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1.
Clinics ; 76: e2683, 2021. graf
Article in English | LILACS | ID: biblio-1249591

ABSTRACT

OBJECTIVES: Ischemia and reperfusion (I/R) in the intestine could lead to severe endothelial injury, compromising intestinal motility. Reportedly, estradiol can control local and systemic inflammation induced by I/R injury. Thus, we investigated the effects of estradiol treatment on local repercussions in an intestinal I/R model. METHODS: Rats were subjected to ischemia via the occlusion of the superior mesenteric artery (45 min) followed by reperfusion (2h). Thirty minutes after ischemia induction (E30), 17β-estradiol (E2) was administered as a single dose (280 μg/kg, intravenous). Sham-operated animals were used as controls. RESULTS: I/R injury decreased intestinal motility and increased intestinal permeability, accompanied by reduced mesenteric endothelial nitric oxide synthase (eNOS) and endothelin (ET) protein expression. Additionally, the levels of serum injury markers and inflammatory mediators were elevated. Estradiol treatment improved intestinal motility, reduced intestinal permeability, and increased eNOS and ET expression. Levels of injury markers and inflammatory mediators were also reduced following estradiol treatment. CONCLUSION: Collectively, our findings indicate that estradiol treatment can modulate the deleterious intestinal effects of I/R injury. Thus, estradiol mediates the improvement in gut barrier functions and prevents intestinal dysfunction, which may reduce the systemic inflammatory response.


Subject(s)
Animals , Male , Rats , Reperfusion Injury/prevention & control , Reperfusion Injury/drug therapy , Estradiol/pharmacology , Permeability , Reperfusion , Estrogens , Intestines , Ischemia
2.
Clinics ; 76: e2096, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153992

ABSTRACT

OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.


Subject(s)
Animals , Female , Pregnancy , Rats , Pregnancy Complications , Hypothyroidism/complications , Hypothyroidism/chemically induced , Kidney/metabolism , Kidney/pathology , Mitochondria , Permeability , Rats, Sprague-Dawley , Retinol-Binding Proteins, Plasma
3.
Article in English | AIM | ID: biblio-1342017

ABSTRACT

Lipophilicity is an important physicochemical parameter of biological relevance; although its in- vivo predictive capability is dependent on accuracy and reliability of platforms used for its determination. This work examines biomimetic attribute of isocratic chromatographic hydrophobicity index (ICHI), experimental logarithm of octanol ­ water partition coefficient (LogP) and some computed lipophilicity indices for eight (8) selected antipsychotic agents and their predictive capability in drug discovery. The retention behavior of 5 first-generation and 3 second-generation antipsychotics was determined on reversed-phase chromatographic platform using methanol-phosphate buffer (pH 6.8) mobile phase. The retardation factor obtained was transformed to Rm, and plotted against volume fraction of organic modifier in the mobile phase to generate linear graph whose x- intercept is ICHI. Experimental LogP values were curled from literature while computed LogP were obtained using respective software. The experimentally determined LogPoctanol/water and ICHI were first correlated with index of brain permeability (BBB); before all lipophilicity indices were comparatively evaluated and correlated with in-vivo-normalized pharmacokinetic parameters curled from literature. ICHI gave better correlation with BBB index (r = 0.976) compared to Log Poctanol/water (r = 0.557). Comparative lipophilicity evaluation shows clustered pattern for second generation antipsychotics compared to first generation. In vivo correlation was poorer for the 8 drugs (r < 0.7), better with subset of phenothiazine homologues (r = 0.51 to 0.97). The ALogP, LogPoctanol/water, cLogP and ICHI gave highest correlation with the pharmacokinetic parameters. The biomimetic attributes of ICHI is better than for LogPoctanol/water in predicting brain permeability, but lower for in-vivo pharmacokinetic prediction.


Subject(s)
Humans , Biomimetics , Hydrophobic and Hydrophilic Interactions , Permeability , Antipsychotic Agents , Pharmacokinetics
4.
Article in English | WPRIM | ID: wpr-787134

ABSTRACT

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.


