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1.
J Neonatal Perinatal Med ; 17(2): 217-224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640173

RESUMO

BACKGROUND: Exposure to toxins during pregnancy is the main modifiable behavior that affects the placenta and, consequently, the fetus. In particular, smoking is a recognized risk factor for negative outcomes. Our study pretended to examine gross and microscopic placental features in women who reported exposure to tobacco, alcohol, or other psychoactive substances. METHODS: In this observational case-control study, we collected 706 placentas to assess precise substance exposure histological-interaction features of in the placenta. We examined gross and microscopic placental features, and then recorded maternal and newborn clinical conditions. RESULTS: We found that 4.8% of mothers admitted to consumption of some type of (harmful) substance. The most common pre-existing maternal condition was obesity (20.3%); predominant complications included amniotic infection (32.3%), urinary tract infection (14.5%) and hypertensive disorders of pregnancy (14.5%). In newborns, we discovered positive associations as respiratory distress syndrome. Macroscopically, exposed mothers had heavier placentas, more true knots, and single umbilical artery; microscopically, they were more likely to exhibit fetal vascular malperfusion (FVM). CONCLUSIONS: Until our present study, no research linked umbilical cord defects to toxic substance exposure; our study results do confirm association with adverse outcomes in neonates and alterations in the neuro-cardio-placental circuit through FVM. IMPLICATIONS: The results are confirming the importance of this modifiable risk factor and how its presence may potentially affect the course of pregnancy, as well as the health of both mother and child.


Assuntos
Placenta , Complicações na Gravidez , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Gravidez , Placenta/patologia , Recém-Nascido , Estudos de Casos e Controles , Adulto , Complicações na Gravidez/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Risco
2.
Rev Esp Cir Ortop Traumatol ; 68(3): T247-T252, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38232936

RESUMO

BACKGROUND: Postoperative outcome measurement typically relies on postoperative radiological results and clinical-functional scales; however, there is a growing interest in considering patient satisfaction (including subjective aspects) as part of the success of forefoot surgery. OBJECTIVE: To determine whether showing a preoperative photograph improves satisfaction in postoperative forefoot surgery patients. MATERIAL AND METHODS: An observational, cross-sectional, analytical study was conducted in the foot and ankle unit of our centre. We included 120 participants between 18 and 90 years old who underwent forefoot surgery. The degree of satisfaction was compared using the PSQ-10 questionnaire between a group of patients who received a preoperative foot appearance image at their 3-month postoperative follow-up and those who did not receive it. RESULTS: The overall satisfaction rate was 78.33% at 3 months after the intervention. The 93.6% of patients who received the photograph were satisfied at the postoperative follow-up, while in the control group, it was 86.2% with a p value of 0.218. CONCLUSION: The degree of satisfaction in patients undergoing forefoot surgery is not associated with the presentation of preoperative photographs.

3.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38043740

RESUMO

BACKGROUND: Postoperative outcome measurement typically relies on postoperative radiological results and clinical-functional scales; however, there is a growing interest in considering patient satisfaction (including subjective aspects) as part of the success of forefoot surgery. OBJECTIVE: To determine whether showing a preoperative photograph improves satisfaction in postoperative forefoot surgery patients. MATERIAL AND METHODS: An observational, cross-sectional, analytical study was conducted in the foot and ankle unit of our center. We included 120 participants between 18 and 90 years old who underwent forefoot surgery. The degree of satisfaction was compared using the PSQ-10 questionnaire between a group of patients who received a preoperative foot appearance image at their 3-month postoperative follow-up and those who did not receive it. RESULTS: The overall satisfaction rate was 78.33% at 3 months after the intervention. The 93.6% of patients who received the photograph were satisfied at the postoperative follow-up, while in the control group, it was 86.2% with a p-value of 0.218. CONCLUSION: The degree of satisfaction in patients undergoing forefoot surgery is not associated with the presentation of preoperative photographs.

