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1.
Infectio ; 23(supl.1): 73-91, dic. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-984511

RESUMO

Resumen: Los pacientes con infección por VIH tienen una mayor incidencia de eventos cardiovasculares en comparación con la población general; los factores que contribuyen al incremento del riesgo de eventos cardiovasculares son la prevalencia de factores de riesgo cardiovascular tradicionales (FRCV), la infección por VIH que condiciona tanto un proceso de inflamación crónica como alteración de la función endotelial y la exposición a los antirretrovirales. Los factores que deben ser objeto de intervención son los FRCV tradicionales, en especial la alta tasa de fumadores entre este grupo de pacientes, la tamización y tratamiento de HTA, el síndrome metabólico y el acceso temprano a la terapia antirretroviral con medicamentos con mayor perfil de seguridad . Esta guía pretende proveer información y recomendaciones en el ámbito nacional acerca de la relación entre la infección por VIH/SIDA (Síndrome de Inmunodeficiencia Adquirida), uso de antirretrovirales y riesgo cardiovascular.


Abstract: Patients with VIH infection have greater risk for cardiovascular diseases compared to general population. Risk factors that increase the frequency of cardiovascular events are: presence of cardiovascular traditional risk factors, chronic inflammation by HIV that impairs endothelial function and the exposure to antiretrovirals. The factors that should be the target for intervention are the traditional know cardiovascular factors such, especially high rate of smokers, screening and treatment for hypertension, metabolic syndrome and early access to HAART. The present guidelines provides information about the use of antiretrovirals in patients with HIV and its relation with cardiovascular risk.

2.
ACS Nano ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31491079

RESUMO

Controlled substitutional doping of two-dimensional transition-metal dichalcogenides (TMDs) is of fundamental importance for their applications in electronics and optoelectronics. However, achieving p-type conductivity in MoS2 and WS2 is challenging because of their natural tendency to form n-type vacancy defects. Here, we report versatile growth of p-type monolayer WS2 by liquid-phase mixing of a host tungsten source and niobium dopant. We show that crystallites of WS2 with different concentrations of substitutionally doped Nb up to 1014 cm-2 can be grown by reacting solution-deposited precursor film with sulfur vapor at 850 °C, reflecting the good miscibility of the precursors in the liquid phase. Atomic-resolution characterization with aberration-corrected scanning transmission electron microscopy reveals that the Nb concentration along the outer edge region of the flakes increases consistently with the molar concentration of Nb in the precursor solution. We further demonstrate that ambipolar field-effect transistors can be fabricated based on Nb-doped monolayer WS2.

3.
PLoS One ; 14(8): e0221436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31442265

RESUMO

Sexual selection promotes the evolution of conspicuous animal ornaments. To evolve as signals, these traits must reliably express the "quality" of the bearer, an indicator of individual fitness. Direct estimates of individual fitness may include the contribution of longevity and fecundity. However, evidence of a correlation between the level of signal expression and these two fitness components are scarce, at least among vertebrates. Relative fitness is difficult to assess in the wild as age at death and extra-pair paternity rates are often unknown. Here, in captive male red-legged partridges, we show that carotenoid-based ornament expression, i.e., redness of the bill and eye rings, at the beginning of reproductive life predicts both longevity (1-7 years) and lifetime breeding output (offspring number and hatching success). The recently proposed link between the individual capacity to produce red (keto) carotenoid pigments and the efficiency of cell respiration could, ultimately, explain the correlation with lifespan and, indirectly, fecundity. Nonetheless, in males of avian species, carotenoid-based coloration in bare parts is also partially controlled by testosterone. We also manipulated androgen levels throughout life by treating males with testosterone or antiandrogen compounds. Treatments caused correlations between signal levels and both fitness components to disappear, thus making the signals unreliable. This suggests that the evolution of carotenoid-based sexual signals requires a tightly-controlled steroid metabolism.

