Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 659-664, 2024 Jun 15.
Artigo em Zh | MEDLINE | ID: mdl-38926385

RESUMO

In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.


Assuntos
Displasia Broncopulmonar , Recém-Nascido Prematuro , Enfisema Pulmonar , Humanos , Recém-Nascido , Brônquios , Displasia Broncopulmonar/etiologia , Pneumonectomia , Enfisema Pulmonar/cirurgia
2.
Chemistry ; 29(36): e202300793, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-36989413

RESUMO

1,5,9-Tribromo-2,3,6,7,10,11-hexamethoxy-4b1 -methyltribenzotriquinacene, a C3 -symmetric TBTQ derivative, can be prepared conveniently and with high regioselectivity from readily available starting materials. It is a versatile key compound for the synthesis of other chiral 1,5,9-trifunctionalized TBTQ derivatives and π-extended congeners in which the bays of the TBTQ skeleton are bridged by vinylene and 1,2-arylene units. X-ray crystal structure analysis and UV-vis spectroscopy show that vinylene bay-bridging enables better π-conjugation with the arene rings of the TBTQ core than 1,2-arylene bay-bridging does.

3.
BMC Anesthesiol ; 20(1): 144, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513111

RESUMO

BACKGROUND: Caudal ketamine has been shown to provide an effective and prolonged post-operative analgesia with few adverse effects. However, the effect of caudal ketamine on the minimum local anesthetic concentration (MLAC) of ropivacaine for intra-operative analgesia is unclear. METHODS: One hundred and sixty-nine children were randomized to five groups: Group C (caudal ropivacaine only), Group K0.25 (caudal ropivacaine plus 0.25 mg/kg ketamine), Group K0.5 (caudal ropivacaine plus 0.5 mg/kg ketamine), Group K0.75 (caudal ropivacaine plus 0.75 mg/kg ketamine), and Group K1.0 (caudal ropivacaine plus 1.0 mg/kg ketamine). The primary outcome was the MLAC values of ropivacaine with/without ketamine for caudal block. RESULTS: The MLAC values of ropivacaine were 0.128% (0.028%) in the control group, 0.112% (0.021%) in Group K0.25, 0.112% (0.018%) in Group K0.5, 0.110% (0.019%) in Group K0.75, and 0.110% (0.020%) in Group K1.0. There were no significant differences among the five groups for the MLAC values (p = 0.11). During the post-operative period the mean durations of analgesia were 270, 381, 430, 494, and 591 min in the control, K0.25, K0. 5, K0.75, and K1.0 groups respectively, which shown that control group is significantly different from all ketamine groups. Also there were significant differences between K0.25 and K0.75 groups, and between K1.0 groups and the other ketamine groups. CONCLUSIONS: Adding caudal ketamine to ropivacaine prolong the duration of post-operative analgesia; however, it does not decrease the MLAC of caudal ropivacaine for intra-operative analgesia in children. CLINICAL TRIAL REGISTRATION: ChiCTR-TRC-13003492. Registered on 13 August 2013.


Assuntos
Anestésicos Locais/farmacologia , Ketamina/farmacologia , Ropivacaina/farmacologia , Pré-Escolar , Método Duplo-Cego , Humanos , Lactente , Estudos Prospectivos
4.
J Am Chem Soc ; 140(13): 4623-4631, 2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29584421

