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1.
Poult Sci ; 102(2): 102354, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36470028

RESUMEN

This experiment aimed to study the effects of dietary calcium (Ca) and non-phytate phosphorus (NPP) levels on performance, serum biochemical indices, and lipid metabolism in Beijing You Chicken (BYC), a local chicken. A 3 × 3 factorial design was adopted, dietary Ca levels were 0.66, 0.71, and 0.76%, NPP levels were 0.25, 0.30, and 0.35%. A total of 648 ten-wk-old BYC growing pullets were randomly divided into 9 groups with 6 replicates per group, and 12 birds per replicate. Growth performance, serum biochemical indices, and lipid metabolism indicators from 10 to 16 wk were measured. The results showed as follows: 1) Dietary Ca and NPP alone did not affect growth performance, but the interaction of dietary Ca and NPP affected average feed intake (AFI) of growing pullets (P < 0.05). The AFI was the lowest for the group with 0.71% Ca and 0.25% NPP (3,550.0 g, P = 0.036). 2) Dietary Ca level significantly affected serum P content (P < 0.05); dietary NPP had an influence trend on serum Ca content (P= 0.054). Dietary NPP levels and the interaction of Ca and NPP significantly affected alkaline phosphatase (AKP) activity. 3) Dietary Ca levels significantly affected TC content and HDL-C content (P < 0.05). Dietary NPP level significantly affected TG content (P < 0.05), the TG content in 0.25% and 0.30% NPP groups was significantly lower than that in 0.35% NPP group (P < 0.05). The interaction of dietary Ca and NPP significantly affected TG, TC and HDL-C contents (P < 0.05). TG, TC, and LDL-C levels were lower and HDL-C levels were the highest in the group with 0.66% Ca and 0.25% NPP. In summary, appropriate dietary Ca level can regulate serum TG, TC, and HDL-C content. Dietary Ca and NPP levels can be adjusted in pullet phase to avoid excessive obesity during the egg-laying period. This study recommended that dietary 0.66% Ca and 0.25% NPP benefit for the lipid metabolism of BYC growing pullets without affecting the performance.


Asunto(s)
6-Fitasa , Fósforo Dietético , Animales , Femenino , Fósforo/metabolismo , Calcio de la Dieta/metabolismo , Pollos/fisiología , Dieta/veterinaria , Metabolismo de los Lípidos , Ácido Fítico/metabolismo , Fósforo Dietético/metabolismo , Alimentación Animal/análisis , Suplementos Dietéticos , 6-Fitasa/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales
2.
Eur Rev Med Pharmacol Sci ; 23(18): 8133-8138, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31599442

RESUMEN

OBJECTIVE: To investigate the correlation of serum vitamin A, D, and E levels with a recurrent respiratory infection (RRI) in children. PATIENTS AND METHODS: The medical records of 422 children with RRI (a study group) in Cangzhou Central Hospital from January 2015 to December 2018 were retrospectively analyzed (the study group was divided into an active group and a stable group). Further 100 healthy children who underwent physical examination at the same time were enrolled as a control group. High-performance liquid chromatography (HPLC) was used to determine vitamin A, D, and E levels, so as to analyze their differences between the groups. RESULTS: Vitamin A, D, and E in the active and stable groups were significantly lower than those in the control group (p < 0.001); in the active group they were significantly lower than those in the stable group (p < 0.001). According to partial correlation analysis, in children with active RRI, vitamin A was respectively positively correlated with vitamin D (r=0.945, p < 0.001), and vitamin E (r=0.988, p < 0.001). Moreover, vitamin E was positively correlated with vitamin D (r=0.959, p < 0.001). CONCLUSIONS: The deficiency of vitamin A, D, and E is positively correlated with the disease activity of children with RRI. Therefore, the supplement of vitamin A, D, and E through dietary adjustment is beneficial to the rehabilitation of the children.


Asunto(s)
25-Hidroxivitamina D 2/sangre , Infecciones del Sistema Respiratorio/sangre , Vitamina A/sangre , Vitamina E/sangre , Estudios de Casos y Controles , Preescolar , China/epidemiología , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Lactante , Masculino , Recurrencia , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiología , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina E/sangre , Deficiencia de Vitamina E/epidemiología
3.
J Dairy Sci ; 102(10): 9017-9027, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31351725

