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A 7-month-old intact female bearded collie dog was admitted after a 2-week history of progressive cough, inappetence, and lethargy, with no response to previous treatment with doxycycline and steroids. Mild attenuation of lung sounds in the right middle hemithorax was the only abnormality detected on physical examination. Abdominal ultrasound and thoracic radiographs were performed and revealed multifocally distributed nodules and masses, well-circumscribed and of variable size in the kidneys and pulmonary parenchyma. Ultrasound-guided fine needle aspirates of the renal and pulmonary masses were taken. A cytologic evaluation of these lesions pointed towards a malignant mesenchymal neoplasia. Euthanasia was elected due to the poor prognosis and rapid progression. The post-mortem histopathology, a positive result to IBA1 immunoperoxidase staining, and a lack of detection of infectious agents, and negative E-cadherin immunostaining enabled the final diagnosis of a disseminated histiocytic sarcoma. We report an atypical form, both in breed and age, of canine disseminated histiocytic sarcoma. While all breeds can be affected, there is a clear predisposition in some, and no cases have been previously described in bearded collies. Moreover, to the authors' knowledge, this is the youngest dog with this histiocytic disorder described to date. Disseminated histiocytic sarcoma should be considered as a differential diagnosis of multinodular tumors in dogs, regardless of the anatomic location and age of the dogs, even in puppies.
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Doenças do Cão , Sarcoma Histiocítico , Sarcoma , Cães , Animais , Feminino , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/veterinária , Sarcoma/patologia , Sarcoma/veterinária , Biópsia por Agulha Fina/veterinária , Histiócitos/patologia , Doenças do Cão/diagnósticoRESUMO
BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.
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Doenças Cardiovasculares , Gordura Intra-Abdominal , Adulto , Masculino , Humanos , Feminino , Composição Corporal , Fatores de Risco Cardiometabólico , Escolaridade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Jejum , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Among antihyperglycemic drugs used for treating diabetes, α-glucosidase inhibitors generate the least adverse effects. This contribution aimed to evaluate the potential antidiabetic activity of Rumex crispus L. by testing its in vitro α-glucosidase inhibition and in vivo antihyperglycemic effects on rats with streptozotocin (STZ)-induced diabetes. Better inhibition of α-glucosidase was found with the methanol extract versus the n-hexane and dichloromethane extracts. The methanol extract of the flowers (RCFM) was more effective than that of the leaves (RCHM), with an IC50 of 7.3 ± 0.17 µg/mL for RCFM and 112.0 ± 1.23 µg/mL for RCHM. A bioactive fraction (F89s) also showed good α-glucosidase inhibition (IC50 = 3.8 ± 0.11 µg/mL). In a preliminary study, RCHM and RCFM at 150 mg/kg and F89s at 75 mg/kg after 30 days showed a significant effect on hyperglycemia, reducing glucose levels (82.2, 80.1, and 84.1%, respectively), and improved the lipid, renal, and hepatic profiles of the rats, comparable with the effects of metformin and acarbose. According to the results, the activity of R. crispus L. may be mediated by a diminished rate of disaccharide hydrolysis, associated with the inhibition of α-glucosidase. Thus, R. crispus L. holds promise for the development of auxiliary drugs to treat diabetes mellitus.
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Diabetes Mellitus Experimental , Rumex , Ratos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , alfa-Glucosidases , Metanol , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Folhas de Planta , Diabetes Mellitus Experimental/tratamento farmacológico , FloresRESUMO
The antibacterial activity (ABA) of honey is associated with the generation of reactive oxygen species (ROS), where polyphenols (PFs) play a key role due to their pro-oxidant action modulated by metallic cations. In this work, the contents of PFs, H2O2, OH radicals, Cu, Fe, Mn, Zn, and ABA against Staphylococcus epidermidis and Pseudomonas aeruginosa were determined in honeys from central Chile. Then, their relationships were evaluated through partial least squares regression. The average contents of phenolic acids, flavonoids and metals in honey ranged from 0.4 to 4 µg/g, 0.3-1.5 µg/g and 3-6 µg/g, respectively. All honeys showed accumulation of H2O2 (1-35 µg/g) and OH radicals. The PLS showed that gallic acid, p-coumaric acid, chrysin, kaempferol, Fe, and Mn stimulate the generation of ROS. Quercetin, Cu, and Zn showed marginal antioxidant effects. PFs favor the ABA of honey against both bacteria and H2O2 against S. epidermidis.
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Mel , Espécies Reativas de Oxigênio , Mel/análise , Peróxido de Hidrogênio , Fenóis/análise , Antioxidantes , Minerais , Antibacterianos/farmacologiaRESUMO
Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure-activity relationship, attaching 4-bromobutoxy or 4'-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and 10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.