4.
J Prev Alzheimers Dis ; 10(3): 488-496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37357289

RESUMO

BACKGROUND: People with cognitive impairment (CI) need to be identified early because of the risk of progression to dementia. OBJECTIVES: The primary objective of the study was to analyze the usefulness of the community pharmacy for early detection of CI in older people through their caregivers. As secondary objective the risk factors related to IQ-CODE classification of risk of CI were identified. DESIGN: A cross-sectional observational study was designed. SETTING: Caregivers were selected by pharmacists from Spanish community pharmacies. PARTICIPANTS: Subjects with a close relationship to persons over 70 years of age who were not previously diagnosed with CI and who did not live in a nursing home or were hospitalized participated in the study. MEASUREMENTS: The proportion of older people who were classified as "at risk of CI" was assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQ-CODE), which was completed by the caregiver. RESULTS: A total of 197 pharmacists selected 910 caregivers with an average age of 53 years, 75.5% of whom were women. In 324 people over the age of 70 (38.5%), "risk of CI" was observed, increasing with age. The risk of CI was 4.3 times higher in older people who complained of memory loss (p<0.001), 2.5 times higher if they had had a stroke in the last two years (p=0.007), 1.9 times higher if they were smokers (p=0.045) and 1.6 times higher if they were diabetic (p=0.028). CONCLUSION: Detection of risk of CI from the community pharmacy showed prevalence figures consistent with the CI figures observed in the Spanish primary care setting, demonstrating the capacity of the community pharmacy to contribute to early detection of CI.


Assuntos
Disfunção Cognitiva , Farmácias , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Cuidadores , Inquéritos e Questionários
8.
Acta Ortop Mex ; 35(5): 436-439, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-35451253

RESUMO

OBJECTIVE: The purpose of this study is to assess the clinical and functional results of patients with acute middle third of Achilles tendon rupture treated conservatively by orthopedic boot and early weight-bearing. MATERIAL AND METHODS: This is a prospective observational study with 19 patients with acute Achilles tendon rupture treated by conservative treatment. Demographic variables, ATRS score, function using heel-rise test, calf circumference and Achilles tendon resting angle were analyzed. The clinical and functional registration was performed at six weeks, three, six and 12 months of injury. A statistical analysis was performed. RESULTS: At one year follow-up, the 94% of patients were capable of standing single heel rise, the mean of twin atrophy was 1.03 cm ± 0.51 compared to uninjured side and the difference of Achilles tendon resting angle was 5.63 degrees ± 4.17 compared to contralateral limb. The 83.24% of patients returned to play and the mean of ATRS score was 87.41 points ± 17.78. Two partial re-rupture (11%) were occurred at three months of follow-up, which continued with orthopedic treatment. CONCLUSIONS: Based on the results, functional orthopedic treatment using orthopedic boot and early weight-bearing presents good clinical and functional outcomes, considering it a valid treatment for acute Achilles tendon ruptures.


OBJETIVO: Analizar los resultados clínicos y funcionales de los pacientes con rotura aguda del cuerpo del tendón de Aquiles tratados de forma conservadora mediante bota ortopédica y carga precoz. MATERIAL Y MÉTODOS: Estudio observacional prospectivo con 19 pacientes con rotura aguda de tendón de Aquiles tratados de forma ortopédica. Se analizaron las variables demográficas, la escala ATRS (Achilles tendon Total Rupture Score), la función mediante el test de puntillas, masa muscular gemelar y el equino en reposo residual. Los registros clínicos y funcionales se realizaron a las seis semanas, tres, seis y 12 meses. Se realizó un análisis estadístico mediante Stata 14. RESULTADOS: A los 12 meses, 94% de los pacientes realizaban puntillas monopodales, la media de la atrofia gemelar fue de 1.03 cm ± 0.51 respecto a extremidad contralateral y la diferencia de equino residual respecto el lado sano era de 5.63 grados ± 4.17, 83.24% de los pacientes realizaban su práctica deportiva habitual previa a la rotura. La media de ATRS de la muestra era de 87.41 puntos ± 17.78. Se registraron dos rerroturas parciales (11%) a los tres meses de seguimiento que continuaron con tratamiento ortopédico. CONCLUSIONES: El tratamiento ortopédico funcional mediante bota ortopédica y carga precoz presenta buenos resultados clínicos y funcionales, considerándolo un tratamiento válido para las roturas agudas del tendón de Aquiles.