RESUMEN

The supply and profile of absorbed AA may affect milk protein synthesis through hormonal changes and mammalian target of rapamycin (mTOR) signaling pathways; and Ile, Leu, Met, and Thr (ILMT) are the 4 AA that have been reported to have the greatest effect on mammary mTOR signaling. The extent to which ILMT and the other remaining AA (RAA) differ in their effects on milk protein synthesis needs to be systematically investigated. In this study, 5 lactating goats, averaging 120 ± 10 d in milk, fitted with jugular vein and carotid artery catheters, were fasted for 24 h, followed by intravenous infusions of a mixture containing AA and glucose for 8 h in a 5 × 5 Latin square design. The AA mixtures were formulated according to the profile of casein. The amounts of AA infused were calculated based on supplies of AA when metabolizable protein (MP) was at requirement (MR). Treatments were an infusate containing glucose without AA (NTAA); an infusate containing 3 × the MR of Ile, Leu, Met and Thr (3F0R); and infusates containing 3F0R plus 1, 2, or 3 × MR of RAA (3F1R, 3F2R, and 3F3R, respectively) according to amounts provided when fed to meet MP requirements for maintenance and lactation for each goat. Milk, arterial blood, and mammary tissue samples were collected immediately after halting the infusion. Relative to NTAA, supplementation of ILMT tended to increase milk protein production and plasma glucose concentrations, and increased milk and lactose production, but had no effects on production or content of milk fat. Graded supplementation of RAA tended to quadratically affect production of milk and lactose. Arterial glucose and glucagon concentrations decreased linearly, and plasma insulin concentrations decreased quadratically with increased RAA. Mammary p70-S6K1 phosphorylation was decreased by addition of ILMT compared with NTAA but increased linearly with increased RAA infusion. Furthermore, EIF4EBP1 gene expression was much lower for 3F-treated goats than for the NTAA treatment. Both MTOR and RPS6KB1 gene expressions were decreased quadratically with increased RAA supply. These results suggested that short-term milk protein yield tended to be increased by elevated ILMT availability, and this trend was not explained by variations in mammary mTOR signaling or pancreatic hormone secretions, whereas graded increase of RAA in combination with ILMT appeared to regulate the efficiency of conversion of glucose to lactose in a manner not involving milk protein production.


Asunto(s)
Aminoácidos/administración & dosificación , Cabras/fisiología , Insulina/administración & dosificación , Proteínas de la Leche/análisis , Leche/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Caseínas/análisis , Femenino , Glucagón/administración & dosificación , Glucosa/metabolismo , Isoleucina/administración & dosificación , Lactancia , Lactosa/análisis , Leucina/administración & dosificación , Glándulas Mamarias Animales/metabolismo , Metionina/administración & dosificación , Leche/química , Fosforilación/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Treonina/administración & dosificación
4.
J Dairy Sci ; 102(9): 7936-7947, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31255267

RESUMEN

Objectives of this study were to investigate the effects of supplementing rumen-protected methionine (RP-Met), threonine (RP-Thr), isoleucine (RP-Ile), and leucine (RP-Leu) individually or jointly to a low-protein diet, on the performance of lactating dairy cows, as well as to determine the effects of these amino acids (AA) on the mammalian target of rapamycin (mTOR) in vivo. Ten lactating Holstein cows were randomly allocated to a repeated 5 × 5 Latin square experiment with five 19-d periods. Treatments were high-protein diet (16% crude protein, positive control; HP), low-protein diet (12% crude protein, negative control; LP), LP plus RP-Met (LPM), LP plus RP-Met and RP-Thr (LPMT), and LP plus RP-Met, RP-Thr, RP-Ile, and RP-Leu (LPMTIL). The dry matter intakes (DMI) of the LP, LPM, and LPMT diets were lower than that of the HP diet, whereas the DMI of the LPMTIL diet was intermediate between the HP diet and the other LP diets. Supplementing RP-Met to the LP diet increased the yields of milk and milk protein, increased the content of milk urea N, and tended to increase milk N efficiency. Co-supplementation of RP-Thr with RP-Met resulted in no further milk production increase. Co-supplementation of all 4 rumen-protected amino acids (RP-AA) increased milk and lactose yields to the level of the HP diet and tended to increase milk protein yield compared with the LPMT diet. We found no significant differences in the contents and yields of milk components between the LPMTIL and HP diets except for a lower milk urea N content in the LPMTIL diet. Venous concentrations of the measured AA were similar across the LP and LP diets supplemented with RP-AA. Relative to levels of the HP diet, LP diets had higher venous concentrations of Met and Gly and tended to have higher Phe concentration and lower concentrations of Val and BCAA. The LPMTIL diet had higher venous concentrations of Arg, Lys, Met, Phe, and Glu, and a lower Val concentration. Phosphorylation status of the measured mTOR components in LPM and LPMT treatments were similar to those in the LP treatment but phosphorylation status of mTOR and eIF4E-binding protein 1 (4eBP1) in LPMTIL treatment were higher. The phosphorylation rates of eukaryotic elongation factor 2 (eEF2) in the 4 LP and LP plus RP-AA diets were higher than that of the HP diet. Overall, results of the present study supported the concept that under the relatively short time of this experiment, supplementing RP-AA, which are believed to stimulate the mTOR signal pathway, can lead to increased milk protein yield. This increase appears to be due to increased DMI, greater mTOR signaling, and greater eEF2 activity.


