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1.
Horm Behav ; 98: 77-87, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29269179

RESUMO

The present study assessed the participation of membrane G-protein coupled estrogen receptor 1 (GPER-1) and gonadotropin releasing hormone 1 (GnRH-1) receptor in the display of lordosis induced by intracerebroventricular (icv) administration of G1, a GPER-1 agonist, and by unesterified 17ß-estradiol (free E2). In addition, we assessed the participation of both estrogen and progestin receptors in the lordosis behavior induced by G1 in ovariectomized (OVX), E2-benzoate (EB)-primed rats. In Experiment 1, icv injection of G1 induced lordosis behavior at 120 and 240min. In Experiment 2, icv injection of the GPER-1 antagonist G15 significantly reduced lordosis behavior induced by either G1 or free E2. In addition, Antide, a GnRH-1 receptor antagonist, significantly depressed G1 facilitation of lordosis behavior in OVX, EB-primed rats. Similarly, icv injection of Antide blocked the stimulatory effect of E2 on lordosis behavior. In Experiment 3, systemic injection of either tamoxifen or RU486 significantly reduced lordosis behavior induced by icv administration of G1 in OVX, EB-primed rats. The results suggest that GnRH release activates both estrogen and progestin receptors and that this activation is important in the chain of events leading to the display of lordosis behavior in response to activation of GPER-1 in estrogen-primed rats.


Assuntos
Estradiol/farmacologia , Postura/fisiologia , Receptores de Estrogênio/fisiologia , Receptores Acoplados a Proteínas G/agonistas , Receptores LHRH/fisiologia , Receptores de Progesterona/fisiologia , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Feminino , Antagonistas de Hormônios/farmacologia , Mifepristona/farmacologia , Oligopeptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Comportamento Sexual Animal/fisiologia , Tamoxifeno/farmacologia
2.
Phys Chem Chem Phys ; 18(45): 31260-31267, 2016 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-27819104

RESUMO

The gas phase structure and excited state lifetime of the p-aminophenolp-cresol heterodimer have been investigated by REMPI and LIF spectroscopy with nanosecond laser pulses and pump-probe experiments with picosecond laser pulses as a model system to study the competition between π-π and H-bonding interactions in aromatic dimers. The excitation is a broad and unstructured band. The excited state of the heterodimer is long lived (2.5 ± 0.5) ns with a very broad fluorescence spectrum red-shifted by 4000 cm-1 with respect to the excitation spectrum. Calculations at the MP2/RI-CC2 and DFT-ωB97X-D levels indicate that hydrogen-bonded (HB) and π-stacked isomers are almost isoenergetic in the ground state while in the excited state only the π-stacked isomer exists. This suggests that the HB isomer cannot be excited due to negligible Franck-Condon factors and therefore the excitation spectrum is associated with the π-stacked isomer that reaches vibrationally excited states in the S1 state upon vertical excitation. The excited state structure is an exciplex responsible for the fluorescence of the complex. Finally, a comparison was performed between the π-stacked structure observed for the p-aminophenolp-cresol heterodimer and the HB structure reported for the (p-cresol)2 homodimer indicating that the differences are due to different optical properties (oscillator strengths and Franck-Condon factors) of the isomers of both dimers and not to the interactions involved in the ground state.

3.
Neurologia ; 30(9): 536-44, 2015.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25066492

RESUMO

INTRODUCTION: Stroke is the main cause of admission to Neurology departments and cardioembolic stroke (CS) is one of the most common subtypes of stroke. METHODS: A multicentre prospective observational study was performed in 5 Neurology departments in public hospitals in the Region of Madrid (Spain). The objective was to estimate the use of healthcare resources and costs of acute CS management. Patients with acute CS at<48h from onset were recruited. Patients' socio-demographic, clinical, and healthcare resource use data were collected during hospitalisation and at discharge up to 30 days after admission, including data for rehabilitation treatment after discharge. RESULTS: During an 8-month recruitment period, 128 patients were recruited: mean age, 75.3±11.25; 46.9% women; mortality rate, 4.7%. All patients met the CS diagnostic criteria established by GEENCV-SEN, based on medical history or diagnostic tests. Fifty per cent of the patients had a history of atrial fibrillation and 18.8% presented other major cardioembolic sources. Non-valvular atrial fibrillation was the most frequent cause of CS (33.6%). Data for healthcare resource use, given a mean total hospital stay of 10.3±9.3 days, are as follows: rehabilitation therapy during hospital stay (46.9%, mean 4.5 days) and after discharge (56.3%, mean 26.8 days), complications (32%), specific interventions (19.5%), and laboratory and diagnostic tests (100%). Head CT (98.4%), duplex ultrasound of supra-aortic trunks (87.5%), and electrocardiogram (85.9%) were the most frequently performed diagnostic procedures. Average total cost per patient during acute-phase management and rehabilitation was €13,139. Hospital stay (45.0%) and rehabilitation at discharge (29.2%) accounted for the largest part of resources used. CONCLUSIONS: Acute CS management in the Region of Madrid resulted consumes large amounts of resources (€13,139), mainly due to hospital stays and rehabilitation.


