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1.
J Spec Oper Med ; 21(2): 85-88, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34105128

RESUMO

BACKGROUND: Female Servicemembers are increasingly being incorporated into the combat arms and Special Operations communities. Female urinary diversion devices (FUDDs) have been used to facilitate urination in the austere environments that are encountered by Servicemembers. Importantly, the potential for the bacterial contamination of these devices has not been evaluated. The goals of this study were to determine whether microorganisms adhere to the surfaces of FUDDs in the field environment and to demonstrate the presence of potential pathogens on the used devices. MATERIALS AND METHODS: A total of 15 devices that were used in a comprehensive 18-24-hour military field exercise were tested for the presence of microorganisms. Briefly, each device was swabbed, and the swabs were used to inoculate blood agar plates to encourage bacterial growth. The resulting bacterial colonies were identified, and the surface topography of the devices was investigated with electron microscopy. RESULTS: Although microscopy revealed few surface features capable of facilitating bacterial attachment, several species were recovered. Significantly, a biofilm-forming strain of Proteus mirabilis (P. mirabilis) was detected on two of the devices. P. mirabilis is a mobile urinary pathogen that can potentially migrate from the surface of the device into the urinary tract of the user. CONCLUSION: Commercial FUDDs can support bacterial growth and harbor potential pathogens. Care should be taken to ensure that Servicemembers are aware of the importance of the proper care and cleaning of these devices in the field environment. To this end, standard operating procedures should be developed and distributed.


Assuntos
Militares , Derivação Urinária , Biofilmes , Feminino , Humanos , Proteus mirabilis
2.
Mol Immunol ; 134: 172-182, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33799071

RESUMO

Macrophages are fundamental for initiation, maintenance, and resolution of inflammation. They can be activated by 'Toll-like receptor' (TLR) engagement, which initiates critical pathways to fight infections. 'Interleukin receptor-associated kinase 2' (IRAK2) is part of the membrane-proximal Myddosome formed at IL-1R/TLRs, but utility and regulation of IRAK2 within is not completely understood. In this study, we addressed the importance of the evolutionary conserved extreme C-terminus of IRAK2 in TLR signaling. The last 55 amino acids lack any known functional domain. The C-terminus deletion mutant IRAK2Δ55 was hypofunctional and disabled to conduct TLR4-inducible NF-κB and ERK2 activation. Accordingly, it could neither fully support subsequent CD40 cell surface expression nor IL-6 and nitric oxide release. Interestingly, IRAK2Δ55 was still capable to bind to 'tumor necrosis factor receptor-associated factor 6' (TRAF6), which is requisite to activate TRAF6 as an E3-ubiquitin ligase for further downstream signaling. However, IRAK-dependent auto-ubiquitination of TRAF6 was impaired, when IRAK2Δ55 was bound. Thus, the conserved last 55 amino acids enable IRAK2 to sustain an optimal TLR response. This knowledge might spark ideas how overshooting inflammatory responses could be modified without blocking the entire immune response.


Assuntos
Quinases Associadas a Receptores de Interleucina-1/metabolismo , Transdução de Sinais/imunologia , Fator 6 Associado a Receptor de TNF/metabolismo , Receptores Toll-Like/metabolismo , Animais , Células HEK293 , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Quinases Associadas a Receptores de Interleucina-1/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Fator 6 Associado a Receptor de TNF/imunologia , Receptores Toll-Like/imunologia , Ubiquitinação
3.
Pacing Clin Electrophysiol ; 39(10): 1070-1076, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27503213

