Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

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.     

Synthesis of Silver Nanoparticles from Extracts of Wild Ginger (Zingiber zerumbet) with Antibacterial Activity against Selective Multidrug Resistant Oral Bacteria

Antibiotic resistance rate is rising worldwide. Silver nanoparticles (AgNPs) are potent for fighting antimicrobial resistance (AMR), independently or synergistically. The purpose of this study was to prepare AgNPs using wild ginger extracts and to evaluate the antibacterial efficacy of these AgNPs against multidrug-resistant (MDR) Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis. AgNPs were synthesized using wild ginger extracts at room temperature through different parameters for optimization, i.e., pH and variable molar concentration. Synthesis of AgNPs was confirmed by UV/visible spectroscopy and further characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy analysis (EDXA), and Fourier-transform infrared spectroscopy (FTIR). Disc and agar well diffusion techniques were utilized to determine the in vitro antibacterial activity of plant extracts and AgNPs. The surface plasmon resonance peaks in absorption spectra for silver suspension showed the absorption maxima in the range of 400–420 nm. Functional biomolecules such as N–H, C–H, O–H, C–O, and C–O–C were present in Zingiber zerumbet (Z. zerumbet) (aqueous and organic extracts) responsible for the AgNP formation characterized by FTIR. The crystalline structure of ZZAE-AgCl-NPs and ZZEE-AgCl-NPs was displayed in the XRD analysis. SEM analysis revealed the surface morphology. The EDXA analysis also confirmed the element of silver. It was revealed that AgNPs were seemingly spherical in morphology. The biosynthesized AgNPs exhibited complete antibacterial activity against the tested MDR bacterial strains. This study indicates that AgNPs of wild ginger extracts exhibit potent antibacterial activity against MDR bacterial strains.     

Substrate modulation of the properties and reactivity of the oxy-ferrous and hydroperoxo-ferric intermediates of cytochrome P450cam as shown by cryoreduction-EPR/ENDOR spectroscopy

EPR/ENDOR studies have been carried out on oxyferrous cytochrome P450cam one-electron cryoreduced by gamma-irradiation at 77 K in the absence of substrate and in the presence of a variety of substrates including its native hydroxylation substrate, camphor (a), and the alternate substrates, 5-methylenyl-camphor (b), 5,5-difluorocamphor (c), norcamphor (d), and adamantanone (e); the equivalent experiments have been performed on the T252A mutant complexed with a and b. The present study shows that the properties and reactivity of the oxyheme and of both the primary and the annealed intermediates are modulated by a bound substrate. This includes alterations in the properties of the heme center itself (g tensor; (14)N, (1)H, hyperfine couplings). It also includes dramatic changes in reactivity: the presence of any substrate increases the lifetime of hydroperoxoferri-P450cam (2) no less than ca. 20-fold. Among the substrates, b stands out as having an exceptionally strong influence on the properties and reactivity of the P450cam intermediates, especially in the T252A mutant. The intermediate, 2(T252A)-b, does not lose H(2)O(2), as occurs with 2(T252A)-a, but decays with formation of the epoxide of b. Thus, these observations show that substrate can modulate the properties of both the monoxygenase active-oxygen intermediates and the proton-delivery network that encompasses them.     

Hepatic nodules in liver transplantation candidates: MR imaging and underlying hepatic disease

OBJECTIVE: To assess by MR imaging the frequency of hepatic nodules in patients waiting on the liver transplant list and to determine whether certain underlying hepatic diseases were more often associated with the development of such hepatic nodules. MATERIAL AND METHODS: We reviewed the MR and clinical records in all patients seen by the liver transplant service at our center since its inception in January 1998 until September 2002. A total of 371 patients (207 men and 164 women, age range 18-68 years, mean 45 years) were included in the study. The presence of hepatic nodules, size, number and underlying hepatic diseases were determined in all patients. Magnetic resonance imaging was performed on a 1.5-T MR imager using T1-weighted, T2-weighted and multi-phase gadolinium-enhanced sequences. Odds ratio (OR) and 95% confidence intervals (CIs) were computed to evaluate the association between the underlying hepatic disease and the development of hepatic nodule. RESULTS: Among 371 liver transplantation candidates, the most common underlying hepatic disease was hepatitis C virus (HCV) infection, either alone (n=93; 25%) or associated with other hepatic diseases (n=40; 10.8%). Of all patients, 33 (8.9%) had regenerative nodules (RNs), 40 (10.7%) dysplastic nodules (DNs) and 57 (15.3%) hepatocellular carcinomas (HCCs). Hepatocellular carcinoma was observed in 35.3% of patients with HCV infection and alcohol abuse combined, 24.5% with cryptogenic cirrhosis, 25% with hemochromatosis and 19% with alcohol abuse. Patients who had either DNs or HCC were 2.5 times more likely to have either alcohol abuse or HCV, alone or combined, as the substrate of their liver disease (OR 2.54, 95% CI 1.56-4.13). Our data suggest a supra-additive interaction between HCV infection and ethanol in their association with MR imaging detected lesions. CONCLUSION: Patients with cryptogenic cirrhosis, alcohol abuse, HCV infection (alone or combined) and hemochromatosis had the greatest likelihood of having HCC, with the combination of HCV infection and alcohol abuse having the highest of all.     

