Progress on the mechanism of n-hexane induced toxic effects in vitro and in vivo / 中华劳动卫生职业病杂志

Hexane is a widely used organic solvent in industry, and chronic hexane poisoning is the main occupational toxic lesion in China. In particular, axonal and myelin lesions in the distal thick fibers of the peripheral nervous system may be caused by 2, 5-hexanedione (2, 5-HD), an intermediate metabolite of n-hexane in humans. Hexane has toxic effects not only on the nervous system but also on the liver, kidneys, and reproductive organs. In this paper, we review the progress of research on the mechanism of n-hexane toxic neuropathy.

Application of high-speed counter current chromatography in extraction and separation of alkaloids in natural products / 中国中药杂志

Alkaloids, widespread in plants, have a series of pharmacological activities and have been widely used to treat various diseases. Because alkaloids are usually presented in multicomponent mixtures and are deeply low in content, they are very difficult to extract and separate by traditional methods. High-speed counter current chromatography(HSCCC) is a kind of liquid-liquid chromatography without solid support phase, which has the advantages of large injection volume, low cost, and no irreversible adsorption. Compared with the traditional methods of extraction and separation of alkaloids, HSCCC can ensure the separation of many different alkaloids at one time, with a high recovery and large amount. In this paper, the advantages and disadvantages of HSCCC compared with traditional separation methods were discussed and the solvent system and elution mode of HSCCC used to separate alkaloids in recent years were summarized by referring to the relevant literature to provide some references for the separation of alkaloids by HSCCC.

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Influence of solvent choice and operating conditions on Chlorzoxazone crystal shape and size

Abstract Solubility of pharmaceutical drugs in organic solvents is one of the important parameters to understand the equilibrium concentration of solute-solvent, which helps optimize and design crystallization conditions to obtain the desired product crystals. In the present study, Chlorzoxazone (CHZ) is used as a model pharmaceutical compound to investigate the equilibrium solubility, the influence of solvent and the operating conditions on the shape, and the size distribution. The solubility of CHZ is determined in organic solvents like Isopropanol, Ethanol, and 2-Ethoxyethylacetate, Ethylacetate and Ethyllactate using shake flask method from -5ºC to 60ºC. The solubility of CHZ in these solvents shows an increasing trend as the temperature increases in the following order: ethyllactate + water (0.5+0.5) < ethylacetate < isopropanol < ethanol < 2-ethoxyethylacetate < ethyllactate + water (0.75+0.25). The solvents, isopropanol, ethanol, and ethyl lactate, produce needle-shaped crystals, while 2-ethoxyethylacetate and ethyl acetate tend to produce plate shaped crystals. CHZ crystals obtained from 2-ethoxyethylacetate tend to have plate shaped crystals with a lower aspect ratio and are selected for batch cooling crystallization experiments performed at different cooling rates, and agitation. It is found that the agitation at 300 rpm and the cooling rate 0.2ºC/min produce more uniform crystal size distribution

Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Formulation of stomach-specific floating microparticles of nizatidine and their radiographic evaluation

Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 µ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer

Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Evaluating awareness of health risks and self-reported symptoms among nail technicians in Johannesburg, South Africa ­ a pilot study

