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1.
BMC Med Imaging ; 20(1): 111, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008329

RESUMO

BACKGROUND: To develop and validate a nomogram for early identification of severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics. METHODS: The initial clinical and CT imaging data of 217 patients with COVID-19 were analyzed retrospectively from January to March 2020. Two hundred seventeen patients with 146 mild cases and 71 severe cases were randomly divided into training and validation cohorts. Independent risk factors were selected to construct the nomogram for predicting severe COVID-19. Nomogram performance in terms of discrimination and calibration ability was evaluated using the area under the curve (AUC), calibration curve, decision curve, clinical impact curve and risk chart. RESULTS: In the training cohort, the severity score of lung in the severe group (7, interquartile range [IQR]:5-9) was significantly higher than that of the mild group (4, IQR,2-5) (P < 0.001). Age, density, mosaic perfusion sign and severity score of lung were independent risk factors for severe COVID-19. The nomogram had a AUC of 0.929 (95% CI, 0.889-0.969), sensitivity of 84.0% and specificity of 86.3%, in the training cohort, and a AUC of 0.936 (95% CI, 0.867-1.000), sensitivity of 90.5% and specificity of 88.6% in the validation cohort. The calibration curve, decision curve, clinical impact curve and risk chart showed that nomogram had high accuracy and superior net benefit in predicting severe COVID-19. CONCLUSION: The nomogram incorporating initial clinical and CT characteristics may help to identify the severe patients with COVID-19 in the early stage.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Nomogramas , Pneumonia Viral/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Criança , Diagnóstico Precoce , Humanos , Pessoa de Meia-Idade , Pandemias , Distribuição Aleatória , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 361-366, 2020 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-32935509

RESUMO

OBJECTIVE: To investigate the protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis (TsadSPI) on sepsis-associated acute kidney injury in mice. METHODS: A total of 18 male BALB/c mice were randomly divided into the sham-operation group, the model group, and the TsadSPI treatment group, of 6 mice in each group. Sepsis-associated acute kidney injury was modeled in the model group and TsadSPI treatment group by cecal ligation puncture (CLP), while mice in the sham-operation group were only given exploratory laparotomy without ligation or perforation of the cecum. After 30 min of CLP, mice in the sham-operation group and the model group were intraperitoneally injected with PBS (100 µL), and mice in the TsadSPI treatment group were intraperitoneally injected with PBS (100 µL) containing TsadSPI (2 µg). At 12 h following modeling, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and urea nitrogen (BUN) were measured to assess the liver and kidney functions, and the changes of the mouse kidney structure were observed using HE staining. In addition, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-ß were measured using an enzyme-linked immunosorbent assay (ELISA), and the myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) p65 expression was determined in kidney tissues using immunohistochemical staining. RESULTS: At 12 h following CLP, there were significant differences in the serum levels of ALT (F = 41.031, P < 0.001), AST (F = 54.757, P < 0.001), Cr (F = 24.142, P < 0.001) and BUN (F = 214.849, P < 0.001) among the three groups, and higher levels of ALT, AST, Cr and BUN were measured in model group than in the sham-operation group (P < 0.001), while lower ALT, AST, Cr and BUN levels were found in the TsadSPI treatment group than in the model group (P < 0.001). HE staining showed severe mouse kidney injuries following CLP, and TsadSPI treatment resulted in remarkable alleviation of the injury. ELISA measured significant differences in the TNF-α (F = 47.502, P < 0.001) and IL-6 levels (F = 222.061, P < 0.001) among the three groups, and showed a remarkable reduction in the TNF-α and IL-6 levels in the TsadSPI treatment group as compared to those in the model group (P < 0.001). In addition, there were significant differences in serum IL-10 (F = 16.227, P < 0.001) and TGF-ß levels (F = 52.092, P < 0.001) among the three groups, and higher IL-10 and TGF-ß levels were seen in the TsadSPI treatment group than in the model group (P < 0.001). Immunohistochemical staining showed greater MyD88 expression and a higher nuclear positive rate of NF-κB p65 in kidney tissues in the model group than in the TsadSPI treatment group. CONCLUSIONS: TsadSPI may reduce the MyD88 expression and nuclear positive rate of NF-κB p65 in mouse kidney tissues to up-regulate the expression of immunomodulatory factors and down-regulate the expression of pro-inflammatory cytokines, thereby protecting sepsis-associated acute kidney injury.


