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1.
Artigo em Inglês | MEDLINE | ID: mdl-31446545

RESUMO

PURPOSE: To investigate if the vaginal microbiome influences the IVF outcome. METHODS: Thirty-one patients undergoing assisted reproductive treatment (ART) with own or donated gametes and with cryotransfer of a single euploid blastocyst were recruited for this cohort study. Two vaginal samples were taken during the embryo transfer procedure, just before transferring the embryo. The V3 V4 region of 16S rRNA was used to analyze the vaginal microbiome, and the bioinformatic analysis was performed using QIIME2, Bioconductor Phyloseq, and MicrobiomeAnalyst packages. Alpha diversity was compared between groups according to the result of the pregnancy test. RESULTS: Fourteen (45.2%) patients did not and seventeen (54.8 %) did achieve pregnancy under ART. A greater index of alpha diversity was found in patients who did not achieve pregnancy comparing to those who did, although this difference was not significant (p = 0.088). In the analysis of beta diversity, no statistically significant differences were observed between groups established as per the pregnancy status. Samples from women who achieved pregnancy showed a greater presence of Lactobacillus spp. The cluster analysis identified two main clusters: the first encompassed the genera Lactobacillus, Gardnerella, Clostridium, Staphylococcus, and Dialister, and the second included all other genera. Women who achieved pregnancy were mainly detected microorganisms from the first cluster. CONCLUSIONS: The vaginal microbiome can influence the results of ART. The profiles dominated by Lactobacillus were associated with the achievement of pregnancy, and there was a relationship between the stability of the vaginal microbiome and the achievement of pregnancy.

2.
Toxins (Basel) ; 11(9)2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461913

RESUMO

Pamphobeteus verdolaga is a recently described Theraphosidae spider from the Andean region of Colombia. Previous reports partially characterized its venom profile. In this study, we conducted a detailed analysis that includes reversed-phase high-performance liquid chromatography (rp-HPLC), calcium influx assays, tandem mass spectrometry analysis (tMS/MS), and venom-gland transcriptome. rp-HPLC fractions of P. verdolaga venom showed activity on CaV2.2, CaV3.2, and NaV1.7 ion channels. Active fractions contained several peptides with molecular masses ranging from 3399.4 to 3839.6 Da. The tMS/MS analysis of active fraction displaying the strongest activity to inhibit calcium channels showed sequence fragments similar to one of the translated transcripts detected in the venom-gland transcriptome. The putative peptide of this translated transcript corresponded to a toxin, here named ω-theraphositoxin-Pv3a, a potential ion channel modulator toxin that is, in addition, very similar to other theraphositoxins affecting calcium channels (i.e., ω-theraphotoxin-Asp1a). Additionally, using this holistic approach, we found that P. verdolaga venom is an important source of disulfide-rich proteins expressing at least eight superfamilies.

3.
J Hazard Mater ; 371: 273-279, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30856437

RESUMO

The presence of levonorgestrel (LNG) in water bodies via direct discharge and human excretion has been reported worldwide, but its effects on the reproduction of aquatic species and humans are still unknown. Owing to its recalcitrant properties, LNG is not completely removed during wastewater treatment plants, and many species may be exposed to low traces of this compound from discharged effluents. Thus, in this study, a photocatalytic process for removing LNG along with screening of endocrine disruptor effects for risk assessment was applied. Although the removal rate of LNG by ultraviolet C (UV-C) radiation was >90%, reproductive toxicity testing using the BeWo cell line exposed to LNG and its degraded fraction showed the reduced production of basal human chorionic gonadotropin hormone (ß-hCG) by more than 73%, from 8.90 mIU mL-1 to <2.39 mIU mL-1, with both LNG and the degraded fraction. ß-hCG hormone has been implicated in the viability of trophoblastic cells during the first trimester of pregnancy; therefore, degraded fractions and waterborne LNG may affect reproduction in some aquatic species and humans with low level of exposure.

