Caracterização físico-química e atividade biológica de um cimento dentário à base de quitosana, nanohidroxiapatita, nanopartículas de óxido de zinco para estimulação de células nervosas de Schwann (HS-SCH-2) / Physical-chemical characterization and biological activity of a dental cement based on chitosan, nano-hydroxyapatite, and zinc oxide nanoparticles for Schwann nervous cell stimulation (hs-sch-2)

Os cimentos dentários e ortopédicos são utilizados amplamente em diversas aplicações clínicas. Novos cimentos vêm sendo propostos visando à preservação ou regeneração tecidual. Contudo, pouco se conhece sobre o papel desses biomateriais na regeneração nervosa. As células mais comumente envolvidas na regeneração nervosa são as células de Schwann (SCs) sendo sua principal função o suporte aos axônios através da liberação de fatores de crescimento e isolamento axonal através da formação da bainha de mielina. Como estratégia da presente pesquisa, foi estudado um cimento à base da quitosana com adição de substâncias que podem atuar sinergicamente na resposta celular nervosa, tais como, as nanopartículas (NPs) de hidroxiapatita e o óxido de zinco, visto que têm propriedades bioativas e biocondutoras, além de promoverem a condução de prolongamento axonal. A doxiciclina (Dox) foi acrescida como antimicrobiano, potente inibidora de metaloproteinases (MMPs) e estimuladora da diferenciação celular no processo de regeneração tecidual. Assim, as propriedades físico-químicas e biológicas do cimento de nano-hidroxiapatita, quitosana, óxido de zinco e doxiciclina foram avaliadas, bem como a capacidade de promover um ambiente favorável para as células nervosas periféricas. Os cimentos foram caracterizados físico-químicamente mediante a determinação do pH, tempo de presa e solubilidade, lixiviação de íons cálcio, liberação controlada de doxiciclina, difração de Raios X, Termogravimetria (TG), espectroscopia Raman, molhabibidade, e testes de atividade biológica, para assim também serem avaliados em contato com células nervosas de Schwann (HS-Sch-2). O cimento apresentou pH neutro (7,0), tempo de presa de 5,7 ± 0,22 minutos, solubilidade menor que 3%, lixiviação de cálcio de 8,14 ± 0,71 mg L-1 após 14 dias, estabilidade térmica e a análise espectroscópica ratificou a presença e diferenciação das estruturas químicas dos componentes do cimento coerentemente com as imagens das análises microscópicas. Além disso, o cimento se mostrou hidrofílico, teve efeito hemolítico baixo (17%), obteve alta citocompabilidade celular em fibroblastos ATCC 3T3 (72%) e ação antimicrobiana. O cimento aumentou significativamente o crescimento das células de Schwann, 48,6% a mais do que o grupo controle (p≤0.05), e maior capacidade metabólica na análise mitótica quando em contato com este material (33%). Pode-se concluir que o cimento proposto à base de quitosana contendo hidroxiapatita e óxido de zinco nanoparticulados com adição de doxiciclina obteve efeito bioativo em células de Schwann promovendo, assim, o crescimento e a atividade mitótica celular, sendo então um biomaterial promissor para estudos de remielinização de nervos periféricos e regeneração nervosa in vivo.

Dental and orthopedic cements are used widely in several clinical applications. New cements have been proposed aimed the tissue preservation or regeneration. Nevertheless, nerve regeneration is not well known. The cells most commonly used in nerve regeneration are Schwann cells (SCs) which represent glial cells in the peripheral nervous system, their main function being supporting axons by releasing growth factors and axonal isolation through the formation of the myelin sheath. As a strategy of this research, chitosan-based cement was studied with the addition of substances that can act synergistically in the nervous cell response, such as the hydroxyapatite and zinc oxide nanoparticles (NPs), since they have bioactive and bioconductive properties; in addition to furthermore, they promote the conduction of axonal prolongation. Doxycycline (Dox) was added as an antimicrobial, a potent inhibitor of MMPs, a stimulator of cell differentiation in the tissue regeneration process. Thus, the physical-chemical and biological properties of nanohydroxyapatite, chitosan, zinc oxide and doxycycline cements were evaluated, as well as the ability to promote a favorable environment for peripheral nerve cells. Blocks of cements were characterized physically and chemically by determining pH, setting time and solubility, calcium ions leaching, controlled release of doxycycline, X-ray diffraction, Thermogravimetry (TG), Raman spectroscopy, wetness, and biological activity tests, so they can also be evaluated in contact with Schwann nerve cells (HS-Sch-2). The cement showed neutral pH (7.0), setting time of 5.7 ± 0.22 minutes, solubility less than 3%, calcium leaching of 8.14 ± 0.71 mg L-1 after 14 days, stability thermal and spectroscopic analysis confirmed the presence and differentiation of the chemical structures of the cement components coherently with the images of the microscopic analysis. In addition, the cement was shown to be hydrophilic, had a low hemolytic effect (17%), and obtained high cell cytocompatibility in ATCC 3T3 fibroblasts (72%) and antimicrobial action. The cement significantly increased the growth of Schwann cells, 48.6% more than the control group (p≤0.05), and greater metabolic capacity in the mitotic analysis when in contact with this material (33%). It can be concluded that the proposed chitosan-based cement containing hydroxyapatite and zinc oxide nanoparticulated with the addition of doxycycline has a bioactive effect in Schwann cells, thus promoting cell growth and mitotic activity, thus being a promising biomaterial for studies of remyelinization of peripheral nerves and nerve regeneration in vivo.