Asunto(s)
Aminoácidos Esenciales/administración & dosificación , Bovinos/fisiología , Suplementos Dietéticos/análisis , Proteínas de la Leche/análisis , Leche/metabolismo , Nitrógeno/metabolismo , Aminoácidos Esenciales/análisis , Animales , Industria Lechera , Dieta/veterinaria , Dieta con Restricción de Proteínas/veterinaria , Femenino , Lactancia/efectos de los fármacos , Lactosa/metabolismo , Metionina/administración & dosificación , Leche/química , Nitrógeno/análisis , Rumen/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Urea/análisis
5.
Eur J Clin Microbiol Infect Dis ; 36(3): 459-466, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27796647

RESUMEN

The purpose of this study was to assess the pharmacokinetic (PK) characteristics, clinical efficiency, and pharmacoeconomic parameters of piperacillin/tazobactam administered by extended infusion (EI) or intermittent infusion (II) in the treatment of hospital-acquired pneumonia (HAP) in critically ill patients with low illness severity in China. Fifty patients completed the study, with 25 patients receiving 4/0.5 g piperacillin/tazobactam over 30 min as the II group and 25 patients receiving 4/0.5 g piperacillin/tazobactam over 3 h every 6 h as the EI group. Drug assay was performed using high-performance liquid chromatography (HPLC). The percentage of the dosing interval for which the free piperacillin concentration (%fT) exceeds the minimum inhibitory concentration (MIC) was calculated. The patients' therapy cost, clinical efficiency, and adverse effects were also recorded. %fT>MIC was about 100, 98.73, and 93.04 % in the EI arm versus 81.48, 53.29, and 42.15 % in the II arm, respectively, when the microorganism responsible for HAP had an MIC of 4, 8, and 16 mg/L. The therapy cost in the EI group was lower than that of the II group ($1351.72 ± 120.39 vs. $1782.04 ± 164.51, p = 0.001). However, the clinical success rate, clinical failure rate, and drug-related adverse events did not significantly differ between groups. EI treatment with piperacillin/tazobactam was a cost-effective approach to the management of HAP, being equally clinically effective to conventional II.


Asunto(s)
Antibacterianos/administración & dosificación , Infección Hospitalaria/tratamiento farmacológico , Ácido Penicilánico/análogos & derivados , Neumonía Bacteriana/tratamiento farmacológico , Inhibidores de beta-Lactamasas/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/economía , Antibacterianos/farmacocinética , Antibacterianos/farmacología , China , Cromatografía Líquida de Alta Presión , Costos y Análisis de Costo , Enfermedad Crítica , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Infusiones Intravenosas/economía , Infusiones Intravenosas/métodos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Ácido Penicilánico/administración & dosificación , Ácido Penicilánico/economía , Ácido Penicilánico/farmacocinética , Ácido Penicilánico/farmacología , Piperacilina/administración & dosificación , Piperacilina/economía , Piperacilina/farmacocinética , Piperacilina/farmacología , Combinación Piperacilina y Tazobactam , Plasma/química , Resultado del Tratamiento , Adulto Joven , Inhibidores de beta-Lactamasas/economía , Inhibidores de beta-Lactamasas/farmacocinética , Inhibidores de beta-Lactamasas/farmacología
6.
Drug Res (Stuttg) ; 66(10): 520-526, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27490936

RESUMEN

A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the quantification of ginkgolides in rat plasma, and the main pharmacokinetic parameters of ginkgolides after oral administration of Ginkgo biloba extract (GBE) was acquired. Methods: Plasma samples were pretreated with ethyl acetate extraction. Sulfamethoxazole was used as the internal standard (IS). Chromatographic separation was achieved on an Eclipse XDB-C18 column (2.1 mm×150 mm, 5 µm) with a mobile phase consisting of methanol/0.1% formic acid water (gradient elution: 0~25 min (77:23)→(60:40), V/V) at a flow rate of 0.3 mL·min-1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization (ESI) source for 25 min. The detection was operated by multiple reaction monitoring(MRM) under negative ionization mode of the transitions of m/z 325→163 for BB, 469→423 for GJ, 439→125 for GC, 453→351 for GA, 423→367 for GB and of m/z 252→156 for sulfamethoxazole (IS) respectively. Results: The pharmacokinetic properties of BB, GJ, GA, GB and GC were in line with the open 2-compartment model after oral administration of GBE in rats; The pharmacokinetic parameters of various lactones were calculated, and drugs-time curve and the curve fitting diagram of 5 ginkgolides were drew; The absorption and distribution rate of BB, GJ, GA, GB and GC were fast in rats in vivo, and half-life of absorption was less than 3 h. Conclusion: The developed LC-ESI (-)/MS/MS (QQQ) method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of ginkgolides in rats after administration of GBE, which can provide basis for further clinical efficacy studies.


