RESUMO
AIM: The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. METHODS AND RESULTS: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7·81-31·25 µg ml-1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. CONCLUSIONS: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.
Assuntos
Acridonas/farmacologia , Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Acridonas/síntese química , Antifúngicos/síntese química , Biofilmes/crescimento & desenvolvimento , Candida/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Sobrevivência Celular , Humanos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Trichophyton/efeitos dos fármacos , Trichophyton/crescimento & desenvolvimentoRESUMO
New species of insect-specific viruses (ISV) have been reported worldwide. In the present study, the complete genome of Culex flavivirus (CxFV) and partial sequences of other ISVs in Culex quinquefasciatus Say 1823 females (n = 3425) sampled in 200 urban areas census tracts of Cuiaba, state of Mato Grosso, were identified via reverse transcriptase-polymerase chain reaction for a NS5 region of flaviviruses, nucleotide and high-throughput sequencing, and viral isolation in C6/36 cells. CxFV was detected in 16 of 403 mosquito pools; sequences found in the study presented a high similarity with isolates from São Paulo, Brazil and other countries in Latin American that belong to genotype II, supporting the geographical influence on CxFV evolution. The monthly maximum likelihood estimation for CxFV ranged from 1.81 to 9.94 per 1000 mosquitoes. In addition to the CxFV complete genome, one pool contained an ORF1 sequence (756 bp) that belongs to a novel Negevirus from the Sandewavirus supergroup most similar to the Santana virus (77.1%) and another pool presented an RNA-dependent RNA polymerase sequence (1081 bp) of a novel Rhabdovirus most similar to Wuhan mosquito virus 9 (44%). After three passages in C6/36 cells, only CxFV was isolated from these co-infected pools. The importance of ISVs relies on their possible ability to interfere with arbovirus replication in competent vectors.
Assuntos
Culex/virologia , Flavivirus/genética , Genoma Viral , Animais , Brasil , Feminino , Flavivirus/classificação , Flavivirus/isolamento & purificação , Genótipo , FilogeniaRESUMO
Context: Fluconazole (FNZ) is a drug used in antifungal therapy. However, the minimum FNZ dose to interfering with immune responses or inducing DNA damage is still unknown. Objective: This study investigated the toxicological profile of FNZ on cultured human peripheral blood mononuclear cells (PBMCs) treated with different concentrations of this azole. Materials and methods: Cultured PBMCs were exposed to FNZ (6, 12, 30, 60 and 120 µg/mL) and the toxicological profile was assessed by the following parameters: cytotoxic and nuclear division index (necrotic, apoptotic and viable cells), DNA damage (alkaline comet test), mutagenic potential (micronucleus test), cytokine modulation (IL-1, IL-6, IL-10, TNF-α, IFN-γ), and predictive toxicity (Osiris® and LAZAR® programs). Results: Our results demonstrated that FNZ induced cellular DNA damage and mutagenicity at concentrations above the plasma peak (>30 µg/mL) and 6 µg/mL, respectively, which was associated with increased TNF-α, and decrease IL-6 and IL-10 concentrations. These effects may be related to increased apoptosis and cytotoxic nuclear division index in the cultured PBMCs. In silico results indicated potential mutagenic, tumorigenic, irritant, and carcinogenic effects, which were partially confirmed by the above assays. Discussion and conclusions: Together, these findings suggest the need to rationalize the use of FNZ, especially if it is used for long periods or with concomitant pathologies requiring azole therapy that may increase FNZ's plasma concentration.