Assuntos
Lesão Renal Aguda , Sepse , Trichinella spiralis , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/etiologia , Animais , Citocinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Sepse/complicações , Inibidores de Serino Proteinase/genética , Inibidores de Serino Proteinase/farmacologia , Inibidores de Serino Proteinase/uso terapêutico , Trichinella spiralis/química , Trichinella spiralis/genética
3.
Bull Environ Contam Toxicol ; 105(4): 582-587, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32948914

RESUMO

Oreochromis niloticus was exposed to 10.0 ppb of organophosphate insecticide chlorpyrifos (CPF) and avermectin insecticides abamectin (ABM) and emamectin benzoate (EB) for 48 and 96 h. RBC and Hb decreased in CPF- and ABM-exposed fish after 96-h. Plasma ALT, AST, cortisol, and glucose increased in 96-h CPF-, ABM- and EB-exposed fish, while plasma ions declined in 96-h CPF-exposed ones. Insecticides caused alterations in liver oxidative stress parameters. In fish exposed to CPF, CAT increased after 48-h whereas it decreased after 96-h. Also, CAT declined in 48- and 96-h ABM-exposed fish, whereas it elevated in 48-h EB-exposed ones. Insecticides caused decreases in SOD at 48- and 96-h and in GR after 96-h. GSH elevated in CPF-exposed fish after 48-h, while it decreased in all the tested insecticide exposures after 96-h. Malondialdehyde of fish exposed to insecticides for 96-h increased. Consequently, toxic effects of insecticides on O. niloticus were generally as CPF > ABM > EB.


Assuntos
Clorpirifos/toxicidade , Ciclídeos , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Poluentes Químicos da Água/toxicidade , Animais , Análise Química do Sangue/veterinária , Testes Hematológicos/veterinária , Ivermectina/toxicidade , Fígado/efeitos dos fármacos , Fígado/enzimologia , Oxirredução , Distribuição Aleatória , Testes de Toxicidade Aguda/veterinária
4.
Biomed Environ Sci ; 33(8): 603-613, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933612

RESUMO

Objective: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. Methods: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. Results: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. Conclusion: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.


Assuntos
Cardiopatias/patologia , Coração/efeitos da radiação , Miocárdio/patologia , Ondas de Rádio/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Cardiopatias/etnologia , Cardiopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
5.
Bone Joint J ; 102-B(8): 1095-1106, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731821

RESUMO

AIMS: Achilles tendon injuries are a frequent problem in orthopaedic surgery due to their limited healing capacity and the controversy surrounding surgical treatment. In recent years, tissue engineering research has focused on the development of biomaterials to improve this healing process. The aim of this study was to analyze the effect of tendon augmentation with a nanostructured fibrin-agarose hydrogel (NFAH) or genipin cross-linked nanostructured fibrin-agarose hydrogel (GP-NFAH), on the healing process of the Achilles tendon in rats. METHODS: NFAH, GP-NFAH, and MatriDerm (control) scaffolds were generated (five in each group). A biomechanical and cell-biomaterial-interaction characterization of these biomaterials was then performed: Live/Dead Cell Viability Assay, water-soluble tetrazolium salt-1 (WST-1) assay, and DNA-released after 48 hours. Additionally, a complete section of the left Achilles tendon was made in 24 Wistar rats. Animals were separated into four treatment groups (six in each group): direct repair (Control), tendon repair with MatriDerm, or NFAH, or GP-NFAH. Animals were euthanized for further histological analyses after four or eight weeks post-surgery. The Achilles tendons were harvested and a histopathological analysis was performed. RESULTS: Tensile test revealed that NFAH and GP-NFAH had significantly higher overall biomechanical properties compared with MatriDerm. Moreover, biological studies confirmed a high cell viability in all biomaterials, especially in NFAH. In addition, in vivo evaluation of repaired tendons using biomaterials (NFAH, GP-NFAH, and MatriDerm) resulted in better organization of the collagen fibres and cell alignment without clinical complications than direct repair, with a better histological score in GP-NFAH. CONCLUSION: In this animal model we demonstrated that NFAH and GP-NFAH had the potential to improve tendon healing following a surgical repair. However, future studies are needed to determine the clinical usefulness of these engineered strategies. Cite this article: Bone Joint J 2020;102-B(8):1095-1106.


Assuntos
Tendão do Calcâneo/cirurgia , Microambiente Celular/efeitos dos fármacos , Colágeno/uso terapêutico , Elastina/uso terapêutico , Regeneração/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Animais , Materiais Biocompatíveis/farmacologia , Modelos Animais de Doenças , Fibrina/farmacologia , Hidrogéis/farmacologia , Masculino , Nanoestruturas , Distribuição Aleatória , Ratos , Ratos Wistar , Tendões/fisiologia , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
6.
Arq Bras Cir Dig ; 33(2): e1513, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32844876

