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1.
Biomed Pharmacother ; 121: 109649, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733571

RESUMO

BACKGROUND: Nephrolithiasis is a common disease in urology, and its pathogenesis is associated with various factors. Recent studies have shown that reactive oxygen species (ROS) can promote autophagy in the formation of kidney stones and exacerbate kidney injury. Endoplasmic reticulum stress (ERS), a key factor in regulating intracellular environmental homeostasis, is also directly related to ROS production. Therefore, this study aimed to investigate the regulatory effect of superoxide dismutase (SOD) on autophagy-ERS response during the formation of calcium oxalate (CaOx) kidney stones in rats. METHODS: Thirty-two rats were randomly divided into four groups (n = 8): normal control group, stone model group, stone model with atorvastatin group, and stone model with diethyldithiocarbamic acid (DETC) group. Rat models of CaOx kidney stones were established by intragastric administration of 0.75 % ethylene glycol for 4 weeks. Kidney/body weight was used to assess renal enlargement. Renal function was assessed by measuring serum SOD, creatinine (CRE), and blood urea nitrogen (BUN) levels. The expression of autophagy-related proteins LC3B and BECN1 was detected through immunohistochemical staining. Meanwhile, the expression of autophagy-ERS response-related proteins LC3B, BECN1, p62, GRP78, and CHOP was detected using Western blot and RT-PCR. Renal tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (Kim-1) were determined through enzyme-linked immunosorbent assay. The apoptosis of renal tubular cells and the expression of their signature proteins cleaved Caspase-3, Bax and Bcl-2 were detected using Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Western blot assays, respectively. Crystal deposition and histological tissue injury were assessed through Von Kossa staining. RESULTS: Compared with the control group, the stone model group showed higher kidney/body weight ratio; evidently higher expression of autophagy-ERS response- and apoptosis-related proteins LC3B, BECN1, GRP78, CHOP, Bax and cleaved Caspase-3; and lower levels of p62, bcl-2 protein, and SOD. The stone model group also showed higher levels of apoptosis, serum CRE, BUN, NGAL, and Kim-1, as well as considerably greater crystal deposition and renal injury, than the control group. Atorvastatin reduced the levels of autophagy-ERS response, kidney injury, and crystal deposition, but they were increased by DETC. CONCLUSION: Enhanced SOD activity can protect the kidneys by reducing autophagy-ERS response and CaOx kidney stone formation. Atorvastatin may be a new option for the prevention and treatment of nephrolithiasis.

2.
J Phys Chem Lett ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791124

RESUMO

Inspired by the superior optoelectronic performances of various 2D semiconductors, their new compositions and structures are being actively pursued in order to foster novel fundamental physics and device applications. As a layered semiconductor with a direct bandgap, few-layer PbI2 should have drawn much research attention due to their capability of emitting photons at short wavelengths of the visible spectrum. Here we chemically synthesize few-layer PbI2 flakes and nanoparticles, which demonstrate unique exciton properties that have rare counterparts in other 2D semiconductors. For three layers and more, the single PbI2 flakes can be utilized to show how the bandgap energy of a 2D semiconductor evolves with the changing layer thickness. The single PbI2 nanoparticles are associated with an ultranarrow photoluminescence linewidth of ~1 meV, thus reflecting the influence of lateral quantum confinement on the energy-level structures of a 2D semiconductor. The above findings mark the emergence of a potent 2D platform that is more than complementary to well-studied transition-metal dichalcogenide monolayers.