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Inibidores de Glicosídeo Hidrolases , Xantonas , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , alfa-Amilases , Hipoglicemiantes/farmacologia , Relação Estrutura-Atividade , Imidazóis/farmacologia , Xantonas/farmacologia , Estrutura MolecularRESUMO
Background: Ruminococcus gnavus (R. Gnavus) is an anaerobic Gram-positive coccus, common commensal of the gastrointestinal tract of animals and humans. Anaerobic organisms as etiologic agents of bone and joint infections (BJI) are uncommon and frequently underestimated. New technologies, such as mass spectrometry techniques and molecular techniques like 16S rRNA, allow for more efficient diagnosis of these anaerobic bacteria. We present the first case report of deep surgical site infection (SSI) due to R. Gnavus, following spinal surgery. Case Description: We report the case of a deep SSI caused by R. Gnavus following posterior spinal instrumentation in an 81-year-old woman. The patient underwent extension of her previous fusion L2-L5, due to adjacent segment disease (ASD). We performed a T10 to S2-alar-iliac instrumentation. During the postoperative period, the patient presented with a paralytic ileus that required the placement of a nasogastric tube followed by gastrointestinal bleeding and two gastroscopies. Subsequently the patient showed signs of deep SSI. We performed surgical irrigation and debridement. All six cultures in anaerobic media showed short Gram-positive diplococci, using matrix-assisted laser desorption/ionization time of flight mass spectrometry (Maldi-TOF MS) all six strains were identified as R. Gnavus. The patient was treated with amoxicilin 1 g/8 h and ciprofloxacin 750 mg/12 h for 4 weeks. Six months postoperative, she was asymptomatic. Conclusions: As is the case with our patient, all previously described cases of R. Gnavus infection had a history of intestinal disease or immunosupression. We believe the isolation of R. Gnavus should raise the possibility of intestinal injury. Immunosuppression is also an important risk factor for the development of R. Gnavus infection.
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Background: Cerebrospinal fluid leakage can cause abducens nerve palsy (ANP) secondary to downward brain traction, caused by intracranial hypotension. We present the first case after cervical fixation and fusion with spinal cord decompression. Case Description: We present a 65-year-old male, who undergone C5-C6 decompression by laminectomy and C3-T2 fixation and fusion, without intraoperative complications. Two months later, the patient referred a 2-week history of diplopia, with no other accompanying symptom. Clinical examination revealed a lack of lateral gaze of the left eye. Cervical MRI disclosed findings compatible with pseudomeningocele. Given the time of evolution, the subacute clinical findings and the absence of image or clinical data of infection or intracranial hypotension, we decided to perform conservative treatment. We submitted the patient to periodic clinical examinations and we confirmed progressive clinical improvement of diplopia, in association with neurologic and ophthalmologic specialists. At this time, six months after surgery, the patient is asymptomatic. The swelling has significantly decreased in size. Control MRI revealed no growth of the pseudomeningocele. Conclusions: ANP secondary to intracranial hypotension after cervical spine surgery requires immediate imaging tests and clinical evaluation from neurology and ophthalmology specialists. Management can be conservative, as long as diplopia is the only clinical and radiological finding and wound does not show signs of infection.
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Grape pomace (GP) is a by-product resulting from the winemaking process and its potential use as a source of bioactive compounds is well known. The GP bioactive compounds can be retained in the well-known polyvinylpolypyrrolidone (PVPP), industrially used in the clarification and stabilization of wine and other drinks. Thus, the polyphenolic compounds (PC) from the Chilean Carménère, Cabernet Sauvignon, and Merlot GP were extracted, and their compositions and antioxidant capacities (ORAC-FL) were determined. In addition, the retention capacity of the PC on PVPP (PC-PVPP) was evaluated. The bioactivities of GP extracts and PC-PVPP were estimated by the agar plate inhibition assay against pathogenic microorganisms. Results showed a high amount of TPC and antioxidant capacity in the three ethanolic GPs extracts. Anthocyanins, flavan-3-ol, and flavonols were the most abundant compounds in the GP extract, with retentions between 70 and 99% on PVPP. The GP extracts showed inhibition activity against B. cereus and P. syringae pv. actinidiae but the GP-PVPP had no antimicrobial activity. The high affinity of the identified PCs from GPs on PVPP polymer could allow the design of new processes and by-products for the food or cosmeceutical industry, promoting a circular economy by reducing and reusing wastes (GPs and PVPP) and organic solvents.