RESUMO

The structural uniqueness of covalent organic frameworks (COFs) has brought these new materials great potential for advanced applications. One of the key aspects yet to be developed is how to improve the robustness of covalently linked reticular frameworks. In order to make the best use of π-conjugated structures, we develop herein a "killing two birds with one stone" strategy and construct a series of ultrastable benzoxazole-based COFs (denoted as LZU-190, LZU-191, and LZU-192) as metal-free photocatalysts. Benefiting from the formation of benzoxazole rings through reversible/irreversible cascade reactions, the synthesized COFs exhibit permanent stability in the presence of strong acid (9 M HCl), strong base (9 M NaOH), and sunlight. Meanwhile, reticulation of the benzoxazole moiety into the π-conjugated COF frameworks decreases the optical band gap and therefore increases the capability for visible-light absorption. As a result, the excellent photoactivity and unprecedented recyclability of LZU-190 (for at least 20 catalytic runs, each with a product yield of 99%) have been illustrated in the visible-light-driven oxidative hydroxylation of arylboronic acids to phenols. This contribution represents the first report on the photocatalytic application of benzoxazole-based structures, which not only sheds new light on the exploration of robust organophotocatalysts from small molecules to extended frameworks but also offers in-depth understanding of the structure-activity relationship toward practical applications of COF materials.

5.
Cell Physiol Biochem ; 50(3): 893-910, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355939

RESUMO

BACKGROUND/AIMS: Vulvovaginal candidiasis (VVC) is a disease commonly occurring in sexually active women. The involvement of microRNAs in several kinds of infectious diseases has been highlighted in a number of researches. Therefore, we conducted the present study in order to investigate whether microRNA-1192 (miR-1192) would significantly target CXCR4 in Th17 cells as well as inflammatory factors in mouse models suffering from VVC. METHODS: Seventy-five mice were selected as test subjects for this study, of which twenty-five were used as the normal control, while the rest were treated with estradiol or oil-treated in order to establish VVC mouse models (each n = 25). Protein expressions of CXCR4, IL-6, IL-17, and IL-23 were all measured using both an immunohistochemistry and ELISA. The Th17 cell percentage in peripheral blood and the expression of RORγt in Th17 cells were detected using a flow cytometry. Mouse vaginal epithelial cells were isolated from normal mice, after which the mice were treated with estradiol to regulate their estrogen, followed by treatments involving the miR-1192 mimic, miR-1192 inhibitor, siRNA-CXCR4, and miR-1192 inhibitor + si-CXCR4. The cell cycle, apoptosis, and proliferation were all examined by using an additional flow cytometry as well as the employment of the MTT assay. The miR-1192, CXCR4, IL-6, IL-17, and IL-23 expressions in tissues and cells were both measured using both RT-qPCR and western blot assay techniques. RESULTS: The mice treated with either estradiol or oil had presented to us lowered levels in miR-1192 expression as well as higher levels in both Th17 cell percentage and expression of RORγt in Th17 cells, along with mRNA and protein expressions of CXCR4, IL-6, IL-17, and IL-23. In cell experiments, the mouse vaginal epithelial cells that had been treated with miR-1192 inhibitor had shown us a decreased cell proliferation rate and contrarily increased expressions of CXCR4, IL-6, IL-17, and IL-23 mRNA, protein, and cell apoptosis rate; these results were opposite to the ones found in the mice treated with miR-1192 mimic. CONCLUSION: Our results provided significant evidence that miR-1192 could directly development and progression of VVC by restraining the CXCR4 gene in the VVC mice.


Assuntos
Candidíase Vulvovaginal/patologia , MicroRNAs/metabolismo , Receptores CXCR4/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Apoptose , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/microbiologia , Pontos de Checagem do Ciclo Celular , Modelos Animais de Doenças , Feminino , Interleucina-17/análise , Interleucina-17/química , Interleucina-17/metabolismo , Interleucina-23/análise , Interleucina-23/genética , Interleucina-23/metabolismo , Interleucina-6/análise , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/genética , Células Th17/citologia , Células Th17/metabolismo
6.
Med Sci Monit ; 24: 6144-6150, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30177674