Subject(s)
Amino Acids , Binding Sites , Calcium , Cytosol , Glutamic Acid , Myocytes, Smooth Muscle , Permeability , Polyamines , Receptors, Muscarinic , Spermine , Transient Receptor Potential Channels
5.
Article in English | WPRIM | ID: wpr-762183

ABSTRACT

PURPOSE: The effect of air pollution-related particulate matter (PM) on epithelial barrier function and tight junction (TJ) expression in human nasal mucosa has not been studied to date. This study therefore aimed to assess the direct impact of PM with an aerodynamic diameter less than 2.5 μm (PM2.5) on the barrier function and TJ molecular expression of human nasal epithelial cells. METHODS: Air-liquid interface cultures were established with epithelial cells derived from noninflammatory nasal mucosal tissue collected from patients undergoing paranasal sinus surgery. Confluent cultures were exposed to 50 or 100 µg/mL PM2.5 for up to 72 hours, and assessed for 1) epithelial barrier integrity as measured by transepithelial resistance (TER) and permeability of fluorescein isothiocyanate (FITC) 4 kDa; 2) expression of TJs using real-time quantitative polymerase chain reaction and immunofluorescence staining, and 3) proinflammatory cytokines by luminometric bead array or enzyme-linked immunosorbent assay. RESULTS: Compared to control medium, 50 and/or 100 µg/mL PM2.5-treatment 1) significantly decreased TER and increased FITC permeability, which could not be restored by budesonide pretreatment; 2) significantly decreased the expression of claudin-1 messenger RNA, claudin-1, occludin and ZO-1 protein; and 3) significantly increased production of the cytokines interleukin-8, TIMP metallopeptidase inhibitor 1 and thymic stromal lymphopoietin. CONCLUSIONS: Exposure to PM2.5 may lead to loss of barrier function in human nasal epithelium through decreased expression of TJ proteins and increased release of proinflammatory cytokines. These results suggest an important mechanism of susceptibility to rhinitis and rhinosinusitis in highly PM2.5-polluted areas.


Subject(s)
Asthma , Budesonide , Claudin-1 , Cytokines , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Fluorescein , Fluorescein-5-isothiocyanate , Fluorescent Antibody Technique , Humans , Interleukin-8 , Mucous Membrane , Nasal Mucosa , Occludin , Particulate Matter , Permeability , Polymerase Chain Reaction , Rhinitis , RNA, Messenger , Tight Junctions
6.
Braz. j. med. biol. res ; 53(5): e9211, 2020. tab, graf
Article in English | LILACS | ID: biblio-1098114

ABSTRACT

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.


Subject(s)
Animals , Male , Rats , Permeability/drug effects , Physical Conditioning, Animal/physiology , Dipeptides/administration & dosage , Intestinal Mucosa/drug effects , Intestinal Mucosa/physiopathology , Rats, Wistar , Models, Animal
7.
Biol. Res ; 53: 12, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100918

ABSTRACT

BACKGROUND: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. RESULTS: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (lECs) to investigate the communication between MCs and lECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into lECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. CONCLUSIONS: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.


Subject(s)
Humans , Animals , Cattle , MicroRNAs/metabolism , Epithelial Cells/metabolism , Intestinal Mucosa/metabolism , Mast Cells/metabolism , Permeability , Inflammatory Bowel Diseases/metabolism , Cells, Cultured , Caco-2 Cells/cytology , Computational Biology , Tissue Array Analysis , Exosomes/metabolism , Claudins/metabolism , Occludin/metabolism , Zonula Occludens-1 Protein/metabolism
8.
Rev. Salusvita (Online) ; 39(1): 7-21, 2020.
Article in Portuguese | LILACS | ID: biblio-1119320

