RESUMO
BACKGROUND AND AIM: Traffic-related ultrafine particle pollution near highways is associated with adverse health. Reducing exposure by use of portable air purifiers in homes is one approach to reducing this risk. However, the reaction of residents to having air purifiers in homes is not well studied. METHODS: Within the framework of our randomized crossover trial of air purifiers in homes near a major highway, we collected data about participants' use and reactions to air purifiers using questionnaires at their 30-day and 90-day home visits, recorded electricity consumption using HOBO monitors, and conducted structured interviews with participants. RESULTS: Nearly all 150 participants reported running the air purifiers virtually 24 h every day in both their living room and their bedroom in the prior month. The units' HOBO electricity use, from a subset of 45 participants, supported the participants' responses from the questionnaire. Approximately 80% of participants reported setting their air purifier on the medium setting. Tolerance to air purifier noise increased significantly between the 30-day and 90-day home visits, with approximately two thirds reporting not being bothered at all by the noise. The qualitative interviews in a subset of 26 participants yielded consistent responses to those from the questionnaires. Size of unit, airflow, and energy consumption were additional concerns that emerged during the interviews. CONCLUSIONS: Results from the questionnaires, HOBO data, and structured interviews all suggest participants had positive reactions towards the presence of in-home APs, and therefore may be receptive to using air purifiers in their homes on a regular basis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04279249 . Registered 09 October 2019.
Assuntos
Filtros de Ar , Estudos Cross-Over , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Poluição do Ar em Ambientes Fechados/prevenção & controle , Poluição do Ar em Ambientes Fechados/efeitos adversos , Emissões de Veículos/prevenção & controle , Emissões de Veículos/análise , Poluição Relacionada com o Tráfego/efeitos adversos , Poluição Relacionada com o Tráfego/prevenção & controle , Inquéritos e Questionários , Habitação , Material Particulado/efeitos adversos , Material Particulado/análise , Fatores de Tempo , Exposição Ambiental/efeitos adversos , Exposição Ambiental/prevenção & controle , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análiseRESUMO
Using molecular dynamics, we simulate the abrasion process of an atomically rough Fe surface with multiple hard abrasive particles. By quantifying the nanoscopic wear depth in a time-resolved fashion, we show that Barwell's macroscopic wear law can be applied at the atomic scale. We find that in this multiasperity contact system, the Bowden-Tabor term, which describes the friction force as a function of the real nanoscopic contact area, can predict the kinetic friction even when wear is involved. From this the Derjaguin-Amontons-Coulomb friction law can be recovered, since we observe a linear dependence of the contact area on the applied load in accordance with Greenwood-Williamson contact mechanics.
RESUMO
A post-processing method for molecular dynamics (MD) simulations of friction based on the smooth particle approach is proposed, allowing--among other features--the introduction and evaluation of a solid-solid contact area arising due to direct asperity interaction. In order to illustrate the feasibility of this scheme, a large number of MD calculations of lubricated nanotribological systems with various asperity geometries and carefully selected numbers of lubricant molecules were carried out and analysed. In this manner, it is shown that the friction force as a function of load agrees very well with a three-parameter friction law which, in addition to the adhesion- and the load-controlled terms, contains a load-independent offset.
RESUMO
In this study the Nano Spray Dryer B-90 (BÜCHI Labortechnik AG, Flawil, Switzerland) was evaluated with regard to the drying of proteins and the preparation of respirable powders in the size range of 1-5 µm. ß-galactosidase was chosen as a model protein and trehalose was added as a stabilizer. The influence of inlet temperature, hole size of the spray cap membrane and ethanol concentration in the spray solution was studied using a 3³ full factorial design. The investigated responses were enzyme activity, particle size, span, yield and shelf life. Furthermore, the particle morphology was examined. The inlet temperature as well as the interaction of inlet temperature and spray cap size significantly influenced the enzyme activity. Full activity was retained with the optimized process. The particle size was affected by the hole size of the spray cap membrane and the ethanol content. The smallest cap led to a monodisperse particle size distribution and the greatest yield of particles of respirable size. Higher product recovery was achieved with lower inlet temperatures, higher ethanol contents and smaller cap sizes. Particle morphology differed depending on the cap size. The protein exhibited higher storage stability when spray dried without ethanol and when a larger spray cap size was used.