4.
J Med Case Rep ; 13(1): 242, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31378205

RESUMO

BACKGROUND: Medullary ischemia secondary to surgical procedures of the infrarenal aorta is an infrequent and mostly devastating complication of this procedure, and its nonspecific clinical presentation makes it difficult to promptly diagnose. Prevention measures for this complication are not yet clear; therefore, the need for anticoagulant and/or antiplatelet therapy is discussed. CASE PRESENTATION: This paper reports a case of a 69-year-old Hispanic man presenting with sudden pain and signs of ischemia on his left lower extremity 8 weeks after endovascular repair with endoprosthesis of an infrarenal aorta and left iliac aneurysm. The patient was admitted to the emergency room, where an extensive arterial thrombosis compromising the right iliac and femoral arteries was diagnosed. Dual anticoagulation and antiplatelet therapies were initiated, and therapeutic ranges were achieved. Nonetheless, the patient presented medullary ischemia by microembolization diagnosed by contrast-enhanced magnetic resonance imaging, with unsatisfactory evolution of an intracranial hemorrhagic event without documented excessive anticoagulation. The patient developed permanent pure motor deficit of his lower extremities, absence of sphincter control, and mild cognitive impairment. CONCLUSIONS: This is a complex and extremely rare case. It is important to continue with clinical investigations that give more clarity about the onset of anticoagulation, antiplatelet therapy, and management of dual schemes to decrease the risk of complications in this type of surgical procedure.

5.
Am J Transplant ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31265753

RESUMO

Combining simultaneously lung and liver procurement in controlled donation after circulatory death (cDCD) using normothermic abdominal perfusion (NRP) for abdominal grafts and cooling and rapid recovery technique (RR) for the lungs increases the complexity of the procurement procedure and might injure the grafts. A total of 19 cDCDs from two centers using this combined procedure were evaluated, and 16 liver and 21 lung transplantations were performed. As controls, 34 donors after brain death (DBDs) were included (29 liver and 41 lung transplantations were performed). Two cDCD liver recipients developed primary nonfunction (12.5%). No cases of ischemic cholangiopathy were observed among cDCD recipients. The 1-year and 2-year liver recipients survival was 87.5% and 87.5% for the cDCD group, and 96% and 84.5% for the DBD group, respectively (P = .496). The 1-year and 2-year lung recipients survival was 84% and 84% for the cDCD group and 90% and 90% for the DBD group, respectively (P = .577). This is the largest experience ever reported in cDCD with the use of NRP combined with RR of the lungs. This combined method offers an outstanding recovery rate and liver and lung recipients survival comparable with those transplanted with DBDs. Further studies are needed to confirm our findings.

6.
J Struct Biol ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31330179

RESUMO

Sticholysin I (StI) is a toxin produced by the sea anemone Stichodactyla helianthus and belonging to the actinoporins family. Upon binding to sphingomyelin-containing membranes StI forms oligomeric pores, thereby leading to cell death. According to recent controversial experimental evidences, the pore architecture of actinoporins is a debated topic. Here, we investigated the StI topology in membranes by site-directed spin labeling and electron paramagnetic resonance spectroscopy. The results reveal that StI in membrane exhibits an oligomeric architecture with heterogeneous stoichiometry of predominantly eight or nine protomers, according to the available structural models. The StI topology resembles the conic pore structure reported for the actinoporin fragaceatoxin C. Our data show that StI coexists in two membrane-associated conformations, with the N-terminal segment either attached to the protein core or inserted in the membrane forming the pore. This finding suggests a 'pre-pore' to 'pore' transition determined by a conformational change that detaches the N-terminal segment.

7.
Neurosurg Focus ; 47(1): E20, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31261125

RESUMO

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.

8.
Neurosurgery ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31298301

RESUMO

BACKGROUND: Hemorrhagic complications are a major concern for aneurysmal subarachnoid hemorrhage patients treated with stenting or stent-assisted coiling and undergoing additional procedures such as shunting, ventriculostomy placement, and craniotomies/craniectomies. OBJECTIVE: To assess the safety and efficacy of using a continuous infusion of tirofiban as a monoantiplatelet therapy in the management of ruptured aneurysms in the setting of either stent-assisted coiling (SAC) or flow diversion devices (FDD) in patients requiring either an external ventricular drain (EVD) or ventriculoperitoneal shunt (VPS). METHODS: Aneurysmal subarachnoid hemorrhage (aSAH) patients between July 2017 and September 2018 who were treated with SAC or FDD were started on a continuous tirofiban infusion protocol (0.10 µg/kg/min) with no preceding loading dose as a monoantiplatelet therapy. Safety analysis was performed retrospectively to assess the complication rate, hemorrhagic rate, and rate of ischemic events. There were no hemorrhages related to the VPS surgery. RESULTS: Nineteen subjects were included in the series. The patients received a total of 25 procedures that included 19 EVDs and 6 VPSs. Two patients (8.3%) developed small asymptomatic track hemorrhages after EVD placement. One patient developed a large retroperitoneal hemorrhage due to renal artery branch injury during procedure, and another patient developed an idiosyncratic transient thrombocytopenia which resolved after stopping the medication. One patient (4%) developed a transient ischemic attack, which resolved after a bolus of tirofiban. CONCLUSION: Our study suggests that long-term use of intravenous tirofiban monotherapy in aSAH subjects for endovascular SAC or FDD is safe in the perioperative setting.