ABSTRACT

Sabe-se que o dente submetido a tratamento endodôntico apresenta um aumento da permeabilidade dentinária, devido a remoção da lama dentinária, pela utilização das substâncias químicas auxiliares (SQA). Logo, uma alteração morfológica acentuada pode deixar superfície dentinária sem suporte mineral, o que pode comprometer a obturação. Assim, a seleção da SQA em relação ao material cimentante é fundamental para uma perfeita adesão às paredes dentinárias. Objetivo: avaliar in vitro o nível da permeabilidade dentinária das substâncias químicas auxiliares mais utilizadas no tratamento endodôntico, na dentina radicular de dentes bovinos. Material e métodos: utilizou-se 40 raízes de espécimes bovinos que foram divididas em quatro grupos (n=10) e irrigados conforme segundo as condições experimentais: G1= 15 ml de hipoclorito de sódio a 0,5% (controle); G2= associação creme Endo-PTC e 15 ml de hipoclorito de sódio a 0,5%; G3= 15 ml de EDTA-T a 17%; G4= 15 ml de ácido cítrico a 10%. Em seguida, os canais radiculares foram preenchidos com corante azul de metileno a 2%, com ph 7,2, por 24 horas. Em seguida, os corpos-de-prova foram seccionados transversalmente em três fragmentos de 2 mm de espessura, para leitura em um estereoscópio, com aumento de 25 vezes. A quantificação do nível de infiltração de corante foi realizada através de uma fórmula matemática. Resultados: após a análise estatística, os resultados mostraram-se estatisticamente significante. Conclusão: concluiu-se que existe uma alta permeabilidade da dentina radicular às substâncias químicas auxiliares utilizadas durante o tratamento endodôntico.


It is known that the tooth submitted to endodontic treatment presents an increase in dentinal permeability, due to the removal of dentinal mud, through the use of auxiliary chemical substances (SQA). Therefore, a marked morphological alteration can leave the dentinal surface without mineral support, which can compromise the filling. Thus, the selection of the SQA in relation to the cementing material is fundamental for a perfect adhesion to the dentinal walls. Objective: to evaluate in vitro the level of dentin permeability of auxiliary chemical substances most used in endodontic treatment, in the root dentin of bovine teeth. Material and methods: 40 roots of bovine specimens were used, which were divided into four groups (n = 10) and irrigated according to the experimental conditions: G1 = 15 ml of 0.5% sodium hypochlorite (control); G2 = Endo-PTC cream association and 15 ml of 0.5% sodium hypochlorite; G3 = 15 ml of 17% EDTA-T; G4 = 15 ml of 10% citric acid. Then, the root canals were filled with 2% methylene blue dye, with ph 7.2, for 24 hours. Then, the specimens were cross-sectioned into three 2 mm thick fragments, for reading on a stereoscope, with a 25-fold magnification. The quantification of the level of dye infiltration was performed using a mathematical formula. Results: after the statistical analysis, the results proved to be statistically significant. Conclusion: it was concluded that there is a high permeability of root dentin to auxiliary chemical substances used during endodontic treatment.


Subject(s)
Permeability , Endodontics
10.
Rev. enferm. UERJ ; 27: e39230, jan.-dez. 2019.
Article in Portuguese | LILACS, BDENF | ID: biblio-1050651

ABSTRACT

Objetivo: atualizar o conhecimento sobre a manutenção da permeabilidade dos Dispositivos de Acesso Vascular Central (DAVC) em paciente com câncer. Conteúdo: os pacientes que fazem uso de quimioterápicos muitas vezes necessitam de DAVC seguros e de longa permanência; a obstrução ocorre em 36% dos pacientes com DAVC inseridos no período de 2 anos, que pode ser classificada como mecânica, por precipitação de medicamento/minerais e pela formação de coágulos. A equipe de enfermagem é responsável por realizar os cuidados para manter a permeabilidade desses dispositivos através do Flushing e Locking. O uso de heparina demonstrou baixa evidência quando comparado ao Soro Fisiológico (SF), em relação a diminuição da obstrução. Conclusão: o uso de SF na manutenção dos DAVC mostra-se seguro, eficaz e com menor custo financeiro.


Objective: to update the knowledge on the maintenance of permeability of Central Vascular Access Devices (CVAD) in cancer patients. Content: Patients on chemotherapy often require safe, long-term CKD. Obstruction occurs in 36% of patients with CVAD inserted in a 2-year period, which can be classified as mechanical due to drug / mineral precipitation and clot formation. The nursing staff is responsible for taking care to maintain the permeability of these devices through Flushing and Locking. The use of heparin showed low evidence when compared to saline (SF), regarding the reduction of obstruction. Conclusion: the use of DES to maintain CVAD is safe, effective and has a lower financial cost.


