Bioequivalence study of two formulations of terazosin hydrochloride capsule in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: This study was conducted to assess the pharmacokinetic and safety profiles between a new oral formulation of terazosin hydrochloride capsule compared with the brand-name drug. MATERIALS AND METHODS: A randomized, open-label, single-dose, 2-period crossover study under fasting or fed conditions was conducted in healthy Chinese subjects. 24 individuals were selected, respectively. Each subject was randomized at the beginning to receive a 2-mg capsule of the test or the reference terazosin during the first period and then received the alternate formulation during the second period following a 1-week washout period. Blood samples were collected at pre-dose and up to 60 hours after administration. Plasma terazosin was quantified by a validated LC-MS/MS method. RESULTS: 48 healthy subjects were enrolled, and 47 completed the study. Cmax, AUC0-t, and AUC0-∞ were similar and the 90% CIs for the geometric mean ratios of these parameters between the two groups were all bounded within the predefined bioequivalence criterion of 80 - 125% under both fasting and fed conditions. Throughout the study period, a total of 30 treatment-emergent adverse events (TEAEs) were reported under fasting condition. 35 TEAEs were observed under fed conditions. No serious adverse event was observed. CONCLUSION: The test and reference formulations of terazosin were bioequivalent and well tolerated under both fasting and fed conditions.

Integrated LC-MS and GC-MS-based untargeted metabolomics studies of the effect of azadirachtin on Bactrocera dorsalis larvae.

Azadirachtin exhibits excellent bioactivities against several hundred arthropods. However, current knowlege of its biochemical effect on B. dorsalis larvae is not deep enough. In this study, integrated LC-MS and GC-MS-based untargeted metabolomics were used to analyze the changes of endogenous metabolites and the biochemical effects of azadirachtin on B. dorsalis larvae. Azadirachtin has excellent bioactivities against B. dorsalis larvae in this study, leading to a longer developmental duration, lower survival rate, and low pupa weight. The effect of azadirachtin was investigated on a total of 22 and 13 differentially abundant metabolites in the LC-MS and GC-MS-based metabolomics results, are selected respectively. Pathway analysis indicated that 14 differentially enriched metabolic pathways, including seven influential pathways, are worthy of attention. Further integrated key metabolic pathway analysis showed that histidine metabolism, D-glutamine and D-glutamate metabolism, biotin metabolism, ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and alanine, aspartate and glutamate metabolism in B. dorsalis larvae are significantly relevant pathways affected by azadirachtin. Although extrapolating the bioactivity results in this study to the practical project of B. dorsalis pest management in the field has limitations, it was found that azadirachtin has a significant effect on the primary metabolism of B. dorsalis larvae.

The comparative metabolic response of Bactrocera dorsalis larvae to azadirachtin, pyriproxyfen and tebufenozide.

Azadirachtin, as the most promising and effective botanical insecticide, exhibits significant growth inhibition activity against agricultural and forestry pests. However, its biochemical effects at the metabolic level compared with those of other insect growth regulators have not been studied. Therefore, in this study, a GC-MS based untargeted metabolomics approach was applied to compare azadirachtin with pyriproxyfen (a juvenile hormone analog) and tebufenozide (a molting hormone analog) in terms of their metabolic effects on Bactrocera dorsalis larvae. The bioactivity of azadirachtin against B. dorsalis larvae was significantly different than those of pyriproxyfen and tebufenozide. A total of 693 mass features were recognized, and 112 metabolites were identified in this study. The results showed that a total of 16, 13 and 10 differentially regulated metabolites corresponding to 12, 5 and 8 pathways occur in Aza versus CK, Pyr versus CK and Teb versus CK group, respectively. Further analysis showed that 6 differentially regulated metabolites corresponding to 5 key pathways could be the primary differential metabolic response of B. dorsalis larvae to the three insect growth regulators. The pathways were myo-inositol corresponding to ascorbate and aldarate metabolism as the specific response of B. dorsalis larvae to azadirachtin; xylitol, xylulose and 3-aminopropionitrile corresponding to pentose and glucuronate interconversions, and cyanoamino acid metabolism as the common responses to azadirachtin and pyriproxyfen; and 3-hydroxypropionic acid and beta-alanine corresponding to propanoate metabolism and beta-alanine metabolism as the specific responses to tebufenozide. The results showed that the metabolic response of B. dorsalis larvae to azadirachitin is closer to that of pyriproxyfen than tebufenozide. The differentially regulated metabolites and pathways responsible for this difference are discussed.