9.
Biochim Biophys Acta Biomembr ; 1861(10): 182996, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150634

RESUMO

Genetic and environmental factors may contribute to high blood pressure, which is termed essential hypertension. Hypertension is a major independent risk factor for cardiovascular disease, stroke and renal failure; thus, elucidation of the etiopathology of hypertension merits further research. We recently reported that the platelets and neutrophils of patients with hypertension exhibit altered biophysical characteristics. In the present study, we assessed whether the major structural elements of erythrocyte plasma membranes are altered in individuals with hypertension. We compared the phospholipid (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingosine) and cholesterol contents of erythrocytes from individuals with hypertension (HTN) and healthy individuals (HI) using LC/MS-MS. HTN erythrocytes contained higher phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine contents and a lower cholesterol content than HI erythrocytes. Furthermore, atomic force microscopy revealed important morphological changes in HTN erythrocytes, which reflected the increased membrane fragility and fluidity and higher levels of oxidative stress observed in HTN erythrocytes using spectrophotofluorometry, flow cytometry and spectrometry. This study reveals that alterations to the lipid contents of erythrocyte plasma membranes occur in hypertension, and these alterations in lipid composition result in morphological and physiological abnormalities that modify the dynamic properties of erythrocytes and contribute to the pathophysiology of hypertension.

10.
Can J Anaesth ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165457

RESUMO

PURPOSE: Postoperative pulmonary complications may be better reduced by reversal of neuromuscular block with sugammadex than by reversal with neostigmine because the incidence of residual block after sugammadex application is lower and diaphragm function is less impaired than after neostigmine administration. The aim of the study was to compare the effect of reversal of neuromuscular block with sugammadex or neostigmine on lung function after major abdominal surgery. METHODS: One hundred and thirty adults scheduled for major abdominal surgery under combined general and epidural anesthesia were randomly allocated to receive 40 µg of neostigmine or 4 mg·kg-1 of sugammadex to reverse neuromuscular block. Two blinded researchers performed spirometry and lung ultrasound before the surgery, as well as 1 hr and 24 hr postoperatively. Differences in mean changes from baseline were analyzed with repeated measures analysis of variance. Forced vital capacity (FVC) loss one hour after surgery was the main outcome. Secondary outcomes were differences in rate and size of atelectasis one hour and 24 hr after surgery. RESULTS: One hundred twenty-six patients were included in the main analysis. In the neostigmine group (n = 64), mean (95% confidence interval [95% CI]) reduction in FVC after one hour was 0.5 (0.4 to 0.6) L. In the sugammadex group (n = 62), the mean (95% CI) reduction in FVC during the first hour was 0.5 (95% CI, 0.3 to 0.6) L. Thirty-nine percent of patients in the neostigmine group and 29% in the sugammadex group had visible atelectasis. Median [interquartile range (IQR)] atelectasis area was 9.7 [4.7-13.1] cm2 and 6.8 [3.6-12.5] cm2, respectively. CONCLUSION: We found no differences in pulmonary function in patients reversed with sugammadex or neostigmine in a high-risk population. TRIAL REGISTRATION: EudraCT 2014-005156-26; registered 27 May, 2015.

11.
PLoS One ; 14(5): e0216893, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120919

RESUMO

CD4+ effector/memory T cells (Tem) represent a leading edge of the adaptive immune system responsible for protecting the body from infection, cancer, and other damaging processes. However, a subset of Tem cells with low expression of CD45Rb (RbLoTem) has been shown to suppress inflammation despite their effector surface phenotype and the lack of FoxP3 expression, the canonical transcription factor found in most regulatory T cells. In this report, we show that RbLoTem cells can suppress inflammation by influencing Treg behavior. Co-culturing activated RbLoTem and Tregs induced high expression of IL-10 in vitro, and conditioned media from RbLoTem cells induced IL-10 expression in FoxP3+ Tregs in vitro and in vivo, indicating that RbLoTem cells communicate with Tregs in a cell-contact independent fashion. Transcriptomic and multi-analyte Luminex data identified both IL-2 and IL-4 as potential mediators of RbLoTem-Treg communication, and antibody-mediated neutralization of either IL-4 or CD124 (IL-4Rα) prevented IL-10 induction in Tregs. Moreover, isolated Tregs cultured with recombinant IL-2 and IL-4 strongly induced IL-10 production. Using house dust mite (HDM)-induced airway inflammation as a model, we confirmed that the in vivo suppressive activity of RbLoTem cells was lost in IL-4-ablated RbLoTem cells. These data support a model in which RbLoTem cells communicate with Tregs using a combination of IL-2 and IL-4 to induce robust expression of IL-10 and suppression of inflammation.