3.
JAMA Cardiol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799987

RESUMO

Importance: Stem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown. Objective: To investigate the association between the change in CPC counts during stress testing and the risk of adverse cardiovascular events in patients with stable coronary artery disease (CAD). Design, Setting, and Participants: This prospective cohort study included a population-based sample of 454 patients with stable CAD who were recruited between June 1, 2011, and August 15, 2014, at Emory University-affiliated hospitals and followed up for 3 years. Data were analyzed from September 15, 2018, to October 15, 2018. Exposures: Myocardial perfusion imaging with technetium Tc 99m sestamibi at rest and 30 to 60 minutes after conventional stress testing. Main Outcomes and Measures: Circulating progenitor cells were enumerated with flow cytometry as CD34-expressing mononuclear cells (CD45med/CD34+), with additional quantification of subsets coexpressing the chemokine (C-X-C motif) receptor 4 (CD34+/CXCR4+). Changes in CPC counts were calculated as poststress minus resting CPC counts. Cox proportional hazards regression models were used to identify factors associated with the combined end point of cardiovascular death and myocardial infarction after adjusting for clinical covariates, including age, sex, race, smoking history, body mass index, and history of heart failure, hypertension, dyslipidemia, and diabetes. Results: Of the 454 patients (mean [SD] age, 63 [9] years; 76% men) with stable CAD enrolled in the study, 142 (31.3%) had stress-induced ischemia and 312 (68.7%) did not, as measured by single-photon emission computed tomography. During stress testing, patients with stress-induced ischemia had a mean decrease of 20.2% (interquartile range [IQR], -45.3 to 5.5; P < .001) in their CD34+/CXCR4+ counts, and patients without stress-induced ischemia had a mean increase of 3.2% (IQR, -20.6 to 35.1; P < .001) in their CD34+/CXCR4+ counts. Twenty-four patients (5.2%) experienced adverse events. After adjustment, baseline CPC counts were associated with worse adverse outcomes, but this association was not present after stress-induced ischemia was included in the model. However, the change in CPC counts during exercise remained significantly associated with adverse events (hazard ratio, 2.59; 95% CI, 1.15-5.32, per 50% CD34+/CXCR4+ count decrease), even after adjustment for clinical variables and the presence of ischemia. The discrimination of risk factors associated with incident adverse events improved (increase in C statistic from 0.72 to 0.77; P = .003) with the addition of the change in CD34+/CXCR4+ counts to a model that included clinical characteristics, baseline CPC count, and ischemia. Conclusions and Relevance: In this study of patients with CAD, a decrease in CPC counts during exercise is associated with a worse disease prognosis compared with the presence of stress-induced myocardial ischemia. Further studies are needed to evaluate whether strategies to improve CPC responses during exercise stress will be associated with improvements in the prognosis of patients with CAD.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31801689

RESUMO

Three novel polyoxovanadoborates namely [V12B18O46(OH)14(H2O)0.75]·20.5H2O 1, Na2[V12B18O48(OH)12(H2O)0.5]·26.5H2O 2 and Cd0.5{[Na(H2O)2]2[Na(H2O)]2[Na(H2O)3]2V12B18O53(OH)7(H2O)0.5}·11H2O 3 have been hydrothermally synthesized and structurally characterized. The boratopolyoxovanadate cage [V12B18O60] backbones in 1-3 are constructed by the combination of two hexameric oxovanadate units [V6O9] and one puckered [B18O42] ring via sharing O atoms. All three compounds were obtained under alkaline conditions, and the cluster anions were all [V12B18O60]. But the cations were different, it is inferred that the protonation of the three compound cluster ions is different, respectively [V12B18O46(OH)14(H2O)0.75] in 1, [V12B18O48(OH)12(H2O)0.5]2- in 2 and [V12B18O53(OH)7(H2O)0.5]7- in 3. The V oxidation states ratio of VIV to VV were 2:1 confirmed by valence bond calculation and XPS. We studied the magnetic properties of three compounds by two methods: The variable temperature magnetic susceptibility and the 2D IR COS under magnetic perturbation. From the 2D IR COS under magnetic perturbation map, it is showed that all three: (1) the presence of VIV. (2) Certain quasi-aromaticity from B3O3 six-membered ring. (3) The difference of protonation and the charge of the cluster anions. This work enriches the theory of two-dimensional correlation spectroscopy and also provides a new approach to the study of magnetic materials.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31717466

