In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

Objective: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. Methods: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4-7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. Results: The nebulization system produced relatively large amounts of aerosol ranging between 0.3 +/- 0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0 +/- 0.1 ml/min for distilled water (H(2)Od) at 6 bar, with MMADs between 2.61 +/- 0.1 mu m for PFD at 7 bar and 10.18 +/- 0.4 mu m for FC-75 at 6 bar. The deposition study showed that for surfactant and H(2)Od aerosols, the highest percentage of the aerosolized mass (similar to 65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH(2)O only increased total airway pressure by 1.59 cmH(2)O at the highest driving pressure (7 bar). Conclusion: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.

Micropropagação e avaliação da potencialidade genotóxica de Petiveria alliacea L.

Petiveria alliacea L. é uma planta pertencente à família Phytolaccaceae, conhecida popularmente no país como guiné, erva-de-alho, erva-tipi ou amansa-senhor. Nativa da Região Amazônica tem sido cultivada em muitas áreas tropicais com propósito medicinal ou ritualístico. O objetivo desse trabalho foi (i) o desenvolvimento e a multiplicação de plantas de P. alliacea L. através de métodos de cultura de tecidos, e monitoramento fitoquímico das culturas, e (ii) avaliação comparativa das potencialidades genotóxica e antigenotóxica entre plantas coletadas no campo e produzidas in vitro. Exemplares de diferentes populações ocorrentes no estado do Rio de Janeiro foram utilizados como matrizes para a cultura. Foi estabelecido um protocolo para multiplicação das plantas em meio MS suplementado com BAP e ANA em diferentes concentrações e combinações, que forneceu como melhor resultado em média 8 plantas por explante na concentração de BAP 4,4 μM + ANA 0,54 μM. A análise fitoquímica foi baseada em métodos cromatográficos de diferentes extratos de plantas de campo e plantas in vitro das populações estudadas resultando em diferentes substâncias identificadas nas amostras analisadas por cromatografia em camada delgada. Os extratos foram também avaliados por cromatografia gasosa acoplada á espectrometria de massas, sendo identificadas diferentes substâncias, entre as quais o dibenzil dissulfeto, um produto de degradação de tiosulfinatos com importantes atividades biológicas na defesa das plantas. Os extratos aquosos das plantas de campo e daquelas estabelecidas in vitro foram submetidos à avaliação da potencialidade genotóxica e antigenotóxica, usando-se como modelo o DNA plasmidial pUC 9.1. Os resultados demonstraram que as concentrações utilizadas do extrato aquoso foram capazes de induzir alterações na conformação estrutural do DNA, indicando a ocorrência de quebras simples e duplas nesta molécula. Observou-se também que as lesões aumentaram, proporcionalmente ao aumento da concentração dos extratos, caracterizando-se, assim, um efeito dose-resposta. Os dados também apontaram para um efeito protetor do extrato aquoso, em relação aos danos oxidativos causados pelo cloreto estanoso, indicando, também, uma potencialidade antigenotóxica do extrato aquoso.

Fumar antecipa a menopausa ? Evidências do Estudo Pró-Saúde

A menopausa é definida pelo momento em que a menstruação cessa permanentemente como conseqüência da falência ovariana. Uma vez estabelecida, há um aumento no risco de doença coronariana, doença de Alzheimer, osteoporose e fraturas e sua antecipação está relacionada a maiores índices de mortalidade. Com o envelhecimento geral da população mundial, as mulheres passaram a viver de um terço a metade de suas vidas no período pós-menopáusico e, conseqüentemente, a pesquisa de condições associadas à menopausa ganham importância. A idade da menopausa e os fatores que a influenciam variam entre os diversos estudos e poucos estudos brasileiros abordam o tema. O fumo tem sido associado à Antecipação da idade da menopausa. O objetivo deste estudo é analisar as diversas dimensões de associação entre o fumo e a idade da menopausa, levando em consideração possíveis relações de dose-resposta. Com base em dados do Estudo Pró-Saúde, foi realizado um estudo seccional utilizando-se para a análise o modelo de sobrevida paramétrico de riscos proporcionais com distribuição de Weibull. Os resultados apontam para uma redução em 32% do risco de menopausa entre fumantes ativas, que a alcançam 2,5 anos mais tarde que nunca fumantes, ajustando-se para escolaridade e paridade. Entre fumantes ativas, no entanto, foram sugeridos aumentos de risco de 123% e 192% para fumantes de 10 a 20 cigarros por dia e de mais de 20 maços-ano respectivamente, quando comparadas às fumantes de menos de 10 cigarros por dia e menos de 10 maços-ano. Nesses grupos, a menopausa foi antecipada em 3,3 anos e 4,4 anos, respectivamente. Em relação ao tempo decorrido entre cessar o tabagismo e a idade menopausa, duração do fumo ou idade de início, não foram encontradas associações. Neste estudo, em possíveis efeitos de dose-resposta, o fumo apresenta-se como fator associado à antecipação da idade da menopausa em alguns aspectos, embora não em outros.

