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This study investigated the antitumoral, anti-inflammatory and oxidative effects of polysaccharides from tucum (Bactris setosa, TUC) using the Ehrlich carcinoma as a tumor model. Additionally, the glycogen content, cytochrome P levels, and gluconeogenesis from lactate were assessed in the liver of healthy animals. Tumor-bearing female mice were orally treated with 50 and 100 mg.kg-1 of TUC or vehicle, once a day, or with 1.5 mg.kg-1 methotrexate via i.p., every 3 days, along 21 days. Both doses of TUC reduced the tumor weight and volume. In the tumor tissue, it decreased GSH and IL-1ß levels, and increased LPO, NAG, NO and TNF-α levels. The tumor histology showed necrosis and leukocytes infiltration. The metabolic effects of TUC were investigated by measurement of total cytochrome P (CYP) and glycogen in tumor-bearing mice, and by ex vivo liver perfusion on non-bearing tumor male mice, using lactate as gluconeogenic precursor. Metabolically, the hepatic glucose and pyruvate productions, oxygen uptake, and the total CYP concentration were not modified by TUC. Thus, tucum-do-cerrado polysaccharides have antitumor effects through the modulation of oxidative stress and inflammation, without impairing glucose production from lactate in the liver, the main organ responsible for the metabolism of organic and xenobiotic compounds.
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Gluconeogênese , Fígado , Polissacarídeos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Gluconeogênese/efeitos dos fármacos , Feminino , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/química , Estresse Oxidativo/efeitos dos fármacos , Frutas/química , Glicogênio/metabolismo , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
BACKGROUND: Hemolysis due to ABO incompatibility is an important differential diagnosis in newborns presenting with jaundice. Clinical studies evaluating ABO hemolytic disease of fetus and newborn (ABO-HDFN) question the diagnostic value of the direct antiglobulin test (DAT) in this situation. GOALS: To determine the clinical and laboratorial findings associated with the occurrence of ABO-HDFN and to evaluate the accuracy of DAT as a diagnostic tool. METHODS: This was a nested case control study with a cohort of 4122 newborns. Clinical and immunohematological data were retrieved from medical files including clinical and laboratorial factors associated with ABO-HDFN. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of positive DAT were calculated. RESULTS: Among the 4122 newborns, 44 had the diagnosis of ABO-HDFN. Positive DAT, group O mother and group A newborn were significantly associated with the occurrence of neonatal jaundice and this association persisted in a multivariable model (p-value <0.001). DAT presented 65.85 % sensitivity, 96.28 % specificity, 16.9 % PPV and 99.6 % NPV for the diagnosis of ABO-HDFN. There were no cases of positive DAT in cases other than O/A and O/B incompatibilities. The newborn hemoglobin was significantly lower in O/A incompatibility (p-value <0.001). CONCLUSION: Positive DAT, mother of group O and newborn of group A are independent risk factors associated with ABO-HDFN. DAT exhibited high NPV for the diagnosis of this complication. Thus, performing DAT in newborns with O/A and O/B incompatibilities is a cost-effective strategy that can be applied as routine by blood banks.