RESUMO

BACKGROUND: Sudden cardiac death (SCD) is the most important cause of late mortality after atrial baffle procedure for d-transposition of the great arteries (d-TGA). Experience with internal cardioverter defibrillator (ICD) therapy in this population is limited. We conducted a multicenter cohort study to determine the current state of ICD therapy in individuals after atrial baffle procedure. METHODS: Demographic and clinical data as well as data on device implantation, programming, ICD discharges, and complications after atrial baffle procedure for d-TGA from four German centers were analyzed retrospectively. RESULTS: ICD implantation was undertaken in 33 subjects. ICD implantation was undertaken as primary prevention in 29 (88%) and secondary prevention in four (12%) individuals. There were 21 (64%) subjects with atrial reentrant tachycardia (IART). During a median follow-up of 4.8 years, seven appropriate ICD therapies were delivered in three (10%) individuals with primary prevention indication. No appropriate shocks were documented in subjects with secondary prevention indication. A total of 12 inappropriate ICD discharges occurred in eight (24%) individuals due to IART (n = 6) or lead failure (n = 2). ICD-related complications were noted in seven individuals (21%): lead dislodgement/failure in five (15%) and ICD infection in two subjects (6%). CONCLUSIONS: The majority of individuals received an ICD for primary prevention of SCD, thus representing a liberal attitude of physicians for ICD implantation. During a median follow-up of 4.8 years, the rate of appropriate ICD therapies was low and clearly exceeded by inappropriate ICD discharges. Lead failure and IART were present in >20% of the individuals and were frequent reasons for inappropriate ICD discharges. Facing these results, rigorous treatment of IART and careful ICD programming seems mandatory.


Assuntos
Desfibriladores Implantáveis , Transposição dos Grandes Vasos/terapia , Adulto , Estudos de Coortes , Desfibriladores Implantáveis/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Taquicardia por Reentrada no Nó Atrioventricular/prevenção & controle
4.
Chem Commun (Camb) ; 49(90): 10581-3, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24091876

RESUMO

A homogeneous organometallic Ir complex was shown to catalyze the electro-oxidation of 4-methoxybenzyl alcohol to p-anisaldehyde at a very low applied potential with remarkably high selectivity and Faradaic efficiency. In the chemical catalysis, when stoichiometric oxidant and anionic base were used to separately accept electrons and protons, aldehyde selectivity was in agreement with electrolysis results.

5.
PLoS One ; 6(11): e27457, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22096576

RESUMO

CONTEXT/OBJECTIVE: Epidemiological studies have demonstrated that women have a significantly better prognosis in chronic renal diseases compared to men. This suggests critical influences of gender hormones on glomerular structure and function. We examined potential direct protective effects of estradiol on podocytes. METHODS: Expression of estrogen receptor alpha (ERα) was examined in podocytes in vitro and in vivo. Receptor localization was shown using Western blot of separated nuclear and cytoplasmatic protein fractions. Podocytes were treated with Puromycin aminonucleoside (PAN, apoptosis induction), estradiol, or both in combination. Apoptotic cells were detected with Hoechst nuclear staining and Annexin-FITC flow cytometry. To visualize mitochondrial membrane potential depolarization as an indicator for apoptosis, cells were stained with tetramethyl rhodamine methylester (TMRM). Estradiol-induced phosphorylation of ERK1/2 and p38 MAPK was examined by Western blot. Glomeruli of ERα knock-out mice and wild-type controls were analysed by histomorphometry and immunohistochemistry. RESULTS: ERα was consistently expressed in human and murine podocytes. Estradiol stimulated ERα protein expression, reduced PAN-induced apoptosis in vitro by 26.5±24.6% or 56.6±5.9% (flow cytometry or Hoechst-staining, respectively; both p<0.05), and restored PAN-induced mitochondrial membrane potential depolarization. Estradiol enhanced ERK1/2 phosphorylation. In ERα knockout mice, podocyte number was reduced compared to controls (female/male: 80/86 vs. 132/135 podocytes per glomerulus, p<0.05). Podocyte volume was enhanced in ERα knockout mice (female/male: 429/371 µm(3) vs. 264/223 µm(3) in controls, p<0.05). Tgfß1 and collagen type IV expression were increased in knockout mice, indicating glomerular damage. CONCLUSIONS: Podocytes express ERα, whose activation leads to a significant protection against experimentally induced apoptosis. Possible underlying mechanisms include stabilization of mitochondrial membrane potential and activation of MAPK signalling. Characteristic morphological changes indicating glomerulopathy in ERα knock-out mice support the in vivo relevance of the ERα for podocyte viability and function. Thus, our findings provide a novel model for the protective influence of female gender on chronic glomerular diseases.