A review of antibiotics, depression, and the gut microbiome.

Emerging evidence indicates that disruption of the intestinal flora play an important role in the pathogenesis of depression. As one of the causes of such disturbances, the role of antibiotics in depression risk is gradually being revealed. Herein, we review recent findings showing that the use of both single and multiple antibiotic regimens may be related to depression by changing the gut microbiota and the brain-gut axis. Based on recent discoveries, we also suggest that several brain-gut interactive mechanisms (particularly those involving nerve and glial cells, neurotransmitters, brain neurotrophic factors, inflammatory factors, short-chain fatty acids, circulating metabolites, blood-brain barrier, and oxidative stress) may help understand the effects of antibiotics on intestinal flora and its relationship with depression.

[Study on characteristics and data mining of 464 cases of lung diseases in Xin'an Wang's medicine].

The purpose of this paper is to study the use rules of drugs for lung diseases in internal medicine department of Xin'an Wang's family, discuss the compatibility of common drugs for lung diseases, guide clinical application, and inherit Xin'an medicine. By retrospective study on lung diseases cases in Wang's internal medicine works, the lung diseases and use frequency of common drugs treated by Wang's medicine were counted, and the systematic clustering and association rule analysis of common drugs were conducted by using SPSS Statistic 20 and SPSS Modeler 18.0, respectively. The results showed that asthma, cold and cough were the main lung diseases treated by Wang's medicine, and the commonly used medicines included antitussive and antiasthmatic drugs, spleen-invigorating and dampness-removing drugs, and expectorants. The medicine taste was mainly bitter, pungent and sweet, with cold and warm properties in a balanced way, without severely cold or hot herbs, mainly attributing to the lung and stomach meridians. In clustering analysis, 10 drug combinations were obtained; association analysis showed that two, three, four association rules respectively had 11, 21, and 10 groups, and each drug group had 11, 16, and 5 items. Core combinations: Poria, Armeniacae Semen Amarum, Asteris Radix et Rhizome, Coicis Semen, Farfarae Flos, Dendrobii Caulis, Perilla Frutescens, Stemonae Radix, Citri Reticulatae Pericarpium, Cynanchi Stauntonii Rhizome et Radix, Meretricis Concha Cyclinae Concha, Belamcandae Rhizoma, and Pinelliae Rhizome. Xin'an Wang's medicine paid attention to the lung nature when treating lung diseases. Lung is a delicate organ, not resistant to coldness or heat, so severely cold or hot herbs shall not be used, and the clear and light drugs with functions of dispersing lung Qi, clearing phlegm evil, strengthening spleen, eliminating phlegm, and relieving cough and asthma are often used. Lung deficiency is a kind of deficiency of Qi and Yin, so both Qi and Yin shall be regulated. Deficiency of Yin would burn the lung and make the lung collaterals blocked. In this case, the lung collaterals shall be dredged for hemostasis. Long time of lung deficiency would hinder the distribution of body fluid, and lung shall be regulated to dissipate phlegm.

Distinction Between Variability-Based Modulation and Mean-Based Activation Revealed by BOLD-fMRI and Eyes-Open/Eyes-Closed Contrast.

Recent BOLD-fMRI studies have revealed spatial distinction between variability- and mean-based between-condition differences, suggesting that BOLD variability could offer complementary and even orthogonal views of brain function with traditional activation. However, these findings were mainly observed in block-designed fMRI studies. As block design may not be appreciate for characterizing the low-frequency dynamics of BOLD signal, the evidences suggesting the distinction between BOLD variability and mean are less convincing. Based on the high reproducibility of signal variability modulation between continuous eyes-open (EO) and eyes-closed (EC) states, here we employed EO/EC paradigm and BOLD-fMRI to compare variability- and mean-based EO/EC differences while the subjects were in light. The comparisons were made both on block-designed and continuous EO/EC data. Our results demonstrated that the spatial patterns of variability- and mean-based EO/EC differences were largely distinct with each other, both for block-designed and continuous data. For continuous data, increases of BOLD variability were found in secondary visual cortex and decreases were mainly in primary auditory cortex, primary sensorimotor cortex and medial nuclei of thalamus, whereas no significant mean-based differences were observed. For the block-designed data, the pattern of increased variability resembled that of continuous data and the negative regions were restricted to medial thalamus and a few clusters in auditory and sensorimotor networks, whereas activation regions were mainly located in primary visual cortex and lateral nuclei of thalamus. Furthermore, with the expanding window analyses we found variability results of continuous data exhibited a rather slower dynamical process than typically considered for task activation, suggesting block design is less optimal than continuous design in characterizing BOLD variability. In sum, we provided more solid evidences that variability-based modulation could represent orthogonal views of brain function with traditional mean-based activation.

