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Objective: To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods: The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 â, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture (n=5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3rd to 6th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 (n=3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated (n=5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results: Both simple hydrogel and composite hydrogel were in a solution state at 55 â and transition to a gel state when cooling to 37 â. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS (P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel (P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone (P<0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced (P<0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased (P<0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group (P<0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group (P<0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group (P<0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions: The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.
Asunto(s)
Chlorella , Nanopartículas del Metal , Anomalías Cutáneas , Masculino , Ratones , Humanos , Femenino , Animales , Niño , Gelatina/farmacología , Plata/farmacología , Nanopartículas del Metal/uso terapéutico , Ratones Endogámicos C57BL , Cicatrización de Heridas , Hidrogeles , Escherichia coli , PolietilenglicolesRESUMEN
Objective: To understand the HIV infection status in male outpatients in sexually transmitted disease (STD) clinics in Tianjin from 2016 to 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional studies were conducted between April and June during 2016-2020 to collect the information about the awareness of AIDS related knowledge, related sex behaviors, HIV infection, syphilis prevalence and HCV infection of male STD outpatients in Tianjin with a sample seize of 400 in each sentinel clinic. Results: From 2016 to 2020, a total of 4 000 male STD outpatients were surveyed. The HIV positive rate increased from 1.13% (9/800) to 2.25% (18/800) (trend χ2=14.22, P<0.001), the positive rate of syphilis increased from 9.38% (75/800) to 13.00% (104/800) (trend χ2=7.30, P=0.007) in this population during this period. The overall HCV positive rate was 0.45% (18/4 000). Multivariate logistic regression analysis showed that compared with those who were unmarried, had registered residence in Tianjin, had no temporary sexual behavior in the past 3 months, had no anal sex and had negative syphilis test result, the risk factors of HIV infection in the male STD outpatients included cohabitation (aOR=7.53, 95%CI:2.13-26.62), being from other provinces (aOR=3.64,95%CI:1.58-8.38), having temporary sexual behavior in the past 3 months (aOR=2.24,95%CI:1.03-4.89), having homosexual anal sex (aOR=85.99,95%CI:38.76-190.74) and suffering from syphilis (aOR=6.06,95%CI:3.18-11.56). Conclusion: The detection rates of HIV infection and syphilis in male STD outpatients in Tianjin showed upward trends from 2016 to 2020. Having temporary sexual behavior and anal sex, and suffering from syphilis were the main risk factors of HIV infection in male STD outpatients.
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Infecciones por VIH , Sífilis , Estudios Transversales , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Pacientes Ambulatorios , Sífilis/epidemiologíaRESUMEN
The objective of this study was to evaluate the effects of continuous low dose infusion of lipopolysaccharide (LPS) on inflammatory responses and milk production and quality in lactating dairy cows. Eight Holstein cows were assigned to two treatments in a cross-over experimental design. Cows were infused intravenously either with saline solution or with saline solution containing LPS from Escherichia coli O111:B4 at a dose of 0.01 µg LPS/kg body weight for approximately 6 hr each day during a seven-day trial. The clinical symptoms and milk production performance were observed. Milk samples were analysed for conventional components, fatty acids and amino acids. And jugular vein and mammary vein plasma samples were analysed for concentrations of cytokines and acute phase proteins. LPS infusion decreased feed intake and milk yield. An increase in body temperature was observed after LPS infusion. LPS infusion also increased plasma concentrations of interleukin-1ß, serum amyloid A, LPS-binding protein, C-reactive protein and haptoglobin. LPS infusion decreased the contents of some fatty acids, such as C17:1, C18:0, C18:1n9 (trans) and C18:2n6 (trans), and most amino acids except for methionine, threonine, histidine, cysteine, tyrosine and proline in the milk. The results indicated that a continued low dose infusion of LPS can induce an inflammatory response, decrease milk production and reduce milk quality.
