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INTRODUCTION: A reduction in the number of interventional cardiology procedures has emerged as a result of the COVID-19 pandemic. A survey was performed to quantify this decrease and the impact on the management of myocardial infarction in Latin America. METHODS: A telematic survey was conducted for all countries in Latin America. Diagnostic catheterisations, coronary and structural interventions, as well as the incidence and delay to reperfusion therapy of myocardial infarction (STEMI), were recorded. Two periods were compared: from 24 February to 8 March 2020 (pre-COVID-19) and another 2week period that varied according to country (COVID-19). RESULTS: Responses were obtained from 79 centres in 20 countries. There was a significant decrease in the number of diagnostic procedures (-65.2%), coronary interventions (-59.4%), structural therapeutics (-86.1%) and STEMI care (-51.2%). A decrease was noted in the incidence of STEMI, but also a delay in the time to STEMI reperfusion. While there was a variation in activity in interventional cardiology between countries, patient behaviour was rather homogeneous. CONCLUSIONS: A significant reduction in healthcare activity has been noted during the COVID-19 pandemic, including STEMI care, with the risk of increased mortality and/or morbidity following STEMI. Healthcare providers should encourage patients with suspected symptoms of STEMI to call for emergency care to ensure rapid diagnosis and timely reperfusion treatment.
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The Se, Hg, and methylmercury (MeHg) levels in raw, cooked (boiled and grilled), and canned tuna (Thunnus spp.) were determined before and after an in vitro digestion, thereby enabling the calculation of the respective bioaccessibility percentages. A risk-benefit evaluation of raw and canned tuna on the basis of the Se and MeHg data was performed. Selenium bioaccessibility was high in tuna, though slightly lower in canned than in raw products. Mercury levels were high in raw and cooked tuna. Hg bioaccessibility percentages were low (39-48%) in the cooked tuna and even lower (<20%) in canned tuna. For the bioaccessible fraction, all molar Se:MeHg ratios were higher than one (between 10 and 74). A probabilistic assessment of MeHg risk vs Se benefit showed that while a weekly meal of canned tuna presents very low risk, raw, boiled, and grilled tuna consumption should not exceed a monthly meal, at least, for pregnant and nursing women.
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Culinária , Conservação de Alimentos , Compostos de Metilmercúrio/análise , Alimentos Marinhos/análise , Selênio/análise , Atum/metabolismo , Animais , Disponibilidade Biológica , Digestão , Humanos , Compostos de Metilmercúrio/farmacocinética , Modelos Biológicos , Medição de Risco , Selênio/farmacocinéticaRESUMO
Helminths use several strategies to evade and/or modify the host immune response, including suppression or inactivation of the host antigen-specific response. Several helminth immunomodulatory molecules have been identified. Our studies have focused on immunosuppression induced by the roundworm Ascaris suum and an A. suum-derived protein named protein 1 from A. suum (PAS-1). Here we assessed whether PAS-1 is an excretory/secretory (E/S) protein and whether it can suppress lipopolysaccharide-induced inflammation. Larvae from infective eggs were cultured in unsupplemented Dulbecco's modified Eagle medium (DMEM) for 2 weeks. PAS-1 was then measured in the culture supernatants and in adult A. suum body fluid at different time points by enzyme-linked immunosorbent assay (ELISA) with the monoclonal antibody MAIP-1. Secreted PAS-1 was detected in both larval culture supernatant and adult body fluid. It suppressed lipopolysaccharide (LPS)-induced leucocyte migration and pro-inflammatory cytokine production, and stimulated interleukin (IL)-10 secretion, indicating that larval and adult secreted PAS-1 suppresses inflammation in this model. Moreover, the anti-inflammatory activity of PAS-1 was abolished by treatment with MAIP-1, a PAS-1-specific monoclonal antibody, confirming the crucial role of PAS-1 in suppressing LPS-induced inflammation. These findings demonstrate that PAS-1 is an E/S protein with anti-inflammatory properties likely to be attributable to IL-10 production.
