Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.
Background : Since up to 90% of a theophylline dose is biotransformed, probably by interaction with one or more the variants of the cytochrome P-450 drug metabolism system, anti-tuberculosis agents including drugs influencing microsomal enzyme systems, such as isoniazid and rifampicin. may be affect the elimination of theophylline. Method : The effect of combination therapy with isoniazid(INH), rifampicin(RFP), ethambutol(EMB) and pyrazinamide(PZA) on the pharmacokinetics of theophylline was evaluated by a computer program using Bayesian method. Three group were divided as follows. Group I is control, Group II is treated with INH. RFP, EMB and PZA and Group III is treated with INH, RFP and EMB. All of them were ilon-smoker who were normal in liver and renal functions, and not administered drugs affecting on the clearance of theophylline with exception of anti-tuberculous agents. Results : When it compared control with test groups, the clearance of theophylline in Group II and Group III was significantly decreased(p<0.001), and half life in Group II and Group III showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group II and Group III. Conclusion : These results suggest that theophylline dose may be need of readjustment in concurrent medication of anti-tuberculous agents including INH, RFP, and EMB.
Background: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. Method : Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400 mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n:19, 500 mg bid), second roxithromycin (n:14. 150 mg bid), third clarithromycin (n:10, 250 mg bid) and fourth azithromycin(n:10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method. Results : When compared with control, erythromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups. Conclusion : These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrently.
Tissue homogenates of 10 kinds of human cancer tissues were incubated in medium containing either one of $C^{14}-1,\; C^{14}-2,\;or\; C^{14}-3-lactate $ as a substrate in order to observe the oxidative pathway of lactate in cancer tissues. Lactate concentration in incubation medium was maintained at 50 mg%. At the end of incubation period, gas samples and incubation media were analyzed for total $CO_2$ production rates, radioactivities of respiratory $CO_2$, lactate uptake rates and pyruvate appearance rates. The following results were obtained. 1. Lactate uptake rates in all of cancer tissues examined were less than $2.5\;{\mu}M/hr/gm$ and much lower than those in normal tissues. 2. In the 10 kind of human cancer tissues, total $CO_2$ production rates were less than $10\;{\mu}M/hr/gm$, in all cases. These lower values impressed that oxidative metabolism in tumor tissues generally inhibited as compared with that in normal tissue. On the other hand, fractions of $CO_2$ derived from lactate to total $CO_2$ production rates were less than 15% except one case These facts showed that oxidation of lactate into $CO_2$ was greatly inhibited in tumor tissues. 3. Respiratory $CO_2$ yields from C-1 carbon of lactate in various cancer tissues were mean of 77.7% of total $CO_2$ yield from lactate and $CO_2$ yields from C-2 and C-3 carbon of lactate were mean of 9.1% and 12.6% respectively. These facts showed that carboxyl carbon of lactate oxidized more easily than ${\alpha}\;and\;{\beta}$ carbon of lactate. 4. In 10 kinds of cancer tissues, fractions of disappeared lacteate from media into $CO_2$ and pyruvate, which expressed as RLD $co_2$ and RLDpy respectively, were about 5% in except 3 cases and less than 3% except one case. These fact showed that almost of disappeared lactate from media were degraded into compounds other than $CO_2$ and pyruvate. From the above date, it was suggested that in the oxidative pathway of lactate in cancer tissues $CO_2$ was easily Produced from carboxyl carbon of lactate by oxidative decarboxylation as in the normal tissue, and further oxidation of 2 carbon unit via TCA cycle was inhibited.
Santoso, B.;Kume, S.;Nonaka, K.;Kimura, K.;Mizukoshi, H.;Gamo, Y.;Takahashi, J.
