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1.
J Diabetes Metab Disord ; 21(1): 623-629, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35673501

RESUMO

Purpose: The aim of this survey is to investigate T1DM patients' expectations for and requirements of an ideal mobile self-management app with a special focus on functions for sports and exercise. Methods: A total of 251 persons participated in the survey. After checking for completeness and plausibility, the answers of 167 patients diagnosed with T1DM (66% female, 34% male) were analyzed. Results: The key features/aspects that were identified as being "rather important"/"very important" by more than 75% of respondents are: data security (96.4%), integration of further health data (e.g., heart rate, step count, calories) from other apps already installed on their smartphone (92.2%), automatic import of glucose data from other apps (91.6%), individual target setting (87.4%), warnings about abnormal glucose levels (82.6%), warnings about other abnormal health data (81.4%), diary function (80.8%), information on the training session after the workout (80.8%) and displaying/processing of further fitness variables (such as heart rate, step count, etc.) from other health-related wearable systems (77.8%). Conclusions: This study identifies the most relevant features of an ideal self-management app with functions for sports and exercise targeted at patients with T1DM that should be considered in the development of such an app.

3.
Nature ; 564(7736): 430-433, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30518863

RESUMO

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.


Assuntos
Transplante de Coração , Xenoenxertos/transplante , Papio , Suínos , Transplante Heterólogo , Animais , Anticorpos/análise , Anticorpos/sangue , Proteínas do Sistema Complemento/análise , Enzimas/sangue , Fibrina/análise , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Xenoenxertos/patologia , Humanos , Fígado/enzimologia , Masculino , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/metabolismo , Miocárdio/enzimologia , Necrose , Perfusão , Contagem de Plaquetas , Tempo de Protrombina , Trombomodulina/genética , Trombomodulina/metabolismo , Fatores de Tempo
4.
Xenotransplantation ; 22(6): 427-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26602740

RESUMO

BACKGROUND: As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient's native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. METHODS: Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/± thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. RESULTS: In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed pre-clinical suspicion of humoral rejection, which was not inhibited by the extended conventional IS including intensified treatments, and signs of thrombotic microangiopathy. Grafts of group 2 presented with only mild-to-moderate features of humoral rejection and thrombotic microangiopathy, except in one case of delayed rejection on day 17. The other experiments in this group were terminated because of untreatable pulmonary oedema, recurring ventricular fibrillation, Aspergillus sepsis, as well as a combination of a large donor organ and late toxic side effects due to TLI. CONCLUSIONS: Longer-term results were difficult to achieve in this model due to the IS regimens used. However, we conclude that heterotopic intrathoracic heart transplantation may be an option for clinical xenotransplantation.


Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Transplante de Coração , Imunossupressores/farmacologia , Animais , Animais Geneticamente Modificados , Anticorpos/imunologia , Anticorpos/farmacologia , Transplante de Coração/métodos , Suínos , Transplante Heterólogo/métodos
5.
Langmuir ; 27(7): 3920-9, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21395277

RESUMO

Wurtzite ZnO hexagonal nanopyramids were successfully synthesized in the liquid phase from homogeneous methanolic solutions of zinc acetate and tetramethylammonium hydroxide at an excess of zinc ions. The formation and properties of the nanocrystals were examined as a function of synthesis conditions. No significant influence of the [Zn(2+)]/[OH(-)] ratio was noticed on the final particle size, in spite of increased amounts of OH(-) ions, which tend to accelerate the particle nucleation and growth. Nevertheless, the reactant concentration ratio influences the surface properties of the ZnO nanocrystals. Mesoporous ZnO films were prepared by doctor blading ethanolic pastes containing ZnO nanoparticles and ethyl cellulose onto FTO conductive glass substrate followed by calcination. Additionally, the influence of a plasticizer (triacetin)-used during the paste preparation-on the film quality was investigated. A higher content of ZnO nanoparticles and plasticizer in the pastes improved the film quality. Four different temperatures (i.e., 400, 425, 450, and 475 °C) were used for the film calcination and their influence on the structural properties of the films was characterized. In principle, increasing the calcination temperature goes hand in hand with an increase of particle size, as well as the pore diameter and reduction of the surface area. Suitable mesoporous films were employed as photoanodes in dye sensitized solar cells (DSSCs). In order to assess the effect of the varied parameters on complete DSSC devices-using cis-diisothiocyanato-bis(2,2'-bipyridyl-4,4'-dicarboxylato) ruthenium(II)bis(tetrabutylammonium (N719) as a sensitizer-incident photon to current efficiency (IPCE) and current voltage measurements were carried out. The IPCE measurements confirmed photoinduced electron injection from the dye, reaching IPCE values up to 76%. Furthermore, current-voltage characteristics of complete cells emphasized the importance of the proper preparation methods and temperatures. These features are important assets for the preparation of nanocrystalline ZnO based photoelectrodes and for improving the DSSC performance.