Background: The professional nailcare industry is expanding rapidly in South Africa. Nail treatment involves the use of solvents and acrylates. Exposure to these chemicals is associated with skin, eye, and respiratory tract irritation, and neurological and reproductive health effects. Objective: To test the feasibility of conducting a study on formal and informal nail technicians, which included testing a self-developed questionnaire, and to collect preliminary data about their knowledge and awareness of health risks associated with exposure to chemicals in nail products, and associated symptoms. Methods: A self-developed questionnaire was administered to 10 formal and 10 informal nail technicians working in conveniently selected nail salons in Johannesburg. Work practices and exposure control measures were observed. Demographic characteristics, working conditions, awareness of health risks, and self-reported symptoms in the two groups are presented as frequency distributions. Results: Poor phrasing was identified in some of the questions. Participants provided the correct terminology to describe nail services. The revised questionnaire comprised 39 questions. Seven of the informal nail technicians were male while all the formal nail technicians were female. Informal nail technicians worked longer hours per week than formal nail technicians (median of 61.5 and 46.5 hours, respectively) and reported more symptoms. Informal nail technicians used a wider range of nail products than formal nail technicians and used some unknown brands. Although all participants indicated that they were aware of health risks associated with nail products, only four of the formal nail technicians and one informal nail technician reported receiving training (although not specific to health and safety). Informal nail technicians reported using personal protective equipment (PPE); however, this practice was inconsistent, and they used the incorrect PPE. Conclusions: We showed that conducting a larger study in nail technicians is feasible. The questionnaire was revised to include more information about the chemical content of nail products, a wider range of symptoms, the frequency of their occurrence, and the work-relatedness nature of the self-reported symptoms. A knowledge gap was identified among nail technicians relating to risks associated with exposure to chemicals in nail products. The questionnaire was refined to assess more accurately nail technicians' understanding of exposure and awareness of health risks associated with chemicals in nail products.

The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice / 中华劳动卫生职业病杂志

Objective: To detect the expression levels of M1-type polarization and autophagy-related indicators in the liver of trichloroethylene (TCE) -sensitized mice, and to explore the role of liver tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1) in regulating M1-type Kupffer cells autophagy in liver injury in TCE-sensitized mice. Methods: In November 2019, according to simple random grouping, 45 SPF grade BALB/c female mice (6-8 weeks old) were divided into 4 groups: blank control group (n=5) , solvent control group (n=5) , TCE treatment group (n=18) , TCE+R7050 (inhibitor) treatment group (n=17) . Transdermally sensitized mice, 24 h after the last challenge, the mice were divided into TCE sensitized group and TCE non-sensitized group according to the skin reaction score. The livers of mice were harvested, and the pathological changes of the livers were observed under light and electron microscopes. Western blotting was used to detect the expressions of TNF-α, TNFR1 and autophagy-related indexes. The expression of inducible nitric oxide synthase (iNOS) , a marker of M1-type Kupffer cells, was detected by immunohistochemistry, and the occurrence of autophagy in M1-type Kupffer cells was detected by immunofluorescence double-labeling method. Results: The sensitization rate of TCE treatment group was 38.9% (7/18) , and TCE+R7050 treatment group was 35.3% (6/17) , with no significant difference between the two groups (P=1.000) . Compared with the blank control group, mice in the TCE sensitized group had abnormal liver ocytes, obvious liver injury, reduced mitochondria and broken endoplasmic reticulum. Western blotting results showed that the expressions of TNF-α and TNFR1 protein in the liver of the mice in the TCE sensitized group increased, the expression of iNOS protein in M1-type Kupffer cells increased, and the expressions of autophagic microtubule-associated protein 1 light-chain 3 (LC3B) and Beclin1 protein were decreased (P<0.05) . The results of immunohistochemistry showed that iNOS was not significantly expressed in the blank control group and solvent control group, and a small amount of expression was found in the TCE non-sensitized group, the positive staining area was obvious in TCE sensitized group, and the expression of iNOS was significantly increased (P<0.05) . Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. Conclusion: TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.

The role of ROS/TXNIP/NLRP3 pathway in the skin injury of trichloroethylene sensitized mice / 中华劳动卫生职业病杂志

