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Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(â ¡)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(â ¡) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.
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Mercurio , Compuestos de Metilmercurio , Ratas , Animales , Mercurio/análisis , Distribución Tisular , Compuestos de Metilmercurio/toxicidad , Compuestos de Metilmercurio/análisis , Cromatografía Líquida de Alta Presión/métodos , SodioRESUMEN
BACKGROUND: There have been no reports of acute-on-chronic liver failure (ACLF) during treatment of chronic hepatitis C (CHC) with direct-acting antivirals (DAAs). CASE SUMMARY: We report a 50-year-old male patient with CHC. The patient sought medical attention from the Department of Infectious Diseases at our hospital due to severe yellowing of the skin and sclera, which developed 3 mo previously and attended two consecutive hospitals without finding the cause of liver damage. It was not until 1 mo ago that he was diagnosed with CHC at our hospital. After discharge, he was treated with DAAs. During treatment, ACLF occurred, and timely measures such as liver protection, enzyme lowering, anti-infective treatment, and suppression of inflammatory storms were implemented to control the condition. CONCLUSION: DAA drugs significantly improve the cure rate of CHC. However, when patients have factors such as autoimmune attack, coinfection, or unclear hepatitis C virus genotype, close monitoring is required during DAA treatment.
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OBJECTIVE: To study the effects of vitamin D supplementation on physical growth and neurologic development of very preterm infants receiving nesting intervention in the neonatal intensive care unit (NICU). METHODS: A total of 196 preterm infants had been hospitalized in NICU with the gestational age (GA) between 28 and 32 weeks. Among them, 98 preterm infants received nesting intervention, and the other 98 cases received both nesting and vitamin D supplementation (400 IU). The interventions were continued until 36 weeks postmenstrual age (PMA). The 25(OH)D serum levels, anthropometric parameters, and Premie-Neuro (PN) scores were compared at 36 weeks PMA. RESULTS: Higher median serum level of 25(OH)D was found in the nesting + vitamin D [38.40 ng/mL (IQR: 17.20 ~ 70.88) ng/mL] as compared to the nesting group [15.95 ng/mL (IQR: 10.80 ~ 24.30) ng/mL] at 36 weeks PMA. Besides, infants receiving combined nesting intervention and vitamin D supplementation had less proportion of vitamin D deficiency [VDD, 25(OH)D levels < 20 ng/mL] than those receiving nesting intervention alone. After intervention, the anthropometric parameters of infants, including weight, length, BMI and head circumference were improved in the nesting + vitamin D group as compared to the nesting group at 36 weeks PMA, with higher scores of neurological, movement and responsiveness. CONCLUSIONS: Vitamin D supplementation effectively decreased the prevalence of VDD and led to higher concentrations of 25(OH)D at 36 weeks PMA. This was one more study that supported the necessity of vitamin D supplementation to improve physical growth and neurologic development of preterm-born newborns who received nesting intervention in the NICU.
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Recien Nacido Prematuro , Deficiencia de Vitamina D , Lactante , Femenino , Recién Nacido , Humanos , Unidades de Cuidado Intensivo Neonatal , Vitamina D/uso terapéutico , Vitaminas , Suplementos DietéticosRESUMEN
Bioaccumulation and biotransformation are critical factors that affect the release of easily metabolizable chemicals to cause human toxicity. The glucoside-type modified mycotoxin Zearalenone-14-Glucoside (Z14G) has attracted global attention for its high occurrence in foodstuffs and the potential threat to humans as its high rate of transformation into parent forms. Given the limited toxicokinetics information, this study assessed the absorption, distribution, biotransformation and excretion of Z14G, aiming to define the potential risk of Z14G. The toxicokinetics of Z14G were assessed after intravenous (IV) or oral administration (PO) in SD rats at doses of 10 mg/kg·b.w. In addition, comparative work with the parent mycotoxin ZEN was performed in parallel. The determination of Z14G and its metabolites (ZEN, α-zearalenol, ß-zearalenol, α-zearalanol, ß-zearalanol) proceeded with a sensitive UHPLC-MS/MS method. Our research indicated that Z14G readily disappeared from the blood, and distributed throughout the tissues via transformation into its parent form ZEN, and excreted primarily through urine. More importantly, the metabolite α-ZEL was observed in most analyzed tissue, urine and feces samples. Overall, our findings highlight the importance of biotransformation with regard to Z14G, providing critical insight for the health risk assessment of co-exposure of humans to glucoside-type modified mycotoxins.
