• Title/Summary/Keyword: Metabolic component

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Metabolic Activation of Marijuana Constituents, Cannabinoids, in Relation to Their Toxicity for Human and Its Oxidation Mechanism

  • Ikuo, Yamamoto
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.194-199
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    • 2002
  • Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

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The Validity and Reliability of the Korean Version of Revised Processes of Change for Weight Control Scale in Adults with Metabolic Syndrome (한국판 체중조절 변화과정 측정도구의 타당도와 신뢰도 검증 - 비만한 대사증후군 대상자를 중심으로 -)

  • Kim, Chun-Ja;Kim, Dae-Jung;Chae, Sun-Mi
    • The Journal of Korean Academic Society of Nursing Education
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    • v.14 no.2
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    • pp.262-272
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    • 2008
  • Purpose: This study examined the validity and reliability of the Korean version of the Revised Process of Change for Weight Control Scale (POC-WCS) in adults with metabolic syndrome. Method: A methodological research design with an exploratory factor analysis for validity and correlational coefficients for reliability was used. The Korean version of the Revised POC-WCS was translated into Korean and a translation equivalency was obtained. It was tested with one hundred and fifty-one obese adults with metabolic syndrome in a university hospital. The data were analyzed using Cronbach's alpha and Guttman coefficients and a principal component factor analysis with SPSS/WIN 12.0. Result: The factor analysis identified eight factors explaining 64.7% of the total variance. The Korean version of the Revised POC-WCS included stimulus control (9 items), dramatic relief (6 items), reinforcement management (6 items), helping relationships (4 items), consciousness raising (3 items), self liberation (3 items), self reevaluation (3 items), and social liberation (4 items). The internal consistency was acceptable with Cronbach's alpha (.94) and Guttman coefficient (.92). Conclusion: The Korean version of the Revised POC-WCS had adequate validity and reliability in adults with metabolic syndrome. It can be used to assess the strategies and processes for weight control in a variety of populations with obesity.

Cytotoxicity and Genotoxicity Study of CKD-712 in Mammalian Cell System

  • Kim, Eun-Young;Yun, Hye-Jung;Kim, Youn-Jung;Ryu, Jae-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.05a
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    • pp.186-186
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    • 2003
  • CKD-712, named S-YS49 is a chiral compound derived from higenamine (one component of Aconite spp.) derivatives. To compare the cytotoxicity of CKD-712 between in the absence and in the presence of S9 metabolic activation system, we performed trypan blue dye exclusion assay in Chinese hamster lung (CHL) cell. In CHL cells, the cytotoxicity (IC50) of CKD-712 was 92.9 $\mu\textrm{g}$/ml and 186.1 $\mu\textrm{g}$/ml in the absence and presence of S9 metabolic activation, respectively. And we also investigated the induction of DNA damages in mammalian cells. To perform the single cell gel electrophoresis, we determined optimum concentration in mouse lymphoma L5178Y cells using frypan blue dye exclusion assay Each IC20 of CKD-712 was determined the concentration of 23.4 $\mu\textrm{g}$/ml and 24.8 $\mu\textrm{g}$/ml in the absence and presence of S9 metabolic activation, respectively. In the comet assay, DNA damage was not observed at the concentration range from 23.4 $\mu\textrm{g}$/ml to 5.9 $\mu\textrm{g}$/ml in the absence of S9 metabolic activation system. In the presence of S9 metabolic activation system, DNA damage was not observed at the concentration range from 24.8 $\mu\textrm{g}$/ml to 6.2 $\mu\textrm{g}$/ml. From these results, it is assumed that CKD-712 may be metabolized to less cytotoxic metabolite(s).

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Metabolic Profiling of Eccentric Exercise-Induced Muscle Damage in Human Urine