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BACKGROUND AND OBJECTIVES: The isolation of neutrophils and subsequent detection of anti-human neutrophil antigens (HNA) antibodies are crucial in clinical medicine for the diagnosis of autoimmune neutropenia, neonatal alloimmune neutropenia (NAIN) and transfusion-related acute lung injury (TRALI). This study reports two cases of maternal anti-Fc-gamma-receptor-IIIb (FcγRIIIb) isoimmunization without NAIN symptoms and compares the efficiency of immunomagnetic negative selection (IMNS) with traditional dextran/Ficoll for neutrophil isolation in HNA serological assays. MATERIALS AND METHODS: Investigating two cases of maternal anti-FcγRIIIb isoimmunization, neutrophils from three donors were isolated from 8 mL of whole blood using IMNS and dextran/Ficoll. Serological assays included the granulocyte agglutination and immunofluorescence test, monoclonal antibody immobilization of granulocyte antigens and the LABScreen Multi (One Lambda). IMNS and dextran/Ficoll were compared in terms of cell yield, viability, time, cost and purity. RESULTS: Maternal anti-FcγRIIIb isoantibodies with FCGR3B gene deletion were detected in both cases. Newborns and fathers exhibited specific gene combinations: FCGR3B*02/FCGR3B*02 (Case 1) and FCGR3B*02/FCGR3B*03 (Case 2). IMNS outperformed dextran/Ficoll, yielding four times more neutrophils (average neutrophil counts: 18.5 × 103/µL vs. 4.5 × 103/µL), efficiently removing non-neutrophil cells and reducing processing time (30-40 min vs. 70-90 min), although it incurred a higher cost (2.7 times). CONCLUSION: Two cases of maternal anti-FcγRIIIb isoantibodies, unrelated to NAIN, were identified. Although neutropenia has not been described in these cases, we emphasize the importance of identifying asymptomatic cases with the potential for severe neutropenia. Additionally, IMNS is introduced as a rapid, high-yield, high-purity neutrophil isolation technique, beneficial for serological assays detecting anti-HNA antibodies.
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Isoanticorpos , Neutrófilos , Receptores de IgG , Humanos , Neutrófilos/imunologia , Feminino , Receptores de IgG/imunologia , Isoanticorpos/imunologia , Isoanticorpos/sangue , Recém-Nascido , Proteínas Ligadas por GPI/imunologia , Masculino , Separação Imunomagnética/métodos , Adulto , Gravidez , Neutropenia/imunologia , Neutropenia/sangueRESUMO
Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.
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Anemia Falciforme , HidroxiureiaRESUMO
Farnesol, a sesquiterpene found in all eukaryotes, precursor of juvenile hormone (JH) in insects, is involved in signalling, communication, and antimicrobial defence. Farnesol is a compound of floral volatiles, suggesting its importance in pollination and foraging behaviour. Farnesol is found in the resin of Baccharis dracunculifolia, from which honeybees elaborate the most worldwide marketable propolis. Bees use propolis to seal cracks in the walls, reinforce the wax combs, and as protection against bacteria and fungi. The introduction within a honeybee hive of a compound with potential hormonal activity can be a challenge to the colony survival, mainly because the transition from within-hive to outside activities of workers is controlled by JH. Here, we tested the hypothesis that exogenous farnesol alters the pacing of developing workers. The first assays showed that low doses of the JH precursor (0.1 and 0.01 µg) accelerate pharate-adult development, with high doses being toxic. The second assay was conducted in adult workers and demonstrated bees that received 0.2 µg farnesol showed more agitated behaviour than the control bees. If farnesol was used by corpora allata (CA) cells as a precursor of JH and this hormone was responsible for the observed behavioural alterations, these glands were expected to be larger after the treatment. Our results on CA measurements after 72 h of treatment showed bees that received farnesol had glands doubled in size compared to the control bees (p < 0.05). Additionally, we expected the expression of JH synthesis, JH degradation, and JH-response genes would be upregulated in the treated bees. Our results showed that indeed, the mean transcript levels of these genes were higher in the treated bees (significant for methyl farnesoate epoxidase and juvenile hormone esterase, p < 0.05). These results suggest farnesol is used in honeybees as a precursor of JH, leading to increasing JH titres, and thus modulating the pacing of workers development. This finding has behavioural and ecological implications, since alterations in the dynamics of the physiological changes associated to aging in young honeybees may significantly impact colony balance in nature.
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Hormônios Juvenis , Própole , Abelhas , Animais , Hormônios Juvenis/metabolismo , Farneseno Álcool , Resinas Vegetais , Insetos/metabolismoRESUMO
To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.
