ABSTRACT
Intravenous Anti-Rhesus-D immunoglobulin (Anti-D) is a first-line treatment option for immune thrombocytopenia in non-splenectomised and RhD-positive patients. In this report, we retrospectively review our experience with intramuscular (IM) Anti-D treatment in 74 adult patients between 1990 and 2018. We found that 73% of patients showed a response; almost all of them had complete responses (68.9%), and 26% achieved complete responses sustained at least 6 months after treatment discontinuation. [Correction added on 02 December 2022, after first online publication: In the preceding sentence, '(68.89%)' has been corrected to '(68.9%)' in this version.] No significant side effects were observed with no cases of acute haemolysis or anaemia reported. We conclude from this study that IM Anti-D is an effective and safe treatment for immune thrombocytopenia.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Adult , Humans , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Retrospective Studies , Rho(D) Immune Globulin , Thrombocytopenia/drug therapyABSTRACT
Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.
ABSTRACT
Vitamin D has been reported to activate macrophage microbicidal mechanisms by inducing the production of antimicrobial peptides and nitric oxide (NO), but conversely has been shown to contribute to a greater susceptibility to Leishmania amazonensis infection in mice. Thus, this study aimed to evaluate the role of vitamin D during intracellular infection with L. amazonensis by examining its effect on macrophage oxidative mechanisms and parasite survival in vitro. Vitamins D2 and D3 significantly inhibited promastigote and amastigote growth in vitro. Vitamin D3 was not able to induce NO and reactive oxygen species (ROS) production in uninfected macrophages or macrophages infected with L. amazonensis. In addition, vitamin D3 in combination with interferon (IFN)-γ did not enhance amastigote killing and in fact, significantly reduced NO and ROS production when compared with the effect of IFN-γ alone. In this study, we demonstrated that vitamin D directly reduces parasite growth in infected macrophages (approximately 50-60% at 50 µm) but this effect is independent of the activation of macrophage oxidative mechanisms. These findings will contribute to a better understanding of the role of vitamin D in cutaneous leishmaniasis.
Subject(s)
Antiparasitic Agents/pharmacology , Cholecalciferol/pharmacology , Ergocalciferols/pharmacology , Leishmania mexicana/drug effects , Vitamins/pharmacology , Leishmaniasis, Cutaneous/metabolism , Leishmaniasis, Cutaneous/parasitology , Macrophages/metabolism , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Background and Purpose- Poststroke, neuronal excitability is tonically reduced in peri-infarct tissue via inhibitory influences of extrasynaptic GABAA receptors. We hypothesized that GABAA α5 blockade by the competitive antagonist S44819 enhances postischemic neurological recovery, brain remodeling, and neuroplasticity. Methods- In an explorative study followed by a confirmation study, male C57Bl6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. Starting 72 hours poststroke, vehicle or S44819 (3 or 10 mg/kg, BID) was delivered orally for 28 days. Neurological recovery, perilesional tissue remodeling, and contralesional pyramidal tract plasticity were evaluated for 42 days, that is, 14 days after completion of S44819 delivery. Results- S44819, delivered at 10 but not 3 mg/kg, persistently improved motor coordination and spatial memory in both studies. Striatal atrophy was reduced by 10 mg/kg S44819 at 42 days post-treatment onset, and neuronal long-term survival in the peri-infarct striatum was increased. Delayed neuroprotection was associated with reduced peri-infarct astrogliosis, increased peri-infarct brain capillary density, and increased neural precursor cell proliferation and differentiation in proximity to the ipsilesional subventricular zone. Contralesional pyramidal tract plasticity, evaluated by anterograde tract tracing at the level of the red nucleus, was not influenced by S44819. Concentrations of neurotrophic (brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) and angiogenic (vascular endothelial growth factor and basic fibroblast growth factor) growth factors were elevated by 10 mg/kg S44819 in peri-infarct but not contralesional brain tissue. Conclusions- Our data demonstrate that S44819 enhances neurological recovery and peri-infarct brain remodeling in the postacute stroke phase.
