Rapid and sensitive RP-LC method with amperometric detection for pharmacokinetic assessment of propafenone in human serum of healthy volunteers

A rapid and sensitive liquid chromatography method with amperometric detection has been developed for the determination of propafenone in serum. Sample preparation based on single extraction with dichloromethane using bupivacaine hydrochloride as internal standard. The compounds were separated on C-18 reversed-phase analytical column with the mobile phase composed of methanol-acetonitrile-10 mM K₂HPO₄ (45: 25: 30, v/v/v). Analytes were detected electrochemically with the use of amperometric detector. The quantification limit for propafenone in serum was 10 ng/mL. Linearity of the method was confirmed in the range of 10–500 ng/mL with correlation coefficient of 0.9998. Inter-day relative standard deviations (RSD) ranged from 0.27 to 11.9% and intra-day RSD equalled from 1.1 to 9.7%. The newly developed method was applied for the monitoring of the drug in blood levels with 18 healthy volunteers taking tablet with propafenone.     

Evaluation of the effect of Ramadan fasting on fat-soluble antioxidants and markers of oxidative stress in healthy Pakistani subjects

The aim of this study is to evaluate the effect of Ramadan fasting on the fat-soluble antioxidants [all-trans-retinol (vitamin A) and α-tocopherol (vitamin E)] in healthy Pakistani subjects. Thirty (30) healthy male volunteers (aged 30–50 years) with Ramadan fasting have participated in the study. Blood sampling from these subjects was conducted 1 day before and on 15th and 28th days of Ramadan. The serum levels of vitamin A and vitamin E were measured using liquid chromatography linked with UV–visible (HPLC–UV). The comparison between the samples taken at different times was made by Minitab software applying two samples and paired t-test at (p?<?0.05) as significant. No significant changes have been found in the levels of all-trans-retinol before and during Ramadan values. The levels of α-tocopherol on 28th Ramadan have been decreased significantly when compared with its values before Ramadan (p?<?0.0001). It is concluded that there is nonsignificant change in the levels of vitamin A during the month of Ramadan while the levels of α-tocopherol have been decreased significantly on the 28th day of Ramadan. It is therefore suggested that the fasting of Ramadan has effect on the levels of α-tocopherol and food-based interventions might be necessary to modify the diet during Ramadan.     

Study on bioequivalence of beraprost in healthy volunteers by liquid chromatography with tandem mass spectrometry

Beraprost sodium is an oral prostacyclin analog that was first approved in 1992 (Japan) for the treatment of peripheral vascular disorders. It is administered orally as a tablet available in strength 20 μg. In this paper, we described a liquid chromatography tandem mass spectrometry method that was developed for the quantification of beraprost in human plasma with high sensitivity at picogram per milliliter concentration. The method had been validated in terms of selectivity, sensitivity, accuracy and precision, matrix effect, linearity, recovery and carry‐over according to the Guideline on Bioanalytical Validation from the European Medicines Agency. The standard calibration curve for beraprost was 9.5–1419 pg/mL. This method has been applied successfully to a bioequivalence study with 60 μg of beraprost (three tablets) in 29 healthy volunteers. The results showed that the two formulations of beraprost are bioequivalent.     

Posthypoxic behavioral impairment and mortality of Drosophila melanogaster are associated with high temperatures,enhanced predeath activity and oxidative stress

Hypoxia is an underlying pathophysiological condition of a variety of devastating diseases, including acute ischemic stroke (AIS). We are faced with limited therapeutic options for AIS patients, and even after successful restoration of cerebral blood flow, the poststroke mortality is still high. More basic research is needed to explain mortality after reperfusion and to develop adjunct neuroprotective therapies. Drosophila melanogaster (D.m.) is a suitable model to analyze hypoxia; however, little is known about the impacts of hypoxia and especially of the subsequent reperfusion injury on the behavior and survival of D.m. To address this knowledge gap, we subjected two wild-type D.m. strains (Canton-S and Oregon-R) to severe hypoxia (<0.3% O₂) under standardized environmental conditions in a well-constructed hypoxia chamber. During posthypoxic reperfusion (21% O₂), we assessed fly activity (evoked and spontaneous) and analyzed molecular characteristics (oxidative stress marker abundance, reactive oxygen species (ROS) production, and metabolic activity) at various timepoints during reperfusion. First, we established standard conditions to induce hypoxia in D.m. to guarantee stable and reproducible experiments. Exposure to severe hypoxia under defined conditions impaired the climbing ability and reduced the overall activity of both D.m. strains. Furthermore, a majority of the flies died during the early reperfusion phase (up to 24 h). Interestingly, the flies that died early exhibited elevated activity before death compared to that of the flies that survived the entire reperfusion period. Additionally, we detected increases in ROS and stress marker (Catalase, Superoxide Dismutase and Heat Shock Protein 70) levels as well as reductions in metabolic activity in the reperfusion phase. Finally, we found that changes in environmental conditions impacted the mortality rate. In particular, decreasing the temperature during hypoxia or the reperfusion phase displayed a protective effect. In conclusion, our data suggest that reperfusion-dependent death might be associated with elevated temperatures, predeath activity, and oxidative stress.Subject terms: Stroke, Molecular neuroscience     