RESUMO

BACKGROUND: Extended vertical gastrectomy is a variation of the vertical gastrectomy technique requiring studies to elucidate safety in relation to gastroesophageal reflux. AIM: To analyze comparatively vertical gastrectomy (VG) and extended vertical gastrectomy (EVG) in rats with obesity induced by cafeteria diet in relation to the presence of reflux esophagitis, weight loss and macroscopic changes related to the procedures. METHODS: Thirty Wistar rats were randomized into three groups, and after the obesity induction period by means of a 28-day cafeteria diet, underwent a simulated surgery (CG), VG and VGA. The animals were followed up for 28 days in the post-operative period, and after euthanasia, the reflux esophagitis evaluation was histopathologically performed. Weight and macroscopy were the other variables; weight was measured weekly and the macroscopic evaluation was performed during euthanasia. RESULTS: All animals presented some degree of inflammation and the presence of at least one inflammation criterion; however, there was no statistically significant difference in the analysis among the groups. In relation to weight loss, the animals in CG showed a gradual increase during the whole experiment, evolving to super-obesity at the end of the study, while the ones with VG and EVG had weight regain after the first post-operative period; however, a less marked regain compared to CG, both for VG and EVG. CONCLUSION: There is no difference in relation to reflux esophagitis VG and EVG, as well as macroscopic alterations, and both techniques have the ability to control the evolution of weight during postoperative period in relation to CG.


Assuntos
Gastrectomia/métodos , Refluxo Gastroesofágico/etiologia , Laparoscopia/efeitos adversos , Obesidade/cirurgia , Animais , Gastrectomia/efeitos adversos , Humanos , Obesidade Mórbida , Distribuição Aleatória , Ratos , Ratos Wistar
7.
PLoS One ; 15(8): e0237441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797088

RESUMO

Umbrella trials have been suggested to increase trial conduct efficiency when investigating different biomarker-driven experimental therapies. An overarching platform is used for patient screening and subsequent subtrial allocation according to patients' biomarker status. Two subtrial allocation schemes for patients with a positive test result for multiple biomarkers are (i) the pragmatic allocation to the eligible subtrial with the currently fewest included patients and (ii) the random allocation to one of the eligible subtrials. Obviously, the subtrials compete for such patients which are consequently underrepresented in the subtrials. To address questions of the impact of an umbrella design in general as well as with respect to subtrial allocation and analysis method, we investigate an umbrella trial with two parallel group subtrials and discuss generalisations. First, we analytically quantify the impact of the umbrella design with random allocation on the number of patients needed to be screened, the biomarker status distribution and treatment effect estimates compared to the corresponding gold standard of an independent parallel group design. Using simulations and real data, we subsequently compare both allocation schemes and investigate weighted linear regression modelling as possible analysis method for the umbrella design. Our results show that umbrella designs are more efficient than the gold standard. However, depending on the biomarker status distribution in the disease population, an umbrella design can introduce differences in estimated treatment effects in the presence of an interaction between treatment and biomarker status. In principle, weighted linear regression together with the random allocation scheme can address this difference though it is difficult to assess if such an approach is applicable in practice. In any case, caution is required when using treatment effect estimates derived from umbrella designs for e.g. future trial planning or meta-analyses.


Assuntos
Biomarcadores/metabolismo , Projetos de Pesquisa , Simulação por Computador , Humanos , Distribuição Aleatória
8.
Ecotoxicol Environ Saf ; 203: 111032, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745774

RESUMO

Titanium dioxide nanoparticles (Np-TiO2) have become the common component of sunscreen cosmetic products. Np-TiO2 can affect especially aquatic ecosystems health, including aquatic organisms such as fish. It is therefore necessary to acquire a better understanding of the effect of Np-TiO2 on aquatic organisms. This study evaluated the biological effects of Np-TiO2 on Danio rerio, such as survival rate and weight change and, in particular, the Ti content or retention in the intestine and liver, as well as the activities of catalase and superoxide dismutase enzymes. In addition, the structure of the intestine, kidney, and liver was investigated through histological analysis. Ninety zebrafish were used, randomly divided into three treatment-groups: a control group (fed with food without adding Np-TiO2) and two groups of fish fed with food containing Np-TiO2 exposed for 7 and 14 days. The amount of Ti in the liver and intestine was measured using atomic absorption spectrophotometry coupled to a graphite furnace (GFAAS). Morphological analysis and enzyme catalase and superoxide dismutase assays were likewise performed. Ti was detected in all fish even in control group; probably Ti must have been introduced during production by the fish food industry. Structural changes were detected in fish fed with Np-TiO2 as vacuolization and disruption of the apical cytoplasm of epithelial cells that covered the intestinal villi. Although kidney morphology appeared intact, the lumen of the proximal tubule was enlarged, and the cells of the distal tubule were vacuolated. No morphological changes in the liver were detected; however, superoxide dismutase activity decreased, suggesting that liver changes occurred at the molecular level. Thus, Np-TiO2 causes morphological changes in the intestine, kidney, and liver of zebrafish and biochemical changes in the liver exposed for 7 and 14 days. Although not highly lethal, Np-TiO2 in the food chain can interfere with the morphophysiology of aquatic organisms. Neither mortalities nor body weight losses were recorded among fish in all groups over the duration of the experiment.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Bioacumulação , Catalase , Relação Dose-Resposta a Droga , Ecossistema , Cadeia Alimentar , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Nanopartículas/metabolismo , Distribuição Aleatória , Protetores Solares/química , Titânio/metabolismo , Poluentes Químicos da Água/metabolismo
9.
Life Sci ; 258: 118225, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771557