Assuntos
Apoptose/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Podócitos/citologia , Podócitos/metabolismo , Animais , Apoptose/genética , Western Blotting , Células Cultivadas , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Glomérulos Renais/metabolismo , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Podócitos/efeitos dos fármacos , Puromicina Aminonucleosídeo/farmacologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Graefes Arch Clin Exp Ophthalmol ; 249(12): 1765-70, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20931217

RESUMO

AIM: To investigate the influence of alcohol consumption on the occurrence of open-globe injuries in adults. METHODS: A retrospective study was made of 100 consecutive patients (81 male, 19 female) with open-globe injuries. Of these patients, 18 exhibited alcohol intoxication (group Ai), and 82 exhibited no alcohol intoxication (group nAi). Investigated parameters were best-corrected visual acuity at day of admission and last examination (logMAR), type of injury according to BETT-classification, extraocular injuries, cause of injury, time and setting of injury, in relation to alcohol consumption and tested for statistical significance with Fisher's exact test or the Mann-Whitney U test, respectively. RESULTS: In group Ai, 83.3% of the patients were male, and in group nAi, 80.5%. Mean logMAR at day of admission was 1.06 ± 0.63 (20/250) in group Ai and 1.08 ± 0.59 (20/250) in group nAi. At last examination, mean logMAR in group Ai was 1.11 ± 0.59 (20/250), in group nAi 0.75 ± 0.60 (20/125). This difference was statistically significant (p = 0.02). In group Ai, significantly more ruptures according to BETT classification occurred (p = 0.05). In group Ai, significantly more additional extraocular injuries occurred compared to group nAi (38.9% versus 6.1%; p = 0.0009). In group Ai, the cause of injury was significantly more often glass (44.4% versus 2.4%; p = 0.0000), in group nAi the injury was more often directly or indirectly caused by tools (74.4% versus 33.3%; p = 0.001). In group Ai, the injury was significantly more often inflicted by others (50.0% versus 9.8%; p = 0.0003). The settings in which the injuries occurred were significantly more often the street in group Ai (44.4% versus 6.1%; p = 0.0002), in group nAi the garden or tool shed (31.7% versus 5.6%; p = 0.02) or the workplace (34.2 % versus 11.1 %; p = 0.04). In group Ai, the injuries occurred significantly more often at night (p = 0.0001) and on weekends (p = 0.0000). CONCLUSIONS: Open-globe eye injuries under alcohol intoxication are more often caused by a third party and have a worse prognosis. Open-globe injuries under alcohol intoxication occur in a different spatio-temporal setting and exhibit a more severe type of injury. Risk behavior combined with alcohol consumption therefore seems to be an independent factor for the incidence of open-globe eye injuries.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Ferimentos Oculares Penetrantes/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intoxicação Alcoólica/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
Chemistry ; 16(42): 12570-81, 2010 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-20967906

RESUMO

The dynamic solution equilibria between molecular Borromean rings (BRs) and Solomon knots (SKs), assembled from transition metal-templated macrocycles, consisting of exo-bidentate bipyridyl and endo-tridentate diiminopyridyl ligands, have been examined with respect to the choice of the metal template and reaction conditions employed in the synthesis of the metalated BRs, otherwise known as Borromeates. Three new Borromeates, their syntheses templated by Cu(II), Co(II), and Mn(II), have been characterized extensively (two by X-ray crystallography) to the extent that the metal centers in the assemblies have been shown to be distanced sufficiently from each other not to communicate. The solid-state structure of the Co(II)-Borromeate reveals that six MeOH molecules, arranged in a [O--H...O] hydrogen bonded, chair-like conformation, are located within its oxophilic central cavity. When a mixture of Cu(II) and Zn(II) is used as the source of templation, there exists a dynamic equilibrium, in MeOH at room temperature, between a mixed-metal BR and a SK, from which the latter has been fractionally crystallized. By employing appropriate synthetic protocols with Zn(II) or Cd(II) as the template, significant amounts of SKs are formed alongside BRs. Modified crystallization conditions resulted in the isolation of both an all-zinc BR and an all-zinc SK, crystals of which can be separated manually, leading to the full characterization of the all-zinc SK by (1)H NMR spectroscopy and X-ray crystallography. This doubly interlocked [2]catenate has been identified retrospectively in recorded spectra, where it was attributed previously to a Borromeate with a Zn(II) cation coordinated to the oxophilic interior walls of the ensemble. Interestingly, these Zn(II)-templated assemblies do not interconvert in MeOH at room temperature, indicating the significant influence of both the metal template and solvent on the solution equilibria. It would also appear that d(10) metal ions favor SK formation-no evidence of Cu(II)-, Co(II)-, or Mn(II)-templated SKs has been found, yet a 1:0.9 ratio of BR:SK has been identified by (1)H NMR spectroscopy when Cd(II) is used as the template.