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In phytophagous insects, adaptation to a new host is a dynamic process, in which early and later steps may be underpinned by different features of the insect genome. Here, we tested the hypothesis that early steps of this process are underpinned by a shift in gene expression patterns. We set up a short-term artificial selection experiment (10 generations) for the use of an alternative host (Cicer arietinum) on populations of the bean beetle Zabrotes subfasciatus. Using Illumina sequencing on young adult females, we show the selected populations differ in the expression of genes associated to stimuli, signalling, and developmental processes. Particularly, the "C. arietinum" population shows upregulation of histone methylation genes, which may constitute a strategy for fine-tuning the insect global gene expression network. Using qPCR on body regions, we demonstrated that the "Phaseolus vulgaris" population upregulates the genes polygalacturonase and egalitarian and that the expression of an odorant receptor transcript variant changes over generations. Moreover, in this population we detected the existence of vitellogenin (Vg) variants in both males and females, possibly harbouring canonical reproductive function in females and extracellular unknown functions in males. This study provides the basis for future genomic investigations seeking to shed light on the nature of the proximate mechanisms involved in promoting differential gene expression associated to insect development and adaptation to new hosts.
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Farnesol is a natural essential oil with antimicrobial properties. Complexation of farnesol in chitosan nanoparticles can be useful to improve its bioavailability and potentiate its antifungal capabilities such as inhibition of hyphal and biofilm formation. The aim of this study was to develop and characterize chitosan nanoparticles with farnesol (NF) and evaluate their toxicity and antifungal action on C. albicans in vivo. The NF were prepared by the ionic gelation method and showed physicochemical characteristics such as diameter less than 200 nm, monodisperse distribution, positive zeta potential, spherical morphology, and stability after 120 days of storage. In the evaluation of toxicity in Galleria mellonella, NF did not reduce the survival rate, indicating that there was no toxicity in vivo at the doses tested. In the assays with G. mellonella infected by C. albicans, the larvae treated with NF had a high survival rate after 48 h, with a significant reduction of the fungal load and inhibition of the formation of biofilms and hyphae. In the murine model of vulvovaginal candidiasis (VVC), histopathological analysis showed a reduction in inflammatory parameters, fungal burden, and hyphal inhibition in mice treated with NF. The produced nanoparticles can be a promising alternative to inhibit C. albicans infection.
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Quitosana , Nanopartículas , Animais , Camundongos , Candida albicans , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farneseno Álcool/farmacologia , Quitosana/farmacologia , Biofilmes , Nanopartículas/químicaRESUMO
Studies and innovations on alternative feed additives, especially on homeopathic remedies have been highlighted in order to replace or reduce the use of antibiotics in pig production. This paper aimed to assess the addition of homeopathic products in pig diet and their effects on the growth performance, serum metabolites, nutrient and energy digestibility, carcass traits and meat quality. A total of 60 immunocastrated male pigs, weighing on average 30.91 ± 0.95 kg, were distributed in two treatments, 10 replicates and three animals/experimental unit. There was no effect (P≥0.05) of treatment on the growth performance and serum metabolites. The percentage of acid-insoluble ash recovered in the diet was greater (P≤0.01) in diets containing homeopathic products. The apparent digestible energy of diets containing homeopathic products was reduced (P≤0.01) in the growing phase and reduced (P≤0.01) the apparent digestibility coefficients of dry matter, crude protein, soluble neutral and acid detergent fibers, and gross energy in the growing and finishing phases. Pig that received diets with homeopathic products had higher (P≤0.05) amount of meat, percentage of meat and marbling. The use of homeopathic products in diets improves the percentage and quality of meat, as well as the marbling of the pig carcass, maintaining the performance.
