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A multifractal characterization to human dentin porosity is made. Micrographs of human dentin samples gotten from scanning electron microscopy (SEM) were studied in order to characterize porosity. We got the generalized dimensions (multifractal moments) D q for pore space and matrix skeleton on gray scale and binary images for samples of both gender. For the case, we found that superficial porosity η s is linked to mass fractal dimension D 0 in an approximately linear relationship as D 0 ≈ η s + d ¯ for binary images. In addition, probability density distribution (PDD) for pore diameters is found a normal PDD type. Other quantities of interest like mean, standard deviation, maximum and minimum pore diameters, voit ratios, and percentage of chemical composition are reported. RESEARCH HIGHLIGHTS: SEM sample, images and procedure for multifractal analysis are detailed. Micro patterns in grayscale are multifractal and in binary scale are monofractals. Superficial porosity is relate to mass fractal dimension approximately linearly. From the porosity values, voit ratios are determined. Pores diameters obey a normal PDD.
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Dentina , Fractais , Humanos , Porosidade , Microscopia Eletrônica de VarreduraRESUMO
BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).
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Cesárea , Países em Desenvolvimento , Criança , Feminino , Humanos , Pobreza , Gravidez , Gestantes , Cuidado Pré-NatalRESUMO
A fundamental understanding of the Ostwald ripening effect (ORE) during the mechanochemical synthesis of PbTe nanostructures is presented. The ripening process involves the coarsening of larger particles from those of smaller size; this phenomenon was systematically evaluated at different stages of milling by microscopy analyses (AFM, TEM, STEM and HRTEM). At the early stage of milling, smaller particles and quantum dots are eventually dissolved to lower the total energy assciated with their surfaces. The ripening process - during milling - involves short-range mass transfer among particles. HRTEM analyses allowed us to identify that coarsening occurs by thermo-mechanically activated cooperative mechanisms. The detachment of the atoms from smaller particles to form bigger ones plays a major role in the particle coarsening. It was found that the coarsening process was not limited to crystalline nanostructures; so grain boundaries, edge dislocations and boundaries among crystalline and amorphous phases also play an important role to determine how species migration contributes to generate coarse particles. Those serve as sites for inducing coarsening in an equivalent way as surfaces do. Secondary ion mass spectrometry and elemental chemical mapping (EDX-STEM) revealed that both the purity and the chemical homogeneity of the PbTe nanostructures are prominent features of this material. Additionally, a direct band gap enhancement (780 nm) compared to bulk PbTe (3859 nm) was detected. It occurred due to the quantum confinement effect, lattice imperfections and even surface properties of the nanostructures. It is important to point out that the whole optical behaviour of the PbTe nanostructures was dependent upon the embedded nanoparticles and quantum dots in the clusters and coarse particles ranging from 15 nm to 35 nm.
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Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23-38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival ( p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.
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Sobrevivência de Enxerto , Imunossupressores/uso terapêutico , Transplante de Rim , Nefrite Lúpica/mortalidade , Nefrite Lúpica/terapia , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , México , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo , Adulto JovemRESUMO
A new α-Al2O3 doped with Tm3+ ions was obtained by combustion method; doped α-Al2O3 in the powder form was mixed with polytetrafluoroethylene resin (PTFE) to obtain dosimeters in pellet form, in order to be used as radiation dosimeter. The glow curve, linearity, lower detection limit, repeatability and fading, were studied. The kinetic parameters were determined by deconvolution method. Morphological characteristics were studied by low vacuum scanning electron microscopy and X-ray diffraction. Results showed that α-Al2O3+PTFE obtained is a promising material to radiation dosimetry.