  • Jang, Hyun-Jun;Lee, Jung Dae;Jeon, Hyun-Sik;Kim, Ah-Ram;Kim, Suhkmann;Lee, Ho-Seong;Kim, Kyu-Bong
    • Toxicological Research
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    • v.34 no.3
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    • pp.199-210
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    • 2018
  • Skeletal muscle can be ultrastructurally damaged by eccentric exercise, and the damage causes metabolic disruption in muscle. This study aimed to determine changes in the metabolomic patterns in urine and metabolomic markers in muscle damage after eccentric exercise. Five men and 6 women aged 19~23 years performed 30 min of the bench step exercise at 70 steps per min at a determined step height of 110% of the lower leg length, and stepping frequency at 15 cycles per min. $^1H$ NMR spectral analysis was performed in urine collected from all participants before and after eccentric exercise-induced muscle damage conventionally determined using a visual analogue scale (VAS) and maximal voluntary contraction (MVC). Urinary metabolic profiles were built by multivariate analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) using SIMCA-P. From the OPLS-DA, men and women were separated 2 hr after the eccentric exercise and the separated patterns were maintained or clarified until 96 hr after the eccentric exercise. Subsequently, urinary metabolic profiles showed distinct trajectory patterns between men and women. Finally, we found increased urinary metabolites (men: alanine, asparagine, citrate, creatine phosphate, ethanol, formate, glucose, glycine, histidine, and lactate; women: adenine) after the eccentric exercise. These results could contribute to understanding metabolic responses following eccentric exercise-induced muscle damage in humans.

Effects of Aerobic Exercise Plus Lifestyle Modification Program on Obese-Induced Metabolic Syndrome in Obese Adolescent Girls (유산소운동과 생활양식 프로그램 병행이 비만 여자청소년의 비만유래 대사증후군에 미치는 효과)

  • Park, Chan-Ho;Park, Tae-Gon
    • Journal of Life Science
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    • v.19 no.2
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    • pp.198-205
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    • 2009
  • The purpose of this study was to find out the effects of a 12-week aerobic exercise plus lifestyle modification on obese-induced metabolic syndrome in obese adolescent girls. A total of 52 obese adolescent girls (13-14 years old; body mass index (BMI) ${\geq}$95th percentiles for age and sex) purposely assigned to aerobic exercise group (AEG, n=15), aerobic exercise plus lifestyle modification group (ALG, n=18), or control group (CG, n=19). The AEG completed 12 weeks of walking exercise (30-60 min/day, 65-75% HRmax, 6 days/week), the ALG completed 12 weeks of walking exercise (30-60 min/day, 65-75% HRmax, 6 days/week) and behavior modification (60 min/day, 1 day/week), and the CG continued their normal life. The presence of the metabolic syndrome and component risk factors were determined before and after 12-week programs. The total prevalence of the metabolic syndrome was 48.1% in this sample (25/52) of participants at baseline. After the programs the prevalence of the metabolic syndrome was improved in the AEG and ALG 33.3, 27.8%, respectively. Group analyses showed significant difference in risk factors of the metabolic syndrome such that the AEG and ALG had significantly greater improvements in waist circumference, triglycerides, blood glucose and systolic blood pressure than the CG, while there were no significant difference in HDL cholesterol and diastolic blood pressure. Also there was no group difference between AEG and ALG in all measured metabolic risk factors after the programs. These results indicate that the positive changes of the ALG were not associated with lifestyle modification (behavior modification) but associated with aerobic exercise. However, long-term follow up studies are necessary to clarify the additive effect of the behavior modification on the metabolic syndrome.

Resuscitation from a pH of 6.5: A Case Report and Review of Pathophysiology and Management of Extreme Acidosis from Hypovolemic Shock after Trauma

  • Balmaceda, Alexander;Arora, Sona;Sondheimer, Ilan;Hollon, McKenzie M.
    • Journal of Trauma and Injury
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    • v.32 no.4
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    • pp.238-242
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    • 2019
  • Extreme acidosis is a life-threatening physiological state that causes disturbances in the cardiovascular, pulmonary, immune, and hematological systems. Trauma patients commonly present to the operating room (OR) in hypovolemic shock, leading to tissue hypoperfusion and the development of acute metabolic acidosis with or without a respiratory component. It is often believed that trauma patients presenting to the OR in severe metabolic acidosis (pH <7.0) will have a nearly universal mortality rate despite aggressive resuscitation and damage control. The current literature does not include reports of successful resuscitations from a lower pH, which may lead providers to assume that a good outcome is not possible. However, here we describe a case of successful resuscitation from an initial pH of 6.5 with survival to discharge home 95 days after admission with almost full recovery. We describe the effects of acute acidosis on the respiratory and cardiovascular systems and hemostasis. Finally, we discuss the pillars of management in patients with extreme acute acidosis due to hemorrhage: transfusion, treatment of hyperkalemia, and consideration of buffering acidosis with bicarbonate and hyperventilation.