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Materia Medica , Masculino , Suínos , Animais , Ração Animal/análise , Dieta/veterinária , Nutrientes , Carne , Fenômenos Fisiológicos da Nutrição AnimalRESUMO
BACKGROUND: Neonatal herpes simplex virus (HSV) infection is rare and has significant morbimortality rates. Approximately 85% of newborns are infected intrapartum, and risk factors for mother-to-child transmission include vaginal delivery, primary maternal infection, and prolonged rupture of membranes. Neonatal HSV can manifest with isolated mucocutaneous lesions, neurological involvement, or disseminated disease. In general, herpetic infection can cause blepharoconjunctivitis or keratitis. We report a rare case of congenital herpes with ophthalmologic manifestations and multisystemic involvement. CASE PRESENTATION: A preterm infant, born at 32 weeks and 2 days, with presumed neonatal infection developed intestinal and respiratory complications, as well as hyperemic lesions on the left nostril and oral mucosa. An ophthalmological assessment was requested and brought up the suspicion of HSV infection, indicating empirical treatment with endovenous acyclovir. Later, a new ocular examination was suggestive of panuveitis. Afterward, serum IgM antibodies to HSV-1 and HSV-2 were positive. Proper antiviral therapy led to an improvement in the condition. DISCUSSION: Neonatal herpes is associated with a high risk of persistent skin lesions, long-term neurological disability and other lasting sequelae. It is essential to consider HSV infection in cases of neonatal conjunctivitis, especially in patients with an epithelial defect and no improvement after initial treatment with topical or systemic antibiotics. CONCLUSIONS: In the management of neonatal HSV, early diagnosis is essential for the timely initiation of antiviral therapy. Our report highlights that ocular assessment can be crucial in the correct diagnostic investigation of this condition.
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Doenças Fetais , Herpes Simples , Complicações Infecciosas na Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , Antivirais/uso terapêutico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Recém-Nascido Prematuro , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
Secondary fungal infections are frequently observed in COVID-19 patients. However, the occurrence of candiduria in these patients and its risk factors are underexplored. We evaluated the risk factors of candiduria in COVID-19 patients, including inflammatory mediators that could be used as prognostic markers. Clinical information, laboratory test results, and outcomes were collected from severely ill COVID-19 patients with and without candiduria. Candida species identification, antifungal susceptibility, and plasma inflammatory mediators' measurements were performed. Regression logistic and Cox regression model were used to evaluate the risk factors. A higher risk of longer hospitalization and mortality were observed in patients with candiduria compared to those with COVID-19 only. Candiduria was caused by Candida albicans, C. glabrata, and C. tropicalis. Isolates with intermediate susceptibility to voriconazole and resistant to caspofungin were identified. Classic factors such as the use of corticosteroids and antibacterials, the worsening of renal function, and hematological parameters (hemoglobin and platelets) were found to predispose to candiduria. The mediators IL-1ß, IL-1ra, IL-2, CXCL-8, IL-17, IFN-γ, basic FGF, and MIP-1ß were significantly increased in patients with COVID-19 and candiduria. Furthermore, IFN-γ, IL-1ra, and CXCL-8 were associated with the occurrence of candiduria in COVID-19 patients, whereas basic FGF, IL-1ß, and CXCL-8 were associated with the risk of death in these patients. Classical and immunological factors were associated with worse prognosis among patients with COVID-19 and candiduria. Some mediators, especially CXCL-8, can be a reliable biomarker of fungal coinfection and may guide the diagnostic and the treatment of these patients.
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COVID-19 , Candidíase , Infecções Urinárias , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Candidíase/microbiologia , Infecções Urinárias/microbiologia , Antifúngicos/uso terapêutico , Fatores de Risco , Candida glabrataRESUMO
ABSTRACT Introduction: The Band 3 is a red blood cell protein that carries the Dia and Dib antigens from the Diego blood system. The SLC4A1 gene encodes Band 3; Band 3 Memphis is a polymorphism of normal Band 3 and has two variants, but only the variant II carries the Dia antigen. Objectives: Describe the frequencies of the DI*A and DI*B alleles and the Band 3 Memphis among blood donors, sickle cell disease (SCD) patients and Amazonian Indians. Methods: A total of 427 blood samples were collected and separated into three groups: 206 unrelated blood donors, 90 patients with SCD and 131 Amazonian Indians. We performed DI*A/B, normal Band 3 and Band 3 Memphis genotyping, using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP). Results: The frequency of the DI*A/DI*A genotype was 0.5% in blood donors and it was not found in other groups. The frequency of the DI*A/DI*B was higher in Amazonian Indians (33.6%) and the frequency of the DI*B/DI*B was highest in blood donors (92.2%). All 105 individuals tested were positive for the presence of normal Band 3 and of these individuals, only 5/105 (4.8%) presented the Band 3 Memphis mutation. Conclusion: We observed a higher frequency of the DI*B allele in blood donors and a low frequency of the DI*A/DI*A genotype in all groups studied. The Band 3 Memphis was found in a higher frequency in the blood donor group. Our findings highlight the importance of analyzing different population groups to gain a better understanding of the genetic association of blood group antigens.