4.
Acta Crystallogr C Struct Chem ; 75(Pt 3): 359-371, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30833533

RESUMO

An efficient approach for the regioselective synthesis of (5-amino-3-methylsulfanyl-1H-1,2,4-triazol-1-yl)(2-fluorophenyl)methanone, C10H9FN4OS, (3), from the N-acylation of 3-amino-5-methylsulfanyl-1H-1,2,4-triazole, (1), with 2-fluorobenzoyl chloride has been developed. Heterocyclic amide (3) was used successfully as a strategic intermediate for the preparation of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide, C10H9FN4OS, (4), through a microwave-assisted Fries rearrangement under catalyst- and solvent-free conditions. Theoretical studies of the prototropy process of (1) and the Fries rearrangement of (3) to provide (4), involving the formation of an intimate ion pair as the key step, were carried out by density functional theory (DFT) calculations. The crystallographic analysis of the intermolecular interactions and the energy frameworks based on the effects of the different molecular conformations of (3) and (4) are described.

5.
Talanta ; 196: 395-401, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683383

RESUMO

A new probe for cyanide detection based on the integrated pyrazolo[1,5-a]pyrimidine-hemicyanine (PpHe) system was synthesized in an efficient and straightforward manner using microwave-assisted heating. Photophysical studies in a 100% aqueous solution demonstrated high cyanide selectivity and detection limits as low as 600 and 86 nmol L-1 for UV-vis absorption and fluorescence emission, respectively. Both values are well below 1900 nmol L-1, which is the maximum concentration permitted for drinking water by the World Health Organization (WHO). HRMS analysis and NMR experiments were performed to confirm the mechanism of detection based on blocking the ICT phenomenon via nucleophilic addition of CN- on the C˭N+ bond (iminium salt moiety) of the probe.

6.
Nutr Metab (Lond) ; 15: 38, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29991958

RESUMO

Background: Maternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysfunction. Using three selective diet formula including a High fat diet (HFD), Cafeteria (CAF) and High Sugar Diet (HSD), we hypothesized that maternal diets exposure program leads to selective changes in hypothalamic mitochondria fusion and fission dynamics in male offspring leading to metabolic dysfunction which is exacerbated by a second exposure after weaning. Methods: We exposed female Wistar rats to nutritional programming including Chow, HFD, CAF, or HSD for 9 weeks (pre-mating, mating, pregnancy and lactation) or to the same diets to offspring after weaning. We determined body weight, food intake and metabolic parameters in the offspring from 21 to 60 days old. Hypothalamus was dissected at 60 days old to determine mitochondria-ER interaction markers by mRNA expression and western blot and morphology by transmission electron microscopy (TEM). Mitochondrial-ER function was analyzed by confocal microscopy using hypothalamic cell line mHypoA-CLU192. Results: Maternal programming by HFD and CAF leads to failure in glucose, leptin and insulin sensitivity and fat accumulation. Additionally, HFD and CAF programming promote mitochondrial fusion by increasing the expression of MFN2 and decreasing DRP1, respectively. Further, TEM analysis confirms that CAF exposure after programing leads to an increase in mitochondria fusion and enhanced mitochondrial-ER interaction, which partially correlates with metabolic dysfunction and fat accumulation in the HFD and CAF groups. Finally, we identified that lipotoxic palmitic acid stimulus in hypothalamic cells increases Ca2+ overload into mitochondria matrix leading to mitochondrial dysfunction. Conclusions: We concluded that maternal programming by HFD induces hypothalamic mitochondria fusion, metabolic dysfunction and fat accumulation in male offspring, which is exacerbated by HFD or CAF exposure after weaning, potentially due to mitochondria calcium overflux.

