RESUMO
The quantitative use of stable isotopes (SIs) for trophic studies has seen a rapid growth whereas fatty acid (FA) studies remain mostly qualitative. We apply the Bayesian tool MixSIAR to both SI and FA data to estimate the diet of three sympatric predators: the crabeater (Lobodon carcinophaga), Weddell (Leptonychotes weddellii) and leopard seal (Hydrurga leptonyx). We used SI data of their vibrissae and FA data of their outer blubber to produce comparable diet estimates for the same individuals. Both SI and FA models predicted the same main diet components, although the predicted proportions differed. For the crabeater seal, both methods identified krill, Euphausia superba, as the main, and almost exclusive, food item, although the FA model estimated a slightly lower proportion, potentially due to the low lipid content of krill compared to the fish species used in the model. For the Weddell seal the FA model identified the fish Pleuragramma antarcticum as the most important prey, whereas the SI model was not able to distinguish among prey species, identifying a 'fish-squid' group as the main diet component. For the leopard seal, both models identified krill as the main contributor; however, the predicted proportions for the secondary sources differed. Although vibrissae and outer blubber may not represent the same timeframe, the use of MixSIAR with FA data provides diet estimates comparable to those obtained with SI data, thus, both approaches were complimentary. The use of both biotracers offers a feasible option to study diets of wild animals in a quantitative manner.
Assuntos
Ácidos Graxos , Focas Verdadeiras , Animais , Regiões Antárticas , Teorema de Bayes , Dieta , Humanos , IsótoposRESUMO
Abstract Impaired wound healing represents a serious complication in some pathologies and the use of plant extracts has proved to improve tissue repair. The objectives of this study were to evaluate the healing potential of the ointment of Sebastiana hispida compared with Aluminum-Gallium Indium-Phosphide Laser (InGaAlP) in surgically induced wounds in rats and to perform the phytochemical analysis. The phytochemical analysis was performed in the classic way and also by HPLC. A controlled study was developed with 80 rats (200-250 g) in which a linear excision was performed in the dorsal region after shaving, measuring 2 cm × 1 cm (epidermis and dermis) exposing the muscle fascia. The rats were randomly divided into four groups of twenty animals each. The experimental groups (n = 5) were G1 (Saline); G2 (crude methanol plant extract 2% + Carbopol Gel 98%); G3 (crude methanol plant extract 2% + lanolin/vaseline) and G4 (laser). The incision healing processes were monitored during 3, 7, 14 and until 21 days after excision. The histologic parameters evaluated were Collagen fiber types, microscopic examination and neovascularization. There was a significant increase in the deposition of collagen fibers, as evidenced by a better organized epithelial tissue, keratinized and showing greater proliferation of new blood vessels in the inflammatory phase in the group treated with both the extract and laser. The results were correlated to the phenolic derivatives found after qualitative and quantitative analysis. These compounds were considered responsible for the healing process. The topical treatment with S. hispida leaves, in the two different formulations, was more effective than the application of the laser (Ingan ALP) 660 nm in the model used.
Resumo A cicatrização deficiente representa uma complicação grave em algumas patologias e o uso de extratos de plantas tem demonstrado melhora no processo de reparação tecidual. O objetivo deste estudo foi avaliar o potencial cicatrizante da pomada de Sebastiania hispida comparado ao Laser Indio Phosphide-Gallium-Aluminum (InGaAlP) em feridas cutâneas induzidas cirurgicamente em ratos e realizar analise fitoquímica. A análise fitoquímica foi via clássica e por CLAE. O experimento foi desenvolvido com 80 ratos (200-250 g), divididos aleatoriamente em quatro grupos (n = 5): G1 (salina); G2 (extrato bruto metanólico 2% + Carbopol Gel 98%); G3 (extrato bruto metanólico 2% + lanolina/vaselina) e G4 (laser). Após a tricotomia da região dorsal realizou uma excisão linear, medindo 2 cm × 1 cm (epiderme e derme), expondo a fáscia muscular. Em sequência os tratamentos e o monitoramento do processo de cicatrização das feridas cirúrgicas ocorreu nos tempos de: 3, 7, 14 e até 21 dias após a excisão. Os parâmetros histológicos avaliados foram: tipos de fibras colágenas, avaliação morfológica e neovascularização. Houve uma deposição significativa de fibras colágenas, evidenciado por um tecido epitelial mais bem organizado, queratinizado e mostrando uma maior proliferação de novos vasos sanguíneos na fase inflamatória do grupo tratado com o extrato e o laser. A eficiência do processo de cicatrização pode estar relacionada com a presença de compostos fenólicos e derivados detectados na análise qualitativa e quantitativa. A utilização do tratamento tópico com as duas formulações diferentes de S. hispida foram mais eficazes do que a aplicação do Laser (InGaAlP) no modelo utilizado.