Objective: To explore the mechanism of reactive oxygen species/thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor 3 (ROS/TXNIP/NLRP3) pathway in the skin injury of trichloroethylene (TCE) sensitized mice. Methods: In August 2020, 40 female BALB/c mice were randomly divided into control group (n=5) , solvent control group (n=5) , TCE treatment group (n=15) and TCE+(2-(2, 2, 6, 6-Tetrameyhylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito TEMPO) treatment group (n=15) . The TCE sensitization model was established. Mice in the TCE treatment group and TCE+Mito TEMPO treatment group were divided into the sensitized positive group and the sensitized negative group according to the skin erythema and edema reactions on the back of the mice 24 h after the last stimulation. The mice were sacrificed 72 h after the last stimulation, the back skin of the mice was taken, and the skin lesions were observed. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3, and the Western Blot was performed to detect the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) , cysteinyl aspartate specific proteinase 1 (Caspase 1) , Interleukin-1β (IL-1β) and TXNIP proteins in the skin of the mice, the reactive oxygen species (ROS) kit was used to detect the level of intracellular ROS in the back skin tissue. Results: The sensitization rates of TCE treatment group and TCE+Mito TEMPO treatment group were 40.0% (6/15) and 33.3% (5/15) , respectively, and there was no significant difference between the two groups (P>0.05) . The back skin of the mice in the TCE sensitized positive group was thickened and infiltrated by a large number of inflammatory cells. The number of mitochondria in the epidermis cells was significantly reduced, the mitochondrial crest disappeared and vacuolar degeneration occurred. TCE+Mito TEMPO sensitized positive group had less damage, more mitochondria and relatively normal cell structure. Compared with the solvent control group and corresponding sensitized negative groups, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE sensitized positive group and TCE+Mito TEMPO sensitized positive group were significantly increased (P<0.05) . Compared with TCE sensitized positive group, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE+Mito TEMPO sensitized positive group were significantly decreased (P<0.05) . Conclusion: ROS/TXNIP/NLRP3 pathway was activated and then encouraged the release of IL-1β, finally aggravated the TCE-induced skin injury.

Pirfenidone alleviates urethral stricture following urethral injury in rats by suppressing TGF-β1 signaling and inflammatory response / 南方医科大学学报

OBJECTIVE@#To investigate the effect of pirfenidone for reducing urethral stricture following urethral injury in rats and explore the possible mechanism.@*METHODS@#Thirty male SD rats were randomly assigned into negative control group, positive control group and pirfenidone group (n=10). In pirfenidone and positive control groups, the rats were subjected to incision of the posterior urethral cavernous body followed by daily intraperitoneal injection of pirfenidone (100 mg/kg) and an equivalent volume of solvent, respectively. The rats in the negative control group were given intraperitoneal injections of solvent without urethral injury. At two weeks after modeling, retrograde urethrography was performed for observing urethral stricture, and the injured urethral tissues were harvested for HE staining, Masson staining, immunohistochemical staining and Western blotting for detecting the protein expressions of α-SMA and TGF-β1. The mRNA expressions of the inflammatory factors TNF-α, IL-6, and IL-1β were detected using qRT-PCR.@*RESULTS@#The body weight of the rats in pirfenidone group was significantly decreased compared with that in the other two groups (P < 0.05). Retrograde urethrography showed significant narrowing of the urethra in the positive control group but not in the pirfenidone group. HE staining of the injured urethral tissues showed obvious proliferation of urethral epithelial cells with narrow urethral cavity and increased inflammatory cells in positive control group. The pathological findings of the urethra were similar between pirfenidone group and the negative control group. Masson staining revealed obviously reduced collagen fibers and regular arrangement of the fibers in pirfenidone group as compared to the positive control group. Compared with those in the negative control group, the expressions of α-SMA and TGF-β1 were significantly increased in the positive control group, and pirfenidone treatment significantly inhibited their expressions (P < 0.05 or 0.01). Pirfenidone also significantly inhibited the mRNA expressions of TNF-α, IL-6, and IL-1β in the injured urethral tissue (P < 0.05 or 0.01).@*CONCLUSION@#Pirfenidone can prevent urethral fibrosis and stricture after urethral injury possibly by inhibiting the TGF-β1 pathway and inflammatory response.