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Humanos , Anemia Falciforme , Doadores de Sangue , Cristalização , EritrócitosRESUMO
Phosphorus (P) is a plant macronutrient that is indispensable for maize (Zea mays L.) production. However, P is difficult to manage in weathered soils, and its fertilization practice has low efficiency because it becomes unavailable for absorption by plant roots. Symbiosis of plants with arbuscular mycorrhizal fungi increases plant growth and enhances P uptake from the soil that is not directly available to the roots. Thus, the objective of this study was to determine how inoculation with Rhizophagus intraradices and phosphate fertilization interacts and influences the development and productivity of second-crop maize. The experiment was conducted in Selvíria, Mato Grosso do Sul, Brazil, in 2019 and 2020, both in a Typic Haplorthox. A randomized block design in subdivided plots was used for the phosphate application during crop sowing (0, 25, 50, 75, and 100% concentrations of the recommended level), and the secondary treatments were the doses of mycorrhizal inoculant (0, 60, 120 and 180 g ha-1) applied to the seed using a dry powder inoculant containing 20,800 infectious propagules per gram of the arbuscular mycorrhizal fungus R. intraradices. Only in the first year of the experiment, inoculation and phosphate fertilization promoted benefits to the maize crop, indicating potential to increase yield.
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Micorrizas , Fosfatos , Zea mays , Raízes de Plantas , Solo , FertilizaçãoRESUMO
Hexamerins, the proteins massively stored in the larval haemolymph of insects, are gradually used throughout metamorphosis as a source of raw material and energy for the development of adult tissues. Such behaviour defined hexamerins as storage proteins. Immunofluorescence experiments coupled with confocal microscopy show a hexamerin, HEX 70a, in the nucleus of the brain and fat body cells from honeybee workers, an unexpected localization for a storage protein. HEX 70a colocalizes with fibrillarin, a nucleolar-specific protein and H3 histone, thus suggesting a potential role as a chromatin-binding protein. This was investigated through chromatin immunoprecipitation and high-throughput DNA sequencing (ChIP-seq). The significant HEX 70a-DNA binding sites were mainly localized at the intergenic, promoter and intronic regions. HEX 70a targeted DNA stretches mapped to the genomic regions encompassing genes with relevant functional attributes. Several HEX 70a targeted genes were associated with H3K27ac or/and H3K27me3, known as active and repressive histone marks. Brain and fat body tissues shared a fraction of the HEX 70 targeted genes, and tissue-specific targets were also detected. The presence of overrepresented DNA motifs in the binding sites is consistent with specific HEX 70a-chromatin association. In addition, a search for HEX 70a targets in RNA-seq public libraries of fat bodies from nurses and foragers revealed differentially expressed targets displaying hex 70a-correlated developmental expression, thus supporting a regulatory activity for HEX 70a. Our results support the premise that HEX 70a is a moonlighting protein that binds chromatin and has roles in the brain and fat body cell nuclei, apart from its canonical role as a storage protein.
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Cromatina , Corpo Adiposo , Animais , Abelhas/genética , Encéfalo , Núcleo Celular/metabolismo , Cromatina/metabolismo , Corpo Adiposo/metabolismo , Larva/genética , Proteínas de Insetos/metabolismoRESUMO
INTRODUCTION: The Band 3 is a red blood cell protein that carries the Dia and Dib antigens from the Diego blood system. The SLC4A1 gene encodes Band 3; Band 3 Memphis is a polymorphism of normal Band 3 and has two variants, but only the variant II carries the Dia antigen. OBJECTIVES: Describe the frequencies of the DI*A and DI*B alleles and the Band 3 Memphis among blood donors, sickle cell disease (SCD) patients and Amazonian Indians. METHODS: A total of 427 blood samples were collected and separated into three groups: 206 unrelated blood donors, 90 patients with SCD and 131 Amazonian Indians. We performed DI*A/B, normal Band 3 and Band 3 Memphis genotyping, using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: The frequency of the DI*A/DI*A genotype was 0.5% in blood donors and it was not found in other groups. The frequency of the DI*A/DI*B was higher in Amazonian Indians (33.6%) and the frequency of the DI*B/DI*B was highest in blood donors (92.2%). All 105 individuals tested were positive for the presence of normal Band 3 and of these individuals, only 5/105 (4.8%) presented the Band 3 Memphis mutation. CONCLUSION: We observed a higher frequency of the DI*B allele in blood donors and a low frequency of the DI*A/DI*A genotype in all groups studied. The Band 3 Memphis was found in a higher frequency in the blood donor group. Our findings highlight the importance of analyzing different population groups to gain a better understanding of the genetic association of blood group antigens.