Objetivo: actualizar los conocimientos sobre el mantenimiento de la permeabilidad del dispositivo de acceso vascular central (DAVC) en pacientes con cáncer. Contenido: los pacientes que usan quimioterápicos a menudo necesitan DAVC seguros y de larga permanência. La obstrucción ocurre en el 36% de los pacientes con DAVC insertados en el período de 2 años y puede ocorir por precipitación de medicamento / minerales y por la formación de coágulos. El equipo de enfermería es responsable de realizar los cuidados para mantener la permeabilidad de estos dispositivos a través del Flushing y Locking. El uso de heparina demostró una baja evidencia en comparación con el Suero Fisiológico (SF), en relación con la disminución de la obstrucción. Conclusión: el uso de SF en el mantenimiento de los DAVC se muestra seguros, eficaz y con menor costo financiero.


Subject(s)
Humans , Permeability , Patient Safety , Vascular Access Devices , Central Venous Catheters , Neoplasms , Permeability/drug effects , Quality of Life , Heparin , Drug Therapy
11.
J. oral res. (Impresa) ; 8(4): 310-315, nov. 5, 2019. tab
Article in English | LILACS | ID: biblio-1145353

ABSTRACT

Purpose: This in vitro study aimed to evaluate the influence of the manual manipulation of two composite resins: Filtek™ Z350XT (3M ESPE) and Herculite Précis® (Kerr), with latex gloves contaminated with powder, human saliva and alcohol, on the microhardness values. Material and Methods: Manual manipulation was evaluated using latex gloves with powder, latex gloves without powder, latex gloves without powder with saliva, latex gloves without powder with alcohol, and without hand manipulation or contaminants (control). Each resin was manually manipulated for 10 seconds and photoactivated for 20 seconds with a light intensity of 1000mW/cm2 using a VALO ­Ultradent LED light­ cured unit, and then each sample was evaluated on the microhardness Vickers tester Leitz (Wetzlar). The collected data were analyzed using Kruskal ­Wallis and Mann ­ Whitney post-test (p<0.05). Results. Microhardness values showed a significant difference between the evaluated and control groups, showing lower microhardness values in the group of latex glove with powder for Filtek™ Z350XT and the group of latex glove without powder with saliva for Herculite Précis®. Conclusion. The manual manipulation of composite resins decreases their surface microhardness.


Propósito: Este estudio in vitrotuvo como objetivo evaluar la influencia de la manipulación manual de dos resinas compuestas: Filtek ™ Z350XT (3M ESPE) y Herculite Précis® (Kerr), con guantes de látex contaminados con polvo, saliva humana y alcohol, sobre los valores de microdureza. Material y Métodos: La manipulación manual se evaluó utilizando guantes de látex con polvo, guantes de látex sin polvo, guantes de látex sin polvo con saliva, guantes de látex sin polvo con alcohol, y sin manipulación manual o contaminantes (control). Cada resina fue manipulada manualmente durante 10 segundos y fotoactivada durante 20 segundos con unaintensidad de luz de 1000mW/cm2 usando una unidad de fotocuración LED VALO - Ultradent, y luego cada muestra fue evaluada en el tester de microdureza Vickers Leitz (Wetzlar). Los datos recopilados se analizaron utilizando Kruska ­Wallis y post-test Mann­ Whitney (p<0.05). Resultados: Se observó una diferencia significativa en los valores de microdureza entre los grupos evaluados y el grupo control, con valores más bajos de microdureza en el grupo de guantes de látex con polvo para Filtek™ Z350XT y el grupo de guantes de látex sin polvo con saliva para Herculite Précis®. Conclusión. La manipulación manual de resinas compuestas disminuye su microdureza superficial.