Improving the thermal stability of Proteus mirabilis lipase based on multiple computational design strategies / 生物工程学报

Proteus mirabilis lipase (PML) features tolerance to organic solvents and great potential for biodiesel synthesis. However, the thermal stability of the enzyme needs to be improved before it can be used industrially. Various computational design strategies are emerging methods for the modification of enzyme thermal stability. In this paper, the complementary algorithm-based ABACUS, PROSS, and FoldX were employed for positive selection of PML mutations, and their pairwise intersections were further subjected to negative selection by PSSM and GREMLIN to narrow the mutation library. Thereby, 18 potential single-point mutants were screened out. According to experimental verification, 7 mutants had melting temperature (Tm) improved, and the ΔTm of K208G and G206D was the highest, which was 3.75 ℃ and 3.21 ℃, respectively. Five mutants with activity higher than the wild type (WT) were selected for combination by greedy accumulation. Finally, the Tm of the five-point combination mutant M10 increased by 10.63 ℃, and the relative activity was 140% that of the WT. K208G and G206D exhibited certain epistasis during the combination, which made a major contribution to the improvement of the thermal stability of M10. Molecular dynamics simulation indicated that new forces were generated at and around the mutation sites, and the rearrangement of forces near G206D/K208G might stabilize the Ca2+ binding site which played a key role in the stabilization of PML. This study provides an efficient and user-friendly computational design scheme for the thermal stability modification of natural enzymes and lays a foundation for the modification of PML and the expansion of its industrial applications.

Progress and prospect of application of traditional Chinese medicine fingerprint (specific chromatogram) in Chinese Pharmacopoeia (2010-2020) / 南方医科大学学报

The Chinese Pharmacopoeia began to apply fingerprints (specific chromatogram) to quality control of traditional Chinese medicine in its 2010 edition, and in its 2015 and 2020 editions, new fingerprints (specific chromatogram) were added for improvement of the Pharmacopoeia-based national standards for drugs. This review analyzes the traditional Chinese medicine fingerprints (specific chromatogram) in Chinese Pharmacopoeia (2010-2020) in terms of the number of varieties listed, application of fingerprints (specific chromatogram), selection of evaluation method, determination method, the selection of extraction or preparation solvents of the test samples. With the expansion of the application of fingerprints (specific chromatogram), the evaluation indicators are constantly improving. The future development of the fingerprints (specific chromatogram) is also discussed in light of the selection of appropriate extraction or preparation solvents to obtain effective substances, which is the basis for the establishment of the fingerprints; multiple fingerprints for one drug based on different functional indications or basic sources, which expands the application of the fingerprints; addition of technical guidelines for traditional Chinese medicine fingerprints to standardize the use of the fingerprints; and the regular revision, update and application expansion of the fingerprints to ensure its essential role in quality control of traditional Chinese medicine.

Influência do uso da proantocianidina em um adesivo autocondicionante: avaliação da resistência de união / Influence of the use of proanthocyanidinin a self-etching adhesive: evaluation of bond strength / Influenciadel uso de proantocianidinaem um adesivo autograbante: evaluación de la fuerza de unión

Introdução:Os sistemas adesivos possibilitama execução de restaurações estéticas e minimamente invasivas, sendo, portanto,objeto de pesquisas para contornar os problemas que se apresentam no procedimento restaurador.Objetivo:Avaliar in vitroa resistência de união de um sistema adesivo autocondicionante, e deste modificado com soluções extrativas de semente de uva.Metodologia:Duas soluções extrativas foram preparadas comextrato de semente de uva em pó dissolvido em acetona e etanol. A partir delas e de umadesivo,seis sistemas adesivos autocondicionantes experimentais foram preparados, diferindo quanto aosolvente utilizado eàsproporções entre adesivo puro e solução extrativa(7,5%, 15% e 30%). Setenta incisivos bovinos hígidos tiveram as raízes removidas com disco de carborundum e as faces vestibulares desgastadas comlixas d'água de granulação 120, 240, 600 e 1200 sob refrigeração até expor a dentina superficial. Os dentes foram distribuídos aleatoriamenteem sete grupos distintos: Controle; A7,5; A15; A30; E7,5; E15; e E30, contendo 10 elementos cada. A aplicação dos adesivos foi executada de acordo com as recomendações do fabricante do adesivo controle. A restauração foi realizada com uma matriz de silicone com dimensões 2mm de altura e 4mm de diâmetro e inserido o material restaurador em incremento único e fotopolimerizado por 40s. Após três meses armazenados em água destilada, os espécimes foram submetidos ao teste de resistência de união. Foi empregado ométodo estatísticoTeste Paramétrico Anova 1 Fator e pós-teste de Tamhane (p<0,05). Resultados:Os grupos A7,5, E7,5 e E30 não apresentaram diferença em relação ao grupo Controle; A15 e A30 mostraram desempenho estatisticamente semelhante entre si; e E15 não apresentou diferença estatística em relação aos outros adesivos.Conclusões:A adição de proantocianidina teve efeitos diferentes,dependendodos solventes e das concentrações utilizadas, mas sem alterar significativamente o desempenho do adesivo (AU).