The challenging approach to a combined neurotrophic and exposure corneal ulcer / Abordagem desafiante de uma úlcera de córnea neurotrófica e por exposição

ABSTRACT This study aims to describe a challenging clinical case of a patient with a neurotrophic and exposure corneal ulcer. A 75-year-old male patient, with history of right eye (RE) limbic stem-cell insuficiency due to complications of recurrent herpetic keratitis, underwent successful limbic stem-cell transplantation in 2008. In 2010, an uneventful penetrating keratoplasty was performed. After a cataract phacoemulsification surgery with intraocular lens implantation done in 2011, best corrected visual acuity was 20/20, and remained stable until 2015. In July 2015, the patient developed right facial nerve palsy and two months later, presented with an extensive central corneal ulcer, with a significant thinning of central stroma, without infection signs, but with an imminent risk of perforation. Treatment with topical ofloxacin and intensive ocular lubrification was started in association with permanent ocular oclusion. Due to lack of any clinical improvement, treatment with RGTA [Poli (carboximetilglucose) sulfate, dextrano T40] (Cacicol®, Thea) was started. After two weeks of treatment, a complete reepithelization and partial stromal filling was observed. Continued monitoring and treatment with artificial tears was maintained, with no recurrence observed. There is an unmet need for a medical therapy that could help corneal neurotrophic ulcers to heal. The presented clinical case shows that the approach of targeting extracellular matrix can be effective in the reepithelialization of neurotrophic and exposure corneal ulcer that do not respond to conventional treatments.

RESUMO Este trabalho relata um caso clínico desafiante de doente com uma úlcera de córnea neurotrófica e de exposição. Doente do sexo masculino, de 75 anos, com antecedentes de queratites herpéticas de repetição no olho direito (OD), complicadas com o desenvolvimento de uma insuficiência límbica, foi submetido com sucesso a transplante de células límbicas em 2008. Em 2010 foi submetido a queratoplastia penetrante e em 2011, após realização de cirurgia de catarata, apresentava uma melhor acuidade visual corrigida (MAVC) de 20/20. A MAVC manteve-se estável até Julho de 2015, altura em que desenvolveu paresia facial periférica à direita. Dois meses depois, o doente desenvolveu uma úlcera de córnea central extensa, com adelgaçamento significativo do estroma central, sem sinais de infeção, mas com risco iminente de perfuração. Foi iniciado tratamento tópico com ofloxacina, lubrificação intensiva e oclusão ocular contínua. Por ausência de melhoria clínica, foi iniciado tratamento tópico com um RGTA [Poli (carboximetilglucose) sulfato, dextrano T40] (Cacicol®, Thea). Após duas semanas de tratamento, observou-se uma reepitelização completa e regeneração parcial do estroma. Foi mantida monitorização regular e tratamento com lágrimas artificiais, sem recidiva do quadro clínico. Há uma grande necessidade de tratamentos médicos que possam ajudar na regeneração de úlceras de córnea neurotróficas e de exposição. O caso clínico apresentado sugere que os fármacos que têm por alvo a matrix extracelular poderão ser eficazes na reepitelização de úlceras de córnea neurotróficas e de exposição que não respondem ao tratamento convencional.

The wound healing potential of collagen peptides derived from the jellyfish Rhopilema esculentum / 中华创伤杂志(英文版)

PURPOSE@#Wound represents a major health challenge as they consume a large amount of healthcare resources to improve patient's quality of life. Many scientific studies have been conducted in search of ideal biomaterials with wound-healing activity for clinical use and collagen has been proven to be a suitable candidate biomaterial. This study intended to investigate the wound healing activity of collagen peptides derived from jellyfish following oral administration.@*METHODS@#In this study, collagen was extracted from the jellyfish--Rhopilema esculentum using 1% pepsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fourier transform infrared (FTIR) were used to identify and determine the molecular weight of the jellyfish collagen. Collagenase II, papain and alkaline proteinase were used to breakdown jellyfish collagen into collagen peptides. Wound scratch assay (in vitro) was done to determine migration potential of human umbilical vein endothelial cells (HUVEC) covering the artificial wound created on the cell monolayer following treatment with collagen peptides. In vivo studies were conducted to determine the effects of collagen peptides on wound healing by examining wound contraction, re-epithelialization, tissue regeneration and collagen deposition on the wounded skin of mice. Confidence level (p < 0.05) was considered significant using GraphPad Prism software.@*RESULTS@#The yield of collagen was 4.31%. The SDS-PAGE and FTIR showed that extracted collagen from jellyfish was type I. Enzymatic hydrolysis of this collagen using collagenase II produced collagen peptides (CP) and hydrolysis with alkaline proteinase/papain resulted into collagen peptides (CP). Tricine SDS-PAGE revealed that collagen peptides consisted of protein fragments with molecular weight <25 kDa. Wound scratch assay showed that there were significant effects on the scratch closure on cells treated with collagen peptides at a concentration of 6.25 μg/mL for 48 h as compared to the vehicle treated cells. Overall treatment with collagen peptide on mice with full thickness excised wounds had a positive result in wound contraction as compared with the control. Histological assessment of peptides treated mice models showed remarkable sign of re-epithelialization, tissue regeneration and increased collagen deposition. Immunohistochemistry of the skin sections showed a significant increase in β-fibroblast growth factor (β-FGF) and the transforming growth factor-β (TGF-β) expression on collagen peptides treated group.@*CONCLUSION@#Collagen peptides derived from the jellyfish-Rhopilema esculentum can accelerate the wound healing process thus could be a therapeutic potential product that may be beneficial in wound clinics in the future.

Nasal Trigeminal Chemoreception / 대한이비인후과학회지

The sensory function of the trigeminal nerve is to provide tactile, proprioceptive, and nociceptive afference by chemical stimulation. Various physical responses of the trigeminal nerve to stimuli help to defend against harmful substances. Recently, many studies have been conducted on solitary chemoreceptor cells innervated by trigeminal nerve. Most volatile organic compounds stimulate both the olfactory and trigeminal nervous systems. In general, the trigeminal nervous system is less sensitive than the olfactory nervous system. Studies have shown that sensation of the trigeminal nerve by chemical stimulation results in inhibition of olfaction. This indicates that the olfactory and trigeminal nerves interact with each other in the central nervous system. It is important to study various noxious stimuli acting on the trigeminal nerve in modern society where environmental concerns are intensifying.