Asunto(s)
Ciclopentanos/farmacocinética , Furanos/farmacocinética , Ginkgo biloba/química , Ginkgólidos/farmacocinética , Extractos Vegetales/farmacocinética , Animales , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Ciclopentanos/sangre , Furanos/sangre , Ginkgólidos/sangre , Masculino , Extractos Vegetales/química , Ratas , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem
7.
J Anim Physiol Anim Nutr (Berl) ; 99(5): 899-904, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25816839

RESUMEN

Multiparous early lactation Holstein cows (n = 16) were used in a randomized complete block design to determine the effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow. Treatments were as follows: (i) feeding low-quality forage without supplying fatty acid calcium (Diet A), (ii) feeding low-quality forage with supplying 400 g fatty acid calcium (Diet B), (iii) feeding high-quality forage without supplying fatty acid calcium (Diet C) and (iv) feeding high-quality forage with supplying 400 g fatty acid calcium. This experiment consisted 30 days. The milk and blood samples were collected in the last day of the trail. Intakes were recorded in the last 2 days of the trail. Supplementation of fatty acid calcium decreased significantly dry matter intake (DMI) (p < 0.01). Addition fatty acid calcium decreased milk protein percentage (p < 0.01) and milk SNF percentage (p < 0.01), but increased MUN (p < 0.05). Supplemented fatty acid decreased concentration of blood BHBA (p < 0.05), but increased TG, NEFA, glucagon, GLP-1, CCK, leptin, ApoA-IV, serotonin and MSH concentration in blood, the CCK concentration and feed intake showed a significant negative correlation (p < 0.05).


Asunto(s)
Alimentación Animal/análisis , Calcio/farmacología , Bovinos/fisiología , Dieta/veterinaria , Ácidos Grasos/farmacología , Lactancia/fisiología , Animales , Calcio/química , Bovinos/sangre , Ácidos Grasos/química , Femenino , Leche/química
8.
Acta Biol Hung ; 60(3): 281-91, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19700387

RESUMEN

The forward and reverse cDNA subtractive libraries before and after the toxic effect of alpha-amanitin were constructed by suppression subtractive hybridization and randomly selected clones from each subtractive library were screened by PCR and dot blot hybridization. A total of 85 genes with altered expression were finally identified, with 41 genes from the forward library and 44 from the reverse library. Subsequently, the antagonistic effects of candidate traditional Chinese medicines were evaluated based on the genetic transcription levels of the genes with significant altered expression, including Catnbeta, Flt3-L, IL-7r and Rpo2-4. The results indicated that Silybum marianum (L.) Gaert and Ganoderma lucidum had significant down-regulated effects on the transcription level of Catnbeta that was up-regulated by alpha-amanitin, and the two herbs also up-regulated the transcription levels of Flt3-L and Rpo2-4. Silybum marianum (L.) had significant up-regulated effects on the IL-7r that was down-regulated by alpha-amanitin. These preliminary studies suggested that Silybum marianum (L.) and Ganoderma lucidum were effective antagonists against the toxicity of alpha-amanitin.


Asunto(s)
Alfa-Amanitina/envenenamiento , Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Reishi/química , Silybum marianum/química , Alfa-Amanitina/antagonistas & inhibidores , Animales , Clonación Molecular , Evaluación Preclínica de Medicamentos , Biblioteca de Genes , Ratones
9.
Drug Metab Dispos ; 34(5): 748-55, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16455802