RESUMO

BACKGROUND The effect of body mass index (BMI) on the spread of spinal anesthesia is not completely clear. The aim of this study was to determine the dose requirements of ropivacaine and the incidence of hypotension in pregnant women with different BMIs during cesarean delivery. MATERIAL AND METHODS In this double-blind study, 405 women undergoing elective cesarean delivery were allocated to group S (BMI <25), group M (25 ≤BMI <30), or group L (BMI ≥30). Women in each group were further assigned to receive 7, 8, 9, 10, 11, 12, 13, 14, or 15 mg of spinal ropivacaine. RESULTS The ED50 and ED95 values of ropivacaine were 9.487 mg and 13.239 mg in Group S, 9.984 mg and 13.737 mg in Group M, and 9.067 mg and 12.819 mg in Group L. There were no significant differences among the 3 groups (p=0.915). Group L had a higher incidence of hypotension and a greater change in MAP after spinal anesthesia compared to the other 2 groups, and also required more doses of ephedrine than the other 2 groups when a dose of 15 mg ropivacaine was used. The incidence of hypotension had a positive correlation with the dose of ropivacaine (OR=1.453, p<0.001) and gestational age (OR=1.894, p<0.001). CONCLUSIONS Spinal ropivacaine dose requirements were similar in the normal BMI range. However, higher doses of spinal ropivacaine were associated with an increased incidence and severity of hypotension in obese patients compared with that in non-obese patients.


Assuntos
Raquianestesia/métodos , Ropivacaina/administração & dosagem , Adulto , Anestésicos Locais/metabolismo , Índice de Massa Corporal , Cesárea/efeitos adversos , China , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hipotensão/etiologia , Gravidez , Estudos Prospectivos , Ropivacaina/metabolismo
7.
J Am Chem Soc ; 138(9): 3031-7, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26878337

RESUMO

Heavy metal ions are highly toxic and widely spread as environmental pollutants. New strategies are being developed to simultaneously detect and remove these toxic ions. Herein, we take the intrinsic advantage of covalent organic frameworks (COFs) and develop fluorescent COFs for sensing applications. As a proof-of-concept, a thioether-functionalized COF material, COF-LZU8, was "bottom-up" integrated with multifunctionality for the selective detection and facile removal of mercury(II): the π-conjugated framework as the signal transducer, the evenly and densely distributed thioether groups as the Hg(2+) receptor, the regular pores facilitating the real-time detection and mass transfer, together with the robust COF structure for recycle use. The excellent sensing performance of COF-LZU8 was achieved in terms of high sensitivity, excellent selectivity, easy visibility, and real-time response. Meanwhile, the efficient removal of Hg(2+) from water and the recycling of COF-LZU8 offers the possibility for practical applications. In addition, X-ray photoelectron spectroscopy and solid-state NMR investigations verified the strong and selective interaction between Hg(2+) and the thioether groups of COF-LZU8. This research not only demonstrates the utilization of fluorescent COFs for both sensing and removal of metal ions but also highlights the facile construction of functionalized COFs for environmental applications.


Assuntos
Corantes Fluorescentes/química , Mercúrio/isolamento & purificação , Sulfetos/química , Cátions Bivalentes/análise , Cátions Bivalentes/isolamento & purificação , Corantes Fluorescentes/síntese química , Hidrazonas/síntese química , Hidrazonas/química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Imageamento por Ressonância Magnética , Mercúrio/análise , Espectroscopia Fotoeletrônica , Sulfetos/síntese química
8.
Med Sci Monit ; 20: 2658-65, 2014 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-25503557

RESUMO

BACKGROUND: The minimum alveolar concentration (MAC) of sevoflurane in neonates is 3.3%, but this value has not been verified in Chinese neonates and the effect of different doses of fentanyl on MAC in neonates has not been investigated. This study was designed to determine the ED50 and ED95 values of sevoflurane in Chinese neonates with and without fentanyl. MATERIAL AND METHODS: Ninety-three neonates were randomly assigned to receive sevoflurane alone (control group, n=30), 1 µg/kg sevoflurane (group fent1, n=29), or 2 µg/kg fentanyl (group fent2, n=32). Following inhalational induction and tracheal intubation, the end-tidal concentration of sevoflurane was adjusted to achieve the designated concentration, which was determined using the modified Dixon's up-and-down method starting with 3.0% in each group, with a 0.25% step size. Success was defined as no motor response within 60 s of skin incision. RESULTS: The MAC (standard deviation) values of sevoflurane were 2.91% (0.27) in the control group, 2.53% (0.31) in the fent1 group, and 2.34% (0.33) in the fent2 group according to Dixon's up-and-down method. Logistic probit regression analysis revealed that the ED50 and ED95 (95% CI) of sevoflurane in neonates were 2.82% (2.66-2.98) and 3.39% (2.89-3.89), respectively, in the control group; 2.44% (2.19-2.68) and 3.30% (2.51-4.09), respectively, in the fent1 group; and 2.21% (1.97-2.45) and 3.11% (2.35-3.88), respectively, in the fent2 group. CONCLUSIONS: The MAC value of sevoflurane in Chinese neonates was lower than previously reported and was reduced by the addition of fentanyl.