Assuntos
Animais , Masculino , Ratos , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Ferimentos Penetrantes/terapia , Euphorbiaceae , Terapia com Luz de Baixa Intensidade , Fitoterapia , Pomadas , Cicatrização/fisiologia , Extratos Vegetais/uso terapêutico , Ratos Wistar , Folhas de PlantaRESUMO
Since the publication of the 2007 dyspepsia guidelines of the Asociación Mexicana de Gastroenterología, there have been significant advances in the knowledge of this disease. A systematic search of the literature in PubMed (01/2007 to 06/2016) was carried out to review and update the 2007 guidelines and to provide new evidence-based recommendations. All high-quality articles in Spanish and English were included. Statements were formulated and voted upon using the Delphi method. The level of evidence and strength of recommendation of each statement were established according to the GRADE system. Thirty-one statements were formulated, voted upon, and graded. New definition, classification, epidemiology, and pathophysiology data were provided and include the following information: Endoscopy should be carried out in cases of uninvestigated dyspepsia when there are alarm symptoms or no response to treatment. Gastric and duodenal biopsies can confirm Helicobacter pylori infection and rule out celiac disease, respectively. Establishing a strong doctor-patient relationship, as well as dietary and lifestyle changes, are useful initial measures. H2-blockers, proton-pump inhibitors, prokinetics, and antidepressants are effective pharmacologic therapies. H.pylori eradication may be effective in a subgroup of patients. There is no evidence that complementary and alternative therapies are beneficial, with the exception of Iberogast and rikkunshito, nor is there evidence on the usefulness of prebiotics, probiotics, or psychologic therapies. The new consensus statements on dyspepsia provide guidelines based on up-to-date evidence. A discussion, level of evidence, and strength of recommendation are presented for each statement.
Assuntos
Dispepsia/diagnóstico , Dispepsia/terapia , Dispepsia/epidemiologia , Dispepsia/etiologia , Endoscopia Gastrointestinal , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/terapia , Helicobacter pylori , Humanos , México/epidemiologiaRESUMO
Impaired wound healing represents a serious complication in some pathologies and the use of plant extracts has proved to improve tissue repair. The objectives of this study were to evaluate the healing potential of the ointment of Sebastiana hispida compared with Aluminum-Gallium Indium-Phosphide Laser (InGaAlP) in surgically induced wounds in rats and to perform the phytochemical analysis. The phytochemical analysis was performed in the classic way and also by HPLC. A controlled study was developed with 80 rats (200-250 g) in which a linear excision was performed in the dorsal region after shaving, measuring 2 cm × 1 cm (epidermis and dermis) exposing the muscle fascia. The rats were randomly divided into four groups of twenty animals each. The experimental groups (n = 5) were G1 (Saline); G2 (crude methanol plant extract 2% + Carbopol Gel 98%); G3 (crude methanol plant extract 2% + lanolin/vaseline) and G4 (laser). The incision healing processes were monitored during 3, 7, 14 and until 21 days after excision. The histologic parameters evaluated were Collagen fiber types, microscopic examination and neovascularization. There was a significant increase in the deposition of collagen fibers, as evidenced by a better organized epithelial tissue, keratinized and showing greater proliferation of new blood vessels in the inflammatory phase in the group treated with both the extract and laser. The results were correlated to the phenolic derivatives found after qualitative and quantitative analysis. These compounds were considered responsible for the healing process. The topical treatment with S. hispida leaves, in the two different formulations, was more effective than the application of the laser (Ingan ALP) 660 nm in the model used.