Assuntos
Antifúngicos/toxicidade , Citocinas/imunologia , Dano ao DNA , Fluconazol/toxicidade , Leucócitos Mononucleares/efeitos dos fármacos , Mutagênicos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/genética , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Interleucina-10/imunologia , Interleucina-6/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Since there is conflicting data on the buffering and ergogenic properties of calcium lactate (CL), we investigated the effect of chronic CL supplementation on blood pH, bicarbonate, and high-intensity intermittent exercise performance. Sodium bicarbonate (SB) was used as a positive control. Eighteen athletes participated in this double-blind, placebo-controlled, crossover, fully counterbalanced study. All participants underwent three different treatments: placebo (PL), CL, and SB. The dose was identical in all conditions: 500 mg/kg BM divided into four daily individual doses of 125 mg/kg BM, for five consecutive days, followed by a 2-7-day washout period. On the fifth day of supplementation, individuals undertook four 30-s Wingate bouts for upper body with 3-min recovery between bouts. Total mechanical work (TMW) for the overall protocol and for the initial (1st+2nd) and final (3rd+4th) bouts was determined at each session. Blood pH, bicarbonate, and lactate levels were determined at rest, immediately and 5 min after exercise. CL supplementation did not affect performance (P > 0.05 for the overall TMW as well for initial and final bouts), nor did it affect blood bicarbonate and pH prior to exercise. SB supplementation improved performance by 2.9% for overall TMW (P = 0.02) and 5.9% in the 3rd+4th bouts (P = 0001). Compared to the control session, SB also promoted higher increases in blood bicarbonate than CL and PL (+0.03 ± 0.04 vs +0.009 ± 0.02 and +0.01 ± 0.03, respectively). CL supplementation was not capable of enhancing high-intensity intermittent performance or changing extracellular buffering capacity challenging the notion that this dietary supplement is an effective buffering agent.
Assuntos
Compostos de Cálcio/administração & dosagem , Exercício Físico , Lactatos/administração & dosagem , Ácido Láctico/sangue , Substâncias para Melhoria do Desempenho/administração & dosagem , Equilíbrio Ácido-Base , Acidose , Adulto , Atletas , Desempenho Atlético , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Teste de Esforço , Treinamento Intervalado de Alta Intensidade , Humanos , Masculino , Bicarbonato de Sódio/administração & dosagem , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto JovemRESUMO
We investigated the effects of supplement identification on exercise performance with caffeine supplementation. Forty-two trained cyclists (age 37 ± 8 years, body mass [BM] 74.3 ± 8.4 kg, height 1.76 ± 0.06 m, maximum oxygen uptake 50.0 ± 6.8 mL/kg/min) performed a ~30 min cycling time-trial 1 h following either 6 mg/kgBM caffeine (CAF) or placebo (PLA) supplementation and one control (CON) session without supplementation. Participants identified which supplement they believed they had ingested ("caffeine", "placebo", "don't know") pre- and post-exercise. Subsequently, participants were allocated to subgroups for analysis according to their identifications. Overall and subgroup analyses were performed using mixed-model and magnitude-based inference analyses. Caffeine improved performance vs PLA and CON (P ≤ 0.001). Correct pre- and post-exercise identification of caffeine in CAF improved exercise performance (+4.8 and +6.5%) vs CON, with slightly greater relative increases than the overall effect of caffeine (+4.1%). Performance was not different between PLA and CON within subgroups (all P > 0.05), although there was a tendency toward improved performance when participants believed they had ingested caffeine post-exercise (P = 0.06; 87% likely beneficial). Participants who correctly identified placebo in PLA showed possible harmful effects on performance compared to CON. Supplement identification appeared to influence exercise outcome and may be a source of bias in sports nutrition.
Assuntos
Ciclismo/fisiologia , Cafeína/farmacologia , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/farmacologia , Adulto , Desempenho Atlético , Cafeína/administração & dosagem , Método Duplo-Cego , Teste de Esforço , Humanos , Masculino , Consumo de Oxigênio , Substâncias para Melhoria do Desempenho/administração & dosagem , Estudo de Prova de Conceito , Fenômenos Fisiológicos da Nutrição EsportivaRESUMO
BACKGROUND: Zygomatic implants are an alternative treatment in the rehabilitation of atrophic maxilla to promote stability in the stomatognathic system. The aim of this study was to compare the electromyographic (EMG) activity of masseter and temporalis muscles in controls and in individuals with complete implant-supported dentures anchored in the zygomatic bone. MATERIALS AND METHODS: Fifty-four volunteers of both genders (mean age 52.5 years) were selected and distributed into two groups: Individuals with zygomatic implant (ZIG; n=27) and fully dentate patients (CG; n=27). MyoSystem-BR1 was used to assess masseter and temporalis muscles EMG activity in different mandibular movements: protrusion, clenching, maximal voluntary contraction (MVC) with Parafilm M®, right and left laterality and chewing (peanuts and raisins). Data was processed, normalized (MVC) and analyzed using the SPSS 21.0. Student t-test (P ≤ 0.05) was used for group comparison. RESULTS: The results were statistically significant (P ≤ 0.05) for protrusion, clenching, right and left laterality and raisin chewing. For the mandibular posture conditions, the ZIG obtained higher EMG activity patterns when compared to CG. For the masticatory performance during chewing of peanuts and raisins, the ZIG showed higher EMG mean values when compared to CG. CONCLUSIONS: The zygomatic implant promoted an active response of the muscle fibers (hyperactivity) during both mandibular posture and chewing conditions, probably due to the absence of periodontal receptors, which play a significant role for preparing a bolus for swallowing.