Influence of carbon on the thermoluminescence and optically stimulated luminescence of α -Al2O3:C crystals

alpha-Al2O3:C crystal shows excellent thermoluminescence (TL) and optically stimulated luminescence (OSL) properties but the real role carbon plays in this crystal is still not clearly understood so far. In this work, alpha-Al2O3:C crystal doping with different amounts of carbon were grown by the temperature gradient technique, and TL and OSL properties of as-grown crystals were investigated. Additionally, a mechanism was proposed to explain the role of carbon in forming the TL and OSL properties of alpha-Al2O3:C. TL and OSL intensities of as-grown crystals increase with the increasing amount of carbon doping in the crystal, but no shift is found in the glow peak location at 465 K. As the amount of carbon doping in the crystals decreases, OSL decay rate becomes faster. With the increase in heating rate, the integral TL response of as-grown crystals decreases and glow peak shifts to higher temperatures. TL response decrease rate increases with the increasing amount of carbon doping in the crystals. All the TL and OSL response curves of as-grown crystals show linear-sublinear-saturation characteristic, and OSL dose response exhibits higher sensitivity and wider linear dose range than that of TL. The crystal doping with 5000 ppm carbon shows the best dosimetric properties. Carbon plays the role of a dopant in alpha-Al2O3:C crystal and four-valent carbon anions replace the two-valent anions of oxygen during the crystal growth process, and large amounts of oxygen vacancies were formed, which corresponds to the high absorption coefficient of F and F+ centers in the crystals.

α-Al_2O_3:C晶体的热释光和光释光特性

以高纯α-Al2O3和石墨为原料,采用温梯法生长了α-Al2O3:C晶体,使用RisΦTL/OSL-DA-15型热释光和光释光仪研究了其热释光和光释光特性.α-Al2O3:C晶体在462K附近有单一热释光峰,发射波长位于410nm.随着辐照剂量的增加,热释光强度逐渐增强,462K的热释光特征峰位置保持不变.α-Al2O3:C晶体的光释光衰减曲线由快衰减和慢衰减两个部分组成,随着辐照剂量的增加,快衰减部分衰减速率变化不大,而慢衰减部分衰减速率加快.在5×10-6—10Gy剂量范围内,α-Al2O3:C晶体的热释光剂量响应呈现良好的线性关系,30Gy时达到饱和;光释光剂量响应在5×10-6—60Gy剂量范围内呈现良好的线性关系,100Gy时达到饱和.与热释光相比,光释光剂量响应具有更高的灵敏度和更宽的线性剂量响应范围.

Neurotoxicidade de pesticidas organofosforados durante o desenvolvimento: alterações bioquímicas e comportamentais

