Levels of Key Enzymes of Methionine-Homocysteine Metabolism in Preeclampsia

Objective. To evaluate the role of key enzymes in the methionine-homocysteine metabolism (MHM) in the physiopathology of preeclampsia (PE).Methods. Plasma and placenta from pregnant women (32 controls and 16 PE patients) were analyzed after informed consent. Protein was quantified by western blot. RNA was obtained with RNA purification kit and was quantified by reverse transcritase followed by real-time PCR (RT-qPCR). Identification of the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and A2756G methionine synthase (MTR) SNP was performed using PCR followed by a high-resolution melting (HRM) analysis. S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) were measured in plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). The SNP association analysis was carried out using Fisher’s exact test. Statistical analysis was performed using a Mann-Whitney test.Results. RNA expression of MTHFR and MTR was significantly higher in patients with PE as compared with controls. Protein, SAM, and SAH levels showed no significant difference between preeclamptic patients and controls. No statistical differences between controls and PE patients were observed with the different SNPs studied.Conclusion. The RNA expression of MTHFR and MTR is elevated in placentas of PE patients, highlighting a potential compensation mechanism of the methionine-homocysteine metabolism in the physiopathology of this disease.

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Pharmacokinetics and pharmacodynamics of a novel amoxicillin/sulbactam/prednisolone intramammary infusion in lactating cows after repeated administrations

Veterinární Medicína ◽

10.17221/7515-vetmed ◽

2014 ◽

Vol 59 (No. 5) ◽

pp. 221-229 ◽

Cited By ~ 2

Author(s):

H. Li ◽

GQ Wu ◽

SS Tang ◽

XL Xiao ◽

JC Li

Keyword(s):

High Performance ◽

Similar Efficacy ◽

Duration Of Action ◽

Lactating Cows ◽

Significant Difference ◽

Liquid Chromatography Tandem Mass ◽

Repeated Administrations ◽

Tandem Mass Spectrometric ◽

The Difference ◽

High Concentrations

The aim of this study was to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of a novel anti-mastitis preparation, amoxicillin/sulbactam/prednisolone intramammary infusion (CAIMM), containing 200 mg amoxicillin, 50 mg sulbactam and 10 mg prednisolone per 3 g formulation, in healthy lactating cows after repeated administrations. A parallel study was performed using the available combination product (Synulox® LC) from Pfizer, with the aim of comparing the two formulations. The concentrations of drugs in quarter milk were determined using the ultra-high performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) method. No significant difference in the major PK parameters (Cmax, Tmax, MRT, t1/2λ, and AUClast) was observed. The MIC90 determined in 106 isolated Staphylococcus spp., 64 Streptococcus spp. and 18 Escherichia coli strains was 0.5, 0.25 and 2 μg/ml, respectively. The PK/PD evaluation showed that the effective duration of action (t > MIC90) for CAIMM (42 ± 2.46 h) was increased by 0.86 times compared with Synulox® LC (34 ± 3.17 h), but the difference was not significant (P > 0.05). This pharmacokinetic and pharmacodynamic study revealed that CAIMM maintained high concentrations in quarter milk for the three ingredients after repeated intramammary administrations and a similar efficacy was achieved with Synulox® LC.

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DNA Damage in Rheumatoid Arthritis: An Age-Dependent Increase in the Lipid Peroxidation-Derived DNA Adduct, Heptanone-Etheno-2′-Deoxycytidine

Autoimmune Diseases ◽

10.1155/2013/183487 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Masako Ogawa ◽

Tomonari Matsuda ◽

Atsushi Ogata ◽

Toshimitsu Hamasaki ◽

Atsushi Kumanogoh ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Dna Adducts ◽

High Performance ◽

Dna Damages ◽

Matrix Metalloproteinase 3 ◽

Reactive Protein ◽

Significant Difference ◽

Age Dependent ◽

Liquid Chromatography Tandem Mass ◽

Whole Blood Cells

Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA).Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), 1,N6-etheno-2′-deoxyadenosine (εdA), and heptanone-etheno-2′-deoxycytidine (HεdC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed.Results. Compared with controls, the levels of HεdC in RA were significantly higher (P<0.0001) and age dependent (r= 0.43,P< 0.01), while there was no significant difference in 8-oxo-dG andεdA accumulation between RA patients and controls. HεdC levels correlated well with the number of swollen joints (r= 0.57,P< 0.0001) and weakly with the number of tender joints (r= 0.26,P= 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3.Conclusion. These findings indicate that HεdC may have some influence on the development of RA and/or its complications.

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Effects of tibial and humerus intraosseous administration of epinephrine in a cardiac arrest swine model

American Journal of Disaster Medicine ◽

10.5055/ajdm.2016.0246 ◽

2016 ◽

Vol 11 (4) ◽

pp. 243-251 ◽

Cited By ~ 4

Author(s):

Denise Beaumont, MSN, CRNA ◽

Asal Baragchizadeh, MS, PhD Candidate ◽

Charles Johnson, MA ◽

Don Johnson, PhD

Keyword(s):

