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1.
Talanta ; 206: 120202, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514885

RESUMO

Tetracycline (TC), a widely-used antibiotic to treat bacterial infections, combines with Eu3+ to form a stable EuTC complex that has a low fluorescence (FL) yield because of Eu3+ coordination with water molecules. We report a simple, label-free ratiometric fluorescent platform for sensitively and selectively sensing of TC, using L-histidine caped gold nanoclusters (His-AuNCs) as a FL indicator and an enhancer of Eu3+ FL. The His-AuNCs were prepared via chemical reduction of Au(III) by L-histidine, which was a reducer and a protecting agent. The His-AuNCs exhibited good photostability, outstanding stability toward high ionic strengths, storage stability, and favorable optical properties. In the absence of TC, the AuNCs-Eu3+ system displays strong FL emission at 475 nm (F475) from the His-AuNCs and weak FL at 620 nm from Eu3+ (F620) with excitation at 375 nm. TC quenches the His-AuNC FL and greatly enhances the Eu3+ emission. This is attributed to an enhancement of the EuTC complex fluorescence by the His-AuNCs. Thus, a ratiometric F620/F475 FL signal can be used for TC detection by simply mixing AuNCs and Eu3+. Under the optimized conditions, the linear range from 10 nM to 60 µM and a detection limit of 4 nM (S/N = 3) for TC were obtained. The application of the assay platform for the detection of TC in environmental and biological samples was demonstrated. The sensing platform has advantages of easy preparation, rapid response, high sensitivity, and good selectivity.

2.
Environ Health Perspect ; 127(10): 107001, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31573832

RESUMO

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown. OBJECTIVES: Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth. METHODS: The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile. RESULTS: Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p-values (ptrend<0.05) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome. CONCLUSIONS: Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.

3.
PLoS One ; 14(10): e0223489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31584993

RESUMO

Stress has become a widely experienced state all around the world, and previous literature has found that stress impacts individuals' cognition, emotion, coping behaviors and psychological well-being in general. Relatively little is known about how stress influences individuals' perception of stimuli changes, a ubiquitous phenomenon known as scope sensitivity. In the current work, we explore whether individuals with higher levels of chronic stress are sensitive to stimuli changes, such as price and quantity differences. Two empirical studies consistently show that chronically stressed individuals exhibit scope insensitivity, as they rated the expensiveness of two hotel rooms with different prices as being less different and indicated a smaller difference in their willingness-to-buy five CDs versus ten CDs. Possible explanations and theoretical and practical implications in the broader field are discussed.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31597608

RESUMO

Advanced glycation end-products (AGEs) have been implicated in chronic hyperglycemia and age-related diseases. Endogenous AGEs produced by humans generate oxidative stress and activation of inflammatory signaling pathways via AGE-specific receptors. The present review summarizes current knowledge on the pathogenic role of AGEs in chronic noncommunicable diseases. Although correlations exist between glycation and the pathogenesis of these diseases, uncertainties remain in light of recurrent intervention failures of apparently promising animal models to be translated into clinically useful anti-AGE strategies. Future intervention of AGEs or their receptors should embrace more carefully executed clinical trials. Nevertheless, suppressing symptoms via lifetime drug application is unlikely to eliminate the burden of chronic diseases unless deep-rooted lifestyle issues that cause these diseases are simultaneously addressed.

5.
Int J Phytoremediation ; : 1-8, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31564121

RESUMO

Microorganisms are used to alleviate heavy metal stress in plants cultivated in contaminated fields. However, the relevant mechanisms have been rarely explored. The goal of this study was to investigate effects of arbuscular mycorrhizal fungus Funneliformis mosseae and two Cd-resistant bacterial strains (Enterobacter sp. EG16 and Enterobacter ludwigii DJ3) on growth and Cd tolerance of tomato when applied with different inoculation strategies (single or dual) and Cd concentrations (50 and 100 mg kg-1). Better plant growth was observed in mycorrhizal alone or combined treatments. In F. mosseae and EG16 co-inoculation treatment, shoot and root dry weight were 119-154% and 91-173% higher than those of the control, respectively. Higher bacterial and mycorrhizal colonization rate and root Cd concentration were also found in this treatment. However, the decrease of shoot Cd concentration and translocation factor values indicated this treatment was effective in improving Cd tolerance of the host plants. In addition, the increase in soil pH and decline in bioavailable Cd in the rhizosphere might be partly involved in reduction of Cd accumulation in plants. Our results suggest that co-inoculation with suitable microorganisms is important in plant growth and tolerance to Cd in Cd-contaminated soil.