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Ascaris suum/fisiologia , Proteínas de Helminto/imunologia , Proteínas de Helminto/metabolismo , Tolerância Imunológica , Imunossupressores/metabolismo , Animais , Ascaris suum/química , Ascaris suum/imunologia , Movimento Celular/efeitos dos fármacos , Meios de Cultura/química , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Interações Hospedeiro-Patógeno , Larva/química , Larva/imunologia , Larva/fisiologia , Leucócitos/metabolismo , Leucócitos/fisiologia , Fatores de TempoRESUMO
In vitro diagnostic procedure in allergology includes determination of serum levels of total and allergen specific IgE antibodies, allergen specific IgG antibodies, plasma tryptase, eosinophil cationic protein (ECP) and basophil activation test (BAT). In vitro tests should be used according to clinical history, physical examination, and in vivo methods for allergy testing. Clinical relevance of elevated total IgE in allergy diagnosis is modest, since it can be caused by other conditions. Elevated serum levels of allergen specific IgE antibodies, together with positive medical history, are indicative of clinically relevant allergy. A recommended laboratory method for total and specific IgE concentration measurement is the sandwich-type fluoroimmunoassay ImmunoCAP, considered as an ideal immunoassay. Serum levels of allergen specific IgG antibodies have no proved clinical relevance in food allergy diagnosis. They can be useful to monitor venom immunotherapy success, as well as to estimate the risk of venom induced anaphylaxis. Elevated plasma tryptase (subtype ß) level is an indication of mast cell activation caused by specific allergen. It should be obtained within 4 hours after an anaphylactic episode. Elevated level of ECP can be detected in patient blood during late phase of allergic reaction. It can be used to monitor patients with chronic allergenic and inflammatory conditions in which eosinophils play a central role. BAT includes measurement of CD 63 (cluster of differentiation) and CD 203 antigens of the molecular surface by flow cytometry. It is useful in the diagnosis of venom, food and drug allergy, estimation of severity of allergic disease and natural tolerance to allergens. In vitro tests based on allergen extracts can be used for in vitro diagnosis in monosensitized patients with clear medical history and symptomatic treatment. Molecular allergy diagnosis should be performed in special clinical indications such as diagnosis of cross reactivity, prescription of specific immunotherapy (especially in polysensitized patients with complex symptoms), diagnosis of idiopathic or cofactor induced anaphylaxis, latex allergy, and assessment of the risk of allergic reaction to specific allergen.
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Alérgenos/imunologia , Basófilos/imunologia , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/imunologia , Imunoglobulina E/sangue , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Reações Cruzadas , Feminino , Hipersensibilidade Alimentar , Humanos , Masculino , Guias de Prática Clínica como Assunto , Testes CutâneosRESUMO
BACKGROUND: It is still uncertain whether house dust mite (HDM) tropomyosin present in allergen extracts can cross-sensitize patients receiving subcutaneous immunotherapy (SCIT) and thus induce food allergy. OBJECTIVES: Our aim was to assess whether new sensitization to tropomyosin occurred during HDM-SCIT, and, if so, whether it was clinically relevant. PATIENTS AND METHODS: The study sample comprised 56 HDM-allergic patients treated with SCIT using HDM extract. All patients were screened for specific IgE (sIgE) to mite tropomyosin (rDer p 10) before and after SCIT. In patients with a positive result, we also monitored the dynamics of sIgE to rDer p 10 and shrimp tropomyosin (rPen a 1) at several time points. The levels of sIgE were measured using the CAP System fluorescent-enzyme immunoassay. RESULTS: sIgE to tropomyosin was found in only 5 patients, 3 of whom expressed low and clinically irrelevant levels of sIgE to Der p 10, while sIgE to Pen a 1 was not found. The remaining 2 patients expressed sIgE to both tropomyosins. In the first, the initial increase and subsequent decrease resembled the dynamics of the IgE antibodies usually seen in SCIT patients and were never accompanied by seafood-induced symptoms. In the other, a decrease in levels of sIgE to both tropomyosins resulted in the complete loss of his reactivity toward seafood. CONCLUSIONS: Immunotherapy using HDM extracts does not induce clinically relevant sensitization to tropomyosin. In certain cases of combined mite and seafood allergy, treatment may even lead to the improvement of food allergy symptoms. The levels of sIgE to Der p 10 and Pen a 1 may be useful monitoring markers.