Assuntos
Tendão do Calcâneo , Traumatismos dos Tendões , Tendão do Calcâneo/lesões , Humanos , Ruptura/terapia , Traumatismos dos Tendões/terapia , Resultado do Tratamento , Suporte de Carga
9.
J Chromatogr A ; 1626: 461381, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797855

RESUMO

A reliable and sensitive analytical approach has been optimized for the extraction of seven polychlorinated biphenyls (PCBs) from human breast milk. Hollow fiber liquid phase microextraction (HF-LPME) was applied for the first time for the extraction and pre-concentration of the analytes. Analytes were separated by gas chromatography with electron capture detector (GC-µECD) for the sensitive detection and mass spectrometry for the unequivocal identification. A rotable central composite design (RCCD) was performed for the multivariate optimization of the method. The best results were obtained at 40 °C during 30 min and 600 rpm of stirring speed using a hollow fiber length of 5 cm and toluene as an extractant phase and salt addition was not required. The detection limits were in the range 7-14 ng L-1 for PCBs. The coefficients of determination of the calibration curves indicated good linearity (R2> 0.96) and the enrichment factors ranged from 74 to 143. This type of study is of great importance due to the deleterious effect that the presence of contaminants can produce in infants health related to the immature character of the defense system. Moreover, exclusive breastfeeding is recommended by neonatologists up to six months of life and as complementary food during the first two years.


Assuntos
Microextração em Fase Líquida/métodos , Leite Humano/química , Bifenilos Policlorados/análise , Cromatografia Gasosa , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Bifenilos Policlorados/isolamento & purificação , Porosidade , Reprodutibilidade dos Testes , Sais/química
10.
Med Oral Patol Oral Cir Bucal ; 23(6): e646-e655, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30341273

RESUMO

BACKGROUND: The purpose of this study was to evaluate nanohardness and viscoelastic behavior of dentin surfaces treated with two canal sealer cements for dentin remineralization. MATERIAL AND METHODS: Dentin surfaces were subjected to: i) 37% phosphoric acid (PA) or ii) 0.5 M ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite), respectively. Samples were stored in simulated body fluid during 24 h or 21 d. The intertubular and peritubular dentin were evaluated using a nanoindenter to assess nanohardness (Hi). The load/displacement responses were used for the nano-dynamic mechanical analysis to estimate complex modulus (E*) and tan delta (δ). The modulus mapping was obtained by imposing a quasistatic force setpoint to which a sinusoidal force was superimposed. AFM imaging and FESEM analysis were performed. RESULTS: After 21 d of storage, dentin surfaces treated with EDTA+calcypatite, PA+calcypatite and EDTA+oxipatite showed viscoelastic discrepancies between peritubular and intertubular dentin, meaning a risk for cracking and breakdown of the surface. At both 24 h and 21 d, tan δ values at intertubular dentin treated with the four treatments performed similar. At 21 d time point, intertubular dentin treated with PA+oxipatite achieved the highest complex modulus and nanohardness, i.e., highest resistance to deformation and functional mineralization, among groups. CONCLUSIONS: Intertubular and peritubular dentin treated with PA+oxipatite showed similar values of tan δ after 21 d of storage. This produced a favorable dissipation of energy with minimal energy concentration, preserving the structural integrity at the dentin surface.