RESUMO

In order to restore degraded grasslands, the Chinese central government initiated the Prohibited Grazing Policy (PGP) in areas of severe grassland degradation and ecologically fragile regions which is an important payment for ecosystem services (PES) program. Since the initiation of this policy in the early 2000s, the PGP has significantly influenced participants' lives. Therefore, in order for the policy to be successful, it is necessary to understand what determines participants' satisfaction in the policy. This paper presents an analysis of survey data from Yanchi County using ordered probit regression models to explore the factors influencing PGP satisfaction and life satisfaction. The empirical results suggest that farmers' policy perception, environmental perception, and livelihood strategies of raising sheep had significant effects on PGP satisfaction. Additionally, PGP satisfaction, marital status, environmental satisfaction, self-reported influence of the PGP on income, self-reported income level, and self-reported income and expenditure had significantly positive effects on overall life satisfaction. These results are important for promoting better implementation of such programs as well as enhancing social stability and sustainable development in these regions.

6.
Zootaxa ; 4614(2): zootaxa.4614.2.7, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31716383

RESUMO

Two new species of the family Xyalidae from the Laizhou Bay of the Bohai Sea, China are described and illustrated herein. Daptonema papillifera sp. nov. is characterized by relatively small body size, L-shaped spicules with a large cephalate proximal end, triangular gubernaculum with a dorsal apophysis, 5-6 conjoint precloacal cuticularized spines and two ventral papillae located at the middle of the tail. Daptonema papillifera sp. nov. is easily distinguished from the other species in this genus by having 5-6 conjoint precloacal cuticularized spines and two ventral caudal papillae. Pseudosteineria anteramphida sp. nov. is characterized by eight groups of long subcephalic setae located posterior to amphideal fovea, curved slender spicules with cephalate proximal end and tapered distal end, tubular gubernaculum without apophysis, precloacal supplements absent, and a short precloacal seta present. In comparison with its most similar congeneric species, P. ventropapillata Tchesunov, 2000 the new species differs in having smaller body, not jointed cephalic setae, absence of precloacal supplements and absence of gubernacular apophysis.


Assuntos
Nematoides , Animais , Baías , Tamanho Corporal , China , Cromadoria
7.
J Dairy Sci ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31733844

RESUMO

This study investigated the antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) isolated from cases of subclinical bovine mastitis in China, as well as resistance mechanisms and virulence genes encoding adhesins and toxins. We determined antimicrobial susceptibility using the disk diffusion method, and analyzed resistance, adhesin, and toxin genes using PCR. We confirmed MRSA in 73 of 498 (14.7%) Staph. aureus isolates recovered from subclinical mastitic milk samples. All isolates were positive for mecA. The MRSA isolates showed high resistance to penicillin (100.0%), gentamicin (100.0%), and tetracycline (98.6%). All MRSA isolates harbored resistance genes blaZ (penicillin), aacA/aphD (gentamicin), and tetM (alone or in combination with tetK, tetracycline). Moreover, all isolates carried the adhesin genes fnbpA, clfA, clfB, cna, sdrE, and map/eap, and most carried sdrC (98.6%), sdrD (95.9%), bbp (94.5%), and ebpS (80.8%). The toxin genes seh, hla, and hld were present in all isolates, and most isolates carried sea (71.2%), seg (84.9%), sei (82.2%), lukE-lukD (97.3%), and hlg (72.6%). These findings of high-level resistance to antimicrobials commonly used in dairy cattle should lead to calls for antibiogram analysis before antimicrobial therapy. The high frequency of adhesin and toxin genes in MRSA indicates their potential virulence in bovine mastitis in China.