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Secondary infections are one of the complications in COVID-19 patients. We aimed to analyze the antimicrobial prescriptions and their influence on drug resistance in fungi and bacteria isolated from severely ill COVID-19 patients. Seventy-nine severely ill COVID-19 hospitalized patients with secondary bacterial or fungal infections were included. We analyzed the prescribed antimicrobial regimen for these patients and the resistance profiles of bacterial and fungal isolates. In addition, the association between drug resistance and patients' outcome was analyzed using correlation tests. The most prescribed antibacterial were ceftriaxone (90.7% of patients), vancomycin (86.0%), polymyxin B (74.4%), azithromycin (69.8%), and meropenem (67.4%). Micafungin and fluconazole were used by 22.2 and 11.1% of patients, respectively. Multidrug-resistant (MDR) infections were a common complication in severely ill COVID-19 patients in our cohort since resistant bacteria strains were isolated from 76.7% of the patients. Oxacillin resistance was observed in most Gram-positive bacteria, whereas carbapenem and cephalosporin resistance was detected in most Gram-negative strains. Azole resistance was identified among C. glabrata and C. tropicalis isolates. Patients who used more antimicrobials stayed hospitalized longer than the others. The patient's age and the number of antibacterial agents used were associated with the resistance phenotype. The susceptibility profile of isolates obtained from severely ill COVID-19 patients highlighted the importance of taking microbial resistance into account when managing these patients. The continuous surveillance of resistant/MDR infection and the rational use of antimicrobials are of utmost importance, especially for long-term hospitalized patients with COVID-19.
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Tratamento Farmacológico da COVID-19 , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Fungos , Prescrições , Resistência a MedicamentosRESUMO
Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure (p = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral (p = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals (p = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio (p = 0.062 and p = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy (p = 0.044) and increased interstitial fibrosis (p = 0.028) compared with controls. Reduced protein carbonyls (PC) (p = 0.030) and catalase activity (p = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC (p = 0.002) and the activity of superoxide dismutase and catalase (p = 0.044 and p = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher (p = 0.039 and p = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.
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BACKGROUND: Chemical seed treatment is an established practice in agriculture to protect crops from soil-borne pathogens and pests. Arbuscular mycorrhizal fungi (AMF) benefit plants by extending soil exploration as well as water and nutrient uptake. The objective of this work was to analyze the effects of combinations of seed treatments with doses of inoculant containing Rhizoglomus intraradices on vegetative development, root colonization and nutrition of Phaseolus vulgaris plants and soil microbiota. RESULTS: Seed treatment benefited the vegetative development and nutrition of beans, with the treatments metalaxyl + fludioxonil + tiabendazole and pyraclostrobin + thiophanate methyl + fipronil standing out regarding the contents of nitrogen (N), phosphorus (P), iron (Fe) and zinc (Zn) of the aerial parts. Mycorrhizal inoculation linearly increased dehydrogenase activity, root biomass and total plant biomass, with increments reaching 27%. There was an interaction between seed treatment and inoculation dose for aboveground biomass and the contents of potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), manganese (Mn) and root colonization, with expressive results for the combination of the two highest doses of inoculant with metalaxyl + fludioxonil + tiabendazole or pyraclostrobin + methylthiophanate + fipronil in the seeds. CONCLUSION: Chemical seed treatment and mycorrhizal inoculation benefited bean plants and their nutritional status. The best combinations for the bean crop were metalaxyl + fludioxonil + tiabendazole with 41.4 mg of the inoculant per 100 seeds and pyraclostrobin + thiophanate methyl + fipronil with 62.1 mg of the inoculant per 100 seeds. © 2022 Society of Chemical Industry.