Assuntos
Prótese Dentária Fixada por Implante , Eletromiografia , Músculo Masseter/fisiologia , Músculo Temporal/fisiologia , Zigoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The success of gene expression studies, protein synthesis, and construction of cDNA libraries directly depends on the purity and integrity of the RNA used in these tests, as even minor amounts of contaminant DNA (<1%) can produce a false positive amplification signal in quantitative real-time PCR. For RNA contaminated with genomic DNA, an essential step in the studies on gene expression is the treatment of the RNA samples with DNase. This study was conducted to test three different concentrations of DNase I (0.02, 0.04, and 0.06 µL/ââng of RNA), which were chosen based on the results of the RNA sample quantifications and as indicated by the manufacturer, to digest genomic DNA present in the RNA samples extracted from sugarcane leaves with the Concert™ Plant RNA Reagent. The results showed that all three concentrations of DNase significantly reduced DNA concentrations. However, RNA was also degraded on DNase I treatment. In addition, the amount of DNA present in the RNA samples after purification with DNase I was sufficient for its amplification in the tests conducted with conventional PCR. Furthermore, the condition of RNA samples obtained after the treatments allowed for real-time PCR. Therefore, we concluded that 0.02 µL DNase I was the ideal concentration for sugarcane RNA purification, as higher concentrations do not increase the efficiency of the genomic DNA digestion in RNA samples and only make the purification process more expensive. This study provides important information on the effect of high concentrations of DNase I and complements previous studies that have so far tested only the DNase concentration recommended by the manufacturer.
Assuntos
Desoxirribonucleases/metabolismo , RNA de Plantas/análise , Saccharum/genética , DNA/metabolismo , Expressão Gênica , Folhas de Planta/genética , RNA de Plantas/normasRESUMO
AIMS: To evaluate the ability of Candida parapsilosis and Candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from Brazilian red propolis (BZP-BRP) as compared to fluconazole (FLC). To investigate possible synergy between BZP-BRP and FLC and anidulafungin (AND). METHODS AND RESULTS: To analyse the development of resistance, isolates susceptible to these antifungals were cultured in increasing concentrations of FLC and BZP-BRP. The increase in FLC minimum inhibitory concentration for all isolates was evident and the majority developed resistance, whereas none isolated became less susceptible to BZP-BRP. Synergism was investigated by checkerboard method. BZP-BRP demonstrated synergy with FLC and indifference with AND for most isolates. CONCLUSIONS: In conclusion, the synergism observed with FLC suggests that BZP-BRP could be a possible therapeutic strategy for the treatment of infections related to FLC-resistant Candida sp. SIGNIFICANCE AND IMPACT OF THE STUDY: The indiscriminate use of antifungals results in the emergence of drug-resistant strains among previously susceptible populations. BZP-BRP can become an alternative for the treatment of persistent infections caused by Candida sp.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Extratos Vegetais/farmacologia , Própole/química , Brasil , Candida/classificação , Candida/genética , Candida/metabolismo , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
