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1.
Artigo em Inglês | MEDLINE | ID: mdl-32041719

RESUMO

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing media reveals certain MRSA strains to be highly susceptible to ß-lactams. We investigated the prevalence of this phenotype ("NaHCO3-responsiveness") to two ß-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3-responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic ß-lactam minimum inhibitory concentrations (MICs) in standard MHB nor population analyses profiles were predictive of this phenotype. Several genotypic markers (CC8; agr I and spa t008) were associated with NaHCO3-responsiveness for OXA.

2.
Zhonghua Wai Ke Za Zhi ; 57(12): 902-907, 2019 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-31826593

RESUMO

Objectives: To evaluate the efficacy of minimally invasive surgery in patients with late severe tricuspid regurgitation after cardiac surgery, and to evaluate the role of leaflets augmentation technique in tricuspid valvuloplasty. Methods: From January 2015 to June 2019, 85 patients undergoing tricuspid valve repair procedure with minimally invasive approach at Department of Cardiovascular Surgery, Guangdong provincial People's Hospital were enrolled. There were 22 males and 63 females, aging of (53.6±12.4) years (range: 15 to 75 years). The interval between the prior and current operations was (16.0±7.3) years (range: 0.2 to 35.0 years). The diameter of right atrium and right ventricle was (77.3±17.2) mm and (61.0±8.4) mm, respectively. Tricuspid regurgitation was severe or extremely severe, the tricuspid regurgitation area was (19.0±10.3) cm(2). All patients underwent minimally invasive tricuspid valvuloplasty or tricuspid valve replacement on beating-heart with totally endoscopic technique and port-access approach through right chest wall. The operations included tricuspid valve replacement and tricuspid valvuloplasty, the technique of tricuspid valvuloplasty including leaflets augmentation with patch, ring implantation, chordae tendineaes reconstruction, release of papillary muscle, edge to edge method, etc. Postoperative hospitalization days, the time of ICU stay, blood transfusion rate, ventilator time and the results of echocardiography were recorded. Follow-up was completed regularly by WeChat, telephone and outpatient visit. Results: Sixty-five patients underwent tricuspid valve repair, and 20 patients underwent tricuspid valve replacement because of prosthetic failure and plasty failure. Five patients died during hospitalization, with mortality rate 5.9%. One patient was transferred to local hospital for anti-infection treatment, the other 79 patients were discharged from hospital in well condition and followed-up. The postoperative hospitalization time was 7.0 (5.5) days (M(Q(R))) days, the mean ventilator time was 18.0 (16.2) hours, and the mean ICU stay time was 68.0 (75.5) hours. There were 35 patients without blood conduction transfusion, the transfusion rate was only 58.9% (50/85). Four cases of severe, 9 cases of moderate and 67 cases of mild to zero tricuspid regurgitation were examined before being discharged, with tricuspid regurgitation area of (2.8±3.5) cm(2) (range: 0 to 19.1 cm(2)). The follow-up time was 1 to 38 months. Two patients died during follow-up, one patient died from infective endocarditis and mitral perivalvular leakage, the other one died of intractable right heart failure. One patient was implanted with permanent pacemaker due to Ⅲ atrioventricular block. Valvular re-replacement was performed in 2 patients who were re-admitted for the artificial valve infection and mechanical valve obstruction. No re-operation of tricuspid valve. Conclusions: Totally endoscopic minimally invasive technique provided satisfactory surgical outcomes for critically sick patients with severe tricuspid regurgitation following cardiac surgery. The application of leaflets augmentation technique achieved ideal repair effect for previously unrepairable lesions.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Insuficiência da Valva Tricúspide/cirurgia , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Reoperação , Resultado do Tratamento , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/etiologia , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-31844004