Cardiac Arrest ◽

Maximum Concentration ◽

High Performance ◽

Spontaneous Circulation ◽

Swine Model ◽

Epinephrine Administration ◽

Life Saving ◽

Significant Difference ◽

Liquid Chromatography Tandem Mass ◽

Over Time

Objective: Compare maximum concentration (Cmax), time to maximum concentration (Tmax), mean serum concentration of epinephrine, return of spontaneous circulation (ROSC), time to ROSC, and odds of survival relative to epinephrine administration by humerus intraosseous (HIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine cardiac arrest model.Design: Prospective, between subjects, randomized experimental design.Setting: TriService Research Facility.Subjects: Yorkshire-cross swine (n = 28).Intervention: Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, a dose of 1 mg of epinephrine was administered by HIO, TIO, or the IV routes. Blood samples were collected over 4 minutes and analyzed by high-performance liquid chromatography tandem mass spectrometry.Main Outcome Measurements: ROSC, time to ROSC, Cmax, Tmax, mean concentrations over time, and odds ratio.Results: There was no significant difference in rate of the ROSC among the TIO, HIO, and IV groups (p 0.05). There were significant differences in Cmax: the HIO group was significantly higher than the TIO group (p = 0.007), but no significant difference between the IV and HIO (p = 0.33) or the IV and TIO group (p = 0.060). The Tmax was significantly shorter for both the IV and HIO versus the TIO group (p 0.05), but no difference between IV and HIO (p = 0.328). The odds of survival were higher in the HIO group compared to all other groups.Conclusion: The TIO and HIO provide rapid and reliable access to administer life-saving medications during cardiac arrest.

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The preclinical pharmacological study on HX0969W, a novel water-soluble pro-drug of propofol, in rats

PeerJ ◽

10.7717/peerj.8922 ◽

2020 ◽

Vol 8 ◽

pp. e8922 ◽

Cited By ~ 1

Author(s):

YuJun Zhang ◽

YingYing Jiang ◽

HaiYan Wang ◽

Bin Wang ◽

Jun Yang ◽

...

Keyword(s):

Liquid Chromatography ◽

Pharmacokinetic Study ◽

High Performance ◽

Lipid Emulsion ◽

Pharmacological Study ◽

Water Soluble ◽

Significant Difference ◽

Liquid Chromatography Tandem Mass ◽

Emulsion Formulation ◽

Righting Reflex

Background Propofol is the most widely used intravenous sedative-hypnotic anesthetic in clinical practice. However, many serious side effects have been related to its lipid emulsion formulation. The pro-drug design approach was used to develop the water-soluble propofol, which could effectively resolve the limitations associated with the lipid emulsion formulation. Thus, the new water-soluble pro-drug of propofol, HX0969W, was designed and synthesized. The objective of this study was to conduct preclinical pharmacological studies on this novel water-soluble pro-drug of propofol. Methods The assessment of the loss of the righting reflex (LoRR) was used for the pharmacodynamic study, and liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography- fluorescence were used for the pharmacokinetic study. Results The potency of HX0969W (ED50 [95% CI], 46.49 [43.89–49.29] mg/kg) was similar to that of fospropofol disodium (43.66 [43.57–43.75] mg/kg), but was lower than that of propofol (4.82 [4.8–14.82] mg/kg). Administered with a dose of 2-fold ED50, propofol required a shorter time to cause LoRR than that of HX0969W and fospropofol. However, the LoRR duration was significantly longer in response to the administration of HX0969W and fospropofol disodium than that caused by propofol. In the pharmacokinetic study, the Cmax of fospropofol was higher than that of HX0969W. HX0969W had a shorter mean residual time and a rapid clearance rate than that of fospropofol disodium. There was no significant difference between the Tmax of the propofol whether it was released by HX0969W or fospropofol disodium; the Cmax of propofol released by HX0969W was similar to that of propofol, which was higher than the propofol released by fospropofol disodium.

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ASSOCIATION OF ACTN3 R577X AND ACE I/D POLYMORPHISMS IN BRAZILIANS WRESTLERS

Revista Brasileira de Medicina do Esporte ◽

10.1590/1517-869220172306171864 ◽

2017 ◽

Vol 23 (6) ◽

pp. 469-472 ◽

Cited By ~ 2

Author(s):

Marcelo Romanovitch Ribas ◽

Zair Candido Oliveira Netto ◽

Fabiano Salgueirosa ◽

Priscila Fernandes ◽

Oslei de Matos ◽

...

Keyword(s):

High Performance ◽

Combat Sports ◽

Chi Square ◽

Male Athletes ◽

Exact Test ◽

Greco Roman ◽

Significant Difference ◽

Allelic Distribution ◽

Chi Square Test ◽

Polymerase Chain

ABSTRACT Introduction: By associating genetics and sport, it is possible to identify subjects with greater capacity to adapt to training, and lower chances of injury. Objective: The investigation evaluated the genotypic and allelic distribution of ACTN3 R577X and ACE I/D polymorphisms in Brazilian high-performance athletes in wrestling and percussion combat sports. Methods: The study included 37 male athletes ranked from first to third place in world scenarios, divided into two groups: wrestling (23 wrestlers, being 11 of Judo, 4 of Greco-Roman style, 8 of Brazilian Jiu Jitsu, with mean age of 27.3 ± 6.9 years) and percussion combat sports (14 athletes with a mean age of 25.7±4.4 years, being 6 of Karate, 3 of Muay Thai, 4 of Taekwondo, 1 Boxing). Genotyping of ACTN3 and ACE I/D polymorphisms was performed by polymerase chain reaction (PCR) from the genomic DNA. Genotypic and allelic distributions were compared with control populations and athletes by Chi-square test and Fisher’s exact test; all analyzes considered p ≤ 0.05. Results: The genotypic distributions and allelic frequencies of ACTN3 RR=46%, RX=38% and XX=16%; R=65% and X=35%, and ACE I/D DD=47.7%, ID=34.3% and II=20%; D=62.9% and I=37.1% did not differ from the control population; however, when compared with wrestling athletes a significant difference was observed. Conclusion: These results suggest an association of ACTN3 R577X and ACE I/D genes with Brazilian high-performance wrestling athletes.

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