Enhancing effect of borneol on pharmacokinetics of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 in healthy volunteers after oral administration of compound Danshen dropping pills

Borneol (Bingpian), a monoterpenoid pharmaceutical ingredient, is commonly used as a main composition in traditional Chinese medicine preparations such as compound Danshen dropping pills (CDDP) and has also been approved by the U.S. Food and Drug Administration as a flavoring substance or adjuvant in food. Borneol plays a regulating and guiding role as a messenger drug in CDDP. However, the effect of borneol on the pharmacokinetics of the components of CDDP in human plasma is unclear. In this study, we investigate the effects of borneol on the pharmacokinetics of ginsenoside Rb₁ (Rb₁), ginsenoside Rg₁ (Rg₁), and notoginsenoside R₁ (NR₁) in CDDP. We used a double-cycle crossover-administration model in 12 healthy male volunteers, administered CDDP with borneol (drug T) and without borneol (drug R). The selective response monitoring mode was used for MS quantification in the positive mode. As a result, we found that borneol could significantly affect the pharmacokinetic parameters of notoginsenosides and increase the absorption and systemic exposure of Rb₁, Rg₁, and NR₁ in human plasma by ~1.85–3.71 times.     

镧、锆改性的氧化铝载体对钯催化氧化甲烷活性的影响

研究了镧、锆改性的氧化铝载体对钯催化氧化甲烷活性的影响,结果表明,nLa∶nZr=2∶1时,所得的改性氧化铝载体在1 050℃焙烧后具有较大的比表面积和孔容;nLa∶nZr=1∶2时,所得的改性氧化铝载体经过1 050℃焙烧后具有较大的储氧量;Pd/Al2O3高温下的烧结情况较为严重,而加入La与Zr后烧结现象得到明显改善;改性后的Pd/La0.13Zr0.065-Al对甲烷氧化的活性最高,Pd/La0.065Zr0.13-Al次之,未改性的Pd/Al2O3活性最低.     

Gas chromatographic-mass spectrometric assessment of the pharmacokinetics of amineptine and its main metabolite in volunteers with liver impairment

A pharmacokinetic study of amineptine (Survector) and its C5 metabolite, resulting from a beta-oxidation of the heptanoic acid side-chain, was undertaken with ten human volunteers, who received a single 100-mg tablet of amineptine orally. They were affected with liver impairment in order to determine if this situation would alter greatly the pharmacokinetic parameters. The internal standard was the octanoic acid homologue. Analyses were carried out by gas chromatography (GC) and GC-mass spectrometry using TMS ester derivatives. Plasma samples were extracted using a C18 reversed-phase cartridge at pH 4.0. Mass fragmentographic measurements on the plasma samples were performed on the m/z ions (M + H)+ and (base peak)+ using ammonia chemical ionization. The global evaluation of precision was good and the coherence between the two modes of measurements, (base peak)+ and (M + H)+ ions, gave a regression factor r close to unity. For amineptine the total body clearance and mean residence time were accurate and precise with eight volunteers, but only four volunteers showed such coherent data for the slope of the elimination curve, beta, and half-life. However, the beta value, half-life and mean residence time of the C5 metabolite were accurate and precise with seven, eight and ten volunteers, respectively. It is concluded that the drug was still detoxified at normal levels.     

Simultaneous optimization of extraction and antioxidant activity from Blumea laciniata and the protective effect on Hela cells against oxidative damage

Blumea was the resource for medicine such as l-borneol showing a great economic value. Interestingly, Blumea laciniata was widely used as a folk medicine in south of China and Asia. But the chemical compounds and specific pharmacological activity were rarely reported. Therefore, in this present work, the chemical components from B. laciniata were determined and the antioxidant ability on scavenging radicals and the protection on Hela cells against H₂O₂ were evaluated. The results showed the antioxidant ability was associated with the presence of polyphenols via response surface method. Additionally, chlorogenic acid, isoorientin, rutin, luteolin-4′-O-glucoside and cinnamic acid were firstly identified in B. laciniata. Moreover, the extract from B. laciniata (EBL) showed a strong antioxidant on clearing DPPH and ABTS free radicals with a lower EC₅₀. Besides, EBL showed no toxicity on Hela cells and even could protect cells from H₂O₂ induced damage by sharply reducing the excessive reactive oxygen species, improving the mitochondrial membrane potential and then decreasing the generation of cell apoptosis. These outcomes could provide a promising understanding on the potential antioxidant.     