Assuntos
Cimentos Dentários/farmacologia , Dentina/efeitos dos fármacos , Hidróxido de Sódio/farmacologia , Remineralização Dentária/métodos , Óxido de Zinco/farmacologia , Humanos , Técnicas In Vitro , Teste de Materiais , Propriedades de Superfície
11.
Int Endod J ; 50 Suppl 2: e109-e119, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28653756

RESUMO

AIM: To evaluate the remineralization ability of two endodontic sealer cements. METHODOLOGY: Mid-coronal dentine surfaces were subjected to: (i) 37% phosphoric acid (PA) or (ii) 0.5 mol L-1 ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide oxiapatite respectively. Samples were stored in simulated body fluid for 24 h or 21 days. Remineralization of the dentine surfaces were studied by Raman spectroscopy (mapping with K-means cluster and hierarchical cluster analysis) was undertaken. Nanoroughness and collagen fibril width measurements were performed with an atomic force microscopy. ANOVA and Student-Newman-Keuls test were performed (α=0.05). RESULTS: Phosphoric acid+oxiapatite promoted both the highest dentine mineralization (P < 0.05) and crystallographic maturity at the dentine surface. Noncrystalline amorphous-like apatites were also formed. Dentine treated with PA+calcypatite attained the roughest surface (P < 0.05) with minimal fibril width (P < 0.05). Cross-linking of collagen only became greater in the group PA+oxiapatite after 21 days. The maximum relative mineral concentration and structure of collagen linked to the amide I and ratio amide III/AGEs was obtained after using PA+calcypatite at 21-days time-point (P < 0.05). EDTA produced a lower stoichiometric hydroxyapatite (P < 0.05) with decreased maturity, at the expense of carbonate band widening, although it favoured the nucleation of carbonated calcium phosphate. CONCLUSIONS: Dentine surfaces treated with PA+oxiapatite attained the highest dentine remineralization with both crystalline-stoichiometric and amorphous apatites, at 21 days. EDTA conditioning facilitated amorphous-bulk mineral precipitation. The amorphization was more intense after using oxiapatite and provided an ion-rich environment favouring in situ dentine remineralization.


Assuntos
Cimentos Dentários/química , Dentina/química , Hidroxiapatitas/química , Óxido de Zinco/química , Teste de Materiais , Ácidos Fosfóricos , Análise Espectral Raman , Propriedades de Superfície , Remineralização Dentária
12.
J Diabetes Complications ; 31(9): 1423-1429, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28648555

RESUMO

AIMS: To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. METHODS: We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). RESULTS: PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. CONCLUSIONS: Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.


Assuntos
Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Técnicas de Diagnóstico Endócrino , Proteínas do Olho/sangue , Resistência à Insulina , Fatores de Crescimento Neural/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Serpinas/sangue , Adulto , Idoso , Feminino , Técnica Clamp de Glucose , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/diagnóstico , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/metabolismo , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo
13.
J Diabetes Res ; 2017: 6943851, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28191471

RESUMO

Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Animais , Neuropatias Diabéticas/metabolismo , Humanos , Hipolipemiantes/farmacologia
14.
Vet Immunol Immunopathol ; 171: 73-80, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26964720

RESUMO

The understanding of virus-host interactions relies on the knowledge of the regulatory mechanisms of the type I interferon (IFN I)-stimulated genes (ISGs). Among ISGs, those coding Mx proteins play a main role due to their direct antiviral activity. The study of these genes in gilthead seabream is interesting, since this species displays high natural resistance to viral diseases, being asymptomatic carrier of infectious pancreatic necrosis virus (IPNV) and viral haemorrhagic septicaemia virus (VHSV). Gilthead seabream has three Mx genes (Mx1, Mx2, and Mx3), encoding proteins with a wide spectrum of antiviral activity. The structure of the three promoters (pMx1, pMx2 and pMx3) has been previously disclosed, and their response to poly I:C in RTG-2 cells characterized. To further analyze these promoters, their response to two viral infections has been evaluated in the present study. For that purpose, RTG-2 cells transiently transfected with the luciferase gene under the control of each promoter were inoculated with either IPNV or VHSV at two different doses. The highest and lowest fold induction values were recorded for pMx2 and pMx3, respectively. The promoter induction was always stronger after VHSV inoculation than in IPNV-inoculated cells. In addition, the higher dose of VHSV tested induced higher response of the three promoters, whereas in IPNV-infected cells the highest induction was recorded after inoculation with the lower viral dose. To further study the response of the Mx2 promoter, RTG-2 cells stably transfected with the luciferase gene under the control of pMx2 were stimulated with poly I:C and subsequently infected with IPNV or VHSV. Interestingly, IPNV infection inhibited the induction caused by poly I:C, suggesting an antagonistic activity of IPNV on Mx2 transcription. In contrast, VHSV infection did not alter the response triggered by poly I:C. These results highlight the specific regulation that controls the activity of each promoter, and support the existence of complex interactions between host cells, specific Mx promoters, and viruses, which are responsible for the final outcome of a viral infection.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças dos Peixes/virologia , Vírus da Necrose Pancreática Infecciosa , Proteínas de Resistência a Myxovirus/genética , Novirhabdovirus , Infecções por Rhabdoviridae/veterinária , Dourada , Animais , Infecções por Birnaviridae/fisiopatologia , Linhagem Celular , Doenças dos Peixes/genética , Regiões Promotoras Genéticas , Transfecção/veterinária
15.
Vet Immunol Immunopathol ; 168(1-2): 83-90, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26319936