Assuntos
Euphorbiaceae , Terapia com Luz de Baixa Intensidade , Fitoterapia , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Ferimentos Penetrantes/terapia , Animais , Masculino , Pomadas , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ratos Wistar , Cicatrização/fisiologiaRESUMO
Objetivo: Proponer a partir del consenso de un panel de expertos de ambito estatal que integre la experiencia clinica y la evidencia disponible mas actual, recomendaciones sobre el uso clinico de los tratamientos por via topica para el manejo del dolor neuropatico periferico (DNP). Métodos: Se proponen, a partir de una revision bibliografica sobre las distintas opciones terapeuticas topicas en DNP, una serie de criterios profesionales y recomendaciones clinicas para la mejora del uso de dichos agentes topicos. Se empleo el metodo Delphi modificado en dos rondas para contrastar las opiniones de un panel nacional de 52 reconocidos expertos, seleccionados mediante una estrategia en bola de nieve de entre el colectivo de anestesiologos de unidades del dolor (94 %) y otros especialistas (neurologos y traumatologos). Se evaluaron 61 recomendaciones clinicas agrupadas en 6 areas tematicas: a) DNP: tratamiento topico versus sistemico (11 items); b) dolor neuropatico postquirurgico, postraumatico y munones dolorosos (12 items); c) neuralgia posherpetica, intercostal y del trigemino (9 items); d) DNP por atrapamiento (8 items); e) sindrome de dolor regional complejo (11 items); y f) neuropatia diabetica (ND) y otras polineuropatias (por VIH, alcohol, toxicidad, etc.) (10 items). Se empleo una escala ordinal de tipo Likert de 9 puntos (desacuerdo/ acuerdo) para evaluar cada recomendacion. Tras la primera ronda de encuesta, se facilito al panel informacion del resultado (resultados estadisticos y opiniones libres de los panelistas) y se solicito la reconsideracion del voto sobre los items no consensuados. Resultados: Tras la primera ronda del panel se logró consenso en 37 de las 61 cuestiones planteadas. Al final de la segunda ronda el acuerdo ascendió hasta 46 ítems (75 %). En general, se aprecia consenso entre los expertos sobre la conveniencia de introducir los tratamientos tópicos en primera línea de tratamiento del DNP y sobre su mejor aceptación por los pacientes frente a los sistémicos. Asimismo, fue criterio compartido que la combinación de estos fármacos tópicos con los tratamientos sistémicos es una opción a considerar en el manejo de varios tipos de DNP. También se alcanzó un alto grado de acuerdo en aceptar, desde un punto de vista fisiopatológico, la indicación del tratamiento con parche de capsaicina al 8 % para varios tipos de DNP. Conclusión: Los expertos en el manejo clínico del DNP muestran un elevado nivel de acuerdo profesional con diversas recomendaciones terapéuticas analizadas en el estudio. La difusión de tales recomendaciones puede ayudar a la mejora del manejo rutinario de fármacos tópicos para el dolor neuropático en nuestro sistema sanitario (AU)
Objective: To propose consensus from a panel of state level that integrates clinical experience and the most current evidence, recommendations on the clinical use of topical treatments for the management of peripheral neuropathic pain (PNP). Methods: We propose, based on a literature review on topical therapeutic options in PNP, a series of professional standards and clinical recommendations for improving the use of these topical agents. We used the modified Delphi method in two rounds to contrast the views of a national panel of 52 renowned experts, selected by a snowball strategy among the group of anesthesiologists pain units (94 %) and other specialists (neurologist and trauma). We evaluated 61 clinical recommendations grouped into 6 areas: a) PNP systemic versus topical treatment (11 items); b) postsurgical neuropathic pain, post-traumatic and painful stumps (12 items); c) post-herpetic neuralgia, intercostal and trigeminal (9 items); d) PNP entrapment (8 items); e) CRPS (11 items); and f) diabetic neuropathy (DN) and other polyneuropathy (HIV, alcohol, toxicity, etc.) (10 items). We used a Likert- type ordinal scale of 9 points (disagree/agree) to evaluate each recommendation. After the first round of the survey, information was provided requested to reconsider the vote on itemsnot agree. Results: After the first round the panel consensus was achieved in 37 of the 61 issues raised. At the end of the second round of the agreement amounted to 46 (75 %). In general, there was consensus among experts on whether to introduce topical treatment in first line treatment of PNP and its greater acceptance by patients compared with systemic. He was also a shared view consider in the management of various types of PNP. Also reached a high level of agreement to accept, from a physiological point of view, the indication for treatment with capsaicin patch 8 % for various types of PNP. Conclusions: Experts in the clinical management of PNP show a high level of professional agreement with various therapeutic recommendations for study. The dissemination of such recommendations can help improving the routine management of topical drugs for neuropathic pain in our health system (AU)