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Enfermedades de los Bovinos/inducido químicamente , Inflamación/veterinaria , Lactancia/efectos de los fármacos , Lipopolisacáridos/toxicidad , Leche/normas , Proteínas de Fase Aguda/metabolismo , Animales , Bovinos , Enfermedades de los Bovinos/metabolismo , Estudios Cruzados , Citocinas/sangre , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/metabolismo , Lactancia/metabolismo , Lipopolisacáridos/administración & dosificaciónRESUMEN
The potential combined effects of oleic, linoleic and linolenic acids supplementation on lactation performance and the milk fatty acid (FA) profile in dairy cows have not been well investigated. Our objective was to examine the effects of supplementation with a combination of these FA as well as the effects of removing each from the combination on lactation performance and the milk FA profile in dairy cows. Eight Holstein cows (101±11 days in milk) received four intravenously infused treatments in a 4×4 Latin square design, and each period lasted for 12 days which consisted of 5 days of infusion and 7 days of recovery. The control treatment (CTL) contained 58.30, 58.17 and 39.96 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively. The other three treatments were designated --C18 : 1 (20.68, 61.17 and 41.72 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively), -C18 : 2 (61.49, 19.55 and 42.13 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively) and -C18 : 3 (60.89, 60.16 and 1.53 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively). Dry matter intake and lactose content were not affected by the treatments, but the milk protein content was lower in cows treated with -C18 : 2 than that in CTL-treated cows. Milk yield as well as milk fat, protein and lactose yields were higher in cows treated with -C18 : 3 than the yields in CTL-treated cows, and these yields increased linearly as the unsaturation degree of the supplemental FA decreased. Compared with the CTL treatment, the -C18 : 2 treatment decreased milk C18 : 2 cis-9 content (by 2.80%) and yield (by 22.12 g/day), and the -C18 : 3 treatment decreased milk C18 : 3 cis-9, cis-12, cis-15 content (by 2.72%) and yield (by 22.33 g/day). In contrast, removing C18 : 1 cis-9 did not affect the milk content or yield of C18 : 1 cis-9. The -C18 : 2-treated cows had a higher C18 : 1 cis-9 content and tended to have a higher C18 : 1 cis-9 yield than CTL-treated cows. The yields of C8 : 0, C14 : 0 and C16 : 0 as well as Asunto(s)
Alimentación Animal/análisis
, Bovinos/fisiología
, Suplementos Dietéticos
, Ácidos Grasos Insaturados/farmacología
, Lactancia/efectos de los fármacos
, Leche/química
, Animales
, Dieta/veterinaria
, Ácidos Grasos/análisis
, Femenino
, Ácido Linoleico/farmacología
, Ácidos Linolénicos/farmacología
, Ácido Oléico/farmacología
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We present an advance toward accurately predicting the arrivals of coronal mass ejections (CMEs) at the terrestrial planets, including Earth. For the first time, we are able to assess a CME prediction model using data over two thirds of a solar cycle of observations with the Heliophysics System Observatory. We validate modeling results of 1337 CMEs observed with the Solar Terrestrial Relations Observatory (STEREO) heliospheric imagers (HI) (science data) from 8 years of observations by five in situ observing spacecraft. We use the self-similar expansion model for CME fronts assuming 60° longitudinal width, constant speed, and constant propagation direction. With these assumptions we find that 23%-35% of all CMEs that were predicted to hit a certain spacecraft lead to clear in situ signatures, so that for one correct prediction, two to three false alarms would have been issued. In addition, we find that the prediction accuracy does not degrade with the HI longitudinal separation from Earth. Predicted arrival times are on average within 2.6 ± 16.6 h difference of the in situ arrival time, similar to analytical and numerical modeling, and a true skill statistic of 0.21. We also discuss various factors that may improve the accuracy of space weather forecasting using wide-angle heliospheric imager observations. These results form a first-order approximated baseline of the prediction accuracy that is possible with HI and other methods used for data by an operational space weather mission at the Sun-Earth L5 point.
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The word "long (stranguria)" is seen both in historical and medical works in the Han Dynasty, but with much different meanings. In medical books, including Nei jing(Inner Canon), Wu shi er bing fang(Prescriptions for Fifty-two Diseases), and Wu wei yi jian(Medical Bamboo slips of Wuwei), Long refers to incontinence of urination. However, in historical books, Long is usually expressed as "pi long" , referring to different conditions, including lame, fatigue, and disability, all congenital or acquired renal deficient illness. It is also seen in unearthed documents as fei ji (disability) and "du long" , referring to congenital or postnatal severe diseases resulting in disability to do anything. Together with orphan, widow, widower, senility, and poverty without relatives for existence, all weak communities need to be supported and saved.