Assuntos
Fentanila/administração & dosagem , Fentanila/farmacologia , Éteres Metílicos/administração & dosagem , Éteres Metílicos/farmacologia , Demografia , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Masculino , Sevoflurano
9.
Small Methods ; : e2400465, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39049798

RESUMO

Porous materials are excellent candidates for water remediation in environmental issues. However, it is still a key challenge to design efficient adsorbents for rapid water purification from various heavy metal ions-contaminated wastewater in one step. Here, two robust nitrogen-rich covalent organic frameworks (COFs) bearing terpyridine units on the pore walls by a "bottom-up" strategy are reported. Benefitting from the strong chelation interaction between the terpyridine units and various heavy metal ions, these two terpyridine COFs show excellent removal efficiency and capability for Pb2+, Hg2+, Cu2+, Ag+, Cd2+, Ni2+, and Cr3+ from water. These COFs are shown to remove such heavy metal ions with >90% of contents at one time after the aqueous metal ions mixture is passed through the COF filter. The nitrogen-rich features of the COFs also endow them with the capability of capturing iodine vapors, offering the terpyridine COFs the potential for environmental remediation applications.

10.
Chemistry ; 19(25): 8078-81, 2013 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-23649505

RESUMO

Organocatalysis: A concise synthesis of L-pyrrolysine has been accomplished in six steps from simple starting materials. The facile synthetic strategy relies on an organocatalytic Michael addition, an efficient amide coupling, and a challenging method for the imine-bond construction.


Assuntos
Lisina/análogos & derivados , Amidas/química , Iminas/química , Lisina/síntese química , Estrutura Molecular , Estereoisomerismo
11.
Neurotoxicology ; 94: 1-10, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334642

RESUMO

Ketamine, a popular anesthetic, is often abused by people for its hallucinogenic effect. Thus, the safety of ketamine in pediatric populations has been called into question for potential neurotoxic effects. However, ketamine also has neuroprotective effects in many brain injury models. The differentiation of neural stem cells (NSCs) was influenced significantly by ketamine, but the molecular mechanism is still unclear. NSCs were extracted from the hippocampi of postnatal day 1 rats and treated with ketamine to induce NSCs differentiation. Our results found that ketamine promoted neuronal differentiation of NSCs dose-dependently in a small dose range (P < 0.001). The main types of neurons from NSCs were cholinergic (51 ± 4 %; 95 % CI: 41-61 %) and glutamatergic neurons (34 ± 3 %; 95 % CI: 27-42 %). Furthermore, we performed RNA sequencing to promise a more comprehensive understanding of the molecules regulated by ketamine. Finally, we combined bioimaging and multiple molecular biology techniques to clarify that ketamine influences NSC differentiation by regulating transient receptor potential canonical 3 (TRPC3) expressions. Ketamine dramatically repressed TRPC3 expression (MD [95 % CI]=0.67 [0.40-0.95], P < 0.001) with a significant increase of phosphorylated glycogen synthase kinase 3ß (p-GSK3ß; MD [95 % CI]=1.00 [0.74-1.27], P < 0.001) and a decrease of ß-catenin protein expression (MD [95 % CI]=0.60 [0.32-0.89], P = 0.001), thereby promoting the differentiation of NSCs into neurons and inhibiting their differentiation into astrocytes. These results suggest that TRPC3 is necessary for ketamine to modulate NSC differentiation, which occurs partly via regulation of the GSK3ß/ß-catenin pathway.