12.
Immunol Lett ; 211: 33-40, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059733

RESUMO

The HIV-1 envelope protein (Env) mediates the membrane fusion process allowing virus entry to target cells and the efficiency to induce membrane fusion is an important determinant of HIV-1 pathogenicity. In addition to virus receptors, other adhesion/signaling molecules on infected and target cells and virus particles can enhance fusion. The presence of antilymphocyte autoantibodies (ALA) in HIV patients' serum suggests that they may contribute to the inhibition of Env-mediated membrane fusion. Here, sera from 38 HIV-1 infected treatment-naïve men and 30 healthy donors were analyzed for the presence of IgG and IgM able to bind to CD4-negative Jurkat cells. The use of CD4-negative cells precluded the binding of virus-antibody immune complexes, and allowed detection of ALA different from anti-CD4 antibodies. IgG and IgM antibodies binding to Jurkat CD4-negative cells was detected in 74% and 84% of HIV-positive sera, respectively. Then, the activity of sera on fusion of CD4+ with HIV Env+ Jurkat cells was determined before and after their adsorption on CD4-negative Jurkat cells to remove ALA. Sera inhibited fusion at variable extents, and inhibitory activity decreased in 58% of serum samples after adsorption, indicating that ALA contributed to fusion inhibition in these sera (herein called fusion inhibitory ALA). The contribution of ALA to fusion inhibition in individual sera was highly variable, with an average of 33%. IgG purified from a pool of HIV+ sera inhibited fusion of primary CD4 T lymphocytes with Jurkat Env+, and adsorption of IgG on CD4-negative Jurkat cells diminished the fusion inhibitory activity. Thus, the inhibitory activity of sera was related to IgG ALA. Our observations suggest that fusion inhibitory ALA other than anti-CD4 antibodies may contribute significantly to the inhibition of Env-mediated cell-cell fusion. Fusion inhibitory ALA, but not total ALA levels, associated with low plasma viral loads, suggesting that specific ALA may participate in virus containment by inhibiting virus-cell fusion in a significant fraction of HIV-infected patients.

14.
Mem Cognit ; 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31001797

RESUMO

The debate about whether compound words are accessed as whole words or via their constituents remains unresolved, especially in the field of language production. In this study, three experiments used a copying task to examine whether compound words are accessed via their constituents in handwriting production. In Experiment 1, production of compound words and noncompounds was compared. The last interletter interval within the first constituent of compounds was observed to be shorter than the same interval in noncompounds, revealing that writing durations are sensitive to morphological processing. In Experiments 2 and 3, the first and second constituent frequency was manipulated respectively. The frequency of both constituents affected writing onset times. Interestingly, the interval between the last two letters of the first constituent was shorter when the second constituent was of high frequency, suggesting that the effect obtained in this position in Experiment 1 was related to the anticipation of the second constituent. Our findings indicate that both constituents are activated before the initiation of the written response and that the second component is reactivated before the production of the first constituent has finished.