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Medicina Tradicional China/historia , Terminología como Asunto , Libros/historia , China , Historia AntiguaRESUMEN
The extracellular matrix (ECM) is the major macromolecule in skeletal muscle, which affects meat quality greatly. The remodeling of the ECM is mainly regulated by matrix metalloproteinases (MMPs). The expression patterns of MMP-1, -2, and -8 in longissimus dorsi muscle were explored using quantitative real-time polymerase chain reaction. The results show that the expression of MMP-1, -2, and -8 decreased significantly from 135 days of pregnancy to postnatal 30 months. While the expression of MMP-1, -2, and -8 showed no significant relationships with intramuscular fat contents, MMP-1 and -2 showed significant negative correlations with the shearing force of the longissimus dorsi muscle in cattle. The expression of MMP-1 also showed a significant negative correlation with cooking loss and a positive correlation with water holding capacity. The expression levels of MMP-1 and -2 were usually higher in fat than in skeletal muscle tissue. The expression of MMP-8 was significantly higher in the mammary fat pad and the longissimus dorsi muscle than in all other tissues. This study indicates that the remodeling of the ECM has important effects both on the development of postnatal skeletal muscle and on meat quality.
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Calidad de los Alimentos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Músculos Paraespinales/metabolismo , Carne Roja , Animales , Bovinos , Desarrollo Fetal , Expresión Génica , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/genética , Músculos Paraespinales/embriología , Músculos Paraespinales/crecimiento & desarrollo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The existence of a strong internal magnetic field allows probing of the interior through both long term changes of and short period fluctuations in that magnetic field. Venus, while Earth's twin in many ways, lacks such a strong intrinsic magnetic field, but perhaps short period fluctuations can still be used to probe the electrical conductivity of the interior. Toward the end of the Venus Express mission, an aerobraking campaign took the spacecraft below the ionosphere into the very weakly electrically conducting atmosphere. As the spacecraft descended from 150 to 140 km altitude, the magnetic field became weaker on average and less noisy. Below 140 km, the median field strength became steady but the short period fluctuations continued to weaken. The weakness of the fluctuations indicates they might not be useful for electromagnetic sounding of the atmosphere from a high altitude platform such as a plane or balloon, but possibly could be attempted on a lander.
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The vitamin D receptor (VDR) is involved in the immune response and bone metabolism, both of which are implicated in the pathogenesis of chronic periodontitis (CP). In this study, we investigated the association between the VDR single nucleotide polymorphism rs2228570 and CP susceptibility in a Han Chinese population consisting of 440 moderate or severe CP patients and 324 controls. Genomic DNA was extracted from buccal epithelial cells and genotyped using matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry. No significant difference in allelic or genotypic frequencies distributions for rs2228570 was found between CP patients and controls. In conclusion, we found no statistically significant association between rs2228570 and CP in our population.
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Periodontitis Crónica/genética , Receptores de Calcitriol/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Observations with the Venus Express magnetometer and low-energy particle detector revealed magnetic field and plasma behavior in the near-Venus wake that is symptomatic of magnetic reconnection, a process that occurs in Earth's magnetotail but is not expected in the magnetotail of a nonmagnetized planet such as Venus. On 15 May 2006, the plasma flow in this region was toward the planet, and the magnetic field component transverse to the flow was reversed. Magnetic reconnection is a plasma process that changes the topology of the magnetic field and results in energy exchange between the magnetic field and the plasma. Thus, the energetics of the Venus magnetotail resembles that of the terrestrial tail, where energy is stored and later released from the magnetic field to the plasma.
RESUMEN
We use approximate entropy and hydrophobicity patterns to predict G-protein-coupled receptors. Adaboost classifier is adopted as the prediction engine. A low homology dataset is used to validate the proposed method. Compared with the results reported, the successful rate is encouraging. The source code is written by Matlab.