8.
Invest Ophthalmol Vis Sci ; 60(14): 4748-4758, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31731295

RESUMO

Purpose: Lens fibrosis involves aberrant growth, migration, and transforming growth factorß (TGFß)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). In this study, we investigated the role of the bromo- and extra-terminal domain (BET) inhibitor in lens fibrotic disorder to identify drug-based therapies. Methods: Rat lens explants, rabbit primary lens epithelial cells (rLECs), human lens explants and human SRA01/04 cells were treated with TGFß2 in the presence or absence of the BET bromodomain inhibitor JQ1 or the MYC inhibitor 10058-F4. Proliferation was determined by MTS assay. Cell migration was measured by wound healing and transwell assays. The expression levels of fibronectin (FN), α-smooth muscle actin (α-SMA), E-cadherin, and phosphorylated downstream Smads were analyzed by Western blot, qRT-PCR, and immunocytochemical experiments. Transcriptome analysis was conducted to explore the molecular mechanism. Results: Blockage of BET bromodomains with JQ1 significantly suppressed rLECs proliferation by inducing G1 cell cycle arrest. Furthermore, JQ1 attenuated TGFß2-dependent upregulation of mesenchymal gene expression and phosphorylation of Smad2/3 during the progression of EMT, whereas E-cadherin expression was preserved. JQ1 repressed MYC expression, which was dose- and time-dependently upregulated by TGFß2. Inhibiting MYC with either the small-molecule inhibitor 10058-F4 or genetic knockdown phenocopied the effects of JQ1 treatment. MYC overexpression partially reversed the JQ1-regulated EMT-related alteration of gene expression. Both JQ1 and 10058-F4 blocked the expression of TGFß receptor II and integrin αv in rLECs and abolished TGFß2-induced opacification and subcapsular plaque formation in rat lens explants. Conclusions: Our results demonstrate the antifibrotic role of JQ1 in maintaining the epithelial characteristics of LECs and blocking TGFß2-induced EMT, possibly by downregulating MYC, thereby providing new avenues for treating lens fibrosis.

9.
J Nat Prod ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742403

RESUMO

Melongenaterpenes A-L (1-12), 12 new sesquiterpenoids with rare spiro[4.5]decane skeletons, were isolated from the roots of Solanum melongena. Their 2D structures and relative configurations were determined based on NMR and HRESIMS data. The absolute configuration of melongenaterpene A (1) was defined by X-ray crystallographic analysis. The absolute configurations of the remaining compounds were determined by comparison of their NMR data with 1 and consideration of the biosynthetic pathway. This is the first report of the crystal structure of a vetispirane-type sesquiterpenoid. None of the compounds exhibited cytotoxic activity against the three human cancer cell lines HepG2, HeLa, and MCF-7.

10.
Lancet Oncol ; 20(11): e619-e626, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31674320

RESUMO

As a result of recent, substantial capacity building, a new landscape for cancer drug trials is emerging in China. However, data on the characteristics of cancer drug trials, and how they have changed over time, are scarce. Based on clinical trials published on the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, we aimed to systematically review changes over time in clinical trials of cancer drugs in mainland China from 2009 to 2018, to provide insight on the effectiveness of the pharmaceutical industry and identify unmet clinical needs of stakeholders. A total of 1493 trials of 751 newly tested cancer drugs were initiated. Increases over time were observed for the annual number of initiated trials, newly tested drugs, and newly added leading clinical trial units, with a sharp increase after 2016. Of the 1385 trials in which cancer types were identified, solid tumours (325 [23%] trials), non-small-cell lung cancer (232 [17%]), and lymphoma (126 [9%]) were the most common. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east China (50 [41%]) and the smallest number located in southwest China (4 [3%]). The growth trends we observed illustrate the progress in and increasing capability of cancer drug research and development achieved in mainland China over the decade from 2009. The low number of clinical trials on tumours with epidemiological characteristics unique to the Chinese population and the unbalanced geographical distribution of leading clinical trial units will provide potential targets for policy makers and other stakeholders. Further research efforts should address cancers uniquely relevant to Chinese populations, globally rare cancers, and the balance between equitable drug access, efficiency, and sustainability of cancer drug research and development in mainland China.

