• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5557-5563
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• 2015

Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. Materials and Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched control subjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. Results: The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone (OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.

• 한국발생생물학회지:발생과생식
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• 제13권3호
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• pp.163-172
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• 2009

Some organotin compounds such as butyltins and phenyltins are known to induce impo-sex in various marine animals and are considered to be endocrine disruptors. In this study, the effect of organotins on follicular steroidogenesis in amphibians was examined using ovarian follicles of Rana dybowskii and Rana catesbeiana. Isolated follicles were cultured for 6 or 18 h in the presence and absence of frog pituitary homogenate (FPH) or various steroid precursors, and the levels of product steroids in the culture media oassay. Among the butyltin compounds, tributyltin (TBT) strongly and dose-dependently inhibited the FPH-induced synthesis of pregnenolone ($P_5$) and progesterone ($P_4$) by the follicles. TBT also strongly suppressed the conversion of cholesterol to $P_5$ and partially suppressed the conversion of $P_5$ to $P_4$. A high concentration of dibutyltin (DBT) also inhibited steroidogenesis by the follicles while monobutyltin and tetrabutyltin had negligible effects. The toxic effect of TBT or DBT was irreversible and a short time of exposure (30 min) was enough to suppress steroidogenesis. All the phenyltin compounds significantly inhibited FPH-induced $P_5$ synthesis by the follicles. The effective dose of 50% inhibition by diphenyltin was $0.04\;{\mu}M$ and those of monophenyltin and triphenyltin were $0.24\;{\mu}M$ and $0.3\;{\mu}M$, respectively. However, none of the phenyltin compounds significantly suppressed the conversion of $P_4$ to $17{\alpha}$-hydroxyprogesterone ($17{\alpha}$-OHP) (by $17{\alpha}$-hydroxylase), $17{\alpha}$-OHP to androstenedione (AD) (by $C_{17-20}$ lyase), or AD to testosterone by the follicles. Taken together, the data show that among the steroidogenic enzymes, P450scc in the follicles is the most sensitive to organotin compounds and that an amphibian follicle culture system can be a useful screening model for endocrine disruptors.

• Fisheries and Aquatic Sciences
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• 제26권3호
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• pp.204-215
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• 2023

The thermolabile haemolysin (tlh) of Vibrio parahaemolyticus (Vptlh) from V. parahaemolyticus is a multiple-function enzyme, initially describes as a haemolytic factor activated by lecithin and phospholipase A2 enzymatic activity (Shinoda, 1991; Vazquez-Morado, 2021; Yanagase et al., 1970). Until now, the tlh structure has hypothesized including N-terminal and C-terminal domain, but what domain of the Vptlh structure does the haemolytic activity has not been refined yet. In this study, a 450-bp VpTLH nucleotide sequence of the entire Vptlh gene encoded the C-terminal domain cloned firstly to examine its responsibility in the activity of the Vptlh. The C-terminal domain fused with a 6-His-tag named the His-tag-VpC-terminal domain was expressed successfully in soluble form in the BL21 (DE3) PlysS cell. Remarkably, both expression and purification results confirmed a high agreement in the molecular weight of the His-tag-VpC-terminal domain was 47 kDa. This work showed the His-tag-VpC-terminal domain lysed the erythrocyte membranes in the blood agar and the phosphate buffered saline (0.9%) media without adding the lecithin substrate of the phospholipase enzyme. Haemolysis occurred at all tested diluted concentrations of His-tag-VpC-terminal domain (p < 0.05), providing evidence for the independent haemolytic activity of the His-tag-VpC-terminal domain. The content of 100 ㎍ of the His-tag-VpC-terminal domain brought the highest haemolytic activity of 80% compared to that in the three remaining contents. Significantly, the His-tag-VpC-terminal domain demonstrated not to involve the phospholipase activity in Luria-Bertani agar supplemented with 1% (vol/vol) egg yolk emulsion. All results proved the vital responsibility of the His-tag-VpC-terminal domain in causing the haemolytic activity without the required activation by the phospholipase enzyme. Raw extracts of Phellinus igniarus and Phellinus pipi at 10^-1 mg/mL inhibited the haemolytic activity of the His-tag-VpC-terminal domain from 67.7% to 87.42%, respectively. Hence applying the His-tag-VpC-terminal domain as a simple biological material to evaluate quickly potential derivatives against the Vptlh in vivo conditions will accessible and more advantageous than using the whole of the Vptlh.