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Aminoácidos/análisis , Receptores Acoplados a Proteínas G/química , Algoritmos , Secuencia de Aminoácidos , Animales , Bovinos , Biología Computacional/métodos , Interpretación Estadística de Datos , Bases de Datos de Proteínas , Entropía , Interacciones Hidrofóbicas e Hidrofílicas , Datos de Secuencia Molecular , Receptores Acoplados a Proteínas G/clasificación , Rodopsina/químicaRESUMEN
Venus, unlike Earth, is an extremely dry planet although both began with similar masses, distances from the Sun, and presumably water inventories. The high deuterium-to-hydrogen ratio in the venusian atmosphere relative to Earth's also indicates that the atmosphere has undergone significantly different evolution over the age of the Solar System. Present-day thermal escape is low for all atmospheric species. However, hydrogen can escape by means of collisions with hot atoms from ionospheric photochemistry, and although the bulk of O and O2 are gravitationally bound, heavy ions have been observed to escape through interaction with the solar wind. Nevertheless, their relative rates of escape, spatial distribution, and composition could not be determined from these previous measurements. Here we report Venus Express measurements showing that the dominant escaping ions are O+, He+ and H+. The escaping ions leave Venus through the plasma sheet (a central portion of the plasma wake) and in a boundary layer of the induced magnetosphere. The escape rate ratios are Q(H+)/Q(O+) = 1.9; Q(He+)/Q(O+) = 0.07. The first of these implies that the escape of H+ and O+, together with the estimated escape of neutral hydrogen and oxygen, currently takes place near the stoichometric ratio corresponding to water.
RESUMEN
Venus has no significant internal magnetic field, which allows the solar wind to interact directly with its atmosphere. A field is induced in this interaction, which partially shields the atmosphere, but we have no knowledge of how effective that shield is at solar minimum. (Our current knowledge of the solar wind interaction with Venus is derived from measurements at solar maximum.) The bow shock is close to the planet, meaning that it is possible that some solar wind could be absorbed by the atmosphere and contribute to the evolution of the atmosphere. Here we report magnetic field measurements from the Venus Express spacecraft in the plasma environment surrounding Venus. The bow shock under low solar activity conditions seems to be in the position that would be expected from a complete deflection by a magnetized ionosphere. Therefore little solar wind enters the Venus ionosphere even at solar minimum.
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The occurrence of lightning in a planetary atmosphere enables chemical processes to take place that would not occur under standard temperatures and pressures. Although much evidence has been reported for lightning on Venus, some searches have been negative and the existence of lightning has remained controversial. A definitive detection would be the confirmation of electromagnetic, whistler-mode waves propagating from the atmosphere to the ionosphere. Here we report observations of Venus' ionosphere that reveal strong, circularly polarized, electromagnetic waves with frequencies near 100 Hz. The waves appear as bursts of radiation lasting 0.25 to 0.5 s, and have the expected properties of whistler-mode signals generated by lightning discharges in Venus' clouds.
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Compared with the conventional amino acid composition (AA), the pseudo amino acid composition (PseAA) as originally introduced by Chou can incorporate much more information of a protein sequence; this remarkably enhances the power to use a discrete model for predicting various attributes of a protein. In this study, based on the concept of Chou's PseAA, a 46-D (dimensional) PseAA was formulated to represent the sample of a protein and a new approach based on binary-tree support vector machines (BTSVMs) was proposed to predict the protein structural class. BTSVMs algorithm has the capability in solving the problem of unclassifiable data points in multi-class SVMs. The results by both the 10-fold cross-validation and jackknife tests demonstrate that the predictive performance using the new PseAA (46-D) is better than that of AA (20-D), which is widely used in many algorithms for protein structural class prediction. The results obtained by the new approach are quite encouraging, indicating that it can at least play a complimentary role to many of the existing methods and is a useful tool for predicting many other protein attributes as well.
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Aminoácidos/química , Biología Computacional/métodos , Reconocimiento de Normas Patrones Automatizadas , Conformación Proteica , Proteínas/química , Análisis de Secuencia de Proteína/métodos , Algoritmos , Inteligencia Artificial , Bases de Datos de Proteínas , Modelos MolecularesRESUMEN
The application of lanthanum (La) in industry, medicine, and agriculture may cause accumulation of the element in human body. This article examines the effects of La on the femur bone mineral of male Wistar rats after administration of La(NO3)3 by gavage at the dose of 2.0 mg La(NO3)3.kg(-1).day(-1) over a 6-month period. Chemical analysis confirmed La accumulation in bone and loss in bone mineral. Thermogravimetric analysis showed a decrease in the mineral-to-matrix ratio and an increase in carbonate content. Fourier-transform infrared spectrometry revealed elevation in the contents of labile carbonate and acidic phosphate. The synchrotron radiation small-angle X-ray scattering study presented a smaller mean thickness of the mineral crystals in the bone of La-treated rats. The synchrotron radiation-extended X-ray absorption fine structure analysis indicated that the La treatment resulted in a lowered disorder in the crystals. The smaller size, more adsorbed labile carbonate, and more acidic phosphate made the bone mineral easier to dissolve, as revealed in the kinetic measurement of bone demineralization. These findings suggest that La retards bone maturation of rats.