Assuntos
Humanos , Masculino , Feminino , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Administração Tópica , Polineuropatias/complicações , Polineuropatias/tratamento farmacológico , Capsaicina/uso terapêutico , Adesivo Transdérmico , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/fisiopatologia , Clínicas de Dor/organização & administração , Clínicas de Dor/normas , Clínicas de Dor , Capsaicina/metabolismo , Capsaicina/farmacocinética , Adesivo Transdérmico/tendênciasRESUMO
Debido a sus grandes diferencias, anatómicas y funcionales, el estudio de la región craneocervical se separa del resto de la columna cervical. El complejo craneocervical se considera responsable de signos y síntomas muy diferentes a los que encontramos en el raquis cervical inferior, como por ejemplo vértigos, cefaleas de distinto origen, etc. El objetivo de la técnica de thrust para una disfunción en rotación del atlas con contacto indexial es devolver la movilidad y funcionalidad a la vértebra. Es importante dominar los principios básicos de realización de la técnica para poder aplicar una correcta intervención terapéutica tras haber descartado los posibles riesgos de la manipulación (AU)
Due to the large anatomical and functional differences, the study of the craniocervical region is separated from the rest of the cervical column. The craniocervical junction is considered as responsible for very different signs and symptoms to those we find in the inferior cervical spine, such as for example vertigo, headaches with different origins, etc. The objective of the thrust technique for an atlas rotation disorder with index finger contact is to return mobility and functionality to the vertebra. It is important to master the basic principles of performing the technique to be able to apply the correct therapeutic procedure after having ruled out the possible risks of manipulation (AU)
Assuntos
Humanos , Masculino , Feminino , Medicina Osteopática , Osteopatia , Atlas Cervical/patologia , Atlas Cervical/lesõesRESUMO
We investigated how virgin olive oil (VOO) affected platelet and hypoxic brain damage in rats. Rats were given VOO orally for 30 days at 0.25 or 0.5 mL kg(-1) per day (doses A and B, respectively). Platelet aggregation, thromboxane B2, 6-keto-PGF(1alpha), and nitrites + nitrates were measured, and hypoxic damage was evaluated in a hypoxia-reoxygenation assay with fresh brain slices. Oxidative stress, prostaglandin E2, nitric oxide pathway activity and lactate dehydrogenase (LDH) activity were also measured. Dose A inhibited platelet aggregation by 36% and thromboxane B2 by 19%; inhibition by dose B was 47 and 23%, respectively. Virgin olive oil inhibited the reoxygenation-induced increase in lipid peroxidation (57% in control rats vs. 2.5% (P < 0.05) in treated rats), and reduced the decrease in glutathione concentration from 67 to 24% (dose A) and 41% (dose B). Brain prostaglandin E2 after reoxygenation was 306% higher in control animals, but the increases in treated rats were only 53% (dose A) and 45% (dose B). The increases in nitric oxide production (213% in controls) and activity of the inducible isoform of nitric oxide synthase (175% in controls) were both smaller in animals given VOO (dose A 84%; dose B 12%). Lactate dehydrogenase activity was reduced by 17% (dose A) and 42% (dose B). In conclusion, VOO modified processes related to thrombogenesis and brain ischemia. It reduced oxidative stress and modulated the inducible isoform of nitric oxide synthase, diminishing platelet aggregation and protecting the brain from the effects of hypoxia-reoxygenation.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Hipóxia Encefálica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Gorduras Insaturadas na Dieta/administração & dosagem , Modelos Animais de Doenças , Masculino , Óxido Nítrico Sintase/metabolismo , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Ratos , Ratos WistarRESUMO
Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos, used as raw material for topical and oral photoprotective formulations, was fractioned by HPLC and the main components with antioxidant capability were identified by means of UV spectra, electrochemical detection, and MSn. Phenolic compounds were identified as 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, vanillic acid, caffeic acid, 4-hydroxycinnamic acid, 4-hydroxycinnamoyl-quinic acid, ferulic acid, and five chlorogenic acid isomers. Total ferric antioxidant capacity (FRAP) of HPLC eluted fractions was measured. The results suggest that the herein identified compounds support, at least partially, the antioxidant and radical scavenging capacities of Fernblock.