Encapsulation of single enzyme in nanogel with enhanced biocatalytic activity and stability

Single protein encapsulated into nanogels with uniformed size and controllable shell thickness were prepared by surface acryloylation of a protein molecule followed by aqueous in situ polymerization. Compared to its free counterpart, the encapsulated protein exhibits similar biocatalytic behavior and significantly improved stability at high temperature and in the presence of organic solvent.     

The effect of the “Inert” support on relative photocatalytic activity in the oxidative decomposition of alcohols on irradiated titanium dioxide composites

Reduced quantum efficiencies for the photocatalytic degradation of cyclohexanol, cyclododecanol, 2-hexanol, and benzyl alcohol are observed on TiO₂ particles included within small pore zeolitic supports suspended in acetonitrile. A modest reduction in photocatalytic activity observed with TiO₂ included within large pore zeolites and pillared clays is attributed to reflective and refractive losses of incident light. No appreciable substrate size selectivity could be observed in this series of supported TiO₂ composites. TS-1, a titanium-containing zeolite with Ti in tetrahedral lattice sites, was photoactive, although ETS-10, a titanium-containing zeolite with Ti in octahedral lattice sites, was less so. The low quantum yield residual photoactivity observed with these alcoholic substrates on unmodified zeolites may derive from surface charge transfer complexation, as suggested by diffuse reflectance absorption measurements.     

Li/MgO catalysts. III. Effect of precursor salts on the catalytic activity in methane oxidative coupling

Oxidative coupling of methane has been studied on Li/MgO catalysts prepared from three different MgO precursors and from lithium carbonate or nitrate. In samples prepared from Li₂CO₃, the persistence of this on the support surface favors formation of carbon oxides.

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Li/MgO, MgO . , Li₂CO₃, .

     

Plasmonic Ag/AgBr nanohybrid: synergistic effect of SPR with photographic sensitivity for enhanced photocatalytic activity and stability

A plasmonic Ag/AgBr nanohybrid has been synthesized by in situ thermal reduction of AgBr nanoparticles in polyols. This directly converted Ag/AgBr shows significant absorption over the full visible spectrum. The enhanced light absorption in the spectral region of 450 nm to 800 nm was due to the plasmonic nanosized Ag grown on the surface of AgBr nanoparticles with mixed morphologies and increased sizes. Under visible light irradiation, the plasmonic Ag/AgBr exhibits high activity and stability for the photodegradation of organic pollutants, e.g. methylene blue. The contribution of the SPR and its synergistic effect with the photosensitive AgBr in the photocatalytic activity were verified. Based on the plasmon-mediated charge injection and the band structure of the metal-semiconductor heterojunction, a mechanism of the plasmon synergistically enhanced photocatalytic process was proposed.     

Thermodynamics of electrolytes. X. Enthalpy and the effect of temperature on the activity coefficients

Heat of dilution and of solution data are fitted to the form of equation corresponding to that used successfully for activity and osmotic coefficients over a wide range of concentrations. The resulting parameters give the change with temperature of the activity and osmotic coefficients. Results are reported for 84 electrolytes of 1-1, 2-1, 3-1, and 2-2 valence types.     

Chlorination reactions of ephedrines revisited. Stereochemistry and functional groups effect on the reaction mechanisms

The stereochemistry of the chlorination reactions with SOCl₂ of free ephedrine and pseudoephedrine and their hydrochlorides, oxamides and sulfonamides was analyzed. Chlorination of free and hydrochloride erythro isomers occurs with 100% inversion of configuration at C-1 (S_N2 mechanism). Chlorination of oxamides and sulfonamides of erythro isomers occurs with retention of the configuration at C-1, (S_Ni mechanism). Chlorination reactions in all threo isomers and derivatives hydrochlorides, oxamides or sulfonamides gave the same ratio of erythro (40%) and threo isomers (60%) (S_N1 mechanism). Treatment of the isomeric mixture of the chlorodeoxyephedrine and chlorodeoxypseudoephedrine hydrochloride in DMSO with HCl changes the isomeric ratio, increasing the erythro isomer content (65%). Using the erythro ethanolamines it is possible to arrive stereoselectively at the erythro chloroamines if the compound is previously tosylated or converted to the amide, or to the threo chloroamines if the compound is directly chlorinated with SOCl₂.     