Assuntos
Embolia/complicações , Cardiopatias/complicações , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Embolia/terapia , Feminino , Cardiopatias/terapia , Custos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reabilitação/economia , Espanha/epidemiologia , Acidente Vascular Cerebral/etiologia
4.
Horm Behav ; 66(2): 361-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24954691

RESUMO

The role of classical estrogen receptors (ERs) in priming female reproductive behavior has been studied previously; however, the participation of this receptor during activation of estrous behavior has not been extensively studied. The purpose of this work was to test the possibility that the facilitation of lordosis behavior in estrogen-primed rats by progesterone (P) and its 5α- and 5ß-reduced metabolites, gonadotropin-releasing hormone (GnRH), leptin, prostaglandin E2 (PGE2) and vagino-cervical stimulation (VCS) involves interactions with classical ERs by using the selective ER modulator, tamoxifen. To further assess the role of ERs, we also explored the effects of the pure ER antagonist, ICI182780 (ICI), on estrous behavior induced by P and GnRH. Ovariectomized, estrogen-primed rats (5µg estradiol benzoate 40h earlier) were injected intraventricularly with the above-mentioned compounds, or they received VCS. All compounds and VCS effectively facilitated estrous behavior when tested at 60, 120 or 240min after infusion or application of VCS. Intraventricular infusion of tamoxifen (5µg), 30min before, significantly attenuated estrous behaviors induced in estradiol-primed rats by P, most of its 5α- and 5ß-reduced metabolites, GnRH, and PGE2, but not by VCS. Although there was a trend for reduction, tamoxifen did not significantly decrease lordosis in females treated with 5ß-pregnan-3,20-dione. ICI also inhibited lordosis behavior induced by P and GnRH at some testing intervals. These results suggest that activation of classical ERs participates in the triggering effects on estrous behavior induced by agents with different chemical structures that do not bind directly to ERs.


Assuntos
Comportamento Animal/efeitos dos fármacos , Dinoprostona/farmacologia , Ciclo Estral/efeitos dos fármacos , Peptídeos/farmacologia , Progestinas/farmacologia , Receptores de Estrogênio/fisiologia , Animais , Antagonistas de Estrogênios/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Injeções Intraventriculares , Leptina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/efeitos dos fármacos , Tamoxifeno/farmacologia
5.
Eur J Neurol ; 20(11): 1451-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23879527

RESUMO

BACKGROUND AND PURPOSE: Drug-induced parkinsonism usually resolves after discontinuation of the causative agent. However, it persists in some patients, who actually have subclinical neurodegenerative parkinsonism. Identification of this condition is important because these patients could benefit from therapeutic measures. The objective of this study was to prove whether transcranial sonography, a technique used in the diagnosis of neurodegenerative parkinsonism, can be used for the said identification. METHODS: In this prospective study, patients with drug-induced parkinsonism were followed for at least 6 months after discontinuation of the causative drug and performance of blinded transcranial sonography. Patients were categorized as having iatrogenic parkinsonism if the clinical presentation had resolved or subclinical drug-exacerbated parkinsonism if it persisted. Once the patient was classified into one of the two groups, an expert assessed the transcranial sonography findings and their agreement with the clinical diagnosis. RESULTS: Twenty patients composed the group for analysis of results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or hyperechogenic lentiform nucleus, differences were detected between the iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups, although they did not reach statistical significance (Fisher's exact test 0.09). Joint assessment of sonographic alterations in both structures had a negative predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a negative likelihood ratio of 0.3. CONCLUSIONS: Although in our study statistically significant differences were not found between the transcranial sonography characteristics of subclinical drug-exacerbated parkinsonism and iatrogenic parkinsonism patients, we believe that transcranial sonography is a valid technique for diagnosis of drug-induced parkinsonism.