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Alérgenos/imunologia , Dessensibilização Imunológica/métodos , Hipersensibilidade Alimentar/imunologia , Pyroglyphidae/imunologia , Tropomiosina/imunologia , Adulto , Alérgenos/administração & dosagem , Animais , Reações Cruzadas , Feminino , Hipersensibilidade Alimentar/prevenção & controle , Humanos , Imunoglobulina E/imunologia , Masculino , Tropomiosina/administração & dosagem , Adulto JovemRESUMO
BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) diagnosis can be difficult in a chronic pancreatitis (CP) background, especially in its mass forming presentation. We aimed to assess the accuracy of glypican-1-positive circulating exosomes (GPC1+crExos) to distinguish PDAC from CP versus the state-of-the-art CA 19-9 biomarker. METHODS: This was a unicentric prospective cohort. Endoscopic ultrasound with fine-needle aspiration or biopsy and blood tests (GPC1+crExos and serum CA 19-9) were performed. RESULTS: The cohort comprised 60 PDAC and 29 CP (7 of which mass forming - MF) patients. Median levels of GPC1+crExos were significantly higher in PDAC (99.7%) versus CP (28.4%; p<0.0001) with an AUROC of 0.96 with 98.3% sensitivity and 86.2% specificity for a cut-off of 45.0% (p<0.0001); this outperforms CA 19-9 AUROC of 0.82 with 78.3% sensitivity and 65.5% specificity at a cut-off of 37 U/mL (p<0.0001). The superiority of% GPC1+crExos over CA 19-99 in differentiating PDAC from CP was observed in both early (stage I) and advanced tumors (stages II-IV). CONCLUSION: Levels of GPC1+crExos coupled to beads enable differential diagnosis between PDAC and CP including its mass-forming presentation.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite Crônica , Biomarcadores Tumorais , Antígeno CA-19-9 , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Diagnóstico Diferencial , Glipicanas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/diagnóstico , Estudos Prospectivos , Neoplasias PancreáticasRESUMO
Bioactive compounds of great interest are found in the saliva of hematophagous organisms. While exploring a cDNA library derived from the salivary glands of the tick Amblyomma cajennense, a transcript that codes for a protein with unique structure (containing an N-terminal Kunitz-type domain and a C-terminus with no homology to any annotated sequences) was found. The recombinant mature form of this protein ( approximately 13.5kDa) was produced in Escherichia coli BL21 (DE3), and it was able to inhibit Factor Xa (FXa) and extend global blood clotting times in vitro and ex vivo. Static and dynamic predictions of its tertiary structure indicate regions that may be related to its FXa inhibitor function.
Assuntos
Inibidores do Fator Xa , Fator Xa/química , Ixodidae/química , Inibidores de Serina Proteinase/química , Animais , Clonagem Molecular , DNA Complementar/genética , Fator Xa/metabolismo , Humanos , Ixodidae/genética , Ixodidae/metabolismo , Estrutura Terciária de Proteína/fisiologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Inibidores de Serina Proteinase/genética , Inibidores de Serina Proteinase/metabolismo , Relação Estrutura-AtividadeRESUMO
Snake venom metalloproteinases (SVMPs) have been extensively studied and their effects associated with the local bleeding observed in human accidents by viper snakes. Representatives of P-I and P-III classes of SVMPs similarly hydrolyze extracellular matrix proteins or coagulation factors while only P-III SVMPs induce significant hemorrhage in experimental models. In this work, the effects of P-I and P-III SVMPs on plasma proteins and cultures of muscle and endothelial cells were compared in order to enlighten the mechanisms involved in venom-induced hemorrhage. To reach this comparison, BnP1 was isolated from B. neuwiedi venom and used as a weakly hemorrhagic P-I SVMPs and jararhagin was used as a model of potently hemorrhagic P-III SVMP. BnP1 was isolated by size exclusion and anion-exchange chromatographies, showing apparent molecular mass of approximately 24kDa and sequence similarity with other members of SVMPs, which allowed its classification as a group P-I SVMP. The comparison of local effects induced by SVMPs showed that BnP1 was devoid of significant myotoxic and hemorrhagic activities and jararhagin presented only hemorrhagic activity. BnP1 and jararhagin were able to hydrolyze fibrinogen and fibrin, although the latter displayed higher activity in both systems. Using HUVEC primary cultures, we observed that BnP1 induced cell detachment and a decrease in the number of viable endothelial cells in levels comparable to those observed by treatment with jararhagin. Moreover, both BnP1 and jararhagin induced apoptosis in HUVECs while only a small increase in LDH supernatant levels was observed after treatment with jararhagin, suggesting that the major mechanism involved in endothelial cell death is apoptosis. Jararhagin and BnP1 induced little effects on C2C12 muscle cell cultures, characterized by a partial detachment 24h after treatment and a mild necrotic effect as evidenced by a small increase in the supernatants LDH levels. Taken together, our data show that P-I and P-III SVMPs presented comparable effects except for the hemorrhagic activity, suggesting that hydrolysis of coagulation factors or damage to endothelial cells are not sufficient for induction of local bleeding.