Subject(s)
Humans , Composite Resins , Dental Materials/adverse effects , Gloves, Surgical , Hardness Tests , Permeability , In Vitro Techniques , Physical Contaminants/adverse effects , Environmental Pollutants/adverse effects , Latex/chemistry
12.
Rev. otorrinolaringol. cir. cabeza cuello ; 79(1): 50-58, mar. 2019. tab, ilus
Article in Spanish | LILACS | ID: biblio-1004383

ABSTRACT

RESUMEN Introducción: El Draf III es una técnica quirúrgica que permite el abordaje endoscópico de los senos frontales. Fue descrita como un procedimiento de rescate para la rinosinusitis crónica (RSCr) frontal en que falla la cirugía estándar. Actualmente, su uso se ha extendido a otras aplicaciones. Objetivo: (1) Revisar las indicaciones del abordaje Draf III, (2) Revisar si el abordaje permitió el manejo adecuado de la patología y (3) Evaluar la permeabilidad de los senos frontales. Material y método: Estudio retrospectivo descriptivo. Se evaluaron los registros de pacientes sometidos a un abordaje Draf III entre los años 2013-2016 (n =11). Se revisaron las indicaciones quirúrgicas, utilidad del Draf III para manejar la patología, permeabilidad de los senos frontales y complicaciones quirúrgicas. Resultados: Indicaciones quirúrgicas incluyeron la RSCr con pólipos, osteoma frontoetmoidal, mucocele frontal, papiloma invertido y estesioneuroblastoma. En todos los casos, el abordaje permitió un adecuado manejo de la patología. Todos los pacientes presentaron permeabilidad adecuada del Draf III al último control. Un paciente debió ser reoperado a los 15,5 meses por recidiva de papiloma invertido. Ningún paciente requirió cirugía de revisión por estenosis crítica del Draf III. No hubo complicaciones quirúrgicas. Discusión: El Draf III fue útil para manejar la RSCr, patologías benignas del seno frontal, y como parte de un abordaje extendido a la fosa craneal anterior. Conclusión: En nuestra serie, el Draf III resultó ser una excelente opción quirúrgica para el tratamiento de diversas patologías del seno frontal.


ABSTRACT Introduction: The Draf III procedure is an effective approach for the management of frontal sinus disorders. It was originally described as a rescue procedure for the treatment of refractory frontal sinusitis. Currently, it can be used to treat a variety of other disorders. Aim: (1) To review the indications for the Draf III procedure, (2) To evaluate if it enabled appropriate management of the disease, and (3) To evaluate frontal sinus patency. Material and Method: Retrospective descriptive study. Clinical records of patients who underwent a Draf III procedure between the years 2013-2016 (n=11) were reviewed. Surgical indications, the appropriateness of the approach to manage the frontal sinus disease, frontal sinus patency, and complications were analyzed. Results: Surgical indications included chronic rhinosinusitis with polyps, frontoethmoidal osteoma, frontal mucocele, inverted papilloma and esthesioneuroblastoma. In all cases, the approach allowed adequate management of the pathology. All patients had adequate patency of the Draf III at their last follow-up. One patient required a revision Draf III at 15.5 months follow-up because of an inverted papilloma recurrence. No patient required revision surgery for critical stenosis of the Draf III. No surgical complications were observed. Discussion: The Draf III procedure was useful for the management of chronic rhinosinusitis, for benign frontal sinus pathologies, and as part of an extended approach to the anterior cranial fossa. Conclusion: In our series, the Draf III procedure was an excellent surgical option for the management of a variety of frontal sinus pathologies.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Nose Neoplasms/surgery , Endoscopy/methods , Frontal Sinus/surgery , Permeability , Tomography, X-Ray Computed , Chile , Epidemiology, Descriptive , Frontal Sinus/pathology , Frontal Sinus/diagnostic imaging
13.
Korean Journal of Medicine ; : 511-518, 2019.
Article in Korean | WPRIM | ID: wpr-786305