Low-dose resveratrol supplementation on heart rate variability in hypertensive volunteers: a controlled double-blind trial / Suplementação de baixa dose de resveratrol na variabilidade da frequência cardíaca em hipertensos: ensaio clinico controlado e duplo cego

OBJECTIVE: Hypertension decreases the heart rate variability (HRV). Resveratrol, a phenolic compound found in grapes and their products, has been explored for its potential to treat hypertension. We evaluated the effects of low-dose resveratrol on HRV in hypertensive volunteers. METHOD: Twenty-one hypertensive volunteers of both sexes were supplemented with resveratrol (n = 11) or placebo (n = 10) for 30 days. HRV parameters were measured before and during a standardized treadmill exercise. One resveratrol- and 3 placebo-treated patients were lost to follow-up. RESULTS: There were no anthropometric differences between resveratrol (n = 10) and placebo (n = 7) other than a difference in body mass index. The measured HRV parameters did not differ between resveratrol and placebo, or between control and treadmill exercise. CONCLUSION: Low-dose resveratrol did not alter HRV in hypertensive patients.

OBJETIVO: A hipertensão arterial diminui a variabilidade da frequência cardíaca (VFC). Resveratrol têm sido estudado como tendo potencial para o tratamento da hipertensão. Foram avaliados os efeitos de baixas doses de resveratrol na variabilidade da frequência cardíaca em voluntários hipertensos. MÉTODO: Vinte e um voluntários hipertensos, de ambos os sexos foram suplementados com resveratrol (n = 11) ou placebo (n = 10) durante 30 dias. Parâmetros da VFC foram medidos antes e durante o exercício em esteira padronizado. Um paciente tratado com resveratrol e três tratados com placebo foram perdidos. RESULTADOS: Não houve diferenças antropométricas entre os integrantes dos grupos resveratrol (n = 10) vs. placebo (n = 7), exceto uma diferença de índice de massa corporal. Não foram observadas diferenças para nenhum dos parâmetros da VFC entre resveratrol vs. placebo, ou entre controle vs. exercício em esteira. CONCLUSÃO: A baixa dose de resveratrol não afetou a VFC em hipertensos.

Contribución de la temperatura fría y el sabor ácido en la intervención fonoaudiológica de la disfagia orofaríngea / Contribution of cold temperature and sour taste in speech and language intervention of oropharyngeal dysphagia

El fonoaudiólogo es el principal profesional en la rehabilitación no farmacológica y no quirúrgica del usuario con disfagia. Su participación es fundamental tanto para el aminoramiento del riesgo de aspiración o penetración laríngea, como para mejorar o restaurar la función deglutoria. Para este fin, posee opciones terapéuticas directas e indirectas, cuya elección y aplicación dependerá de la patología que curse el usuario, las redes que posea para su recuperación y la motivación intrínseca del mismo. Entre las estrategias de intervención indirecta se encuentra el Tratamiento Sensorio-Motor Oral (OSMT, por sus siglas en inglés), el cual pretende producir una aceleración en el desencadenamiento del proceso deglutorio mediante la ejercitación de los músculos orofaciales en conjunto con diferentes estímulos sensoriales (específicamente la temperatura fría y el sabor ácido). La presente revisión tiene por objetivo dilucidar si la utilización de la temperatura fría y el sabor ácido son útiles como mecanismo de intervención indirecta de la disfagia. Se concluye que las acciones propuestas son efectivas simplemente como mecanismos compensatorios en el proceso deglutorio, puesto que modifican las características del bolo alimenticio e incrementan momentáneamente las sensaciones intraorales.

The speech-language pathologist (SLP) is the main professional in the nonpharmacological and non-surgical rehabilitation of patients with dysphagia. Their role is essential for both reducing the risk of aspiration or laryngeal penetration and improving or restoring the swallowing function. To this end, the SLP has direct and indirect therapeutic options, whose choice and application will depend on the patient’s condition, support networks, and their intrinsic motivation. As part of the indirect intervention strategies, the oral sensorymotor treatment (OSMT) aims to exercise the orofacial muscles, and introduce sensory input by the application of cold temperature and sour taste to increase the triggering speed of the swallowing reflex. This review seeks to determine whether the use of cold temperature and sour taste are effective indirect mechanisms for treating patients with dysphagia. It is concluded that the proposed actions in this review are useful simply as compensatory mechanisms in the swallowing process, as they modify the bolus properties and increase, temporarily, the intra-oral sensations.

Efecto de las cargas articulares sobre el flujo y pH salival / Effect of TMJ loading on salivary flow and pH

Una alteración del flujo salival es clave en el desarrollo de caries, enfermedad periodontal e infecciones oportunistas. El flujo salival está determinado por diversos estímulos que actúan sobre receptores de distinta naturaleza, entre ellos mecanoreceptores articulares. Algunos estudios demuestran que las cargas articulares actúan sobre estos receptores, modificando cualitativa y cuantitativamente la secreción salival. El objetivo de este estudio fue determinar si existe una relación entre la aplicación controlada de cargas articulares y cambios en el flujo y pH salival. 30 voluntarios fueron seleccionados según criterios de inclusión establecidos. Se elaboró un dispositivo interoclusal que en relación a piezas 1.5 y 2.5, tenía botones acrílicos de 1 mm de espesor, los que al ejercer fuerzas sobre ellos provocan cargas reversibles sobre la ATM. Antes de usar el dispositivo, en cada individuo se midió flujo salival no estimulado (FSNE) el flujo salival estimulado (FSE) y el pH de ambos. Tras un periodo de adaptación diaria por una semana, cada participante usó el dispositivo durante 1 hora, ejerciendo fuerza masticatoria sostenida. Luego se midieron ambos flujos y el pH correspondiente. El procedimiento fue repetido por 7 días, bajo supervisión. No se observó una relación aparente entre la aplicación controlada de cargas articulares y cambios volumétricos de flujo salival. Las mujeres tuvieron un FSE y FSNE menor al de los hombres. La aplicación de sobrecargas articulares por un breve período de tiempo provoca una caída del pH del FSE luego de 3 días de aplicación.