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Bothrops/metabolismo , Venenos de Crotalídeos/química , Metaloendopeptidases/farmacologia , Metaloproteases/farmacologia , Sequência de Aminoácidos , Animais , Benchmarking , Fatores de Coagulação Sanguínea , Células Cultivadas , Venenos de Crotalídeos/farmacologia , Células Endoteliais/efeitos dos fármacos , Hemorragia/induzido quimicamente , Humanos , Metaloendopeptidases/química , Metaloproteases/química , Camundongos , Dados de Sequência Molecular , Veneno de Bothrops jararacaRESUMO
Fermentative protein hydrolysates (FPH) were prepared with a proteolytic bacterium, Bacillus strain exhibiting high proteolytic activity. Three FPH with 1, 2, and 4 % of cod protein hydrolysate (CPH) and 0.5 % of yeast extract in the culture were prepared. The yields achieved varied between 30 and 58 % based on protein content. A general decrease of leucine, isoleucine, valine, alanine, arginine, threonine, proline, and glutamic acid was observed. All FPHs showed higher reducing power and DPPH radical scavenging activity than CPH, but similar ABTS radical scavenging activity. However, FPHs exhibited lower Cu(+2)-chelating activity than CPH. The ACE inhibitory activity of FPHs was not improved relatively to that recorded in CPH. The fermentative process seems to have potential to obtaining hydrolysates with improved biological activities or even to produce protein hydrolysates from native fish proteins.
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Antioxidantes/farmacologia , Bacillus/metabolismo , Proteínas de Peixes/farmacologia , Aminoácidos/química , Animais , Quelantes/química , Cromatografia em Gel , Cobre/química , Gadus morhua , Hidrólise , Ferro/química , Peso MolecularRESUMO
Oestradiol (E2) acts in the hypothalamus to regulate luteinising hormone (LH) and prolactin (PRL) secretion. Tamoxifen (TX) has been extensively used as a selective oestrogen receptor modulator, although its neuroendocrine effects remain poorly understood. In the present study, we investigated the hypothalamic effects of TX in rats under low or high circulating E2 levels. Ovariectomised (OVX) rats treated with oil, E2 or TX, or E2 plus TX, were evaluated for hormonal secretion and immunohistochemical analyses in hypothalamic areas. Both E2 and TX reduced LH levels, whereas TX blocked the E2 -induced surges of LH and PRL. TX prevented the E2 -induced expression of progesterone receptor (PR) in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), although it did not alter PR expression in OVX rats. TX blocked the E2 induction of c-Fos in AVPV neurones, consistent with the suppression of LH surge. However, TX failed to prevent E2 inhibition of kisspeptin expression in the ARC. In association with the blockade of PRL surge, TX increased the phosphorylation of tyrosine hydroxylase (TH) in the median eminence of OVX, E2 -treated rats. TX also precluded the E2 -induced increase in TH expression in the ARC. In all immunohistochemical analyses, TX treatment in OVX rats caused no measurable effect on the hypothalamus. Thus, TX is able to prevent the positive- but not negative-feedback effect of E2 on the hypothalamus. TX also blocks the effects of E2 on tuberoinfundibular dopaminergic neurones and PRL secretion. These findings further characterise the anti-oestrogenic actions of TX in the hypothalamus and provide new information on the oestrogenic regulation of LH and PRL.