Assuntos
Antioxidantes/química , Fenóis/análise , Extratos Vegetais/química , Polypodium , Antioxidantes/análise , Ácidos Cafeicos/análise , Ácidos Cafeicos/química , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/análise , Ácidos Cumáricos/química , Eletroquímica , Compostos Férricos/química , Espectrometria de Massas , Oxirredução , Parabenos/análise , Parabenos/química , Fenóis/química , Componentes Aéreos da Planta/química , Propionatos , Ácido Vanílico/análise , Ácido Vanílico/químicaRESUMO
Enteroliths are calculi primarily formed in the intestine. Enterolithiasis is a rare condition frequently associated with intestinal stasis. Usually it causes no symptoms in most cases, but it can be an important diagnostic clue in patients presenting intestinal occlusive symptoms. We report a case of multiple enterolithiasis, very infrequent pathology, coexisting with bladder and gall bladder lithiasis in a patient with colon adenocarcinoma. Diagnosis was made by X-rays and CT images. Calculi were analysed by several methods: chemical, infrared spectroscopy, stereoscopic microscopy and atomic emission spectroscopy; they showed that caluli are made up of organic material and whilokita (calcium and magnesium ortophosphate). No risk factors for lithogenesis were found in this patient excluding the intestinal stasis caused by intestinal narrowing as a result of adenocarcinoma. Genetic factors are suggested as main contributors to hyperlithogenesis observed in this patient. The physiopathological conditions were studied in depth and literature about this subject reviewed.
Assuntos
Adenocarcinoma/complicações , Cálculos/complicações , Colelitíase/complicações , Neoplasias do Colo/complicações , Enteropatias/complicações , Cálculos da Bexiga Urinária/complicações , Dor Abdominal/etiologia , Adenocarcinoma/genética , Idoso , Idoso de 80 Anos ou mais , Cálcio/análise , Cálculos/química , Cálculos/genética , Doenças do Ceco/complicações , Doenças do Ceco/genética , Colelitíase/química , Colelitíase/genética , Neoplasias do Colo/genética , Dilatação Patológica/etiologia , Predisposição Genética para Doença , Humanos , Doenças do Íleo/complicações , Doenças do Íleo/genética , Enteropatias/genética , Doenças do Jejuno/complicações , Doenças do Jejuno/genética , Magnésio/análise , Masculino , Fósforo/análise , Cálculos da Bexiga Urinária/química , Cálculos da Bexiga Urinária/genéticaRESUMO
UNLABELLED: Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate. RESULTS: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins. CONCLUSIONS: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.
Assuntos
Compostos de Epóxi/uso terapêutico , Falência Renal Crônica/sangue , Fosfatos/sangue , Polietilenos/uso terapêutico , Equilíbrio Ácido-Base/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bicarbonatos/sangue , Cálcio , Quelantes/uso terapêutico , Avaliação de Medicamentos , Quimioterapia Combinada , Compostos de Epóxi/efeitos adversos , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Humanos , Hipercalcemia/tratamento farmacológico , Hipercolesterolemia/sangue , Hipolipemiantes/uso terapêutico , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Aceitação pelo Paciente de Cuidados de Saúde , Poliaminas , Polietilenos/efeitos adversos , Estudos Retrospectivos , SevelamerRESUMO
OBJECTIVE: This study was performed to evaluate the acute effect of a single repetitive transcranial magnetic stimulation (rTMS) session in a focal hyperperfusion epileptogenic region to induce a transitory decrease of epileptiform activity. CASE REPORT: Two epilepsia partialis continua (EPC)-diagnosed patients, received one session with 15 trains of rTMS (20 Hz; 2 s train, inter-train of 58 s). Before rTMS session, a brain ictal single photon emission computed tomography (SPECT) was performed to localize the focal frontal hyperperfusion region to establish the stimulation site. Immediately after the rTMS session another ictal SPECT was performed. Both patients showed a decrease of perfusion in the stimulated regions. For patient 1 epileptic seizures became intermittent until they stopped in the following 24 h. Patient 2 showed only a minimal improvement with a frequency decrease of epileptic spikes. CONCLUSIONS: Our findings suggest that a single rTMS session reduces focal epileptogenic activity and could be an alternative approach for epileptic-resistant patients, but efficacy should be confirmed in a larger series.