9.
Eur J Gastroenterol Hepatol ; 18(11): 1217-25, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17033444

RESUMO

BACKGROUND: The Erlangen Active Simulator for Interventional Endoscopy (EASIE) using ex-vivo porcine organs was introduced in 1997. The present study should analyze whether repeated EASIE simulator training in endoscopic hemostasis led to superior performance compared with a traditionally educated group. The results were compared with a similar project in New York. METHODS: Thirty-five French GI fellows were enrolled. Baseline skills evaluation was performed in four disciplines (manual skills, injection/coagulation, clip application and variceal ligation) using the compactEASIE-simulator equipped with an upper gastrointestinal organ package for bleeding simulation. The same, translated evaluation forms (from the prior New York project) were used. Subsequently, fellows were randomized into group A (n=17, only clinical education) and group B (n=18, additional three simulator trainings). Group B was trained the next day and after 4 and 7 months by experts of the French Society of Gastrointestinal Endoscopy. Both groups performed routine and emergency endoscopies at their home hospitals during the study period. Both groups were re-evaluated blindly after 9 months. RESULTS: The learning curve for group B showed a significant improvement in all disciplines (P<0.004) whereas group A improved significantly in only two of four disciplines at blinded final evaluation (manual skills P=0.02, injection/coagulation P=0.013). The direct comparison of groups B and A at blinded final evaluation showed significantly superior ratings for group B in all disciplines (P<0.006) and significantly shorter performance times in two disciplines (P=0.016 each). The comparison with the similar 'New York project' revealed that preexisting differences in skills were adjusted by the training. CONCLUSION: Complementary trainings (three workshops in 7 months) in endoscopic hemostasis using the compactEASIE improved skills compared with a solely clinical education. The results of the 'New York project' were confirmed and benefits were independent from the medical educational system.


Assuntos
Instrução por Computador/métodos , Educação de Pós-Graduação em Medicina/métodos , Endoscopia Gastrointestinal/métodos , Hemostase Endoscópica/educação , Animais , Competência Clínica , Avaliação Educacional , França , Humanos , Modelos Animais , Estudos Prospectivos , Suínos , Estados Unidos
10.
J Glaucoma ; 15(4): 299-305, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16865006

RESUMO

PURPOSE: The aim of this study was to determine, whether the combination of morphologic data of the optic nerve head and visual field (VF) data would improve diagnosis of glaucoma, on the basis of the measurements alone. PATIENTS AND METHODS: Eighty-eight perimetric glaucomatous and 88 normal optic discs from the Erlangen Glaucoma Registry were matched for age. All normals and patients were examined in a standardized manner (Slitlamp biomicroscopy, gonioscopy, 24 h-applanation tonometry, automated VF testing, 15-degree optic disc stereographs, and Heidelberg Retina Tomograph (HRT)-scanning of the optic disc). The HRT variables were calculated in 4 optic disc sectors. All variables were calculated with the software's standard reference plane. To gain the same allocation of sectors as provided by the HRT software, the VF responses were averaged within 4 sectors. Classification results of these VF responses were compared with the summarized results within 4 sectors. Six different combinations of morphologic and VF data were used to assess their suitability to diagnose the disease. HRT measurements, and the standard output of the Octopus (HRT/PERI1), HRT measurements and the summarized sectors and their standard deviations (HRT/PERI2), HRT measurements, standard output of the octopus and the summarized sectors and their standard deviations (HRT/PERI1/PERI2), standard output of the Octopus (PERI1), summarized sectors of the Octopus and their standard deviations (PERI2) and HRT measurements. To assess the diagnostic value of the different data sets machine learning classifiers, stabilized linear discriminant analysis, classification trees, bagging, and double-bagging were applied. RESULTS: Combination of morphologic and VF data improved the automated classification rules. The accuracy to diagnose glaucoma just by VF and HRT indices was maximized for double-bagging using both diagnostic tools. An estimated misclassification probability of less than 0.07 could be achieved for the primary open angle glaucoma patients combining HRT and VF sectors by double bagging. So highest sensitivity was 95% and specificity 91%, achieved by double-bagging and combination of HRT, PERI1, and PERI2. CONCLUSIONS: The combination of optic disc measurements and VF data could not only improve glaucoma diagnosis in future, but could also help to find an objective way to diagnose glaucomatous optic atrophy. The limitation of the topographic relationship between structure and function is the individual variability of the optic disc morphology and the subjective variability of VF testing.


