Optimized J to T peak and T peak to T end measurements in nonclinical species administered moxifloxacin and amiodarone.

Introduction: Cardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug development. TdP is associated with a delayed ventricular repolarization represented by QT interval prolongation in the electrocardiogram (ECG), typically due to block of the potassium channel encoded by the human ether-a-go-go related gene (hERG). Importantly however, not all drugs that prolong the QT interval are torsadagenic and not all hERG blockers prolong the QT interval.

[Mechanism of total saponins of Panax japonicus against liver injury induced by acetaminophen in mice based on ERK/NF-κB/COX-2 signaling pathway].

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days.

Electrophysiological Changes in the Rabbit Ventricular Wedge and Human-Induced Pluripotent Stem-Cell Derived (IPSC) Cardiomyocytes Translate to Severe Arrhythmia Observed in a Canine Toxicology Study, Not Predicted by Standard In Vitro Ion Channel Assays.

During drug discovery, small molecules are typically assayed in vitro for secondary pharmacology effects, which include ion channels relevant to cardiac electrophysiology. Compound A was an irreversible inhibitor of myeloperoxidase investigated for the treatment of peripheral artery disease. Oral doses in dogs at ≥5 mg/kg resulted in cardiac arrhythmias in a dose-dependent manner (at Cmax, free ≥1.

The incidence of spontaneous arrhythmias in telemetered beagle dogs, Göttingen Minipigs and Cynomolgus non-human primates: A HESI consortium retrospective analysis.

Introduction: Characterization of the incidence of spontaneous arrhythmias to identify possible drug-related effects is often an important part of the analysis in safety pharmacology studies using telemetry.

Methods: A retrospective analysis in non-clinical species with and without telemetry transmitters was conducted. Electrocardiograms (24 h) from male and female beagle dogs (n = 131), Göttingen minipigs (n = 108) and cynomolgus non-human primates (NHP; n = 78) were analyzed.

[Impacts of long-term different fertilization managements on soil acid hydrolysable organic nitrogen fractions in double-cropping rice field].

To clarify the impacts of long-term different fertilization modes on the soil acid hydrolysable organic nitrogen and its components in the double-cropping rice field of southern China, a long-term (36-year) location field experiment was used as a platform to systematically analyze the variations of soil acid hydrolysable organic nitrogen and its components (amino acid nitrogen, amino sugar nitrogen, ammonium nitrogen, unidentified hydrolysable nitrogen) at 0-10 cm and 10-20 cm soil layers under four fertilization treatments, including chemical fertilizer alone (CF), rice straw and chemical fertilizer (RF), 30% organic manure and 70% chemical fertilizer (OM), and control (CK). The relationships of soil acid hydrolysable organic nitrogen content and soil total nitrogen, soil organic carbon content were also analyzed. The results showed that compared with CK, OM and RF treatments significantly increased the contents of total nitrogen, available nitrogen, and organic carbon at both soil layers.

Cholesterol Metabolic Markers for Differential Evaluation of Patients with Hyperlipidemia and Familial Hypercholesterolemia.

The cholesterol metabolism in humans can be indirectly reflected by measuring cholesterol metabolism marker levels. We aimed to investigate the association of cholesterol homeostasis markers on standard lipid profiling components in familial hypercholesteremia and hyperlipidemia patients. A total of 69 hyperlipidemia patients, 25 familial hypercholesteremia (FHC) patients, and 64 healthy controls were enrolled in this study.

Effects of long-term fertilizer management on soil labile organic carbon fractions and hydrolytic enzyme activity under a double-cropping rice system of southern China.

Fertilization is an effective way to improve soil quality, increase soil fertility and soil microbial diversity in paddy soil. To explore the changes of soil labile organic carbon (C) fractions and hydrolytic enzyme activity after 34 years fertilization treatments in a field experiment in double-cropping rice system of southern China. There were four treatments, including chemical fertilizer alone (MF), rice residue and chemical fertilizer (RF), 30% organic matter and 70% chemical fertilizer (OM), and the control without fertilizer input (CK).

Respiratory Rates Derived From Arterial Blood Pressure Waveforms in Telemetered Dogs.