Assuntos
Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Terapia por Estimulação Elétrica , Campos Eletromagnéticos , Epilepsia Parcial Contínua/fisiopatologia , Epilepsia Parcial Contínua/terapia , Encéfalo/diagnóstico por imagem , Criança , Epilepsia Parcial Contínua/diagnóstico por imagem , Feminino , Humanos , Masculino , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Inmunoferon is a glycoconjugate of natural origin with immunomodulatory properties. It has recently been shown to regulate TNF-alpha expression induced by lipopolysaccharide (LPS) challenge through a hypothalamo-pituitary-adrenal (HPA)-dependent mechanism. Inmunoferon is orally administered to immunocompromised patients as an adjuvant during immune therapy such as vaccination or infectious diseases treatment. Due to its mainly adjuvant nature, it is necessary to determine if coadministration of Inmunoferon affects the activity of other drugs. In this study we analyzed the possible modification of the hepatic drug biotransformation system by using Inmunoferon in a rat model, which may result in changes in the biological activity of other drugs administered simultaneously. Inmunoferon-treated animals showed no differences to control littermates in antipyrine metabolism. No differences were found in either cytochrome P-450 and b5 levels or cytochrome P-450-dependent activities and phase II conjugation enzymes in lysates from Inmunoferon-treated rat hepatic cells. The same treatment reduced levels of serum TNF-alpha in LPS-challenged animals. In summary, Inmunoferon is unable to affect the hepatic bioconjugation system during administration and thus seems unlikely to interact with, or modify the effect of, coadministered drugs.
Assuntos
Adjuvantes Imunológicos/farmacologia , Fosfatos de Cálcio/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Glicopeptídeos/farmacologia , Fígado , Animais , Antibacterianos/farmacocinética , Biotransformação , Fígado/efeitos dos fármacos , Fígado/enzimologia , Macrolídeos , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Inmunoferon is a glycoconjugate of natural origin, formed by the noncovalent association of a protein from Ricinus communis and a polysacharidic moiety, and endowed with immunomodulatory as well as pharmacological activities. This study investigated the nature of polypeptidic component of Inmunoferon. Through biochemical procedures and comparison with protein databases, the isolated protein was identified as the processed form of the seed of Ricinus communis 2S storage polypeptide, which has been termed RicC3. Further analysis of the isolated protein has revealed that it is composed of two different subunits, alpha and beta, which form an heterodimer of high stability and resistance to denaturation, acidic pH and proteolytic cleavage. These findings confirm the excellent properties of the product after oral administration and provide additional support for the pharmacological activities of Inmunoferon.
Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Fosfatos de Cálcio/química , Fosfatos de Cálcio/isolamento & purificação , Glicoconjugados/química , Glicoconjugados/isolamento & purificação , Glicopeptídeos/química , Glicopeptídeos/isolamento & purificação , Peptídeos/química , Peptídeos/isolamento & purificação , Adjuvantes Imunológicos/metabolismo , Albuminas/química , Fosfatos de Cálcio/metabolismo , Bases de Dados de Proteínas , Dimerização , Glicoconjugados/metabolismo , Glicopeptídeos/metabolismo , Peso Molecular , Peptídeos/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/metabolismo , Conformação Proteica , Desnaturação Proteica , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Ricinus/química , Análise de Sequência de Proteína/métodos , Homologia de Sequência de Aminoácidos , Tripsina/metabolismoRESUMO
In this report, we have examined the mechanism of action of Inmunoferon, a patented glycoconjugate (GC) of natural origin with immunomodulatory properties, in the regulation of TNF-alpha expression induced by LPS challenge in a rodent model. GC was found to be dependent on a normal HPA response to exert its regulatory effect on TNF-alpha expression. Adrenalectomized mice were unresponsive to the drug in terms of TNF-alpha levels after LPS challenge, whereas control mice showed lower serum TNF-alpha levels when treated with GC than vehicle-treated animals. GC treatment also induced the expression of acute phase proteins but it did not alter the normal metabolism or viability of hepatic cells. These data suggested the employment of GC as a novel adjuvant during antibacterial treatment without disadvantages such as side effects in the metabolism of the liver, thus, acting as an enhancer of the host response against infection.