Assuntos
Biofarmácia/instrumentação , Biofarmácia/métodos , Nanopartículas/administração & dosagem , Proteínas/administração & dosagem , Projetos de Pesquisa , Administração por Inalação , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Desenho de Equipamento , Etanol/química , Membranas Artificiais , Nanopartículas/química , Tamanho da Partícula , Pós , Proteínas/química , Propriedades de Superfície , Trealose/química , beta-Galactosidase/administração & dosagem , beta-Galactosidase/químicaRESUMO
Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic-lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic-lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic-lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3-16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System.
Assuntos
Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Sacarose/análogos & derivados , Administração Oral , Lubrificação , Tamanho da Partícula , Porosidade/efeitos dos fármacos , Padrões de Referência , Sacarose/química , Comprimidos , Resistência à Tração/efeitos dos fármacos , Temperatura de Transição/efeitos dos fármacosRESUMO
By studying metal growth on Pt(111), we determine the reasons for the high island densities observed in pulsed laser deposition (PLD) compared to conventional thermal deposition. For homoepitaxy by PLD with moderate energies ( < or approximately 100 eV) of the deposited ions, high island densities are caused by the high instantaneous flux of arriving particles. Additional nuclei are formed at high ion energies (> or approximately 200 eV) by adatoms created by the impinging ions. For heteroepitaxy, the island density is also increased by intermixing (deposited material implanted in the surface), creating an inhomogeneous potential energy surface for diffusing atoms. We discuss implications for layer-by-layer growth and sputter deposition.
RESUMO
Quantitative applications for pharmaceutical solid dosage forms using near-infrared (NIR) spectroscopy are central to process analytical technology (PAT) manufacturing designs. A series of studies were conducted to evaluate the use of NIR transmission mode under various pharmaceutical settings. The spectral variability in relation to tablet physical parameters were investigated using placebo tablets with different thickness and porosity steps and both variables showed an exponential relationship with the detected transmittance signal drop. The drug content of 2.5% m/m folic acid tablets produced under extremely different compaction conditions was predicted and found to agree with UV assay results after inclusion of extreme physical outliers to the training sets. NIR transmission was also shown to traverse a wide section of the tablet by comparing relative blocking intensities from different regions of the tablet surface and >90% of the signal was detected through a central area of 7 mm diameters of the tablet surface. NIR Quantification of both film thickness and active ingredient for film-coated tablets are examined in part II of this study.
Assuntos
Espectroscopia de Luz Próxima ao Infravermelho/métodos , Comprimidos/química , Calibragem , Composição de Medicamentos , Ácido Fólico/administração & dosagem , Ácido Fólico/química , Porosidade , Pressão , Espectrofotometria Ultravioleta , Propriedades de SuperfícieRESUMO
Upon impact on a solid surface, the potential energy stored in slow highly charged ions is primarily deposited into the electronic system of the target. By decelerating the projectile ions to kinetic energies as low as 150 x q eV, we find first unambiguous experimental evidence that potential energy alone is sufficient to cause permanent nanosized hillocks on the (111) surface of a CaF(2) single crystal. Our investigations reveal a surprisingly sharp and well-defined threshold of potential energy for hillock formation which can be linked to a solid-liquid phase transition.
RESUMO
The influence of free-air ozone (O(3)) fumigation on the levels of gene transcripts and compounds of defence and signalling were analysed in leaves of adult beech trees from the "Kranzberg Forest" research site in 2003 and 2004. This includes the precursor of the stress hormone ethylene, ACC (1-aminocyclopropane-1-carboxylic acid), conjugated salicylic acid, lignin content as well as of the expression level of genes connected with oxidative stress and stress signalling. At this site mature beech trees were exposed to an enhanced O(3) regime by a free-air O(3) canopy exposure system. Levels of conjugated ACC and conjugated salicylic acid in leaves were increased under O (3) fumigation whereas lignin content was only slightly enhanced. Quantitative real-time RT-PCR (qRT-PCR) was performed on transcripts of genes connected with lignin, salicylic acid, and ethylene formation, the shikimate pathway, abscisic acid biosynthesis as well as with the antioxidative system. Genes which showed O(3)-dependent increases included FSCOMT (caffeic-acid O-methyltransferase) connected with lignin formation, the stress response genes FSACS2 (ACC synthase) and FSPR1 (PR10 - pathogenesis-related protein), as well as FSNCED1 (9-cis-epoxicarotenoid dioxygenase), the rate-limiting enzyme of the ABA synthesis. For FSNCED1 expression level, a significant O(3) effect was found with an 8-fold (sun) and 7-fold (shade) induction in July 2003 and a 3-fold and 2.5-fold induction in July 2004. While the observed effects were not continuous, elevated O(3) is concluded to have the potential to disrupt the defence and signalling system.