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Estradiol/farmacologia , Hipotálamo/efeitos dos fármacos , Hormônio Luteinizante/sangue , Prolactina/sangue , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/metabolismo , Feminino , Hipotálamo/metabolismo , Kisspeptinas/metabolismo , Ovariectomia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Progesterona/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
A serine proteinase inhibitor isolated from Leucaena leucocephala seeds (LlTI) was purified to homogeneity by acetone fractionation, ion exchange chromatography, gel filtration and reverse phase chromatography (HPLC). SDS-PAGE indicated a protein with M(r) 20000 and two polypeptide chains (alpha-chain, M(r) 15000, and beta-chain, M(r) 5000), the sequence being determined by automatic Edman degradation and by mass spectroscopy. LlTI is a 174 amino acid residue protein which shows high homology to plant Kunitz inhibitors, especially those double chain proteins purified from the Mimosoideae subfamily. LlTI inhibits plasmin (K(i) 3.2 x 10(-10) M), human plasma kallikrein (K(i) 6.3 x 10(-9) M), trypsin (K(i) 2.5 x 10(-8) M) and chymotrypsin (K(i) 1.4 x 10(-8) M). Factor XIIa activity is inhibited but K(i) was not determined, and factor Xa, tissue kallikrein and thrombin are not inhibited by LlTI. The action of LlTI on enzymes that participate in the blood clotting extrinsic pathway is confirmed by the prolongation of activated partial thromboplastin time, used as clotting time assay. The inhibition of the fibrinolytic activity of plasmin was confirmed on the hydrolysis of fibrin plates. LlTI inhibits kinin release from high molecular weight kininogen by human plasma kallikrein in vitro and, administered intravenously, causes a decrease in paw edema induced by carrageenin or heat in male Wistar rats. In addition, lower concentrations of bradykinin were found in limb perfusion fluids of LlTI-treated rats.
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Coagulação Sanguínea/efeitos dos fármacos , Bradicinina/metabolismo , Proteínas de Plantas/química , Inibidores de Serina Proteinase/química , Sequência de Aminoácidos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Edema/tratamento farmacológico , Edema/etiologia , Fibrinólise/efeitos dos fármacos , Calicreínas/antagonistas & inibidores , Masculino , Dados de Sequência Molecular , Tempo de Tromboplastina Parcial , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Ratos , Ratos Wistar , Sementes , Inibidores de Serina Proteinase/farmacologiaRESUMO
During the first two weeks of August 2003, Portugal was affected by a severe heat wave. Following the identification in Portugal of the influence of heat waves on mortality in 1981 and 1991 (estimated excess of about 1900 and 1000 deaths respectively), the Observatório Nacional de Saúde (ONSA) - Instituto Nacional de Saúde Dr. Ricardo Jorge, together with the Vigilância Previsão e Informação - Instituto de Meteorologia, created a surveillance system called ÍCARO, which has been in operation since 1999. ÍCARO identifies heat waves with potential influence on mortality [1]. Before the end of the 2003 heat wave, ONSA had produced a preliminary estimate of its effect on mortality. The results based on daily number of deaths from 1 June to 12 August 2003 were presented within 4 working days. Data was gathered from 31 National Civil registrars, covering the district capitals of all 18 districts of mainland Portugal, and representing approximately 40% of the mainland's mortality. The number of deaths registered in the period 30 July to 12 August was compared with the ones registered during 3 comparison periods: (in July): 1-14 July, 1-28 July, and 15-28 July). 15-28 July, the period best resembling the heat wave in time and characteristics, produced an estimation of 37.7% higher mortality rate then the value expected under normal temperature conditions. From this value, an estimate of 1316 death excess was obtained for mainland Portugal. The main purpose of this article is to present the method used to identify and assess the occurrence of an effect (excess mortality) during the heat wave of summer 2003.
RESUMO
During the first two weeks of August 2003, Portugal was affected by a severe heat wave. Following the identification in Portugal of the influence of heat waves on mortality in 1981 and 1991 (estimated excess of about 1900 and 1000 deaths respectively), the Observatorio Nacional de Saude (ONSA) - Instituto Nacional de Saude Dr. Ricardo Jorge, together with the Vigilancia Previsao e Informacao - Instituto de Meteorologia, created a surveillance system called iCARO, which has been in operation since 1999. iCARO identifies heat waves with potential influence on mortality [1]. Before the end of the 2003 heat wave, ONSA had produced a preliminary estimate of its effect on mortality. The results based on daily number of deaths from 1 June to 12 August 2003 were presented within 4 working days. Data was gathered from 31 National Civil registrars, covering the district capitals of all 18 districts of mainland Portugal, and representing approximately 40% of the mainland's mortality. The number of deaths registered in the period 30 July to 12 August was compared with the ones registered during 3 comparison periods: (in July): 1-14 July, 1-28 July, and 15-28 July). 15-28 July, the period best resembling the heat wave in time and characteristics, produced an estimation of 37.7% higher mortality rate then the value expected under normal temperature conditions. From this value, an estimate of 1316 death excess was obtained for mainland Portugal. The main purpose of this article is to present the method used to identify and assess the occurrence of an effect (excess mortality) during the heat wave of summer 2003.