6.
Pediatr Res ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578036

RESUMO

BACKGROUND: Cigarette smoking is associated with shorter telomere lengths in adults, but evidence on the effect of prenatal tobacco exposure is limited. We aimed to investigate the association between prenatal second-hand smoke exposure and newborn telomere length. METHODS: We recruited 762 mother-newborn pairs from Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) between November 2013 and March 2015. Information on second-hand smoke exposure was obtained via questionnaires. Relative telomere length was measured in DNA extracted from umbilical cord blood. We used linear regression to assess the associations between prenatal second-hand smoke exposure and newborn telomere length. RESULTS: In the fully adjusted model, prenatal second-hand smoke exposure was associated with 9.7% shorter newborn telomere length (percent difference: -9.7%; 95% confidence interval (CI): -15.0, -4.0). The estimate for boys was lower (percent difference: -10.9%; 95% CI: -18.6, -2.5) than that for girls (percent difference: -8.5%; 95% CI: -15.8, -0.5), but the interaction term between newborn sex and prenatal second-hand smoke was not significant (P = 0.751). CONCLUSIONS: This study demonstrated that prenatal second-hand smoke exposure may be a preventable risk factor for accelerated biological aging in the intrauterine stage, and further suggested possible sex differences in the susceptibility to prenatal second-hand smoke.

7.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2943-2946, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602837

RESUMO

Hugan Tablets is a Chinese patent medicine,it has the function of anti-inflammation and reducing transaminase. Based on questionnaire investigation of doctors and a systematic review of research literature on Hugan Tablets,using international clinical practice guidelines' developing methods,with the best available evidence and fully combining expert experience,and following the principle of " evidence-based,consensus-based and experience-based",Expert consensus statement on Hugan Tablets in clinical practice was developed by more than 30 multidisciplinary experts from the nationwide,aimed at guiding and standardizing the rational use of Hugan Tablets by clinicians and to improve clinical efficacy and safety. The expert consensus adopts internationally recognized recommendation criteria for classification of evidence: GRADE. The formation of expert consensus adopts the nominal group technique. Six main considerations are quality of evidence,curative effect,safety,economical efficiency,patient acceptability and other factors. If there is sufficient evidence,a " recommendation" is formed,using GRADE grid voting rule. If there isn' t sufficient evidence,a " consensus opinion" is formed,using majority counting rule. Focus on the indication,usage and dosage,drug use in special population and safety of Hugan Tablets,two recommendations and eight consensus opinions were put forward. Through expert meetings and correspondence,a nationwide consultation and peer review was conducted. This consensus applies to clinicians in hospitals and grass-roots health services,to provide guidance and reference for the rational use of Hugan Tablets.

8.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3022-3034, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602849

RESUMO

To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 µm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 µL; the column temperature was 40 ℃; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 ℃,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 ℃,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.

9.
FASEB J ; : fj201900883RR, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31569998

RESUMO

Iron is a necessary nutrient for humans and nearly all bacterial species. During Salmonella infection, macrophages limit the availability of iron to intracellular pathogens in one of the central components of nutritional immunity. However, Salmonella also have mechanisms to interfere with the antimicrobial effect of host iron withdrawal and meet their own nutrient requirements by scavenging iron from the host. Here, we provide what is, to our knowledge, the first report that SpvB, a pSLT-encoded cytotoxic protein whose function is associated with the intracellular stage of salmonellosis, perturbs macrophage iron metabolism, thereby facilitating Salmonella survival and intracellular replication. In investigating the underlying mechanism, we observed that the Salmonella effector SpvB down-regulated nuclear factor erythroid-derived 2-related factor 2 (NRF2), and its C-terminal domain was necessary and sufficient for NRF2 degradation via the proteasome pathway. Decreased NRF2 expression in the nucleus resulted in a decrease in its transcriptional target ferroportin, encoding the sole macrophage iron exporter, thus ultimately decreasing iron efflux and increasing the intracellular iron content. Additionally, SpvB contributes to the pathogenesis of Salmonella including severe serum hypoferremia, increased splenic and hepatic bacterial burden, and inflammatory injury in vivo. Together, our observations uncovered a novel contribution of SpvB to Salmonella pathology via interference with host intracellular iron metabolism.-Yang, S., Deng, Q., Sun, L., Dong, K., Li, Y., Wu, S., Huang, R. Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2.