AIMS: To investigate the antidermatophytic action of a complementary set imidazolium salts (IMS), determining structure-activity relationships and characterizing the IMS toxicological profiles. METHODS AND RESULTS: The susceptibility evaluation of 45 dermatophytic clinical isolates, treated in vitro with eleven different IMS (ionic compounds) and commercial antifungals (nonionic compounds), was performed by broth microdilution, following the standard norm of CLSI M38-A2. All dermatophytes were inhibited by IMS, where the lowest minimum inhibitory concentration (MIC) values were observed for salts with n-hexadecyl segment in the cation side chain, containing either the chloride or methanesulfonate anion. 1-n-Hexadecyl-3-methylimidazolium chloride (C16 MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS) acted as fungicides, even in extremely low concentrations, wherein C16 MImMeS exerted this effect on 100% of the tested dermatophytes. Some of these IMS provoked evident alterations on the fungi cell morphology, causing a total cell damage of ≥ 70%. Importantly, none of the screened IMS were cytotoxic, mutagenic or genotoxic to human leucocyte cells. CONCLUSIONS: This report demonstrates for the first time the strong antifungal potential of IMS against multidrug-resistant dermatophytes, without presenting toxicity to human leucocyte cells at MIC. SIGNIFICANCE AND IMPACT OF THE STUDY: The expressive antifungal activity of IMS, combined with the in vitro nontoxicity, makes them promising compounds for the safe and effective treatment of dermatophytoses, mainly when this skin mycosis is unresponsive to conventional drugs.
Assuntos
Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Dermatomicoses/microbiologia , Farmacorresistência Fúngica Múltipla , Imidazóis/farmacologia , Arthrodermataceae/crescimento & desenvolvimento , Dermatomicoses/tratamento farmacológico , Humanos , Testes de Sensibilidade MicrobianaRESUMO
We used immunocytochemical and fluorometric techniques to show that gill cells of two marine invertebrates, the crab Neohelice granulata (osmoregulator) and the clam Mesodesma mactroides (osmoconformer), increase the expression of membrane transporters [Na(+)/K(+)-ATPase and aquaporin (AQP1)] after whole-animals exposure (96 h) to sublethal concentrations of copper in water of salinity 30 ppt, when both clams and crabs are isosmotic with respect to the environmental medium. A plausible interpretation of our findings is that this increased expression in membrane transporters may serve as an attempt to ameliorate the deleterious effects of copper on the mechanisms involved in ion and volume regulation in gill cells.
Assuntos
Aquaporina 1/biossíntese , Bivalves/efeitos dos fármacos , Braquiúros/efeitos dos fármacos , Cobre/toxicidade , ATPase Trocadora de Sódio-Potássio/biossíntese , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/enzimologia , Bivalves/metabolismo , Braquiúros/enzimologia , Braquiúros/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/enzimologia , Membrana Celular/metabolismo , Monitoramento Ambiental , Brânquias/efeitos dos fármacos , Brânquias/enzimologia , Brânquias/metabolismo , Imuno-Histoquímica , Microscopia de Fluorescência , Osmose , SalinidadeRESUMO
Here we analyze the trends of rainfall and the frequency of rainy days over the Brazilian Cerrado between 1960 and 2021 in four distinct periods according to the seasonal patterns over the region. We also evaluated trends in evapotranspiration, atmospheric pressure, winds, and atmospheric humidity over the Cerrado to elucidate the possible reasons for the detected trends. We recorded a significant reduction in rainfall and frequency of rainy days in the northern and central Cerrado regions for all periods except at the beginning of the dry season. The most pronounced negative trends were recorded during the dry season and the beginning of the wet season, where we recorded reductions of up to 50% in total rainfall and the number of rainy days. These findings are associated with the intensification of the South Atlantic Subtropical Anticyclone, which has been shifting atmospheric circulation and raising regional subsidence. Moreover, during the dry season and the beginning of the wet season, there was a reduction in regional evapotranspiration, which also potentially contributed to the rainfall reduction. Our results suggest an expansion and intensification of the dry season in the region, potentially bringing broad environmental and social impacts that transcend the Cerrado boundaries.