RESUMO

AIM: The aim of this study was considering the effects of taurine supplementation with combined aerobic and resistance training (CARE) on myocardial apoptosis and Protein Kinase B (akt) level changes in diabetic rat. MAIN METHODS: Forty male Wistar rats were randomly divided in to 5 groups of 8 animals in each: 1) control, 2) Diabetes Mellitus (DM), 3) DM with taurine supplementation (DM/T), 4) DM with CARE (DM/CARE), and 5) DM with combination of taurine and CARE (DM/T/CARE). DM was induced by injection of streptozotocin (STZ) and nicotine amid (NA) for 2, 3, 4 and 5 groups. Supplement groups received taurine in gavage, 100 mg/kg of body weight, 6 day per weeks, 8 weeks. CARE was performed at maximal speed and 1RM (40-60% of maximum for both). KEY FINDINGS: The results of this study showed that DM significantly increased blood glucose and caspase 3, caspase 9 expressions and apoptosis cells in heart tissue and reduced Akt expression (p < 0.001). However, taurine and CARE interventions significantly decreased apoptosis markers (caspase 3 and caspase 9) and significantly increased Akt in heart of diabetic rats compare to DM groups (p < 0.05). The highest improvement observed in DM/T/CARE group (p < 0.05). SIGNIFICANCE: Based on these results, it seems that the use of taurine with combined aerobic and exercise training minimize the cardiac damage caused by diabetes (especially apoptosis) trough increasing protein kinase Akt expression. This could improve cardiac remodeling after diabetes. However, more research is needed, especially on the human samples.


Assuntos
Apoptose/fisiologia , Diabetes Mellitus Experimental/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal/fisiologia , Proteínas Proto-Oncogênicas c-akt/biossíntese , Taurina/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Terapia Combinada/métodos , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Masculino , Miocárdio/patologia , Condicionamento Físico Animal/tendências , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
10.
PLoS One ; 15(8): e0236995, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785245

RESUMO

Blended therapy is a new approach combining advantages of face-to-face psychotherapy and Internet- and mobile-based interventions. Acceptance is a fundamental precondition for its implementation. The aim of this study was to assess 1) the acceptance of psychotherapists towards blended therapy, 2) the effectiveness of an acceptance facilitating intervention (AFI) on psychotherapists' acceptance towards blended therapy and 3) to identify potential effect moderators. Psychotherapists (N = 284) were randomly assigned to a control (CG) or an intervention group (IG). The IG received a short video showing an example of blended therapy, the CG an attention placebo video. Both groups received a reliable online questionnaire assessing acceptance, effort expectancy, performance expectancy, facilitating conditions, social influence and internet anxiety. Between group differences were examined using t-tests and Mann-Whitney tests. Exploratory analysis was conducted to identify moderators. Psychotherapists in CG showed mixed baseline acceptance towards blended therapy (low = 40%, moderate = 33%, high = 27%). IG showed significantly higher acceptance compared to CG (d = .27, pone-sided = .029; low = 24%, moderate = 47%, high = 30%). Bootstrapped confidence intervals were overlapping. Performance expectancy (d = .35), effort expectancy (d = .44) and facilitating conditions (d = .28) were significantly increased (p < .05). No effects on social influence and internet anxiety were found (p>.05). Exploratory analysis indicated psychodynamic oriented psychotherapists profiting particularly from the AFI. Blended therapy is a promising approach to improve healthcare. Psychotherapists show mixed acceptance, which might be improvable by AFIs, particularly in subpopulations of initially rather skeptical psychotherapists. Forthcoming studies should extend the present study by shifting focus from attitudes to the impact of different forms of AFIs on uptake.