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Micotoxinas , Espectrometría de Masas en Tándem , Ratas , Humanos , Animales , Toxicocinética , Espectrometría de Masas en Tándem/métodos , Distribución Tisular , Ratas Sprague-Dawley , Micotoxinas/toxicidad , Glucósidos/toxicidadRESUMEN
OBJECTIVE: To identify factors associated with YMDD mutation in patients with chronic hepatitis B before and after lamivudine treatment in Zunyi region. METHODS: 53 patients with chronic hepatitis B were enrolled in this study, HBV DNA,HBV markers, ALT, AST, TBil, albumin in the serum were examined at 0, 3, 6, 12, 18 and 24 months after lamivudine treatment. HBV genotype and YMDD mutation were determined by sequencing before lamivudine treatment. YMDD mutation was checked again if serum HBV DNA rebound to more than 1 x 10(4) copies/ml after the initial decrease. RESULTS: HBV genotype in Zunyi region is constitute of B, C and B+C genotype. YMDD mutation occurred in 18 cases after lamivudine treatment, the rate of YMDD mutation was 15.1%, and 34.0% after 1 year and 2 years treatment. There are four types of mutation: rtL180M/M204V, rtL180M/M204I, rtM204I, rtL180M. rtM204V mutation in C gene was always accompanied by rtL180M mutation (100%). The rate of rtL180M/M204V mutation in genotype C group was significantly higher than that in genotype B group (77.8% to 25.0%), the same was true for the rtL180M/ M204I mutation (22.2% to 12.5%). There was no point mutation in genotype C group. The point mutation of rtM204I and rtL180M appeared only in genotype B group. Gender, nation, family history of hepatitis B and HBeAg were not associated with YMDD mutation (P more than 0.05), while the mutation rate was associated with the disease course and severity of disease. YMDD mutation did not occur in patients with low HBV DNA level (less than 10(5) copies/ml). CONCLUSION: YMDD mutation after lamivudine therapy is associated with HBV genotype and P gene mutation type, and prolonged treatment increases the the mutation rate. In order to reduce the incidence of YMDD mutation, patients with shorter disease course, lower HBV DNA level, more serious liver damage should be treated with lamivudine.
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Antivirales/uso terapéutico , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Mutación , Adulto , Alanina Transaminasa/sangre , Antivirales/farmacología , Aspartato Aminotransferasas/sangre , China/epidemiología , Análisis Mutacional de ADN , Cartilla de ADN , ADN Viral/sangre , ADN Viral/genética , Farmacorresistencia Viral , Femenino , Genotipo , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Humanos , Lamivudine/farmacología , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
Development of the eye is morphologically similar among vertebrates, indicating that the underlying mechanism regulating the process may have been highly conserved during evolution. Herein we analyzed the promoter of the human betaB1-crytallin gene in zebrafish by transgenic experiments. To delineate the evolutionarily conserved regulatory elements, we performed serial deletion assays in the promoter region. The results demonstrated that the -90/+61-bp upstream proximal promoter region is sufficient to confer lens-tissue specificity to the human betaB1-crystallin gene in transgenic zebrafish. Through phylogenetic sequence comparisons and an electrophoretic mobility shift assay (EMSA), a highly conserved cis-element of a six-base pair sequence TG(A/C)TGA, the consensus sequence for the Maf protein binding site, within the proximal promoter region was revealed. Further, a site-mutational assay showed that this element is crucial for promoter activity. These data suggest that the fundamental transcriptional regulatory mechanism of the betaB1-crystallin gene has been well conserved between humans and zebrafish, and plausibly among all vertebrates, during evolution.