Altered salivary flow is key for the onset of dental caries, periodontal disease and opportunistic infections. Salivary flow is determined by various stimuli on several receptors, including joint mechanoreceptors. Some studies show that loads on the TMJ affect these receptors causing changes on the quality and quantity of saliva secretion. The aim of this study was to determine whether a relation exists between controlled load application and changes on salivary flow and pH. Thirty volunteer subjects were recruited after excluding by inclusion criteria. A total coverage intraoral appliance was made with 1 mm acrylic buttons on tooth 1.5 and 2.5. The buttons were intentioned to direct the force vectors to apply a reversible load on the TMJ. Before using it, the Unstimulated salivary flow (USF), the Stimulated salivary flow (SSF) and the pH from each flow was obtained from each subject. After an adaptation period of a day, each volunteer used the appliance exerting steady moderate loads 1 hour/day for one week. Under the supervision of the examiner, the USF, SSF and both pH were daily registered for the entire week. There was not an apparent association between applying controlled loads on the TMJ and volumetric changes of the salivary flow. Women, however, showed lower USF and SSF than men. Load application through an oral appliance is associated with SSF pH drop from the third day.

Sensibilidad diagnóstica de los distintos tiempos de la prueba de estímulo con clonidina, indicada para descartar deficiencia de hormona de crecimiento en niños con talla baja / Timing of growth hormone peaks during the clonidine provocation test

Background: Clonidine provocative test is used for the diagnosis of growth hormone (GH) deficiency. The duration of the test is not uniform across places where it is performed. Aim: To evaluate the frequency and timing of GH peaks during the clonidine test. To determine the timing with the highest diagnostic yield for GH deficiency. Patients and Methods: Analysis of the GH response during a clonidine test performed to 93 children with low stature, aged 11 +/- 3 years (41 percent women), with mean z scores of -2.3 +/- 0.8 for height and of 0.4 +/- 0.9 for body mass index, that were consecutively studied. A oral dose of 0.15 mg/m2 of clonidine was administered and GH levels were determined by the chemiluminescent enzyme immunoassay method of solid phase at 0, +30, +60, +90 and +120 minutes after. The cut-off point for GH deficiency was set at 7 ng/dL. Results: In ten children GH levels were lower than 7 ng/dL during the test and were considered as having GH deficiency. In 86 percent of the 83 patients without GH deficiency, the peak over 7 ng/mL appeared at +60 minutes and in 89 percent the peak had appeared at +90 minutes. In only 11 percent of these children, the peak appeared at +120 minutes. Conclusions: The timing with the highest diagnostic yield for GH is +60 minutes after the administration of clonidine. However the sample at +120 minutes should not be eliminated, considering that the highest GH peak appears at that time in 11 percent of children.

Improved sexual behavior in male rats treated with a Chinese herbal extract: hormonal and neuronal implications / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior of adult male rats.</p><p><b>METHODS</b>The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely (one time, 45 min before mating test) or subchronically (daily for 10 days) in sexually potent and sexually sluggish/impotent rats. Sexual behavior, serum levels of luteinizing hormone (LH) and testosterone (T) were evaluated in treated rats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmission was assessed in the nucleus accumbens using a microdialysis technique.</p><p><b>RESULTS</b>In sexually potent rats, both acute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromission latency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculation latency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission and ejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kg significantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens, 30 min after the acute administration.</p><p><b>CONCLUSION</b>The improvement in both appetitive and consummatory components of sexual behavior observed in male rats treated with the extract could be ascribed to increased serum T level in parallel with the activation of the central dopaminergic system.</p>

O ensaio de tiroglobulina com melhor sensibilidade funcional enquanto os pacientes tomam L-T4 substituirá a tiroglobulina estimulada pelo TSH no seguimento dos pacientes com câncer diferenciado da tiróide? / Will the thyroglobulin assay with lower functional sensitivity whilst the patients are on L-T4 treatment replace the TSH-stimulated thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer?

O autor apresenta evidências recentes da literatura que mostram que ensaios de tiroglobulina sérica (sTg) com maior sensibilidade funcional apresentam a mesma qualidade que a obtenção da sTg estimulada por rhTSH ou hipotiroidismo, no seguimento de pacientes com câncer diferenciado de tiróide (CDT). Desta forma, propõe modificar a prática recomendada pelas diretrizes de sociedades internacionais para o seguimento desses pacientes (desenvolvidas enquanto os ensaios disponíveis apresentavam sensibilidade de 1 ng/mL), substituindo-se a obtenção da sTg estimulada por rhTSH ou hipotiroidismo pelo acompanhamento dos pacientes na vigência da terapia com L-T4 com a medida da sTg desde que se empreguem técnicas com sensibilidade funcional da ordem de 0,1-0,2 ng/mL.

The author reviews the literature on the new assays for serum thyroglobulin (sTg) presenting lower functional sensitivity and demonstrates that its use, whilst the patients are taking L-T4, presents better results than sTg following TSH stimulation in the follow-up of patients with differentiated thyroid carcinoma. Therefore, he suggests a revision on the guidelines for the follow-up of these patients (developed when the available assays present a sensitivity of 1 ng/mL), proposing the use of sTg assays with functional sensitivity of 0.1-0.2 ng/mL with the patients on L-T4 treatment instead of sTg stimulated by TSH.