RESUMO
This work describes the use of ultrasound biomicroscopy (UBM) to follow up the degeneration-regeneration process after a laceration injury induced in the lateral gastrocnemius (LG) and soleus (SOL) muscles of rats. UBM (40 MHz) images were acquired and used for biomechanical characterization of muscular tissue, specifically using pennation angle (PA) and muscle thickness (MT). The animals were distributed in three groups: the variability group (VG; N=5), the gastrocnemius injured group (GG; N=6) and the soleus injured group (SG; N=5). VG rats were used to assess data variability and reliability (coefficients of variation of 9.37 and 3.97% for PA and MT, respectively). GG and SG rats were submitted to the injury protocol in the LG and SOL muscles of the right legs, respectively. UBM images of muscles of both legs were acquired at the following time points: before and after injury (immediately, 7, 14, 21 and 28 days). We observed an increase in PA for the non-injured leg 28 days after injury for both GG and SG rats (GG=10.68 to 16.53 deg and SG=9.65 to 14.06 deg; P<0.05). Additionally, MT presented a tendency to increase (GG=2.92 to 3.13 mm and SG=2.12 to 2.35 mm). Injured legs maintained pre-injury PA and MT values. It is suggested that a compensatory hypertrophic response due to the overload condition imposed to healthy leg. The results indicate that UBM allows qualitative and quantitative muscle differentiation among healthy and injured muscle at different stages after lesion.
Assuntos
Microscopia Acústica , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Regeneração , Animais , Fenômenos Biomecânicos , Feminino , Microscopia Acústica/métodos , Músculo Esquelético/lesões , Ratos , Ratos WistarRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belém, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3'UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations.
Assuntos
Proteínas de Transporte de Cátions/genética , Etnicidade/genética , Marcadores Genéticos , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , Receptores KIR/genética , Adulto , Idade de Início , Brasil , Cidades , Feminino , Frequência do Gene , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Receptores KIR3DS1/genéticaRESUMO
The purpose of this study was to evaluate the effects of systemic administration of the probiotic Bifidobacterium animalis subsp. lactis HN019 (HN019) on ligature-induced periodontitis in rats with experimental rheumatoid arthritis (RA). 28 rats were divided into four groups (n=7): RA (rheumatoid arthritis), RA/PROB (probiotic), RA/EP (experimental periodontitis) and RA/EP/PROB. From day zero, HN019 was added daily to the water of the PROB groups animals until the end of the experiment. From day seven, RA was induced. On day 28, in EP groups, ligatures were positioned around mandibular first molars and remained in position for 11 days, in order to induce periodontitis. The animals were euthanised on day 39. Microtomographic, histomorphometric, immunoenzymatic and microbiological analyses were performed. Data were statistically analysed (P<0.05). Group RA/EP/PROB presented reduced alveolar bone loss, tumour necrosis factor-α and interleukin (IL)-6 levels and increased IL-17 levels when compared with group RA/EP. There were no significant differences regarding connective tissue attachment level and IL-10 levels between groups RA/EP and RA/EP/PROB. Group RA/PROB showed decreased anti-citrullinated protein antibodies levels when compared with groups RA and RA/EP. Group RA/EP/PROB presented a higher rate of aerobic/anaerobic bacteria than group RA/EP. Systemic administration of HN019 promoted a protective effect against periodontal tissue destruction, decreasing both bone loss and inflammatory mediators and increasing the proportion of bacteria compatible with periodontal health, in rats with experimental RA and EP.