Assuntos
Fosfatos de Cálcio/farmacologia , Glicoconjugados/farmacologia , Glicopeptídeos/farmacologia , Hepatócitos/patologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Fígado/patologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Células Cultivadas , Hepatócitos/efeitos dos fármacos , Hepatócitos/imunologia , Hepatócitos/metabolismo , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/imunologia , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/biossínteseRESUMO
We have analyzed the effect of a patented glycoconjugate (GC) of natural origin, Inmunoferon, in the development of the response to endotoxemia induced by administration of LPS in rodents. We have observed that oral treatment with the drug reduced the levels of serum TNF-alpha induced by an intravenous pulse of LPS. The serum of pretreated mice blocked TNF-alpha production by peritoneal macrophages. The drug increased the levels of TNF-alpha regulators such as IL-10 and corticosteroids, whereas it inhibited TNF-alpha-dependent IL-6 production. Further TNF-alpha-dependent responses, such as cell extravasation, was decreased in treated mice. According to these results, Inmunoferon is postulated as an inhibitor of the systemic response to LPS. Correlation of the observations made in mice with a rat model suggests the efficacy of this product in reducing TNF-alpha production in a species-independent fashion and opens the possibility of its trial as an adjuvant of antibiotics in treatment against gram-negative bacterial infection.
Assuntos
Adjuvantes Imunológicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Fosfatos de Cálcio/farmacologia , Glicopeptídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Animais , Cromatografia Gasosa , Corticosterona/sangue , Ensaio de Imunoadsorção Enzimática , Indicadores e Reagentes , Inflamação/patologia , Inflamação/prevenção & controle , Interleucina-6/biossíntese , Contagem de Leucócitos , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Endogâmicos LewRESUMO
A new method for the labeling of polysaccharides by using tyrosine derivatives after CNBr activation is presented, along with its use for pharmacokinetic studies of an orally active immunomodulating noncovalent glycoconjugate, which was administered labeled either in the polysaccharide or the protein moiety. The relationship between the obtained results and the mechanism of action are also discussed.
Assuntos
Adjuvantes Imunológicos/farmacocinética , Fosfatos de Cálcio/farmacocinética , Glicopeptídeos/farmacocinética , Marcação por Isótopo/métodos , Adjuvantes Imunológicos/sangue , Adjuvantes Imunológicos/química , Animais , Fosfatos de Cálcio/sangue , Fosfatos de Cálcio/química , Cromatografia em Gel , Trânsito Gastrointestinal/efeitos dos fármacos , Glicopeptídeos/sangue , Glicopeptídeos/química , Radioisótopos do Iodo , Masculino , Camundongos , Polissacarídeos/química , Distribuição Tecidual , TirosinaRESUMO
Green leaf volatiles (GLVs) from Brassica oleracea subsp. capitata L. have been identified as 1-hexanol, (Z)-3-hexen-1-ol, 1-hexen-3-ol, hexanal, (E)-2-hexenal, hexyl acetate, and (Z)-3-hexenyl acetate, by their mass spectra and retention times in comparison with authentic samples. No isothiocyanates were found in the extract. The activity of these chemicals has been determined on mated and unmated males and females of the diamondback moth (DBM) Plutella xylostella in the laboratory (wind tunnel) and in the field. On unmated males, mixtures of (Z)-3-hexenyl acetate, (E)-2-hexenal, and (Z)-3-hexen-1-ol with the pheromone induced attractant/arresting behavior in 80-100% of the males tested, significantly higher than the effect induced by the pheromone alone. On mated males and unmated females the effect of the GLVs alone or in combination with the pheromone was poor, while on mated females these compounds elicited upwind flight and arresting behavior in 40-60% of the females assayed. There was no synergism when these chemicals were mixed with the pheromone. In the field, (Z)-3-hexenyl acetate, the most active GLV in laboratory tests, when mixed with the pheromone in 1:1 ratio, enhanced 6-7-fold the number of females and 20-30% the number of males caught by traps over those baited with the pheromone alone. Our results indicate that the enhancement of the attraction of both males and females of the DBM to traps baited with pheromone blended with the relatively inexpensive and environmentally safe (Z)-3-hexenyl acetate may be important for future control strategies of the pest.