7.
J Org Chem ; 83(18): 10887-10897, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30051714

RESUMO

A one-pot route for the regioselective synthesis of 3-formylpyrazolo[1,5- a]pyrimidines 4a-k in good yields through a microwave-assisted process is provided. The synthesis proceeds via a cyclocondensation reaction between ß-enaminones 1 with NH-3-aminopyrazoles 2, followed by formylation with an iminium salt moiety (Vilsmeyer-Haack reagent). These N-heteroaryl aldehydes 4 were successfully used as strategic intermediates for the preparation of novel functional fluorophores with yields up to 98%. The structures of the products obtained and regioselectivity of the reactions were determined on the basis of NMR measurements and X-ray diffraction analysis. Since pyrazolo[1,5- a]pyrimidines (PPs) 3 have shown an important fluorescence, photophysical properties of four 2-methylderivatives substituted at position 7 with different acceptor (A) or donor (D) groups were investigated. The compounds evaluated exhibited large Stokes shift in different solvents, but only the substituted p-methoxyphenyl (4-An) showed a strong fluorescence intensity with quantum yields up to 44% due to its greater ICT. Therefore, hybrid systems based on pyrazolo[1,5- a]pyrimidines could be used as fluorescent probes to detect biologically or environmentally relevant species.

8.
Toxins (Basel) ; 10(2)2018 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-29462980

RESUMO

The Colombian rattlesnake Crotalus durissus cumanensis is distributed in three geographic zones of the country: the Atlantic Coast, the upper valley of the Magdalena River, and the eastern plains of the Colombian Orinoquía. Its venom induces neurological symptoms, such as eyelid ptosis, myasthenic facies, and paralysis of the respiratory muscles, which can lead to death. Identification and analysis of C. d. cumanensis showed nine groups of proteins responsible for the neurotoxic effect, of which the crotoxin complex was the most abundant (64.71%). Immunorecognition tests of C. d. cumanensis showed that the use of a commercial antivenom manufactured in Mexico resulted in immunoreactivity.

9.
Acta Crystallogr C Struct Chem ; 74(Pt 1): 82-93, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29303501

RESUMO

An efficent access to a series of N-(pyrrol-2-yl)amines, namely (E)-1-tert-butyl-5-[(4-chlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, C16H16ClN3, (7a), (E)-1-tert-butyl-5-[(2,4-dichlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, C16H15Cl2N3, (7b), (E)-1-tert-butyl-5-[(pyridin-4-ylmethylene)amino]-1H-pyrrole-3-carbonitrile, C15H16N4, (7c), 1-tert-butyl-5-[(4-chlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, C16H18ClN3, (8a), and 1-tert-butyl-5-[(2,4-dichlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, C16H17Cl2N3, (8b), by a two-step synthesis sequence (solvent-free condensation and reduction) starting from 5-amino-1-tert-butyl-1H-pyrrole-3-carbonitrile is described. The syntheses proceed via isolated N-(pyrrol-2-yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P-1 from compound (7a) to (8a) and P21/c to P-1 from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)-H...N hydrogen bonds. However, in the case of (7a)-(7c), C-H...Cl interactions are strong enough to help in the three-dimensional architecture, as observed in Hirshfeld surface maps.

10.
J Org Chem ; 82(23): 12674-12681, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29125772

RESUMO

A novel series of fully substituted pyrazolo[3,4-b]pyridines 4 has been prepared in a regioselective manner by the microwave-assisted reaction between N-substituted 5-aminopyrazoles 1 and 3-(3-oxo-2-benzofuran-1(3H)-ylidene)pentane-2,4-dione (2). This is the second reported example of a cyclocondensation reaction using substrate 2 as a 1,3-bis-electrophilic reagent. Remarkably, this synthesis offers functionalized products with acetyl and carboxyl groups in one step, in good yields, and with short reaction times. Additionally, the cyclization intermediate 3 was isolated, allowing us to postulate a mechanism for this reaction, which is initiated via isobenzofuranone ring opening of 2 in a Michael-type reaction. The structures of the products and regioselectivity of the reactions were determined on the basis of NMR measurements and X-ray diffraction. For this new reaction using substrate 2, the optimal reaction conditions and its scope were investigated.