Assuntos
Perda do Osso Alveolar , Artrite Reumatoide/complicações , Periodontite , Probióticos/farmacologia , Perda do Osso Alveolar/tratamento farmacológico , Animais , Anticorpos Antiproteína Citrulinada/análise , Bactérias/isolamento & purificação , Bifidobacterium animalis , Osso e Ossos/imunologia , Osso e Ossos/metabolismo , Osso e Ossos/microbiologia , Osso e Ossos/patologia , Modelos Animais de Doenças , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Periodontite/tratamento farmacológico , Periodontite/prevenção & controle , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Exposure to aluminum (Al) and aluminumâ¯+â¯manganese (Mn) can trigger an increase in reactive oxygen species (ROS) and modify the activity of oxidative defense enzymes. This study investigated whether exposure to Al and Alâ¯+â¯Mn at acid pH for 24 and 96â¯h causes oxidative stress evidenced by antioxidants and oxidative damage in the gills and liver of sexually mature Astyanax altiparanae males. The fish were subsequently immersed in metal-free water for 24 and 96â¯h to see whether they recovered from the effects of these metals. Exposure to an acid pH boosted the activity of gill superoxide dismutase (SOD) at 96â¯h and the fish did not recover when immersed for the same period in water at neutral pH. Exposure to Al increased glutathione (GSH) levels (24â¯h) in the gills, returning to control levels during the recovery period, showing the efficiency of the antioxidant system in preventing lipid peroxidation of the gills and liver. Mn did not modify the activity of the enzymes studied, but did trigger late hepatic lipid peroxidation during the recovery period. The group exposed to Alâ¯+â¯Mn exhibited several alterations, including increased concentration of GSH, as well as higher GPx and GR activity in the gills. Despite the defensive responses triggered by acute exposure, during the recovery period there were alterations in catalase (96â¯h) and an increase in hepatic metallothionein (24â¯h), but this did not prevent hepatic lipid peroxidation. Al and Alâ¯+â¯Mn produced different effects, and the timing of enzymatic and non-enzymatic antioxidant defenses also differed.
Assuntos
Alumínio/toxicidade , Characidae/fisiologia , Brânquias/efeitos dos fármacos , Fígado/efeitos dos fármacos , Manganês/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluição Química da Água/efeitos adversos , Adaptação Fisiológica , Animais , Catalase/metabolismo , Sinergismo Farmacológico , Proteínas de Peixes/agonistas , Proteínas de Peixes/metabolismo , Brânquias/enzimologia , Brânquias/metabolismo , Glutationa/agonistas , Glutationa/metabolismo , Concentração de Íons de Hidrogênio , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Metalotioneína/metabolismo , Reprodutibilidade dos Testes , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Testes de Toxicidade AgudaRESUMO
The objective of the present study was to test the hypothesis that treatment of schistosomiasis mansoni with praziquantel can alter significantly the immune response of patients and generate a reversal of the level of fibrosis. Peripheral blood mononuclear cell (PBMC) samples were collected from, and abdominal ultrasound examinations conducted on, volunteers infected with Schistosoma mansoni and living in an area where the disease is endemic, both prior to and one year after treatment with praziquantel. Subjects were classified into groups according to the level of pathology (i.e., absent, incipient, moderate, or severe fibrosis). PBMCs were stimulated with schistosome soluble egg antigens (SEA), and the levels of production of the cytokines gamma interferon (IFN-gamma), tumor necrosis factor alpha, transforming growth factor beta, and interleukin-4 (IL-4), IL-10, and IL-13 were determined. The chemotherapy was effective in reducing morbidity, particularly for individuals presenting with severe fibrosis. When levels of cytokine production in posttreatment PBMC cultures stimulated by SEA were categorized as low or high, significant differences in the distribution of IL-13 levels between groups presenting with or not presenting with fibrosis were established. Comparison of pre- and posttreatment SEA-induced cytokine levels in individuals who had experienced no change in the grade of fibrosis following chemotherapy revealed that the level of IFN-gamma decreased in subjects with fibrosis whereas that of IL-10 decreased in individuals with and without fibrosis. The data suggest that chemotherapy is effective in reducing the morbidity of the disease and that the level of IL-13 may be a useful indicator of the persistence of fibrosis following treatment.
Assuntos
Anti-Helmínticos/uso terapêutico , Citocinas/sangue , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-13/sangue , Interleucina-4/sangue , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Esquistossomose mansoni/sangue , Esquistossomose mansoni/diagnóstico por imagem , Fator de Crescimento Transformador beta/sangue , Ultrassonografia , Adulto JovemRESUMO
The rodent Deltamys kempiThomas, 1917 is found on the Coastal Plain - a recently formed geographic region located on Brazil's south-east coast. Considering that Deltamys is the only South American sigmodontine with a sex chromosome system of type X(1)X(1)X(2)X(2)/X(1)X(2)Y, this investigation was focused on the phylogeographic history of this taxon by using gene sequence analysis, trying to clarify when Deltamys differentiated, what was its centre of diversification, and what were the probable routes it used to reach its present distribution. We analysed sequences of the mitochondrial cytochrome b gene and nuclear recombination activating gene 2, performed cranial measurements and searched for centric fusions in individuals collected in distinct localities. The results, clearly demonstrate that D. kempi, on the Coastal Plain, divided into two groups, one occupying a small portion to the north of this region and the other spreading widely to the south. In this process, the phenomena of marine transgression and regressions which moulded its habitat, together with the occurrence of successive chromosomal rearrangements, were certainly the fundamental factors in shaping D. kempi diversification.