15.
BMC Genomics ; 20(1): 226, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890123

RESUMO

BACKGROUND: Despite the tremendous therapeutic advances that have stemmed from somatic oncogenetics, survival of some cancers has not improved in 50 years. Osteosarcoma still has a 5-year survival rate of 66%. We propose the natural canine osteosarcoma model can change that: it is extremely similar to the human condition, except for being highly heritable and having a dramatically higher incidence. Here we reanalyze published genome scans of osteosarcoma in three frequently-affected dog breeds and report entirely new understandings with immediate translational indications. RESULTS: First, meta-analysis revealed association near FGF9, which has strong biological and therapeutic relevance. Secondly, risk-modeling by multiple logistic regression shows 22 of the 34 associated loci contribute to risk and eight have large effect sizes. We validated the Greyhound stepwise model in our own, independent, case-control cohort. Lastly, we updated the gene annotation from approximately 50 genes to 175, and prioritized those using cross-species genomics data. Mostly positional evidence suggests 13 genes are likely to be associated with mapped risk (including MTMR9, EWSR1 retrogene, TANGO2 and FGF9). Previous annotation included seven of those 13 and prioritized four by pathway enrichment. Ten of our 13 priority genes are in loci that contribute to risk modeling and thus can be studied epidemiologically and translationally in pet dogs. Other new candidates include MYCN, SVIL and MIR100HG. CONCLUSIONS: Polygenic osteosarcoma-risk commonly rises to Mendelian-levels in some dog breeds. This justifies caninized animal models and targeted clinical trials in pet dogs (e.g., using CDK4/6 and FGFR1/2 inhibitors).


Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Modelos Estatísticos , Herança Multifatorial , Osteossarcoma/veterinária , Animais , Neoplasias Ósseas/genética , Cruzamento , Estudos de Casos e Controles , Estudos de Coortes , Modelos Animais de Doenças , Doenças do Cão/patologia , Cães , Predisposição Genética para Doença , Genoma , Osteossarcoma/genética , Medição de Risco/métodos
16.
Sensors (Basel) ; 19(7)2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30925832

RESUMO

In this paper we analyze an experiment for the use of low-cost gas sensors intended to detect bacteria in wounds using a non-intrusive technique. Seven different genera/species of microbes tend to be present in most wound infections. Detection of these bacteria usually requires sample and laboratory testing which is costly, inconvenient and time-consuming. The validation processes for these sensors with nineteen types of microbes (1 Candida, 2 Enterococcus, 6 Staphylococcus, 1 Aeromonas, 1 Micrococcus, 2 E. coli and 6 Pseudomonas) are presented here, in which four sensors were evaluated: TGS-826 used for ammonia and amines, MQ-3 used for alcohol detection, MQ-135 for CO2 and MQ-138 for acetone detection. Validation was undertaken by studying the behavior of the sensors at different distances and gas concentrations. Preliminary results with liquid cultures of 108 CFU/mL and solid cultures of 108 CFU/cm2 of the 6 Pseudomonas aeruginosa strains revealed that the four gas sensors showed a response at a height of 5 mm. The ammonia detection response of the TGS-826 to Pseudomonas showed the highest responses for the experimental samples over the background signals, with a difference between the values ​​of up to 60 units in the solid samples and the most consistent and constant values. This could suggest that this sensor is a good detector of Pseudomonas aeruginosa, and the recording made of its values ​​could be indicative of the detection of this species. All the species revealed similar CO2 emission and a high response rate with acetone for Micrococcus, Aeromonas and Staphylococcus.


Assuntos
Gases/análise , Compostos Orgânicos Voláteis/química , Infecção dos Ferimentos/diagnóstico , Álcoois/análise , Amônia/análise , Candida/química , Candida/metabolismo , Escherichia coli/química , Escherichia coli/metabolismo , Humanos , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/metabolismo , Compostos Orgânicos Voláteis/análise , Infecção dos Ferimentos/microbiologia
17.
J Neurosurg ; : 1-9, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925474

RESUMO

OBJECTIVE Revascularization of a symptomatic, medically refractory, cervical chronically occluded internal carotid artery (COICA) using endovascular techniques (ETs) has surfaced as a viable alternative to extracranial-intracranial bypass. The authors aimed to assess the safety, success, and neurocognitive outcomes of recanalization of COICA using ETs or hybrid treatment (ET plus carotid endarterectomy) and to identify candidate radiological markers that could predict success. METHODS The authors performed a retrospective analysis of their prospectively collected institutional database and used their previously published COICA classification to assess the potential benefits of ETs or hybrid surgery to revascularize symptomatic patients with COICA. Subjects who had undergone CT perfusion (CTP) imaging and Montreal Cognitive Assessment (MoCA) testing, both pre- and postprocedure, were included. The authors then performed a review of the literature on patients with COICA to further evaluate the success and safety of these treatment alternatives. RESULTS The single-center study revealed 28 subjects who had undergone revascularization of symptomatic COICA. Five subjects had CTP imaging and MoCA testing pre- and postrevascularization and thus were included in the study. All 5 patients had very large penumbra involving the entire hemisphere supplied by the ipsilateral COICA, which resolved postoperatively. Significant improvement in neurocognitive outcome was demonstrated by MoCA testing after treatment (preprocedure: 19.8 ± 2.4, postprocedure: 27 ± 1.6; p = 0.0038). Moreover, successful revascularization of COICA led to full restoration of cerebral hemodynamics in all cases. Review of the literature identified a total of 333 patients with COICA. Of these, 232 (70%) showed successful recanalization after ETs or hybrid surgery, with low major and minor complication rates (3.9% and 2.7%, respectively). CONCLUSIONS ETs and hybrid surgery are safe and effective alternatives to revascularize patients with symptomatic COICA. CTP imaging could be used as a radiological marker to assess cerebral hemodynamics and predict the success of revascularization. Improvement in CTP parameters is associated with significant improvement in neurocognitive functions.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30853116