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Micorrizas , Phaseolus , Estado Nutricional , Raízes de Plantas/microbiologia , Sementes , Solo , Simbiose , Tiofanato/farmacologiaRESUMO
Chronic myeloid leukemia (CML), a hematopoietic neoplasm arising from the fusion of BCR (breakpoint cluster region) gene on chromosome 22 to the ABL (Abelson leukemia virus) gene on chromosome 9 (BCR-ABL1 oncogene), originates from a small population of leukemic stem cells with extensive capacity for self-renewal and an inflammatory microenvironment. Currently, CML treatment is based on tyrosine kinase inhibitors (TKIs). However, allogeneic hematopoietic stem cell transplantation (HSCT-allo) is currently the only effective treatment of CML. The difficulty of finding a compatible donor and high rates of morbidity and mortality limit transplantation treatment. Despite the safety and efficacy of TKIs, patients can develop resistance. Thus, microRNAs (miRNAs) play a prominent role as biomarkers and post-transcriptional regulators of gene expression. The aim of this study was to analyze the miRNA profile in CML patients who achieved cytogenetic remission after treatment with both HSCT-allo and TKI. Expression analyses of the 758 miRNAs were performed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Bioinformatics tools were used for data analysis. We detected miRNA profiles using their possible target genes and target pathways. MiR-125a-3p stood out among the downregulated miRNAs, showing an interaction network with 52 target genes. MiR-320b was the only upregulated miRNA, with an interaction network of 26 genes. The results are expected to aid future studies of miRNAs, residual leukemic cells, and prognosis in CML.
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Antineoplásicos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , MicroRNAs/metabolismo , Adulto , Biologia Computacional , Regulação para Baixo/efeitos dos fármacos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Mapas de Interação de Proteínas/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
A erupção pigmentar fixa (EPF) é uma reação cutânea adversa a drogas relativamente comum, envolvendo cerca de 10% de todas as reações de hipersensibilidade a medicamentos (RHM). Envolve uma reação imunológica não imediata, mediada por células T CD8+ sensibilizadas, relacionada ao mecanismo do tipo IVc na classificação de Gell e Coombs. Um dos grupos mais frequentemente implicados nesse tipo de reação é o dos antiinflamatórios. Relatamos o caso de um homem que, 24 horas após iniciar tratamento com nimesulida para lombalgia, apresentou um quadro de lesões cutâneas tipo máculas eritemato-violáceas bem delimitadas e disseminadas pelo corpo. A nimesulida é um fármaco anti-inflamatório não esteroidal (AINE) pertencente à classe das sulfonanilidas, que atua como inibidor seletivo da enzima da síntese de prostaglandina, a ciclo-oxigenase, inibindo preferencialmente a COX-2. O diagnóstico foi comprovado pela realização do teste de contato, também conhecido como patch test, que traduziu positividade na segunda leitura realizada após 72 horas da sua colocação.
Fixed pigmented erythema (FPE) is a relatively common adverse drug reaction, consisting of approximately 10% of all drug hypersensitivity reactions. It involves a non-immediate immune reaction mediated by sensitized CD8+ T cells and related to the type IVc mechanism in the Gell-Coombs classification. One of the groups most frequently involved in this type of reaction is that of anti-inflammatory drugs. We report the case of a man who, 24 hours after starting treatment with nimesulide for low back pain, presented with well-defined cutaneous lesions consisting of erythematous-violaceous macules and spread throughout the body. Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) belonging to the sulfonanilide class that acts as a selective inhibitor of the prostaglandin synthesis enzyme, cyclooxygenase (COX), preferentially inhibiting COX-2. The diagnosis was confirmed by a patch test, which translated positively in the second reading performed 72 hours after its placement.