxia, in the T24 xenograft mouse model. Collectively, these findings strongly indicate that the anti-agngiogenic activity of magnolol is, at least in part, mediated by suppressing HIF-1α/VEGF-dependent pathways, and suggest that magnolol may be a potential drug for human bladder cancer therapy. © 2013 Elsevier Inc.

Tang-Peronard J.L.,Institute of Preventive Medicine | Tang-Peronard J.L.,University of Southern Denmark | Andersen H.R.,University of Southern Denmark | Jensen T.K.,University of Southern Denmark | And 2 more authors.
Obesity Reviews | Year: 2011

This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

Ziegler R.,Institute Hiscia | Grossarth-Maticek R.,Institute of Preventive Medicine
Evidence-based Complementary and Alternative Medicine | Year: 2010

Mistletoe preparations such as Iscador are in common use as complementary/anthroposophic medications for many cancer indications, particularly for solid cancers. The efficacy is still discussed controversially. This paper presents an individual patient data meta-analysis of all published prospective matched-pair studies with breast cancer patients concerned with long-term application of a complementary/anthroposophic therapy with the mistletoe preparation Iscador. Six sets of data were available for individual patient meta-analysis of breast cancer patients, matched according to prognostic factors into pairs with and without mistletoe (Iscador) therapy. The main outcome measures were overall survival and psychosomatic self-regulation. Overall survival was almost significant in favor of the Iscador group in the combined data set of the randomized studies: estimate of the hazard ratio with 95% confidence interval 0.59 (0.34, 1.02). Overall survival was highly significant in the combined data set of the non-randomized studies: 0.43 (0.34, 0.56). In the combined analysis of the randomized studies, improvement of psychosomatic self-regulation, as a measure of autonomous coping with the disease, was highly significant in favor of the Iscador group: estimate of the median difference 0.45 (0.15, 0.80), P=0.0051. The analyzed studies show that therapy with Iscador might prolong overall survival and improve psychosomatic self-regulation of breast cancer patients. © 2008 The Author(s).

Grossschadl F.,Medical University of Graz | Haditsch B.,Institute of Preventive Medicine | Stronegger W.J.,Medical University of Graz
Public Health Nutrition | Year: 2012

Objective Epidemiological studies have shown that adults tend to underestimate their weight and overestimate their height. This may lead to a misclassification of their BMI in studies based on self-reported data. The aim of the present study was to assess the validity of self-reported weight and height in Austrian adults. Design Data on weight, height, health behaviour and sociodemographic characteristics of adults were collected in a standardized procedure via a self-filling questionnaire and a medical examination including measurements of weight and height. Setting A publicly accessible out-patient clinic in southern Austria. Subjects Austrian residents (n 473) aged 18 years and older who attended a health check participated in the study. Results The mean difference between reported and measured BMI was not significant in younger adults (<35 years: mean difference -0.21 kg/m 2; P < 0.08) but increased significantly with age (≥55 years: mean difference -0.68 kg/m 2; P < 0.001). The prevalence of normal weight (BMI = 18.5-24.9 kg/m 2) and overweight (BMI = 25.0-29.9 kg/m 2) was overestimated based on the self-reported data on BMI, while that for underweight (BMI < 18.5 kg/m 2) and obesity (BMI ≥ 30.0 kg/m 2) was underestimated (P < 0.001). The self-reported data showed an obesity prevalence of 12.5 %, while measurement showed a prevalence of 15.4 % (P < 0.001). Conclusions Our results indicate that prevalence rates of obesity are probably underestimated for Austrian adults when using self-reported weight and height information. The deviations from the measured data clearly increased with age. Analyses based on self-reported data should therefore be adjusted for the age dependency of the validity. © The Authors 2011.

Kau J.H.,Institute of Preventive Medicine
PloS one | Year: 2010

Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT-mediated immunosuppressive effects. However, the involvement of MAPK independent pathways has not been clearly elucidated; nor has the crucial role played by LT in the early stages of infection. Determining whether LT exerts any pathological effects before being enriched to an MEK inhibitory level is an important next step in the furtherance of this field. Using a cell culture model, we determined that low doses of LT inhibited phagocytosis of macrophages, without influencing MAPK pathways. Consistent low doses of LT significantly suppressed bacterial clearance and enhanced the mortality of mice with bacteremia, without suppressing the MEK1 of splenic and peripheral blood mononuclear cells. These results suggest that LT suppresses the phagocytes in a dose range lower than that required to suppress MEK1 in the early stages of infection.

Rong-Hwa S.,Institute of Preventive Medicine | Shiao-Shek T.,Institute of Preventive Medicine | Der-Jiang C.,Institute of Preventive Medicine | Yao-Wen H.,Institute of Preventive Medicine
Food Chemistry | Year: 2010

The lateral flow assay (LFA), a rapid, sensitive, and reproducible technique, was successfully applied to detect staphylococcal enterotoxin B (SEB). The assay was based on a double-antibody sandwich format on a porous nitrocellulose membrane. When SEB-containing samples were applied to the LFA-device, the toxin initially reacted with polyclonal antibody (Pab)-coated colloidal gold particles and then reacted with the fixed Pab on the membrane. These reactions resulted in a red line at the detection zone, with intensity proportional to the SEB concentration (under 100 ng/ml). With this method, 1 ng/ml of SEB can be detected in less than 5 min and was highly reproducible. Signal can be amplified to 10 pg/ml by silver enhancement. This assay also showed no cross-reaction with other SEs, such as SEA, SEC, SED and SEE. The assay was significantly faster than the ELISA or real-time PCR assay and should facilitate early and rapid SEB detection in clinical and food samples. © 2009 Elsevier Ltd. All rights reserved.

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