11.
Nat Prod Res ; : 1-8, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674834

RESUMO

Investigation into the chemical diversity of Artemisia argyi led to the discovery of two new (1, 4) and four known (2-3, 5-6) sesquiterpenoids. The new structures were determined via extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 1.91 to 36.52 µM.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31778353

RESUMO

In this study, we report a novel Gram-negative bacterium, designated as strain CS412T, isolated from deep-sea sediment collected in a cold seep area of the South China Sea. Growth of strain CS412T occurred at 4-40 °C (optimum, 28 °C), pH 5.0-11.0 (optimum, pH 6.0) and with 0-19 % (w/v) NaCl (optimum, 1-2 %). Phylogenetic analysis based on 16S rRNA gene sequence data indicated that strain CS412T belonged to the genus Marinobacter. The closest phylogenetic neighbours of strain CS412T were Marinobacter pelagius HS225T (96.9 %), Marinobacter szutsaonensis NTU-104T (96.8%), Marinobacter santoriniensis NKSG1T (96.4%) and Marinobacter koreensisdd-M3T (96.3 %). The genomic DNA G+C content of strain CS412T was 58.0 mol%. The principal respiratory quinone was ubiquinone-9 (Q-9). The polar lipids of CS412T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipidand and four glycolipids. The major fatty acids of CS412T contained cyclo-C19 : 0ω8c, C16 : 0, C18 : 1ω7c and C18 : 1ω7c 11-methyl. The results of phylogenetic, physiological, biochemical and morphological analyses suggested that strain CS412T represents a novel species of the genus Marinobacter, and the name Marinobacter fonticola sp. nov. is proposed with the type species CS412T (=CCTCC AB 2019197T=KCTC 72475T).

13.
Bioorg Med Chem Lett ; : 126824, 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31780304

RESUMO

Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3ß-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4 µM in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic triterpenoid 3ß-ester derivatives and CETP protein for the further modification and optimization.

14.
Chem Commun (Camb) ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782437

RESUMO

An unusual high-valent Sb(v)-based unit [SbL2]- (L = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol) was developed for the first time to combine with various cuprous-halide clusters for the construction of a brand-new class of heterometallic MOFs. This work not only promotes the limited development of Sb-based MOFs, but also provides a practical strategy for developing new types of composite materials.

15.
J Ethnopharmacol ; : 112380, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31707048

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yueju-Ganmaidazao Decoction (YG) is a multiherbal medicine prescribed for treatment of mood disorder, consisting of two classical traditional Chinese herbal medicine Yueju and Ganmaidazao. Yueju and Ganmaidazao both are used for depression treatment. The combined decoction of Yueju and Ganmaidazao is prescribed to achieve optimal clinical outcomes by dealing with different symptoms of depression. Recent studies indicated ethanol extract of Yueju was capable to confer rapid antidepressant-like response. The antidepressant activity of YG decoction with fast-onset feature remains to be investigated. AIM OF THE STUDY: Rapid and safe antidepressant treatment is urgently needed. This study aimed to assess the rapid antidepressant-like activity of YG and the underlying mechanism, focusing on NMDA/NO/cGMP signaling. MATERIALS AND METHODS: The optimal doses for immediate and persistent antidepressant-like response were first screened using tail suspension test (TST) and forced swimming test (FST) post a single administration of YG. The rapid action was further confirmed by using the chronic mild stress (CMS) and learned helplessness (LH) paradigms. The expressions of NMDA receptor subunits were evaluated post stress and YG. The contributions of NMDA, NO, and cGMP signaling to the antidepressant effect of YG were investigated systematically using pharmacological interventions. RESULTS: The optimal dose for immediate and persistent antidepressant potential, evidenced with reduced immobility times in TST or FST from 30 min to 7 days, was determined. The rapid antidepressant-like effect was confirmed in CMS and LH paradigms, including instant normalization of sucrose preference behavior. The expression of NMDA subunit NR1 in the hippocampus was reduced from 30 min to 5 days post YG. In animals subjected to CMS and LH, hippocampal NR1 expression increased, reversed by YG. YG's antidepressant-like effect was blunted by pretreatment with the agonists along the signalings including NMDA (75 mg/kg), L-arginine (750 mg/kg) and sildenafil (5 mg/kg) in TST or FST. Conversely, administration of subeffective dose of individual antagonists, including MK-801 (0.05 mg/kg), 7-nitroindazole (30 mg/kg), methylene blue (10 mg/kg), in combination with a subeffective dose of YG, elicited antidepressant effects. CONCLUSION: YG conferred rapid antidepressant-like effects, and the antidepressant response was essentially dependent on suppression of NMDA/NO/cGMP signaling.