RESUMO

Supplementation of standard growth media (cation-adjusted Mueller-Hinton Broth [CAMHB]) with bicarbonate (NaHCO3 ) increases ß-lactam susceptibility of selected MRSA strains ("NaHCO3-responsive"). This "sensitization" phenomenon translated to enhanced ß-lactam efficacy in a rabbit model of endocarditis. The present study evaluated NaHCO3-mediated ß-lactam MRSA sensitization using an ex vivo pharmacodynamic model, featuring simulated endocardial vegetations (SEVs), to more closely mimic the host microenvironment. Four previously-described MRSA were used: two each exhibiting in vitro NaHCO3-responsive or NaHCO3-nonresponsive phenotypes. Cefazolin (CFZ) and oxacillin (OXA) were evaluated in CAMHB±NaHCO3 Intra-SEV MRSA killing was determined over 72 hr exposures. In both "responsive" strains, supplementation with 25 mM or 44 mM NaHCO3 significantly reduced ß-lactam MICs to below the OXA susceptibility breakpoint (≤ 4 mg/L) and resulted in bactericidal activity (≥ 3 log kill) in the model for both OXA and CFZ. In contrast, neither in vitro-defined non-responsive MRSA strains showed significant sensitization in the SEV model to either ß-lactam. At both NaHCO3 concentrations, the fractional time-above-MIC was >50% for both CFZ and OXA in the responsive MRSA strains. Also, in RPMI+10% LB media (proposed as a more host-mimicking microenvironment and containing 25 mM NaHCO3), both CFZ and OXA exhibited enhanced bactericidal activity against NaHCO3-responsive strains in the SEV model. Neither CFZ nor OXA exposures selected for emergence of high-level ß-lactam-resistant mutants within SEVs. Thus, in this ex vivo model of endocarditis, in the presence of NaHCO3 supplementation, both CFZ and OXA are highly active against MRSA strains that demonstrate similar enhanced susceptibility in NaHCO3-supplemented media in vitro.

4.
Zhonghua Fu Chan Ke Za Zhi ; 54(12): 833-839, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874473

RESUMO

Objective: To examine the association of pre-pregnancy obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM) with the risk of large for gestational age (LGA), and assess the dynamic changes in population attributable risk percent (PAR%) for having these exposures. Methods: A retrospective cohort study was conducted to collect data on pregnant women who received regular health care and delivered in Beijing Obstetrics and Gynecology Hospital from January to December in 2011, 2014 and 2017, respectively. Information including baseline characteristics, metabolic indicators during pregnancy, pregnancy complications, and pregnancy outcomes were collected. Multivariate logistic regression model was constructed to assess their association with LGA delivery. Adjusted relative risk and prevalence of these factors were used to calculate PAR%and evaluate the comprehensive risk. Results: (1)The number of participants were 11 132, 13 167 and 4 973 in 2011, 2014 and 2017, respectively. Corresponding prevalence of LGA were 15.19% (1 691/11 132), 14.98% (1 973/13 167) and 16.21% (806/4 973). No significant change in the prevalence of LGA was observed across all years investigated (all P>0.05). (2)According to results from multivariate logistic regression model, advanced maternal age, multiparity, pre-pregnancy overweight or obesity, GWG,GDM and serum triglyceride level≥1.7 mmol/L in the first trimester were associated with high risk of LGA (all P<0.05). Among these factors, pre-pregnancy overweight or obesity, excessive GWG and multiparity were common risk factors of LGA. GDM was not associated with risk of LGA in 2017 database. (3) Dynamic change of PAR% in these years were notable. PAR% of GWG for LGA decreased (32.6%, 27.2% and 22.2% in 2011, 2014 and 2017, respectively), while PAR% of pre-pregnancy overweight or obesity showed an upward trend (4.2%, 3.3% and 8.4%). In addition, PAR% of multiparity increased as well (3.5%, 6.3% and 15.9%). (4) Further analysis showed that excessive GWG in the first and second trimesters contributed the most (20.2% and 19.0% in 2014 and 2017). Conclusions: Excessive GWG, pre-pregnancy overweight or obesity and multiparity are the important risk factors what contribute to LGA. PAR% of excessive GWG for LGA decrease in recent years. However, GWG in the first and second trimesters is a critical factor of LGA. Appropriate weight management in pre-pregnancy, the first or second trimester is the key point to reduce the risk of LGA.