Defect-rich and ultrathin nitrogen-doped carbon nanosheets with enhanced peroxidase-like activity for the detection of urease activity and fluoride ion

Although carbon nanozymes have attracted great interest due to their good biocompatibility, low cost,and high stability, designing high-active carbon nanozymes still faces great challenges. Herein, ultrathin nitrogen-doped carbon nanosheets with rich defects(d-NC) were prepared through a high-temperature annealing process, using potassium chloride and ammonium chloride as templates. Owing to the large specific surface area, rich defects and the high exposure of active sites, the proposed d-NC na...     

On the effect of stress on oxidative destruction of polymers. The action of ozone on polyolefines

A promoting effect of tensile stress has been revealed for the rate of oxidation of high- and low-density polyethylene and isotactic polypropylene films with ozone. The degree of oxidation and the presence of overstressed bonds on the sample surface were detected by infrared spectroscopy in transmitted and reflected light. Overstressed bonds on the surface were set up by using various quenching regimes and in the bulk by applying a load. The stress-induced changes in segmental mobility of macromolecules were studied by ESR spectroscopy using a stable nitroxyl radical-probe. Supramolecular structure of the samples was investigated by using birefringence, polarized infrared spectroscopy and X-ray diffraction methods. A substantial difference has been found between the stress and the strain dependences of the rate of oxidation of the polymer films with ozone.     

Thermodynamics of electrolyte mixtures. Enthalpy and the effect of temperature on the activity coefficient

The temperature dependence of the parameters for symmetrical mixing of ions of the same sign in the virial-coefficient (Pitzer) system are evaluated from literature data on heats of mixing in the presence of a common ion for 20 systems. The higher-order limiting law for symmetrical mixing is used in the form of an expression for the ionic strength dependence of the binary mixing parameter. Heats of mixing of the MX-NYtype (without common ion) are calculated for eight systems from these parameters and found to be in excellent agreement with experimental values. Since pure-electrolyte parameters are required for the non-common-ion calculations, these are calculated as needed from recently published data.     

Enzymatic detoxification of jojoba meal and effect of the resulting meal on food intake in rats

When defatted jojoba meal is used as animal food, it causes food-intake reduction and growth retardation. Detoxification procedures by chemical, microbiological, and solvent extraction methods are reported by several authors. Here we report a successful detoxification of jojoba meal using enzymes. We establish reaction conditions that yield new meal which has the same nutritional qualities in proteins as the original meal. The enzymatic reaction gives rise to one major compound to which the structure of an amide is assigned on the basis of IR, 1H and 13C NMR spectra. The effect of the resulting jojoba meal on the food intake in rats is checked. In contrast, the detoxified meal containing the amide derivatives shows no toxicological activity since rats receiving oral administration of the obtained meal show normal growth. Thus, it is expected that this meal could be used as an animal feed ingredient.     

A longitudinal study of ethanol and acetaldehyde in the exhaled breath of healthy volunteers using selected-ion flow-tube mass spectrometry

Selected-ion flow-tube mass spectrometry (SIFT-MS) has been used to monitor the volatile compounds in the exhaled breath of 30 volunteers (19 male, 11 female) over a 6-month period. Volunteers provided breath samples each week between 8:45 and 13:00 (before lunch), and the concentrations of several trace compounds were obtained. In this paper the focus is on ethanol and acetaldehyde, which were simultaneously quantified by SIFT-MS using H3O+ precursor ions. The mean ethanol level for all samples was 196 parts-per-billion (ppb) with a standard deviation of 244 ppb, and the range of values for breath samples analysed is 0 to 1663 ppb. The mean acetaldehyde level for all samples was 24 ppb with a standard deviation of 17 ppb, and the range of values for breath samples analysed is 0 to 104 ppb. Background (ambient air) levels of ethanol were around 50 ppb, whereas any background acetaldehyde was usually undetectable. Increased ethanol levels were observed if sweet drink/food had been consumed within the 2 h prior to providing the breath samples, but no increase was apparent when alcohol had been consumed the previous evening. The measured endogenous breath ethanol and acetaldehyde levels were not correlated. These data relating to healthy individuals are a prelude to using breath analysis for clinical diagnosis, for example, the recognition of bacterial overload in the gut (ethanol) or the possibly of detecting tumours in the body (acetaldehyde).