ABSTRACT

BACKGROUND/AIMS: Previous studies have reported that endotoxemia is associated with pathogenesis and complications in cirrhosis. Endotoxin stimulates the secretion of inflammatory cytokines, which contributes to the development of complications. In addition, endotoxin easily invades the gut barrier system because of the increased intestinal permeability due to portal hypertensive enteropathy. In this report, we explored changes in cytokine levels and intestinal permeability and measured the thickness and elasticity of the bowel wall using ultrasonography in cirrhotic patients.METHODS: We enrolled 40 patients with cirrhosis classified as Child-Pugh B or C and 20 healthy volunteers. Abdominal ultrasonography examinations were used to evaluate bowel wall parameters in the ascending colon and terminal ileum. Intestinal permeability was measured using dual sugar absorption tests with lactulose and mannitol. Levels of tumor necrosis factor (TNF)-α and IL-10 were determined from blood samples. We compared these outcomes between cirrhotic patients and healthy controls and between Child-Pugh B and C patients. In addition, we explored the correlation between cytokine levels, intestinal permeability ratio, and bowel wall parameters in cirrhotic patients.RESULTS: In cirrhotic patients, the ascending colon wall elasticity decreased (20.4 vs. 10.9 kPa, p = 0.048) and the terminal ileum wall thickness increased (4.2 vs. 1.9 mm, p < 0.001). The intestinal permeability ratio and levels of the cytokines TNF-α and IL-10 increased (0.219 vs. 0.017, p < 0.001; 22.47 vs. 13.48 pg/mL, p < 0.001; and 14.91 vs. 8.57 pg/mL, p = 0.019, respectively) in cirrhotic patients. However, there were no significant differences between Child-Pugh classes and no significant correlations between bowel wall parameters and intestinal permeability or cytokine levels.CONCLUSIONS: Ultrasonography revealed bowel wall thickening and decreases in elasticity; in addition, intestinal permeability and cytokine levels increased in cirrhotic patients compared with healthy controls.


Subject(s)
Absorption , Ascites , Colon, Ascending , Cytokines , Elasticity , Endotoxemia , Fibrosis , Healthy Volunteers , Humans , Ileum , Interleukin-10 , Intestines , Lactulose , Liver Cirrhosis , Mannitol , Permeability , Tumor Necrosis Factor-alpha , Ultrasonography
14.
Article in Chinese | WPRIM | ID: wpr-773669

ABSTRACT

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.


Subject(s)
Biopharmaceutics , Humans , Intestinal Absorption , Intestines , Medicine, Chinese Traditional , Perfusion , Permeability
15.
Article in Chinese | WPRIM | ID: wpr-773668

ABSTRACT

For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).


Subject(s)
Biopharmaceutics , Classification , Drugs, Chinese Herbal , Chemistry , Flavanones , Chemistry , Humans , Intestinal Absorption , Materia Medica , Classification , Permeability , Solubility
16.
Article in English | WPRIM | ID: wpr-773366

ABSTRACT

OBJECTIVE@#To comparatively study the toxicity of four metal-containing nanoparticles (MNPs) and their chemical counterparts to the air-blood barrier (ABB) permeability using an in vitro model.@*METHODS@#ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs (divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3 (sheet and short-rod-shaped), nano-ZnO, nano-PbS, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min. Every 10 min following exposure, the cumulative cleared volume (ΔTCL) of Lucifer yellow by the model was calculated. A clearance curve was established using linear regression analysis of ΔTCL versus time. Permeability coefficient (P) was calculated based on the slope of the curve to represent the degree of change in the ABB permeability.@*RESULTS@#The results found the increased P values of CuO-40, CuO-80, sheet, and short-rod-shaped nano-Al2O3, Al2(SO4)3, and Pb(NO3)2. Among them, small CuO-40 and CuO-80 were stronger than CuO-100 and CuSO4; no difference was observed between Al2(SO4)3 and sheet and short-rod-shaped nano-Al2O3; and nano-PbS was slightly weaker than Pb(NO3)2. So clearly the MNPs possess diverse toxicity.@*CONCLUSION@#ABB permeability abnormality means pulmonary toxicity potential. More studies are warranted to understand MNPs toxicity and ultimately control the health hazards.