Assuntos
Psicoterapia/métodos , Telemedicina/métodos , Adulto , Feminino , Alemanha , Humanos , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Relações Profissional-Paciente , Psicoterapia/educação , Psicoterapia Psicodinâmica/métodos , Distribuição Aleatória , Inquéritos e Questionários , Gravação em Vídeo
11.
Exp Parasitol ; 217: 107965, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32818513

RESUMO

Saturated salt floatation method is widely used for coccidian oocyst purification. However, the repeated procedures and inefficient oocysts recovery rate are a continuous challenge. This study aimed to investigate the best suitable floatation solution, along with optimal centrifugation speed and time for Eimeria tenella (E. tenella) oocyst and sporocyst purification. Different floatation solutions i-e, saturated salt, Sheather's sugar and sodium hypochlorite (NaClO) at 20-60% concentrations were used to purify oocyst. It was found that about 96.99% oocysts (8609×g for 10 min) were recovered under these conditions without any effect on the viability of sporocysts. The recovery rate of oocysts using 50% NaClO (V/V) was significantly higher than 35% saturated salt flotation solution (P < 0.05). The optimal method for purification of oocysts based our experimentation was centrifugation at 8609×g for 3 min using 50% NaClO floatation solution, and the optimized centrifugation conditions for improved recovery of sporocysts (about 99.3%) were at 2152×g for 5 min. The present study provided a better method for the coccidian oocyst purification, which could be successfully adopted as a better alternative to existing techniques commonly used for investigations/research pertaining to coccidia.


Assuntos
Centrifugação/normas , Eimeria tenella/isolamento & purificação , Análise de Variância , Animais , Galinhas , Eimeria tenella/crescimento & desenvolvimento , Fezes/parasitologia , Oocistos/isolamento & purificação , Oxidantes/administração & dosagem , Distribuição Aleatória , Hipoclorito de Sódio/administração & dosagem , Organismos Livres de Patógenos Específicos , Fatores de Tempo
12.
Ecotoxicol Environ Saf ; 204: 110973, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32781346

RESUMO

Arsenic (As) exerts a wide range of adverse effects on biological systems, including the reproductive organs in males and females. However, the mechanisms of As-induced reproductive toxicity are mostly obscure. Recently, we showed that autophagy is an essential route for As2O3-induced reprotoxicity through the hypothalamic-pituitary-gonadal-sperm (HPG-S) axis in pubertal and matured F1-male mice. However, the role of autophagy in As2O3- induced ovarian toxicity is mostly unknown. Hence, this study aimed to elucidate the role of oxidative stress, mitochondrial impairment, and autophagic processes in the ovary of As-exposed female mice. For this purpose, mature female mice were challenged with 0, low (0.2), medium (2), and high (20 ppm) As2O3 from 35-days before mating till weaning their pups, and the F1- females from weaning until maturity. Then, all the mice were sacrificed, and oxidative stress parameters, mitochondrial indices, electron microscopic evaluation of the ovaries, expression of autophagic-related genes and proteins, and autophagosome formation were assessed. It was shown that medium and high As2O3 doses were a potent inducer of oxidative stress, mitochondrial dysfunction, and autophagy in the ovary of F1-generation. A dose-dependent increment in the gene expression of PDK1, PI3K, TSC2, AMPK, ULK1, ATG13, Beclin1, ATG12, ATG5, LC3, P62, ATG3, ATG7, and p62, as well as protein expression of Beclin1, and LC3- I, II, was evident in the ovaries of the As-treated animals. Moreover, a dose-dependent decrease in the expression of mTOR and Bcl-2 genes, and mTOR protein was detected with increasing doses of As, suggesting that As treatment-induced autophagy. Along with a dose-dependent increase in the number of MDC-labeled autophagic vacuoles, transmission electron microscopy also confirmed more autophagosomes and injured mitochondria in medium and high As2O3 doses groups. As2O3 also negatively affected the mean body weight, litter size, organ coefficient, and stereological indices in female mice. Finally, in physiological conditions, arsenic trioxide (As2O3) leads to an increased level of autophagy in the oocyte when many oocytes were being lost. These findings indicated that an imbalance in the oxidant-antioxidant system, mitochondrial impairment, and the autophagic process, through inhibition of mTOR, dependent and independent pathways, and Bcl-2, as well as activation of AMPK/PI3K/Beclin1/LC3 routes, could play a pivotal role in As-induced reproductive toxicity through ovarian dysfunction in females.


Assuntos
Arsênico/toxicidade , Autofagia/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Folículo Ovariano/crescimento & desenvolvimento , Ovário/ultraestrutura , Distribuição Aleatória
13.
PLoS One ; 15(8): e0237096, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756603

RESUMO

Careful design of experiments using living organisms (e.g. mice) is of critical importance from both an ethical and a scientific standpoint. Randomization should, whenever possible, be an integral part of such experimental design to reduce bias thereby increasing its reliability and reproducibility. To keep the sample size as low as possible, one might take randomization one step further by controlling for baseline variations in the dependent variable(s) and/or certain known covariates. To give an example, in animal experiments aimed to study atherosclerosis development, one would want to control for baseline characteristics such as plasma triglyceride and total cholesterol levels and body weight. This can be done by first defining blocks to create balance among groups in terms of group size and baseline characteristics, followed by random assignment of the blocks to the various control and intervention groups. In the current study we developed a novel, user-friendly tool that allows users to easily randomize animals into blocks and identify random block divisions that are well-balanced based on given baseline characteristics, making randomization time-efficient and easy-to-use. Here, we present the resulting software tool that we have named RandoMice.