Subject(s)
Benzodiazepines/pharmacology , GABA Antagonists/pharmacology , Oxazoles/pharmacology , Recovery of Function/drug effects , Stroke/drug therapy , Animals , Brain/drug effects , Brain/metabolism , Infarction, Middle Cerebral Artery/metabolism , Male , Mice, Inbred C57BL , Neuronal Plasticity/drug effects , Neurons/drug effects , Neurons/metabolism , Neuroprotection/drug effects , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Stroke/physiopathologyABSTRACT
In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against Leishmania amazonensis. Its antileishmanial activity has been associated with oxidative stress in L. amazonensis promastigotes and L. amazonensis-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of L. amazonensis treated with VOSalophen presented apoptotic cells features, such as cell volume decrease, phosphatidylserine externalization, and DNA fragmentation. An increase in autophagic vacuoles formation in treated promastigotes was also observed, showing that autophagy also may be involved in the death of these parasites. In intracellular amastigotes, DNA fragmentation was observed after treatment with VOSalophen, but this effect was not observed in host cells, highlighting the selective effect of this vanadium complex. In addition, VOSalophen showed activity in the murine model of cutaneous leishmaniasis, without hepatic and renal damages. The outcome described here points out that VOSalophen had promising antileishmanial properties and these data also contribute to the understanding of the mechanisms involved in the death of protozoa induced by metal complexes.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/pathology , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Stilbenes/chemistry , Vanadium/chemistry , Animals , DNA Fragmentation/drug effects , Disease Models, Animal , Female , Leishmaniasis, Cutaneous/genetics , Mice , Mice, Inbred BALB C , Organometallic Compounds/therapeutic useABSTRACT
The aim of this study was to investigate the phenolic composition of a natural food colourant (G8000™) as well as its effects on plasma markers after 28-day consumption by healthy individuals at a dietary dose (70 g). Parameters of total cholesterol and its fractions, triglycerides and plasma enzymes biomarkers of muscle injury were measured. Major compounds identified in G8000™ by ESI-MS showed the presence of anthocyanins, organic acids, phenolic acids as well as monosaccharides. HDL levels significantly increased from 43 ± 10.2 mg/dL to 95 ± 16.9 mg/dL. LDL levels significantly decreased from 110 ± 40.9 mg/dL to 69 ± 39 mg/dL (p < 0.001). No significant statistical differences (p > 0.05) were observed for total cholesterol, triglycerides and VLDL. After the intake, plasma enzyme CK-MB decreased from 20 ± 12.1 U/L to 10 ± 1.9 U/L while LDH levels increased from 275 ± 124.4 U/L to 317 ± 114.7 U/L (p < 0.005). No significant differences were observed for CK levels. Taken together, dietary intake of natural colourant G8000™ was able to exert beneficial effects on atherosclerosis biomarkers.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Food Coloring Agents/pharmacology , Plant Extracts/blood , Plant Extracts/pharmacology , Vitis , Adult , Biomarkers/blood , Female , Food Coloring Agents/metabolism , Humans , Male , Phenols/blood , Phenols/pharmacology , Triglycerides/blood , Young AdultABSTRACT
Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG-DTA) analyses, and FT-IR and UV-Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC50 values below 5.7 µM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.
Subject(s)
Antiprotozoal Agents/pharmacology , Benzimidazoles/chemistry , Leishmania/drug effects , Organogold Compounds/chemical synthesis , Organogold Compounds/pharmacology , 3T3 Cells , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Macrophages/drug effects , Mice , Mice, Inbred BALB C , Molecular Structure , Organogold Compounds/chemistry , Quantum Theory , Structure-Activity RelationshipABSTRACT
A case study A previously healthy woman, aged 37 years, presented with a 4-week history of pruritic periungual rash and subungual pain. Physical examination revealed scaly, fissured, erythematous plaques around her fingernails (Figure 1). Underneath the acrylic artificial nails that she had been wearing for 6 weeks, onycholysis and nail bed hyperkeratosis were evident. Oral terbinafine and amorolfine nail polish were prescribed by the general practitioner but had no clinical benefit.