Estimulación iterativa (EI) de TSH endógena (TSH-En) mediante el uso de la hormona liberadora de tirotrofina (TRH) en pacientes portadores de carcinoma diferenciado de tiroides / Rapid iterative stimulation (IS) of endogenous tsh (En-TSH) utilizing thyrotropin releasing hormone (TRH) in patients with differentiated thyroid carcinoma (DTC)

En el CDT es indispensable elevar los valores de TSH para efectuar Tg y barrido (RCT) con 131I, debiéndose suspender la opoterapia (HT) durante 4/5 sem. con el consecuente hipotiroidismo (H) y los trastornos que conlleva. Nuestro objetivo fue incrementar en forma rápida TSH-E acortando el tiempo de abstinencia. Se efectuaron 43 estudios en 37 pacientes con CDT (G-1); de entre 19 y 78 años, 34 con forma papilar y 3 folicular de CDT, 12 de sexo masculino y 25 femenino Se consideraron 2 subgrupos, G-1A, 7 p. para ablación (A); G-1B, 36 p. para seguimiento (S) y/o tratamiento (T) entre 6 meses y 5 años poscirugía; 6 p. efectuaron dos estudios, 4 para A y S y 2 para 2 veces S. Como comparación se revisaron 41 estudios en 35 p (G-2) que efectuaron suspensión de opoterapia por 4/5 semanas, entre 18 y 81 años; 28 de sexo femenino y 7 masculino; 32 papilares y 3 foliculares; 18 para A (G-2 A) y 21 para S, primer control (G-2B); 4 p. efectuaron 2 estudios, A y S. G-1A: entre 8/10 días poscirugía se les administra TRH 200 mcg i.v los días 1, 3, 5 y 6. A los 30 min de la 3ra aplicación, determinación de TSH y RCT con 370 MBq de 99mT; a igual lapso en la 4ta aplicación determinación de TSH, Tg y antiTg y 5,55 o 7,4 GBq de 131I, para A; a los 8 días RCT con 131I. G-1B: se suspende T4 y reemplaza por T3 por 3 semanas. Se suspende T3; a las 24 horas se inicia el esquema indicado para G-1A . A la 4ta aplicación de TRH, se administra el 131I, 14,8 MBq y RCT a las 48 horas en S o la actividad terapéutica indicada para T. En ambos grupos se indicó dieta hipoyódica. Resultados: En G-1, los valores de TSH ascendieron a 26-360 UI/L; promedio 83 UI/L ± 54; G-1A : 137 ±109; G-1B 7, 62 ± 52 . Los RCT no mostraron diferencias con ambos trazadores. En G-1A todos los p presentaron remanentes tiroideos y Tg positivas. En G-1B, 21 p. mostraron RCT y Tg negativas; 7 áreas activas y Tg positivas y 8 p RCT negativos con valores elevados de Tg . En G-2, TSH, 23-170 UI/L ( 63 ± 3 UI/L) ; G-2 A: 71 ± 41 ; G-2B, 63 ± 42. Conclusiones: Estos hallazgos indican que a) la metodología propuesta es adecuada para acortar sensible-mente el tiempo de abstinencia de opoterapia y reducir la sintomatología del H que pasa desapercibida en la mayoría de los casos; b) los valores de TSH-En obtenidos son similares y aun superiores a los alcanzados por suspensión de opoterapia por lapsos prolongados; c) el empleo del RCT con 99mTc como indicador de tejido captante disminuye el uso terapéutico a ciegas de 131I al señalar casos de ausencia de concentración y permite, cuando sea necesario, obtener anticipadamente 131I para su empleo terapéutico.

In the follow up (F) of p with DTC it is necessary to obtain high figures of serum TSH for determination of serum Tg and 131I scan (WBS). For this object, he method, for a long time, was to withdrawal thyroid hormone therapy (generally l-T4) that produce hypothyroidism with the inconvenient for the p, dramatics in certain cases. Our objective was to increase TSH by IS to shortening time of L-T4 withdrawal for F, ablation (A) or treatment (T) with 131I. In 37 p. with DTC (G-1), aged 19-78 y., 34 with pap. DTC and 3 with foll. form, 25 females, 12 males, 43 studies were carried out; 6 p carried 2 studies. The group was divided in 2 sub-groups: G-1A,7 p derived for A; G-1 B 36 p. for F or T with 131I. Six p carried out 2 studies; 4 of them for A and for F and 2 realizes 2 times F. All p treated with l-T4 replaced this hormone for T3 during 3 weeks ,that was withdrawal the day before IS. In G-1A, between 8/10 days after surgery they begin IS. IS: At days 1, 3, 5 and 6, the p were injected i.v. with 200 mcg of TRH; at 30 minutes of the 3rd injec. blood TSH determination ; immediately 370 MBq of 99mT was administered and at 30 minutes a WBS was carried out. At 30 minutes of the 4th injec. blood figures of TSH, Tg and Tg-ab were determined; immediately the activity of 131I indicated for each group was given to the p; in G-1A, at 8 days and in G1-B, at 48 hours WBS were carried out. As a control group (G-2) 41 studies in 35 DTC p. that withdrawal l-T4 for 4/5 weeks, were studied, aged 18-81 years, 31 females and 4 males; 32 with pap. and 3 folli.c form; 18 for A (G-2A) and 23 for F (G-2B); 6 p carried out 2 studies. One for A and the second as the first control. In G-1, TSH values obtained were 26-360 UI/L ( 83 ± 54. In G-1A : 137 ± 109 and in G-1B 62 ± 52). The 2 tracers 131I and 99mTc-Tc, produce show similar figures. In G-1A all p present thyroid remnants and elevated Tg. In G-1B, 7 p showed positive WBS and Tg; 8 p present Tg positive and WBS negative and 21 WBS and Tg negative. In G-2, the TSH values obtained were 23-179 UI/L (63 ± 39 ); G-2A 71 ± 41 and G-2B 63 ± 42. These findings indicate that the methods is adequate to shortened the time of withdrawal of l-T4 and reduce the signs/symptoms of hypothyroidism to an acceptable status. Also allow us to considered the use of 99mTc as an indicator of existence of remnants, relapses or metastases and avoid blind use of therapeutic activities of 131I.

Necesidad de estimulación ventricular rápida en la inducción de taquicardia por reentrada del nodo aurículo-ventricular: Caso clínico / Requirement of fast ventricular stimulation to induce atrio ventricular nodal tachycardia: Report of one case

We report a 59 year-old woman who had recurrent episodes of paroxystic supraventricular tachycardia despite pharmacologic therapy. A previous electrophysiological study (EPS) was done two years earlier without induction of any sustained arrhythmia. A new EPS was performed, during which atrial and ventricular programmed stimulation failed to induce tachycardia, and only by fast ventricular stimulation during intravenous isoproterenol infusion, a typical atrio ventricular nodal reentrant tachycardia (AVNRT) was induced. We successfully ablated the slow nodal pathway. After ablation the tachycardia was not inducible. We comment the occasional difficulties to induce AVNRT and the importance of a complete induction protocol to avoid false negative studies during the EPS.