Introduction:Adhesive systems make it possible to perform aestheticand minimally invasive restorations, being the subject of research to circumvent the problems that arise in the restorative procedure.Objective:Evaluate in vitrothe bond strength of a self-etching adhesive system,and modified with extractive grape seed solutions. Methodology:Two extractive solutions were prepared with powdered grape seed extract dissolved in acetone and ethanol. From them and an adhesive, six experimental self-etching adhesive systems were prepared, differing in terms of the solvent used and the proportions between pure adhesive and extractive solution(7.5%, 15% and 30%). Seventy healthy bovine incisors had their roots removed with carborundum disc and the vestibular faces were worn with sandpaper with granulation water 120, 240, 600 and 1200 under refrigeration until the superficial dentin was exposed. The teeth were randomly assigned to seven different groups: Control; A7.5; A15; A30; E7.5; E15; and E30, containing 10 elements each. The application of the adhesives was carried out according to the recommendations of the manufacturer of the control adhesive. The restoration was performed with a silicone matrix with dimensions 2mm high and 4mm indiameter and the restorative material was inserted in a single increment and light cured for 40s. After three months stored in distilled water, the specimens were submitted to the bond strength test. The statistical method Parametric Test Anova 1 Factor and Tamhane post-test (p<0.05) were used. Results:Groups A7.5, E7.5 and E30 showed no difference in relation to the Control group; A15 and A30 showed a statistically similar performance; and E15 showed no statistical difference in relation to the other adhesives. Conclusions:The addition of proanthocyanidin had different effects, depending on the solvents and concentrations used, but without significantly altering the performance ofthe adhesive (AU).

Introducción: Sistemas adhesivos permiten realizar restauraciones estéticas y mínimamente invasivas, siendo objeto de investigación para sortear problemas que surgen en elprocedimiento restaurador. Objetivo: Evaluar in vitrola fuerza de unión de un sistema adhesivoautograbante y modificado con soluciones extractivas de semilla de uva. Metodología: Se prepararon dos soluciones extractivas con extracto de semilla de uva en polvo disuelto en acetona y etanol. A partir de ellos y de un adhesivo, se prepararon seis sistemas experimentales de adhesivos autograbantes, que se diferencian en cuanto al solvente utilizado y las proporciones entre adhesivo puro y solución extractiva (7,5%, 15% y 30%). Setenta incisivos bovinos sanos fueron removidos con un disco de carborundo y las caras vestibulares fueron usadas com lija de agua de granulación 120, 240, 600 y 1200 bajo refrigeración hasta que la dentina superficial quedo expuesta. Los dientes se asignaron aleatoriamente a siete grupos diferentes: Control; A7,5; A15; A30; E7,5; E15; y E30, que contiene 10 elementos cada uno. La aplicación de los adhesivos se realizó siguiendo las recomendaciones del fabricante del adhesivo de control. La restauración se realizó con matriz de silicona con 2mm de altura y 4mm de diámetro y el material restaurador se insertó en un solo incremento y se fotopolimerizó durante 40s. Tres meses después, almacenados em agua destilada, las muestras se sometieron a la prueba de resistencia de la unión. Se utilizó el método estadístico Prueba Paramétrica Factor Anova 1 y post-prueba de Tamhane (p<0,05). Resultados: Los grupos A7,5, E7,5 y E30 no mostraron diferencias em relación con el grupo Control; A15 y A30 mostraron un desempeño estadísticamente similar; y E15 no mostró diferencia estadística en relación con los otros adhesivos. Conclusiones: La adición de proantocianidina tuvo diferentes efectos, dependiendo de los disolventes y concentraciones utilizadas, pero sin alterar significativamente el rendimiento del adhesivo (AU).