16.
Theranostics ; 9(26): 8138-8154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754386

RESUMO

Thermosensitive liposomes have demonstrated great potential for tumor-specific chemotherapy. Near infrared (NIR) dyes loaded liposomes have also shown improved photothermal effect in cancer theranostics. However, the instability of liposomes often causes premature release of drugs or dyes, impeding their antitumor efficacy. Herein, we fabricated a highly stable thermo-responsive bubble-generating liposomal nanohybrid cerasome with a silicate framework, combined with a NIR dye to achieve NIR light stimulated, tumor-specific, chemo-photothermal synergistic therapy. Methods: In this system, NIR dye of 1,1'-Dioctadecyl-3,3,3',3'- Tetramethylindotricarbocyanine iodide (DiR) with long carbon chains was self-assembled with a cerasome-forming lipid (CFL) to encapsulate ammonium bicarbonate (ABC), which was further used for actively loading doxorubicin (DOX), affording a thermosensitive and photosensitive DOX-DiR@cerasome (ABC). Results: The resulting cerasome could disperse well in different media. Upon NIR light mediated thermal effect, ABC was decomposed to generate CO2 bubbles, resulting in a permeable channel in the cerasome bilayer that significantly enhanced DOX release. After intravenous injection into tumor-bearing mice, DOX-DiR@cerasome (ABC) could be efficiently accumulated at the tumor tissue, as monitored by DiR fluorescence, lasting for more than 5 days. NIR light irradiation was then performed at 36h to locally heat the tumors, resulting in immediate CO2 bubble generation, which could be clearly detected by ultrasound imaging, facilitating the monitoring process of controlled release of the drug. Significant antitumor efficacy could be obtained for the DOX-DiR@cerasome (ABC) + laser group, which was further confirmed by tumor tissue histological analysis.

17.
Med Ultrason ; 21(4): 441-448, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31765453

RESUMO

AIM: Studies on the usefulness of speckle tracking echocardiography (STE) in the evaluation of the left ventricle in rats with stress cardiomyopathy (SCM) are limited. Our aim was to investigate whether strain values by STE and cardiac troponin I (cTnI) could predict early myocardial injury in rats with SCM. MATERIAL AND METHODS: SCM was induced in Sprague-Dawley female rats using immobilization (IMO) stress. Biomarkers and echocardiographic parameters were evaluated and compared among groups (group 1 - 30 minutes after IMO stress, group 2 - 24 hours after IMO stress, and control group). We defined myocardial injury as a left ventricular ejection fraction <50%. Possible predictors of early myocardial injury were determined by univariate logistic regression, and independent predictors of early myocardial injury were investigated with multivariable logistic regression. RESULTS: A total of 44 rats with a mean weight of 426±33 g were evaluated. Group 1 had the highest plasma epinephrine and norepinephrine levels (p<0.001) and the highest heart rate (p<0.001). In univariate logistic regression, cTnI (OR=2.61 [1.02‒10.25], p=0.043) and global longitudinal strain (GLS) (OR=2.13 [1.12‒6.26], p=0.022) were predictive of early myocardial injury. When GLS and cTnI were included in a multivariate analysis, only GLS remained an independent predictor of early myocardial injury (OR=2.67 [1.14‒14.76], p=0.027). CONCLUSIONS: STE is useful for the quantitative detection of subtle myocardial abnormalities in rats with SCM. GLS may provide a reliable and non-invasive method to predict early myocardial injury.