Assuntos
Experimentação Animal , Bioestatística/métodos , Software , Animais , Grupos Controle , Camundongos , Distribuição Aleatória
14.
Ecotoxicol Environ Saf ; 204: 111049, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758698

RESUMO

Recent studies identified a novel programmed and regulated cell death that was characterized by a necrotic cell death morphology, termed necroptosis. Lead (Pb) is known as a persistent inorganic environmental pollutant that affects the health of humans and animals worldwide. However, there are no detailed reports of Pb-induced necroptosis of immune tissue. Selenium (Se) is a trace element that antagonizes the toxicity of heavy metals. Here, chickens were randomly divided into four groups, treated with Pb ((CH3OO)2Pb, 150 mg/kg) and/or Se (Na2SeO3, 2 mg/kg), aim to study the effect and mechanism of necroptosis in Pb-induced spleen injury and the antagonistic effects of Se on Pb toxicity. Our results showed that Pb exposure evidently increased the accumulation of Pb in spleen and caused necroptosis by upregulating the expression of RIP1, RIP3 and MLKL, and decreasing Caspase8 expression. Meanwhile, Pb treatment inhibited the activities of SOD, GPX, and CAT, caused the accumulation of NO and MDA, and induced oxidative stress, which promoted the expression of MAPK/NF-κB pathway genes (ERK, JNK, P38, NF-κB and TNF-α) and activated HSPs (HSP27, HSP40, HSP60, HSP70 and HSP90). However, the increased content of Pb in spleen and Pb-caused necroptosis were inhibited by Se cotreatment. Overall, we conclude that Se can prevent Pb-induced necroptosis by restoring antioxidant functions and blocking the MAPK/NF-κB pathway and HSPs activation in chicken spleen.


Assuntos
Galinhas/fisiologia , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Necroptose/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Baço/efeitos dos fármacos , Animais , Proteínas Aviárias/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Proteínas de Choque Térmico/metabolismo , NF-kappa B/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Baço/fisiologia
15.
Ecotoxicol Environ Saf ; 204: 111051, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32763565

RESUMO

The present study was performed to determine the effect of waterborne cadmium (Cd) exposure on oxidative stress, autophagy and mitochondrial dysfunction, and to explore the mechanism of Cd-induced liver damage in freshwater teleost Procypris merus. To this end, P. merus were exposed to waterborne 0, 0.25 and 0.5 mg/L Cd for 30 days (equal to 0, 2.22 and 4.45 µmol Cd/l). The waterborne Cd exposure significantly increased hepatic Cd accumulation and impaired histological structure of the liver of P. merus. both low and high-dose waterborne Cd exposure induced oxidative stress in the liver of P. merus, through increases Malondialdehyde (MDA) and reactive oxide species (ROS) accumulation in the liver. The Cd-induced oxidative stress in liver may result from reduction of enzyme activities (superoxide dismutases (SOD), catalases (CAT), GSH-S-transferases (GST)) and transcriptional expression of antioxidant related genes (gpx1, gpx2, cata, gsta1, sod1). Furthermore, the present study showed that waterborne Cd exposure decreased the transcriptional factor (nrf2) expression, which might lead to the down-regulation of antioxidant gene expression. Transmission electron microscopy (TEM) observations demonstrated that waterborne Cd exposure induced autophagy in the liver of P. merus. Gene expression analysis showed that waterborne Cd exposure also induced mRNA expression of a set of genes (beclin1, ulk1, atg5, lc3a, atg4b, atg9a, and p62) involved in the autophagy process, indicating that the influence of Cd on autophagy involved transcription regulation of autophagy gene expression. Waterborne Cd exposure induced a sharp decrease in ATP content in the liver of P. merus. In addition, the expression of mitochondrial function genes (sdha, cox4i1, cox1, atp5f1, and mt-cyb) are significantly decreased in the liver of P. merus in Cd treated groups, manifesting the suppression of Cd on mitochondrial energy metabolism. Taken together, our experiments demonstrate that waterborne Cd exposure induced oxidative stress, autophagy and mitochondrial dysfunction in the liver of P. merus. These results may contribute to the understanding of mechanisms that hepatotoxicity of Cd in teleost.


