•Successful immobilization of a laccase on bacterial cellulose for wound dressings.•Bacterial cellulose structure is manly formed by pure crystalline Iα cellulose.•Activation energies and optimum pH ...of free laccase depend on the substrate employed.•Entrapped laccase maintains some flexibility and accessibility of the substrate.•Antimicrobial effect of immobilized laccase in Gram-positive and negative bacteria
This work studied the physical immobilization of a commercial laccase on bacterial nanocellulose (BNC) aiming to identify the laccase antibacterial properties suitable for wound dressings. Physico-chemical analysis demonstrates that the BNC structure is manly formed by pure crystalline Iα cellulose. The pH optimum and activation energy of free laccase depends on the substrate employed corresponding to pH 6, 7, 3 and 57, 22, 48kJmol−1 for 2,6-dimethylphenol (DMP), catechol and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), respectively. The Michaelis–Menten constant (Km) value for the immobilized laccase (0.77mM) was found to be almost double of that of the free enzyme (0.42mM). However, the specific activities of immobilized and free laccase are similar suggesting that the cage-like structure of BNC allows entrapped laccase to maintain some flexibility and favour substrate accessibility. The results clearly show the antimicrobial effect of laccase in Gram-positive (92%) and Gram-negative (26%) bacteria and cytotoxicity acceptable for wound dressing applications.
Background Impaired signaling in the IFN-γ/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal ...transducer and activator of transcription 1 ( STAT1 ) have been associated with chronic mucocutaneous candidiasis. Objective We sought to identify the molecular defect in patients with disseminated dimorphic yeast infections. Methods PBMCs, EBV-transformed B cells, and transfected U3A cell lines were studied for IFN-γ/IL-12 pathway function. STAT1 was sequenced in probands and available relatives. Interferon-induced STAT1 phosphorylation, transcriptional responses, protein-protein interactions, target gene activation, and function were investigated. Results We identified 5 patients with disseminated Coccidioides immitis or Histoplasma capsulatum with heterozygous missense mutations in the STAT1 coiled-coil or DNA-binding domains. These are dominant gain-of-function mutations causing enhanced STAT1 phosphorylation, delayed dephosphorylation, enhanced DNA binding and transactivation, and enhanced interaction with protein inhibitor of activated STAT1. The mutations caused enhanced IFN-γ–induced gene expression, but we found impaired responses to IFN-γ restimulation. Conclusion Gain-of-function mutations in STAT1 predispose to invasive, severe, disseminated dimorphic yeast infections, likely through aberrant regulation of IFN-γ–mediated inflammation.
Renalase is a recently identified FAD/NADH-dependent amine oxidase mainly expressed in kidney that is secreted into blood and urine where it was suggested to metabolize catecholamines. The present ...study evaluated central and peripheral dopaminergic activities in the renalase knockout (KO) mouse model and examined the changes induced by recombinant renalase (RR) administration on plasma and urine catecholamine levels. Compared with wild-type (WT) mice, KO mice presented increased plasma levels of epinephrine (Epi), norepinephrine (NE), and dopamine (DA) that were accompanied by increases in the urinary excretion of Epi, NE, DA. In addition, the KO mice presented an increase in urinary DA-to-l-3,4-dihydroxyphenylalanine (l-DOPA) ratios without changes in renal tubular aromatic-l-amino acid decarboxylase (AADC) activity. By contrast, the in vivo administration of RR (1.5 mg/kg sc) to KO mice was accompanied by significant decreases in plasma levels of Epi, DA, and l-DOPA as well as in urinary excretion of Epi, DA, and DA-to-l-DOPA ratios notwithstanding the accompanied increase in renal AADC activity. In addition, the increase in renal DA output observed in renalase KO mice was accompanied by an increase in the expression of the L-type amino acid transporter like (LAT) 1 that is reversed by the administration of RR in these animals. These results suggest that the overexpression of LAT1 in the renal cortex of the renalase KO mice might contribute to the enhanced l-DOPA availability/uptake and consequently to the activation of the renal dopaminergic system in the presence of renalase deficiency.
Puromycin aminonucleoside-induced nephrotic syndrome (PAN-NS) is characterized by cardiac remodeling and increased local inflammatory activity. Patients with NS and animal models of NS have vitamin ...D3 deficiency. The aim of the present study was to evaluate the influence of calcitriol on cardiac remodeling and local inflammatory state in PAN-NS rat model. Male Sprague-Dawley rats were injected with PAN or vehicle on day 0. PAN and control rats were divided into two subgroups for the administration of calcitriol (PAN-D and Ct-D groups) or the vehicle (PAN-V and Ct-V groups) during 21 days. On day 21, the renal function, metabolic balance, calcitriol and FGF-23 plasma levels, prohypertrophy and proinflammatory markers (ET-1, TGF-β1, TNF-α, and IL-1β), and calcium signaling molecules (PLB and SERCA-2a) were evaluated. Twenty-one days after injection, PAN-V group presented cardiac hypertrophy and a modulation of proinflammatory markers local expression. Calcitriol treatment of PAN rats prevented cardiac hypertrophy and was associated with marked reduction in the cardiac expression levels of proinflammatory markers. Our results suggest that vitamin D3 deficiency in PAN-NS may contribute to cardiac remodeling and to the increase in local inflammatory activity. Calcitriol treatment prevents both cardiac repercussions and local inflammatory processes in PAN-NS.