Chemical modulation on heterogeneous growth in Prochilodus lineatus (Valenciennes, 1847) (Pisces; Characiformes)

In the present study, the effect of chemical factors released by conspecifics on growth variability (heterogeneous growth - HetG) in a gregarious fish species (Prochilodus lineatus) was tested. HetG was assessed by the weight variation coefficient in two consecutive 21-day periods. The fish were grouped in tanks (4 fish in each) that received running water with constant draining. The tanks contained either conspecifics (C) or non-conspecifics (N). Four conditions were established in accordance with the tank water supply: a) water with previous contact with conspecifics throughout the experiment (CC); b) water without previous contact with conspecifics throughout the experiment (NN); c) water with previous contact with conspecifics in just the first period, 0 to 21 days (CN); and d) just in the period from 21 to 42 days (NC). At the end of the experiments, the occurrence of chemical modulation on the growth variability in P. lineatus was verified: the fish that received water with previous contact with a conspecific (C) presented exacerbation of HetG. This corroborates the notion that the predominant mechanism in the determination of intraspecific growth variation in the gregarious species is associated to chemical factors released by conspecifics.

No presente trabalho, testou-se o efeito de fatores químicos liberados por coespecíficos sobre o crescimento e sua variabilidade no grupo (crescimento heterogêneo, CHet), numa espécie gregária, o curimbatá, Prochilodus lineatus. O CHet foi avaliado pelo coeficiente de variação do peso dos animais, em dois períodos consecutivos de 21 dias. Os peixes foram agrupados em aquários (4 peixes cada) que receberam água corrente, com vazão constante, de tanques contendo (C) ou não (N) coespecíficos. Quatro condições foram delineadas de acordo com a água que abastecia os aquários: a) água com contato prévio com coespecíficos durante todo o experimento (CC); b) água sem contato prévio com coespecíficos durante todo o experimento (NN); c) água com contato prévio com coespecíficos apenas no primeiro período, 0 a 21 dias (CN); e d) apenas no período de 21 a 42 dias (NC). Ao término dos experimentos, verificou-se que ocorre modulação química sobre a variabilidade de crescimento em P. lineatus: os peixes que receberam água com contato prévio com coespecífico (C) apresentaram exacerbação do CHet. Fato que corrobora a idéia de que o mecanismo predominante da determinação da variação intra-específica do crescimento, em espécies gregárias, está associado à ação de fatores químicos liberados por coespecíficos.

The VR1-Positive Primary Afferent-Mediated Expression of pERK in the Lumbosacral Neurons in Response to Mechanical and Chemical Stimulation of the Urinary Bladder in Rats

OBJECTIVE: This study characterized the neurons in the lumbosacral cord that express phospho ERK (pERK) after distension or irritation of the bladder, and their relation to the vanilloid receptor 1 (VR1) positive primary afferents. METHODS: Mechanical distension and chemical irritation of the bladder were induced by intravesical injection of the saline and mustard oil, respectively. Spinal neurons expressing pERK and the primary afferent fibers were characterized using multiple immunofluorescence for neurokinin 1 (NK1), neuronal nitric oxide synthetase (nNOS) and VR1. RESULTS: Neurons in lamina I, medial dorsal horn (MDH), dorsal gray commissure (DGC) and sacral parasympathetic nucleus (SPN) were immunoreactive for pERK after either mechanical or chemical stimulation. The majority of pERK positive cells were positive for NK1 in lamina I and SPN, but not in the DGC. Most of pERK positive cells are not stained for nNOS except in a small population of the cells in the SPN and DGC. Contacts between perikarya and dendrites of pERK-positive cells and terminals of primary afferents expressing VR1 were identified in lamina I, lateral collateral path (LCP) and SPN. CONCLUSION: In this study, the lumbosacral neurons activated by mechanical and chemical stimulation of the urinary bladder were identified with expression of the pERK, and also provided the evidence that VR1-positive primary afferents may mediate the activation of these neurons.

Analisis ecocardiografico del efecto de diferentes inhibidores del intercambiador Na+/H+ sobre la estructura y funcion sistolica del ventriculo izquierdo en ratas espontaneamente hipertensas / Echocardiographic analysis of the effect of different Na+/H+ exchanger inhibitors on left

El presente estudio fue proyectado para analizar mediante ecocardiograma los efectos del HOE 642 (cariporide) (HOE) y del BIIB 723 (BIIB) sobre la estructura y función sistólica del ventrículo izquierdo en ratas espontáneamente hipertensas (SHR)- 8 con 30 mg/kg/día de HOE, 8 con 30 mg/kg/día de BIIB durante 30 días y 4 sin tratamiento (grupo control) durante esos 30 días. Los distintos parámetros analizados no mostraron cambios durante ese período en las ratas controles. Si bien el HOE determinó un leve descenso de la presión arterial (C: 184 ± 1.75 mm Hg; 30d:176.20 ± 2.60 mm Hg, p <0.01), no detectada con BIIB,ambas drogas provocaron un aumento del estrés sistólico pico (HOE C:166 ± 29 kdinas/cm2; 30d: 204 ± 34kdinas/cm2, p <0.04. BIIB C: 164 ± 25.90 kdinas/cm2; 30d: 234 ± 29.30 kdinas/cm2, p<0.02).Tanto HOE comoBIIB redujeron significativamente la masa ventricular izquierda (MVI) (HOE C: 612.50±50 mg; 30d:452 ± 37 mg,p <0.01; BIIB C: 544 ± 16mg; 30 d: 374 ± 25 mg, p<0.01). El porcentaje de acortamiento endocárdico no semodificó luego del tratamiento con HOE (C: 62.30 ± 2.75; 30d 65.50 ± 2.40%, ns) y BIIB (C: 63.20 ± 2.39%;30d 67.20 ± 1.62%, ns). Los resultados analizados permiten concluir que ambos inhibidores determinaron similarreducción de la MVI. Esa reducción se acompañó de mejoría en los índices de evaluación de la función sistólica ventricular izquierda, pese al incremento del estrés sistólico pico. Estas evidencias sugieren que independientemente del inhibidor utilizado se encuentra un aumento del inotropismo, previamente comprometidodurante el desarrollo de la hipertrofia