RESUMEN

The potential cancer therapeutic agent, 6,7-(dimethoxy-2, 4-dihydroindeno[1,2-c]pyrazol-3-yl)-(3-fluoro-phenyl)-amine (JNJ-10198409), formed three N-glucuronides that were positively identified by liquid chromatography-tandem mass spectrometry and NMR as N-amine-glucuronide (Glu-A), 1-N-pyrazole-glucuronide (Glu-B), and 2-N-pyrazole-glucuronide (Glu-C). All three N-glucuronides were detected in rat liver microsomes, whereas only Glu-A and -B were found in monkey and human liver microsomes. In contrast to common glucuronides, Glu-B was completely resistant to beta-glucuronidase. Kinetic analyses revealed that glucuronidation of JNJ-10198409 in human liver microsomes exhibited atypical kinetics that may be described by a two-site binding model. For the high affinity binding, K(m) values were 1.2 and 5.0 microM, and V(max) values were 2002 and 2,403 nmol min(-1) mg(-1) for Glu-A and Glu-B, respectively. Kinetic constants of low affinity binding were not determined due to low solubility of the drug. Among the human UDP-glucuronosyltransferases (UGTs) tested, UGT1A9, 1A8, 1A7, and 1A4 were the most active isozymes to produce Glu-A; for the formation of Glu-B, UGT1A9 was the most active enzyme, followed by UGT1A3, 1A7, and 1A4. Glucuronidation of JNJ-10198409 by those UGT1A enzymes followed classic Michaelis-Menten kinetics. In contrast, no glucuronides were formed by all UGT2B isozymes tested, including UGT2B4, 2B7, 2B15, and 2B17. Collectively, these results suggested that glucuronidation of JNJ-10198409 in human liver microsomes is catalyzed by multiple UGT1A enzymes. Since UGT1A enzymes are widely expressed in various tissues, it is anticipated that both hepatic and extrahepatic glucuronidation will likely contribute to the elimination of the drug in humans. Additionally, conjugation at the nitrogens of the pyrazole ring represents a new structural moiety for UGT1A-mediated reactions.


Asunto(s)
Glucuronosiltransferasa/metabolismo , Indanos/metabolismo , Pirazoles/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Animales , Cromatografía Líquida de Alta Presión , ADN Complementario/biosíntesis , Glucurónidos/metabolismo , Glucuronosiltransferasa/biosíntesis , Haplorrinos , Humanos , Técnicas In Vitro , Cinética , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Microsomas Hepáticos/enzimología , Oxidación-Reducción , Propofol/farmacología , Ratas
10.
Br Poult Sci ; 45(5): 684-94, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15623224

RESUMEN

(1) This in vivo trial was conducted to study the effects of polysaccharide extracts of two mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and a herb, Astragalus membranaceus (AstE) on growth performance, and the weights of organs and the gastrointestinal tract (GIT) of broiler chickens. (2) Three extracts (LenE, TreE and AstE) were supplemented at inclusion rates of 0.5, 1, 2, 3 and 4 g/kg from 7 to 14 d of age and compared with an antibiotic treatment group (20 mg/kg, virginiamycin (VRG) as well as a group of non-supplemented birds. (3) Body weight (BW) gain, feed intake and feed conversion ratio (FCR) of the extract-supplemented groups were not significantly different from those of the antibiotic group. Significant effects of type of extract and concentration on growth performance were found from 7 to 28 d of age. Generally, birds fed with LenE showed higher BW gain and lower FCR from 7 to 28 d of age than those fed with TreE and AstE and 2 g/kg LenE was considered the optimal inclusion rate for enhanced broiler growth. However, the extracts had no significant effect on the relative weights of organs and GIT compared with the antibiotic group. (4) The birds fed the extracts showed better growth performance than the non-supplemented birds, but were not significantly different from those fed VRG. Of the three extracts, LenE appeared to be a potential growth promoter. Future studies are needed to investigate whether the extracts can be used as alternatives for antibiotic growth promoters in challenged birds, and to elucidate the mechanisms for potentially enhanced growth performance in poultry.


Asunto(s)
Astragalus propinquus/química , Basidiomycota/química , Pollos/crecimiento & desarrollo , Polisacáridos/farmacología , Hongos Shiitake/química , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Antibacterianos/farmacología , Dieta , Suplementos Dietéticos , Tracto Gastrointestinal/anatomía & histología , Tamaño de los Órganos/efectos de los fármacos , Virginiamicina/farmacología , Aumento de Peso/efectos de los fármacos
11.
Bioorg Med Chem Lett ; 14(11): 2927-30, 2004 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-15125961

RESUMEN

Peptide nucleic acids (PNAs) C- or N-modified with dioxime ligands were prepared by solid-phase synthesis using iron(II)-clathrochelates as protected dioxime building blocks. These PNA bind complementary DNA sequence specifically, though with much reduced affinity in comparison with nonmodified PNA. The dioxime-PNA conjugates bind Cu2+ and Ni2+ at microM concentration.