Assuntos
Fagus/efeitos dos fármacos , Fagus/efeitos da radiação , Ozônio/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/efeitos da radiação , Transdução de Sinais , Luz Solar , Ácido Abscísico/biossíntese , Aminoácidos Cíclicos/biossíntese , Antioxidantes/metabolismo , Europa (Continente) , Fagus/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Genes de Plantas , Glutationa/metabolismo , Lignina/metabolismo , Folhas de Planta/metabolismo , Ácido Salicílico/metabolismo , Ácido Chiquímico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Superóxido Dismutase/genética , Árvores/efeitos dos fármacos , Árvores/metabolismo , Árvores/efeitos da radiaçãoRESUMO
Ozone and light effects on endophytic colonization by Apiognomonia errabunda of adult beech trees (Fagus sylvatica) and their putative mediation by internal defence compounds were studied at the Kranzberg Forest free-air ozone fumigation site. A. errabunda colonization was quantified by "real-time PCR" (QPCR). A. errabunda-specific primers allowed detection without interference by DNA from European beech and several species of common genera of plant pathogenic fungi, such as Mycosphaerella, Alternaria, Botrytis, and Fusarium. Colonization levels of sun and shade leaves of European beech trees exposed either to ambient or twice ambient ozone regimes were determined. Colonization was significantly higher in shade compared to sun leaves. Ozone exhibited a marginally inhibitory effect on fungal colonization only in young leaves in 2002. The hot and dry summer of 2003 reduced fungal colonization dramatically, being more pronounced than ozone treatment or sun exposure. Levels of soluble and cell wall-bound phenolic compounds were approximately twice as high in sun than in shade leaves. Acylated flavonol 3- O-glycosides with putatively high UV-B shielding effect were very low in shade canopy leaves. Ozone had only a minor influence on secondary metabolites in sun leaves. It slightly increased kaempferol 3- O-glucoside levels exclusively in shade leaves. The frequently prominent hydroxycinnamic acid derivative, chlorogenic acid, was tested for its growth inhibiting activity against Apiognomonia and showed an IC50 of approximately 8 mM. Appearance of Apiognomonia-related necroses strongly correlated with the occurrence of the stress metabolite, 3,3',4,4'-tetramethoxybiphenyl. Infection success of Apiognomonia was highly dependent on light exposure, presumably affected by the endogenous levels of constitutive phenolic compounds. Ozone exerted only minor modulating effects, whereas climatic factors, such as pronounced heat periods and drought, were dramatically overriding.
Assuntos
Ascomicetos/metabolismo , Clima , Fagus/microbiologia , Fagus/efeitos da radiação , Folhas de Planta/microbiologia , Folhas de Planta/efeitos da radiação , Luz Solar , Ascomicetos/efeitos dos fármacos , Compostos de Bifenilo/metabolismo , Ácido Clorogênico/farmacologia , DNA Fúngico/metabolismo , Ozônio/farmacologia , Fenóis/metabolismo , Fatores de TempoRESUMO
Suppression subtractive hybridization (SSH) was performed to isolate cDNAs representing genes that are differentially expressed in leaves of Fagus sylvatica upon ozone exposure. 1248 expressed sequence tags (ESTs) were obtained from 2 subtractive libraries containing early and late ozone-responsive genes. Sequences of 1139 clones (91 %) matched the EBI/NCBI database entries. For 578 clones, no putative function could be assigned. Most abundant transcripts were O-methyltransferases, representing 7 % of all sequenced clones. ESTs were organized into 12 functional categories according to the MIPS database. Among them, 12 % (early)/15 % (late) were associated with disease and defence, 19/11 % with cell structure, 4/10 % with signal transduction, and 9/6 % with transcription. The expression pattern of selected ESTs (ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit [rbcS], WRKY-type transcription factor, ultraviolet-B-repressible protein, aquaporine, glutathione S-transferase, catalase, caffeic acid O-methyltransferase, and pathogenesis-related protein 1 [PR1]) was analysed by quantitative real-time RT-PCR (qRT-PCR) which confirmed changed transcript levels upon ozone treatment of European beech saplings. The ESTs characterized will contribute to a better understanding of forest tree genomics and also to a comparison of ozone-responsive genes in woody and herbaceous plants.