Assuntos
Diabetes Gestacional/epidemiologia , Macrossomia Fetal/epidemiologia , Obesidade/complicações , Peso ao Nascer , Índice de Massa Corporal , China/epidemiologia , Feminino , Macrossomia Fetal/etiologia , Idade Gestacional , Humanos , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , Ganho de Peso
5.
Eur Rev Med Pharmacol Sci ; 23(21): 9259-9266, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31773677

RESUMO

OBJECTIVE: This meta-analysis aims to clarify the correlation between N-acetyltransferases 2 (NAT2) polymorphisms and susceptibility of acute leukemia. MATERIALS AND METHODS: Articles reporting the correlation between NAT2 polymorphisms and susceptibility of acute leukemia were searched from PubMed, Embase, and Cochrane. Citations in eligible articles were manually reviewed. Only cohort studies and case-control studies which provided odds ratio (OR) and 95% confidence interval (CI) of the correlation between NAT2 polymorphisms and susceptibility of acute leukemia up to December 1st, 2018 were enrolled. The included data were weighted by an inverse variance and analyzed using the fixed-effects or random-effects model. The data acquisition and the heterogeneity test were conducted. STATA 12.0 was used for statistical analysis. RESULTS: This meta-analysis enrolled 10 independent case-control studies with 1,874 leukemia patients and 2,789 healthy volunteers. No significant difference was found between the fast-acetylator incidence of NAT2 haplotype and the onset risk of acute lymphoblastic leukemia (ALL, OR=0.70, 95% CI=0.45-1.08) or acute myeloid leukemia (AML, OR=0.79, 95% CI=0.46-1.47). The subgroup analysis was conducted based on the sources of controls (SOCs). We did not find statistical difference in population-based (PB) group (OR=0.82, 95% CI=0.47-1.42) and hospital-based (HB) group (OR=0.54, 95% CI=0.27-1.08). In addition, the fast-acetylator incidence of NAT2 haplotype was only observed to be higher in ALL patients compared with HB group (OR=0.52, 95% CI=0.33-0.83), rather than the PB group (OR=0.82, 95% CI=0.47-1.44). CONCLUSIONS: Except for ALL patients and those hospital-based controls, no evidence has shown the relationship between NAT2 polymorphisms and the susceptibility of acute leukemia. This conclusion still needs to be further verified in multi-center hospital with a large sample size.

7.
Eur Rev Med Pharmacol Sci ; 23(16): 6914-6926, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31486491

RESUMO

OBJECTIVE: To investigate the molecular mechanisms of long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in gastric cancer (GC) development progress. MATERIALS AND METHODS: Relative mRNA and protein expression levels were quantified by quantitative Reverse Transcription-PCR (qRT-PCR) or Western blot analysis. Cell proliferation and cell apoptosis were measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry, respectively. Binding sites of miR-497-5p on NEAT1 or phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were determined by RNA pull-down assay or dual-luciferase reporter assay. Finally, the tumorigenic role of NEAT1 in GC was assessed using a xenograft model on nude mice. RESULTS: NEAT1 was upregulated in GC tissues, promoted proliferation, and inhibited apoptosis of GC cells. NEAT1 could directly bind to and negatively regulate miR-497-5p expression. PIK3R1 was then identified as a downstream target of miR-497-5P. In GC cell models, PIK3R1 was found to be directly negatively regulated by miR-497-5p and indirectly positively regulated by NEAT1. Finally, NEAT1 knockdown inhibited tumor growth, increased miR-497-5p expression, and decreased PIK3R1 expression in xenograft model mice compared with the negative control. CONCLUSIONS: Functioned as an oncogene, NEAT1 promoted cell growth in GC by regulating miR-497-5p/PIK3R1 axis. These results provided valuable insights into the underlying regulation signaling in gastric cancer development, shedding light on NEAT1 a promising therapeutic target from bench to clinic.