Subject(s)
Acrylates/adverse effects , Dermatitis, Allergic Contact/diagnosis , Exanthema/etiology , Nails , Adult , Anti-Inflammatory Agents/therapeutic use , Betamethasone/analogs & derivatives , Betamethasone/therapeutic use , Cosmetics/adverse effects , Dermatitis, Allergic Contact/drug therapy , Dermatitis, Allergic Contact/etiology , Diagnosis, Differential , Female , Humans , Onychomycosis/diagnosis , Patch Tests , Psoriasis/diagnosisABSTRACT
AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving procedure for supporting patients with cardiogenic shock after cardiac surgery. This work aimed to analyse the impact of changes in blood lactate levels on the survival of patients on post-cardiotomy ECMO (PC-ECMO) and whether lactate clearance (LC) performs better than absolute lactate levels. METHODS AND RESULTS: We retrospectively analysed the data of adult patients who received PC-ECMO at our centre between 2016 and 2022. The primary outcome was the in-hospital mortality rate. Arterial lactate levels were measured at ECMO initiation, peak and 12 and 24 h after VA-ECMO support. LC was calculated at 12 and 24 h. Out of 2368 patients who received cardiac surgeries, 152 (median age, 48 years; 57.9% of them were men) received PC-ECMO. Of them, 48 (31.6%) survived and were discharged, while 104 (68.4%) died during the index hospitalization. Non-survivors had higher frequencies of atrial fibrillation (41.35% vs. 12.5%, P < 0.001), chronic kidney disease (26.9% vs. 6.3%, P = 0.004), prolonged cardiopulmonary bypass (237 vs. 192 min, P = 0.016) and aortic cross-clamping times (160 vs. 124 min, P = 0.04) than survivors. Non-survivors had a significantly higher median Sequential Organ Failure Assessment (SOFA) score at ECMO initiation (13.5 vs. 9, P < 0.001) and a lower median Survival After Veno-arterial ECMO (SAVE) score (-3 vs. 3, P < 0.001) with higher SAVE classes (P < 0.001) than survivors. After 12 h of VA-ECMO support, the blood lactate level was negatively correlated with LC in survivors (r = -0.755, P < 0.001) and non-survivors (r = -0.601, P < 0.001). After 24 h, the same negative correlation was identified between survivors (r = -0.764, P < 0.001) and non-survivors (r = -0.847, P < 0.001). Blood lactate levels measured at 12 h to determine hospital mortality [>8.2 mmol/L, area under the receiver operating characteristic curve (AUROC): 0.868] and 24 h (>2.6 mmol/L, AUROC: 0.896) had the best performance, followed by LC-T12 (<21.94%, AUROC: 0.807), LC-T24 (<40.3%, AUROC: 0.839) and peak blood lactate (>14.35 mmol/L, AUROC: 0.828). The initial pre-ECMO blood lactate (>6.25 mmol/L, AUROC: 0.731) had an acceptable ability to discriminate mortality but was less than the following measurements and clearance. Kaplan-Meier curves demonstrated that LC of <21.94% at T12 h and <40.3% at T24 h was associated with decreased survival (log-rank P < 0.001). Cox proportional hazards regression analysis for mortality revealed that LC of <21.94% at T12 h had an adjusted hazard ratio (HR) of 2.73 [95% confidence interval (CI): 1.64-5.762, P < 0.001] and LC of <40.3% at T24 h had an adjusted HR of 1.98 (95% CI: 1.46-4.173, P < 0.001). The predictors of hospital mortality after PC-ECMO were the lactate level at 12 h [odds ratio (OR): 1.67, 95% CI: 1.121-2.181, P = 0.001], initial SOFA score (OR: 1.593, 95% CI: 1.15-2.73, P < 0.001), initial blood lactate (OR: 1.21, 95% CI: 1.016-1.721, P = 0.032) and atrial fibrillation (OR: 6.17, 95% CI: 2.37-57.214, P = 0.003). Bivariate models using lactate levels and clearance at the same points revealed that blood lactate levels performed better than the clearance percentage. CONCLUSIONS: Serial measurements of arterial blood lactate and LC help in obtaining early prognostic guidance in adult patients supported by VA-ECMO after cardiac surgery. Absolute lactate levels, compared with LC at the same time points, demonstrated better performance in differentiating mortality.