Assuntos
Corpo Estriado/diagnóstico por imagem , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
6.
Rev Clin Esp (Barc) ; 223(6): 331-339, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37169081

RESUMO

INTRODUCTION: Post-dural puncture headache (PDPH) is the most common complication following lumbar puncture. However, its incidence varies according to the series consulted. Different factors associated with its onset have been identified. OBJECTIVES: The purpose of this study is to determine the incidence of PDPH and to identify predisposing factors for its appearance. METHOD: Prospective, descriptive study in 57 patients who underwent lumbar puncture procedures. To this end, variables associated with patient-related risk factors, clinical and procedural factors with the presence of PDPH were analysed. The incidence of PDPH was 38.6% and factors associated with onset included young age and previous history of headache. RESULTS: The incidence of PDPH was higher in women and presented greater intensity in this group, though studies with a larger sample size would need to be conducted. CONCLUSIONS: We must bear in mind the factors associated with the appearance of PDPH, which include: young age, history of headache, and the perception of procedural difficulty, to better inform patients and optimise the techniques used.


Assuntos
Cefaleia Pós-Punção Dural , Humanos , Feminino , Cefaleia Pós-Punção Dural/epidemiologia , Cefaleia Pós-Punção Dural/etiologia , Estudos Prospectivos , Cefaleia/complicações , Cefaleia/epidemiologia , Fatores de Risco , Punção Espinal/efeitos adversos
7.
Genes Immun ; 13(2): 191-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22012429

RESUMO

Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P(FDR)=2.07 × 10(-4), odds ratio=1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.


Assuntos
Doenças Autoimunes/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Escleroderma Sistêmico/genética , Adulto , Doenças Autoimunes/imunologia , Loci Gênicos , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/imunologia
8.
Tissue Antigens ; 80(3): 254-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22742541

RESUMO

Systemic sclerosis (SSc) is a complex autoimmune disease which genetic component has not been yet completely understood. IL6 encodes a cytokine with a crucial role in the development of autoimmunity and fibrosis and its actions mainly are controlled by IL-6 receptor (IL-6R). We aimed to investigate whether the functional genetic variants rs8192284 and rs2228044 previously associated with several autoimmune diseases, located within the IL-6 receptor (IL-6R) subunits IL6R and IL6ST genes, respectively, are involved in the susceptibility to SSc and/or its major clinical subphenotypes. A Spanish cohort including 1013 SSc patients and 1375 controls was genotyped using the TaqMan® allelic discrimination technology. SSc patients were subdivided according to the major clinical forms, autoantibody status and presence of fibrotic lung affection. Our data showed no influence of the selected variants in global SSc susceptibility (rs8192284: P=0.67, odds ratios (OR)=0.98; rs2228044: P=0.99, OR=1.00). Similarly, the clinical/autoantibody subphenotype analyses did not yielded significant results. Our data suggest that the analyzed polymorphisms may not play a significant role in the SSc susceptibility.


Assuntos
Receptor gp130 de Citocina/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores de Interleucina-6/genética , Escleroderma Sistêmico , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , Escleroderma Sistêmico/genética
9.
Ann Rheum Dis ; 70(3): 454-62, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21131644

RESUMO

OBJECTIVE: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. METHODS: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. RESULTS: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). CONCLUSION: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.


Assuntos
Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Escleroderma Sistêmico/genética , Autoanticorpos/sangue , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Escleroderma Sistêmico/imunologia
10.
Rev Clin Esp ; 211(5): 240-4, 2011 May.
Artigo em Espanhol | MEDLINE | ID: mdl-21458794

