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Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 339
Author(s):  
Guru R. Valicherla ◽  
Roshan A. Katekar ◽  
Shailesh Dadge ◽  
Mohammed Riyazuddin ◽  
Anees A. Syed ◽  
...  

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood–plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood–plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.


Author(s):  
Jade Chaker ◽  
David Møbjerg Kristensen ◽  
Thorhallur Ingi Halldorsson ◽  
Sjurdur Frodi Olsen ◽  
Christine Monfort ◽  
...  

Author(s):  
Aristides Reis ◽  
André Santos ◽  
Amison Souza ◽  
Luiz Arrais Junior ◽  
Heberty Facundo ◽  
...  

Abstract High levels of nitric oxide (NO) can signal nitrosative stress, but its analysis is challenging considering the high reactivity, short half-life and transient behavior of this target molecule in biological milieu. In this work, a cardanol-based salophen-modified carbon paste electrode (CDN-salophen/MCPE) was developed and successfully applied to assess NO bioavailability in blood plasma of mice under induced stress. The results revealed that the modifier improved the device performance in terms of signal-to-noise ratio, charge-transport and fouling resistance. NO reactivity on CDN-salophen/MCPE was higher in 0.1 mol L‒1 H2SO4, and the resulting redox process involves adsorption steps that control the reaction kinetics. Monitoring molecule oxidation by square-wave voltammetry (100 s−1 frequency, 30 mV amplitude, 2 mV scan increment, after electrode preconditioning at 0.9 V for 15 s for analyte accumulation), it was possible to identify and quantify NO with great sensitivity (detection and quantification limit < 0.1 µmol L‒1) and low data variance (RSD ≤ 9.4% for repeatability and reproducibility tests), through a simple, fast and reliable electroanalytical protocol. The robustness acquired with CDN-salophen/MCPE allowed to detect changes in NO content in blood plasma during nitrosative stress, proving its efficiency for research on this subject.


2021 ◽  
Vol 100 (12) ◽  
pp. 1430-1435
Author(s):  
Olga M. Zhurba ◽  
Alexey V. Merinov ◽  
Anton N. Alekseenko ◽  
Irina V. Kudaeva

Introduction. Vibration is one of the leading unfavourable physical factors of the working environment and leads to vibration disease (VD) development. The study of metabolic profiles of markers of fatty acids (FA) metabolism is one of the directions in the early diagnosis of vascular diseases and metabolic syndrome (MS), caused, among other things, by exposure to vibration. The aim of this work is to study the spectrum of esterified fatty acids of the omega-3 and omega-6 families in the blood of patients with vibration disease (VD) and combination with metabolic syndrome (MS). Materials and methods. The study involved 66 people, divided into two groups: Group I - 34 patients with an established diagnosis of VD; Group II - 32 patients with an established diagnosis of VD in combination with metabolic syndrome (MS). The levels of esterified forms (EF) of polyunsaturated fatty acids (PUFA) of the ω-3 and ω-6 families in blood plasma samples were determined using the method of gas chromatography-mass spectrometry on an Agilent 7890A gas chromatograph with an Agilent 5975C mass selective detector. Results. The distribution of quantitative indices of PUFA of the ω-3 and ω-6 families in the examined groups was studied. In VD patients with MS, compared with VD patients, there was a statistically significant increase in the level of eicosapentaenoic, α-linolenic acids of the ω-3 family, the sum of ω-3 PUFAs, γ-linolenic and linoleic acids of the ω-6 family. Conclusion. The study of the quantitative indices of EF of the families ω-3 and ω-6 in the blood plasma of VD patients with MS showed the levels of ω-6 to be 4.5-5.4 times statistically higher than the levels of ω-3 fatty acids.


2021 ◽  
pp. 2100460
Author(s):  
Tomáš Riedel ◽  
Andres de los Santos Pereira ◽  
Johanka Táborská ◽  
Zuzana Riedelová ◽  
Ognen Pop‐Georgievski ◽  
...  

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