The objective of this study was to extract low frequency respiratory "artifacts" from a standard arterial blood pressure (ABP) waveform to simultaneously derive reliable breathing rates (BR). Arterial blood pressure derived BR values were characterized against respiratory rates simultaneously obtained from the Respiratory Inductive Plethysmography (RIP) system (EMKA). Reference compounds were introduced to evaluate responsiveness of the derived measures to respiratory depressants and stimulants.

Echocardiographic and hemodynamic indices of myocardial contractility simultaneously evaluated in telemetered beagle dogs: A HESI-sponsored cross-company evaluation.

Introduction: Alterations in cardiac contractility can have significant clinical implications, highlighting the need for early detection of potential liabilities. Pre-clinical methods to assess contractility are typically invasive and their translation to human measures of cardiac function are not well defined. Clinically, cardiac function is most often measured non-invasively using echocardiography.

[Microbial Carbon Source Metabolic Profile in Rice Rhizosphere and Non-rhizosphere Soils with Different Long-term Fertilization Management].

Rhizosphere and non-rhizosphere soil samples under different long-term fertilization treatments including control without fertilizer (CK), chemical fertilization alone (NPK), rice residues combined with NPK (NPKS), 30% manure plus 70% chemical fertilizers (LOM), and 60% manure plus 40% chemical fertilizers (HOM) were collected from a paddy field in a red soil hilly area in Ningxiang City, Hunan Province, China. The characteristics of microbial carbon utilization in the soils were studied. Results of O-HO tracer analysis showed that both soil microbial biomass carbon content (MBC) and microbial growth rate () were highest in the HOM treatment, whereas they were lowest in CK.

[Effects of different manure nitrogen input ratio on rhizosphere soil microbial biomass carbon, nitrogen and microbial quotient in double-cropping rice field].

To explore the characteristics of rhizosphere soil microorganisms in paddy fields with different manure nitrogen (N) input ratios at different growth stages of early and late rice in double-cropping rice system, a field experiment was conducted with five different treatments: 1) 100% N of chemical fertilizer (M), 2) 30% N of organic matter and 70% N of chemical fertilizer (M), 3) 50% N of organic matter and 50% N of chemical fertilizer (M), 4) 100% N of organic matter (M), and 5) no N fertilizer input as a control (M). The rhizosphere soil microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and microbial quotient (SQ) of the paddy fields were measured using the fumigation-extraction and chemical analysis methods. The results showed that the rhizosphere MBC, MBN, and SQ of the paddy fields at main different growth stages of early and late rice were increased by fertilization, which increased first and then decreased with the development of rice growth period, peaked at the heading stage, and reached the minimum value at the maturity stage.

[Effects of different planting patterns on the apparent balance of soil nutrients and nitrogen production efficiency in paddy soil].

To investigate the effects of different planting patterns on soil nutrient contents, rice yield, nitrogen production efficiency, and apparent nutrient balance, a long-term field experiment was conducted in Changsha, Hunan, China. Four planting patterns were examined, including winter fallow-double cropping rice (CK), ryegrass-double cropping rice (Ry-R-R), Chinese milk vetch-double cropping rice (Mv-R-R), rape-double cropping rice (Ra-R-R). Compared with CK, soil total nitrogen (N) and available N were significantly higher under Ry-R-R, Mv-R-R and Ra-R-R.

[Characteristics of amino sugar accumulation in rhizosphere and non rhizosphere soil of rice under different fertilization treatments].

Soil samples were collected from paddy ecosystem under five long-term fertilization treatments, including control without fertilizer (CK), chemical fertilization alone (NPK), rice residue combined with NPK (NPKS), 30% manure plus 70% chemical fertilizer (LOM), and 60% manure plus 40% chemical fertilizer (HOM) in Ningxiang City, Hunan Province. The cha-racteristics of amino sugars accumulation in the rhizosphere and non-rhizosphere soils at rice tillering stage were analyzed. Results showed that the contents of soil organic carbon, total amino sugars and three amino monosaccharides (muramic acid, glucosamine and galactosamine) with long-term application of organic materials (rice residue or manure) were significantly higher compared with CK and NPK.

[Effects of Long-term Fertilization Regimes on Microbial Biomass, Community Structure and Activity in a Paddy Soil].