RESUMO

OBJECTIVES: To describe the epidemiological and clinical characteristics of Q fever in an urban zone of the Community of Madrid (Spain). MATERIAL AND METHODS: An observational, retrospective study was performed of a cohort of cases diagnosed of Q fever within a single center in Madrid from January 2001 to December 2008. The diagnosis of acute Q fever was made by detection of antibodies against phase II antigen by Enzyme-Linked Immunosorbent Assay (ELISA) and indirect immunofluorescence (IFA), based on isolated titer ≥ 1/80 or when they showed seroconversion or seroreinforcement. Chronic Q fever was diagnosed using antibodies against phase I with a positive value if IgG ≥ 1/800. RESULTS: A total of 54 cases of Q fever in adults were diagnosed; 51 patients had acute Q fever and only 3 chronic. There was a predominance of men over > 50 years and from urban areas. The most frequent manifestation was pneumonia (54%), followed by renal failure (33%), hepatitis and fever without focality (25% in both), with concomitant infection in 37% of the cases. The clinical and serological monitoring in most of the patients were inadequate. The best response to treatment was with doxycycline in acute illness, although duration was inadequate in 10%.


Assuntos
Febre Q/diagnóstico , Febre Q/epidemiologia , Adulto , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Saúde da População Urbana
11.
Neurologia (Engl Ed) ; 2021 Mar 19.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33812762

RESUMO

INTRODUCTION: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease. METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined. RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed. CONCLUSIONS: The incidence of COVID-19 was slightly lower in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.

12.
Neurologia (Engl Ed) ; 36(9): 698-703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103271

RESUMO

INTRODUCTION: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease. METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined. RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed. CONCLUSIONS: The incidence of COVID-19 was slightly higher in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.


Assuntos
COVID-19 , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Idoso , Humanos , Esclerose Múltipla/epidemiologia , SARS-CoV-2 , Estudos Soroepidemiológicos
13.
Semergen ; 47(3): 144-150, 2021 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-33268265

RESUMO

AIM: Minor Surgery (MS) is an ever-increasing programmed activity in Primary Health Care Centres (PHC). The aim of this study is to establish the clinical and histopathology diagnostic agreement between PHC and MS and evaluating the efficacy of this activity. METHODS AND MATERIALS: A retrospective, observational, and reliability study was performed. A total of 234 patient specimens were sent to Histopathology between January 2014 and December 2018 in basic health area of San Benito-La Laguna, Santa Cruz de Tenerife. Of these, 203 specimens met criteria, with 31 being excluded due to death or absence of diagnosis. Sociodemographic and diagnostic variables were analysed, and 10 possible diagnoses were grouped into 3 categories according to their nature. Cohen kappa coefficient was used as the main evaluation measure. RESULTS: The majority of specimens were obtained from women (51.2%), and the mean age was 52.82±17.82 years. The most frequently referred lesion was the epidermoid cyst (20.2-21.67%). A clinical-pathological agreement of 60% was obtained in Minor Surgery, with a specificity of 98.3% and a sensitivity of 61.9%. In Primary Care agreement was 36.1%, with a specificity of 98.4% and a sensitivity of 42.8%. Infectious lesions represented the largest concordance difference obtained, with 27% less in Primary Care compared to Minor Surgery. CONCLUSIONS: Minor Surgery is an effective support in the initial diagnosis of lesions referred for evaluation at Primary Care. However, it is necessary to implement improvements in diagnostic efficacy of Primary Care.


Assuntos
Procedimentos Cirúrgicos Menores , Atenção Primária à Saúde , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Espanha
14.
Nat Commun ; 12(1): 3060, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031385

RESUMO

The pelagic brown macroalgae Sargassum spp. have grown for centuries in oligotrophic waters of the North Atlantic Ocean supported by natural nutrient sources, such as excretions from associated fishes and invertebrates, upwelling, and N2 fixation. Using a unique historical baseline, we show that since the 1980s the tissue %N of Sargassum spp. has increased by 35%, while %P has decreased by 44%, resulting in a 111% increase in the N:P ratio (13:1 to 28:1) and increased P limitation. The highest %N and δ15N values occurred in coastal waters influenced by N-rich terrestrial runoff, while lower C:N and C:P ratios occurred in winter and spring during peak river discharges. These findings suggest that increased N availability is supporting blooms of Sargassum and turning a critical nursery habitat into harmful algal blooms with catastrophic impacts on coastal ecosystems, economies, and human health.


