The use of IBH-5 decreased the k
deg
values and increased the half-life of the compounds PNZ, TCP, Cpd I and Cpd II with k
deg
values of 1.10 × 10
−4
s
− 1
(t
1/2
=
115 min), 4 × 10
−5
s
−1
(t
1/2
...= 289 min), 4 × 10
−5
s
−1
(t
1/2
= 289 min), and 3 × 10
−5
s
−1
(t
1/2
= 385 min) respectively, compared to k
deg
values of 1.25 × 10
−2
s
−1
(t
1/2
= 0.9 min), 1.1 × 10
−4
s
−1
(t
1/2
= 105 min), 1.0 × 10
−3
s
−1
(t
1/2
= 11.5 min) and 4.5 × 10
−4
s
−1
(t
1/2
= 26 min
)
in FBH
The use of lower temperature (4 °C) for the determination of f
u,brain
in this study is not successful due to the instability of the compounds during longer equilibration times required at lower temperatures.
The f
u,brain
values for a set of 15 CNS drugs determined in FBH and IBH-5 using HT-dialysis were similar and are consistent with the literature values. The use of IBH-5 led to the determination of f
u,brain
for unstable compounds that could not be determined by other methods.
The use of IBH-5 is an easy and convenient method to determine the f
u,brain
of unstable compounds in FBH during drug discovery and development.
Mixing mass transfer process of the gas-liquid-solid multiphase flow is a crucial manufacturing technology in some industrial applications, such as the material mixing of the high-end chemical ...industry and the lithium electric homogenate dispersion of the new energy. The complicated multiphase mass transfer mechanism is a fluid-structure coupling mechanic problem with intensive shear and nonlinear characteristics, making the flow field face challenges in regulating. Here, a fluid-structure coupling-based mechanic model is set up based on the coupled volume-of-fluid and discrete element model (VOF-DEM) to explore the multiphase mixing mass transfer mechanism. A porous interphase optimization and dynamic mesh technique are proposed to reveal flow pattern regularities under the inflating disturbance. Then, an experimental observation platform is built, and the fractal geometric analysis method is utilized to reveal the chaotic evolution property. Research results illustrate that the presented modelling method can well obtain the multiphase mixing mass transfer regularities. The appropriate inflation rate can improve particle suspension effects, and promote interphase mixing mass transfer, and achieve the dynamic control of the multiphase flow filed. The results can provide a valuable reference for mass transfer and flow pattern identification and support technical support for lithium electric homogenate mixing and chemical extraction.
•VOF-DEM coupling-based multiphase flows mechanic modeling method is presented.•A porous interphase optimization method and dynamic mesh technique is proposed.•Mixing mass transfer mechanism and particle flow pattern regularities are revealed.•The chaotic evolution property with the fractal geometric analysis method is discussed.
Drone brood is a collection of developing individuals (larvae, prepupae and pupae) of drones - males of a bee colony. Drone brood is used to produce a homogenate, which is stabilized in one way or ...another to achieve optimal preservation of biologically active substances. Interest in drone brood as a rich source of macro- and micronutrients is steadily increasing. The purpose of this review is to summarize the collected data on the use of drone brood in rational nutrition and apitherapy. The indicators of the quality and safety of drone brood are reviewed, the requirements of regulatory documents for products based on it are given. The necessity of strict adherence to the storage conditions of the drone brood homogenate is shown, in case of violation of which there is a rapid deterioration of the homogenate. This necessitates stabilization of the drone brood, which makes it possible to preserve its properties with lower requirements for storage conditions. The groups of nutrients that make up the drone brood and determine its biological activity and directions of application are given. Among them are lipids, including phospholipids and unique decenoic acids, proteins, peptides and amino acids, substances containing sulfhydryl groups, flavonoid and other phenolic compounds, carbohydrates, steroid substances, including hormones and hormone-like compounds, mineral elements. Products based on drone brood and biological effects of their use are described: actoprotective, anabolic, immunomodulatory, endocrinotropic, neurotropic, nutritional and cosmetic. The analyzed data indicate the high relevance of the further introduction of drone brood preparations into nutritional and apitherapeutic practice, which will serve as a tool for correcting the diet of a modern person suffering from a disease of civilization, largely associated with a violation of the ratio and amount of nutrients in the diet.