Assuntos
Citocromos b/genética , Proteínas de Ligação a DNA/genética , Filogenia , Sigmodontinae/fisiologia , Animais , Brasil , Variação Genética , Geografia , Dados de Sequência Molecular , Análise de Sequência de DNA , Sigmodontinae/genética , Crânio/anatomia & histologia , Fatores de TempoRESUMO
Knowledge about the spatial distribution and the local concentration of trace elements in tissues is of great importance, since trace elements are involved in many biological functions of living organisms. However, there are few methods available to measure the spatial (two (three)-dimensional) elemental distribution in animal brain. X-ray microfluorescence with synchrotron radiation is a multielemental mapping technique, which was used in this work to determine the topographic of iron, zinc and copper in coronal sections of female Wistar rats of different ages. Young (14 days old) and middle-aged (20 months old) rats (n = 8) were analyzed. The measurements were carried out at the XRF beam line at the Synchrotron Light National Laboratory (Campinas, Brazil). Two-dimensional scanning was performed in order to study the tendency of elemental concentration variation. The acquisition time for each pixel was 10 s/step and the step size was 300 microm/step in both directions. It was observed that the iron distribution was more conspicuous in the cortical area, thalamus and bellow the thalamus. On the other hand, the zinc distribution was more pronounced in the hippocampus. The iron, copper and zinc levels increased with advancing age. Therefore, this study reinforces the idea that these elements are involved in the chemical mechanisms of the brain that induce some neurological diseases, since they are also present in high levels in specific areas of the brain, such as the hippocampus and the substantia nigra of patients with these disorders.
Assuntos
Encéfalo , Espectrometria por Raios X/métodos , Síncrotrons , Oligoelementos/análise , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Córtex Cerebral/química , Córtex Cerebral/patologia , Cobre/análise , Feminino , Hipocampo/química , Hipocampo/patologia , Ferro/análise , Radiografia , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Espectrometria por Raios X/instrumentação , Substância Negra/química , Substância Negra/patologia , Tálamo/química , Tálamo/patologia , Zinco/análiseRESUMO
OBJECTIVE: This study investigated the acute residual effects induced by different frequencies of whole-body vibration (WBV) on postural control of elderly women. DESIGN: Thirty physically active elderly women (67 ± 5 years) were randomly divided into three groups: two experimental groups (high WBV frequency: 45 Hz and 4 mm amplitude, n = 10; low WBV frequency: 30 Hz and 4 mm amplitude, n = 10) and one control group (n = 10), with no treatment. The participants were first subjected to stabilometry tests and were then guided through three sets of isometric partial squats for 60 s while the WBV stimulation was applied. The control group was subjected to the same conditions but without the WBV stimulation. The participants were again subjected to body balance tests immediately following the end of the intervention period and again at 8, 16, and 24 min. To measure body sway control, three 60 s tests were performed at 10 s intervals for each of the following experimental conditions: (1) eyes opened and (2) eyes closed. The following variables were investigated: the average velocity of the displacement of the centre of pressure in the anterior-posterior and medial-lateral planes as well as in the elliptical area. RESULTS: A 3 (condition) × 5 (test) two-way repeated-measures ANOVA did not identify significant differences in the stabilometric variables, regardless of group, time, or experimental condition. CONCLUSIONS: The effect of WBV, regardless of the stimulation frequency, did not have a significant effect immediately after or up to 24 minutes after vibration cessation, on the variables involved in the control of postural stability in physically active elderly women.