Assuntos
Nitrogênio/análise , Nutrientes , Sargassum/química , Água do Mar/química , Animais , Oceano Atlântico , Biomassa , Ecossistema , Peixes , Proliferação Nociva de Algas , Biologia Marinha , Rios , Sargassum/crescimento & desenvolvimento , Alga Marinha
15.
Ann Rheum Dis ; 69(4): 700-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19815934

RESUMO

OBJECTIVE: To investigate the possible association of the BANK1 gene with genetic susceptibility to systemic sclerosis (SSc) and its subphenotypes. METHODS: A large multicentre case-control association study including 2380 patients with SSc and 3270 healthy controls from six independent case-control sets of Caucasian ancestry (American, Spanish, Dutch, German, Swedish and Italian) was conducted. Three putative functional BANK1 polymorphisms (rs17266594 T/C, rs10516487 G/A, rs3733197 G/A) were selected as genetic markers and genotyped by Taqman 5 allelic discrimination assay. RESULTS: A significant association of the rs10516487 G and rs17266594 T alleles with SSc susceptibility was observed (pooled OR=1.12, 95% CI 1.03 to 1.22; p=0.01 and pooled OR=1.14, 95% CI 1.05 to 1.25; p=0.003, respectively), whereas the rs3733197 genetic variant showed no statistically significant deviation. Stratification for cutaneous SSc phenotype showed that the BANK1 rs10516487 G, rs17266594 T and rs3733197 G alleles were strongly associated with susceptibility to diffuse SSc (dcSSc) (pooled OR=1.20, 95% CI 1.05 to 1.37, p=0.005; pooled OR=1.23, 95% CI 1.08 to 1.41, p=0.001; pooled OR=1.15, 95% CI 1.02 to 1.31, p=0.02, respectively). Similarly, stratification for specific SSc autoantibodies showed that the association of BANK1 rs10516487, rs17266594 and rs3733197 polymorphisms was restricted to the subgroup of patients carrying anti-topoisomerase I antibodies (pooled OR=1.20, 95% CI 1.02 to 1.41, p=0.03; pooled OR=1.24, 95% CI 1.05 to 1.46, p=0.01; pooled OR=1.26, 95% CI 1.07 to 1.47, p=0.004, respectively). CONCLUSION: The results suggest that the BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase I antibody subsets.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Membrana/genética , Esclerodermia Difusa/genética , População Branca/genética , Autoanticorpos/análise , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Esclerodermia Difusa/imunologia
16.
Clin Exp Rheumatol ; 28(4): 468-76, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20525449

RESUMO

OBJECTIVES: To analyse the safety and efficacy of the off-label use of rituximab in patients with severe, refractory systemic autoimmune diseases. METHODS: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases refractory to standard therapies (failure of at least two immunosuppressive agents). RESULTS: One hundred and ninety-six patients with systemic autoimmune diseases treated with rituximab have been included in the Registry (158 women and 38 men, mean age 43 years). Systemic autoimmune diseases included systemic lupus erythematosus (107 cases), inflammatory myopathies (20 cases), ANCA-related vasculitides (19 cases), Sjögren's syndrome (15 cases) and other diseases (35 cases). A therapeutic response was evaluable in 194 cases: 99 (51%) achieved a complete response, 51 (26%) a partial response and 44 (23%) were classified as non-responders. After a mean follow-up of 27.56+/-1.32 months, 44 (29%) out of the 150 responders patients relapsed. There were 40 adverse events reported in 33 (16%) of the 196 patients. The most frequent adverse events were infections, with 24 episodes being described in 19 patients. Thirteen (7%) patients died, mainly due to disease progression (7 cases) and infection (3 cases). CONCLUSIONS: Although not yet licensed for this use, rituximab is currently used to treat severe, refractory systemic autoimmune diseases, with the most favourable results being observed in Sjögren's syndrome, inflammatory myopathies, systemic lupus erythematosus and cryoglobulinemia.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Uso Off-Label , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etnologia , Anticorpos Monoclonais Murinos/efeitos adversos , Doenças Autoimunes/etnologia , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/etnologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/etnologia , Estudos Retrospectivos , Rituximab , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/etnologia , Espanha , Resultado do Tratamento , Adulto Jovem
17.
Neurosci Lett ; 714: 134612, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31698025