Asunto(s)
ADN/metabolismo , Ácidos Nucleicos de Péptidos/síntesis química , Ácidos Nucleicos de Péptidos/farmacología , Secuencia de Bases , Cobre/química , Estructura Molecular , Níquel/química , Desnaturalización de Ácido Nucleico , Oximas/síntesis química , Oximas/farmacología , Relación Estructura-Actividad , Temperatura
12.
Food Chem Toxicol ; 39(9): 959-62, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11498273

RESUMEN

China is the only country that produces brick tea, and more than 90% of the brick tea is consumed in the western minority nationality regions of China. The high fluorine content of brick tea is possibly associated with the special processing procedures, but no investigation has been conducted in this field. To explore the characteristic features of brick tea manufacturing and the alterations in fluorine content during the processing procedures, we performed a field survey involving two brick tea factories and the nearby tea plantations. For the fluorine contents of the initial, intermediate and final processing products, altogether eight types of specimens were collected and determined by using the ion-selective electrode standard curve technique. It was found that the raw material tea leaf for brick tea processing was old, coarse and not the tender delicate tea leaf used for ordinary green or black tea processing. For the fluorine content of the raw material tea leaf, the intermediate and the final products showed that the fresh raw leaf contained a fluorine content as high as 489.31-512.68 mg/kg. During one fermentation-like processing procedure, the fluorine content rose by 4.67% and 1.88% in the specimens from the two factories, respectively, which revealed no statistical significance (P>0.5). These results suggest that the high fluorine content in brick tea might be due to the high content in the raw material and not related with the processing procedures.


Asunto(s)
Flúor/análisis , Manipulación de Alimentos/métodos , Té/química , China , Electrodos de Iones Selectos
13.
Curr Top Med Chem ; 1(5): 353-66, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11899102

RESUMEN

The attrition rates of new chemical entities (NCEs) in preclinical and clinical development are staggeringly high. NCEs are abandoned due to insufficient efficacy, safety issues, and economic reasons. Uncovering drug defects that produce these failures as early as possible in drug discovery would be highly effective in lowing the cost and time of developing therapeutically useful drugs. Unfortunately, there is no single factor that can account for these NCE failures in preclinical and clinical development since factors, such as solubility, pKa, absorption, metabolism, formulation, pharmacokinetics, toxicity and efficacy, to name a few, are all interrelated. In addition, there are many problems in scaling-up drug candidates from the laboratory bench scale to the pilot plant scale. To address the problem of attrition rates of NCEs in preclinical and clinical development and drug scale-up issues, pharmaceutical companies need to reorganize their preclinical departments from a traditional linear approach to a parallel approach. In this review, a strategy is put forth to integrate certain aspects of drug metabolism/pharmacokinetics, toxicology functions and process chemistry into drug discovery. Compound optimization in early and late phase drug discovery occurs by relating factors such as physicochemical properties, in vitro absorption, in vitro metabolism, in vivo pharmacokinetics and drug scale-up issues to efficacy optimization. This pre-preclinical paradigm will improve the success rate of drug candidates entering development.


Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Farmacología/normas , Animales , Disponibilidad Biológica , Células Cultivadas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Cobayas , Humanos , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Conejos , Ratas
14.
Curr Top Med Chem ; 1(5): 403-25, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11899105

RESUMEN

To reduce the high attrition rates of NCEs in preclinical and clinical development uncovering pharmacokinetics, toxicokinetics, drug metabolism, and drug-drug interactions early in drug discovery would be highly valuable. There have been many in vitro screens developed for these areas that have higher sample throughput, which is consistent with the iterative cycle of a typical drug discovery research project. We have presented the present status and given detailed descriptions of biotransformation, metabolic stability assays, identification of drug metabolizing P450 enzymes, prediction of pharmacokinetic parameters from in vitro metabolism data, structure elucidation of metabolites, CYP450 inhibition assays and CYP450 induction assays from a drug discovery perspective. Strategies for the proper sequencing of primary and secondary assays employedfor drug metabolism and CYP450 inhibition & induction is discussed.


Asunto(s)
Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Hígado/enzimología , Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Animales , Sistema Enzimático del Citocromo P-450/biosíntesis , Interacciones Farmacológicas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Inducción Enzimática/efectos de los fármacos , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo
15.
Environ Res ; 83(3): 333-7, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10944077

RESUMEN

As the first report of the environmental fluoride level in Tibet, the determination by the fluoride ion-selective electrode method of fluoride concentration in water, soil, fuel, grains, food, vegetables, and tea was made for the Tibetan people living on various land types with various ecological characteristics. The average level of fluoride concentration in water in Tibet was 0.06 mg/L; the level of dissolved fluoride in the soil was 0.45 mg/kg; the fluoride concentration in main fuels was 0.10 mg/kg; the levels in main grains, food, and vegetables were 0.06-0.33 mg/kg; those in buttered tea and Zanba mixed with brick tea were 3.09-3.61 mg/kg; and water-dissolved fluoride concentrations in the brick tea produced in Sichuan Province and Yunan Province were 533.89-617.32 mg/kg. Tibet is the prevailing area of brick tea fluorosis.


