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Using field observations followed by petrological, geochemical, geochronological, and geophysical data we infer the presence of a previously unknown Miocene subglacial volcanic center ~230 km from the South Pole. Evidence of volcanism is from boulders of olivine-bearing amygdaloidal/vesicular basalt and hyaloclastite deposited in a moraine in the southern Transantarctic Mountains. 40Ar/39Ar ages from five specimens plus U-Pb ages of detrital zircon from glacial till indicate igneous activity 25-17 Ma. The likely source of the volcanism is a circular -735 nT magnetic anomaly 60 km upflow from the sampling site. Subaqueous textures of the volcanics indicate eruption beneath ice or into water at the margin of an ice mass during the early Miocene. These rocks record the southernmost Cenozoic volcanism in Antarctica and expand the known extent of the oldest lavas associated with West Antarctic rift system. They may be an expression of lithospheric foundering beneath the southern Transantarctic Mountains.
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INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.
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Extrofia Vesical , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Extrofia Vesical/cirurgia , Urodinâmica , Bexiga Urinária/cirurgia , Micção , Estudos RetrospectivosRESUMO
Nanofibers were prepared by electrospinning from pure polyvinyl alcohol (PVA), polyhydroxybutyrate (PHB), and their blends. Miscibility and morphology of both polymers in the nanofiber blends were studied by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC), revealing that PVA and PHB were miscible with good compatibility. DSC also revealed suppression of crystallinity of PHB in the blend nanofibers with increasing proportion of PVA. The hydrolytic degradation of PHB was accelerated with increasing PVA fraction. Cell culture experiments with a human keratinocyte cell line (HaCaT) and dermal fibroblast on the electrospun PHB and PVA/PHB blend nanofibers showed maximum adhesion and proliferation on pure PHB. However, the addition of 5 wt % PVA to PHB inhibited growth of HaCaT cells but not of fibroblasts. On the contrary, adhesion and proliferation of HaCaT cells were promoted on PVA/PHB (50/50) fibers, which inhibited growth of fibroblasts.
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Hidroxibutiratos/química , Nanofibras/química , Poliésteres/química , Álcool de Polivinil/química , Pele/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais , Adesão Celular , Linhagem Celular , Proliferação de Células , Técnicas de Química Analítica , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Proibitinas , Pele/citologiaRESUMO
Cationic liposomes composed of a novel lipid (N-{6-amino-1-[N-(9Z) -octadec9-enylamino] -1-oxohexan-(2S) -2-yl} -N'- {2- [N, N-bis(2-aminoethyl) amino] ethyl} -2-hexadecylpropandiamide) (OO4) and dioleoylphosphatidylethanolamine (DOPE) possess high amounts of amino groups and are promising systems for lipofection. Moreover, these cationic liposomes can also be used as a polycationic entity in multilayer formation using layer-by-layer technique (LbL), which is a method to fabricate surface coatings by alternating adsorption of polyanions and polycations. Since liposomes are suitable for endocytosis by or fusion with cells, controlled release of their cargo on site is possible. Here, a polyelectrolyte multilayer (PEM) system was designed of chondroitin sulfate (CS) and collagen type I (Col I) by LbL technique with OO4/DOPE liposomes embedded in the terminal layers to create an osteogenic microenvironment. Both, the composition of PEM and cargo of the liposomes were used to promote osteogenic differentiation of C2C12 myoblasts as in vitro model. The internalization of cargo-loaded liposomes from the PEM into C2C12 cells was studied using lipophilic (Rhodamine-DOPE conjugate) and hydrophilic (Texas Red-labeled dextran) model compounds. Besides, the use of Col I and CS should mimic the extracellular matrix of bone for future applications such as bone replacement therapies. Physicochemical studies of PEM were done to characterize the layer growth, thickness, and topography. The adhesion of myoblast cells was also evaluated whereby the benefit of a cover layer of CS and finally Col I above the liposome layer was demonstrated. As proof of concept, OO4/DOPE liposomes were loaded with dexamethasone, a compound that can induce osteogenic differentiation. A successful induction of osteogenic differentiation of C2C12 cells with the novel designed liposome-loaded PEM system was shown. These findings indicate that designed OH4/DOPE loaded PEMs have a high potential to be used as drug delivery or transfection system for implant coating in the field of bone regeneration and other applications.