Assuntos
Transtornos de Estresse por Calor/mortalidade , Temperatura Alta/efeitos adversos , Tempo (Meteorologia) , Métodos Epidemiológicos , Humanos , Portugal/epidemiologia , Estações do AnoRESUMO
The bioaccessibility of total lipids, EPA, DHA, Se, Hg, and MeHg in raw and cooked meagre (Argyrosomus regius) was studied by using an in vitro digestion method. A risk-benefit assessment of raw and cooked meagre on the basis of the bioaccessibility data was carried out. The bioaccessibility of total lipids was generally high in raw and cooked meagre with exception of grilled fish. For EPA and DHA, bioaccessibility percentages were low never surpassing the 50% in raw, boiled, and grilled meagre. The bioaccessibility percentage of Se was equal or higher than 82% (grilling treatment). Likewise, for Hg and MeHg, high bioaccessibility values were determined with exception of grilled meagre, displaying lower values of 54% and 64%, respectively. The risk-benefit probabilistic assessment brought about a recommendation of a maximum consumption of two weekly meals for boiled or roasted meagre and three weekly meals for grilled meagre.
Assuntos
Culinária/métodos , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/química , Mercúrio/análise , Compostos de Metilmercúrio/química , Selênio/análise , Animais , Técnicas In Vitro , Medição de RiscoRESUMO
Antimicrobial peptides (AMPs) represent a large and ubiquitous group of peptides. The current crisis in antibiotic therapy has led to an intensified search for new antimicrobial agents. In this regard, scorpion venom constitutes a rich source of biologically active peptides including AMPs. In the present study, the purification of a novel peptide with antimicrobial activity against the Gram-negative bacteria Klebsiella pneumoniae is described. This antimicrobial peptide, named Cm38, was purified from Centruroides margaritatus scorpion venom using a two-step chromatographic strategy using C8 and C18 columns. This toxin inhibits the proliferation of the Gram-negative bacteria Klebsiella pneumoniae with a Minimal Inhibitory Concentration (MIC) of 64 µM. An analysis of the N-terminal sequence of Cm38 revealed a close structural relationship to Cn11, a Na+-channel modulator toxin previously isolated from Centruroides noxius scorpion venom. Therefore, to test Cm38 for effects on ion channels, we measured its effects on action potential firing in cultured dorsal root ganglion neurons. Cm38 depolarized and increased action potential firing in a subset of neurons tested. The present work reports a new peptide related to Cn11 with antimicrobial properties that is also active in neurons.
Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Gânglios Espinais/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Venenos de Escorpião/química , Sequência de Aminoácidos , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Eletrofisiologia , Gânglios Espinais/citologia , Hemólise/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Neurônios/citologia , Ratos , Ratos Wistar , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The pharmacokinetic profiles of single and repeated oral doses of telithromycin 800 mg/day were compared in patients with hepatic impairment and healthy subjects in two open-label, non-randomized, parallel-group, multicentre studies. The maximal plasma concentrations (Cmax) and the area under the plasma concentration-time (AUC) curves for telithromycin were similar in hepatically impaired patients and healthy subjects in the single- and repeated-dose studies. The extent of formation of RU 76363, the major circulating metabolite of telithromycin, was decreased following single and repeated doses in patients with hepatic impairment compared with healthy subjects. In the single-dose study, the Cmax of RU 76363 was 2-fold lower (P<0.01) and the initial elimination half-life (t(1/2lambda1)) was 44% higher (P<0.01). The Cmax and AUC from 0 to 24 h post-dose were approximately 50% lower on Day 1 (P< or =0.01) and Day 7 (P< or =0.001) in the repeated-dose study. The terminal elimination half-life (t(1/2lambdaz)) of telithromycin was 1.4-fold higher (P<0.001) in the hepatically impaired patients compared with the healthy subjects in the single-dose study. However, t(1/2lambda1) and t(1/2lambdaz) were similar after repeated doses in both populations, suggesting that the decrease in formation of RU 76363 is compensated by an increase in clearance via other pathways. Telithromycin 800 mg was well tolerated in both populations. In conclusion, a once-daily dose of telithromycin is well tolerated in patients with hepatic impairment. Exposure to telithromycin was comparable in patients with hepatic impairment and healthy subjects and thus, no dosage adjustment is required in this patient group providing renal function is not severely impaired.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Cetolídeos , Hepatopatias/metabolismo , Macrolídeos/administração & dosagem , Macrolídeos/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Arritmias Cardíacas/induzido quimicamente , Tolerância a Medicamentos , Feminino , Meia-Vida , Humanos , Macrolídeos/efeitos adversos , Macrolídeos/sangue , Masculino , Pessoa de Meia-Idade , SegurançaRESUMO