Pesticidas organofosforados são amplamente usados e seu uso constitui um grave problema de saúde pública. A ação clássica destes compostos é a inibição irreversível da acetilcolinesterase, promovendo acúmulo de acetilcolina nas sinapses e hiperestimulação colinérgica. No entanto, as consequências da exposição a baixas doses podem se estender a outros mecanismos de ação e sistemas neurotransmissores. Considerando que crianças constituem um grupo particularmente vulnerável aos efeitos de pesticidas, neste trabalho investigamos os efeitos da exposição aos organofosforados metamidofós (MET) e clorpirifós (CPF) durante o desenvolvimento sobre os sistemas colinérgico e serotoninérgico e sobre o comportamento de camundongos. Para isso, camundongos suíços foram expostos a injeções subcutâneas de MET, clorpirifós ou veículo do terceiro (PN3) ao nono (PN9) dias de vida pós-natal. As doses de exposição foram previamente escolhidas através da construção de uma curva dose-resposta que identificou como mais adequadas para este estudo as doses de 1mg/kg de MET e 3mg/kg de CPF, as quais promoveram em torno de 20% de inibição da acetilcolinesterase. Em PN10, parte dos animais foi sacrificada e foram avaliados os sistemas colinérgico e serotoninérgico no tronco encefálico e córtex cerebral. De PN60 a PN63, os animais foram submetidos a uma bateria de testes comportamentais. Em seguida, estes animais também foram sacrificados tendo sido avaliados os sistemas colinérgico e serotoninérgico. Em PN10, MET e CPF causaram alterações que sugerem aumento da atividade colinérgica respectivamente no tronco e córtex em fêmeas. No sistema serotoninérgico, apenas CPF promoveu alterações, aumentando a ligação ao receptor 5HT1A e transportador 5HT em fêmeas e diminuindo na ligação ao 5HT2. Em PN63, a atividade da acetilcolinesterase foi reestabelecida em todos os grupos. Ainda assim, MET diminuiu a atividade da colina acetiltransferase no córtex e a ligação ao transportador colinérgico no tronco. Quanto aos efeitos do CPF, no tronco, houve redução da atividade da colina acetiltransferase em fêmeas e aumento em machos. Sobre o sistema serotoninérgico, MET e CPF promoveram diminuições no 5HT1A respectivamente no tronco e córtex das fêmeas e CPF aumentou a ligação no córtex de machos. A ligação ao 5HT2 foi aumentada após o tratamento com MET e ao transportador 5HT foi diminuída em fêmeas após o tratamento com clorpirifós. Sobre o comportamento, identificamos comportamento associado à depressão em animais expostos a MET e aumento dos níveis de ansiedade, além de prejuízo de aprendizado/memória após exposição à CPF. Desta forma, nossos resultados indicam que a exposição à metamidofós e clorpirifós durante o desenvolvimento é capaz de alterar, de diferentes formas, a atividade colinérgica e serotoninérgica, mesmo que as doses de exposição sejam toxicologicamente equivalentes. Foram verificados efeitos nas vias neuroquímicas logo após a exposição e após um longo período de interrupção do tratamento, indicando efeitos tardios em sistemas importantes que podem estar associados às alterações comportamentais. Finalmente, o presente estudo reforça a associação epidemiológica entre pesticidas e alterações psiquiátricas e a capacidade da programação de alterações a longo-prazo quando a exposição se dá durante o desenvolvimento.

Modeling red sea urchin (Strongylocentrotus franciscanus) growth using six growth functions

The growth of red sea urchins (Strongylocentrotus franciscanus) was modeled by using tag-recapture data from northern California. Red sea urchins (n=211) ranging in test diameter from 7 to 131 mm were examined for changes in size over one year. We used the function Jt+1 = Jt + f(Jt) to model growth, in which Jt is the jaw size (mm) at tagging, and Jt+1 is the jaw size one year later. The function f(Jt), represents one of six deterministic models: logistic dose response, Gaussian, Tanaka, Ricker, Richards, and von Bertalanffy with 3, 3, 3, 2, 3, and 2 minimization parameters, respectively. We found that three measures of goodness of fi t ranked the models similarly, in the order given. The results from these six models indicate that red sea urchins are slow growing animals (mean of 7.2 ±1.3 years to enter the fishery). We show that poor model selection or data from a limited range of urchin sizes (or both) produces erroneous growth parameter estimates and years-to-fishery estimates. Individual variation in growth dominated spatial variation at shallow and deep sites (F=0.246, n=199, P=0.62). We summarize the six models using a composite growth curve of jaw size, J, as a function of time, t: J = A(B – e–Ct) + Dt, in which each model is distinguished by the constants A, B, C, and D. We suggest that this composite model has the flexibility of the other six models and could be broadly applied. Given the robustness of our results regarding the number of years to enter the fishery, this information could be incorporated into future fishery management plans for red sea urchins in northern California.