The effect of dichlorvos on control of drosophila and its safety evaluation under different application methods.

Drosophila is a common strawberry pest. In this work, toxicities of the 77.5% EC dichlorvos to 3rd instar larvae and adults of drosophila were evaluated through indoor bioassays and field bioassays, respectively. To insure the safety, dichlorvos dissipation and terminal residue in strawberry by different application methods under field conditions were determined by high-performance liquid chromatography. The decline curves of dichlorvos residues in strawberry corresponded with first-order kinetics, and dichlorvos dissipated rapidly in strawberry with half-life (t1/2) of 7.58-13.17 h. Terminal residues below the maximum residue limit of strawberry and soil in different distance were achieved after 24 h under different application methods. This article provides guidance to the proper and safe use of dichlorvos in agriculture; it is more reasonable that dichlorvos is applied by embedding on the ground near the strawberry plants covered plastic film with holes.

A CONSORT-compliant, randomized, double-blind, placebo-controlled pilot trial of purified anthocyanin in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid family, has been shown to ameliorate NAFLD-associated pathologies in rodents.The aim of this CONSORT-compliant pilot study is to evaluate the effects of anthocyanin supplementation on insulin resistance and liver injury biomarkers in patients with NAFLD.A total of 74 subjects with NAFLD were divided into 2 groups in this double-blind, randomized study. Patients received either purified anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12 weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and a set of biomarkers related to NAFLD were evaluated before and after intervention.No significant differences were observed in nutrient intake, physical activity, anthropometric parameters, or plasma lipid profile between patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin group exhibited significant decreases (P < 0.05, all comparisons) in plasma alanine aminotransferase (-19.1% vs 3.1%), cytokeratin-18 M30 fragment (-8.8% vs 5.6%) and myeloperoxidase (-75.0% vs -44.8%). Significant decreases from baseline in fasting blood glucose and homeostasis model assessment for insulin resistance were observed in the anthocyanin group; however, these differences were not significant relative to placebo controls. In addition, the oral glucose tolerance test indicated that anthocyanin supplementation significantly decreased the 2-hour loading glucose level compared to control (-18.7% vs -3.8%, P = 0.02).A 12-week supplement of purified anthocyanin improved insulin resistance, indicators of liver injury, and clinical evolution in NAFLD patients. Further studies are warranted to determine the clinical applications of anthocyanin in NAFLD.This trial was registered at clinicaltrials.gov as NCT01940263.

DLC-1 expression levels in breast cancer assessed by qRT- PCR are negatively associated with malignancy.

OBJECTIVE: The aim of this study was to explore the expression of DLC-l in breast carcinoma and any association with tumor metastasis. METHODS: 51 surgical specimens of human breast carcinoma, divided into high invasive and low invasive groups according to their clinicopathological features, 30 cases of adjacent normal tissue and 28 benign breast lesions were examined by qRT-PCR for expression of DLC-1. RESULTS: Expression level of DLC-1 in adjacent normal tissue and benign breast lesion specimens was higher than that in breast carcinoma (P<0.0001); the values in the high invasive group with synchronous metastases were also lower than in the low invasive group (P=0.0275). The correlation between DLC-1 expression level and tumor progression and metastasis of breast cancer was negative. CONCLUSION: As an anti-oncogene, DLC-1 could play an important part in breast carcinoma occurrence, progression, invasiveness and metastasis. Detecting the changes of the expression of DLC-1 in the breast carcinoma may contribute to earlier auxiliary diagnosis of invasiveness, metastasis and recrudescence.