Preeclampsia (PE) is a multisystemic disorder characterized by abnormal placentation. Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged organelles, and it seems ...to be essential for cell survival during stress, hypoxia, and for implantation and development of the placenta. p62/SQSTM1 is an autophagy marker that not only binds proteins destined for elimination but is also constitutively degraded by this mechanism. Considering that the placenta plays an important role in the pathogenesis of PE, the present study aimed to evaluate the gene and protein expression of p62/SQSTM1 in placentas from pregnant women with PE. Placental tissues from 20 women with PE classified into three groups according to gestational age, 27–31 weeks (n = 8); 32–36 weeks (n = 6); 37–39 weeks (n = 6), and 20 normotensives (NT) pregnant women were collected and employed for p62/SQSTM1 expression by quantitative polymerase chain reaction (qPCR), immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) techniques. p62/SQSTM1 mRNA levels were significantly lower, while protein expression was significantly higher in the placenta of pregnant women with PE than in NT pregnant women, and these results remained similar after separating the groups by gestational age. In conclusion, the results suggest that there is a reduction of autophagic activity in pregnant women with PE. Studies involving cross-talk between autophagy, inflammasomes, nuclear transcription factor (NF-κB) activation pathways, and aggregation of protein in the placenta from women with PE might help to better understand the pathogenesis of this important obstetric pathology.
In this study, 10 different natural surfactants were compared as additives for the simultaneous extraction of lipophilic regaloside A and water-soluble polysaccharides from tiger lily (Lilium ...lancifolium Thunb.) bulbs by homogenate-ultrasound-synergistic extraction. Four significant factors that affect the yields of regaloside A and polysaccharides, including homogenate speed, ultrasound irradiation power, reaction temperature and ultrasound irradiation time, were screened by single-factor experiments and Plackett-Burman design and then optimized using Doehlert matrix design combined with a desirability function. The optimal extraction process conditions were obtained as follows: APG06 (n-hexyl glucoside) surfactant concentration of 0.6%, homogenate speed of 20000 r/min, homogenate time of 6 min, liquidsolid ratio of 20 mL/g, ultrasound irradiation power of 300 W, ultrasound irradiation time of 52 min, reaction temperature of 62.8 °C, and buffer and cavitation times of 1.5 s and 2.0 s, respectively. Under the optimal extraction conditions, regaloside A and polysaccharides yields of 2.797 ± 0.084 mg/g and 0.493 ± 0.016 g/g are obtained with relative standard deviations of 3.00% and 3.50%, respectively. The results of the method validation and comparison with the conventional method show that homogenate-ultrasound-synergistic extraction with APG06 as an additive is a green, efficient and energy-saving extraction method. Compared with the traditional extraction method, HUSE with APG06 as an additive is an effective method to extract regaloside A and polysaccharides from L. lancifolium bulbs. This study provides a reference for the development of green low carbon natural product extraction process.
•Use homogenate-ultrasound-synergistic extraction of regaloside A and polysaccharides.•Alkyl polyglucoside was first added to extract phenolic acid glycerides (regaloside A).•0.6% n-hexyl glucoside was chosen as the extraction additive.•Use combination of Plackett-Burman design and Doehlert matrix design.•Alkyl polyglucoside has obvious advantages on yield and safety compared with ethanol.
•Drone brood homogenate (DBH) was tested for antioxidant properties.•Vitamin C, coenzyme Q10, α-tocopherol, and retinol in DBH samples was assessed.•Condition of bees and apiary environment affect ...the amount of lipophilic antioxidants.•DBH is a rich source of coenzyme Q10, α-tocopherol, vitamin C, and phenols.