Asian-Australasian Journal of Animal Sciences
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v.16
no.4
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pp.534-540
/
2003
This study was conducted to investigate the effect of supplementation of galacto-oligosaccharides (GOS) on methane emission, nutrient digestibility, energy utilization and blood metabolites by Holstein cows fed silages. In two sequential digestion and respiratory trials, two non-lactating Holstein cows were arranged to a balanced incomplete block design. Experimental diets consisted of two silage types; orchardgrass (Dactylis glomerata L.) based silage (OS), mixed silage (orchardgrass based silage and alfalfa (Medicago sativa L.) silage) (MS), while two GOS levels were without supplementation (0) and 2% of dry matter intake supplementation (2). Four combination diets were OS-0, OS-2, MS-0 and MS-2. Significant effects of silage types and GOS supplementation levels were not observed for DM and OM intake. Whereas the digestibility of OM, NDF and ADF was significantly (p<0.05) higher in cows fed OS with and without GOS compared cows fed MS diets. As percentage of GE intake, fecal energy loss for OS diets was significantly (p<0.05) declined than for MS diets. In contrast, cows fed MS diets had lower (p<0.05) urine energy loss as a proportion of GE intake compared to OS diets. Energy loss as CH4 and heat production was numerically increased when cows fed both OS and MS with GOS supplementation. Compared to OS, CH4 emission in cows fed MS was numerically decreased by 10.8 %. Methane conversion ratio (energy loss as CH4 per unit of GE intake) for OS-0, OS-2, MS-0 and MS-2 were 7.1, 7.2, 6.8 and 7.0, respectively. Plasma of glucose and urea-N concentration were significantly (p<0.05) elevated from 1 h to 6 h after feeding, otherwise total protein in plasma was declined (p<0.01) at 6 after feeding.
Background: Garlic and its constituents are reported to have been effective in reducing methane emission and also influence glucose metabolism in body; however, studies in ruminants using garlic leaves are scarce. Garlic leaves contain similar compounds as garlic bulbs, but are discarded in field after garlic bulb harvest. We speculate that feeding garlic leaves might show similar effect as garlic constituents in sheep and could be potential animal feed supplement. Thus, we examined the effect of freeze dried garlic leaves (FDGL) on rumen fermentation, methane emission, plasma glucose kinetics and nitrogen utilization in sheep. Methods: Six sheep were fed Control diet (mixed hay and concentrate (60:40)) or FDGL diet (Control diet supplemented with FDGL at 2.5 g/kg $BW^{0.75}$ of sheep) using a crossover design. Methane gas emission was measured using open-circuit respiratory chamber. Plasma glucose turnover rate was measured using isotope dilution technique of [$U-^{13}C$]glucose. Rumen fluid, feces and urine were collected to measure rumen fermentation characteristics and nitrogen utilization. Result: No significant difference in rumen fermentation parameters was noticed except for rumen ammonia tended to be higher (0.05 < P < 0.1) in FDGL diet. Methane emission per kg dry matter ingested and methane emission per kg dry matter digested were lower (P < 0.05) in FDGL diet. Plasma glucose concentration was similar between diets and plasma glucose turnover rate tended to be higher in FDGL diet (0.05 < P < 0.1). Nitrogen retention was higher (P < 0.05) and microbial nitrogen supply tended to be higher (0.05 < P < 0.1) in FDGL diet. Conclusion: FDGL diet did not impair rumen fermentation, improved nitrogen retention; while absence of significant results in reduction of methane emission, glucose turnover rate and microbial nitrogen supply, further studies at higher dose would be necessary to conclude the merit of FDGL as supplement in ruminant feedstuff.