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Objetivo: Determinar la influencia de la vía de administración sobre efecto de distintas dosis del extracto etanólico de la semilla de Jatropha curcas L en la motilidad intestinal de ratones. Materiales y Métodos: Se utilizaron ratones albinos machos con un peso promedio de 23 g, a los que, por vía oral e intraperitoneal, y a dosis escalonadas y no tóxicas, se les administraron extracto etanólico de la semilla de Jatropha curcas L. Los grupos experimentales fueron: suero fisiológico 0,1 mL/10 g, atropina 1 mg/Kg, extracto etanólico de semilla de Jatropha curcas L. 500, 750 y 1000 mg/Kg, respectivamente, y neostigmina 0,4 mg/Kg. Para la validación estadística se usó ANOVA con post-hoc de Sidak. Resultados: Se encontró diferencias significativas al analizar los porcentajes de motilidad intestinal de todos los grupos, sin embargo, al realizar la comparación por parejas solo se halló diferencias entre los grupos que recibieron atropina y neoestigmina (p=0,038), J. curcas L. vía oral a dosis de 500 mg/Kg y 1000 mg/Kg (p=0,001 en ambos casos). Se encontraron diferencias significativas (p>0,05) en las comparaciones entre la administración por vía oral y por vía peritoneal del extracto de J. curcas L. a dosis de 500 mg/Kg y 1000 mg/Kg. Conclusión: Se encontró influencia de la vía de administración, sobre el efecto del extracto etanólico de Jatropha curcas L. en la la motilidad intestinal en ratones albinos.
Objectives. To determine the influence of administration route of Jatropha curcas L. seeds ethanolic extract (in different doses) on intestinal motility of albino mice. Methods. Male albino mice were used with an average weight of 23 g., which the ethanolic extract of Jatropha curcas L. seeds were administered in different administration routes (oral and intraperitoneal), using staggered and non-toxic doses. The experimental groups were 0,1 mL/10 g physiological saline, atropine 1mg/Kg, neostigmine 0.4 mg/kg and Jatropha curcas L seed ethanolic extract in doses of 500, 750 and 1000mg/kg. One-way ANOVA test with Sidak post-hoc test were used to do a statistical inferences. Results. Significant differences were found when all-groups intestinal charcoal transit distance (%) were analyzed. However, when paired comparisons were made, significant differences were found between neostigmine group (p=0,038); and oral administration of J curcas L extracts in doses of 500 mg/Kg and 1000 mg/Kg (p=0.001 in both cases). Significant differences were found (p>0.05) in comparisons made between orally and intraperitoneal administration of J. curcas L. extract in doses of 500 mg/Kg and 1000 mg/Kg. Conclusion. There is some influence caused by route of administration of Jathropa curcas L. seeds ethanolic extract on intestinal motility in albino mice.
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Animais , Masculino , Camundongos , Extratos Vegetais , Jatropha , Motilidade Gastrointestinal , Plantas Medicinais , Atropina , Experimentação Animal , Medicina TradicionalRESUMO
Due to their physicochemical properties, metallic nanoalloys have potential applications in biomedicine, electrocatalysis and electrochemical sensors, among many other fields. New alternative procedures have emerged in order to reduce production costs and the use of toxic substances. In this study we present a novel low-toxicity synthesis method for the fabrication of nanowire networks (NWNs) and Ag-Au hollow nanospheres. The synthesis process is performed at room temperature without any sophisticated equipment, such as special cameras or furnaces, etc. Transmission electron microscopy showed that the NWNs contain random alloys with a diameter of between 10-13 nm. The radius for the hollow nanospheres is approximately located between 70-130 nm. The absorption bands in the UV-vis spectrum associated with the surface plasmon in Ag-Au bimetallic nanoparticles are highlighted at 385 nm for the NWNs and 643 nm for the hollow nanospheres. The study was performed with low-toxicity substances, such as rongalite, ascorbic acid and sucrose, and showed high efficiency for the fabrication of these types of nanostructures, as well as good stability for long periods of time.
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Resumen OBJETIVO: describir un caso clínico de tumor de células de la granulosa de tipo adulto, en forma bilateral, con diagnóstico inicial erróneo de carcinoma de vejiga urinaria. CASO CLÍNICO: paciente de 43 años de edad, con antecedente de hiperplasia endometrial sin atipia. El padecimiento se inició en marzo de 2015, con dolor en la fosa renal izquierda. En la exploración física se documentó distensión abdominal, dolor ocasional y pérdida de peso (3 kg) en cuatro meses; masa abdominal, sólida, dolorosa, tacto vaginal con abultamiento y desplazamiento de la pared lateral izquierda de la vagina. La tomografía axial computada evidenció tres masas en el hueco pélvico. En la laparotomía se resecaron ambos tumores ováricos. Se inició tratamiento con quimioterapia coadyuvante, con cisplatino-etopósido (CDDP/VP-16). CONCLUSIÓN: la manifestación bilateral del tumor de células de la granulosa del adulto aparece en sólo 3% de los casos. Luego de practicar estudios radiológicos y de inmunohistoquímica se estableció el diagnóstico correcto. La quimioterapia coadyuvante con cisplatino-etopósido, ha demostrado resultados satisfactorios. Actualmente no existen datos de actividad tumoral y la paciente permanece en seguimiento.