Assuntos
Brassica/química , Mariposas/fisiologia , Animais , Comportamento Animal , Feminino , Masculino , Extratos Vegetais/química , Atrativos Sexuais , Comportamento Sexual AnimalRESUMO
Fifty-five human immunodeficiency virus-infected patients with Salmonella bacteremia were studied to assess the rate of and causes for recurrence and to determine the influence on relapse of zidovudine, cotrimoxazole, and antimicrobial suppressive therapy according to the susceptibility of the isolates. Overall, 22% of patients relapsed in a median time of 87 days, independent of CD4 cell count, Salmonella serotype, or duration of antibiotic therapy. The use of zidovudine was associated with the lowest rate of recurrences compared with cotrimoxazole or amoxicillin as suppressive therapy. In the microbiologic assay, zidovudine showed bactericidal effect on Salmonella species at current dosages, and resistance to zidovudine was uncommon (2 cases, 4%). Due to its direct effect on Salmonella species, a zidovudine-containing regimen may protect against the recurrence of the disease.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Fármacos Anti-HIV/uso terapêutico , Bacteriemia/prevenção & controle , Infecções por Salmonella/prevenção & controle , Zidovudina/uso terapêutico , Adulto , Amoxicilina/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bacteriemia/complicações , Ciprofloxacina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Recidiva , Infecções por Salmonella/complicações , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
Energy Filtered Transmission Electron Microscopy (EFTEM) has been used to study nucleic acids localization in unstained thin sections of virus-infected cells. For this purpose, phosphorus maps (P-maps) have been obtained by applying the N-windows Egerton model for background subtraction from data acquired by a non-dedicated TEM Jeol 1200EXII equipped with a post-column PEELS Gatan 666-9000 and a Gatan Image Filter (GIF-100). To prevent possible errors in the evaluation of elemental maps and thus incorrect nucleic acid localization, we have studied different regions of swine testis (ST) cells with similar local density containing either high concentration of nucleic acids (condensed chromatin and ribosomes) or a very low concentration (mitochondria). Special care was taken to optimize the sample preparation conditions to avoid as much as possible the traditional artifacts derived from this source. Selection of the best set of pre-edge images for background fitting was also considered in order to produce "true P-maps". A new software for interactive processing of images series has been applied to estimate this set. Multivariate Statistical Analysis was used as a filtering tool to separate the "useful information" present in the inelastic image series (characteristic signal) from the "non-useful information" (noise and acquisition artifacts). The reconstitution of the original image series preserving mainly the useful information allowed the computation of P-maps with improved signal-to-noise ratio (SNR). This methodology has been applied to study the RNA content of maturation intermediate coronavirus particles found inside infected cells.
Assuntos
Microscopia Eletrônica/métodos , Ácidos Nucleicos/análise , Fósforo/análise , RNA Viral/análise , Animais , Processamento de Imagem Assistida por Computador , Masculino , Análise Multivariada , Ácidos Nucleicos/ultraestrutura , RNA Viral/ultraestrutura , Software , Suínos , Testículo/ultraestrutura , Testículo/virologia , Vírus da Gastroenterite Transmissível/ultraestruturaRESUMO
The cases of four liver transplant recipients who developed invasive candidiasis (2 cholangitis, 1 perihepatic abscess, 1 candidemia) due to azole-resistant, Candida glabrata are reported. Three patients were receiving azolic compounds (2 itraconazole, 1 fluconazole) when the infection was diagnosed. All four patients received fluconazole as intestinal decontamination during the first three weeks post transplantation. The infections occurred two months after transplantation in all patients, and in one patient Candida infection was the direct cause of death. Infection of the biliary tree was the origin of candidiasis in three patients; the fourth patient developed neutropenic-related candidemia. Fluconazole MICs exceeded 16 micrograms/ml in all cases; itraconazole MICs were 16, 2, 1, and 2 micrograms/ml, respectively. The potential role of Candida species other than albicans in these patients after administration of azole agents is discussed.