Assuntos
Ketamina , Células-Tronco Neurais , Animais , Ratos , beta Catenina/metabolismo , Diferenciação Celular , Proliferação de Células , Glicogênio Sintase Quinase 3 beta/metabolismo , Ketamina/toxicidade
12.
Front Cardiovasc Med ; 8: 665038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937364

RESUMO

Objectives: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) is complex and diverse that has led to a variety of treatment strategies. Experience has been largely obtained in the advanced countries. The clinical diversity is greater in China. We evaluated our surgical approaches and outcomes of these patients. Methods: We reviewed 127 patients undergoing varied surgeries in our center in 2010-2019. Results: Thirty patients underwent single-stage complete repair by unifocalizing MAPCAs and VSD closure (aged 3.9-131.4 months, median 22) with 3 (10%) early deaths. Ninety-seven underwent the first-stage rehabilitation strategy including systemic-to-pulmonary shunt in 29 (aged 0.5-144 month, median 8), and palliative RV-PA conduit in 68 (aged 2.2-209.6 months, median 14) with 5 (5.2%) early deaths. Eight-one patients (63.8%) eventually achieved complete repair with a median right/left ventricular (RV/LV) pressure ratio of 0.7 (ranged 0.4-1.0). Fourteen patients (11.0%) accepted palliation as final destination. Survival for the entire cohort was 89.5, 85.2, and 76.1% at 1, 5, and 10 years, respectively. Survival for those undergoing complete repair was 88.2 and 76.6% at 1 and 5 year, respectively. RV/LV pressure ratio ≥0.8 was risk factor for mortality (HR10.3, p = 0.003). Conclusions: Our cohort, the largest from China, had distinctive clinical features with substantially wider age range and higher RV/LV pressure ratio. Using the combined approaches tailored to individual patients, complete repair was achieved in 64% of patients. The early and intermediate outcomes are acceptable compared to many of the previous reports.

13.
Chem Commun (Camb) ; 54(60): 8391-8394, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-29998276

RESUMO

The synthesis of a click poly(amide-triazole) bearing multiple azobenzene units along the main chain was reported. The polymer was found to form strong physical polymer organogels. This structural design facilitates a much more efficient photomechanical effect upon photochemical excitation, and a highly reversible sol-gel transformation can be smoothly triggered by light irradiation and thermal treatment.

14.
Chin Med J (Engl) ; 131(6): 684-688, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29521291

RESUMO

BACKGROUND: Previous studies conducted in various geographical and ethnical populations have shown that Alpha-1-antitrypsin (Alpha-1-AT) expression affects the occurrence and progression of chronic obstructive pulmonary disease (COPD). We aimed to explore the associations of rs9944155AG, rs1051052AG, and rs1243166AG polymorphisms in the Alpha-1-AT gene with the risk of COPD in Uygur population in the Kashgar region. METHODS: From March 2013 to December 2015, a total of 225 Uygur COPD patients and 198 healthy people were recruited as cases and controls, respectively, in Kashgar region. DNA was extracted according to the protocol of the DNA genome kit, and Sequenom MassARRAY single-nucleotide polymorphism technology was used for genotype determination. Serum concentration of Alpha-1-AT was detected by enzyme-linked immunosorbent assay. A logistic regression model was used to estimate the associations of polymorphisms with COPD. RESULTS: The rs1243166-G allele was associated with a higher risk of COPD (odds ratio [OR] = 2.039, 95% confidence interval [CI]: 1.116-3.725, P = 0.019). In cases, Alpha-1-AT levels were the highest among participants carrying rs1243166 AG genotype, followed by AA and GG genotype (χ2 = 11.89, P = 0.003). Similarly, the rs1051052-G allele was associated with a higher risk of COPD (OR = 19.433, 95% CI: 8.783-43.00, P < 0.001). The highest Alpha-1-AT levels were observed in cases carrying rs1051052 AA genotype, followed by cases with AG and GG genotypes (χ2 = 122.45, P < 0.001). However, individuals with rs9944155-G allele exhibited a lower risk of COPD than those carrying the rs9944155-A allele (OR = 0.121, 95% CI: 0.070-0.209, P < 0.001). In both cases and controls, no significant difference in Alpha-1-AT levels was observed among various rs9944115 genotypes. CONCLUSIONS: rs1243166, rs9944155, and rs1051052 sites of Alpha-1-AT may be associated with the COPD morbidity in Uygur population. While rs1243166-G allele and rs1051052-G allele are associated with an increased risk of developing COPD, rs9944155-G allele is a protect locus in Uygur population. Alpha-1-AT levels in Uygur COPD patients were lower than those in healthy people and differed among patients with different rs1051052 AG and rs1243166 AG genotypes.