8.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(7): 510-514, 2019 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-31365967

RESUMO

Objective: To investigate the clinical and epidemiological characteristics of influenza A (H3N2) infected patients in Jinhua area, and therefore to improve the understanding of infection with H3N2 influenza virus. Methods: The pharynx swab specimens for pathogenic detection were collected from acute respiratory infection (ARI) cases in the fever clinic of the sentinel hospital in Jinhua area from 2014 to 2017. Descriptive statistics method was used to analyze the clinical features and pathogenics characteristics of the patients infected with H3N2 influenza virus. The t test or χ(2) test of independent samples were used for comparison between groups. Results: A total of 3 803 cases of acute respiratory infection (ARI) were reported in the sentinel hospital in Jinhua area from 2014 to 2017. Among them, 245 cases (6.4%) of H3N2 influenza were diagnosed, including 153 males (62.4%) and 92 females (37.6%), aged from 0.5 to 95 years, with an average age of (50.1+15.7) years. They were divided into 5 age groups, with 107 (43.7%) patients aged 60 years and older. The incidence of major diseases was 43.7%. There was no significant difference in the gender in different age groups (χ(2)=4.581, P=0.333). The seasonal peak of H3N2 influenza A virus infection was mainly in summer (In June-September), but was also seen in other months. In the 4 years from 2014 to 2017, there were a total of 4 peaks, which occurred in July-September, July-August, June-August, and June-August. The body temperature of most patients (73.1%) was between 38.0 and 38.9 ℃. The main positive signs of H3N2 influenza A virus infection were different degrees of pharyngeal hyperemia and tonsillar enlargement. Fever (>38 ℃), cough, dizziness, fatigue, sore throat, headache, chills, shortness of breath, runny nose, myalgia, expectoration, nasal congestion were the main symptoms of H3N2 cases. The proportion of abnormal X-ray/CT manifestations in H3N2 influenza A virus infection cases was lower than that of other influenza viruses. 89.8% of the patients were positive for H3N2 influenza A. The average lymphocyte count was (1.1±0.5) × 10(9)/L, total platelet count (157±39) × 10(9)/L in H3N2 influenza A infection group, which were lower than those in other influenza positive patients [(1.2±0.6)×10(9)/L and (165±42) × 10(9)/L], while the neutrophil count (3.6±0.8) × 10(9)/L was higher than that in other influenza positive patients (3.4±1.0) × 10(9)/L(all P<0.05). Conclusions: Patients with H3N2 influenza A in Jinhua mostly presented with throat congestion and tonsillar enlargement in varying degrees, fever (>38 ℃), cough and sputum production. The seasonal peak of influenza A was in summer (June-September). Elderly aged 60 years or older were the susceptible group.


Assuntos
Vírus da Influenza A Subtipo H3N2 , Influenza Humana/epidemiologia , Infecções Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Tosse/etiologia , Feminino , Febre/etiologia , Humanos , Lactente , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/diagnóstico , Estações do Ano , Adulto Jovem
9.
Molecules ; 24(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382389

RESUMO

Acinetobacter baumannii bacteremia represents a serious and increasing clinical problem due to the high mortality and treatment failures because of high rates of antibiotic resistance. Any additional new therapies for A. baumannii bacteremia would address a growing unmet medical need. ARV-1502 (designated as Chex1-Arg20 or A3-APO monomer in prior publications) is a designer proline-rich antimicrobial peptide chaperone protein inhibitor derived from insects and has demonstrated potent activity against multi-drug resistant (MDR) Gram-negative bacteria. In the current studies, we investigated the therapeutic efficacy of ARV-1502 administered intravenously (iv) alone and in combination with imipenem/cilastatin (IPM/CIL) in a mouse bacteremia model due to a MDR clinical A. baumannii strain, HUMC1. All ARV-1502 regimens (1.25, 2.5 and 5.0 mg/kg) significantly reduced bacterial density in the target tissues in a dose-dependent manner, as compared to the untreated control and IPM/CIL monotherapy (40 mg/kg) groups in the model. In addition, ARV-1502 treatment, even at the lowest dose, significantly improved survival vs. the control and IPM alone groups. As expected, IMP/CIL monotherapy had no therapeutic efficacy in the model, since the HUMC1 strain was resistant to IMP in vitro. However, the combination of ARV-1502 and IPM/CIL significantly enhanced the efficacy of ARV-1502, except the lowest dose of ARV-1502. The superior efficacy of ARV-1502 in the bacteremia model caused by MDR A. baumannii provides further support for studying this compound in severe infections caused by other MDR Gram-positive and -negative pathogens.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bacteriemia/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Modelos Animais de Doenças , Camundongos , Testes de Sensibilidade Microbiana
10.
Acta Pharm Sin B ; 9(3): 496-504, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31193801