ABSTRACT
The present study describes the immature stages of Opoptera syme (Hübner, [1821]) using SEM and Micro-CT to generate 2D and 3D models to study the morphology and chaetotaxy, and present information on the natural history, behavior, and population biology. In laboratory, eggs were laid singly, and the isolated larvae passed through six to seven instars. Host plant in the study site is unknown, but larvae are known to feed on bamboos; in laboratory, larvae accepted the ornamental bamboo Bambusa textilis McClure, 1940. Adults are diurnal and univoltine, flying from December to April (the austral summer). The present study adds information to the biology and natural history of Brassolini, an iconic and still poorly known tribe of Neotropical butterflies.
Subject(s)
Butterflies , Lepidoptera , Animals , Butterflies/anatomy & histology , Brazil , Larva/anatomy & histology , Seasons , BiologyABSTRACT
OBJECTIVES: The isolated Príncipe is at malaria pre-elimination stage. Autochthonous clinical cases have been reported sporadically on the island, signalling the possibility of a sizable subpatent (ie, RDT- and microscopy-negative and PCR-positive) parasite reservoir. METHODS: Asymptomatic low-density infections were detected by quantitative PCR (qPCR) targeting Plasmodium falciparum multicopy genes (pfr364 and varATS). Positivity rates were assayed for samples surveyed by active case detection (ACD) (n=112) and reactive case detection (RACD) (n=221) in 2022. RESULTS: qPCR unveiled 70% of low parasitemia carriers, reaching >90% in RACD. The high P. falciparum prevalence was confirmed by the two high-sensitivity qPCR protocols. Higher positivity rates were observed in the localities where most malaria cases were reported in 2022. Most parasitemias were very low (<2 Pf /µl). CONCLUSIONS: These findings suggest that pre-elimination surveillance can benefit from the routine application of highly sensitive tools to unveil otherwise invisible but potentially relevant parasite populations.
ABSTRACT
Despite efforts, available alternatives for the treatment of leishmaniasis are still scarce. In this work we tested a class of 15 quinolinylhydrazone analogues and presented data that support the use of the most active compound in cutaneous leishmaniasis caused by Leishmania amazonensis. In general, the compounds showed activity at low concentrations for both parasitic forms (5.33-37.04 µM to promastigotes, and 14.31-61.98 µM to amastigotes). In addition, the best compound (MHZ15) is highly selective for the parasite. Biochemical studies indicate that the treatment of promastigotes with MHZ15 leads the loss of mitochondrial potential and increase in ROS levels as the primary effects, which triggers accumulation of lipid droplets, loss of plasma membrane integrity and apoptosis hallmarks, including DNA fragmentation and phosphatidylserine exposure. These effects were similar in the intracellular form of the parasite. However, in this parasitic form there is no change in plasma membrane integrity in the observed treatment time, which can be attributed to metabolic differences and the resilience of the amastigote. Also, ultrastructural changes such as vacuolization suggesting autophagy were observed. The in vivo effectiveness of MHZ15 in the experimental model of cutaneous leishmaniasis was carried out in mice of the BALB/c strain infected with L. amazonensis. The treatment by intralesional route showed that MHZ15 acted with great efficiency with significantly reduction in the parasite load in the injured paws and draining lymph nodes, without clinical signs of distress or compromise of animal welfare. In vivo toxicity was also evaluated and null alterations in the levels of hepatic enzymes aspartate aminotransferase, and alanine aminotransferase was observed. The data presented herein demonstrates that MHZ15 exhibits a range of favorable characteristics conducive to the development of an antileishmanial agent.