Assuntos
Glaucoma/diagnóstico , Disco Óptico/patologia , Tomografia/métodos , Testes de Campo Visual/métodos , Campos Visuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Índice de Gravidade de Doença
12.
Doc Ophthalmol ; 112(1): 1-11, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16633720

RESUMO

PURPOSE: Pattern stimulation is widely used to detect inner retinal dysfunction. In this work we describe a pattern stimulation technique with LEDs and compare the results with conventional methods. METHODS: PERG and VEP were derived from three normal subjects. Three different techniques were used to generate a checkerboard pattern reversal stimulus: a 70 Hz monitor, a Maxwellian-view system equipped with a Xenon-arc lamp and a mechanical mirror system, and a LED array (Roland Consult) consisting of 100 white LEDs. Two kinds of luminance (125 and 340 cd/m2) and four temporal frequencies (4, 8, 12 and 24 reversals per second) were studied on three healthy subjects. Additionally, a luminance tuning experiment (30, 60, 90, 125 and 340 cd/m2) was performed on one subject. RESULTS: Comparison of different stimulation techniques shows reproducible responses of PERG and VEP with all three methods. The LED array leads to slightly smaller amplitudes than both other techniques, which we ascribe to the design of the LED field. No difference of peak times or phases was noticed between different stimulation techniques. A luminance dependency of PERG and VEP is noticeable using stimulation with LED: with decreasing luminance we measured increasing peak times of PERG and VEP and decreasing amplitude of PERG. CONCLUSION: We conclude that central retinal stimulation with checkerboard pattern reversal is possible with LED. It gives comparable results to monitor and Maxwellian-view system.


Assuntos
Potenciais Evocados Visuais/fisiologia , Retina/fisiologia , Adulto , Eletrorretinografia/métodos , Desenho de Equipamento , Feminino , Humanos , Estimulação Luminosa/instrumentação , Valores de Referência , Reprodutibilidade dos Testes
13.
J Biol Chem ; 281(19): 13663-13671, 2006 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-16551634

RESUMO

Most Bcl-2 family members can localize to intracellular membranes via hydrophobic sequences within their C-terminal portion. We found that the C terminus of the anti-apoptotic family member A1 did not function as a membrane anchor. Instead, this stretch of the protein rendered A1 highly unstable by mediating its polyubiquitination and rapid proteasomal degradation. Moreover, the domain did not only function independently of its position within the A1 protein but when transferred could even destabilize unrelated proteins like enhanced green fluorescent protein and caspase-3. A1 was, however, much more stable in the presence of the Bcl-2 homology-only protein BimEL, suggesting that direct interaction of A1 with pro-apoptotic members of the Bcl-2 family strongly reduces its rate of turnover. We further show that the C-terminal end of A1 also contributes to the anti-apoptotic capacity of the protein. In conclusion, our data demonstrate that the C terminus serves a dual function by controlling the stability of A1 and by amplifying the capacity of the protein to protect cells against apoptosis.