10.
Nat Methods ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501551

RESUMO

We introduce an interferometric single-molecule localization method for super-resolution fluorescence microscopy. Fluorescence molecules are located by the intensities of multiple excitation patterns of an interference fringe, providing around a twofold improvement in the localization precision compared with the conventional imaging with the same photon budget. We demonstrate this technique by resolving nanostructures down to 5 nm in size over a large 25 × 25 µm2 field of view.

11.
Mol Med Rep ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31545442

RESUMO

Cell migration is important for renal recovery from tubular cell injury. Heat shock transcription factor 1 (HSF1) is a well­studied regulatory factor that is active during acute kidney injury. HSF1 is also involved in the migration process during tumor metastasis. Therefore, we hypothesized that HSF1 may promote the recovery of renal function by affecting kidney tubular cell migration. A wound healing assay was used to examine the cell migration rate. The results demonstrated that the migration of rat kidney proximal tubular cells (RPTCs) was increased following knockdown of HSF1. In addition, the invasion ability of HSF1 knockdown RPTCs was also significantly upregulated. The present study also identified that transforming growth factor­ß1 (TGF­ß1) was highly expressed at the edge of the wound in control cells, and its expression was further increased upon knockdown of HSF1. Inhibition of TGF­ß1 signaling prevented RPTC HSF1 knockdown cell migration, suggesting that HSF1­regulated RPTC cell migration was dependent on the TGF­ß1 signaling pathway. Furthermore, phosphorylation of TGF­ß1 and Smad2/3 was induced in HSF1 knockdown cells. Together, these results suggest that HSF1 may suppress RPTC migration by inhibiting the activation of the TGF­ß1­Smad2/3 signaling pathway.

12.
PLoS One ; 14(9): e0223101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557248

RESUMO

Research has found that preschoolers' imitation demonstrates in-group bias and is guided by behavior efficacy. However, little is known about whether children's sensitivity to behavior efficacy affects their in-group imitation. This study aimed to investigate preschoolers' imitation tendency when group preference and behavior efficacy are in conflict. Participants were 4-year-old (N = 72) and 6-year-old (N = 72) preschoolers in China. They observed two demonstrators (one in-group and one out-group) pressing two different buttons, respectively, to turn on a music box, and were then asked to try it themselves. In the experimental condition, the out-group demonstrator always succeeded, whereas the in-group demonstrator failed half the time. The results showed that more 6-year-old children imitated the less-effective behaviors of the in-group demonstrator, whereas 4-year-old children showed no such inclination. Two control conditions confirmed that children chose to imitate in-group rather than out-group members (Control 1: both in-group and out-group demonstrators succeeded all four times), and could imitate according to efficacy (Control 2: two in-group demonstrators succeeded two and four times, respectively). These results indicated that 6-year-olds faithfully followed the in-group modeled behavior, regardless of behavior efficacy. Results are discussed through the social function of in-group imitative learning.

13.
Mol Pain ; : 1744806919882511, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558093

RESUMO

Trigeminal neuralgia (TN) commonly results in pain behaviors and cognitive impairment. Convincing evidence suggests that TWIK-related spinal cord K+ (TRESK) exerts antinociceptive and neuroprotective effects. However, its possible potentials in TN remain unclear. TN model was established in rats by generating an infraorbital nerve chronic constriction injury (ION-CCI), and rats received intrathecal injections of TRESK overexpressing lentivirus (LV-TRESK) and siRNA expression vector targeted against TRESK (si-TRESK) into the trigeminal ganglions. Mechanical allodynia was evaluated by mechanical withdrawal threshold (MWT). Cognitive capacity was tested using Morris water maze (MWM). The TRESK expression was determined by quantitative real-time PCR (qRT-PCR) and western blotting. Results showed that the mRNA and protein levels of TRESK were significantly downregulated in trigeminal ganglions in injured rats. Intrathecal treatment with TRESK reduced mechanical allodynia and relieved learning and memory deficits in TN rats, while si-TRESK injection caused neuropathic pain and cognitive deficits. In summary, the present study concluded that TRESK ameliorated pain-associated behaviors and cognitive deficits, which was useful as an alternative approach in management of TN.