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Silver nanoclusters of five atoms (Ag5) display outstanding catalytic activities for the deactivation of radicals. Using 2,2-diphenyl-1picrylhydrazyl (DPPH) radical as a model system, we observed a fast radical reduction to DPPH anions using only [Ag5] 3 to 4 orders of magnitude less than [DPPH]. Moreover, nanoclusters remain stable at the end of the reaction, and can deactivate again DPPH radicals at the same rate, indicating that they act as anti-radical catalysts. The radical scavenger catalytic activity of Ag5 proceeds selectively through the oxidation of methanol (used to dissolve the radical) to formaldehyde, which is supported by DFT calculations. The obtained catalytic rate constants are almost 2 orders of magnitude higher than oxidases, and more than 4 orders of magnitude larger than graphene quantum dots. We also show that Ag5 not only catalyze the reduction of radicals but also their oxidation, promoting the inhibition of the autoxidation mechanisms of hydrocarbon polymers, which are very sensitive to the presence of radicals. For this purpose, thin films of two industrially relevant polymers (polyisoprene and acrylonitrile-butadienestyrene copolymer), were exposed to standard simulated photo-ageing conditions in the presence of Ag5. Using Attenuated Total Reflection-FTIR and DFT modeling we observed that, although Ag5 nanoclusters, with ≈ 15% surface coverage, do not totally inhibit the oxidation, they favour a decomposition that yields inactive products, in contrast with the more detrimental ketone formation pathway. These results not only open new possibilities for developing a post-process inhibition of polymer degradation, for which nowadays there are no efficient procedures, but also, they could be used as very efficient dual-redox catalytic radical scavengers for different industrial or biomedical purposes.
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Acrilonitrila , Grafite , Ânions , Compostos de Bifenilo , Formaldeído , Cetonas , Metanol , Oxirredução , Oxirredutases , Polímeros , PrataRESUMO
We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
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Using an incentivized experiment with statistical power, this paper explores the role of stakes in charitable giving of lottery prizes, where subjects commit to donate a fraction of the prize before they learn the outcome of the lottery. We study three stake levels: 5 (n = 177), 100 (n = 168), and 1,000 (n = 171). Although the donations increase in absolute terms as the stakes increase, subjects decrease the donated fraction of the pie. However, people still share roughly 20% of 1,000, an amount as high as the average monthly salary of people at the age of our subjects. The number of people sharing 50% of the pie is remarkably stable across stakes, but donating the the whole pie-the modal behavior in charity-donation experiments-disappears with stakes. Such hyper-altruistic behavior thus seems to be an artifact of the stakes typically employed in economic and psychological experiments. Our findings point out that sharing with others is a prevalent human feature, but stakes are an important determinant of sharing. Policies promoted via prosocial frames (e.g., stressing the effects of mask-wearing or social distancing on others during the Covid-19 pandemic or environmentally-friendly behaviors on future generations) may thus be miscalibrated if they disregard the stakes at play.
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Altruísmo , Estudantes/psicologia , Feminino , Doações , Humanos , Masculino , Adulto JovemRESUMO
The urgency for the availability of new antibacterial/disinfectant agents has become a worldwide priority. At the same time, along with the extensive use of other metal nanoparticles (NPs), the investigation of magnetic NPs (MNPs) in antibacterial studies has turned out to be an increasingly attractive research field. In this context, we present the preparation and characterization of superparamagnetic iron oxide NPs, electrodecorated with antimicrobial copper NPs, able to modulate the release of bioactive species not only by the NP's stabilizer, but also through the application of a suitable magnetic field. Antimicrobial synergistic CuNPs stabilized by benzalkonium chloride have been used in the current study. We demonstrate the successful preparation of Cu@Fe3O4 MNPs composites through morphological and spectroscopic results. Additionally, an extensive magnetic characterization is reported, along with hyperthermia-induced copper ionic release. On the basis of our results, we propose a new generation of antimicrobial magnetic nanomaterials, whose bioactivity can be also tuned by the application of a magnetic field.
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A small percentage of an impurity was shown, via scanning tunneling microscopy, to drastically change the on-surface self-assembly behavior of an aromatic tetracarboxylic acid, by initiating the nucleation and growth of a different polymorph. Molecular modelling simulations were used to shed further light onto the dopant-controlled assembly behaviour.
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BACKGROUND: Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated. METHODS: Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences. RESULTS: More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified. CONCLUSIONS: Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
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Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Encéfalo/patologia , Sono , Actigrafia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição , Família , Feminino , Humanos , Padrões de Herança/genética , Modelos Lineares , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Linhagem , Fenótipo , Temperamento , Adulto JovemRESUMO
Bipolar disorder is a highly heritable illness, associated with alterations of brain structure. As such, identification of genes influencing inter-individual differences in brain morphology may help elucidate the underlying pathophysiology of bipolar disorder (BP). To identify quantitative trait loci (QTL) that contribute to phenotypic variance of brain structure, structural neuroimages were acquired from family members (n = 527) of extended pedigrees heavily loaded for bipolar disorder ascertained from genetically isolated populations in Latin America. Genome-wide linkage and association analysis were conducted on the subset of heritable brain traits that showed significant evidence of association with bipolar disorder (n = 24) to map QTL influencing regional measures of brain volume and cortical thickness. Two chromosomal regions showed significant evidence of linkage; a QTL on chromosome 1p influencing corpus callosum volume and a region on chromosome 7p linked to cortical volume. Association analysis within the two QTLs identified three SNPs correlated with the brain measures.