RESUMO

The effects of 4NO2PDPMe and 4APDPMe, which are thalidomide (Tha) analogs that act as selective phosphodiesterase (PDE-4) inhibitors, on estrous behavior (lordosis and proceptive behaviors) and on uterine contraction were studied in ovariectomized (OVX) estrogen-primed Sprague Dawley (SD) and in intact non-pregnant Wistar rats, respectively. We found that intracerebroventricular (ICV) infusion of either 4NO2PDPMe or 4APDPMe (20 to 80 µg) stimulated intense lordosis and proceptive behavior in response to mounts from a sexually active male, within the first 4 h after infusion, and persisting for up to 24 h. Inhibitors of the progesterone receptor (RU486, administered subcutaneously), the estrogen receptor (tamoxifen, ICV), the adenylate cyclase (AC)/ cyclic AMP (cAMP)/protein kinase A (PKA) pathway (administered ICV), and the mitogen activated protein kinase (MAPK) pathway (administered ICV) significantly decreased lordosis and proceptive behavior induced by Tha analogs. Uterine contractility studies showed that Tha analogs inhibited both the K+- and the Ca2+-induced tonic contractions in rat uterus. Tha analogs were equally effective, but 4APDPMe was more potent than 4NO2PDPMe. These results strongly suggest the central role of cAMP in both processes, sexual behavior, and uterine relaxation, and suggest that Tha analogs may also act as Ca2+-channel blockers.


Assuntos
AMP Cíclico/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Ftalimidas/farmacologia , Propionatos/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Talidomida/análogos & derivados , Contração Uterina/efeitos dos fármacos , Adenilil Ciclases/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , Cálcio , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Didesoxiadenosina/farmacologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios/farmacologia , Estro , Feminino , Técnicas In Vitro , Infusões Intraventriculares , Injeções Subcutâneas , Lordose , Luteolíticos/farmacologia , Mifepristona/farmacologia , Ovariectomia , Potássio , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Receptores de Progesterona , Tamoxifeno/farmacologia , Talidomida/farmacologia , Contração Uterina/metabolismo , Útero/efeitos dos fármacos
18.
Clin Exp Rheumatol ; 27(2): 267-71, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19473567

RESUMO

OBJECTIVES: The aim of this study was to evaluate the relevance of genetic variants of TLR5 (rs5744168) and TLR7 (rs179008) gene in systemic lupus erythematosus (SLE) in a Spanish population. MATERIAL AND METHODS: Our study population consisted of 752 SLE patients and 1107 healthy controls. All individual were of Spanish Caucasian origin. The TLR5 and TLR7 polymorphisms were genotyped using a PCR system with pre-developed TaqMan allelic discrimination assay. RESULTS: No statistically significant differences were observed when the allele and genotype distribution of TLR5 rs5744168 and TLR7 rs179008 polymorphisms was compared between SLE patients and healthy controls. A significant increase frequency in the CC genotype of the TLR5 rs5744168 polymorphism among SLE patients without nephritis was found (93% vs. 87% in SLE patients with nephritis, p=0.03, OR=2.11 95%CI 0.93-3.51). However, this difference did not reach statistical significance in the allele frequencies (p=0.08). CONCLUSION: These results suggest that the tested variations of TLR5 and TLR7 genes do not confer a relevant role in the susceptibility or severity to SLE in the Spanish population.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptor 5 Toll-Like/genética , Receptor 7 Toll-Like/genética , Estudos de Casos e Controles , Humanos , Razão de Chances , População Branca
20.
Food Chem ; 293: 486-490, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151638

RESUMO

Fresh fruit beverages are a tasty way to follow the recommendations of World Health Organization. A study on the rheological behaviour of water-based and milk-based fruit beverages with emphasis on the temperature effect was made. The power law model adjusted data of apparent viscosity. The flow index of each beverage was practically constant with temperature variation. Then, one could discuss the variation with temperature of the consistency index. This parameter decreased around 40% in both cases in the temperature interval 5-30 °C. The stability of beverages against the sedimentation of the fruit pulp was clearly affected by the increase of temperature. Viscoelastic moduli were obtained in the linear region. Temperature dependency of both moduli was described in the interval 5-30 °C. The activation energy for linear viscoelastic flow was slightly higher than the activation energy for viscous flow. This result was interpreted as an indication of the strength of the microstructure-at-rest.


Assuntos
Sucos de Frutas e Vegetais/análise , Leite/química , Água/química , Animais , Elasticidade , Reologia , Resistência ao Cisalhamento , Temperatura , Viscosidade
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