RESUMO

Due to their direct antiviral activity, Mx proteins play a main role in the response mediated by type I interferon against viral infections. The study on gilthead seabream Mx proteins is especially interesting, since this species is unusually resistant to viral diseases, being asymptomatic carrier of several viruses pathogenic to other fish species. Gilthead seabream has three Mx proteins (Mx1, Mx2 and Mx3) that, separately, display antiviral activity against a wide range of viruses, showing interesting differences in their antiviral specificities. In this work, the possible synergy between the three Mx isoforms has been studied using in vitro systems consisting of CHSE-214 cells stably expressing two or the three gilthead seabream Mx proteins. The antiviral activity of these Mx combinations has been tested against the Infectious Pancreatic Necrosis Virus (IPNV), the Viral Haemorrhagic Septicaemia Virus (VHSV), the European Sheatfish Virus (ESV) and the Lymphocystis Disease Virus (LCDV). A synergistic effect of the Mx proteins was only detected against ESV, no synergy was observed against LCDV, and a negative interference was detected against the two RNA viruses tested, IPNV and VHSV, as viral replication was higher in cells expressing certain Mx combinations than in cells expressing these proteins separately. These results suggest a functional interaction between gilthead seabream Mx isoforms, which results in a higher or lower antiviral activity depending on the virus tested, thus supporting the idea of complex virus-host interactions and finely tuned mechanisms controlling the antiviral activity of Mx proteins.


Assuntos
Antivirais/imunologia , Proteínas de Peixes/imunologia , Proteínas de Resistência a Myxovirus/imunologia , Dourada/imunologia , Animais , Linhagem Celular , Efeito Citopatogênico Viral , Proteínas de Peixes/genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Vírus da Necrose Pancreática Infecciosa/patogenicidade , Iridoviridae/imunologia , Iridoviridae/patogenicidade , Proteínas de Resistência a Myxovirus/genética , Novirhabdovirus/imunologia , Novirhabdovirus/patogenicidade , Ranavirus/imunologia , Ranavirus/patogenicidade , Dourada/genética , Dourada/virologia
16.
Org Biomol Chem ; 13(10): 3144-54, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25634805

RESUMO

Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assembly and they present good cytotoxicity against different cell lines. Molecular modelling studies show that they could bind, within the vinca domain, in similar spatial regions as those of vinca and phomopsin thanks to the flexibility provided by the glycine linker used to elaborate these hybrids.


Assuntos
Glicina/química , Micotoxinas/síntese química , Tubulina (Proteína)/química , Alcaloides de Vinca/síntese química , Alcaloides/química , Apoptose , Sítios de Ligação , Linhagem Celular , Guanosina Trifosfato/química , Humanos , Células K562 , Microtúbulos/metabolismo , Modelos Moleculares , Micotoxinas/química , Peptídeos/química , Estrutura Terciária de Proteína , Transdução de Sinais , Vimblastina/análogos & derivados , Vimblastina/química , Alcaloides de Vinca/química , Vinorelbina
17.
Fish Shellfish Immunol ; 38(2): 311-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24704419