12.
Rev. Investig. Salud. Univ. Boyacá ; 4(1): 16-31, 2017. ilus, graf, tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-910750

RESUMO

Introducción. Los venenos de serpientes representan una fuente importante de proteínas y péptidos, los cuales exhiben diversas actividades biológicas, tales como antibacterianas, antiparasitarias, antivi-rales, antitumorales, antifúngicas y contra la agregación plaquetaria, entre otras.Las fosfolipasas A2 presentes en los venenos de serpientes son las proteínas más estudiadas en estos modelos. Se ha demostrado que las fosfolipasas A2, activas e inactivas, poseen actividad catalítica contra células tumorales. Objetivo. Aislar, purificar y caracterizar la fosfolipasa A2 del veneno de Crotalus durissus cumanensis para evaluar su actividad antitumoral in vitro. Materiales y métodos. El aislamiento, la purificación y la identificación de la crotoxina B se hizo mediante la cromatografía de exclusión molecular, la cromatografía líquida de alto rendimiento de fase inversa (Reversed Phase High-Performance Liquid Chromatography, RP-HPLC) y la espectrometría de masas. El efecto citotóxico sobre células tumorales (K562) y células normales (células mononucleares de sangre periférica) se determinó utilizando la técnica de MTT. Resultados. La separación y posterior identificación de la crotoxina B del veneno de C. d. cumanensis de Colombia, permitieron evidenciar que esta fosfolipasa A2 posee efecto citotóxico sobre las células mononucleares de sangre periférica con una dosis de 18,23 ± 0,57 µg/ml, mientras que, para las células K562, fue de 2,34 ± 0,199 µg/ml. Conclusiones. Los resultados sugieren la posibilidad de utilizar la crotoxina B aislada del veneno de C. d. cumanensis como un posible recurso terapéutico para su aplicación en humanos.


Introduction. Snake venoms are an important source of proteins and peptides, which display various biological activities such as antibacterial, antiparasitic, antiviral, antitumor, antifungal and against platelet aggregation, among others.Phospholipases A2 present in snake venoms are the most studied proteins in these models. Active and inactive A2 phospholipases have been shown to possess catalytic activity against tumor cells. Objective. To isolate, purify and characterize the phospholipase A2 of the venom of Crotalus durissus cumanensis to evaluate its in vitro antitumor activity. Materials and methods. Isolation, purification and identification of crotoxin B was done with Size Exclusion Chromatography, Reversed Phase High-Performance Liquid Chromatography, RP-HPLC, and Mass Spectrometry. The cytotoxic effect on tumor cells (K562) and normal cells (peripheral blood mononuclear cells) was determined using the MTT technique. Results. The separation and subsequent identification of crotoxin B, found in the venom of C. d. cumanensis from Colombia, showed that this phospholipase A2 has a cytotoxic effect on peripheral blood mononuclear cells at a dose of 18.23 ± 0.57 µg / ml, whereas for K562 cells, it was 2.34 ± 0.199 µg/ml Conclusions. The results suggest the use of crotoxin B, isolated from the venom of C. d. cumanensis, as a possible therapeutic resource for human application.


Introdução. Os venenos da serpentes constituem uma importante fonte de proteínas e péptidos, os quais exibem várias actividades biológicas, tais como agentes antibacterianos, antiparasitárias, antivi-rais, antitumorais, antifúngicas e contra a agregação de plaquetas, entre outros. As fosfolipases A2 presentes no veneno da serpentes são as proteínas mais estudadas nestes modelos. Tem sido demostrado que as fosfolipases A2, activas e inactivas, possuem actividade catalítica contra células tumorais. Objetivo. Isolar, purificar e caracterizar a fosfolipase A2 do veneno da Crotalus durissus cumanensis para avaliar a sua actividade anti-umoral in vitro. Materiais e métodos. O isolamento, a purificação e identificação da crotoxina B foi realizada por cromatografia de exclusão molecular, cromatografia líquida de alta eficiência de fase reversa (Reversed Phase High-Performance Liquid Chromatography, RP-HPLC) e espectrometria de massa. O efeito cito-tóxico sobre células tumorais (K562) e células normais (células mononucleares do sangue periférico) foi determinada usando a técnica de MTT. Resultados. A Separação e subsequente identificação da crotoxina B do veneno da C. d. cumanensis da Colômbia, permitiu constatar que esta fosfolipase A2 tem um efeito citotóxico em células mono-nucleares de sangue periférico, com uma dose de 18,23 ± 0,57 µg/ ml, enquanto que para as células K562, foi 2,34 ± 0,199 ug/ml. Conclusões. Os resultados sugerem a possibilidade de utilizar crotoxina B isolada a partir do veneno da C. d. cumanensis como recurso para o potencial uso terapêutico em humanos.