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Densidad Ósea/efectos de los fármacos , Fémur/química , Fémur/efectos de los fármacos , Lantano/farmacología , Absorciometría de Fotón , Animales , Cristalización , Masculino , Ratas , Ratas Wistar , Espectrofotometría InfrarrojaRESUMEN
Effects of arsenite, arsenate and vanadate on human erythrocyte membrane have been assessed according to their routes passing through the membrane, their binding modes to the membrane and their influences on membrane proteins and lipids. The uptake of arsenate (1.0 mM) by cells approached a limit with intracellular arsenic of about 0.2 mM in 5 h, and was strongly inhibited (approximately 95%) by 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), indicating that arsenate, similar to vanadate, passed across the membrane through the anion exchange protein, band 3. Arsenite (1.0 mM) influx reached a maximum of about 0.4 mM in 30 min, and was not inhibited by DIDS. The transformed species of arsenite bound to the membrane from cytosol. In contrast, arsenate bound rapidly from the outside, followed by releasing and re-binding. The binding to the membrane via sulfhydryl was indicated by the decrease of the sulfhydryl level of membrane proteins. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE) analysis revealed that the proteins, bands 1-3, were among the targets of arsenite, arsenate and vanadate. Their binding to the membrane also induced changes in the fluidity of membrane lipids and in the negative charge density in the outer surface of the membrane.
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Arseniatos/farmacología , Arsenitos/farmacología , Membrana Eritrocítica/efectos de los fármacos , Compuestos de Sodio/farmacología , Vanadatos/farmacología , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Arsénico/sangre , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Hemólisis , Humanos , Cinética , Lípidos de la Membrana/sangre , Proteínas de la Membrana/sangre , Proteínas de la Membrana/efectos de los fármacosRESUMEN
The cytotoxicity of chloroalkene-derived cysteine S-conjugates is thought to be associated with the formation of alpha-chloroenethiolates and thioketenes as reactive intermediates. Recent studies indicate that the formation of 1,2-dichloroethenethiolate, which may give rise to chlorothioketene, is a key step in the bioactivation of 5,6-dichloro-4-thia-5-hexenoic acid (Fitzsimmons et al. (1995) Biochemistry 34, 4276-4286). We report here the use of Fourier-transform ion cyclotron resonance mass spectrometry to provide the first direct evidence for the formation of alpha-chloroenethiolate and thioketene species from a cytotoxic 4-thiaalkanoate. The bioactivation of 5,6-dichloro-4-thia-5-hexenoic acid involves conversion to the corresponding CoA thioester 5,6-dichloro-4-thia-5-hexenoyl-CoA and subsequent processing by the fatty acid beta-oxidation pathway. It has been proposed that the bioactivation of 5,6-dichloro-4-thia-5-hexenoyl-CoA involves loss of 1,2-dichloroethenethiolate, followed by loss of chloride to form chlorothioketene. 1,2-Dichloroethenethiolate and related alpha-chloroalkenethiolates have not been observed directly in aqueous solution. Fourier-transform ion cyclotron resonance mass spectrometric experiments show that S-propyl 5,6-dichloro-4-thia-5-hexenethioate reacts in the gas phase with base (hydroxide ion) to release 1,2-dichloroethenethiolate, which is observed directly in the mass spectrum of the products of the gas-phase reaction. Furthermore, the elimination of chloride from 1,2-dichloroethenethiolate on collision-induced decomposition is facile and provides evidence for chlorothioketene formation. Preliminary evidence for the formation of 1,2-dichloroethenethiolate and chlorothioketene from S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine methyl ester was also obtained. These observations support the intermediacy of alpha-chloroenethiolates and chlorothioketenes in the bioactivation of cytotoxic, chloroalkene-derived 4-thiaalkanoates and cysteine S-conjugates and demonstrate the utility of Fourier-transform ion cyclotron mass spectrometry in studying the formation of reactive intermediates.