Assuntos
Fagus/efeitos dos fármacos , Fagus/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ozônio/farmacologia , Transcrição Gênica/efeitos dos fármacos , Europa (Continente) , Etiquetas de Sequências Expressas , Biblioteca Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/genéticaRESUMO
Using the molecular-dynamics technique, cluster emission for 5 keV Ar bombardment of a Cu (111) surface has been investigated using a many-body (tight binding) potential for the Cu-Cu interaction. The calculations allow us to analyse the basic processes underlying cluster emission. It is found that two distinct processes can be distinguished which lead to cluster emission under energetic ion bombardment. The first process causes the emission of small clusters, which are emitted by a collective motion during the development of the collision cascade within the first picosecond after impact. Thus, emission times of such clusters agree with the emission times of atoms in sputtering. Such a process can be envisioned if, for example, a few layers below the surface, an energetic recoil causes the development of a subcascade. Energy transferred by this event to the surface is strongly directional and can lead to the simultaneous emission of a group of neighbouring surface atoms, which in some cases will remain bounded and form a cluster after emission. Typically, clusters emitted by this mechanism consist of atoms, which are neighbouring in the target and are almost exclusively surface atoms, similar to all sputtered atoms. Emission of large clusters (cluster sizes of 10 or more atoms), as observed experimentally, is a puzzling phenomenon. From our calculations we conclude that the emission of such large clusters does not occur during the collisional phase of sputtering, but happens much later (5-10 ps after ion impact). Emission can occur for spike events, where all the energy of the impinging ion is deposited locally in a small volume near to the surface, and the sputtering yield is 3-5 times the average yield. Such events are rare, but we have found a few cases in our calculations where stable clusters consisting of more than 20 atoms were emitted. Melting of the spike volume occurs, and the high temperatures and pressures produced can cause emission of large fragments during the thermal phase. The composition of such large clusters is quite different from that of small clusters. They consist of atoms from different layers and the constituents are also generally not next-neighbour atoms. This change in origin of the cluster atoms reflects the mixing and diffusion processes occurring in the melted zone before emission. The calculations indicate that hydrodynamical phenomena might play a role in the emission of large fragments. Additional calculations, where the energy was distributed 'thermally' in a three-dimensional volume under the surface for 500 fs, give very similar results, even in such cases where the kinetic phase of the collision-cascade development was absent.
RESUMO
The interaction of liposome formulations consisting of Phospholipon 80 and sphingomyelin with human skin was investigated. These formulations were shown previously to have a composition-dependent effect on the penetration of Heparin into the skin. Fluorescence labelled phosphatidylethanolamine (PE-NBD) was incorporated in the liposomes and the depth in which the fluorescent phospholipid label enters into epidermal membrane and full thickness skin was studied by confocal laser scanning microscopy (CLSM). Confocal sections parallel to the surface of the skin were recorded in heat separated epidermis. An even distribution of phospholipid in the lipid matrix of the stratum corneum surrounding the corneocytes was observed with Phospholipon 80 but not when sphingomyelin was included in the formulation. The addition of Heparin which formed a coating around the liposomes, caused a strong localization of fluorescence within the epidermis. For full thickness skin, mechanical cross sections of skin were made and optical sections were recorded parallel to the plane of cut. Phospholipid penetrated and was distributed fairly homogeneously in the lower dermis layers within 30 min of application regardless of liposome composition and the presence of Heparin. This rather quick penetration process seemed to follow distinct pathways along the epidermis and the upper dermis, notably the hair follicle route. Thus, a strong and in some respects composition-dependent interaction of phospholipids with skin is evident. These observations, however, are limited to the level of phospholipid molecules, rather than of entire liposomes interacting with skin.
Assuntos
Lipossomos/química , Pele/química , Esfingomielinas/química , Administração Tópica , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Portadores de Fármacos , Feminino , Corantes Fluorescentes , Heparina/administração & dosagem , Heparina/farmacocinética , Humanos , Técnicas In Vitro , Microscopia Confocal , Microtomia , Peso Molecular , Absorção Cutânea , Fixação de TecidosRESUMO
The transport of unfractionated (UH) and low molecular weight Heparin (LMWH) in human skin was investigated in vitro using heat separated epidermal membrane and dermis and the effect of liposomal formulations with Phospholipon(R) 80 (PL80) and Sphingomyelin (SM) was assessed. The distribution of Heparin within skin tissue was studied by the tape stripping method. Heparin concentrations were measured with a biological assay. Transepidermal water loss was determined to characterize barrier properties of skin. No consistent permeation of Heparin through epidermal membrane was detected. Penetration into the epidermal membrane was for LMWH significantly greater than for UH. Accumulation of UH was largely restricted to the outermost layers of the stratum corneum while LMWH penetrated into deeper epidermal layers. UH penetration into epidermis was detected for the PL80 liposomal formulation only. The extent of LMWH penetration was independent of the formulation, LMWH, however, showed a trend to accumulate in deeper epidermal layers for the PL80 compared to the aqueous formulation. Thus, molecular weight and liposomal formulations influenced the penetration pattern of Heparin in the epidermis. It can not be concluded whether the concentration of LMWH achieved at the blood capillaries is sufficient to exert a pharmacological effect. UH permeated readily through dermis irrespectively of formulation and its accumulation in the dermis was significantly enhanced and its lag time of permeation increased in the presence of SM liposomes.