RESUMO

As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of d-serine alone and in combination with ß-lactams against methicillin-resistant Staphylococcus aureus (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, ß-lactams alone and in combinations was evaluated both in vitro by standard MICs, time-kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of d-serine and ß-lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to ß-lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with ß-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of d-serine alone or in combination with ß-lactams, d-serine is worth following up as new anti-MRSA infection strategies.

11.
Antibiotics (Basel) ; 8(2)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146412

RESUMO

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection.

12.
J Infect Dis ; 220(6): 1019-1028, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31177268

RESUMO

BACKGROUND: MgrA is an important global virulence gene regulator in Staphylococcus aureus. In the present study, the role of mgrA in host-pathogen interactions related to virulence was explored in both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) strains. METHODS: In vitro susceptibilities to human defense peptides (HDPs), adherence to fibronectin (Fn) and endothelial cells (ECs), EC damage, α-toxin production, expression of global regulator (eg, agr RNAIII) and its downstream effectors (eg, α-toxin [hla] and Fn binding protein A [fnbA]), MgrA binding to fnbA promoter, and the effect on HDP-induced mprF and dltA expression were analyzed. The impact of mgrA on virulence was evaluated using a mouse bacteremia model. RESULTS: mgrA mutants displayed significantly higher susceptibility to HDPs, which might be related to the decreased HDP-induced mprF and dltA expression but decreased Fn and EC adherence, EC damage, α-toxin production, agr RNAIII, hla and fnbA expression, and attenuated virulence in the bacteremia model as compared to their respective parental and mgrA-complemented strains. Importantly, direct binding of MgrA to the fnbA promoter was observed. CONCLUSIONS: These results suggest that mgrA mediates host-pathogen interactions and virulence and may provide a novel therapeutic target for invasive S. aureus infections.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31010857

RESUMO

Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major health care concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as "resistant" to ß-lactams, often leading to the use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO3) supplementation: one highly susceptible to the antistaphylococcal ß-lactams oxacillin and cefazolin (NaHCO3 responsive) and one resistant to such agents (NaHCO3 nonresponsive). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each ß-lactam. Mechanistically, NaHCO3 reduced the expression of two key genes involved in the MRSA phenotype, mecA and sarA, leading to decreased production of penicillin-binding protein 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergistically killed NaHCO3-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO3-supplemented media. These findings suggest that AST of MRSA strains in NaHCO3-containing media may potentially identify infections caused by NaHCO3-responsive strains that are appropriate for ß-lactam therapy.

14.
Fa Yi Xue Za Zhi ; 35(1): 89-94, 2019 Feb.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-30896127

RESUMO

Amphetamines are chemical synthetic drugs that are becoming increasingly popular in China. As a common sample in the inspection of poisons, hair has the advantages of easy storage, good stability, and long detection time compared with traditional human body fluid samples (blood, urine), thus possesses an unique application value in the field of forensic toxicology analysis. By now, methods for detecting amphetamines in human hair have been widely used, and validity of the results has been recognized and adopted by the court. This paper reviews domestic and foreign research progress of the detection of amphetamines in hair samples, including the pretreatment and analytic methods.


Assuntos
Anfetaminas , Cabelo , Detecção do Abuso de Substâncias , Anfetaminas/análise , China , Toxicologia Forense , Cabelo/química , Humanos
15.
Int J Mol Sci ; 20(4)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30781382