RESUMO

Mx proteins are main effectors of the antiviral innate immune response mediated by type I interferon (IFN I). Actually, diverse Mx proteins from fish proved highly active against fish viruses, standing out among them the Mx1, Mx2 and Mx3 from gilthead seabream (Sparus aurata), a species exhibiting a natural resistance to viral diseases. In this study, the structure and functional activity of their corresponding promoters (pMx1, pMx2 and pMx3) have been assessed. The three promoters present an identical 3' region of 157 bp, exhibiting a single canonical interferon-stimulated response element (ISRE), which is indispensible for the poli:IC induction of pMx1 and pMx3, while not for that of pMx2. In the remaining part of the three promoters other regulatory motifs were identified, as gamma IFN activated sites in variable number (1, 4 and 2 in pMx1, pMx2 and pMx3, respectively), as well as several independent GAAA elements or ISRE core sequences (13, 15 and 12 in pMx1, pMx2 and pMx3, respectively). The structural dissimilarities shown by the three promoters parallels with the differences observed in their response profiles, in terms of the time course of the induction, and basal and induced expression levels of each promoter. Altogether, these findings indicate that the expression of Mx1, Mx2 and Mx3 genes from the gilthead seabream might be specifically regulated, in accordance with the functional role of each Mx protein in the successful antiviral response shown by this species.


Assuntos
Proteínas de Peixes/genética , Regulação Enzimológica da Expressão Gênica , Proteínas de Resistência a Myxovirus/genética , Regiões Promotoras Genéticas , Dourada/genética , Animais , Linhagem Celular , Clonagem Molecular , Proteínas de Peixes/metabolismo , Dados de Sequência Molecular , Proteínas de Resistência a Myxovirus/metabolismo , Oncorhynchus mykiss , Poli I-C/imunologia , Dourada/imunologia , Dourada/metabolismo , Análise de Sequência de DNA/veterinária
18.
J Ethnopharmacol ; 149(3): 676-84, 2013 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-23906782

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Based on ethnobotanical data obtained from Nigerien and Senegalese traditional healers, two Euphorbiaceae plants, Sebastiania chamaelea and Chrozophora senegalensis, traditionally used to treat malaria, were selected for further investigations. MATERIALS AND METHODS: Plant extracts were prepared with different solvents and tested both in vitro on several strains of Plasmodium falciparum, and in vivo to evaluate their antiplasmodial properties and isolate their active principles. RESULTS: With IC50 values around 6.5µg/ml and no significant cytotoxicity (>50µg/ml), the whole plant aqueous extract from S. chamaelea showed the best in vitro results. In vitro potentiation assays showed strong synergistic activity of S. chamaelea extract with the antiplasmodial drug chloroquine on the chloroquine-resistant P. falciparum strain W2-Indochina. In other respects, the aqueous crude extract of C. senegalensis leaves showed the most significant antiplasmodial activity in vitro (IC50 values less than 2µg/ml). We also demonstrated the prophylactic activity of C. senegalensis in vivo in a murine malaria model. Bioassay-guided fractionation of aqueous extracts of these plants enabled the isolation and identification of ellagic acid (EA, 1) as the main compound responsible for their antiplasmodial activity. Together with EA, other derivatives belonging to different chemical groups were isolated but showed moderate antimalarial activity: gallic acid (2), brevifolin carboxylic acid (3), protocatechuic acid (4), corillagin (5), rutin (6) and 3,4,8,9,10-pentahydroxy-dibenzo(b,d)pyran-6-one (7). The structures were determined by the usual spectroscopic methods and by comparison with published data. Furthermore, we report here the quantification of compound 1 (EA) by RP-HPLC in the dried extracts of these plants, reported for the first time in both these species, and possessing the highest in vitro antiplasmodial activity with IC50 values from 180 to 330nm. CONCLUSIONS: These in vitro and in vivo results support the traditional use in Africa of crude extracts of both S. chamaelea and C. senegalensis as an antimalarial treatment and prove the significant antiplasmodial property of EA.