• Archives of Pharmacal Research
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• 제27권5호
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• pp.547-553
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• 2004

The pyrrolizidine alkaloids (PAs), contained in a number of traditional remedies in Africa and Asia, show wide variations in metabolism between animal species but little work has been done to investigate differences between animal strains. The metabolism of the PA senecionine (SN) in Fischer 344 (F344) rats has been studied in order to compare to that found in the previously investigated Sprague-Dawley (SO) rats (Drug Metab. Dispos. 17: 387, 1989). There was no difference in the formation of ($\pm$) 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, bioactivation) by hepatic microsomes from either sex of SO and F344 rats. However, hepatic microsomes from male and female F344 rats had greater activity in the Noxidation (detoxication) of SN by 88% and 180%, respectively, when compared to that of male and female SD rats. Experiments conducted at various pH showed an optimum pH of 8.5, the optimal pH for flavin-containing monooxygenase (FMO), for SN N-oxidation by hepatic microsomes from F344 females. In F344 males, however, a bimodal pattern was obtained with activity peaks at pH 7.6 and 8.5 reflecting the possible involvement of both cytochrome P450 (CYP) and FMO. Use of specific inhibitors (SKF525A, 1-benzylimidazole and methimazole) showed that the N-oxide of SN was primarily produced by FMO in both sexes of F344 rats. In contrast, SN N-oxide formation is known to be catalyzed mainly by CYP2C11 rather than FMO in SD rats. This study, therefore, demonstrated that there were substantial differences in the formation of SN N-oxide by hepatic microsomes from F344 and SD rats and that this detoxification is catalyzed primarily by two different enzymes in the two rat strains. These findings suggest that significant variations in PA biotransformation can exist between different animal strains.

• 한국전기전자재료학회논문지
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• 제30권1호
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• pp.17-22
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• 2017

Effects of pH value and deposition time on the electrical properties of (NMC) Ni-Mn-Cu-O and (NMCC) Ni-Mn-Cu-Co-O thin films were investigated. The NMC and NMCC films were prepared by spin spray method. The crystal structure and thickness of the annealed films were changed by the pH value and deposition time, respectively. A single phase of cubic spinel structure was confirmed for the annealed films deposited from solutions with pH 7.6. The resistivity of the annealed films was affected by the crystal structure and microstructure. The TCR (temperature coefficient of resistance) was dependent on the $Mn^{3+}/Mn^{4+}$. Typically, the resistivity of $70.5{\Omega}{\cdot}cm$ and TCR of -3.56%/K at room temperature were obtained for NMCC films deposited from solutions with pH 7.6 for 5 min, and annealed at $450^{\circ}C$ for 3 h.

• Asian-Australasian Journal of Animal Sciences
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• 제17권4호
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• pp.497-503
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• 2004

The effect of adding carbohydrate-rich feedstuffs to sweet potato leaves (SPL) on silage quality was studied using a total of 180 laboratory silos. Silage quality was assessed by changes of pH, dry matter (DM), crude protein (CP) and ammonia nitrogen ($NH_{3}$-N). Pre-wilted SPL was mixed with cassava root meal (CRM), sweet potato root meal (SPM) or sugar cane molasses (Mo) at levels of 0, 30, 60 and 90 g $kg^{-1}$ (air-dry weight of additives to pre-wilted weight of SPL). Samples for assessing silage quality were collected after mixing the SPL with the additive and thereafter at 7, 14, 28 and 56 days of ensiling. There was a marked decrease in pH after 7 days and the pH remained low and stable until day 56. Addition of 60 and 90 g $kg^{-1}$ resulted in a lower pH (p<0.05) than the other treatments. The DM content of the silage increased (p<0.05) with increasing levels of additive, while there were no differences in DM with time of ensiling. The CP content of the silage decreased (p<0.05) with increasing levels of additive. The CP content did not change up to 28 days, but was lower (p<0.05) after 56 days in all treatments. The $NH_{3}$-N levels were increasing (p<0.05) with time of ensiling, and were lower (p<0.05) with additive levels of 60 g $kg^{-1}$ or higher. Also, the additive source affected the $NH_{3}$-N values, with the lowest values found for Mo. Castrated male pigs (Large White$\times$Mongcai) were used in 4$\times$4 Latin square design to study the total tract digestibility and nitrogen (N) utilisation of diets with inclusion of ensiled SPL. The diets were based on cassava root meal with inclusion of protein from either fish meal (C) or SPL ensiled with CRM (D1), SPL ensiled with SPM (D2) and SPL ensiled with Mo (D3). The digestibility of DM, organic matter (OM) and CP were higher (p<0.05), and the digestibility of crude fibre (CF) was lower (p<0.05), in diet C than in diets D1, D2 and D3. However, there were no differences (p>0.05) in digestibility of dietary components between diets D1, D2 and D3. Also, the excretion of N in faeces was higher (p<0.05) and the N retention was lower (p<0.05) in diets D1, D2 and D3 than in diet C. It can be concluded from the present experiments, that a good quality silage can be produced from pre-wilted SPL by addition of 60 g $kg^{-1}$ of either CRM, SPM or Mo. Diets with inclusion of 450 g ensiled SPL $kg^{-1}$ DM showed a high digestibility of dietary components and thus ensiled SPL should be considered as a potential feed resource for growing pigs.