Stress within the postseizure time window inhibits seizure recurrence

Recurrence is a key characteristic in the development of epilepsy. It remains unclear whether seizure recurrence is sensitive to postseizure stress. Here, tonic-clonic seizures were induced with a convulsive dose of pentylenetetrazole (PTZ), and acute seizure recurrence was evoked with a subconvulsive dose of the drug. We found that stress inhibited seizure recurrence when applied 30 minutes or 2 hours, but not 4 hours, after the tonic-clonic seizure. The time-dependent anti-recurrence effect of stress was mimicked by the stress hormone corticosterone and blocked by co-administration of mineralocorticoid and glucocorticoid receptor antagonists. Furthermore, in a PTZ-induced epileptic kindling model, corticosterone administered 30 minutes after each seizure decreased the extent of seizures both during the kindling establishment and in the following challenge test. These results provide novel insights into both the mechanisms of and therapeutic strategies for epilepsy. (C) 2010 Elsevier Inc. All rights reserved.

Towards the formation of neuro-transistor artificial chemical synapse

Highly sensitive biosensor for detection of acetylcholine (ACh) and competitive acetylcholinesterase (AChE) inhibitor, eserine, is investigated. Peculiar microelectronic configuration of an ion-sensitive field-effect transistor (ISFET) in addition to a right choice of the pH-transducing nanolayers allows recording a response of the enzyme-modified ISFET (EnFET) to a wide range of ACh concentrations. We demonstrate a remarkable improvement of at least three orders of magnitude in dose response to ACh. Described bioelectronic system reveals clear response, when the catalytic activity of the immobilized AChE is inhibited in a reversible manner by eserine, competitive inhibitor of AChE. ©2007 IEEE.

Highly efficient detector of the neurotransmitter ACh and AChE inhibitors

Among the variety of applications for biosensors one of the exciting frontiers is to utilize those devices as post-synaptic sensing elements in chemical coupling between neurons and solid-state systems. The first necessary step to attain this challenge is to realize highly efficient detector for neurotransmitter acetylcholine (ACh). Herein, we demonstrate that the combination of floating gate configuration of ion-sensitive field effect transistor (ISFET) together with diluted covalent anchoring of enzyme acetylcholinesterase (AChE) onto device sensing area reveals a remarkable improvement of a four orders of magnitude in dose response to ACh. This high range sensitivity in addition to the benefits of peculiar microelectronic design show, that the presented hybrid provides a competent platform for assembly of artificial chemical synapse junction. Furthermore, our system exhibits clear response to eserine, a competitive inhibitor of AChE, and therefore it can be implemented as an effective sensor of pharmacological reagents, organophosphates, and nerve gases as well. © 2007 Materials Research Society.

Evaluation of soot particles of biomass fuels with endocrine-modulating activity in yeast-based bioassay

Exposure to indoor air pollution (IAP) from the combustion of biomass fuels is an important cause of morbidity and mortality in developing countries. In the work discussed in this paper we evaluated the endocrine activity of soot particles from biomass fuels by using yeast bioassay. These pollutants could have beta-galactosidase activity with a relative potency (RP) about 10(-7)-10(-9) that of estradiol. Soot particles from wood and straw combustion only partially induced beta-galactosidase activity whereas others produced fully inductive activity in the yeast assay system. These pollutants did not have estrogen antagonist and progesterone agonist activity within the defined concentration range. However, these pollutants require 2-4 orders of magnitude higher IC50 to inhibit the activity of progesterone in a similar dose-response manner to mifepristone. We therefore propose that the endocrine activity of some environmental pollutants may be because of inhibition of the progesterone receptor (hPR). GC-MS results showed that substituted polycyclic aromatic hydrocarbon (PAH) compounds, substituted phenolic compounds and derivatives, aromatic carbonyl compounds, and phytosteroids in these soot particles may be mimicking endogenous hormones.