Burkholderia multivorans is a Gram-negative bacterium and a member of the Burkholderia cepacia complex, which is frequently associated with respiratory infections in people with cystic fibrosis (CF) ...and chronic granulomatous disease (CGD). We are reporting the genome sequences of 4 B. multivorans strains, 2 from CF patients and 2 from CGD patients.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the ...diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
The Burkholderia cepacia complex (BCC) is a group of closely related bacteria that are responsible for respiratory infections in immunocompromised humans, most notably those with cystic fibrosis ...(CF). We report the genome sequences for Burkholderia cenocepacia ET12 lineage CF isolates K56-2 and BC7.
Human exposure to heavy metals makes it necessary to monitor these elements in the human body if the objective is to relate heavy metal exposure to adverse health effects. In Portugal, biomonitoring ...projects on heavy metals are being carried out on people living in the vicinity of solid waste incinerators. The projects are being developed in the ambit of two environmental health surveillance programs related to solid waste incineration facilities, one near Lisbon and the other on Madeira Island, that have the main objective of guaranteeing the safeguard of public health in relation to the potential negative impact of incineration processes on human health. These programs are the only ones in the country that integrate a systematic observation of human exposure to heavy metals as determined by the respective body burden in several population groups. Therefore, they are the only ones that are currently able to provide systematic data from Portuguese regions on the extent and pattern of human exposure to this type of pollutants. The present paper is the first of a series of three prepared papers with the objective of presenting and discussing available data. It addresses exposure to lead, cadmium and mercury as determined by their levels in blood of general population adults. Results suggest the effectiveness of source control measures in relation to both incinerators under study, similarly to what has been concluded from previous studies addressing exposure to dioxins. They also show, in relation to the baseline situation, a general significant trend for reduction of exposure to all studied heavy metals. Individuals from Lisbon seem to have a significantly higher body burden of the studied metals than those living in Madeira and, in general, metal exposure in men is significantly higher than in women, with the most relevant exception being the case of higher mercury levels in women, at the baseline and for both communities. Compared with published reference values for similar conditions, blood levels of cadmium, lead, and mercury of the present investigation seem to be relatively higher, in median terms and for extreme values, mainly in the case of cadmium and mercury. In the case of lead the differences are not so marked.
As part of environmental health surveillance programs related to solid waste incinerators located near Lisbon and on Madeira Island, human biomonitoring projects have been implemented in Portugal, ...some of them focused on cross-sectional surveys of heavy metals in blood. One of the general aims of these programs is to provide Portuguese data on the extent and pattern of human exposure to the pollutants potentially released in the stack gases from the incinerators, namely heavy metals. The present investigation reports information specifically on blood lead levels of newborn–mother pairs living in the vicinity of the incinerators under study, as well as of statistically similar participants living outside the exposed area. For Lisbon, lead levels determined at the baseline period (T0), as well as three subsequent evaluations of potential specific impacts of the incinerator (T1, T2 and T3) are described in order to investigate spatial and temporal trends of human exposure to lead. Available data for Madeira, namely lead levels in blood from the study population before the incinerator started operation, is also described. For Lisbon, analyses showed a statistically significant decrease of lead concentrations in maternal
(
p
<
0.001
)
and umbilical cord blood
(
p
<
0.001
)
during the whole monitoring period. Practically “overt” transplacental exposure to lead was observed only in the Lisbon biomonitoring project and for some cross-sectional surveys. Baseline levels for Madeira were the lowest found in all observations already performed in both programs (maternal and umbilical cord mean lead levels of 0.4
μg/dl and 0.3
μg/dl, respectively). No statistical associations have been found between lead levels in blood and age neither for global populations from Lisbon and Madeira nor for specific groups included in the different observational periods.
Eighty-eight immunocompetent patients with deep mycoses from eight countries were evaluated with the same protocol for efficacy of fluconazole monotherapy. Entry doses were raised from 100 to 400 mg ...as safety was shown in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44 months were studied. Results were very similar in different countries. Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19 with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight with histoplasmosis demonstrated objective responses to therapy, as did one patient each with zygomycosis and alternariosis. For these patients, relapses have been unusual thus far. In contrast, one patient with chromoblastomycosis responded but relapsed, and six did not respond; one patient with mycetoma responded but relapsed, and two did not respond. The drug was well tolerated by patients, including six who received intravenous therapy. In vitro susceptibility tests suggested that clinical response was correlated with susceptibility but that resistance did not preclude clinical response. Fluconazole therapy appears efficacious for several deep mycoses; dosages of >200 mg daily may be needed for some diseases. The further evaluation of fluconazole for these entities is warranted.
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