6.
J Am Chem Soc ; 132(50): 17910-20, 2010 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-21121664

RESUMO

A new concept for the efficient synthesis of cationic dendrons, 4-tert-butyl-1-(3-(3,4-dihydroxybenzamido)benzyl)pyridinium bromide (17), 1,1'-(5-(3,4-dihydroxybenzamido)-1,3-phenylene)bis(methylene)bis(4-tert-butylpyridinium) bromide (18), N1,N7-bis(3-(4-tert-butyl-pyridium-methyl)phenyl)-4-(3-(3-(4-tert-butyl-pyridinium-methyl)phenyl-amino)-3-oxopropyl)-4-(3,4-dihydroxybenzamido)heptanediamide tribromide (19), and N1,N7-bis(3,5-bis(4-tert-butyl-pyridium-methyl)phenyl)-4-(3-(3,5-bis(4-tert-butyl-pyridinium-methyl)phenylamino)-3-oxopropyl)-4-(3,4-dihydroxybenzamido)heptanediamide hexabromide (20), and their facile binding to zinc oxide (ZnO) nanostructures is introduced. Dendrons containing highly reactive benzylic bromides reacted readily with 4-tert-butyl-pyridine and resulted in cationic dendrons. Furthermore, these permanently positively charged dendrons were equipped with a catechol anchor group. This enabled ZnO surface functionalization by simple immersion. The adsorption of 17, 18, 19, and 20 on the colloidal nanoparticles was monitored by Langmuir isotherms. The highest obtained experimental loadings correspond to 99.5%, 98.6%, 99.1%, and 42.5% of the particle surface for 17, 18, 19, and 20, respectively. These results indicate insufficient adsorption of the largest molecule 20 leading to reduced colloidal stability of the nanoparticles, while an enhanced stability after grafting with 17, 18, and 19 was observed. Mesoporous films suitable for the use as electrodes in dye-sensitized solar cells (DSSCs) were prepared. Subsequently, the films were functionalized with 18, 19, or 20 and sensitized with zinc-5,15-bis-[2',6'-bis-{2'',2''-bis-(carboxy)-ethyl}-methyl-4'-tert-butyl-pheny]-10,20-bis-(4'-tert-butylphenyl)porphyrin-octasodium-salt. UV-vis absorption spectra confirmed that 18, 19, and 20 are suitable for the stable electrostatic attachment of the dye. Current-voltage characteristics of complete cells demonstrated that increasing positive functionalization of the ZnO surface leads to decreased open circuit voltages (V(oc)). All V(oc) values were around 0.4 V with a maximum for the 18 functionalized ZnO film of 0.45 V. The maximum cell efficiency obtained (0.31%) is rather high, considering the narrow spectral absorption of the dye and the rather thin ZnO films used. Finally, incident photon to current efficiency (IPCE) measurements confirmed photoinduced electron injection from the dye. These features are important assets for applications in particle technology and even facilitated advanced devices like a supramolecular DSSC complete with a subsequent layer of negatively charged porphyrins.