Asunto(s)
Fluoruros/análisis , Fluorosis Dental/etiología , Contaminación de Alimentos , Té/química , Abastecimiento de Agua , Exposición a Riesgos Ambientales/análisis , Fluoruros/efectos adversos , Humanos , Salud Pública , Té/efectos adversos , Tibet , Verduras/química
16.
J Reprod Fertil ; 116(2): 269-75, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10615252

RESUMEN

The objective of the present study was to determine the effects of inhibition of mevalonate biosynthesis on fertility and embryonic survival in laying chickens. White Leghorn hens were fed for 5 weeks with a control diet alone or a diet supplemented with one of two concentrations (0.03 or 0.06%) of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors atorvastatin, lovastatin or simvastatin. The hens were artificially inseminated once a week and eggs that were not analysed for cholesterol content were incubated. When averaged across dietary groups and expressed as a percentage of all eggs incubated, the incidence of unfertilized eggs was 1.6% (controls), 29.1% (atorvastatin), 4.4% (lovastatin) and 7.9% (simvastatin). In contrast, with the exception of lower values for birds fed 0.06% atorvastatin, all groups had comparable hatchabilities of fertilized eggs. Hatchability of all eggs incubated was decreased in both atorvastatin groups compared with the other treatments. However, embryonic mortality of fertilized eggs was unaffected (P > 0.05) by diet. Compared with controls, maximum decreases in egg cholesterol of 46, 22 and 7% were obtained with atorvastatin, lovastatin and simvastatin, respectively. Although the overall correlation of egg cholesterol content with hatchability was high (r = 0.82), the hatch rate of eggs containing approximately 105 mg cholesterol ranged from 0 to 67%, indicating that egg cholesterol content was not the only factor influencing embryo survival. This is the first study to indicate that a mevalonate-derived product or products plays an important role in avian fertility. In addition, this work challenges the contention that virtually all of the cholesterol in chicken egg yolk is essential for embryonic development and survival.


Asunto(s)
Pollos , Fertilidad/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Animales , Atorvastatina , Inhibidores Enzimáticos/farmacología , Femenino , Ácidos Heptanoicos/farmacología , Inseminación Artificial , Lovastatina/farmacología , Ácido Mevalónico , Oviposición , Pirroles/farmacología , Simvastatina/farmacología
17.
Se Pu ; 16(5): 411-3, 1998 Sep.
Artículo en Chino | MEDLINE | ID: mdl-11498920

RESUMEN

Guanxingao is a kind of traditional Chinese rubber electuary medicine which is able to either cure or guard against coronary heart disease and angina pectoris. The contents of camphora, mentholum, isoborneol and borneol in Guanxingao are determined by gas chromatography. The purpose of the study is to detect and control the loss of the four volatile components through production and standing and to guarantee the curative effect. Chromatographic analysis was performed on a GC-4004 gas chromatograph(FID). The column was a 3 mm i.d. x 2 m stainless steel tube packed with 7% PEG-1500 on 100-110 mesh 102 non-silanized white support. The column and the FID temperatures were 115 degrees C and 180 degrees C respectively. H2 was the carrier gas, 30 mL/min. Internal standard method was used for the quantitative estimation with naphthalene as the internal standard. The linear ranges were at least within 50-450 mg/L (r = 0.9999, n = 4). The correction factors against naphthalene were 1.262-1.286 and the RSDs were 0.32%-1.5%(n = 12). The recoveries were 98.44%-101.9%. In comparison with the theoretical contents, the average loss percentages are 71.72% (camphora), 65.60% (mentholum) and 66.31% (isoborneol + borneol). The samples were pretreated by means of isothermal (35 degrees C) water-bath extraction with acetone for 6 times with four hours each.