Subject(s)
Apoptosis , Hydrazones , Leishmaniasis, Cutaneous , Mice, Inbred BALB C , Mitochondria , Animals , Apoptosis/drug effects , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Hydrazones/pharmacology , Hydrazones/chemistry , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/therapeutic use , Leishmania/drug effects , Reactive Oxygen Species/metabolism , Female , Leishmania mexicana/drug effects , Membrane Potential, Mitochondrial/drug effectsABSTRACT
ETNOPHARMACOLOGICAL RELEVANCE: Lantana camara L. is a species known for its broad spectrum of bioactivities and is commonly used in folk therapy to address inflammatory, dermatological, gastrointestinal, intestinal worms and protozoan diseases. It boasts a diverse array of secondary metabolites such as terpenes, flavonoids, and saponins. However, despite its rich chemical profile, there remains a scarcity of studies investigating its antileishmanial properties. AIM OF THE STUDY: This research aims to explore the antileishmanial potential of L. camara, focusing also on its mechanism of action against Leishmania amazonensis. MATERIAL AND METHODS: The ethanolic extract of L. camara leaves (LCE) was obtained through static maceration, and its phytoconstituents were identified using UFLC-QTOF-MS. The colorimetric MTT method was conducted to determine the effect of LCE on promastigotes of L. amazonensis and murine macrophages. The anti-amastigote activity was evaluated by counting intracellular parasites in macrophages after Giemsa staining. Additionally, investigations into the mechanisms underlying its action were conducted using cellular and biochemical approaches. RESULTS: LCE exhibited significant activity against both promastigotes and intracellular amastigotes of L. amazonensis, with IC50 values of 12.20 µg/mL ± 0.12 and 7.09 µg/mL ± 1.24, respectively. These IC50 values indicate very promising antileishmanial activity, comparable to those found for the positive control miltefosine (5.10 µg/mL ± 1.79 and 8.96 µg/mL ± 0.50, respectively). Notably, LCE exhibited negligible cytotoxicity on macrophages (IC50 = 223.40 µg/mL ± 47.02), demonstrating selectivity towards host cells (SI = 31.50). The antileishmanial activity of LCE involved a multi-targeted cell death process, characterized by morphological and ultrastructural alterations observed through SEM and TEM analyses, as well as oxidative effects evidenced by the inhibition of trypanothione reductase, elevation of ROS and lipid levels, and mitochondrial dysfunction evaluated using DTNB, H2DCFDA, Nile red, and JC-1 assays. Additionally, extraction of ergosterol and double labeling with annexin V and PI revealed modifications to the organization and permeability of the treated parasite's plasma membrane. LCE was found to consist predominantly of terpenes, with lantadenes A, B, and C being among the eleven compounds identified through UFLC-QTOF-MS analysis. CONCLUSIONS: The extract of L. camara presents a diverse array of chemical constituents, prominently featuring high terpene content, which may underlie its antileishmanial properties through a combination of apoptotic and non-apoptotic mechanisms of cell death induced by LCE. This study underscores the therapeutic potential of L. camara as a candidate for antileishmanial treatment, pending further validation.
ABSTRACT
Interest in rational use and reuse of water has increased in recent years, especially in forest nurseries. However, before water can be reused in nurseries, it must be properly treated to eradicate plant pathogens to reduce risks of pathogen dispersal and losses to disease. In the present study, the efficacy of irrigation water treatment by ultrafiltration and conventional physical-chemical treatment was studied to eliminate Botrytis cinerea, Cylindrocladium candelabrum, Ralstonia solanacearum, and Xanthomonas axonopodis, the pathogens most commonly found in Brazilian forest nurseries. Ultrafiltration eradicated over 99% of R. solanacearum, X. axonopodis, and B. cinerea and 100% of C. candelabrum. The few remaining cells or conidia of R. solanacearum and B. cinerea did not induce disease in irrigated rooted cuttings. Flocculation and fast sand filtration used in physical-chemical treatment completely eliminated C. candelabrum but the other pathogens were only removed after chlorination of the filtered water. Both forms of treatment are viable, practical, and safe methods for plant pathogen removal from irrigation water.