Assuntos
Antimaláricos/uso terapêutico , Euphorbiaceae/química , Malária/tratamento farmacológico , Medicinas Tradicionais Africanas , Extratos Vegetais/uso terapêutico , Plasmodium/efeitos dos fármacos , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Ácido Elágico/isolamento & purificação , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Malária/parasitologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Camundongos , Níger , Testes de Sensibilidade Parasitária , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plasmodium falciparum/efeitos dos fármacos , Senegal
19.
Mol Immunol ; 56(4): 630-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23911421

RESUMO

Mx proteins are important components of the antiviral innate immune response mediated by type I interferon. Classically, these proteins have been considered to be triggered by viral RNA, thus showing activity against RNA viruses. Actually, three Mx proteins (SauMx1, SauMx2 and SauMx3) from gilthead seabream (Sparus aurata) have previously shown antiviral activity against a dsRNA virus: the infectious pancreatic necrosis virus (IPNV) in vitro. For further characterizing their antiviral spectrum, the activity of SauMx proteins were tested against three different viral pathogens of fish: the lymphocystis disease virus (LCDV, a dsDNA virus), a pathogen of gilthead seabream; the viral haemorrhagic septicaemia virus (VHSV, a ssRNA virus), to which gilthead seabream is considered a reservoir species; and the European sheatfish virus (ESV, a dsDNA virus), that has not been detected in gilthead seabream to date. Three clonal populations of CHSE-214 cells developed in a previous study, stably expressing SauMx1, SauMx2 and SauMx3, respectively, were challenged with the three viruses. Results combining cytopathic effects and virus yield reduction assays showed that SauMx1 protected the cells against VHSV and LCDV, SauMx2 protected against ESV and LCDV, and SauMx3 showed activity only against VHSV. This study, besides confirming the antiviral activity of the three gilthead seabream Mx proteins, is the first report of the protective effect of a fish Mx against DNA viruses. Additionally, it discloses a clear specificity between Mx proteins and virus targets, supporting the idea that the relationship between virus and Mx proteins is finely tuned.


Assuntos
Vírus de DNA/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Proteínas de Resistência a Myxovirus/imunologia , Vírus de RNA/imunologia , Dourada/imunologia , Animais , Linhagem Celular , Vírus de DNA/fisiologia , Doenças dos Peixes/genética , Doenças dos Peixes/virologia , Proteínas de Peixes/genética , Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/imunologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Vírus da Necrose Pancreática Infecciosa/fisiologia , Iridoviridae/imunologia , Iridoviridae/fisiologia , Proteínas de Resistência a Myxovirus/genética , Novirhabdovirus/imunologia , Novirhabdovirus/fisiologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Vírus de RNA/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Dourada/genética , Dourada/virologia
20.
Vet Immunol Immunopathol ; 153(3-4): 240-8, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23548865

RESUMO

Mx proteins are key components of the antiviral state triggered by interferon type I in response to viral infections. In this study, two different Mx genes have been identified in European sea bass (Dicentrarchus labrax), and their sequences were cloned and characterized. MxA cDNA consists of 1881 bp coding for a putative 626 aminoacids protein, while MxB cDNA has 1920 bp and results in a protein with 639 residues. Their corresponding genomic sequences contain 3538 bp and 5326 bp, respectively, and both present 12 exons and 11 introns. The expression patterns of the two Mx genes after an in vivo challenge with the viral nervous necrosis virus (VNNV), a serious pathogen in farmed European sea bass, have been characterized by real-time PCR. The results showed interesting differences in the transcription profile of both Mx, thus suggesting a differential role for each Mx isoform in the immune response of European sea bass to VNNV, and most likely in the general viral response of this species.


Assuntos
Bass/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Ligação ao GTP/genética , Nodaviridae/imunologia , Infecções por Vírus de RNA/veterinária , Sequência de Aminoácidos , Animais , Bass/genética , Proteínas de Ligação ao GTP/fisiologia , Dados de Sequência Molecular , Proteínas de Resistência a Myxovirus , Infecções por Vírus de RNA/imunologia
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