Asunto(s)
Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Mentol/análisis , Canfanos/análisis , Cromatografía de Gases , Combinación de Medicamentos
18.
Gene ; 181(1-2): 199-206, 1996 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-8973331

RESUMEN

In this study, we describe the cloning of the mouse homologue of the orphan receptor, RZR/ROR gamma, a member of the nuclear receptor superfamily, from a mouse muscle cDNA library. The amino acid sequence of mouse ROR gamma (mROR gamma) is highly homologous to that of human ROR gamma, with an overall identity of 88%. Northern blot analysis using RNA from different tissues showed that mROR gamma was found to be highly expressed in skeletal muscle, liver and kidney. Analysis of the ROR gamma-response element using in vitro synthesized ROR gamma revealed that it binds as a monomer to response elements composed of a single core motif GGTCA preceded by a 6 bp AT-rich sequence. The ROR gamma-binding specificity was further defined by mutational analysis of the consensus RORE. ROR gamma was able to activate RORE-dependent transcription of the CAT reporter gene in mouse fibroblast D1 cells. ROR alpha 1 and ROR gamma inhibit the transactivation induced by GAL4(DBD)-ROR gamma in fibroblast D1 cells suggesting that these receptors compete for binding to the same coactivators.


Asunto(s)
Receptores Citoplasmáticos y Nucleares/genética , Receptores de Ácido Retinoico , Receptores de Hormona Tiroidea , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , Cloranfenicol O-Acetiltransferasa/genética , Clonación Molecular , Secuencia de Consenso , ADN Complementario , Genes Reporteros , Humanos , Ratones , Datos de Secuencia Molecular , Mutagénesis , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Receptores Citoplasmáticos y Nucleares/metabolismo , Homología de Secuencia de Aminoácido , Distribución Tisular , Activación Transcripcional
19.
Am J Ind Med ; 30(1): 7-15, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8837676

RESUMEN

Nested case-control interview studies of lung cancer (610 incident cases), stomach cancer (292 incident cases), and 959 controls were conducted to follow up leads from a proportional mortality analysis of deaths among male workers in a large integrated iron-steel complex in Anshan, China. For lung cancer, after adjusting for the significant non-occupational risk factors (smoking, other pulmonary disease, family history of lung cancer, and low consumption of fruit or tea), risks were significantly elevated for those employed for 15 or more years in smelting and rolling (OR = 1.5, CI = 1.1-2.2), in the fire-resistant brick factory (OR = 2.9, CI = 1.4-5.9), in general loading (OR = 2.5, CI = 1.0-6.1), and as coke oven workers (OR = 3.4; CI = 1.4-8.5). For stomach cancer, after adjusting for consumption of pickled vegetables, prior gastric diseases, family history of stomach cancer, low intake of fruits and vegetables, and education, risks were significantly elevated for those employed for 15 or more years in ore sintering and transportation (OR = 2.1, CI = 1.0-4.4), in the fire-resistant brick factory (OR = 2.5, CI = 1.1-5.8), in general loading (OR = 3.2, CI = 1.2-8.9), as boilerworkers and cooks (OR = 2.6, CI = 1.2-5.6), and as coke oven workers (OR = 5.4, CI = 1.8-16.0). For both lung and stomach cancers, significant dose-response gradients were observed for exposure to total dust and benzo(a)pyrene, but not for specific chemical components of dust. Overall, long-term steel workers with exposure to workplace pollutants had a 40% increased risk of both lung and stomach cancers. These case-control studies confirm many of the occupational findings reported in the proportionate mortality analysis, and suggest avenues for further work to evaluate the carcinogenicity of individual components of dust.


Asunto(s)
Hierro , Neoplasias Pulmonares/epidemiología , Metalurgia , Enfermedades Profesionales/epidemiología , Acero , Neoplasias Gástricas/epidemiología , Adulto , Anciano , Benzo(a)pireno/efectos adversos , Estudios de Casos y Controles , China/epidemiología , Polvo/efectos adversos , Escolaridad , Contaminación Ambiental/efectos adversos , Conducta Alimentaria , Femenino , Estudios de Seguimiento , Frutas , Humanos , Incidencia , Enfermedades Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Exposición Profesional , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar/epidemiología , Gastropatías/epidemiología , Neoplasias Gástricas/genética , , Factores de Tiempo , Verduras
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 16(6): 466-8, 1994 Dec.
Artículo en Chino | MEDLINE | ID: mdl-7720147

RESUMEN

Three more triterpenoids were isolated from total glucosides of tripterygium wilfordii (T1). T16 and T17 were identified as salaspermic acid and as wilforlide B. T18 was a new compound. The structure of T18 was determined, as 3-oxo-22 alpha-hydroxy-delta 12-oleanen-29-oic acid by detail spectroscopic and chemical analysis, and named triptotriterpenonic acid A.


Asunto(s)
Medicamentos Herbarios Chinos/química , Ácido Oleanólico/análogos & derivados , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Tripterygium , Triterpenos/química , Triterpenos/aislamiento & purificación
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