ABSTRACT
The way the media portrays aquaculture-related events can influence how this industry is perceived by the public and affect its success. Since media are an important source of public information, media content analysis has been carried out in several regions of the world. This study aimed to determine which aspects of aquaculture were more exposed and how they were discussed by regional media in the Madeira archipelago, an oceanic group of Portuguese islands. Analysis of aquaculture's media coverage in the two most-read regional newspapers of Madeira was carried out over a 5-year period (2017 to 2021). For each news article, the assessment focused on the geographic scope, the main topics covered, the stakeholders with access to the debate, and the general tone of the article (risk/benefit framework). A total of 297 articles were analyzed. Results indicate the occurrence of trigger events that contributed to a shift in the amount of news published and in the way media framed aquaculture. In general, political and economic issues dominated the coverage, whereas social, environmental, scientific, and landscape matters received less media attention. The voice of the government was predominant throughout the 5 years in analysis and aquaculture was generally framed with a balanced tone, slightly more negative. Open and transparent communication between the stakeholders and the media is fundamental for the sustainable development of the aquaculture industry.
ABSTRACT
Araçá is a Brazilian native fruit belonging to the Myrtaceae family. Although some studies already prove its health benefits, it is still necessary to explore the phenolic compounds in all its parts separately. This study aimed to investigate the free, esterified, glycosylated, and insoluble phenolics in two morphotypes of araçá, red and yellow, evaluating peel, pulp, and seed separately, using liquid chromatography coupled to mass spectrometry (LC-ESI-QqQ-MS/MS). Fourteen phenolics and five anthocyanins were quantified in both morphotypes. The peels presented the highest contents, followed by the pulp and seeds. Red araçá stood out over the yellow one only in the phenolic fractions resulting from the peel, with the yellow araçá being superior in the phenolic fractions of the pulp and seed. The highest antioxidant capacities were detected for the pulp-esterified phenolics (498.3 µmol g-1) and peel-free phenolics (446.7 µmol g-1) of yellow araçá. Principal component analysis (PCA) indicated specific markers to differentiate the samples. All parts of the araçá proved to be a rich source of phenolic compounds, in different fractions, mainly in the peel. This information will be beneficial to stimulate the consumption of native fruits and their possible use in the development of new products.
ABSTRACT
Aggregates of the tau protein are a well-known hallmark of several neurodegenerative diseases, collectively referred to as tauopathies, including frontal temporal dementia and Alzheimer's disease (AD). Monitoring the transformation process of tau from physiological monomers into pathological oligomers or aggregates in a high-throughput, quantitative manner and in a cellular context is still a major challenge in the field. Identifying molecules able to interfere with those processes is of high therapeutic interest. Here, we developed a series of inter- and intramolecular tau biosensors based on the highly sensitive Nanoluciferase (Nluc) binary technology (NanoBiT) able to monitor the pathological conformational change and self-interaction of tau in living cells. Our repertoire of tau biosensors reliably reports i. molecular proximity of physiological full-length tau at microtubules; ii. changes in tau conformation and self-interaction associated with tau phosphorylation, as well as iii. tau interaction induced by seeds of recombinant tau or from mouse brain lysates of a mouse model of tau pathology. By comparing biosensors comprising different tau forms (i.e. full-length or short fragments, wild-type, or the disease-associated tau(P301L) variant) further insights into the tau transformation process are obtained. Proof-of-concept data for the high-throughput suitability and identification of molecules interfering with the pathological tau transformation processes are presented. This novel repertoire of tau biosensors is aimed to boost the disclosure of molecular mechanisms underlying pathological tau transformation in living cells and to discover new drug candidates for tau-related neurodegenerative diseases.
Subject(s)
Alzheimer Disease , Tauopathies , Mice , Animals , tau Proteins/genetics , tau Proteins/metabolism , Alzheimer Disease/metabolism , Tauopathies/pathology , Microtubules/metabolism , Neurons/physiology , Brain/metabolismABSTRACT
This study aimed to analyze the multiple characteristics of the decentralization of the Brazilian National Food and Nutritional Security System (SISAN) in a period before the institutional dismantling. Data from the 26 Brazilian states were collected in two public information systems, referring to the years 2017/2018. An exploratory and descriptive study was performed using a hierarchical cluster analysis, based on an analysis model with multiple characteristics of the system decentralization. The results indicated the formation of three clusters, showing the similarity among states with greater intersectoral and participatory character, better relationship with municipalities, and allocation of resources. On the other hand, states with less intersectoral and participatory character, linked to the low allocation of resources, execution of food security actions, and municipal support were clustered. These clusters composed mainly of North and Northeastern states, with a lower Gross Domestic Product, average Human Development Index, and a higher occurrence of food insecurity, expressed characteristics that may be related to greater obstacles in the system decentralization process. This information can help in the decision-making about the SISAN in a more equitable manner, supporting the actors involved in its maintenance and defense, at a time when the country presents an austere political and economic situation, marked by the progressive worsening of food insecurity.