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The occupied and unoccupied electronic structure of thin epitaxial CoSi(2) films grown on Si(111) substrates was studied using time-resolved two-photon photoemission and valence-band photoemission spectroscopy. The work function of the sample surfaces and the Schottky barrier height at the metal-semiconductor interface were measured as a function of annealing temperature. The photoemission data reveal several occupied and unoccupied electronic states which exhibit a high sensitivity to the annealing temperature. Time-resolved measurements show a behavior typical for a short-lived hot-electron gas and indications for an image-potential resonance.
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SHORT INTRODUCTION/BACKGROUND: Surgical intervention for acute testicular torsion can require either orchiopexy or orchiectomy. The decision of which surgery to perform is dependant on the amount of time that the testicle experienced ischemia and the viability of the testicle after reperfusion. OBJECTIVE: It is hypothesized that (1) there is a difference in orchiectomy and orchiopexy rates between prepubertal and postpubertal males with acute testicular torsion and (2) presenting symptoms may vary between the two age groups as prepubertal males may present with atypical symptoms, which could result in delayed presentation and diagnosis. STUDY DESIGN: A retrospective chart review was conducted on pediatric patients who were diagnosed with acute testicular torsion between June 2010 and August 2017. Demographic and clinical characteristics were extracted: age, ethnicity, referral pattern, primary insurance status, symptoms at presentation, prior history of ipsilateral testicular pain or intermittent torsion, recent trauma to genitalia, duration of symptoms (hours), gradual vs. acute onset of symptoms, time/weekday/season at presentation, and time interval from arrival at the study institution to surgical intervention (minutes). Patients were categorized into two groups: prepubertal group (age 1-12 years) and postpubertal group (age 13-18 years). Statistical analyses were performed using R, version 3.3.1. RESULTS: Ninety-one patients were included in the study. The overall orchiectomy rate was 30.8%. More prepubertal males underwent orchiectomy than postpubertal males (42.4% vs. 24.1%, respectively). Prepubertal males were more likely to present with abdominal pain than postpubertal males (27.3% vs. 10.3%, respectively). Those who underwent orchiectomy were more likely to present with longer duration of symptoms, testicular swelling, and abdominal pain than those who underwent orchiopexy. The risk of orchiectomy decreased by 14% per 1-year increase in age (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.94-1.00, p = .009). A steady decline in the proportion of patients undergoing orchiectomy was seen from 1 to 12 years of age. DISCUSSION: This study found that prepubertal males are at higher risk for orchiectomy than postpubertal males. The risk of orchiectomy decreases by 14-16% per 1-year increase in age. Prepubertal males are more likely to present with atypical symptoms and delayed presentation and diagnosis, leading to delayed surgical intervention. It is important for providers to perform a genital examination in prepubertal males who present with abdominal pain to rule out acute testicular torsion. Patients presenting with longer duration of symptoms, testicular swelling, and abdominal pain are at higher risk for orchiectomy. No correlation was found between orchiectomy rate and ethnicity, referral status, primary insurance status, and time/weekday/season at presentation. CONCLUSION: Among patients presenting to a tertiary pediatric hospital with acute testicular torsion, prepubertal males (younger than 12 years) are at higher risk for orchiectomy than postpubertal males. Prepubertal males are more likely to present with atypical symptoms which results in delayed presentation and diagnosis, leading to delayed in surgical intervention.
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Orquiectomia/estatística & dados numéricos , Orquidopexia/estatística & dados numéricos , Puberdade , Torção do Cordão Espermático/cirurgia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Torção do Cordão Espermático/diagnóstico , Testículo/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
The maintenance of endothelial cell (EC) monolayer architecture requires stable adhesions not only between neighboring cells but also between cells and the extracellular matrix. While the influence of biomaterials surface wettability on cell-substratum adhesion is rather well studied, its impact on cell-cell cohesion has not been extensively investigated. In the present study a model system consisting of hydrophilic and hydrophobic glass pre-coated with fibronectin and fibrinogen was used to study the influence of surface wettability on both types of cell adhesions. It was demonstrated that the substrate wettability controls the adhesion and cytoskeletal organization of endothelial cells, which has an impact on the subsequent ability of cells to establish stable cell-cell cohesions. These effects were related to the accessibility of specific domains of the adsorbed proteins. While the hydrophobic substratum promoted cell-cell cohesion, on hydrophilic substrata cell-substrate adhesion was dominant. In addition, evidence for an influence of surface wettability on the cross talk between integrins and cadherins was found.
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Proteínas de Membrana/química , Proteínas de Membrana/fisiologia , Adsorção , Caderinas/química , Caderinas/fisiologia , Adesão Celular/fisiologia , Células Cultivadas , Fibrinogênio/química , Fibrinogênio/fisiologia , Fibronectinas/química , Fibronectinas/fisiologia , Vidro , Humanos , Integrinas/química , Integrinas/fisiologia , Silanos , Propriedades de Superfície , MolhabilidadeRESUMO
Stress urinary incontinence (SUI) is a common problem affecting up to 35% of the female population. SUI results from a laxity of the pelvic floor anatomy, neuromuscular injury of the external urinary sphincter mechanism or both. Evaluation of the condition includes careful history, physical examination and urine analysis. Additional tests such as urodynamic studies and cystoscopic inspection are determined on a case by case basis. Treatment options range from behavior modification to medications to surgery. We present a review of the incidence, pathophysiology, evaluation and medical/surgical treatment options for SUI.
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Incontinência Urinária por Estresse , Idoso , Feminino , Humanos , Incontinência Urinária por Estresse/diagnóstico , Incontinência Urinária por Estresse/fisiopatologia , Incontinência Urinária por Estresse/terapiaRESUMO
INTRODUCTION/BACKGROUND: Bladder exstrophy is a rare diagnosis that presents major reconstructive challenges. To increase experience and proficiency in the care of bladder exstrophy (BE), the Multi-Institutional BE Consortium (MIBEC) was formed, with a focus on refining technical aspects of complete primary repair of bladder exstrophy (CPRE) and subsequent care. OBJECTIVE: Outcome measures included successful CPRE (absence of dehiscence), complications, and integrated points of technique and care over the short-term. STUDY DESIGN: Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as the host, with observation, commentary and critique by visiting collaborating surgeons. CPRE with bilateral iliac osteotomy was performed at 1-3 months of age. High-definition video capture of the surgery allowed local and distant broadcast to facilitate real-time observation and teaching, and recording of all procedures. RESULTS: From February 2013 to February 2015, MIBEC participating surgeons performed CPRE on 27 consecutive patients (22 classic BE, five epispadias). There were no dehiscences in 27 patients (0%, 95% CI 0-12.5%). Thirteen girls and 14 boys underwent CPRE at a median age of 2.3 months (range 0.1-51.6). One boy had a hypospadiac urethral meatus at CPRE completion. Hydronephrosis of mild or moderate grade was present postoperatively in eight girls and two boys. Additional results, per gender, are presented in the Summary table below. DISCUSSION: Absence of dehiscence in this cohort was comparable or compared favorably with the literature. However, several girls had significant obstructive complications following CPRE. The rate of bladder outlet obstruction (BOO) in girls was increased compared with published reports. A low complication rate was noted in the boys following CPRE, which was comparable to reports in the literature, and early signs of continence and spontaneous voiding were noted in some boys and girls. Limitations included variation in patient age at presentation, thereby introducing a wide age range at CPRE. Outcome data were limited by short follow-up regarding voiding with continence. CONCLUSION: This collaborative effort proved beneficial regarding significantly increased surgeon exposure to CPRE, refinement of CPRE technique, surgeon learning and expertise. Technical refinement of CPRE is ongoing.
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Extrofia Vesical/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Procedimentos de Cirurgia Plástica/métodos , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in advanced PD patients demonstrated improvement in UPDRS scores and in frequent clinical ratings on a global treatment response scale. Further analysis of data from these studies was performed to find predictive factors related to degree of improvement with infusion. Pearson's correlation coefficients between measures of improvement and baseline variables were calculated. Using data from one study, a prediction model was designed and was then evaluated using the other study's data. Correlations were found indicating that patients with more severe symptoms at baseline were most improved after infusion.
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Carbidopa/administração & dosagem , Dopaminérgicos/administração & dosagem , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Vias de Administração de Medicamentos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
As the Editors of leading international biomedical informatics journals, the authors report on a recent pattern of improper manuscript submissions to journals in our field. As a guide for future authors, we describe ethical and pragmatic issues related to submitting work for peer-reviewed journal publication. We propose a coordinated approach to the problem that our respective journals will follow. This Editorial is being jointly published in the following journals represented by the authors: Computer Methods and Programs in Biomedicine, International Journal of Medical Informatics, Journal of Biomedical Informatics, Journal of the American Medical Informatics Association, and Methods of Information in Medicine.
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Pesquisa Biomédica , Editoração , Retratação de Publicação como Assunto , Humanos , Jornalismo MédicoRESUMO
The role of osmotic forces and cell swelling in the influenza virus-induced fusion of unsealed or resealed ghosts of human erythrocytes was investigated under isotonic and hypotonic conditions using a recently developed fluorescence assay (Hoekstra, D., De Boer, T., Klappe, K., Wilschut, J. (1984) Biochemistry 23, 5675-5681). The method is based on the relief of fluorescence selfquenching of the fluorescent amphiphile octadecyl rhodamine B chloride (R18) incorporated into the ghost membrane as occurs when labeled membranes fuse with unlabeled membranes. No effect neither of the external osmotic pressure nor of cell swelling on virally mediated ghost fusion was established. Influenza virus fused unsealed ghosts as effectively as resealed ghosts. It is concluded that neither osmotic forces nor osmotic swelling of cells is necessary for virus-induced cell fusion. This is supported by microscopic observations of virus-induced fusion of intact erythrocytes in hypotonic and hypertonic media. A disruption of the spectrin-actin network did not cause an enhanced cell fusion at acidic pH of about 5 or any fusion at pH 7.4.
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Membrana Eritrocítica/metabolismo , Vírus da Influenza A/fisiologia , Fusão de Membrana , Eritrócitos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Pressão OsmóticaRESUMO
The structure of the glycocalyx of the membrane of human erythrocytes and spectrin-depleted vesicles was studied under various conditions by two spin-labelling approaches: covalently labelling sialic acid residues of the glycocalyx and incorporation of a charged hydrophobic spin probe, CAT 16, being sensitive to alterations on the membrane surface into the lipid phase. Although cell electrophoretic measurements which were performed, additionally, indicated an erection of the glycocalyx upon decreasing the ionic strength of the suspension medium a more restricted mobility of spin-labelled sialic acid residues was found, in this case probably due to electrostatic interactions. The enhanced mobility of the spin probe CAT 16 at low ionic strength as well as in the case of neuraminidase-treated cells could be caused by reduced steric and electrostatic interaction with glycoproteins and glycolipids. La3+ adsorption and virus attachment on the human erythrocyte membrane were accompanied with a reduced mobility of sugar headgroups of the surface coat. No indication of cluster formation or lateral segregation of glycophorin molecules was found upon virus binding. After denaturation of the spectrin cytoskeleton of intact erythrocytes, increased mobility of spin-labelled sialic acid residues was observed.
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Membrana Eritrocítica/análise , Glicoproteínas , Polissacarídeos , Espectroscopia de Ressonância de Spin Eletrônica , Agregação Eritrocítica , Humanos , Lantânio/metabolismo , Matemática , Concentração Osmolar , Ácidos Siálicos/sangueRESUMO
Biomedical technology has opened up possibilities of treating the failure of internal organs like kidney and liver by artificial organ therapy. Most of these techniques are based on polymer membranes, which allow the removal of excess of water, salts and toxins from the circulation. However, haemodialysis for the replacement of kidney function results in an increased morbidity and mortality of patients after long-term application. Conventional therapy, such as haemofiltration for the treatment of acute liver failure does not improve significantly the survival rate of patients. Biohybrid organ support as a combination of the artificial organ therapy with the functional activity of immobilised cells seems to be a solution of the problem. Membranes applied in these devices have to face both tissue cells and blood. Organ cells in biohybrid organs have to make intimate contact with the surface of membrane but must also develop close cell-cell-connections as a prerequisite for their survival and high functional activity. Blood to be detoxified will contact the other side of membrane and may not become activated by the synthetic material. New polymer membranes based on acrylonitrile were developed to address these requirements by tailoring the composition of copolymers and to be applied in a specific hollow fibre bioreactor with an outer fibre for blood contact, and an inner fibre for tissue contact or vice versa.
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Membranas Artificiais , Polímeros , Diálise Renal/métodos , Animais , Materiais Biocompatíveis , Coagulação Sanguínea , Linhagem Celular , Proteínas do Sistema Complemento/metabolismo , Cães , Células Epiteliais/fisiologia , Células Epiteliais/ultraestrutura , Hemofiltração , Heparina , Humanos , Microscopia Eletrônica , Ativação Plaquetária , Adesividade Plaquetária , Diálise Renal/instrumentação , UltrafiltraçãoRESUMO
To evaluate the developmental and sex-specific changes in spontaneous GH secretion in terms of both secretory rate and pulsatile pattern, we investigated 24-h GH profiles (integrated 20-min samples) in 208 healthy children (91 girls and 117 boys) of normal heights at all stages of puberty. The plasma GH concentrations were transformed to GH secretion rates by means of a deconvolution technique. In prepubertal boys and girls, the mean secretion rates were comparable (0.66 and 0.68 U/24 h), but increased during puberty differently: earlier in girls, already at stage 2, with the highest rates at stages 3 and 4 (1.70 and 1.96 U/24 h); later in boys, at stage 4 (1.66 U/24 h). In both sexes the GH secretion rate decreased to prepubertal values at stage 5. The GH secretion rate correlated negatively with weight for height expressed in SD scores only in puberty (boys, r = -0.44, P < 0.001; girls, r = -0.22; P < 0.05). The number of peaks with high amplitudes increased with the progress of puberty in both boys (stage 2) and girls (stages 3 and 4). In both prepubertal girls and boys, a marked day-night rhythm was observed, which disappeared in midpuberty in boys owing to a greater increase in peak amplitudes during the day than at night. The mean number of peaks per 24 h was unchanged in girls, but decreased in late pubertal boys. In summary, we found a sex-specific increase in the GH secretion rate during pubertal development that occurs at an earlier pubertal stage and is more pronounced in girls than in boys. There are underlying changes in the mean GH amplitudes in both boys and girls as well as an increased baseline secretion in girls. In puberty, body composition modulates the GH secretion rate in both sexes.
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Hormônio do Crescimento/sangue , Puberdade/sangue , Adolescente , Criança , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Masculino , Fatores Sexuais , Fatores de TempoRESUMO
The influence of the antivirus drugs amantadine and rimantadine and of the anionic analogue 1-adamantane-carboxylic acid on a range of properties of human erythrocyte membrane and of thrombocytes has been compared with the effect of the local anaesthetic tetracaine. At low antiviral drug concentrations the abilities of the drugs to induce erythrocyte shape change and suppress osmotic haemolysis were quantitatively proportional to their clinical potency (rimantadine more effective than amantadine at the same concentration). Rimantadine was also more effective than amantadine in suppressing influenza virus-erythrocyte fusion and viral induced haemolysis. The antiviral drug effects were qualitatively similar to those induced by tetracaine. At the quantitative level, tetracaine was more efficient than the antiviral drugs in inhibiting osmotic haemolysis, virus membrane fusion and platelet aggregation. In the absence of any specificity of the antiviral drug effects we argue for a lysosomotropic mode of drug action, i.e. that the drugs modify virus-membrane interactions by changing the endosomal or lysosomal pH.
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Adamantano/análogos & derivados , Amantadina/farmacologia , Antivirais/farmacologia , Plaquetas/efeitos dos fármacos , Membrana Eritrocítica/efeitos dos fármacos , Rimantadina/farmacologia , Tetracaína/farmacologia , Fracionamento Celular , Espectroscopia de Ressonância de Spin Eletrônica , Hemaglutinação por Vírus , Humanos , Fragilidade Osmótica , Agregação PlaquetáriaRESUMO
OBJECTIVE: To evaluate the benefit of determining the maximal elimination rate (Vmax) and the endogenous production of hyaluronan (HYA) in relation to the basal HYA concentration (c0) in rheumatoid arthritis (RA) patients; and to evaluate the compatibility of a new model for HYA kinetics, taking renal elimination into separate account in the overall clearance of HYA from the blood. METHODS: The calculations of production and elimination of HYA were based on the HYA loading test, which was performed in 21 patients with RA and 15 healthy controls. A blood sample was drawn before the loading test, followed by an intravenous (i.v.) injection of HYA as a single bolus dose of 7.5 mg. Blood samples were taken regularly during the next 60 minutes. A theoretical model with computational analysis of the data collected was used for calculating HYA production and elimination. RESULTS: Patients with RA had significantly higher c0 than healthy controls, although in 10 of 21 patients c0 was within the normal range. The RA patients also had higher Vmax than healthy controls, but the difference was not significant. The calculated production of HYA was increased in RA patients (P = .001) and correlated with c0 (P < .0001). The new model for HYA kinetics, in which the renal elimination was taken separately into account, proved to be more compatible than the previous model. CONCLUSION: The HYA loading test can help determine whether the increased serum level of HYA in RA patients is due to a high production or reduced elimination of HYA or both.
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Artrite Reumatoide/sangue , Ácido Hialurônico/biossíntese , Ácido Hialurônico/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Valores de Referência , Análise de Regressão , Sensibilidade e EspecificidadeRESUMO
In a previous study we observed that protein tyrosine phosphorylation was significantly diminished in the focal adhesions of human fibroblasts attached on a hydrophobic surface in comparison with hydrophilic glass. This result raises the possibility that the tyrosine phosphorylation pathway may be involved in the regulation of cell-biomaterial interaction. To learn more about the interaction of anchorage-dependent cells with biomaterials, four different materials with wettability ranging from hydrophilic (water contact angle 25 degrees) to hydrophobic (water contact angle 111 degrees) were investigated, i.e. clean glass (glass), aminopropylsilane (APS), octadecylsilane (ODS) and silicone (SI). Immunofluorescence microscopy revealed increased stress formation and fibronectin (FN) receptor-rich focal adhesions for fibroblasts attached on more hydrophilic surfaces (glass and APS) in comparison to the relatively hydrophobic materials (ODS and SI). Phosphorylation of tyrosine residues, also studied by immunofluorescence microscopy, was considerably higher on glass and APS, lower for ODS, negligible for SI, and was found to colocalize with FN receptor-rich focal adhesions. Preadsorption of FN tended to restore cell adhesion and spreading on the hydrophobic ODS and SI. Quantitative data on cell proliferation and tyrosine phosphorylation showed moderate wettable material maximum values for APS, followed by glass. ODS and SI, demonstrating a non-linearity of these parameters with the wettability of materials. Interestingly, the preadsorption of FN increased both parameters, particularly for the hydrophobic materials ODS and SI. Phosphorylation of tyrosine on FN-coated substrata was corroborated by the accessibility of binding sites estimated by ELISA using polyclonal and monoclonal FN antibodies. Our results suggest that measurement of the phosphotyrosine activity of cells may be a sensitive parameter for the ability of biomaterials to support the attachment and proliferation of cells.
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Materiais Biocompatíveis/farmacologia , Fibroblastos/citologia , Tirosina/metabolismo , Adsorção , Anticorpos , Anticorpos Monoclonais , Adesão Celular , Divisão Celular/fisiologia , Fibroblastos/fisiologia , Fibroblastos/ultraestrutura , Fibronectinas/metabolismo , Fibronectinas/farmacocinética , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Fosforilação , Receptores de Fibronectina/metabolismo , Transdução de Sinais/fisiologia , Pele/citologia , Pele/ultraestrutura , Fenômenos Fisiológicos da Pele , Tirosina/fisiologia , MolhabilidadeRESUMO
Regioselective derivatization was carried out introducing sulfate, phosphate or quaternary ammonia groups in C2-, C3- and C6-position of the anhydroglycose unit of cellulose. The anticoagulant potential of these derivatives was estimated with common clotting assays, such as thrombin time and partial thromboplastin time. It was found that a pronounced anticoagulant activity of cellulose derivatives could be achieved if the degree of substitution (DS) with sulfate was above 1.0. The anticoagulant activity was maximal at a DS of about 1.5 and then decreased again. Further, it was detected that particularly sulfation in C2-position resulted in a pronounced anticoagulant activity of cellulose derivatives. Development and application of assays specific for thrombin and factor Xa indicated that the anticoagulant potential of these cellulose derivatives was mainly due to anti-thrombin activity. The comparison of cellulose sulfates and cellulose derivatized with phosphate and quaternary ammonium groups demonstrated that the negative charge and type of the substituent is an important prerequisite for the anticoagulant activity of cellulose derivatives. Indeed, derivatization with sulfate produced superior activity in comparison with phosphate.
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Anticoagulantes/farmacologia , Celulose/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Celulose/química , Fator Xa/farmacologia , Heparina/química , Heparina/farmacologia , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Peso Molecular , Protrombina/farmacologiaRESUMO
The influence of surface wettability and preadsorption of plasma proteins on cell adhesion was studied using human peripheral blood lymphocytes (PBL). Hydrophilic glass and hydrophobic octadecyl glass were used as model surfaces with known wettability. The adhesion of PBL was investigated under non-flow conditions that are considered as a model for the adhesion of migrating lymphocytes in the tissue. Furthermore, adhering lymphocytes were exposed to increasing shear forces to investigate the detachment under laminar flow conditions to simulate the situation during blood flow. The proteins used in this study were attachment proteins such as fibrinogen, fibronectin and vitronectin. Human serum albumin was used as a control. It was found under both conditions (static and dynamic) that PBL adhesion was strongly influenced by the wettability of the surfaces. Furthermore, it was shown that the properties of the underlying surface influenced the interaction between preadsorbed attachment proteins and PBL.