Assuntos
Animais , Crotalus , Crotoxina , Citotoxicidade Imunológica , Fosfolipases A2
13.
J Org Chem ; 81(24): 12364-12373, 2016 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-27978735

RESUMO

A microwave-assisted approach for the regioselective synthesis of functionalized 6-(aryldiazenyl)pyrazolo[1,5-a]pyrimidin-7-amines from the cyclization of 3-oxo-2-(2-arylhydrazinylidene)butanenitriles with 5-amino-1H-pyrazoles under solvent-free conditions has been developed. This methodology was distinguished by its broad substrate scope, operational simplicity, high atom economy, and high-yielding without requiring chromatographic purification. In addition, an efficient and versatile palladium-catalyzed reductive azo cleavage is disclosed for the synthesis of diverse heteroaromatic 1,2-diamines, a valuable synthetic building block to develop new fused heteroaromatic systems. As synthetic example, several substituted pyrazolo[5,1-b]purines were synthesized in yields up to 96% by using microwave irradiation in the cyclocondensation of these 1,2-diamines with orthoesters.

14.
JAMA ; 316(10): 1083-92, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27623462

RESUMO

IMPORTANCE: Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing transcatheter aortic valve replacement (TAVR). OBJECTIVE: To determine the associated factors, clinical characteristics, and outcomes of patients who had infective endocarditis after TAVR. DESIGN, SETTING, AND PARTICIPANTS: The Infectious Endocarditis after TAVR International Registry included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015. EXPOSURE: Transcatheter aortic valve replacement for incidence of infective endocarditis and infective endocarditis for in-hospital mortality. MAIN OUTCOMES AND MEASURES: Infective endocarditis and in-hospital mortality after infective endocarditis. RESULTS: A total of 250 cases of infective endocarditis occurred in 20 006 patients after TAVR (incidence, 1.1% per person-year; 95% CI, 1.1%-1.4%; median age, 80 years; 64% men). Median time from TAVR to infective endocarditis was 5.3 months (interquartile range [IQR], 1.5-13.4 months). The characteristics associated with higher risk of progressing to infective endocarditis after TAVR was younger age (78.9 years vs 81.8 years; hazard ratio [HR], 0.97 per year; 95% CI, 0.94-0.99), male sex (62.0% vs 49.7%; HR, 1.69; 95% CI, 1.13-2.52), diabetes mellitus (41.7% vs 30.0%; HR, 1.52; 95% CI, 1.02-2.29), and moderate to severe aortic regurgitation (22.4% vs 14.7%; HR, 2.05; 95% CI, 1.28-3.28). Health care-associated infective endocarditis was present in 52.8% (95% CI, 46.6%-59.0%) of patients. Enterococci species and Staphylococcus aureus were the most frequently isolated microorganisms (24.6%; 95% CI, 19.1%-30.1% and 23.3%; 95% CI, 17.9%-28.7%, respectively). The in-hospital mortality rate was 36% (95% CI, 30.0%-41.9%; 90 deaths; 160 survivors), and surgery was performed in 14.8% (95% CI, 10.4%-19.2%) of patients during the infective endocarditis episode. In-hospital mortality was associated with a higher logistic EuroSCORE (23.1% vs 18.6%; odds ratio [OR], 1.03 per 1% increase; 95% CI, 1.00-1.05), heart failure (59.3% vs 23.7%; OR, 3.36; 95% CI, 1.74-6.45), and acute kidney injury (67.4% vs 31.6%; OR, 2.70; 95% CI, 1.42-5.11). The 2-year mortality rate was 66.7% (95% CI, 59.0%-74.2%; 132 deaths; 115 survivors). CONCLUSIONS AND RELEVANCE: Among patients undergoing TAVR, younger age, male sex, history of diabetes mellitus, and moderate to severe residual aortic regurgitation were significantly associated with an increased risk of infective endocarditis. Patients who developed endocarditis had high rates of in-hospital mortality and 2-year mortality.