Assuntos
Apoptose/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sequência de Aminoácidos , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Sobrevivência Celular , Células Cultivadas , Humanos , Membranas Intracelulares/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Antígenos de Histocompatibilidade Menor , Dados de Sequência Molecular , Transporte Proteico , Proteínas Proto-Oncogênicas/metabolismo
14.
Chemistry ; 12(1): 261-79, 2005 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-16320367

RESUMO

We report on the kinetics and ground-state thermodynamics associated with electrochemically driven molecular mechanical switching of three bistable [2]rotaxanes in acetonitrile solution, polymer electrolyte gels, and molecular-switch tunnel junctions (MSTJs). For all rotaxanes a pi-electron-deficient cyclobis(paraquat-p-phenylene) (CBPQT4+) ring component encircles one of two recognition sites within a dumbbell component. Two rotaxanes (RATTF4+ and RTTF4+) contain tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) recognition units, but different hydrophilic stoppers. For these rotaxanes, the CBPQT4+ ring encircles predominantly (>90 %) the TTF unit at equilibrium, and this equilibrium is relatively temperature independent. In the third rotaxane (RBPTTF4+), the TTF unit is replaced by a pi-extended analogue (a bispyrrolotetrathiafulvalene (BPTTF) unit), and the CBPQT4+ ring encircles almost equally both recognition sites at equilibrium. This equilibrium exhibits strong temperature dependence. These thermodynamic differences were rationalized by reference to binding constants obtained by isothermal titration calorimetry for the complexation of model guests by the CBPQT4+ host in acetonitrile. For all bistable rotaxanes, oxidation of the TTF (BPTTF) unit is accompanied by movement of the CBPQT4+ ring to the DNP site. Reduction back to TTF0 (BPTTF0) is followed by relaxation to the equilibrium distribution of translational isomers. The relaxation kinetics are strongly environmentally dependent, yet consistent with a single electromechanical-switching mechanism in acetonitrile, polymer electrolyte gels, and MSTJs. The ground-state equilibrium properties of all three bistable [2]rotaxanes were reflective of molecular structure in all environments. These results provide direct evidence for the control by molecular structure of the electronic properties exhibited by the MSTJs.

15.
J Org Chem ; 70(20): 7956-62, 2005 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-16277315

RESUMO

[Structure: See text] In addition to a parent zinc(II) Borromean ring (BR) complex, the preparation and characterization of two hexasubstituted BR complexes with either 4-acetoxymethylphenyl or 4-methylthiophenyl substituents associated in turn with all six pyridyl rings has been achieved convergently in good yields by appealing to the dynamic features of the reactions between primary amino groups in a preformed acyclic ligand and 2,6-diformylpyridine. Two molecules of the acyclic ligands react with two molecules of 2,6-diformylpyridine to form a cyclic [2 + 2] tetraimine in the presence of Zn(II) ions as templates in 2-propanol at 70 degrees C. The successful preparation of the two derivatives by convergent template-directed syntheses opens up opportunities to self-assemble, under equilibrium control, numerous nanoscale metallo-organic particles with potentially useful properties.

16.
Chem Commun (Camb) ; (27): 3394-6, 2005 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-15997275

RESUMO

Borohydride reduction of a Borromean Ring (BR) complex containing six zinc(II) ions and 12 imine bonds has resulted in its demetallation, producing a neutral BR compound and also its free macrocycle, following cleavage of at least one of the imine bonds in the ethanolic reaction mixture.

17.
Cancer ; 104(2): 395-404, 2005 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-15952189

RESUMO

BACKGROUND: The authors investigated whether microarray-based gene expression analysis of primary tumor biopsy material could be used to predict lymph node status in patients with colorectal carcinoma (CRC). Lymphatic metastasis strongly determines treatment algorithms in CRC. Currently, postoperative histology results are needed to determine lymph node status. Reliable preoperative information would be useful to advance treatment strategies. METHODS: In specimens from 66 patients with CRC from the Erlangen Registry of Colorectal Cancer, 41 shock-frozen samples of International Union Against Cancer (UICC) Stage I-II CRC and 25 samples of UICC Stage III CRC were microdissected manually, RNA was isolated, and gene chips (HG-U133A; Affymetrix) were hybridized. Prediction rates for lymphatic metastasis were calculated using conventional clinicopathologic parameters, gene expression data, and a combination of both. Prediction error, specificity, and sensitivity were analyzed using six different statistical classifiers. RESULTS: Analysis of conventional parameters produced a positive prediction rate that ranged between 53% and 61%, sensitivity of 42%, and specificity of 72%. Microarray prediction rates were between 62% and 67% for lymphatic metastasis. Specificity was between 76% and 83%, and sensitivity was between 38% and 48%, depending on the statistical procedure. The conventional estimates were improved by 9-12% when array data were added. CONCLUSIONS: Current data show that the prediction of lymphatic metastasis can be improved by gene expression profiling of the primary tumor biopsy, alone or in combination with conventional parameters. Gene expression profiling may become valuable increasingly in planning treatment for patients with CRC.