RESUMO

INTRODUCTION: In previous studies we showed that prevalence of myocardial fibrosis as assessed by late enhancement on cardiac MRI in SSc patients is 45% and is associated to diffuse disease (dcSSc) and lower left ventricle ejection fraction; microvascular damage defined as decreased perfusion on cardiac MRI after adenosine infusion, was also very frequent (79%). Our aim was to identify baseline characteristics associated to the development of cardiovascular outcomes (heart failure, coronary artery disease, arrhythmias, vasculopathy, elevated systolic pulmonary artery pressure and death) in SSc patients with previously documented myocardial fibrosis and microvascular damage. PATIENTS AND METHODS: We included 62 SSc patients who participated in the study of prevalence of myocardial fibrosis (2008-2010) and in our local SSc cohort. We performed baseline clinical evaluation, cardiac MRI, coronary CT angiography, transthoracic echocardiogram, and yearly clinical and cardiovascular evaluation that included Medsger's severity scale items, electrocardiogram, echocardiogram, chest X-ray or HRCT and spirometry; we registered presence and severity of internal organ involvement and cardiovascular outcomes. Ordinal variables were analyzed using Chi square test and Fisher test when appropriate, numeric variables were compared using Student's t-test or Mann Whitney U when appropriate, logistic regression and Cox proportional hazard ratio were used to perform multivariable analysis. RESULTS: We obtained follow-up information from 62 patients (29 dcSSc, 33 lcSSc), mean follow-up was 43.5 months. Multivariable analysis showed that elevated basal ultrasensitive CRP was associated to mortality (p = 0.004, OR: 11.9, 95% CI 2.1-65.7) and recurrent digital tip ischemic ulcers (p = 0.001, OR 26.8, 95% CI 3,9-181.3) on follow-up. Myocardial fibrosis, particularly in the middle segments (p = 0.01, OR: 11.49, 95% CI 1.6-83), and older age (p = 0.02, OR: 1.11, 95% CI 1.01-1.22) were associated to heart failure on follow-up. Higher maximum mRSS was associated to coronary artery disease (p = 0.02, OR: 1.2, 95% CI 1.02-1.38), while insertion point fibrosis (p = 0.001, OR: 12.5 95% CI 2.7-56.6) was associated to recurrent digital tip ischemic ulcers. CONCLUSIONS: This study shows that myocardial fibrosis, elevated ultrasensitive CRP, and higher maximum mRSS are independent predictors of cardiovascular outcomes in SSc patients. Future studies should focus on early preventive and therapeutic strategies for this group of patients.

20.
Methods Mol Biol ; 1954: 25-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30864121

RESUMO

Capsular polysaccharides are a dominant class of antigens from bacteria, both pathogenic and symbiotic or commensal. With the rise of awareness for the influence of the microbiota over immune system development and immune homeostasis, analysis of the antigens is more important than ever. Here we describe a method for the isolation of capsular polysaccharide from gram-negative bacteria, with the purification of polysaccharide from the commensal bacterium Bacteroides fragilis serving as an example. The method efficiently removes all detectable endotoxins and other lipid components, proteins, and nucleic acids, providing a source of capsular polysaccharide for immunologic study.


Assuntos
Cápsulas Bacterianas/química , Bacteroides fragilis/química , Fracionamento Químico/instrumentação , Polissacarídeos Bacterianos/isolamento & purificação , Infecções por Bacteroides/microbiologia , Fracionamento Químico/métodos , Precipitação Química , Cromatografia/métodos , Eletroforese em Gel de Poliacrilamida/métodos , Desenho de Equipamento , Éteres/química , Humanos , Fenóis/química , Polissacarídeos Bacterianos/química
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