Four paddy soils were collected in Ningxiang County, Hunan province. These used with different long-term fertilization regimes, including a control without fertilizer (CK), chemical fertilization with nitrogen, phosphate, and kalium (NPK), straw fertilization combined with NPK (ST), and manure fertilization combinedwith NPK (OM). Phospholipid fatty acid (PLFA) technology and Microresp method were used to study the effect of long-term fertilization on soil microorganism abundance, community structure, and activity.

Integrated TK-TD modeling for drug-induced concurrent tachycardia and QT changes in beagle dogs.

Drug-induced cardiotoxicity, including tachycardia and QT prolongation, remains a major safety concern that needs to be identified and its risk mitigated in early stages of drug development. In the present study, an integrated toxicokinetic-toxicodynamic (TK-TD) modeling approach within a nonlinear mixed-effect modeling framework is applied to investigate concurrent abnormal heart rate and QT changes in three beagle dogs, using a Novartis internal compound (NVS001) as the case example. By accounting for saturable drug absorption, circadian rhythms, drug-effect tolerance, and nonlinear rate-dependency of QT interval, the dynamic TK-TD model captures the experimentally observed drug effects on heart rate and QT interval across a wide dosing range of NVS001 in beagle dogs.

[Effects of different winter cover crops on soil organic carbon in a double cropping rice paddy field.].

In a double cropping rice field experiment, effects of five winter cover crops on the total organic carbon (TOC), active organic carbon (AOC), carbon pool management index (CPMI) and organic carbon storage were studied in three soil layers (0-5, 5-10 and 10-20 cm).Winter cover crops of ryegrass (Ry), Chinese milk vetch (Mv), potato (Po), and rape (Ra) between two rice crops were compared with fallow as control (CK). The results showed that the TOC and AOC contents under Ry, Mv, Po and Ra treatments were higher than those of CK in all three la-yers.

Evaluation of the effects of the water-soluble total flavonoids from Isodon lophanthoides var.gerardianus (Benth.) H. Hara on apoptosis in HepG2 cell: Investigation of the most relevant mechanisms.

Ethnopharmacological Relevance: The water-soluble total flavonoids (WSTF) were extracted from Isodon lophanthoides var. gerardianus (Benth.) H.

Translational assessment of cardiac contractility by echocardiography in the telemetered rat.

Introduction: Cardiac contractility was evaluated using standard inotropic agents in rats. We compared indices of cardiac contractility, i.e.

[Determination of six C-Glycoside flavones and antitumor activity of water-soluble total flavonoids from Isodon lophanthoides var. gerardianus].

This research established an HPLC method for determination of six C-Glycoside flavones of warer-soluble total flavonoids from Isodon lophanthoides var. gerardianus (Benth.) H.

Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation.

Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A.

[Effects of long-term tillage and rice straw returning on soil nutrient pools and Cd concentration].

The objective of this study was to assess the effects of tillage and straw returning on soil nutrient and its pools, and soil Cd concentration, and to identify the strategies for rational tillage and remediation of Cd contaminated paddy fields. The experiment was established with no-tillage with straw retention (NTS) , rotary tillage with straw incorporation (RTS) , conventional plow tillage with straw incorporation (CTS), conventional plow tillage with straw removed ( CT) from 2005 to 2013. The results indicated that tillage and rice straw retention had a great impact on soil properties at 0-10 cm soil depth.

Effects of winter cover crops straws incorporation on CH4 and N2O emission from double-cropping paddy fields in southern China.

Residue management in cropping systems is believed to improve soil quality. However, the effects of residue management on methane (CH4) and nitrous oxide (N2O) emissions from paddy field in Southern China have not been well researched. The emissions of CH4 and N2O were investigated in double cropping rice (Oryza sativa L.

Effects of winter cover crops residue returning on soil enzyme activities and soil microbial community in double-cropping rice fields.

Residue management in cropping systems is useful to improve soil quality. However, the studies on the effects of residue management on the enzyme activities and microbial community of soils in South China are few. Therefore, the effects of incorporating winter cover crop residue with a double-cropping rice (Oryza sativa L.

Emissions of CH4 and N2O under different tillage systems from double-cropped paddy fields in Southern China.

Understanding greenhouse gases (GHG) emissions is becoming increasingly important with the climate change. Most previous studies have focused on the assessment of soil organic carbon (SOC) sequestration potential and GHG emissions from agriculture. However, specific experiments assessing tillage impacts on GHG emission from double-cropped paddy fields in Southern China are relatively scarce.