RESUMO

BACKGROUND: Antibiotic-resistant H. pylori was increasingly found in infected individuals, which resulted in treatment failure and required alternative therapeutic strategies. Daphnetin, a coumarin-derivative compound, has multiple pharmacological activities. METHODS: The mechanism of daphnetin on H. pylori was investigated focusing on its effect on cell morphologies, transcription of genes related to virulence, adhesion, and cytotoxicity to human gastric epithelial (GES-1) cell line. RESULTS: Daphnetin showed good activities against multidrug resistant (MDR) H. pylori clinical isolates, with minimal inhibitory concentration (MIC) values ranging from 25 to 100 µg/mL. In addition, daphnetin exposure resulted in H. pylori morphological changes. Moreover, daphnetin caused increased translocation of phosphatidylserine (PS), DNA damage, and recA expression, and RecA protein production vs. control group. Of great importance, daphnetin significantly decreased H. pylori adhesion to GES-1 cell line vs. control group, which may be related to the reduced expression of colonization related genes (e.g., babA and ureI). CONCLUSIONS: These results suggested that daphnetin has good activity against MDR H. pylori. The mechanism(s) of daphnetin against H. pylori were related to change of membrane structure, increase of DNA damage and PS translocation, and decrease of H. pylori attachment to GES-1 cells.


Assuntos
Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Umbeliferonas/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Transformada , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Claritromicina/farmacologia , Dano ao DNA , Células Epiteliais/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/ultraestrutura , Humanos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Umbeliferonas/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-30670427

RESUMO

Bacteriophage-derived lysins are cell-wall-hydrolytic enzymes that represent a potential new class of antibacterial therapeutics in development to address burgeoning antimicrobial resistance. CF-301, the lead compound in this class, is in clinical development as an adjunctive treatment to potentially improve clinical cure rates of Staphylococcus aureus bacteremia and infective endocarditis (IE) when used in addition to antibiotics. In order to profile the activity of CF-301 in a clinically relevant milieu, we assessed its in vitro activity in human blood versus in a conventional testing medium (cation-adjusted Mueller-Hinton broth [caMHB]). CF-301 exhibited substantially greater potency (32 to ≥100-fold) in human blood versus caMHB in three standard microbiologic testing formats (e.g., broth dilution MICs, checkerboard synergy, and time-kill assays). We demonstrated that CF-301 acted synergistically with two key human blood factors, human serum lysozyme (HuLYZ) and human serum albumin (HSA), which normally have no nascent antistaphylococcal activity, against a prototypic methicillin-resistant S. aureus (MRSA) strain (MW2). Similar in vitro enhancement of CF-301 activity was also observed in rabbit, horse, and dog (but not rat or mouse) blood. Two well-established MRSA IE models in rabbit and rat were used to validate these findings in vivo by demonstrating comparable synergistic efficacy with standard-of-care anti-MRSA antibiotics at >100-fold lower lysin doses in the rabbit than in the rat model. The unique properties of CF-301 that enable bactericidal potentiation of antimicrobial activity via activation of "latent" host factors in human blood may have important therapeutic implications for durable improvements in clinical outcomes of serious antibiotic-resistant staphylococcal infections.

17.
Animal ; 13(1): 90-97, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29644945

RESUMO

Methane produced from formate is one of the important methanogensis pathways in the rumen. However, quantitative information of CH4 production from formate has been rarely reported. The aim of this study was to characterize the conversion rate (CR) of formic acid into CH4 and CO2 by rumen microorganisms. Ground lucerne hay was incubated with buffered ruminal fluid for 6, 12, 24 and 48 h. Before the incubation, 13C-labeled H13COOH was also supplied into the incubation bottle at a dose of 0, 1.5, 2.2 or 2.9 mg/g of DM substrate. There were no interactions (P>0.05) between dose and incubation time for all variables evaluated. When expressed as an absolute amount (ml in gas sample) or a relative CR (%), both 13CH4 and 13CO2 production quadratically increased (P<0.01) with the addition of H13COOH. The total 13C (13CH4 and 13CO2) CR was also quadratically increased (P<0.01) when H13COOH was added. Moreover, formate addition linearly decreased (P<0.031) the concentrations of NH3-N, total and individual volatile fatty acids (acetate, propionate and butyrate), and quadratically decreased (P<0.014) the populations of protozoa, total methanogens, Methanosphaera stadtmanae, Methanobrevibacter ruminantium M1, Methanobrevibacter smithii and Methanosarcina barkeri. In summary, formate affects ruminal fermentation and methanogenesis, as well as the rumen microbiome, in particular microorganisms which are directly or indirectly involved in ruminal methanogenesis. This study provides quantitative verification for the rapid dissimilation of formate into CH4 and CO2 by rumen microorganisms.