14.
Methods Cell Biol ; 154: 163-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493817

RESUMO

The zebrafish kidney has been used effectively for studying kidney development, repair and disease. New gene editing capability makes it a more versatile in vivo vertebrate model system to investigate renal epithelial cells in their native environment. In this chapter we focus on dissecting gene function in basic cellular biology of renal epithelial cells, including lumen formation and cell polarity, in intact zebrafish embryos.

15.
Ecotoxicol Environ Saf ; 184: 109657, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31526923

RESUMO

Concerns on minimizing health risks of phthalates have been raised due to their widespread exposure and well-documented endocrine disrupting properties, but the determinants of levels, metabolism, and health risks of phthalate exposures have not been thoroughly characterized among the Chinese population, particularly pregnant women. The metabolites of five phthalates were analyzed: diethyl (DEP), diisobutyl (DiBP), di-n-butyl (DnBP), di-(2-ethylhexyl) (DEHP), and benzyl butyl phthalate (BBzP) were analyzed in urine samples collected from 946 mothers in Wuhan during 2014-2015. We applied linear mixed models to investigate the relationships between biomarkers (e.g., urinary concentrations of phthalate metabolites, phthalates, and ratios of metabolites) and factors including sampling seasons and epidemiological characteristics. We calculated estimated daily intake (EDI) using average phthalate concentrations over three trimesters and hazard index (HI) by dividing EDI by tolerance daily intake. About 24.9% of participants were at health risks with HI > 1. The largest health risks were driven by one specific phthalate (DnBP or DEHP). We observed lower urinary levels of phthalate metabolites in winter. Elevated levels were found in mothers with higher education levels or those employed. Mothers who got pregnant on purpose had lower phthalate concentrations than those got pregnant by accident. More recent exposure to phthalates was observed among groups of mothers giving birth to girls, or those who got excessive gestational weight gain. Younger mothers were more susceptible to phthalate exposure. This repeated measurement study suggests that the intervention should be taken to limit application and production of DnBP and DEHP, and highlights that typical demographic factors should be taken into account in demographic studies.

16.
Sci China Life Sci ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31564034

RESUMO

Paternal imprinted genes (H19 and Gtl2) are pivotal for prenatal embryonic development in mice. Nongrowing oocytes and sperm- or oocyte-originated haploid embryonic stem cells (haESCs) carrying both H19-DMR (differentially DNA-methylated region) and IG (intergenic)-DMR deletions that partially mimic paternal imprinting of H19-Igf2 and Dlk1-Dio3 can be employed as sperm replacement to efficiently support full-term embryonic development. However, how H19-DMR and IG-DMR act together to regulate embryonic development is still largely unknown. Here, using androgenetic haESC (AG-haESC)-mediated semi-cloned (SC) technology, we showed that paternal H19-DMR and IG-DMR are not essential for pre-implantation development of SC embryos generated through injection of AG-haESCs into oocytes. H19-DMR plays critical roles before 12.5 days of gestation while IG-DMR is essential for late-gestation of SC embryos. Interestingly, we found that combined deletions of H19 and H19-DMR can further improve the efficiency of normal development of SC embryos at mid-gestation compared to DKO SC embryos. Transcriptome and histology analyses revealed that H19 and H19-DMR combined deletions rescue the placental defects. Furthermore, we showed that H19, H19-DMR and IG-DMR deletions (TKO) give rise to better prenatal and postnatal embryonic development of SC embryos compared to DKO. Together, our results indicate the temporal regulation of paternal imprinted loci during embryonic development.