Assuntos
Antioxidantes/fisiologia , Autofagia/efeitos dos fármacos , Cádmio/toxicidade , Cyprinidae/fisiologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Fígado/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Distribuição Aleatória
16.
Farm. comunitarios (Internet) ; 12(3): 5-13, jul. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-191369

RESUMO

OBJETIVOS: evaluar la percepción de los usuarios de las farmacias sobre la repercusión de la pandemia COVID-19 en su salud, el conocimiento sobre su posible inclusión en grupos de riesgo y su actitud ante una posible vacuna. MATERIAL Y MÉTODOS: estudio observacional transversal aleatorizado, en farmacias de Pontevedra y Ourense, desde marzo a junio de 2020 al comienzo y después de la restricción de movimientos. Sujetos: usuarios ≥ 18 años que acuden a las farmacias participantes en demanda de medicamentos y/o material de higiene y protección. Procedimiento: el usuario cumplimentaba un cuestionario anónimo, depositándolo hasta la noche en una bandeja de plástico desinfectada diariamente. El procedimiento se repetirá tras cesar el confinamiento. Resultados de la primera fase: se realizaron 706 encuestas. 415 (58,8 %) mujeres, edad media 48,9 (DE=16,9) años. 100 participantes (14,2 %) viven solos.637 (90,2 %) creen que la COVID-19 es más peligrosa que la gripe, 189 (26,8 %) desconocen estar en algún grupo de riesgo. 107 (15,1 %) dicen sentirse mal o muy mal con el aislamiento. Los aspectos más afectados son: familiar 350 (49,6 %) y emocional 338 (47,9 %). En 2019/20 se vacunaron de la gripe 172 (24,4 %) y en 2020/21 piensan vacunarse 243 (34,4 %). 448 (63,5 %) se vacunarán frente a la COVID-19 cuando exista vacuna, esté o no financiada por el Sistema Nacional de Salud, 183 (25,9 %) se lo pensarán. CONCLUSIONES: los encuestados consideran la COVID-19 más peligrosa que la gripe estacional. En esta primera fase la afectación sobre bienestar y salud no parece elevada. Un alto porcentaje se vacunará frente a la COVID-19


AIMS: to assess the pharmacy users' perception on the impact of the COVID-19 pandemic on their health, the knowledge of their possible inclusion in risk groups and their attitude towards a potential vaccine. MATERIAL AND METHODS: Randomized, cross-sectional, observational study in pharmacies of Pontevedra and Ourense, from March to June 2020 at the beginning and after movement restrictions. Subjects: users ≥ 18 years old who go to the participating pharmacies to purchase medicines and/or hygiene and protection material. Procedure: the user completed an anonymous questionnaire, which was then placed until night in a plastic tray that was disinfected daily. The procedure will be repeated after the confinement has been terminated. Results of the first phase: 706 surveys were conducted. 415 (58.8%) women, aged 48.9 9 years on average (SD=16.9). 100 participants (14.2%) live alone. 637 (90.2%) believe that COVID-19 is more dangerous than influenza, 189 (26.8%) don't know if they belong to any risk group. 107 (15.1%) say they feel bad or very bad about isolation. The most affected aspects are: familiar 350 (49.6%) and emotional 338 (47.9%). In 2019/20, 172 (24.4%) were vaccinated against influenza and in 2020/21 243 (34.4%) are planning to get vaccinated. 448 (63.5%) will be vaccinated against COVID-19 when the vaccine is available, whether or not it is financed by the National Health System, and 183 (25.9%) will think about it. CONCLUSIONS: respondents consider COVID-19 more dangerous than seasonal influenza. In this first phase, the impact on well-being and health does not seem to be high. A high percentage of people will be vaccinated against COVID-19


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pandemias , Farmácias , Inquéritos e Questionários , Estudos Transversais , Distribuição Aleatória
17.
Zhongguo Zhen Jiu ; 40(7): 749-55, 2020 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-32648400