Hydrogen permeability and catalytic activity of membranes made from palladium-copper alloys in the dehydrogenation of 1,2-cyclohexanediol

Conclusions Palladium-copper alloys, which contain from 37 to 42% Cu, have both a high hydrogen permeability and a substantial catalytic activity in the de hydrogenation of 1,2-cyclohexanediol, which makes it possible to use them as membrane catalysts for this reaction.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1620–1622, July, 1977.     

7-Amino-1-naphthol-3,6-disulphonic acid (2R-acid) as a chromophoric reagent for trivalent iron

Summary 7-Amino-1-naphthol-3,6-disulphonic acid forms a stable red coloured complex with trivalent iron. Studies on the composition and stability of this complex are described.

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Zusammenfassung 7-Amino-1-naphthol-3,6-disulfonsäure bildet mit Eisen(III) einen beständigen, rotgefärbten Komplex. Über die Untersuchungen zur Zusammensetzung und Stabilität dieses Komplexes wird berichtet.

     

Synthesis,swelling properties,and network structure of new stimuli‐responsive poly(N‐acryloyl‐N′‐ethyl piperazine‐co‐N‐isopropylacrylamide) hydrogels

Poly(N‐acryloyl‐N′‐ethyl piperazine‐co‐N‐isopropylacrylamide) hydrogels were prepared by thermal free‐radical copolymerization of N‐acryloyl‐N′‐ethyl piperazine (AcrNEP) and N‐isopropylacrylamide (NIPAM) in solution using N, N′‐methylene bisacrylamide as the crosslinking agent. The gels were responsive to changes in external stimuli such as pH and temperature. The pH and temperature responsive character of the gels was greatly dependent on the monomer content, namely AcrNEP and NIPAM, respectively. The gels swelled in acidic (pH 2) and de‐swelled in basic (pH 10) solutions with a response time of 60 min. With increase in temperature from 23 to 80 °C the swelling of the gels decreased continuously and this effect was different in acidic and basic solutions. The temperature dependence of equilibrium water content of the gels was evaluated by the Gibbs–Helmholtz equation. Detailed analysis of the swelling properties of these new gels in relation to molecular heterogeneity in acidic (pH 2) and basic (pH 10) solutions were performed. Water transport property of the gels was studied gravimetrically. In acidic solution, the diffusion process was non‐Fickian (anomalous) while in basic solution, the diffusion was quasi‐Fickian. The effect was more evident in solution of pH 2 than in pH 10. Various structural parameters of the gels such as number‐average molar mass between crosslink (M_c), the crosslink density (ρ_c), and the mesh size (ξ) were evaluated. The mesh sizes of the hydrogels were between 64 and 783 Å in the swollen state in acidic solution and 20 and 195 Å in the collapsed state in basic solution. The mesh size increased between three to four times during the pH‐dependent swelling process. The amount of unbound water (free water) and bound water of the gels was also evaluated using differential scanning calorimetry. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Wave propagation in double-period quasi-regular one-dimensional photonic crystals composed of single-negative metamaterials

In this paper, we theoretically study the propagation of electromagnetic waves in one-dimensional double-period quasi-regular structures consisting of negative-permittivity and negative-permeability metamaterials. A Drude-type dispersive response for both permittivity and permeability of single-negative metamaterials is considered. From the numerical results performed by transfer matrix method and effective medium theory, it is found that double-period photonic crystals can exhibit an omnidirectional gap at given microwave frequency. Such an omnidirectional gap is insensitive to incident angle and polarization, and is invariant upon the change of scale length. It is also found that this gap exists in all double-period sequences, and it is independent of structure sequence. Moreover, electromagnetic field distributions in this structures show that the fields are localized at each interface of two media. These results can lead to further applications of quasi-regular structures.