Subject(s)
Food Supply , Food , Humans , Brazil/epidemiology , PoliticsABSTRACT
Background: Risk factors for postoperative chylothorax in children who had cardiothoracic procedures are not always clear. Due to complex course in post-operative care, It's always challenging to find the risk factors, and their management. Objective: The aim of our study was to identify the incidence, risk factors and effective treatment approaches for chylothorax after pediatric heart surgery. Methods: Children who had the cardiac surgery and subsequently developed chylothorax were included in the study. The ratio of the experimental group to the control group was 1:2. Decannulations of extracorporeal membrane oxygenation (ECMO) were not included in the analysis of patient outcomes. For each patient, we keep track of their age, weight, gender, syndrome, RACH-1 scoring, fluid balance, bypass time, clamp time, redo operations, open or close heart surgeries, and rhythm difficulties. Care logs were kept for every single therapy that was administered. Primary outcome was chylothorax, with secondary outcomes included time in the intensive care unit (ICU), length of hospital stay (LOS), and death. Results: 5210 surgeries were performed in six years. 96 patients developed the chylothorax with incidence of 1.8%. In chylothorax group, mean weight was 6.7 ± 4.2, while mean age was 11.7 ± 15.2. Clamp time was 74.5 ± 53.5 versus 39.9 ± 13.7. Mean bypass time was 128.34(76.25) versus 84.3 ± 25.1 with an odds ratio 1.02 (Z test 0.0001). Six (6.3%) children with chylothorax had redo cardiac surgeries in the same admission (p-value 0.01) while none in other. Five (5.2%) cases got operated by thoracotomy, three from left side. Mean Chest tube duration was 10±7.8 days versus 3.8±2.4 in control group. (p-value 0.02). chylothorax resolved (mean resolving time = 4 days) in 76 (79.2%) children with monogen formula. Two patients receive midodrine with no significant effect. Four children underwent surgical repair for chylothorax. Conclusion: Bypass time linearly increases incidence of chylothorax. Younger age, low weight, syndromic children, redo operations, non-open-heart surgeries, and arrhythmias also contribute to this. Gender, fluid balance, and RACHS-1 Scoring were not significant. While further research and testing are required for the use of midodrine. However, the low-fat formula of Monogen has proven to be an effective treatment.
ABSTRACT
BACKGROUND: Traditional methods for assessing individual energy consumption often involve lengthy and intricate procedures. This study aims to introduce an Energy Consumption Estimation Scale, utilizing Item Response Theory (IRT) for adolescents aged 18-19 years. METHODS: This psychometric investigation applies IRT to 93 items extracted from a validated food frequency questionnaire. The study encompasses a representative sample of 2515 adolescents from the São Luís birth cohort in Brazil. The latent trait, energy intake, is derived using IRT and subsequently validated through hierarchical multiple linear regression modeling. Significance was established at p < 0.05. RESULTS: A Samejima's model was successfully fitted (CFI and TLI > 0.9 and RMSEA < 0.08), effectively capturing variations across all energy consumption levels. Factors associated with the latent trait demonstrate consistent behavioral patterns. Adolescents with higher energy intake exhibited increased consumption of dairy products, artificially sweetened beverages, and seasonal fruits and vegetables. CONCLUSIONS: The proposed Energy Consumption Estimation Scale demonstrates a reliable measurement of energy intake and serves as a practical and concise alternative for assessing energy consumption among adolescents. These findings suggest the potential for adapting similar models for different age groups and incorporating diverse food items based on the obtained results.