Assuntos
Endocardite Bacteriana/epidemiologia , Endocardite/etiologia , Mortalidade Hospitalar/tendências , Substituição da Valva Aórtica Transcateter/efeitos adversos , Fatores Etários , Idoso , Endocardite Bacteriana/etiologia , Feminino , Seguimentos , Insuficiência Cardíaca , Humanos , Masculino , Razão de Chances , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/etiologia , Staphylococcus aureus , Resultado do Tratamento
15.
Acta Trop ; 153: 70-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26477848

RESUMO

We report the first biochemical, biological, pharmacological and partial proteomic characterization studies of the Opisthancanthus elatus venom (Gervais, 1844) from Colombia. The Reverse Phase High-Performance Liquid Chromatography venom profile showed 28 main well-defined peaks, most eluting between 20 and 45min (18-30% of acetonitrile, respectively). High-resolution mass analysis indicates the presence of 106 components ranging from 806.59742Da to 16849.4139Da. O. elatus venom showed hemolytic activity and hydrolyzed the specific substrate BapNa suggesting the presence of proteins with serine-protease activity. Collected RP-HPLC fractions eluting at 52.6, 55.5, 55.8, 56.2, and 63.9min (PLA2 region between 33 and 40% of acetonitrile), showed hemolytic activity and hydrolyzed the synthetic substrate 4-nitro-3-octanoyloxy-benzoic acid, indicating the presence of compounds with phospholipases A2 activity. These RP-HPLC fractions, showed molecular masses values up to 13978.19546Da, corroborating the possible presence of the mentioned enzymes. Tryptic digestion and MS/MS analysis showed the presence of a phospholipase like fragment, similar to on described in other Opisthacanthus genus studies. No coagulant activity was observed. No larvicidal or antimicrobial activity was observed at concentrations evaluated. Lethal and toxic activity is expected at doses above 100mg/kg, no neurotoxic effects were detected at lower doses. In conclusion, O. elatus exhibits a venom with a predominant phospholipase A2 activity than thought; mammal's neurotoxic activity is expected above the 100mg/kg, which is very high compared to the venom from other neurotoxic scorpions.


Assuntos
Hemolíticos/toxicidade , Neurotoxinas/toxicidade , Venenos de Escorpião/química , Venenos de Escorpião/toxicidade , Escorpiões/química , Animais , Cromatografia Líquida de Alta Pressão , Colômbia , Peso Molecular , Espectrometria de Massas em Tandem
16.
Europace ; 18(6): 836-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26705558

RESUMO

AIMS: Use of cardiac pacing devices has grown in recent years. Our aim was to evaluate changes in epidemiology and clinical features of infective endocarditis (IE) involving pacemaker devices in a large series of IE over the last 27 years (1987-2013). METHODS AND RESULTS: From 1987 to December 2013, 413 consecutive IE cases were diagnosed in our hospital. During this period, 7424 pacemaker devices were implanted (6917 pacemakers, 239 implantable cardiac defibrillators, 158 resynchronization devices, and 110 resynchronization/defibrillator devices). All consecutive cases of IE on pacemaker devices were included and analysed. Infective endocarditis on pacemaker devices represented 6.1% of all endocarditis cases (25 patients), affecting 3.6/1000 of all implanted pacemakers. Its proportion increased from 1.25% of all endocarditis in 1987-1993 to 4.08% in 1994-2000, 7.69% in 2001-2007 and 9.32% in 2008-2013 (P < 0.01). Its incidence also increased from 1.4/1000 of all pacemaker implants in the period of 1987-1993 to 2.5/1000 in 1994-2000, 3.3/1000 in 2001-2007 and 4.5/1000 implanted devices in 2008-2013 (P < 0.05). Mean age of patients was 68 years, and 80% were male. Causative microorganisms predominantly were Staphylococci (84%: Staphylococcus aureus 48%, Staphylococcus epidermidis 36%). Rate of severe complications was high: persistent sepsis in 60% of cases, heart failure in 20%, and stroke in 12%. Device was removed in 19 patients (76%), mostly by surgery (18 of the 19 cases). Early mortality was 24% (33% of medically, 21% of surgically treated patients, P = 0.82). CONCLUSION: Infective endocarditis on pacemaker devices has shown an increasing incidence during the past decades, representing almost 10% of all IE in the last 6 years. This is a severe disease, with a high rate of severe complications and requiring removal of device in most cases. In spite of therapy, early mortality is high.