The organic phosphorus compounds have been widely used as an insecticide, since toxicity of these compounds is especially drastic to the insects than to men and other mammals. The organic phosphates are rapidly hydrolized and hence have little cumulative and ecologic effects. However, due to their acute toxic effects organophosphate have recorded rather high fatalities in men and domestic animals. The organic phosphorus compounds are powerful inhibitors to the carboxylic esterase enzymes such as acetylcholinesterase and pseudocholinesterase. As a result of firm binding characteristics of phosphate radicals to the active sites of enzyme, the activities of these enzymes are inhibited by the organophosphates. The organophosphates such as diazinon is easily observed from skin, gastrointestinal tract, conjunctivas and respiratory tract, and it is converted to more toxic form during metabolism in the liver The present study was carried out in order to investigate the hepatotoxicity of diazinon by observing the changes in the ultrastructure of cytoplasmic organelles of hepatic cells in albino mice. The animals were killed at 6, 12 and 24 hours after administration of 25mg/kg diazinon. The piece of hepatic tissue obtained from each animal was ultrathinly sectioned. The specimens stained by uranyl acetate and lead citrate double contrast methods were observed with JEM model 100B electron microscope. The results obtained were as follows: 1) A prominent dilatation and sacculation of the cisternae of rough endoplasmic reticulum associated with detachment of membrane bound-ribosomes, and disaggregation of the free ribosomes were recognized. 2) The hypertrophy of the smooth endoplasmic reticulum associated with depletion of the glycogen particles was observed. 3) The atrophy of cisternae of Golgi complex was observed. 4) A large number of secondary lysosomes (autophagic vacuoles and residual bodies) were formed. Consequently it is suggested that diazinon would induce disorganization of the cytoplasmic organelles of hepatocytes in albino mice.
The aim of this study was to investigate influence of body build on body composition, energy metabolic state and insulin concentration of blood. 29 male athletes and 36 male non-athletic students were recruited for the study. Anthropometry including chest depth and breadth, fat mass, fat fee mass, tricep skinfold thickness were measured. fasting glucose, lactate, triglyceride, fee fatty acid, and insulin concentration in serum were measured . Body build was assessed using metric index, which calculated by regression equations of Mohr and Greil. The athletic and non-athletic students were allocated to 3 body build, that is leptomorph, mesomorph, and pyknomorph. Resting metabolic rate was calculated. Respiratory quotient was determined through ratio of measured VO$_2$, and V$CO_2$. Most non-athletes have a leptomorphic body build, in contrast to athletes mesomorphic type. The body build type influenced body composition differently between non-athletic group and athletic group. Weight, body mass index, body fat mass and fat mass proportion (%), and fat-free mass increased from leptomorph to pyknormorph in non-athletic group. Pyknormorphic athletes have a significant higher body mass index, fat mass, fat free mass than other body build type. Serum glucose, triglyceride, lactate, insulin showed significant differences only in non-athletic group between leptomorph and mesomorph. RMR increased significantly from leptomorph to mesomorph in non-athletes. There was no significant difference of RQ among 3 body build types in both athletes and non-athletes. This study gives a coherent data on body build and body composition for athletes and non-athletes students. The influence of body builds on energy metabolic status of serum was different between athletes and non-athletes.
Jung Jae Hyuck;Kwon Se Ryun;Lee Eun Hye;Kim Sung Mi;Jeong Hyun Do;Chung Joon Ki;Kim Ki Hong
Fisheries and Aquatic Sciences
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v.6
no.4
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pp.209-212
/
2003
Lucigenin (Lg)- and luminol (Lm)-dependent chemiluminescence (CL) was used to compare the respiratory burst of rockfish (Sebastes schlegeli) phagocytes after stimulation with phorbol myristate acetate (PMA). To establish which reactive oxygen species (ROS) contributes to the observed CL, the modulators of ROS metabolism, such as superoxide dismutase (SOD), catalase, and sodium azide $(NaN_3)$ were used. Although LgCL responses were inhibited significantly by the addition of either SOD or catalase, in comparison to the control, significantly lower LgCL responses were recorded by SOD than catalase. LmCL also showed significantly decreased responses by the addition of SOD and catalase. However, there were no statistical differences in CL responses between SOD and catalase additions. More profound and significant decrease of LmCL responses were recorded by simultaneous addition of SOD and catalase. Sodium azide markedly enhanced LgCL responses, while it significantly inhibited LmCL responses. These results indicate that LgCL and LmCL can be used to measure extracellular $O_2$ production and myeloperoxidase (MPO)-mediated ROS production in fish phagocytes, respectively. Furthermore, LmCL can be used for analyzing intracellular ROS production by simultaneous addition of both SOD and catalase.
Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.
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