A trypsin inhibitor was isolated from Enterolobium contortisiliquum seeds. Starting with a saline extract, ECTI (E. contortisiliquum trypsin inhibitor) was purified as a homogeneous protein by acetone precipitation, ion-exchange chromatography (DEAE-Sephadex A-50), gel filtration (Sephadex G-75 and Superose 12) and reversed phase HPLC (mu-Bondapak C-18). The amino acid sequence was determined by automatic degradation and by DABITC/PITC microsequence analysis of the reduced and carboxymethylated protein and also of purified peptides derived from the protein by cleavage with iodosobenzoic acid and by enzymic digestion with trypsin, chymotrypsin and Staphylococcus aureus V8 protease. ECTI contains 174 amino acid residues in two polypeptide chains, an alpha-chain consisting of 134 residues and a beta-chain made up of 40 residues. The inhibitor displays a high degree of sequence identity with other Kunitz-type proteinase inhibitors isolated from the Mimosoideae subfamily. The reactive site was identified (by homology) as the arginine-isoleucine peptide bond at position 64-65. ECTI inhibits trypsin and chymotrypsin in the stoichiometric ratio of 1:1 and also Factor XIIa, plasma kallikrein and plasmin, but not thrombin and Factor Xa.
Assuntos
Aprotinina/química , Sementes/química , Árvores/química , Sequência de Aminoácidos , Aprotinina/isolamento & purificação , Aprotinina/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Cromatografia em Gel , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Humanos , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
The extract of the pericarp of castor bean (Ricinus communis) showed some typical central nervous system stimulant effects when administered to mice. The animals became exophthalmic, presented tremors and clonic seizures and died a few minutes after receiving larger doses of the extract. At lower doses the extract improved memory consolidation and showed some neuroleptic-like properties, such as a decrease in exploratory behavior and catalepsy. The memory-improving effect and the seizure-eliciting properties of the extract were also observed with the administration of ricinine, a neutral alkaloid isolated from the extract. However, the neuroleptic-like properties of the extract were not observed with ricinine. As the therapeutic index of ricinine is of the order of 200, the compound may be considered as a promising cognition-enhancing drug that may be used for the treatment of human amnesias.
Assuntos
Alcaloides/farmacologia , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Plantas Tóxicas , Piridonas , Ricinus/química , Alcaloides/química , Animais , Ansiolíticos/farmacologia , Antipsicóticos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Catalepsia/induzido quimicamente , Estimulantes do Sistema Nervoso Central/química , Exoftalmia/induzido quimicamente , Força da Mão/fisiologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pupila/efeitos dos fármacosRESUMO
The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.
RESUMO
Laurus nobilis L. is an aromatic plant frequently used as a spice in Mediterranean cookery and as a traditional medicine for the treatment of several infectious diseases. The aim of this study was to characterise the antibacterial and antioxidant activities of bay laurel essential oil (EO), ethanolic extract (EE) and hot/cold aqueous extract (AE). The major components detected in bay laurel EO were eucalyptol (27.2%), α-terpinenyl acetate (10.2%), linalool (8.4%), methyleugenol (5.4%), sabinene (4.0%) and carvacrol (3.2%). The EO exhibited strong antibacterial activity against all tested foodborne spoilage and pathogenic bacteria, whereas this activity was less pronounced or even nonexistent in the EE and AE. In contrast, EO exhibited low antioxidant activity compared to extracts (EX), and among the EX, the hot AE revealed the highest antioxidant ability. The results show that bay laurel EO and its EX have potential as natural alternatives to synthetic food preservatives, in order to enhance food safety and increase food shelf life.