The aim of this study was to analyze by echocardiogram, the action of two Na+/H+ exchange, inhibitors, HOE 642 (HOE) and BIIB 723 (BIIB) on left ventricular (LV) mass and LV systolic function. We studied 16 spontaneously hypertensive rats (SHR), 8 treated with HOE 30 mg/kg/day, 8 with 30 mg/kg/day of BIIB during 30 days and 4 SHR as controls during those 30 days. Results are expressed as mean values ± SEM. The systolic blood pressure and theechocardiograpic parameters examined did not evidence changes during that period in the controls rats. Eventhough HOE determined a slight decrease in blood pressure (HOE C: 184 ± 1.75 mm Hg; HOE 30d: 176.20 ±2.60 mm Hg - p <0.01) which was not detected with BIIB, both drugs provoked an increase of peak systolic stress (HOE C: 166 ± 29 kdynes/cm2; HOE 30d: 204 ± 34 kdynes/cm2, p <0.04; BIIB C: 164 ± 25.90 kdynes/cm2; BIIB 30d: 234 ± 29.30 kdynes/cm2, p <0.02). HOE and BIIB reduced LV mass after 30 days of administration (HOE C: 612.50 ± 50 mg; 30d: 452 ± 37 mg, p <0.01. BIIB C: 544 ± 16mg; 30d: 374 ± 25 mg, p <0.01). LV endocardial shortening was similar independently of the NHE inhibitors used (HOE C: 62.30 ± 2.75%; 30d: 65.50 ± 2.40%, ns. BIIB C: 63.20 ± 2,39%; 30d 67,20 ± 1.62%, ns). These data demonstrate that long-treatment with HOE or BIIB produced similar LV mass regression without changes in endocardial fractional shortening in spite of the increase of peak systolic stress. This finding could represent an increased inotropism previously depressed by the development of hypertrophy

Sitios de acción inhibitoria de la prolactina sobre la síntesis de estradiol inducida por la hormona folículo estimulante en las células de la granulosa / Sites of prolactin inhibition on gonadotropin-induced estrogen production in cultured rat granulosa cells

En este estudio se investigaron los sitios probables de la acción inhibitoria de prolactina (Prl) sobre la esteroidogénesis ovárica inducida por la hormona folículo estimulante (FSH). Para esta finalidad se estudió la capacidad de cultivos primarios de células de la granulosa de la rata de sintetizar estradiol y AMPc bajo la estimulación con FSH o de activadores de la vía dependiente de AMPc en presencia de Prl humana. La participación de otros sistemas de transducción de señal como los dependientes de PKC y proteínas Gi en los mecanismos de acción inhibitoria de la Prl fue también investigada utilizando inhibidores de estos sistemas como la calfostina C y la toxina pertusis. Los resultados demostraron la habilidad de la Prl de alterar la esteroidogénesis previa y posterior a la generación de AMPc, muy probablemente por mecanismos que involucran la activación de la subunidad catalítica de la adenilato ciclasa, así como a través de interactuar con sistemas de transducción de señal dependientes de PKC y proteínas sensibles a la toxina pertusis. Nuestros resultados sugieren un mecanismo de interacción entre receptores acoplados a proteínas G con aquéllos acoplados a cinasas de tirosinas mediado muy probablemente por vías de señalización dependientes de proteínas Gi.

We studied the sites of prolactin inhibition upon FSH induced ovarian steroidogenesis and the ability of prolactin (Prl) to inhibit the synthesis of estradiol and cAMP accumulation under the stimulation of FSH or cAMP dependent activators. The participation of other signal pathways such as PKC and Gi proteins on the inhibitory actions of Prl was also investigated using calfostine C andpertusis toxin as inhibitors. Results showed a dose dependent prolactin decrease in FSH-induced estradiol and cAMP production prior and after the generation of the cyclic nucleotide by a mechanism involving the catalytic subunit of adenyl cyclase and/or through activation of PKC or by the interaction with pertusin toxin sensitive G proteins. Our results suggest a mechanism by which G protein coupled receptors are linked with those coupled with tyrosine kinase through the involvement of a Gi protein mediated mechanism.

Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratos / Effects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts

OBJETIVO: Avaliar o efeito, na contratilidade miocárdica e no fluxo coronariano, de drogas comumente utilizadas na prática clínica (diazepam, midazolam, propofol e etomidato). MÉTODO: Foram estudados 50 corações isolados de ratos Wistar divididos em cinco grupos de dez, em preparação de Langendorff com líquido de perfusão de Krebs-Henseleit (K-H), mantendo-se constantes a pressão de perfusão (90 centímetros de água) e a temperatura (37° + 0,5 graus Celsius). Com exceção do Grupo I (Controle), foram feitas infusões únicas, em um minuto, de diazepam (50 microgramas) - Grupo II; midazolam (25 microgramas) - Grupo III; propofol (25 e 50 microgramas) - Grupo IV e etomidato (25 microgramas) - Grupo V. Cada dose foi diluída e administrada em 0,1 mililitro de K-H, mantendo-se o fluxo e a pressão de perfusão coronarianos do sistema, durante sua infusão. Aferiu-se a freqüência cardíaca em batimentos por minuto (BPM), a tensão miocárdica em gramas (g), e o fluxo coronariano em mililitros por minuto (ml/min) em 1, 3, 5, 10, 15, 20, 25 e 30 minutos; a contratilidade miocárdica foi avaliada pelo cálculo da primeira derivada tensão/tempo (dT/dtmax), naquelas marcas. RESULTADOS: A freqüência cardíaca apresentou variações nos Grupos I, III e IV. Em relação à tensão miocárdica, apenas o Grupo I não sofreu declínio; o fluxo coronariano, exceto no Grupo IV, apresentou variações para menos, ao longo do estudo; a contratilidade miocárdica decresceu em todos os grupos estudados, exceto no Grupo I. CONCLUSÃO: As drogas ensaiadas diminuíram a contratilidade miocárdica (p<0,05); as alterações do fluxo coronariano não se relacionaram com as variações da contratilidade miocárdica (p>0,05).