Abstract OBJETIVO: Describes a clinical case of adult granulosa cell tumor, bilaterally, with initial misdiagnosis of urinary bladder carcinoma. CLINICAL CASE: 43 year old female with antecedent of endometrial hyperplasia without atypia. Starts condition in March 2015 with pain in renal fossa. At the time of consultation presented abdominal distention, occasional pain, weight loss (3 kg) in 4 months. On physical exploration an abdominal mass was found, it was solid and painful. Vaginal touch with presence of a lump and displacement of the left side wall of the vagina. In the computerized axial tomography 3 masses were seen in pelvic hollow. The patient underwent a laparotomy and both tumors were resected. Adjuvant chemotherapy was initiated. CONCLUSION: The bilateral presentation of this type occurs only in 3% of these tumors. After radiological and immunohistochemistry studies a correct diagnosis was established. Adjuvant chemotherapy based in cisplatin/etoposide has shown satisfactory results. Currently these are no data of tumor activity. Continuous surveillance is been performed.
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In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4(+) T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. Here we provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory (TSCM) CD4(+) T cells). This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the TSCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies.
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Linfócitos T CD4-Positivos/virologia , Reservatórios de Doenças , Infecções por HIV/fisiopatologia , HIV-1/fisiologia , Latência Viral/fisiologia , Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular/fisiologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Subpopulações de Linfócitos T/patologia , Subpopulações de Linfócitos T/virologia , Fatores de Tempo , Carga ViralRESUMO
A cross sectional survey was performed to identify gastrointestinal helminths and protozoans in naturally infected horses from the biosphere reserve known as "La Sierra Madre de Chiapas", Mexico (El Triunfo and La Sepultura). During a three-year survey, fecal samples from 90 horses and parasites from 2 necropsied animals were collected. Five families from the Nematoda class: Ascaridae, Kathlanidae, Oxyuridae, Strongylidae and Trichostrongylidae were found, whereas, only one family from the class Cestoda, was observed: Anoplocephalidae. One family from the class Insecta, was observed: Gasterophiilidae. The number of species of parasites ranged from 13 to 18 with an average of 15 per animal. Adult parasites were recovered from the large intestine luminal contents at necropsy. Species recovered included: Strongylus vulgaris, S. equinus, S. edentatus, Oxyuris equi, Parascaris equorum, Coronocyclus coronatum, C. labiatus, C. labratus, Cyathostomum tetracanthum, Cylicocyclus insigne, C. leptostomus, Cylicodontophorus bicoronatus, Cylicostephanus asymetricus, C. bidentatus, C. minutus, C. longibursatus, Petrovinema poculatum, Poteriostomum imparidentatum, Cylicostephanus goldi, Tridentoinfundibulum gobi, Triodontophorus serratus and T. tenuicollis. One species of Diptera were recovered from stomach and identified: Gasterophilus intestinalis. Furthermore, different species of protozoa were recovered from fresh horse-dung and identified in four classes: Sporozoa, Litostomatea, Ciliasida and Suctoria. Nine families: Cryptosporidiidae, Eimeriidae, Balantidiidae, Buetschliidae, Blepharocorythidae, Cycloposthiidae, Spirodiniididae, Ditoxidae, Acinetidae; and 31 ciliates species were recorded: Allantosoma dicorniger, A. intestinalis, Alloiozona trizona, Blepharosphaera intestinalis, Blepharoprosthium pireum, Blepharoconus benbrooki, Bundleia postciliata, Didesmis ovalis, D. quadrata, Sulcoarcus pellucidulus, Blepharocorys angusta, B. cardionucleata, B. curvigula, B. juvata, B. uncinata, B. valvata, Cycloposthium bipalmatum, C. edentatum, C. scutigerum, Charonina equi, Ditoxum funinucleum, Spirodinium equi, Tetratoxum unifasciculatum, Triadinium caudatum, T. galea, T. minimum and Tripalmaria dogieli. Other ciliate observed and recorded was Ochoterenaia appendiculata. This study describes the biodiversity and distribution of common and new helminths and protozoas found in the gastrointestinal tract from horses in the biosphere reserve "Sierra Madre de Chiapas" in Mexico.