纳米水基磁性液体在肿瘤治疗领域的研究进展

结合作者在纳米磁性液体方面的研究经历，介绍了生物医学应用领域纳米磁性粒子的组成结构及特点，指出高分子改性纳米磁性粒子具有生物相容性好、稳定性强、载药量高的优点，并对目前高分子改性纳米四氧化三铁颗粒的制备方法及特点进行了对比分析。指出进一步研制磁响应性强、载药量高、粒度分布均匀的纳米磁性粒子，使之对癌细胞具有亲和作用，尽量避免对毛细血管网状内皮系统的清除，是未来肿瘤治疗领域纳米磁性粒子的研发目标，并对目前制备方法中存在的不足提出了改进的建议。

Flower color chimera and abnormal leaf mutants induced by C-12(6+) heavy ions in Salvia splendens Ker-Gawl.

The effect of C-12(6+) heavy ions bombardment on mutagenesis in Salvia splendens Ker-Gawl. was studied. Dose-response studies indicated that there was a peak of malformation frequency of S. splendens at 200 Gy. Abnormal leaf mutants of the bileaf, trileaf and tetraleaf conglutination were selected. Meanwhile, a bicolor flower chimera with dark red and fresh red flower was isolated in M1 generation of S. splendens. Random amplified polymorphic DNA (RAPD) analysis demonstrated that DNA variations existed among the wild-type, fresh and dark red flower shoots of the chimera. The dark red flower shoots of the chimera were conserved and cultivated at a large-scale through micropropagation. MS supplemented with 2.0 mg/L BA and 0.3 mg/L NAA was the optimal medium in which the maximum proliferation ratio (5.2-fold) and rooting rate (88%) were achieved after 6 weeks. Our findings provide an important method to improve the ornamental quality of S. splendens.

Chromosomal aberrations induced by C-12(6+) ions and Co-60 gamma-rays in mouse immature oocytes

The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of C-12(6+) ion or Co-60 gamma-ray. Chromosomal aberrations were analyzed in metaphase II oocytes at 7 weeks after irradiation. The relative biological effectiveness (RBE) of C C-12(6+) ion was calculated with respect to Co-60 gamma-ray for the induction of chromosornal aberrations. The C-12(6+) ion and Co-60 gamma-ray dose-response relationships for chromosomal aberrations were plotted by linear quadratic models. The data showed that there was a dose-related increase in frequency of chromosomal aberrations in all the treated groups compared to controls. The RBE values for C-12(6+) ions relative to (CO)-C-60 gamma-rays were 2.49, 2.29, 1.57, 1.42 or 1.32 for the doses of 0.5, 1.0, 2.07 4.0 or 6.0 Gy, respectively. Moreover, a different distribution of the various types of aberrations has been found for C-12(6+) ion and Co-60 gamma-ray irradiations. The dose-response relationships for C-12(6+) ion and (CO)-C-60 gamma-ray exhibited positive correlations. The results from the present study may be helpful for assessing genetic damage following exposure of immature oocytes to ionizing radiation.

Assessment of DNA damage of Lewis lung carcinoma cells irradiated by carbon ions and X-rays using alkaline comet assay

DNA damage and cell reproductive death determined by alkaline comet and clonogenic survival assays were examined in Lewis lung carcinoma cells after exposure to 89.63 MeV/u carbon ion and 6 MV X-ray irradiations, respectively. Based on the survival data, Lewis lung carcinoma cells were verified to be more radiosensitive to the carbon ion beam than to the X-ray irradiation. The relative biological effectiveness (RBE) value, which was up to 1.77 at 10% survival level, showed that the DNA damage induced by the high-LET carbon ion beam was more remarkable than that induced by the low-LET X-ray irradiation. The dose response curves of '' Tail DNA (%)'' (TD) and "Olive tail moment" (OTM) for the carbon ion irradiation showed saturation beyond about 8 Gy. This behavior was not found in the X-ray curves. Additionally, the carbon ion beam produced a lower survival fraction at 2 Gy (SF2) value and a higher initial Olive tail moment 2 Gy (OTM2) than those for the X-ray irradiation. These results suggest that carbon ion beams having high-LET values produced more severe cell reproductive death and DNA damage in Lewis lung carcinoma cells in comparison with X-rays and comet assay might be an effective predictive test even combining with clonogenic assay to assess cellular radio sensitivity