Estudio de la relación entre las características electromoleculares de los digitálicos y su acción farmacológica / Relationship between the electromolecular properties of digitalis compounds and their pharmacological properties

Pese a su reducido margen de seguridad, los digitálicos siguen utilizándose en el tratamiento de la insuficiencia cardiaca congestiva y la fibrilación auricular crónica. Con el descubrimiento de su estructura, se han realizado remodelaciones para disminuir su toxicidad. Investigaciones recientes reportan que la eficacia digitálica radica en la electronegatividad del anillo "D" esteroideo, generada por la lactona e hidroxilo que poseen estos compuestos. En el presente trabajo, damos cuenta de la importancia que tiene esta propiedad molecular, que aunada a la conformación estructural, dan lugar a cambios significativos en las propiedades farmacológicas como el inotropismo y el margen de seguridad. Así, evaluamos una serie de once compuestos derivados de digitoxigenina, con grupos que sustituyen sobre el anillo "D" al hidroxilo y/o la lactona, los cuales denominamos -OH, -Lac, D-01, D-02, D-03, D-07, D-14, D-15, D-20, D-21 y D-22. La electronegatividad y la energía conformacional de cada compuesto se determinaron por el método Duhamm. El estudio farmacológico se realizó en corazones aislados de cobayo con base en el modelo de Langendorff y, en corazón de perro conforme al modelo cardiopulmonar de Starling. Los resultados permiten observar que la modulación de la acción digitálica está centrada, estructuralmente, en los sustituyentes de la fracción "D". El efecto inotrópico positivo y el margen de seguridad, medido como el cociente de la dosis tóxica sobre la dosis inotrópica, están relacionados con el aumento de electronegatividad y con una disminución de las energías rotacional y translacional que definen la conformación molecular; en consecuencia, estas propiedades son imprescindibles en la eficacia digitálica.

In spite their reduced therapeutic index, digitalis-type drugs continue being used for treating diseases such as congestive heart failure and chronic atrial fibrillation. Thanks to the development of several methods, their structural determination has been feasible, so, structural modifications have been worked out to modulate their toxicity. Several reports realizes that efficacy for these digitalis-type drugs lies on the electronegativity centered on the steroidal moiety (D-ring) generated by either lactone and hydroxyl sub-stituents attached to the steroidal moiety. In this work, we report how electronegativity, and so structural conformation, does modify their pharmacological properties, e.g., inotropism and safety margin. Thus, we evaluated a series of eleven drugs derived from digitoxigenin, named -OH, -Lac, D-01, D-02, D-03, D-07, D-14, D-15, D-20, D-21 and D-22, with groups that substitute both lactone and hydroxyl groups on the steroidal D-ring. Electronegativity and conformational energy were determined by Duhamm's method. The pharmacological evaluation for these drugs was accomplished in guinea pigs isolated hearts (according to the model proposed by Langendorff) and dog's isolated heart (as established by Starling's in vivo model). The results may suggest that digitalis-like action lies on the substituents attached to the D-ring. Positive inotropic effect and therapeutic index are related with increases in electronegativity as well with decreases in rotational and traslational energies; therefore, these molecular properties have such importance for the digitalis efficacy. (Arch Cardiol Mex 2003; 73:11-17).

Análise da coagulação sangüínea em pacientes submetidas à hiperestimulação ovariana para fertilização in vitro / Analysis of coagulation parameters in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization

OBJETIVO: Identificar alteraçöes na coagulaçäo sangüínea em mulheres submetidas à fertilizaçäo in vitro (FIV). MÉTODOS: Trata-se de um estudo prospectivo onde foram incluídas 15 pacientes submetidas à FIV. No período pré-ovulatório imediato, do ciclo menstrual precedente à FIV, foi coletada amostra sangüínea para coagulograma, com dosagem de Estradiol, Hemograma, Fibrinogênio, Tempo de Protrombina, Tempo de Tromboplastina Parcial Ativada, Tempo de Coagulaçäo e Plaquetas. Durante a hiperestimulaçäo ovariana para FIV, nova amostra para coagulograma foi coletada no dia da aplicaçäo da Gonadotrofina Coriônica Humana. Os dados referentes à análise das duas amostras foram avaliados usando teste estatístico Paired T-Test. RESULTADOS: O estudo comparativo das médias das amostras identificou aumento significativo nos níveis de fibrinogênio, 304,9 pg/ml na primeira amostra e 383,1 pg/ml na segunda (p=0,01), já os níveis de hematócrito tiveram um decréscimo significativo, com valores de 40,5 por cento e 38,4 por cento, respectivamente (p=0,0001). As demais provas de coagulaçäo näo apresentaram diferença significativa. As médias do estradiol foram significativamente diferentes, sendo 167pg/ml na primeira amostra e 1435pg/ml na segunda (p=0,0001). CONCLUSÖES: Os Dados refletem uma tendência a um estado de hipercoagüabilidade sangüínea, o que é esperado nas situaçöes de hiperestrogenismo. Apesar da significância estatística nos níveis de fibrinogênio e hematócrito, esses resultados têm pouca expressäo clínica, visto que os valores máximos das duas amostras permaneceram dentro dos limites da normalidade. A pesquisa sugere que, apesar do grande aumento nos níveis de estradiol e mudanças nas provas de coagulaçäo, os programas de FIV mostram-se seguros quanto aos riscos tromboembólicos