Assuntos
Desfibriladores Implantáveis/efeitos adversos , Endocardite Bacteriana/epidemiologia , Insuficiência Cardíaca/epidemiologia , Marca-Passo Artificial/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Desfibriladores Implantáveis/estatística & dados numéricos , Remoção de Dispositivo/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial/estatística & dados numéricos , Espanha
17.
JAMA ; 316(10): 1083-1092, 2016.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-34665

RESUMO

IMPORTANCE: Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing transcatheter aortic valve replacement (TAVR). OBJECTIVE: To determine the associated factors, clinical characteristics, and outcomes of patients who had infective endocarditis after TAVR. DESIGN, SETTING, AND PARTICIPANTS: The Infectious Endocarditis after TAVR International Registry included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015. EXPOSURE: Transcatheter aortic valve replacement for incidence of infective endocarditis and infective endocarditis for in-hospital mortality. MAIN OUTCOMES AND MEASURES: Infective endocarditis and in-hospital mortality after infective endocarditis. RESULTS: A total of 250 cases of infective endocarditis occurred in 20 006 patients after TAVR (incidence, 1.1% per person-year; 95% CI, 1.1%-1.4%; median age, 80 years; 64% men). Median time from TAVR to infective endocarditis was 5.3 months (interquartile range [IQR], 1.5-13.4 months). The characteristics associated with higher risk of progressing to infective endocarditis after TAVR was younger age (78.9 years vs 81.8 years; hazard ratio [HR], 0.97 per year; 95% CI, 0.94-0.99), male sex (62.0% vs 49.7%; HR, 1.69; 95% CI, 1.13-2.52), diabetes mellitus (41.7% vs 30.0%; HR, 1.52; 95% CI, 1.02-2.29), and moderate to severe aortic regurgitation (22.4% vs 14.7%; HR, 2.05; 95% CI, 1.28-3.28). Health care-associated infective endocarditis was present in 52.8% (95% CI, 46.6%-59.0%) of patients...(AU)


Assuntos
Endocardite , Substituição da Valva Aórtica Transcateter , Endocardite Bacteriana
19.
J Org Chem ; 80(19): 9767-73, 2015 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-26340342

RESUMO

Pseudo-three-component reactions are described for the conversion of simple N-aryl imines into 1,2-dihydroisoquinoline-type products. The approach relies on a regioselective cascade reaction involving two equivalents of the aryne component iteratively as a dienophile and as an electrophile. Some examples of related, more complex pseudo-four-component cascade processes are also reported.

20.
Org Lett ; 17(13): 3374-7, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26086988

RESUMO

Two cascade reactions have been developed for the time-efficient preparation of a variety of functionalized aromatic heterocyclic products exhibiting an isoquinoline core. The approach is based on the normal electron-demand [4 + 2] aza-Diels-Alder cycloaddition of electron-rich N-aryl imines with arynes. Using this strategy, an expeditious total synthesis of the naturally occurring benzo[c]phenanthridine alkaloid nornitidine was achieved.


Assuntos
Alcaloides/síntese química , Benzo(a)Antracenos/síntese química , Isoquinolinas/síntese química , Alcaloides/química , Benzo(a)Antracenos/química , Catálise , Ciclização , Reação de Cicloadição , Iminas/síntese química , Isoquinolinas/química , Estrutura Molecular , Estereoisomerismo
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