The subject of the present research is the evaluation of health-promoting properties caused by the presence of some vitamins as well as the antioxidative potential of the honeybee drone brood homogenate (DBH). The study used 139 homogenate samples obtained from various apiaries and collected over 3 years, three times during each beekeeping season. Samples differed in terms of varroa infestation, stage of brood development, location of the apiary, and the degree of environmental contamination. The content of ascorbic acid, α-tocopherol, all-trans-retinol, and coenzyme Q10 in the tested samples was determined through the application of HPLC/DAD/UV and LC/QQQ/MS methods. The antioxidant potential of samples was assessed using the Folin-Ciocalteu and DPPH methods.
PF-03715455, an inhaled p38 α/β mitogen-activated protein (MAP) kinase inhibitor (MAPK), has being identified as an agent with potential therapeutic action on lung diseases such as COPD and severe ...asthma. However, little is known about this MAPKs local and systemic pharmacokinetics after pulmonary delivery. Consequently, the aim of the present work was to develop and validate a method of extraction and quantification of PF-03715455 in rat plasma and lung tissues and to determine the drug biodistribution in plasma and respiratory tissues after intratracheal administration of the drug solution in rats. The method was validated in rat plasma samples and resulted selective and linear in the concentration range of 0.08−100 ng/ml. Then a partial validation was carried out on samples obtained by the extraction and quantification of PF-03715455 from rat lung homogenate in order to ascertain method applicability on lung tissue samples. The intratracheal administration of drug in solution to rats evidenced a rapid elimination from the plasma, while on the contrary a prolonged residence time in lung tissue was evidenced.
In conclusion, a linear, accurate, precise and reproducible method has been developed and validated according to FDA and EMA guidelines to quantify plasmatic and tissue-associated concentrations of PF-03715455 in order to investigate this compound in pharmacokinetics pre-clinical studies in rats. The administration of drug solution evidenced a prolonged permanence of the drug in the lungs that could be related to a slow absorption/poor permeability of the drug across airways epithelia.
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•Fungal suspension homogenate of Alternaria panax promoted ginsenoside accumulation of adventitious roots of Panax ginseng.•Ginsenoside content reached the maximum when adventitious roots were ...treated with 200 mg/L fungal elicitor for 8 days.•Fungal elicitor induced burst of nitric oxide, putrescine, and hydrogen peroxide.•Nitric oxide, putrescine, and hydrogen peroxide involved in fungal elicitor-induced ginsenoside synthesis.
The adventitious root (AR) culture is an effective approach for mass and rapid production of Panax ginseng C. A. Mey ginsenosides. During AR culture, methyl jasmonate (MeJA) is widely used to increase ginsenoside content. However, its high price is a burden to producers. To replace MeJA using a cheaper elicitor, the present study prepared the fungal suspension homogenate using the pathogenic fungi (Alternaria panax Whetz.) of field-grown ginseng and the homogenate was used as a fungal elicitor. Ginsenoside accumulation was affected by the concentrations and elicitation times of fungal elicitor. The maximum content (29.6 mg/g dry weight) was determined when 30-day-old bioreactor cultured-ARs were treated with 200 mg/L of the fungal elicitor for 8 days, thereby indicating a desirable elicitation effect. Furthermore, the present study investigated whether nitric oxide (NO), polyamines (PAs), and hydrogen peroxide (H2O2) were involved in regulating ginsenoside synthesis to elucidate the mechanism underlying the fungal elicitor’s effect. The fungal elicitor-induced NO, putrescine (Put, a kind of PAs), and H2O2 burst, which peaked at 12 h for NO or Put and at 24 h for H2O2. However, the increased contents of these three molecules were decreased by the inhibitors. Subsequently, the reduction of ginsenoside content was determined. The NO, PAs, and H2O2 probably acted as signaling molecules that are involved in regulation of fungal elicitor-induced ginsenoside synthesis during P. ginseng AR culture.
Background The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and ...maternal marijuana use as defined by the presence of tetrahydrocannabinol in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. Objective Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. Study Design We conducted secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of tetrahydrocannabinol in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. tetrahydrocannabinol cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, χ2 , and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. Results Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by tetrahydrocannabinol in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56–2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18–5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40–6.91). Conclusion Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.
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