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Apicomplexa/classificação , Helmintíase Animal/parasitologia , Helmintos/classificação , Doenças dos Cavalos/parasitologia , Infecções Protozoárias em Animais/parasitologia , Animais , Biodiversidade , Conservação dos Recursos Naturais , Ecossistema , Helmintíase Animal/epidemiologia , Doenças dos Cavalos/epidemiologia , Cavalos , Masculino , México/epidemiologia , Infecções Protozoárias em Animais/epidemiologia , Estações do AnoRESUMO
AIMS: Belatacept is a new recombinant molecule (CTLA4-Ig) that interferes with the second activation signal of T lymphocytes. CTLA4-Ig induced T cell allograft tolerance in rodents but not in primates. We examined the changes in peripheral lymphocyte subsets, including regulatory T cells, in renal transplant patients treated with Belatacept. METHODS: A cross-sectional immunological study was carried out 6 months after transplantation in 28 patients enrolled in the Belatacept phase II study. Eighteen patients received Belatacept, mycophenolate mofetil and steroids (Belatacept group), while the control group of 10 patients received cyclosporine, mycophenolate mofetil and steroids (CsA group). Lymphocyte subsets were examined by flow cytometry. Foxp3 mRNA expression was measured by quantitative PCR. RESULTS: The number of T lymphocytes and the percentage of CD3+ T cells were similar in both groups. However, the percentage of CD3+ CD4+ T cells was lower in the Belatacept group than in the control CsA group (B=42.5%+/-13.7 vs CsA=52.9%+/-9, p<0.005), and the percentage of CD3+ CD8+ cells was higher in the Belatacept group than in the control (B=32.9%+/-6.7 vs CsA=19.5%+/-8.2, p<0.0002). The percentage of CD19+ cells was similar in both groups. Among CD56+cells, only the percentage of CD16+ cells was significantly higher in the Belatacept group than in the control (B=82%+/-12 vs CsA=59.7%+/-25, p=0.01). Among CD4 and CD8 T cells the percentage of activated lymphocytes expressing CTLA4, HLA-DR or CD40L was similar in both groups. The percentage of CD4+CD25+ T cells was higher in the CsA group. The percentage of regulatory CD4+CD25+ cells with bright CD25 staining was similar in both groups (B=3.6+/-2.3% vs CsA=4.7+/-1.9%, ns) as was the expression of FoxP3. CONCLUSION: Our results indicated that Belatacept did not induce regulatory T cell expansion in vivo. We suggest that Belatacept treatment should be maintained after transplantation to allow graft acceptance.
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Imunoconjugados/administração & dosagem , Imunossupressores/administração & dosagem , Transplante de Rim , Linfócitos T Reguladores/efeitos dos fármacos , Tolerância ao Transplante/efeitos dos fármacos , Abatacepte , Adulto , Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Antígenos CD28/imunologia , Antígenos CD4/análise , Movimento Celular/efeitos dos fármacos , Ciclosporina/administração & dosagem , Feminino , Fatores de Transcrição Forkhead/análise , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Tolerância ao Transplante/imunologiaRESUMO
Objetivo: Identificar mutaciones puntuales relacionadas con resistencia a drogas en VIH-1 de pacientes peruanos.Materiales y métodos: Se seleccionaron 11 muestras de VIH provenientes de sangre total de sujetos con tratamientoantirretroviral (ARV). Posteriormente se realizó la optimización de la amplificación de 337 pb del gen de la transcriptasareversa (tr) y 377 pb de todo el gen de la proteasa (prt). Los productos de PCR fueron secuenciados directamentepara el análisis de mutaciones de resistencia. Las secuencias finales fueron analizadas en programas de análisis demutaciones de la HIV Drug Resistance Database de la Universidad de Stanford. Resultados: La optimización de laconcentración de ADN (2,5 ng / μL) así como la concentración de magnesio (4 mM) fueron factores críticos para la amplificaciónde la tr y la prt respectivamente. De otro lado, el análisis de secuencia reveló la presencia de las mutacionesT215Y y la M184V en tr, implicadas en conferir resistencia a zidovudina (AZT) y estavudina (D4T) así como a lamivudina(3TC) y emtricitabina (FTC) respectivamente. En prt se observaron las mutaciones D30N y N88D implicadas enconferir resistencia a nelfinavir (NFV). Es importante señalar que sólo tres muestras de VIH-1 presentaron mutacionesde resistencia, las demás mostraron mutaciones compensatorias. Conclusiones: Se demuestra la existencia de mutacionesde resistencia a ARV a nivel de tr y prt de VIH-1 en sujetos peruanos que reciben terapia TARGA. Se requierende mayores estudios para establecer un perfil de resistencia a ARV en la población peruana.