18.
J Phys Chem B ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31718186

RESUMO

We report a kinetics and mechanistic study on the 1O2 oxidation of 9-methylguanine (9MG) and the cross-linking of the oxidized intermediate 2-amino-9-methyl-9H-purine-6,8-dione (9MOGOX) with Nα-acetyl-lysine-methyl ester (abbreviated as LysNH2) in aqueous solutions of different pH. Experimental measurements include the determination of product branching ratios and reaction kinetics using mass spectrometry and absorption spectroscopy, and the characterization of product structures by employing collision-induced dissociation. Strong pH dependence was revealed for both 9MG oxidation and the addition of nucleophiles (water and LysNH2) at the C5 position of 9MOGOX. The 1O2 oxidation rate constant of 9MG was determined to be 3.6 × 107 M-1·s-1 at pH 10.0 and 0.3 × 107 M-1·s-1 at pH 7.0, both of which were measured in the presence of 15 mM LysNH2. The ωB97XD density functional theory coupled with various basis sets and the SMD implicit solvation model was used to explore the reaction potential energy surfaces for the 1O2 oxidation of 9MG and the formation of C5-water and C5-LysNH2 adducts of 9MOGOX. Computational results have shed light on reaction pathways and product structures for the different ionization states of the reactants. The present work has confirmed that the initial 1O2 addition represents the rate-limiting step for the oxidative transformations of 9MG. All of the downstream steps are exothermic with respect to the starting reactants. The C5-cross-linking of 9MOGOX with LysNH2 significantly suppressed the formation of spiroiminodihydantoin (9MSp) resulting from the C5-water addition. The latter became dominant only at the low concentration (∼1 mM) of LysNH2.

19.
Parasitol Res ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760499

RESUMO

The wide application of pyrethroids has led to the rapid development of insecticide resistance in mosquitoes, leading to a rise in mosquito-borne diseases. We previously identified five differentially expressed lipase family genes upon evaluating the transcriptomes of deltamethrin-resistant and deltamethrin-susceptible strains of Culex pipiens pallens. Herein, the gene expression levels were verified by quantitative real-time PCR, and two lipase family genes, lipase A and pancreatic triacylglycerol lipase A, were chosen for further investigations. Using cell viability assays and Centers for Disease Control and Prevention bottle bioassays, lipase A was found to increase the resistance of mosquitoes against deltamethrin both in vitro and in vivo. Our findings indicate that lipase A is involved in conferring deltamethrin resistance in Cx. pipiens pallens.

20.
Int J Pharm ; : 118829, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715348

RESUMO

Current work investigates a typical issue in formulating a physically stable solution especially when more than one counter ions exist in the composition. The impact of different counter ions on solubilization of monohydrate esylate salt of a free base GSK-497,[BH+:C2H5SO3-:H2O] (1:1) (pKa value 8.0) was investigated to formulate ready to use small volume injectable solution. The concentration dependent aggregation was also appeared to be responsible for hemolytic nature of the drug, therefore a careful investigation was needed to select appropriate counter ion solution without compromising solubilization and leading into higher order aggregation. The esylate salt's native pH in water was closer to pHmax, thus it was risky to render the solution unbuffered. Generally, it is recommended to formulate at least two pH unit away from pHmax to prevent disproportionation related physical instability. This was achieved by buffering solution away from pHmax, using a lactate counter ion (other than esylate salt of API salt) that did not compromise solubility of the given phase and did not appear to promote higher order of aggregation. The rationale for selecting second counter ion was primarily based on the comparison of esylate salt's solubility product (Ksp), with the Ksp value generated from equilibrium solubility of the free base combined with several different counter ions (chloride, lactate, aspartate, citrate and tartrate) at equimolar molar ratio. This approach suggested that the use of a counter ion with higher Ksp (lactate and aspartate) value did not compromise the solubility of original esylate salt but a higher extent of aggregation was possible if aspartate is used to achieve higher solubility. In contrary, use of a counter ion with lower Ksp (citrate, tartrate, chloride) reduced the solubility hence did not favor higher order of aggregation. Thus, based on Ksp comparison a rationale of selecting second counter ion to buffer the salt solution is discussed in this work and optimal formulation concentration is determined based on drug aggregation threshold in solution.

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