Assuntos
Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Alelos , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , alfa 1-Antitripsina/genética
15.
Curr Drug Deliv ; 2(2): 191-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16305420

RESUMO

The development of oral insulin using the eligen technology represents a significant advance in insulin administration which is expected to improve the quality of life of diabetic patients. As clinical studies progress, a great deal of interest has focused on the process by which this technology enables insulin absorption from the intestinal lumen into the bloodstream. The eligen technology employs low molecular weight compounds (termed drug delivery agents or carriers) which interact weakly and non-covalently with insulin, increasing its lipophilicity and thereby its ability to cross the gastrointestinal epithelium. In this study we investigated the mechanism of insulin absorption across caco-2 cell monolayers with one of these drug delivery agents, N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC). Our results show that SNAC increases insulin permeability approximately ten fold across cell monolayers and does so without affecting mannitol permeability or disrupting cell membranes. Confocal microscopy and immunocytochemistry revealed that insulin is transported transcellularly without detectable alteration of the tight junctions between adjacent cells. SNAC also appears to play some role in protecting insulin from proteolytic degradation, potentially allowing for more intact insulin to be available at the site of absorption.


Assuntos
Caprilatos/administração & dosagem , Insulina/administração & dosagem , Absorção , Administração Oral , Células CACO-2 , Sistemas de Liberação de Medicamentos , Humanos , Insulina/farmacocinética , Permeabilidade , Solubilidade
16.
Pharm Res ; 19(8): 1180-4, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12240944

RESUMO

PURPOSE: The oral bioavailability of heparin is negligible. Recent studies, however, have shown that sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC) and other N-acylated amino acids enable oral heparin absorption. To investigate the mechanism by which heparin crosses the intestinal epithelium in the presence of SNAC, we have used fluorescence microscopy to follow the transport of heparin across Caco-2 cell monolayers. METHODS: The experiments were carried out on Caco-2 monolayers and Caco-2 cells grown to confluence on culture dishes, using different concentrations of SNAC. The localization of fluorescently labeled heparin was determined using epi-fluorescence and confocal microscopy. DNA dyes were used to determine the effect of SNAC on the plasma membrane integrity. F-actin was labeled with fluorescent phalloidin to investigate the stability of perijunctional actin rings in the presence of SNAC. RESULTS: Heparin was detected in the cytoplasm only after incubation of the cells with heparin and SNAC. No DNA staining was observed in cells incubated with a DNA dye in the presence of SNAC concentrations at which heparin transport occurred. In addition, no signs of actin redistribution or perijunctional ring disbandment were observed during the transport of heparin. CONCLUSIONS: The results indicate that SNAC enables heparin transport across Caco-2 monolayers via the transcellular pathway. Heparin transport in the presence of SNAC is selective and does not involve permeabilization of the plasma membrane or tight junction disruption.


Assuntos
Caprilatos/farmacocinética , Heparina/farmacocinética , Administração Oral , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Células CACO-2 , Caprilatos/administração & dosagem , Heparina/administração & dosagem , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA