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Materials science is nowadays facing challenges in optimizing properties of materials which are needed for numerous technological applications and include, but are not limited to, mechanics, electronics, optics, etc. The key issue is that for emerging applications materials are needed which incorporate certain properties from polymers or biopolymers and metals or ceramics at the same time, thus fabrication of functional hybrid materials becomes inevitable. Routes for the synthesis of functional hybrid materials can be manifold. Among the explored routes vapor phase processing is a rather novel approach which opts for compatibility with many existing industrial processes. This topical review summarizes the most important approaches and achievements in the synthesis of functional hybrid materials through vapor phase routes with the goal to fabricate suitable hybrid materials for future mechanical, electronic, optical or biomedical applications. Most of the approaches rely on atomic layer deposition (ALD) and techniques related to this process, including molecular layer deposition (MLD) and vapor phase infiltration (VPI), or variations of chemical vapor deposition (CVD). The thus fabricated hybrid materials or nanocomposites often show exceptional physical or chemical properties, which result from synergies of the hybridized materials families. Even though the research in this field is still in its infancy, the initial results encourage further development and promise great application potential in a large variety of applications fields such as flexible electronics, energy conversion or storage, functional textile, and many more.
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Prediction (regression) equations are widely used, but their reliability as predictive tools is questionable as they provide contradicting results. The key point is that values calculated by regression equations are not precisely defined numbers but lie within a range of possible values in the standard deviation interval, none of which can be considered as the most probable. Ignoring this point leads to illicit/improper calculations, generating wrong results, which may have adverse consequences for human health. To demonstrate this, we applied the equations of Harris and Benedict in a reverse method, i.e. calculating (predicting) the daily energy expenditure in the same subjects used to obtain the equations and comparing values with the original measured data. We used the Bland-Altman and frequency distribution analyses. We found large differences in both individual data and population characteristics, showing that prediction equations are not predictive tools.
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Metabolismo Basal , Análise de Regressão , Adulto , Ingestão de Energia , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population. METHODS: A total of 314 women with placenta previa were enrolled prospectively and underwent transabdominal and transvaginal ultrasound examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of placental attachment disorder (PAD) was based on the detection of at least two of the following ('two-criteria system'): loss/irregularity of the retroplacental clear zone, thinning/interruption of the uterine serosa-bladder wall interface, turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm, increased vascularity of the uterine serosa-bladder wall interface, loss of vascular arch parallel to the basal plate and/or irregular intraplacental vascularization. Definitive diagnosis was made at delivery by Cesarean section. Maternal outcome in cases diagnosed antenatally was compared with that in cases diagnosed at delivery. RESULTS: There were 37/314 cases of PAD (29 anterior and eight posterior). The two-criteria system identified 30 cases of placenta accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior and posterior placentae were considered separately, the detection rates of PAD were 89.7 and 50.0%, respectIvely. Maternal outcome was better in women with prenatal diagnosis of PAD, as seen by less blood loss and shorter hospitalization. CONCLUSIONS: Our data confirmed that grayscale and color Doppler ultrasound have good performance in the diagnosis of PAD and that prenatal diagnosis improves maternal outcome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
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Placenta Acreta/diagnóstico por imagem , Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal/métodos , Adulto , Cesárea , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta Acreta/patologia , Gravidez , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia Doppler em Cores/métodos , Útero/diagnóstico por imagem , Útero/patologiaRESUMO
OBJECTIVE: To assess the feasibility and utility of contrast-enhanced microcomputed tomography (micro-CT) for identifying structural anomalies in ex-vivo first- and second-trimester human fetuses and isolated fetal hearts. METHODS: Radiopaque iodine staining and micro-CT scanning protocols were first developed in rodent studies and then used to examine routinely fixed whole human fetuses (n = 7, weight 0.1-90 g, gestational age, 7-17 weeks) and isolated fetal hearts (n = 14, weight 0.1-5.2 g, gestational age, 11-22 weeks). Samples were scanned using an isotropic resolution of 18 (and, if necessary, 9 or 35) µm and findings were interpreted jointly by four fetal pathologists, a fetal cardiologist and a radiologist. Samples with gestational ages ≥ 13 weeks also underwent conventional autopsy or dissection. RESULTS: Micro-CT identified all anatomical structures and abnormalities documented by the macroscopic examination. In all seven cases involving fetuses ≤ 13 weeks (four fetuses, three isolated hearts), micro-CT excluded the presence of structural anomalies. In the remaining 14 cases, it provided all the information obtained with invasive autopsy or dissection and in seven of the 14 (two fetuses, five isolated hearts) it furnished additional diagnostic details. CONCLUSIONS: This pilot study confirms the feasibility of postmortem contrast-enhanced micro-CT assessment of structural anomalies in whole small fetuses and fetal hearts. Further study is needed to confirm our findings, particularly in whole fetuses, and to define the extent to which this virtual examination might be used instead of conventional invasive autopsy.
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Feto/anormalidades , Microtomografia por Raio-X/métodos , Animais , Autopsia , Meios de Contraste , Estudos de Viabilidade , Feminino , Coração Fetal/anormalidades , Coração Fetal/diagnóstico por imagem , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Iodetos , Camundongos Endogâmicos C57BL , Projetos Piloto , Gravidez , Segundo Trimestre da Gravidez , Ratos Sprague-DawleyRESUMO
BACKGROUND: Optimizing immune checkpoint inhibitor (ICI) therapy may require identification of co-targetable checkpoint pathways via immune profiling. Herein, we analyzed the transcriptomic expression and clinical correlates of V-domain immunoglobulin suppressor of T-cell activation (VISTA), a promising targetable checkpoint. PATIENTS AND METHODS: RNA sequencing was carried out on 514 tissues reflecting diverse advanced/metastatic cancers. Expression of eight immune checkpoint markers [lymphocyte-activation gene 3 (LAG-3), tumor necrosis factor receptor superfamily 14 (TNFRSF14), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), B- and T-lymphocyte attenuator (BTLA), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cytotoxic T-lymphocyte antigen 4 (CTLA-4)], in addition to VISTA, was analyzed, along with clinical outcomes. RESULTS: High VISTA RNA expression was observed in 32% of tumors (66/514) and was the most common highly expressed checkpoint among the nine assessed. High VISTA expression was independently correlated with high BTLA, TIM-3, and TNFRSF14, and with a diagnosis of pancreatic, small intestine, and stomach cancer. VISTA transcript levels did not correlate with overall survival (OS) from metastatic/advanced disease in the pan-cancer cohort or with immunotherapy outcome (progression-free survival and OS from the start of ICI) in 217 ICI-treated patients. However, in ICI-treated pancreatic cancer patients (n = 16), median OS was significantly shorter (from immunotherapy initiation) for the high- versus not-high-VISTA groups (0.28 versus 1.21 years) (P = 0.047); in contrast, VISTA levels were not correlated with OS in 36 pancreatic cancer patients who did not receive ICI. CONCLUSION: High VISTA expression correlates with high BTLA, TIM-3, and TNFRSF14 checkpoint-related molecules and with poorer post-immunotherapy survival in pancreatic cancer, consistent with prior literature indicating that VISTA is prominently expressed on CD68+ macrophages in pancreatic cancers and requiring validation in larger prospective studies. Immunomic analysis may be important for individualized precision immunotherapy.
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Antígenos B7 , Neoplasias , Humanos , Neoplasias/imunologia , Antígenos B7/metabolismo , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Proteínas de Checkpoint Imunológico/metabolismo , IdosoRESUMO
The two main Afrotropical malaria vectors - Anopheles coluzzii and An. gambiae - are genetically distinct and reproductively isolated across West Africa. However, populations at the western extreme of their range are assigned as "intermediate" between the two species by whole genome sequence (WGS) data, and as hybrid forms by conventional molecular diagnostics. By exploiting WGS data from 1,190 specimens collected across west Africa via the Anopheles gambiae 1000 Genomes network, we identify a novel putative taxon in the far-west (provisionally named Bissau molecular form), which did not arise by admixture but rather originated at the same time as the split between An. coluzzii and An. gambiae. Intriguingly, these populations lack insecticide resistance mechanisms commonly observed in the two main species. These findings lead to a change of perspective on malaria vector species in the far-west region with potential for epidemiological implications, and a new challenge for genetic-based mosquito control approaches.
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OBJECTIVE: Vulvovaginal atrophy is a condition closely related to low circulating estrogen levels, with post-menopause being the main cause. However, patients of childbearing age may also present with these symptoms due to treatments that reduce estrogen production. Local estrogen therapy is the causal treatment of local symptoms, but it is not always accepted and is often abandoned by patients. In recent years, alternative therapies have been proposed: fractional CO2 laser or the conjugate treatment with normobaric oxygen and hyaluronic acid, the latter being the subject of this study. The study aimed to evaluate the effectiveness of conjugate topical treatment with normobaric oxygen and hyaluronic acid. PATIENTS AND METHODS: 50 patients were evaluated and treated with 5 applications of 15 minutes each, every 15 days, with Caressflow®. All patients presented at least one of the symptoms related to vulvovaginal atrophy: dryness, burning, and dyspareunia. In all cases, vulvoscopy, colposcopy, and cervicovaginal cytology were performed. The patients were interviewed with an analogic scale (VAS) concerning the severity of symptoms before and after the treatment. Colposcopy and PAP-smear were assessed by mean of Vaginal Health Index Score (VHI) at baseline and at the end of the treatment. RESULTS: All patients completed the treatment scheme and presented with a significant improvement in subjective symptoms. The colposcopy and PAP-smear performed 10 days after the end of the last treatment showed a significant improvement in the appearance and elasticity of the vaginal epithelium and the cytological picture, which showed, in the sample taken after treatment, hyaluronic acid vesicles within the cell cytoplasm. CONCLUSIONS: This study corroborates the data presented in the latest published papers on the effectiveness of treatment with normobaric O2 and hyaluronic acid on vaginal atrophy. Efficacy has been confirmed both in terms of subjective symptoms reported by the patients and objective improvement at colposcopy and PAP-smear cytology.
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Lasers de Gás , Doenças Vaginais , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Estudos Prospectivos , Oxigênio , Resultado do Tratamento , Vulva/patologia , Atrofia/patologia , Vagina/patologia , EstrogêniosRESUMO
BACKGROUND AND AIMS: Metabolic syndrome (MS) has recently been claimed to be an important new risk factor for the occurrence of coronary heart disease (CHD) and cardiovascular disease (CVD) events, although it is simply a combination of known risk factors used in a dichotomized fashion. The aims of this analysis were to explore the predictive role of MS for CHD and CVD events in a population study, in comparison with using the same factors in a continuous fashion, with special emphasis on HDL cholesterol. METHODS AND RESULTS: In the second examination of the Gubbio population study from central Italy, 2650 cardiovascular disease-free men and women, aged 35-74 years around 1990, were examined and followed-up for 12 years. The classic risk factors (sex, age, systolic blood pressure, serum cholesterol and smoking habits) were studied as predictors of CHD and CVD events, alone and with the contribution of other factors (HDL cholesterol, blood glucose, serum triglycerides and waist circumference) included in the so-called MS, based on several multivariate models. MS was also tested after adjustment for other risk factors. MS produced a predictive significant relative risk of 1.67 for CHD events and 1.82 for CVD events, but considering its single risk factors, the only ones contributing to prediction were HDL cholesterol and systolic blood pressure. Dedicated analyses showed that MS does not add anything to the power of prediction beyond the role of the single risk factors treated in a continuous fashion, while the best predictive power is obtained using classic risk factors (sex, age, smoking habits, total cholesterol, systolic blood pressure) with the addition of HDL cholesterol. CONCLUSIONS: The predictive power of MS is bound only to the presence of HDL cholesterol and blood pressure and does not add anything to using the same risk factor treated in a continuous fashion.
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HDL-Colesterol/sangue , Doença das Coronárias/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Idoso , Glicemia/análise , Pressão Sanguínea , Estudos de Coortes , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Modelos Teóricos , Análise Multivariada , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco , FumarRESUMO
BACKGROUND: Mutations in the SLC26A4 gene, coding for the anion transporter pendrin, are responsible for Pendred syndrome, characterized by congenital sensorineural deafness and dyshormonogenic goiter. The physiological role of pendrin in the thyroid is still unclear and the lack of a thyroid phenotype in some patients with SLC26A4 mutations and in Slc26a4 (-/-) mice indicate the existence of environmental or individual modifiers able to compensate for pendrin inactivation in the thyroid. Since pendrin can transport iodide in vitro, variations in iodide supply have been claimed to account for the thyroid phenotype associated with pendrin defects. AIM: The Slc26a4 (-/-) mouse model was used to test the hypothesis that iodide supply may influence the penetrance and expressivity of SLC26A4 mutations. MATERIALS AND METHODS: Slc26a4 (-/-) and (+/+) mice were fed up to 6 months on a standard or low iodine diet and were evaluated for thyroid structural abnormalities or biochemical hypothyroidism. RESULTS: A 27-fold iodide restriction induced similar modifications in thyroid histology, but no differences in thyroid size, T4 or TSH levels were observed between between Slc26a4 (-/-) and (+/+) mice, either in standard conditions and during iodine restriction. CONCLUSIONS: Iodide restriction is not able to induce a thyroid phenotype in Slc26a4 (-/-) mice. These experimental data, together with those coming from a review of familial Pendred cases leaving in regions either with low or sufficient iodide supply, support the idea that the expression of thyroid phenotype in Pendred syndrome is more powerfully influenced by individual factors than by dietary iodide.
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Proteínas de Transporte de Ânions/genética , Dieta , Bócio/fisiopatologia , Hipotireoidismo/fisiopatologia , Iodo/administração & dosagem , Animais , Proteínas de Transporte de Ânions/metabolismo , Modelos Animais de Doenças , Bócio Nodular/genética , Bócio Nodular/fisiopatologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Iodo/metabolismo , Camundongos , Camundongos Knockout , Fenótipo , Transportadores de Sulfato , Glândula Tireoide/citologia , Glândula Tireoide/patologia , Glândula Tireoide/fisiologia , Tireotropina/metabolismo , Tiroxina/metabolismoRESUMO
OBJECTIVES: Campomelic dysplasia is a rare congenital skeletal disorder characterized by bowing of the long bones and a variety of other skeletal and extraskeletal defects, many of which can now be identified prenatally using advanced ultrasound equipment. The disorder is caused by mutations in SRY-box 9 (SOX9), a gene that is abundantly expressed in chondrocytes as well as in other tissues. However, the correlation between genotype and phenotype is still unclear. We report five cases of prenatally detected campomelic dysplasia in which the diagnosis was confirmed by molecular analysis. METHODS: Ultrasound examinations were performed between 12 and 32 weeks. Standard fetal biometric measurements were obtained. Fetal sex was determined sonographically and confirmed by chromosomal analysis. Genomic DNA was obtained in four cases before termination of pregnancy from chorionic villi or amniocytes and in one case postnatally from peripheral blood. RESULTS: Skeletal dysplasia, most often limb shortening and bowed femora, was observed in one case in the first trimester, in three cases in the second trimester and in one case, presenting late for antenatal care, in the third trimester. Four of the pregnancies were terminated and one was carried to term. Postmortem/postnatal physical and radiographic examinations confirmed the presence of anomalies characteristic of campomelic dysplasia. A de novo mutation in the SOX9 gene was detected in all four cases that underwent termination. The father of the proband in the case that went to term was a carrier of a somatic mosaic mutation without clinical or radiographic signs of campomelic dysplasia. CONCLUSIONS: It is likely that the integrated expertise of ultrasonographers, obstetricians, pediatricians and clinical geneticists will markedly improve the likelihood of accurate prenatal clinical diagnoses of campomelic dysplasia. This will, in turn, encourage more specific molecular testing and facilitate comprehensive genetic counseling.
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Displasia Campomélica/diagnóstico por imagem , Displasia Campomélica/genética , Fatores de Transcrição SOX9/genética , Aborto Induzido , Adulto , Displasia Campomélica/embriologia , Feminino , Aconselhamento Genético , Genótipo , Idade Gestacional , Humanos , Fenótipo , Mutação Puntual/genética , Gravidez , Primeiro Trimestre da Gravidez , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
In this study, we evaluated the activity of two novel pyrazolopyrimidine derivatives (Si 34 and Si 35) against ARO cells, a human anaplastic thyroid cancer cell line. ARO cells exposed to different concentrations of the drugs showed a reduced growth rate and an increase of mortality. After 72 h incubation, doses of 5 and 10 microM Si 34 determined a decrease of cell counts by approximately 25% and approximately 75% compared with those of control cells respectively. Similar findings were observed using Si 35. Treatment with both Si 34 and Si 35 at 10 microM increased cell mortality also ( approximately 29% and approximately 18% respectively). At these concentrations, a decrease in cyclin D1 levels was observed. To improve the biopharmaceutical properties, a liposome formulation was prepared. When entrapped in unilamellar liposomes, Si 34 exerted its cytotoxic effects even at lower doses (maximal inhibition at 5 microM) and after shorter incubation time (48 h) either in ARO or other thyroid cancer cell lines. The effects were associated with weak apoptotic death. Inhibition of epidermal growth factor-stimulated src and ERK phosphorylation, as well as reduction of migration properties of ARO cells was also observed. Moreover, the growth of tumor xenografts induced in severe combined immunodeficiency (SCID) mice was inhibited by i.v. administration of 25-50 mg/kg of the drug liposomal formulation. In conclusion, the liposomal preparation of this novel pyrazolopyrimidine derivative appears to be a promising tool for the treatment of anaplasic thyroid cancer.
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Lipossomos/farmacocinética , Pirazóis/farmacocinética , Pirimidinas/farmacocinética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Triazóis/farmacocinética , Animais , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Pirazóis/síntese química , Pirimidinas/síntese química , Fator de Transcrição STAT1/efeitos dos fármacos , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Triazóis/síntese química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We studied the expression and the hormonal regulation of the PDS gene product, pendrin, which is, in thyrocytes, responsible for the iodide transport out of the cell. We show that PC Cl3 cells, a fully differentiated thyroid cell line, grown without TSH and insulin, express very low level of PDS mRNA; such expression is greatly increased after stimulation with insulin or TSH. (125)I pre-loaded cells showed an (125)I efflux accelerated in chloride-containing buffer with respect to chloride-free buffer, suggesting that this efflux is chloride dependent. By immunoblotting, pendrin was found in agonists-stimulated cells, whereas it was barely detectable in un-stimulated cells. An increase in both PDS mRNA and protein was also obtained using phorbol ester PMA, or using 8-Br-cAMP and forskolin. Stimulation with insulin (1 microg/ml; 0-40 min) provoked the cytosol-to-membrane translocation of pendrin and a decrease of intracellular I(-) content in (125)I pre-loaded cells. Insulin- or PMA-treated cells also showed a cytosol-to-membrane translocation of PKC-delta and -epsilon. Inhibition of both PKC-delta and -epsilon activities by GF109203X blocked pendrin translocation, whilst the inhibition of PKA did not. The selective inhibition of PKC-delta by rottlerin did not affect the insulin-provoked translocation of pendrin whilst it was inhibited by a PKC-epsilon translocation inhibitor peptide and also by PKC-epsilon downregulation using the small interfering RNA, thus indicating that such translocation was due to PKC-epsilon activity. In conclusion, our study demonstrates that, in PC Cl3 cells, pendrin expression and localisation are regulated by insulin and influenced by a PKC-epsilon-dependent intracellular pathway.
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Membrana Celular/metabolismo , Antiportadores de Cloreto-Bicarbonato/metabolismo , Citosol/metabolismo , Proteína Quinase C-épsilon/metabolismo , Glândula Tireoide/metabolismo , Animais , Western Blotting , Linhagem Celular , Membrana Celular/química , Citosol/química , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Iodetos/metabolismo , Transporte Proteico/fisiologia , RNA Interferente Pequeno , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transportadores de Sulfato , Glândula Tireoide/citologiaRESUMO
Glutathione (GSH) is one of the most important defense mechanisms against oxidative stress in the respiratory epithelial lining fluid. Considering that GSH secretion in respiratory cells has been postulated to be at least partially electrogenic, and that the mucoregulator S-carbocysteine lysine salt monohydrate (S-CMC-Lys) can cause an activation of epithelial Cl(-) conductance, the purpose of this study was to verify whether S-CMC-Lys is able to stimulate GSH secretion. Experiments have been performed by patch-clamp technique, by high-performance liquid chromatography (HPLC) assay, and by Western blot analysis on cultured lines of human respiratory cells (WI-26VA4 and CFT1-C2). In whole-cell configuration, after cell exposure to 100 microM S-CMC-Lys, a current due to an outward GSH flux was observed, which was inhibitable by 5-nitro-2-(3-phenylpropylamino)-benzoate and glibenclamide. This current was not observed in CFT1-C2 cells, where a functional cystic fibrosis transmembrane conductance regulator (CFTR) is lacking. Inside-out patch-clamp experiments (GSH on the cytoplasm side, Cl(-) on the extracellular side) showed the activity of a channel, which was able to conduct current in both directions: the single channel conductance was 2-4 pS, and the open probability (P(o)) was low and voltage-independent. After preincubation with 100 microM S-CMC-Lys, there was an increase in P(o), in the number of active channels present in each patch, and in the relative permeability to GSH vs Cl(-). Outwardly directed efflux of GSH could also be increased by protein kinase A, adenosine 5'-triphosphate, and cyclic adenosine monophosphate (cAMP) added to the cytoplasmic side (whole-cell configuration). The increased secretion of GSH observed in the presence of S-CMC-Lys or 8-bromoadenosine-3',5'-cyclic monophosphate was also confirmed by HPLC assay of GSH on a confluent monolayer of respiratory cells. Western blot analysis confirmed the presence of CFTR in WI-26VA4 cells. This study suggests that S-CMC-Lys is able to stimulate a channel-mediated GSH secretion by human respiratory cells: electrophysiological and pharmacological characteristics of this channel are similar to those of the CFTR channel.
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Carbocisteína/análogos & derivados , Glutationa/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Carbocisteína/farmacologia , Linhagem Celular , Cloretos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Humanos , Técnicas de Patch-Clamp , Mucosa Respiratória/citologiaRESUMO
There is no effective treatment for recurrent or metastatic medullary thyroid carcinoma (MTC), a tumor arising from thyroid C-cells commonly presenting an inherited or acquired RET mutation. In this study we examined the sensitivity of two human MTC cell lines to novel pyrazolopyrimidine derivates, able to inhibit src-family tyrosine kinase activity. In TT cells [carrying the multiple endocrine neoplasia (MEN)2A Ret mutation Cys 634Trp] and MZ-CRC-1 cells (carrying the MEN2B RET mutation Met891Thr), one of these compounds, namely Si 34, determined a significant growth inhibitory effect (approximately 90% vs control for TT, 80% vs control for MZ-CRC-1) mainly due to enhanced cell mortality after a 6-day incubation. At concentrations that increased cell mortality, neither biochemical or morphological characteristics of apoptosis were detected in TT and MZCRC- 1 cells treated with Si 34. These results, when confirmed in other in vivo preclinical models, suggest that this novel tyrosine kinase inhibitor may be useful for the treatment of MTC.
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Carcinoma Medular/tratamento farmacológico , Carcinoma Medular/patologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasia Endócrina Múltipla Tipo 1/tratamento farmacológico , Neoplasia Endócrina Múltipla Tipo 1/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidoresRESUMO
Asian soybean rust (ASR), caused by Phakopsora pachyrhizi Syd. & P. Syd., has been reported in Argentina on soybean (Glycine max) and kudzu (Pueraria lobata and Pueraria javanica) since the 2002 growing season (1-4). On 29 May 2006, plants of Phaseolus spp. were found to have tan ASR-like rust lesions on leaves at eight different field plots located in the northwestern province of Salta, Argentina. Growth stages of infected bean plants within plots were between pod setting and physiological maturity. Diagnosis of ASR on bean leaves was performed with a stereoscopic microscope to view rust pustules, and suspected uredinia of P. pachyrhizi were observed, furthermore, typical ASR urediniospores also were also observed at ×400. ELISA and PCR methods gave positive results for ASR. Rust spores from these plants were used to inoculate soybean plants at the V3 growth stage with rust spores from field bean plants produced under greenhouse conditions. Typical ASR tan pustules developed within 21 days of inoculation. Bean rust caused by Uromyces phaseoli also was seen in some of the bean plots but was easily differentiated from ASR because the uredinia were much darker and affected the upper leaves, while the ASR uredinia were lighter and spread from the lower leaves to the upper leaves. This finding is of significance in Argentina because bean is an important crop grown in the northwestern region of the country and is planted approximately 2 months after soybean planting. Given this planting time difference, bean may provide an overwintering host for the survival of ASR spores, thereby providing a green bridge for infection of soybean plants during the following growing season. References: (1) A. J. Ivancovich. Soybean rust situation in Argentina. Oral presentation. Symposium: Soybean Rust: Too Close for Comfort. Annual Meeting of the American Phytopathological Society. 2003. (2) A. J. Ivancovich. Plant Dis. 89:667, 2005. (3) A. J. Ivancovich and G. Botta. Rev. Tecnología Agropecuaria 7(21):16, 2002. (4) A. J. Ivancovich et al. Phytopathology (Abstr.) 94(suppl.):S44, 2004.
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AIM: Acute postoperative pancreatitis is a rare event, but, at the same time, it represents one of the most frightening complications, because it is associated with high mortality risk. METHODS: From January 1985 to December 2005, we observed 30 cases (12 males, 18 females) of acute postoperative pancreatitis. Twenty cases of low and medium gravity have been treated with only medical therapy, 10 cases, instead, have requested surgical therapy (necrosectomy and application of abdominal drains in 7 cases, necrosectomy and ileostomy in 1 case, necrosectomy and colostomy in 1 case, ligation of pancreatic vessels in 1 case of haemorrhagic pancreatitis). RESULTS: In the form of low and medium gravity, fast and pharmacological support (somatostatin and gabexate mesilate) are enough to resolve the event. In the form of high gravity the early surgical treatment has represented the clinical solution in 7 patients, while 3 others patients have died for septic and metabolic complication. CONCLUSIONS: Still today acute postoperative pancreatitis represents a frightening complication associated with high mortality risk that the surgeon has to treat with great care to avoid each bilio-pancreatic injury.
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Pancreatite/terapia , Complicações Pós-Operatórias/terapia , Doença Aguda , Feminino , Humanos , MasculinoRESUMO
The author reports about the organization of the phlebology center at the University of Siena, directed since 1985 by Professor Mancini. The center is equipped with 5 phlebology outpatient settings, with own instruments for non-invasive vascular diagnostics, with one operating theatre and with own equipment for phlebological rehabilitation. At present, in this center a group of specialist doctors and experts in phlebological formation works and practices everyday more than 30 performances instrumental vascular diagnostic both in election, both also in urgency for the patients coming from the Ready Aid. The therapeutic performance, which the phlebology surgical activity, the sclerotherapy, the ulcer dressing, are carried out on specific days of the week. The organization of the Center of Phlebology has to answer indeed to the demands of the use, simplifying the procedures of access, decreasing the times of attended of the diagnostic performance and the therapeutics and the reducing to the least one the interferences with the common habits of life, kind of the elderly patients.