• Journal of Pharmaceutical Investigation
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• 제41권5호
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• pp.301-307
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• 2011

The aim of this study was to investigate the effects of kaempferol on the pharmacokinetics of nimodipine in rats. Nimodipine and kaempferol interact with cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), and the increase in the use of health supplements may result in kaempferol being taken concomitantly with nimodipine as a combination therapy to treat orprevent cardiovascular disease. The effect of kaempferol on P-gp and CYP3A4 activity was evaluated and Pharmacokinetic parameters of nimodipine were determined in rats after an oral (12 mg/kg) and intravenous (3 mg/kg) administration of nimodipine to rats in the presence and absence of kaempferol (0.5, 2.5, and 10 mg/kg). Kaempferol inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of $17.1{\mu}M$. In addition, kaempferol significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared to the oral control group, the area under the plasma concentration-time curve ($AUC_{0-\infty}$) and the peak plasma concentration ($C_{max}$) of nimodipine significantly increased, respectively. Consequently, the absolute bioavailability of nimodipine in the presence of kaempferol (2.5 and 10 mg/kg) was 29.1-33.3%, which was significantly enhanced compared to the oral control group (22.3%). Moreover, the relative bioavailability of nimodipine was 1.30- to 1.49-fold greater than that of the control group. The pharmacokinetics of intravenous nimodipine was not affected by kaempferol in contrast to those of oral nimodipine. Kaempferol significantly enhanced the oral bioavailability of nimodipine, which might be mainly due to inhibition of the CYP3A4-mediated metabolism of nimodipine in the small intestine and /or in the liver and to inhibition of the P-gp efflux transporter in the small intestine by kaempferol. The increase in oral bioavailability of nimodipine in the presence of kaempferol should be taken into consideration of potential drug interactions between nimodipine and kaempferol.

• International Journal of Industrial Entomology and Biomaterials
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• 제17권2호
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• pp.165-168
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• 2008

The hybrid ($CSR2{\times}CSR4$) eggs treated with acid were taken up for the study with an objective to develop long-term preservation schedule. The hybrid eggs obtained with two mating duration (3 h and 6 h) and oviposition period (6 h and 24 h) with two age groups of eggs (24 h and 36 h) were treated with Hydrochloric acid. These eggs were subjected to preservation at $5^{\circ}C$ in single step refrigeration and at $5^{\circ}C$ and $2.5^{\circ}C$ under double step refrigeration from $10{\sim}120$ days. These eggs were released from the cold storage as per the specified durations and incubated at standard conditions and allowed 2 h for hatching at 450 lux light. Hatchability was found to be significantly higher or on par with the control in three treatments (T1, T2 and T4) where the eggs are preserved continuously at $5^{\circ}C$ up to 30 days. However under double step refrigeration, hatching was not significantly affected in 20+60 day's combination of T1 treatment up to 80 days. Bioassay studies of the promising treatment i.e.. T1 with (20+60) days indicated that early stage loss and cocoon yield was found to be on par with the control. Hence this treatment was recommended for preservation of acid treated new bivoltine hybrid layings. Details of the hatchability and rearing performance of long term preservation of acid treated eggs are discussed.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.438-445
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• 2009

We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

• 한국환경보건학회지
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• 제11권2호
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• pp.17-27
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• 1985

The objectives of this study is to examine efficiency of swinery wastewater treatment by trickling filters' pilot plant. The results of this study are as follows: 1. The characteristics of sample. The BOD$_5$ was from 2,450 to 2,880mg/l, COD(KMnO$_4$ acid method) was from 910 to 1,064mg/l, and SS was from 920 to 990mg/l. The pH of influent was from 7.3 to 7.6, and the temperature of water was from 17.0$\circ$C to 22.5$\circ$C. 2. For experiment by recirculation, the BODs removal efficiency is 65.2% at recirculation ratio (r)=0, and 70.7% at r=1. The ramoval efficiency of this study is higher than NRC formula of U.S.A.. The recirculation is not significant effect on removal efficiency. 3. For experiment by hydraulic load, the BOD$_5$ removal rate decreased from 73.1% at $3.1m^3/m^2\cdot d$ to 65.3% at $9.2m^3/m^2\cdot d$. The design formula of this study which shows the removal rate of soluble BOD is $Le/Li =10^{-0.24} D/Q^{0.24}$ (Q: hydraulic load, D: depth of filter). 4. For experiment by organic load, the BOD$_5$ removal rate is increased from 70.2% at $0.77kg/m^3\cdot d$ to 75.4% at $4.28kg/m^3\cdot d$. We can obtain the straight line y=0.749 x (y: removed BOD, x :applied BOD) by the least squares method. 5. We can know that trickling filters is strong with the hydraulic load and the organic matter shock load. Here, we can judge that trickling filters is a good method for the treatment of swinery wastewater which containing high concentrated organic matter.