Assuntos
Anticoagulantes/farmacocinética , Heparina/farmacocinética , Absorção Cutânea , Idoso , Algoritmos , Anticoagulantes/administração & dosagem , Feminino , Heparina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/farmacocinética , Humanos , Técnicas In Vitro , Lipossomos , Soluções Farmacêuticas , Perda Insensível de ÁguaRESUMO
The dynamics of the laser-ablation (-desorption) process of metals (Al, Ag, Fe, and Ni) initiated by 30 fs laser pulses has been investigated by interferometric time-resolved pump-probe measurements. It is postulated that a sufficiently high density of hot electrons is essential for achieving desorption of metal ions. In addition, we have observed a new and unexpected behavior characterized by delayed ablation for a pump-probe beam delay in the range of several ps for Al, Ni, and Fe. This second peak is attributed to the development of a liquid surface layer developing after a few ps. Molecular dynamics simulations support this assumption.
RESUMO
The large and varied multigene families of tissue kallikreins of rat and mouse are considered to selectively release as many bioactive peptides. In order to determine whether a similar family of enzymes is expressed in the organs of the guinea pig purification studies were performed. Tissue kallikreins from the submandibular gland, coagulating gland/prostate complex and the pancreas were separated by affinity chromatography on benzamidine-Sepharose. Amino-terminal sequences, the patterns of hydrolysis rates of a number of peptide p-nitroanilides, inactivation rates by active site-directed irreversible inhibitors, specific kininogenase activities and types of kinin released were used to probe the identity of the isolated enzymes. Guinea pig tissue kallikreins 1 and 2 have been reported previously. In the present study we have identified a third type, designated tissue kallikrein 1a because of its sequence similarity to kallikrein 1, which differs from the latter in the catalytic properties. The inferred occurrence of not more than two or three independent tissue kallikrein genes in the guinea pig contrasts with the varied family of enzymes expressed by the large number of such genes present in rats and mice. Expression in the guinea pig (and also in humans) of only a small number of tissue kallikreins makes specific processing of a multitude of biologically active peptides by such enzymes unlikely.
Assuntos
Calicreínas/isolamento & purificação , Pâncreas/enzimologia , Próstata/enzimologia , Glândula Submandibular/enzimologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Cobaias , Calicreínas/antagonistas & inibidores , Calicreínas/metabolismo , Cininas/metabolismo , Masculino , Dados de Sequência Molecular , Família Multigênica , Inibidores de Serina Proteinase/farmacologia , Especificidade por Substrato , Calicreínas TeciduaisRESUMO
OBJECTIVE: To determine if the number of diagnostic laparoscopies done on women without tubal adhesive disease could be reduced by testing for tubal disease with Chlamydia trachomatis antibody titers and hysterosalpingography (HSG), either singly or together. DESIGN: Historical prospective chart review. SETTING: The Colorado Kaiser Permanente Reproductive Endocrinology Clinic. PATIENTS: All 703 infertility patients who had C. trachomatis antibody titers done from March 2, 1988 to April 30, 1992. The final study group was comprised of 218 patients who had antibody titers, HSG, and laparoscopy. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sensitivity, negative predictive value, and false-positive rate were the test characteristics of interest. Tubal disease was identified by laparoscopy. RESULTS: For HSG testing, the sensitivity was 78% and the negative predictive value was 85%. For C. trachomatis titers, the sensitivity was also 78% and the negative predictive value was 82%. Ninety-five percent confidence intervals for sensitivity and negative predictive value overlapped, indicating that there was no significant difference. However, false-negative rates were the same for the two tests, but false-positive rates were lowest for HSG and series testing. CONCLUSIONS: To minimize false-positive tests and thus, to minimize unnecessary laparoscopies, HSG testing either alone or combined with the C. trachomatis antibody titer as series tests yielded a significantly lower false-positive rate. In our study group, if both tests were negative, tubal disease was identified on laparoscopy in only 5% of cases. Choice of most cost-effective test sequence will depend on who bears the cost. Further studies of cost-benefit using well-defined testing sequences are needed to determine if C. trachomatis antibody titers in series with HSG would be more cost effective than HSG alone in detecting tubal disease.