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Instituições de Assistência Ambulatorial/organização & administração , Doenças Vasculares/diagnóstico , Veias , Procedimentos Cirúrgicos Ambulatórios , Ecocardiografia Doppler , Humanos , Itália , Doenças Vasculares/reabilitação , Doenças Vasculares/cirurgiaRESUMO
The apical membranes of rabbit gallbladder epithelial cells were isolated by treating the homogenate with Ca2+ or Mg2+ and centrifuging the suspension in Percoll gradient. In this way brush-border membranes were obtained with enrichment factors ranging between 10 and 20 and yields of 15-30%. A second method is described with which membranes were isolated, without any preliminary treatment, first by differential centrifugation, then with Percoll gradient; the final membrane enrichment was over 15, however the yield was very low (3%). Many possible enzymatic markers of the apical plasma membrane were investigated: L-gamma-glutamyltransferase, alkaline phosphatase, leucine aminopeptidase, sucrase. The first appears to be that of choice. Apical membrane fraction could be also evidenced by autofluorescence or by labeling with Lotus tetragonolobus lectin. Preliminary experiments showed that apical plasma membranes isolated in this way form vesicles.
Assuntos
Fracionamento Celular/métodos , Membrana Celular/análise , Vesícula Biliar/citologia , Animais , Cálcio/farmacologia , Centrifugação com Gradiente de Concentração , Células Epiteliais , Fluorescência , Magnésio/farmacologia , CoelhosRESUMO
The function of the gallbladder is not only to store bile, but also to concentrate it during the interdigestive phase by means of salt-dependent water reabsorption. On the contrary, secretions of water and salt take place during the digestive phase. Dysregulation of ion absorption or secretion are common in many gallbladder diseases, such as colelithiasis. Transepithelial absorptions are determined by the Na+/K+ pump on the basolateral membrane, and by several apical membrane Na(+)-coupled transporters. Among these, some isoforms of Na+/H+ and Cl-/HCO3(-) exchangers have been studied. The presence of a Na(+)-Cl(-) simport has been molecularly and functionally characterized in some animal species. The ion transepithelial secretion is mainly dependent on an apical chloride transport attributable to a CFTR-like cAMP-activated channel with high permeability to HCO3(-). The apical membrane electrical potential is one of the factors influencing anion secretion and is maintained by the activity of cAMP-dependent K+ channels. The regulation of the activity of these channels is complex, because of their sensitivity to voltage, and to intracellular calcium and pH. The coordinated interplay underlying the regulation of transporters and channels needs to be clarified yet, as well as the interactions between transporters, channels and aquaporins.
Assuntos
Vesícula Biliar/metabolismo , Animais , Bile/metabolismo , Transporte Biológico Ativo , Proteínas de Transporte/metabolismo , Epitélio/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Íons/metabolismo , Rim/metabolismoRESUMO
In recent years there has been a significant upsurge in research on the characterisation and verification of the potential health benefits associated with the use of probiotics. In addition, the market for probiotics continues to expand exponentially as consumers (mostly healthy individuals) rely on health claims made by manufacturers to make their choices. This review appraises the available evidence for and against the health claims associated with probiotics. The use of probiotics in promoting gastrointestinal health and immunity, and their use in the prevention of urogenital infections, allergies and cancer are reviewed. Furthermore, issues surrounding the use of probiotics in healthy individuals, the safety of probiotics and regulatory concerns are addressed. There is scientific evidence that specific strains of probiotic microorganisms confer health benefits on the host and are safe for human use. However, this evidence cannot be extrapolated to other strains, as these effects are strain-specific. Probiotics have potential health benefits for conditions such as gastrointestinal infections, genitourinary infections, allergies and certain bowel disorders, all of which afflict a considerable proportion of the global population. However, considerable work is still needed to confirm these potential health benefits.