Subject(s)
A549 Cells , Blood-Air Barrier , Metabolism , Epithelium , Metabolism , Humans , Metal Nanoparticles , Toxicity , Particle Size , Permeability
17.
Article in Chinese | WPRIM | ID: wpr-773235

ABSTRACT

To establish a determination method for the contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid of Baimai Ointment,and investigate the percutaneous permeability of Baimai Ointment and the effects of two kinds of penetration enhancers on percutaneous absorption of three components. The contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid were determined by high pressure liquid chromatography( HPLC). The vertical modified Franz diffusion cell was used to perform a transdermal experiment in vitro with the abdominal skin of mice( treated and untreated). The transdermal receptor liquid was preferably used to investigate the transdermal absorption rule of the Baimai Ointment and the effect of the penetration enhancer. The results showed that the comprehensive solubility of PEG-ET-NS( 3 ∶3 ∶4) was best among three types of receptor liquid PG-ET-NS( 3 ∶3 ∶4),PEG-ET-NS( 3 ∶3 ∶4),ET-NS( 3 ∶7). PEG-ET-NS was used as the receptor liquid for in vitro transdermal experiments. The cumulative permeation area of ammonium glycyrrhetate,nardosinone and curcumin within 24 h was 5. 73,18. 99,0. 38 μg·cm~(-2)respectively. Taking QEFand ER as comprehensive evaluation indicators of permeation performance,the comprehensive penetration-promoting performance of ammonium glycyrrhizinate: 3% PEG 400-ethanol-normal saline ≈ 1. 19 times( 3%azone) = 1. 94 times( blank); comprehensive penetration-promoting performance of nardosinone: 3% PEG 400-ethanol-normal saline≈1. 28 times( 3% azone) = 1. 37 times( blank); the comprehensive penetration performance of curcumin: 3% PEG 400-ethanol-normal saline≈1. 77 times( 3% azone) ≈3. 42 times( blank). The comprehensive penetration enhancement properties of the two penetration enhancers were as follows: 3% PEG 400-ethanol-normal saline>3%azone>blank. The transdermal absorption curve of ammonium glycyrrhetate,nardosinone and curcumin in Baimai Ointment were consistent with the zero-order equation,indicating that the transdermal absorption process was irrelevant to the concentration of three components,and its was a diffusion process. This experiment provides reference for the study of ointment transdermal preparations.


Subject(s)
Administration, Cutaneous , Animals , Mice , Ointments , Pharmacokinetics , Permeability , Skin , Skin Absorption
18.
Article in English | WPRIM | ID: wpr-776892

ABSTRACT

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.


Subject(s)
ATP-Binding Cassette Transporters , Genetics , Metabolism , Antifungal Agents , Chemistry , Metabolism , Pharmacology , Azoles , Pharmacology , Biosynthetic Pathways , Genetics , Candida albicans , Chemistry , Metabolism , Cell Membrane , Chemistry , Metabolism , Coculture Techniques , Drug Resistance, Fungal , Ergosterol , Metabolism , Fungal Proteins , Genetics , Metabolism , Lipids , Chemistry , Molecular Structure , Permeability , Phenyl Ethers , Chemistry , Metabolism , Pharmacology , Sterols , Chemistry , Metabolism , Stilbenes , Chemistry , Metabolism , Pharmacology , Triterpenes , Chemistry , Metabolism , Pharmacology
19.
Article in English | WPRIM | ID: wpr-760060

ABSTRACT

PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.


Subject(s)
Adenosine , Blotting, Western , Cyclic GMP , Dipyridamole , Humans , Matrix Metalloproteinases , Nitric Oxide , Permeability , Phosphodiesterase Inhibitors , Theophylline , Trabecular Meshwork
20.
Article in English | WPRIM | ID: wpr-758995

ABSTRACT

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.


Subject(s)
Aquaporin 2 , Arginine Vasopressin , Body Water , Cell Membrane , Diabetes Insipidus, Nephrogenic , Gene Expression Regulation , Homeostasis , Kidney , Kidney Tubules, Collecting , Osmolar Concentration , Permeability , Phenobarbital , Receptors, Vasopressin , Water
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