Assuntos
Neoplasias Colorretais/diagnóstico , Perfilação da Expressão Gênica , Metástase Linfática/diagnóstico , Análise em Microsséries , Técnicas de Diagnóstico Molecular , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
18.
Acc Chem Res ; 38(1): 1-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15654731

RESUMO

The molecular expression of topologically interesting structures represents a formidable challenge for synthetic chemists. The nontrivial link known as the Borromean rings has long been regarded as one of the most ambitious targets in this field. Of ancient provenance, this symbol comprises three interlocked rings in an inseparable union, but cut any one of the rings and the whole assembly unravels into three separate pieces. This Account delineates different strategies that can be applied to the formation of molecules possessing this distinctive topology, culminating with two successful syntheses of such compounds, thus cutting the Gordian knot of topological chemistry.


Assuntos
2,2'-Dipiridil/síntese química , DNA/química , Nanotecnologia , 2,2'-Dipiridil/análogos & derivados , Alcanos/química , Cristalografia por Raios X , Ciclização , Éteres/química , Ligantes , Modelos Moleculares , Conformação de Ácido Nucleico , Compostos de Amônio Quaternário/química
20.
Chemistry ; 10(24): 6558-64, 2004 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-15562404

RESUMO

The influences of different physical environments on the thermodynamics associated with one key step in the switching mechanism for a pair of bistable catenanes and a pair of bistable rotaxanes have been investigated systematically. The two bistable catenanes are comprised of a cyclobis(paraquat-p-phenylene) (CBPQT4+) ring, or its diazapyrenium-containing analogue, that are interlocked with a macrocyclic polyether component that incorporates the strong tetrathiafulvalene (TTF) donor unit and the weaker 1,5-dioxynaphthalene (DNP) donor unit. The two bistable rotaxanes are comprised of a CBPQT4+ ring, interlocked with a dumbbell component in which one incorporates TTF and DNP units, whereas the other incorporates a monopyrrolotetrathiafulvalene (MPTTF) donor and a DNP unit. Two consecutive cycles of a variable scan rate cyclic voltammogram (10-1500 mV s(-1)) performed on all of the bistable switches (approximately 1 mM) in MeCN electrolyte solutions (0.1 M tetrabutylammonium hexafluorophosphate) across a range of temperatures (258-303 K) were recorded in a temperature-controlled electrochemical cell. The second cycle showed different intensities of the two features that were observed in the first cycle when the cyclic voltammetry was recorded at fast scan rates and low temperatures. The first oxidation peak increases in intensity, concomitant with a decrease in the intensity of the second oxidation peak. This variation changed systematically with scan rate and temperature and has been assigned to the molecular mechanical movements within the catenanes and rotaxanes of the CBPQT4+ ring from the DNP to the TTF unit. The intensities of each peak were assigned to the populations of each co-conformation, and the scan-rate variation of each population was analyzed to obtain kinetic and thermodynamic data for the movement of the CBPQT4+ ring. The Gibbs free energy of activation at 298 K for the thermally activated movement was calculated to be 16.2 kcal mol(-1) for the rotaxane, and 16.7 and 19.2 kcal mol(-1) for the bipyridinium- and diazapyrenium-based bistable catenanes, respectively. These values differ from those obtained for the shuttling and circumrotational motions of degenerate rotaxanes and catenanes, respectively, indicating that the detailed chemical structure influences the rates of movement. In all cases, when the same bistable compounds were characterized in an electrolyte gel, the molecular mechanical motion slowed down significantly, concomitant with an increase in the activation barriers by more than 2 kcal mol(-1). Irrespective of the environment--solution, self-assembled monolayer or solid-state polymer gel--and of the molecular structure--rotaxane or catenane--a single and generic switching mechanism is observed for all bistable molecules.

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