Supramolecular Solvent Extraction-Gas Chromatography-Tandem Mass Spectrometry for Detection of Benzodiazepines in Urines / 法医学杂志

Objective To establish a method using supramolecular solvent and gas chromatography-tandem mass spectrometry （GC-MS/MS） to analyze 9 benzodiazepines in urines. Methods Urine samples containing 9 benzodiazepines reference substance were subjected to liquid-liquid extractions with supramolecular solvent, which consisted of tetrahydrofuran and 1-hexanol. The solvent layer was evaporated to dryness by stream of nitrogen. The residue was reconstituted with methanol, and GC-MS/MS analysis was performed on it. The way of data collection was multiple reaction monitoring （MRM） mode; internal standard method was employed for quantification. Results In urine samples, when the range of mass concentration was 1-100 ng/mL for diazepam, midazolam, flunitrazepam and clozapine, 5-100 ng/mL for lorazepam and alprazolam, 2-100 ng/mL for nitrazepam and clonazepam, and 0.2-100 ng/mL for estazolam, respectively, good linearities were obtained, correlation coefficients were 0.999 1-0.999 9, the lower limits of the quantifications ranged from 0.2 to 5 ng/mL, the extraction recovery rates were 81.12%-99.52%. The intra-day precision ［relative standard deviation （RSD）］ and accuracy （bias） were lower than 9.86% and 9.51%, respectively; the inter-day precision （RSD） and accuracy （bias） were lower than 8.74% and 9.98%, respectively. Nine drugs in urine samples showed good stability at ambient temperature and -20 ℃ within 15 days. The mass concentrations of alprazolam in urine samples obtained from 8 volunteers who took alprazolam tablets orally within 8-72 h after ingestions ranged from 6.54 to 88.28 ng/mL. Conclusion The supramolecular solvent extraction GC-MS/MS method for analysis of 9 benzodiazepines in urines provided by this study is simple, fast, accurate and sensitive, which can provide technical support for monitoring of poisoning by benzodiazepines for clinical treatment and judicial identification.

Difference of Chemical Bonds Between UDMA Bonding Agents with Ethanol Solvent and Acetone Solvent on Dentin Collagen

ABSTRACT Objective: To investigate the difference of chemical bonds between urethane dimethacrylate (UDMA) bonding agents with ethanol solvent and acetone solvent on dentin collagen. Material and Methods: This experimental comparison study used three groups: G1 (Control): UDMA and collagen; G2: UDMA, collagen and ethanol; and G3: UDMA, collagen and acetone. The groups were then pelleted and analysed with FTIR, then the peak value of carbonyl absorption band from each study group was calculated. The result of FTIR analysis and the peak of carbonyl absorption band (P) was calculated using the formula: P = (BC / AB) X 100; AB. BC is measured in centimeters. The study of chemical bond differences between ethanol-solvent UDMA agents compared with acetone-solvent on dentin collagen resulted in a graph of peak of carbonyl absorption bands of UDMA and dentin collagen groups. To determine the chemical bonds of UDMA from the top of the carbonyl ester absorption bands with wavenumber absorption in range 1700-1750 cm-1, the decreasing peak of the carbonyl absorption bands is assumed as more chemical bonds that formed. Data were analysed using Anova one way and Tukey HSD test. Results: There were significant differences between the three study groups (p<0.05). Conclusion: UDMA bonding agents' chemical bonds with acetone solvent are much higher than the chemical bonds between UDMA bonding agents with ethanol solvent on dentin collagen.

Application of design technology for preparing Lingzhu Powder particles based on solvent evaporation method / 中国中药杂志

Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.

