Assuntos
COVID-19 , Síndrome de Down , Síndrome de Down/diagnóstico , Humanos , Prognóstico , SARS-CoV-2RESUMO
BACKGROUND: SARS-CoV-2 predisposes patients to secondary infections; however, a better understanding of the impact of coinfections on the outcome of hospitalized COVID-19 patients is still necessary. AIM: To analyse death risk due to coinfections in COVID-19 patients. METHODS: The odds of death of 212 severely ill COVID-19 patients were evaluated, with detailed focus on the risks for each pathogen, site of infection, comorbidities and length of hospitalization. FINDINGS: The mortality rate was 50.47%. Fungal and/or bacterial isolation occurred in 89 patients, of whom 83.14% died. Coinfected patients stayed hospitalized longer and had an increased odds of dying (odds ratio (OR): 13.45; R2 = 0.31). The risk of death was increased by bacterial (OR: 11.28) and fungal (OR: 5.97) coinfections, with increased levels of creatinine, leucocytes, urea and C-reactive protein. Coinfections increased the risk of death if patients suffered from cardiovascular disease (OR: 11.53), diabetes (OR: 6.00) or obesity (OR: 5.60) in comparison with patients with these comorbidities but without pathogen isolation. The increased risk of death was detected for coagulase-negative Staphylococcus (OR: 25.39), Candida non-albicans (OR: 11.12), S. aureus (OR: 10.72), Acinetobacter spp. (OR: 6.88), Pseudomonas spp. (OR: 4.77), and C. albicans (OR: 3.97). The high-risk sites of infection were blood, tracheal aspirate, and urine. Patients with coinfection undergoing invasive mechanical ventilation were 3.8 times more likely to die than those without positive cultures. CONCLUSION: Severe COVID-19 patients with secondary coinfections required longer hospitalization and had higher risk of death. The early diagnosis of coinfections is essential to identify high-risk patients and to determine the right interventions to reduce mortality.
Assuntos
Infecções Bacterianas/mortalidade , COVID-19/mortalidade , Coinfecção/mortalidade , Micoses/mortalidade , Adulto , Idoso , Infecções Bacterianas/complicações , COVID-19/complicações , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Respiração ArtificialRESUMO
AIMS: To determine the effects of cytochalasin E, isolated from the extremophile fungus Aspergillus felis, on the cells of Paracoccidioides brasiliensis Pb18. METHODS AND RESULTS: Cytochalasin E showed a minimal inhibitory concentration of 3·6 µmol l-1 and minimum fungicidal concentration of 7·2 µmol l-1 on P. brasiliensis by in vitro microdilution and IC50 >964·0 µmol l-1 on murine macrophages. Its selectivity index (>263) indicated that this compound has selectivity for fungal cells. Morphological alterations were determined by optical and fluorescence microscopy, as well as scanning and transmission electron microscopy. Cytochalasin E affected P. brasiliensis bud-forming pseudohyphae, cell morphology, cell walls and cell membranes; caused the release of cellular material; and resulted in the production of reactive oxygen species. In murine macrophages, it affected cytoskeletal actin and inhibited phagocytosis. CONCLUSION: Cytochalasin E may be useful as an antifungal prototype against P. brasiliensis and in studies on phagocytosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM). Treatment is prolonged to control the clinical manifestations and prevent relapse. The study on the effects of cytochalasin E in P. brasiliensis is important because it can be used as a prototype for new antifungal drugs and consequently, broadens the treatment options for PCM.
Assuntos
Antifúngicos/farmacologia , Citocalasinas/farmacologia , Paracoccidioides/efeitos dos fármacos , Antifúngicos/isolamento & purificação , Aspergillus/química , Citocalasinas/isolamento & purificação , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: To study the effects of cannabinoid, glutamate, and dopamine agonists and antagonists on the calcium current rat sympathetic neurons. METHODS: Calcium current was recorded using the whole-cell variant of the patch-clamp technique. After expression in neuronal membranes of the cannabinoid CB1, glutamate mGluR2, or dopamine D1 receptor (by microinjection of the levant receptor's cDNA into the neuron's nucleus) agonists' and antagonists' effects were observed. RESULTS: Applications of agonists of the expressed receptor (0.1-10 microM) decreased the calcium current. The calcium current was increased after application of cannabinoid antagonists (AM251 and AM630); these compounds thus act as inverse agonists in this preparation. Glutamate and dopamine antagonists had no effects on the calcium current by themselves. Combined application of cannabinoids and dopamine, but not glutamate, agonists produced a decrement in the calcium current that was bigger than either of the effects seen when one agonist was applied alone. CONCLUSIONS: These results suggest that cannabinoid with dopamine receptors have an interactive inhibitory effect on the calcium current in this preparation, indicating that within the nervous system, receptor interactions may be important in the regulation of ion-channel functions.
Assuntos
Cálcio/metabolismo , Neurônios/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Masculino , Neurônios/citologia , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Gânglio Cervical Superior/citologia , Gânglio Cervical Superior/metabolismoRESUMO
HLA-DQB1, -DQA1, and -DRB1 genes were typed by polymerase chain reaction with sequence-specific primer (PCR-SSP) in 159 healthy volunteers from 32 families living in Guadalajara, Mexico. Three-locus genotype data from all family members were used to infer haplotypes in 54 unrelated individuals of the sample, from which estimate of segregating haplotype frequencies and linkage disequilibrium (LD) between loci were computed. Genotype distributions were concordant with Hardy-Weinberg expectations (HWE) for all three loci, and allele distributions were similar to the ones observed in other Latin-American populations. Of the 56 distinct three-site (DQB1-DQA1-DRB1) haplotypes observed in the sample, the five most common (i.e., with frequencies of five counts or more) were: *0302-*0301-*04, *0201-*0201-*07, *0301-*0501-*14, *0402-*0401-*08, and *0501-*0101-*01. These common three-locus haplotypes also contributed to the majority of the significant two-locus linkage disequilibria of these three sites.
Assuntos
Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Indígenas Norte-Americanos , População Branca , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Haplótipos , Humanos , Desequilíbrio de Ligação , México , Reação em Cadeia da PolimeraseRESUMO
A 24-year-old female with a Swyer syndrome phenotype was found to have a 46,X,del (Y) (p11) karyotype. This observation is consistent with the recently confirmed assignment of the testis-determining master gene to the deletion interval 1A of the Y (Page et al., 1987). Otherwise, it illustrates the etiological heterogeneity of the Swyer phenotype and allows to emphasize the de novo origin of XYp-females.