Assuntos
Dióxido de Carbono/metabolismo , Formiatos/metabolismo , Microbioma Gastrointestinal/fisiologia , Metano/metabolismo , Rúmen/metabolismo , Animais , Técnicas de Cultura Celular por Lotes/veterinária , Isótopos de Carbono/análise , Cabras/metabolismo , Técnicas In Vitro/veterinária , Marcação por Isótopo/veterinária , Masculino
18.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 32(19): 1511-1514, 2018 Oct 05.
Artigo em Chinês | MEDLINE | ID: mdl-30550202

RESUMO

Two cases with piriform fossa cancer underwent larynx lateral wall repair surgery. Case 1: The patient was admitted to the hospital because of pharyngeal discomfort with swallowing pain for 2 months Electronic laryngoscopy revealed neoplasm in the left piriform fossa. Space occupying lesion in left piriform fossa and paranasal space was found in MRI scan. The pathological diagnosis of this patient was squamous cell squamous cell carcinoma (T2N1M0). Case 2: The patient was admitted to the hospital because of blood in the sputum for more than 1 year. The electronic laryngoscope suggested neoplasm in the pharyngeal space and left vocal cord paralysis.Soft tissue thickening of the oropharynx and hypopharyngeal right wall was found in MRI scan. The pathological diagnosis of this patient was squamous cell carcinoma (T1N2M0).

20.
J Dairy Sci ; 101(12): 11143-11149, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30268613

RESUMO

The objectives of this study were to evaluate the prediction performance of the single-step genomic BLUP method using a multi-trait random regression model in genomic evaluation for milk production traits of Chinese Holsteins, and investigate how parameters w, τ, and ω used in the construction of the combined relationship matrix (H) affected prediction accuracy and bias. A total of 2.8 million test-day records from 0.2 million cows were available for milk, protein, and fat yields. Pedigree information included 0.3 million animals and 7,577 of them were genotyped with medium-density single nucleotide polymorphism marker panels. Genotypes were imputed into Geneseek Genomic Profiler HD (GeneSeek, Lincoln, NE) including 77K markers. A reduced data set for evaluating models was extracted from the full data set by removing test-day records from the last 4 yr. Bull and cow validation populations were constructed for each trait. We evaluated the prediction performance of the multiple-trait multiple-lactation random regression single-step genomic BLUP (RR-ssGBLUP) models with different values of parameters w, τ, and ω in the H matrix, taking consideration of inbreeding. We compared RR-ssGBLUP with the multiple-trait multiple-lactation random regression model based on pedigree and genomic BLUP. De-regressed proofs for 305-d milk, protein, and fat yields averaged over 3 lactations, which were calculated from the full data set, were used for posteriori validations. The results showed that RR-ssGBLUP was feasible for implementation in breeding practice, and its prediction performance was superior to the other 2 methods in the comparison, including prediction accuracy and unbiasedness. For bulls, RR-ssGBLUP models with w0.05τ2.0ω1.0,w0.05τ2.5ω1.0, and w0.1τ1.6ω0.4 achieved the best performance for milk, protein, and fat yields, respectively. For cows, the RR-ssGBLUP with w0.2τ1.6ω0.4 performed the best for all 3 traits. The H matrix constructed with larger τ and smaller ω gave better convergence in solving mixed model equations. Among different RR-ssGBLUP models, the differences in validation accuracy were small. However, the regression coefficient indicating prediction bias varied substantially. The increase of w and τ, and decrease of ω, led to an increase in the regression coefficient. The results demonstrated RR-ssGBLUP is a good alternative to the multi-step approach, but the optimal choice of parameters should be found via preliminary validation study to achieve the best performance.


Assuntos
Bovinos/genética , Bovinos/metabolismo , Leite/metabolismo , Característica Quantitativa Herdável , Animais , Cruzamento , Feminino , Genômica , Genótipo , Lactação , Modelos Lineares , Masculino , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único
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