Effect of alternative solvent evaporation techniques on mechanical properties of primer-adhesive mixtures / Efeito de técnicas alternativas utilizando evaporação de solvente nas propriedades mecânicas da mistura primer-adesivo

ABSTRACT This study evaluated the influence of the mode and time of solvent evaporation on the tensile strength (TS), flexural strength (FS) and elastic modulus (EM) of two adhesive systems: Scotchbond Multipurpose (SBMP) and Clearfil SE (CSEB). For this purpose, rectangular samples (2x1x7 mm) were prepared with 10 μL of primer and the solvents were evaporated with air spray at (23±1) ºC, (40±1) ºC and negative control (without spray). For each temperature, the times of 5, 20, 30, and 60 seconds were investigated. The statistical results showed that evaporation at 40±1ºC resulted in better EM for the two adhesives tested and all the evaporation times evaluated. However, there were no significant differences between the times and modes of evaporation for TS. The results of this study indicate that evaporation at a temperature of (40±1) °C could improve the elastic modulus of both adhesives tested, regardless of the evaporating time.

RESUMO Este estudo avaliou a influência do modo e do tempo de evaporação do solvente na resistência à tração (RT), resistência à flexão (RF) e módulo de elasticidade (MR) de dois sistemas adesivos: Scotchbond Multipurpose (SBMP) e Clearfil SE (CSEB). Para isso, amostras retangulares (2x1x7 mm) foram preparadas com 10 μL de primer e os solventes foram evaporados com aerossol a (23±1) ºC, (40±1) ºC e controle negativo (sem aerossol). Para cada temperatura, foram avaliados os tempos de 5, 20, 30 e 60 segundos. Os resultados estatísticos mostraram que a evaporação a (40±1) ºC resultou em melhor MR para os dois adesivos testados e todos os tempos de evaporação avaliados. No entanto, não houve diferenças significativas entre os tempos e modos de evaporação na RT. Os resultados deste estudo indicam que a evaporação a uma temperatura de (40±1) °C poderia melhorar o módulo de elasticidade de ambos os adesivos testados, independentemente do tempo de evaporação.

Evaluación de riesgo de cáncer en personas expuestas ocupacionalmente a solventes orgánicos / Cancer risk evaluation in individuals occupationally exposed to organic solvents

RESUMEN Objetivo Evaluar la frecuencia de micronúcleos (MN) e influencia de los polimorfismos en los genes del metabolismo GSTM1 y GSTT1 como biomarcadores de riesgo de cáncer en pintores de carros (n=152) con respecto a individuos no expuestos (n=152). Métodos Estudio Epidemiológico Molecular, tipo Corte Transversal analítico, interacción gen-ambiente. La evaluación de MNs y polimorfismos genéticos se determinó con pruebas moleculares en linfocitos de los individuos objeto de estudio. Resultados Se determinó que la frecuencia de MNs es 1.6 más alta en el grupo expuesto con relación al grupo referente (1.39±0.92 versus 0,87±0.78, p<0,0001). No se determinó un incremento en la frecuencia de MNs asociado a los polimorfismos en GSTM1 y GSTT1. Conclusiones El incremento de MNs en pintores de carros sirve para alertar al incremento de riesgo de cáncer en esta población expuesta a solventes orgánicos. Estos resultados pueden servir en Programas de Vigilancia Epidemiológica Ocupacional, como estrategia de prevención y en otros países con un amplio sector informal de individuos expuestos a estos químicos para reducir el riesgo de cáncer.(AU)

ABSTRACT Objective To evaluate the frequency of micronuclei (MNs) and influence of GSTM1 and GSTT1 gene polymorphisms as biomarkers of cancer risk in car painters (n=152) compared to unexposed individuals (n=152). Methods Molecular epidemiology study, cross-sectional analysis of gen and environment interaction. The evaluation of MN and genetic polymorphisms was determined by molecular tests in lymphocytes from subjects involved in the study. Results It was determined that the frequency of MNs is 1.6 higher in the exposed group compared to the reference group (1.39 ± 0.92 versus 0.87 ± 0.78, p<0.0001). There was no increase in the frequency of MNs associated with the polymorphisms in GSTM1 and GSTT1. Conclusions The increase of MNs in car painters serves to alert the increased risk of cancer in this population exposed to organic solvents. These results can be used in Occupational Epidemiological Surveillance Programs, as a prevention strategy and policies to regulate and control the use of solvents at a national level and in other countries with a large informal sector of individuals exposed to these chemicals to reduce the risk of cancer.(AU)