Assuntos
Corantes/química , Dendrímeros/química , Nanopartículas/química , Óxido de Zinco/química , Cátions , Estrutura Molecular , Fotoquímica , Energia Solar , Eletricidade Estática , Propriedades de Superfície
7.
J Phys Chem B ; 114(45): 14671-8, 2010 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-20608700

RESUMO

Novel types of binding motives have been investigated within the context of sensitizing ZnO-based dye-sensitized solar cells with metalloporphyrins. In particular, a complementary class of metalloporphyrin has been synthesized to probe the impact of a face-to-edge/orthogonal versus face-to-face/parallel orientation of the metalloporphyrin with respect to ZnO and has been compared to TiO(2)-based dye-sensitized solar cells. Our studies provide a deep and detailed understanding of the individual electron-transfer processes at the ZnO/metalloporphyrin interface, that is, electron injection, recombination, and dye regeneration, by means of steady-state and time-resolved techniques. Interestingly, we found that for our novel ZnO/metalloporphyrin systems, the injection efficiencies are close to unity, despite their long, nonconjugated anchoring group length.

8.
J Am Chem Soc ; 130(34): 11503-9, 2008 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-18661981

RESUMO

We describe the functionalization of single-wall carbon nanotubes (SWNTs) with 4-(2-trimethylsilyl)ethynylaniline and the subsequent attachment of a zinc-phthalocyanine (ZnPc) derivative using the reliable Huisgen 1,3-dipolar cycloaddition. The motivation of this study was the preparation of a nanotube-based platform which allows the facile fabrication of more complex functional nanometer-scale structures, such as a SWNT-ZnPc hybrid. The nanotube derivatives described here were fully characterized by a combination of analytical techniques such as Raman, absorption and emission spectroscopy, atomic force and scanning electron microscopy (AFM and SEM), and thermogravimetric analysis (TGA). The SWNT-ZnPc nanoconjugate was also investigated with a series of steady-state and time-resolved spectroscopy experiments, and a photoinduced communication between the two photoactive components (i.e., SWNT and ZnPc) was identified. Such beneficial features lead to monochromatic internal photoconversion efficiencies of 17.3% when the SWNT-ZnPc hybrid material was tested as photoactive material in an ITO photoanode.


Assuntos
Materiais Biocompatíveis/síntese química , Indóis/química , Nanotecnologia/métodos , Nanotubos de Carbono/química , Compostos Organometálicos/química , Isoindóis , Teste de Materiais , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Fotoquímica , Análise Espectral Raman , Propriedades de Superfície , Compostos de Zinco
9.
Proc Natl Acad Sci U S A ; 99(14): 9300-5, 2002 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-12077321

RESUMO

DGAT1 encodes diacylglycerol O-acyltransferase (EC ), a microsomal enzyme that catalyzes the final step of triglyceride synthesis. It became a functional candidate gene for lactation traits after studies indicated that mice lacking both copies of DGAT1 are completely devoid of milk secretion, most likely because of deficient triglyceride synthesis in the mammary gland. Our mapping studies placed DGAT1 close to the region of a quantitative trait locus (QTL) on bovine chromosome 14 for variation in fat content of milk. Sequencing of DGAT1 from pooled DNA revealed significant frequency shifts at several variable positions between groups of animals with high and low breeding values for milk fat content in different breeds (Holstein-Friesian, Fleckvieh, and Braunvieh). Among the variants was a nonconservative substitution of lysine by alanine (K232A), with the lysine-encoding allele being associated with higher milk fat content. Haplotype analysis indicated the lysine variant to be ancestral. Two animals that were typed heterozygous (Qq) at the QTL based on marker-assisted QTL-genotyping were heterozygous for the K232A substitution, whereas 14 animals that are most likely qq at the QTL were homozygous for the alanine-encoding allele. An independent association study in Fleckvieh animals confirmed the positive effect of the lysine variant on milk fat content. We consider the nonconservative K232A substitution to be directly responsible for the QTL variation, although our genetic studies cannot provide formal proof.


Assuntos
Aciltransferases/genética , Leite/química , Polimorfismo Genético , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Mapeamento Cromossômico , DNA/genética , Diacilglicerol O-Aciltransferase , Gorduras na Dieta/análise , Feminino , Variação Genética , Haplótipos , Dados de Sequência Molecular , Característica Quantitativa Herdável , Homologia de Sequência de Aminoácidos
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