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Transtorno Bipolar , Transtorno Bipolar/genética , Encéfalo/diagnóstico por imagem , Ligação Genética/genética , Humanos , Linhagem , Fenótipo , Locos de Características Quantitativas/genéticaRESUMO
Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants.
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Transtorno Bipolar , Transtorno Bipolar/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Oocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis.
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Doenças Genéticas Inatas/terapia , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/terapia , Oogênese/genética , Tubulina (Proteína)/genética , Adulto , Análise Mutacional de DNA , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/epidemiologia , Humanos , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/genética , México , Mutação , Linhagem , Gravidez , Prognóstico , Técnicas de Reprodução Assistida/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Soluble ST2 (sST2), which is the soluble form of interleukin (IL)-1 receptor-like 1, identifies risk in acutely decompensated heart failure (ADHF). IL-1ß is an inflammatory cytokine that has deleterious effects in myocardial remodeling and function. IL-1ß inhibition has beneficial effects after acute myocardial infarction. However, the role of IL-1ß in ADHF and its relationship to ST2 remain unclear. OBJECTIVES: This study sought to investigate the relationship between IL-1ß and sST2, and the prognostic impact of such a relationship in patients with ADHF. METHODS: This study examined 316 consecutive patients who were hospitalized with ADHF (72 ± 12 years of age, 57% male, and left ventricular ejection fraction 45 ± 17%). Blood samples were collected at presentation, and IL-1ß and sST2 levels were measured. All-cause mortality was obtained for all patients at 1 year. RESULTS: The IL-1ß concentration at presentation was associated with prior HF hospitalizations, functional impairment, and higher N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T concentrations. IL-1ß was higher in patients who died during the year after hospitalization (n = 52, 16.5%) (p = 0.005), and the optimal threshold was identified with levels over 49.1 pg/ml (hazard ratio: 2.5; 95% confidence interval: 1.43 to 4.49; p = 0.0014). Circulating IL-1ß positively correlated with sST2 (ρ = 0.65; p < 0.001). Considering the prognostic thresholds of IL-1ß (≥49.1 pg/ml) and sST2 (≥35.0 ng/ml) concentrations: all patients with low sST2 also presented with low IL-1ß; among patients with high sST2, only those with also high IL-1ß had a significantly higher risk of death (30% vs. 14%; hazard ratio: 2.52; 95% confidence interval: 1.40 to 4.56; p = 0.002). CONCLUSIONS: Circulating IL-1ß concentrations are clinically meaningful in ADHF patients and interplay with the predictive ability of sST2. IL-1 axis-related inflammation signaling may represent a therapeutic target in ADHF.
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Insuficiência Cardíaca/sangue , Interleucina-1/sangue , Sistema de Registros , Medição de Risco/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Doença Aguda , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Ensaio de Imunoadsorção Enzimática , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Serum concentrations of ST2 (interleukin-1 receptor-like 1) represent a meaningful prognostic marker in cardiac diseases. Production of soluble ST2 (sST2) may be partially extracardiac. Identification of sST2 sources is relevant to design strategies for modulating its signaling. METHODS AND RESULTS: An experimental model of ischemic heart failure was used. sST2, membrane-bound ST2 (ST2L), and IL-33 were measured in lungs, heart, kidney, and liver by quantifying mRNA and protein expression in tissue samples obtained at different times (1, 2, 4, and 24 weeks). Primary human type II pneumocyte cell cultures were subjected to strain. sST2 was measured in samples of bronchial aspirate and serum obtained from patients treated with invasive respiratory support. In the experimental model, sST2 increased significantly from the first week in both lungs and myocardium, whereas ST2L/IL-33 response was unfavorable in lungs (decrease) and favorable in myocardium (increase). No changes were observed in liver and kidneys. ST2 immunostaining was intensely observed in alveolar epithelium, and sST2 was secreted by primary human type II pneumocytes in response to strain. sST2 levels in lung aspirates were substantially higher in the presence of cardiogenic pulmonary edema (median, 228 [interquartile range, 28.4-324.0] ng/mL; P<0.001) than bronchopneumonia (median, 5.5 [interquartile range, 1.6-6.5]) or neurological disorders (median, 2.9 [interquartile range, 1.7-10.1]), whereas sST2 concentrations in serum did not differ. CONCLUSIONS: The lungs are a relevant source of sST2 in heart failure. These results may have implications for the progression of disease and the development of therapies targeting the ST2 system in patients with heart failure.