Evaluation of the action of precipitating agents to obtain allergenic proteins from crude mite extracts / Avaliação da ação de agentes precipitantes na obtenção de proteínas alergênicas presentes em extratos brutos de ácaros

Introduction: Allergen proteins found in dust mite extracts, such as Dermatophagoides farinae (DF), Dermatophagoides pteronyssinus (DP) and Tyrophagus putrescentiae (TP), are relevant for scientific studies in the allergy and immunotherapy fields. The precipitation/concentration of protein extracts may favor the aggregation of the allergens in homogenates. Objective and method: This paper investigates the precipitation process by submitting crude mite extracts to compounds such as ammonium sulfate (NH4)2SO4, trichloroacetic acid (TCA) and acetone. Results: The best results were obtained by fractionation with (NH4)2SO4 at 80% (w/v) saturation (~0° C), observing the protein markings on the electrophoresis gel. Major allergens were identified by immunoblot at 25 kDa (cysteine protease) for Der f and Der p; and 25 kDa, 30 kDa (tropomyosin) and Try p 3, near 26 kDa. For this percentage the total protein contents were 12.83 mg mL-1 for Der f, 24.78 mg mL-1 for Der p and 27.35 mg mL-1 for Try. Conclusion: An advantage of precipitation with (NH4)2SO4 over precipitation with acetone was the possibility of gradually obtaining protein fractions, which does not happen when using the latter. The addition of 80% (v/v) acetone to the mite extracts favored total protein precipitation in the concentrations 16.42 mg mL-1, 28.47 mg mL-1 and 13.41 mg mL-1. The use of TCA in concentrations above 20% (w/v) forms peptides that are not retained in the gel under the established experimental conditions, and dilute solutions of this acid are more efficient.

Introdução: As proteínas alergênicas presentes nos extratos dos ácaros de poeira, tais como Dermatofagoides farinae (DF), Dermatofagoides pteronyssinus (DP) e Tyrophagus putrescentiae (TP) são relevantes para estudos científicos na área de alergias e aplicação em imunoterapias. A precipitação/concentração desses extratos proteicos pode favorecer a agregação de alérgenos nos homogenatos. Objetivo e método: O trabalho investiga o processo de precipitação, submetendo os extratos brutos de ácaros de poeira a compostos como sulfato de amônio (NH4)2SO4, ácido tricloroacético (ATC) e acetona. Resultados: Os melhores resultados foram obtidos por fracionamento com (NH4)2SO4 em 80% (m/v) de saturação (~ 0°C), observando as marcações proteicas no gel de eletroforese. Os alérgenos principais foram identificados por immunoblot em 25 kDa (cisteína protease) para Der f 1 e Der p 1; e 25 kDa, 33 kDa (tropomyosin), 11 kDa para Tyr. Para esse percentual, os teores de proteína total foram de 12.83 mg mL-1 para DF; 24,78 mg mL-1 para DP; e 27,35 mg mL-1 para TP. Conclusão: A vantagem da precipitação com (NH4)2SO4 frente à precipitação com acetona foi a possibilidade de gradativamente se obter frações proteicas, o que não acontece quando utilizado esse solvente. A adição de 80% (v/v) de acetona aos extratos de ácaros favoreceu a precipitação total de proteína nas concentrações 16,42 mg mL-1; 28,47 mg mL-1; e 13,41 mg mL-1. O uso de ATC em concentrações acima de 20% (m/v) forma peptídeos que não são retidos no gel nas condições experimentais estabelecidas, sendo eficiente soluções mais diluídas desse ácido.