Objective: Identify point mutations related to HIV-1 drug resistance in Peruvian patients. Materials and methods: A total of 11 HIV-1 positive samples were selected, all were obtained from the whole blood of subjects undergoing anti-retro viral (ARV) treatment. 337 gene base pairs (bp) from reverse transcriptase (rt) and 377 bp from the whole protease gene (prt) were optimized. PCR products were sequenced directly for the analysis of resistance mutations. Final sequences were analyzed in the University of Stanford HIV Drug Resistance Database programs. Results: Optimization of DNA concentration (2,5 ng / µL), as well as magnesium concentration (4mM) were critical factors for rt and prt amplification, respectively. On the other hand, the sequence analysis showed the presence of T215Y and M184V mutations in rt , implicated in zidovudine (AZT), stavudine (D4T), lamivudina (3TC) and emtricitabine (FTC) resistance, respectively. In prt, mutations D30N and N88D were observed. These mutations have been implicated in nelfinavir (NFV) resistance. It must be highlighted that only three HIV-1 positive samples showed resistance mutations. The remaining samples showed compensatory mutations. Conclusions: This study demonstrated the existence of ARV resistance mutations at the HIV-1 rt and prt levels in Peruvian patients undergoing HAART therapy. Further studies are required to establish an ARV resistance pattern in the Peruvian population.
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HIV , DNA Polimerase Dirigida por RNA , Genótipo , Mutação Puntual , Peptídeo Hidrolases , PeruRESUMO
Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work was to study the action of betahistine in the vestibular endorgans. Experiments were done in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM; n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 microM) and with the cholinergic antagonists atropine (10 microM; n = 3) and d-tubocurarine (10 microM; n = 3) were studied. The action of betahistine when co-administered with these drugs was the same as that in control experiments, indicating that its effects did not include nitric oxide production or the activation of cholinergic receptors. In contrast, 0.01-1 mM betahistine reduced the excitatory action of kainic acid (10 microM; n = 6) and quiscualic acid (1 microM; n = 13). These results indicate that the action of betahistine on the spike discharge of afferent neurons seems to be due to a post-synaptic inhibitory action on the primary afferent neuron response to the hair cell neurotransmitter.
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beta-Histina/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Agonistas dos Receptores Histamínicos/farmacologia , Inibição Neural/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Vestíbulo do Labirinto/citologia , Vestíbulo do Labirinto/efeitos dos fármacos , Ambystoma , Animais , Atropina/farmacologia , beta-Histina/administração & dosagem , Relação Dose-Resposta a Droga , Agonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Tubocurarina/farmacologiaRESUMO
Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work was to study the betahistine action mechanism at the vestibular end organs. Experiments were carried out in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM, n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with antagonists of nitric oxide sintethizing enzyme, cholinergic drugs, and excitatory amino acids were studied. Betahistine 1 mM (n = 5) was coadministered with NG-nitro-L-arginine 3 microM. The action of betahistine remained as in control experiments. Betahistine 1 mM reduced the excitatory action of carbachol (200 microM, n = 5) in a 30 +/- 3.4%. Cholinergic antagonists atropine (10 microM, n = 3) and d-tubocurarine (10 microM, n = 3) did not modify betahistine actions. Betahistine 1 mM also reduced kainic acid (10 microM, n = 4) excitatory action in 45.5 +/- 9.8%. These results corroborate that betahistine has a peripheral inhibitory action in the spike discharge of the afferent neurons in the vestibule. This action seems to involve neither NO production nor modifications in the release of acetylcholine from the efferent fibers. The inhibitory action of betahistine seems to be due to a postsynaptic binding site on the afferent neurons.