17.
ACS Appl Mater Interfaces ; 11(38): 35451-35457, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483595

RESUMO

Transparent wood (TW) is an emerging optical material combining high optical transmittance and haze for structural applications. Unlike nonscattering absorbing media, the thickness dependence of light transmittance for TW is complicated because optical losses are also related to increased photon path length from multiple scattering. In the present study, starting from photon diffusion equation, it is found that the angle-integrated total light transmittance of TW has an exponentially decaying dependence on sample thickness. The expression reveals an attenuation coefficient which depends not only on the absorption coefficient but also on the diffusion coefficient. The total transmittance and thickness were measured for a range of TW samples, from both acetylated and nonacetylated balsa wood templates, and were fitted according to the derived relationship. The fitting gives a lower attenuation coefficient for the acetylated TW compared to the nonacetylated one. The lower attenuation coefficient for the acetylated TW is attributed to its lower scattering coefficient or correspondingly lower haze. The attenuation constant resulted from our model hence can serve as a singular material parameter that facilitates cross-comparison of different sample types, at even different thicknesses, when total optical transmittance is concerned. The model was verified with two other TWs (ash and birch) and is in general applicable to other scattering media.

18.
J Med Virol ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475735

RESUMO

A series of butene lactones were synthesized and these compounds were tested for anti-respiratory syncytial virus (RSV) activity in vitro. Three compounds exhibited an antiviral effect, the highest of which was compound 6b3 with an effective concentration 50% of 6.35 µM. The effects of 6b3 were then evaluated in vivo and a significant reduction in the lung index caused by RSV was detected. Reduced inflammatory infiltration and necrosis of the lungs were revealed by histopathology and gross pathology. Activation of an early immune response by 6b3 was also observed by cytokine analysis via a real-time polymerase chain reaction. These results indicated that 6b3 has an anti-RSV effect both in vitro and in vivo, and is a possible candidate compound for the development of an anti-RSV drug in the future.

19.
J Agric Food Chem ; 67(40): 11089-11098, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31509411

RESUMO

Reactive oxygen species and subsequent oxidative stress are reported to play important roles in chronic metabolic diseases. Plant-derived polyphenols, especially food-derived phenolics, have attracted a lot of attention due to their potential usage against oxidative stress-related diseases. The leaf of Psidium guajava (known as guava) is regarded as a good resource of polyphenols and its products are commercially available in Japan as functional foods against multiple chronic metabolism disorders. In the course of finding novel polyphenols with antioxidative activities from guava leaf, 11 acylated phenolic glycosides (1-11), including 5 new oleuropeic acid-conjugated phenolic glycosides, named guajanosides A-E (1, 2, and 5-7), along with 17 known meroterpenoides (12-28), were isolated and identified. Their structures were determined by spectroscopic data analysis, chemical degradation, and acid hydrolysis. Compounds 1, 2, and 5-11 displayed potent reactive oxygen species-scavenging activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Western blot revealed that compound 6 markedly increased the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and the glutamate-cysteine ligase catalytic subunit. The current study revealed the presence of oleuropeic acid-derived phenolic glycosides in guava leaf and highlighted the potential usage of this type of phenolics against oxidative stress-related metabolic diseases via activation of the Nrf2 signaling pathway.

20.
Xenobiotica ; : 1-4, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31556335

RESUMO

Atorvastatin combined with amlodipine (ALDP) can efficiently treat the hypertension with coronary heart disease. However, the drug-drug interaction between atorvastatin and ALDP are still unknown. This study investigates the effects of atorvastatin on the pharmacokinetics of ALDP in rats and clarifies its main mechanism. The pharmacokinetic profiles of oral administration of ALDP (1 mg/kg) in Sprague-Dawley rats, with or without pretreatment of atorvastatin (1.5 mg/kg/d for 7 d) were investigated. The effects of atorvastatin on the metabolism of ALDP were also investigated using rat liver microsomes. The results showed that atorvastatin could significantly increase the peak plasma concentration (from 18.28 ± 2.65 to 24.13 ± 1.96 ng/mL) and decrease the oral clearance (from 4.57 ± 1.15 to 1.79 ± 0.28 L/h/kg) of ALDP. In the rat liver microsome systems, the intrinsic clearance rate of ALDP was decreased by the pretreatment with atorvastatin (39.26 ± 2.1 vs. 33.24 ± 3.3 µL/min/mg protein). Those results indicated that atorvastatin could significantly affect the pharmacokinetic of ALDP, via inhibiting the metabolism of ALDP in rats.

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