Consequences of being born small for gestational age : More than being small (부당경량아. 크기만 작은가?)

  • Yoo, Eun-Gyong
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.152-158
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    • 2009
  • Reduced fetal growth is independently associated with increased risk of health problems in later life, particularly type 2 diabetes and cardiovascular diseases. Insulin resistance appears to be a key component underlying these metabolic complications. It is suggested that detrimental fetal environment may program insulin resistance syndrome. An insulin-resistant genotype may also result in both low birth weight and insulin resistance syndrome, and it is likely that the association of low birth weight with insulin resistance is the result of both genetic and environmental factors. Early postnatal rapid catch-up growth is closely related to risk for subsequent metabolic diseases. Fat mass is strikingly reduced in neonates born small for gestational age (SGA), and recent data suggest that insulin resistance seen in catch-up growth is related to the disproportionate catch-up in fat mass compared with lean mass. Endocrine disturbances are also recognized in SGA children, but overt clinical problems are infrequent in childhood. Cognitive impairment is reported in some children born SGA, especially those who do not show catch-up growth, in whom early neurodevelopmental evaluation is required. Breast feeding, also known to be protective against the long-term risk of obesity, may prevent some intellectual impairment in SGA children. Calorie-dense feeding does not seem to be appropriate in SGA infants. We must balance the positive effect of nutrition on neural development against rapid fat deposition and the future risk of insulin resistance.

Serum Cholesterol and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (혈청 콜레스테롤과 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase)

  • Choi, Yong-Soon;Lee, Sang-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.21 no.5
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    • pp.580-593
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    • 1992
  • Cholesterol have many essential functions as a component of cellular and subcellular membranes, metabolic precursor of bile acids and steroid hormones, and obligatory part of the metabolic systems involved in DNA synthesis and cell division. These essential funtions demand a continuous and appropriate supply of cholesterol to the tissues. Body cholesterol pool is maintained by the balance of acquirement from diets, de novo synthesis, and excretion either as bile acids or neutral steroids. In these metabolic process, cholesterol biosynthesis is controlled by the change in the activity of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase. Under most physiological or nutritional situations, the activity of this enzyme is adroitly regulated to maintain tissue cholesterol balance. Excess cholesterol accumulation in the cells induces the decrease in the number of LDL-receptor, followed by the increase in the level of serum LDL-cholesterol. Increase in the level of serum cholesterol appears to be an important determinant for the incidence of the coronary heart disease. Dietary intervention may be helpful in alleviating an increase in the level of serum cholesterol or body cholesterol pool.

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Obesity and Insulin Resistance in Childhood (소아에서의 비만과 인슐린 저항성)

  • Choi, Kwang Hae
    • Journal of Yeungnam Medical Science
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    • v.29 no.2
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    • pp.73-76
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    • 2012
  • More and more children are becoming obese and overweight due to several factors that include a high energy density in the diet (a high fat intake) and low energy expenditure. Consequently childhood obesity is becoming a significant health problem. Fat tissue releases many cytokines such as resistin, tumor necrosis factor-${\alpha}$, leptin, interleukin-6. These adipocytokines induce obesity-related insulin resistance. Insulin resistance is a key component of obesity-related metabolic problems such as hypertension, type 2 diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, acanthosis nigricans and polycystic ovarian syndrome. This review article focused on insulin resistance and its related metabolic diseases.

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Cytotoxicity and Genotoxicity Study of CKD-712 in mammalian cell system

  • Kim, Eun-Young;Yun, Hye-Jung;Kim, Youn-Jung;Ryu, Jae-Chun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.179.1-179.1
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    • 2003
  • CKD-712, named S-YS49 is a chiral compound derived from higenamine (one component of Aconite spp.) derivatives. To compare the cytotoxicity of CKD-712 between in the absence and in the presence of S9 metabolic activation system, we performed try pan blue dye exclusion assay in Chinese hamster lung (CHL) cell. In CHL cells, the cytotoxicity ($IC_{50}$) of CKD-712 was 92.9 ${\m}g$/$m\ell$ and 186.1 ${\m}g$/$m\ell$ in the absence and presence of S9 metabolic activation, respectively. (omitted)

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