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beta-Histina/farmacologia , Vasodilatadores/farmacologia , Vestíbulo do Labirinto/efeitos dos fármacos , Ambystoma , Animais , Vestíbulo do Labirinto/fisiologiaRESUMO
RATIONALE AND OBJECTIVES: To determine the acute physiological and subacute neurohistological effects of gadopentetate dimeglumine (GdD) administered intrathecally. METHODS: Twenty-four rats were separated into two study groups. In the first group, the acute effects of intrathecal GdD on cortical electroencephalographic activity, renal sympathetic nerve activity, arterial blood pressure, and heart rate were determined. In the second group, histological evaluation of the neural tissues was performed 10 days after treatment. In both the physiological and histological studies, a single GdD dose of 2.5 micromol/g brain (10 microL) was administered intrathecally. Control animals were injected intrathecally with the same volume of a sucrose solution that had the same osmolality as GdD. RESULTS: In the physiological study, GdD and sucrose injections elicited no significant change in any of the parameters recorded. In the histologic study, examination revealed two cases of pre-existing chronic spinal cord gliosis; one of these rats also exhibited signs of pre-existing chronic choroid plexus inflammation. No acute or subacute alterations observed could be specifically linked to the intrathecal administration of GdD. CONCLUSIONS: Intrathecally administered GdD was accompanied by no significant change in any of the physiologic or histologic parameters examined. Based on the relatively short time interval between GdD treatment and histologic examination, the neural tissue abnormalities (gliosis/inflammation) observed in two animals were judged to be incidental and likely due to prior chronic pre-existing processes such as viral infection. Although additional studies are required to verify the safety and effectiveness of intrathecal GdD in humans, data from the present study in animals provide evidence that when intrathecal GdD is used in doses sufficient to improve MRI of the cerebrospinal fluid compartment, it is likely to be accompanied by a low incidence of acute changes in neural function or structure.
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Sistema Nervoso Central/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Gadolínio DTPA/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiologia , Eletroencefalografia , Frequência Cardíaca/efeitos dos fármacos , Injeções Espinhais , Masculino , Ratos , Ratos Sprague-Dawley , Sacarose/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologiaRESUMO
Macrocarpins A (1), B (2), C (3) and D (4), four new nor-triterpenes, have been isolated from the roots of Maytenus macrocarpa. The structures were established by spectroscopic examinations. Natural compounds 1, 2, 4 and the acetyl derivative 1a are cytotoxic against four tumoral cell lines with IC50 values ranging between 0.4 and 5.2 microM.
Assuntos
Plantas Medicinais/química , Triterpenos/isolamento & purificação , Estrutura Molecular , Análise Espectral , Triterpenos/químicaRESUMO
The aerial parts of Maytenus macrocarpa yielded three new beta-dihydroagarofuran sesquiterpene polyol esters. Their structures were elucidated by spectroscopic analyses including 2D NMR techniques as 6beta,8beta,15-triacetoxy-1alpha, 9alpha-dibenzoyloxy-4beta-hydroxy-beta-dihydroagarofuran (1); 1alpha, 6beta,8beta, 15-tetraacetoxy-9alpha-benzoyloxy-4beta-hydroxy-beta-dihydroagarofura n (2) and (1S,4S,6R,7R,8R,9R)-1,6,15-triacetoxy-8, 9-dibenzoyloxy-4-hydroxy-beta-dihydroagarofuran (3). Compounds 1 and 2 showed marginal antitumor activity against four cell lines.
Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Propranolol/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Quimioterapia Combinada , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Metilfenidato/uso terapêuticoRESUMO
The new nortriterpene methylene quinones amazoquinone (1) and (7S, 8S)-7-hydroxy-7,8-dihydro-tingenone (2), and the new norphenolic triterpenes 7,8-dihydro-6-oxo-tingenol (3), 23-nor-6-oxo-tingenol (4), and 23-oxo-iso-tingenone (5) were isolated from Maytenus amazonica. Their structures were elucidated by spectroscopic methods. Compounds 1, 2, 3, and 5 showed low antitumor activity against four cancer cell lines.