RESUMO

OBJECTIVE: To observe the impacts of electroacupuncture (EA) on neurological function, the pathological morphology in brain tissue, apoptosis level and the protein expressions of apoptosis-related cytochrome C (Cyt-C) and cysteine aspartic acid protease-9 (Caspase-9) in the rats with traumatic brain injury (TBI) and explore the potential mechanism of EA in treatment of TBI. METHODS: A total of 70 clean-grade SD mice were randomized into a blank group (8 rats), a sham-operation group (8 rats), a model group (27 rats) and an EA group (27 rats). In terms of interventions of 3, 7 and 14 days, 3 subgroups were divided in the model group and the EA group successively, 9 rats in each subgroup. The modified Feeney free-fall percussion method was adopted to establish TBI models of rats. In the sham-operation group, only the skull was exposed and drilled and no free-fall percussion was exerted. One day after modeling, EA was given in the rats of EA group at "Shuigou" (GV 26), "Baihui" (GV 20) and "Neiguan" (PC 6) and "Zusanli" (ST 36) on the affected side, with intermittent wave, 2 Hz in frequency, once daily, 10 min each time, for 3, 7 and 14 days successively. Separately, on the day 3, 7 and 14 of intervention, the modified neurological severity scale (mNSS) was used to evaluate the degree of neurological function injury in the rats, HE staining and Nissl staining were to observe the pathological and morphological changes in brain tissue, TUNEL method was to observe the level of apoptosis in brain tissue and immunohistochemistry (IHC) method and Western blot were to determine the protein expressions of Cyt-C and Caspase-9 in brain tissue. RESULTS: Compared with the sham-operation group, on the day 3, 7 and 14 of intervention, mNSS scores were increased obviously in the rats of the model group respectively (P<0.01). Compared with the model group, on the day 3, 7 and 14 of intervention, mNSS scores were reduced in the rats of the EA group respectively (P<0.05). On day 3 of intervention, in brain injury region of the rats in the model group and the EA group, gross tissue necrosis, nuclear fragmentation, consolidation and obvious vacuolar changes, reduced Nissl bodies and scattered arrangement were found. On day 7 and 14 of intervention, in the model group and the EA group, the new connective tissue filling and normal cells were visible and Nissl bodies increased. The overall repair and Nissl body quantity in the EA group were better than the model group. Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the numbers of apoptotic cells were increased obviously in the model group (P<0.01) and they were reduced in the EA group as compared with the model group (P<0.05). Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue were all increased obviously in the model group (P<0.01) and they were all reduced in the EA group as compared with the model group successively (P<0.05). CONCLUSION: Electroacupuncture remarkably improves the condition in the neurological function injury and reduces apoptosis degree in TBI model rats, which is likely related to the down-regulation of the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue and further to bring the impacts on mitochondria mediated apoptosis process.


Assuntos
Apoptose , Lesões Encefálicas Traumáticas/terapia , Eletroacupuntura , Animais , Caspase 9/metabolismo , Citocromos c/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
18.
Zhongguo Zhen Jiu ; 40(7): 765-70, 2020 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-32648402

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expressions of tyrosine kinase Lyn and spleen tyrosine kinase (Syk) in mast cells of subcutaneous loose connective tissue in the rats with urticaria and explore the potential biological mechanism of EA in the intervention of urticaria. METHODS: A total of 32 SD rats were randomized into a blank group, a model group, an EA group and a positive medication group, 8 rats in each one. Except of the blank group, the passive cutaneous anaphylaxis (PCA) was adopted to prepare the model of urticaria in the rats of the rest three groups. In the EA group, EA was applied to bilateral "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36), with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, once daily, for 20 min each time, consecutively for 7 days. In the positive medication group, loratadine (1 mg•kg-1•d-1) was for intragastric administration, once daily, consecutively for 7 days. The samples were collected for index detection 30 min after PCA antigen challenge in the rats of each group. Spectrophotometer was adopted to determine the effusion quantity of Evans blue in the allergized site of skin. HE staining was used to observe the morphological changes in the allergized site of skin. Toluidine blue staining was provided to observe mast cell degranulation in subcutaneous loose connective tissue in the allergized site of skin. Immunohistochemistry was applied to determine the protein expressions of Lyn and Syk during degranulation of mast cells. RESULTS: In the rats of the odel group, the eipdermis of allergized site was thickening, cells were disorganized in hierarchy and inflammatory cells were infiltrated largely in the dermis. In the positive medication group and the EA group, the epidermis was getting thin, cell arrangement was clear and the inflammatory cell infiltration was obviously alleviated as compared with the model group. Compared with the blank group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all increased in the model group (P<0.01). Compared with the model group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all reduced in the EA group and the positive medication group (P<0.01). Compared with the positive medication group, the degranulation rate of mast cells was increased significantly in the EA group (P<0.01). CONCLUSION: Electroacupuncture at "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36) reduces vascular permeability and gives play to the role of anti-allergy by the way of regulating and controlling the degranulation of mast cells in the rats with urticaria and the effect mechanism of electroacupuncture may be related to the inhibition of protein expressions of Lyn and Syk in mast cells.


Assuntos
Tecido Conjuntivo/metabolismo , Eletroacupuntura , Mastócitos/metabolismo , Quinase Syk/metabolismo , Urticária/terapia , Quinases da Família src/metabolismo , Pontos de Acupuntura , Animais , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
19.
BMC Med Res Methodol ; 20(1): 176, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615934

RESUMO

BACKGROUND: The capacity of the current molecular testing convention does not allow high-throughput and community level scans of COVID-19 infections. The diameter in the current paradigm of shallow tracing is unlikely to reach the silent clusters that might be as important as the symptomatic cases in the spread of the disease. Group testing is a feasible and promising approach when the resources are scarce and when a relatively low prevalence regime is observed on the population. METHODS: We employed group testing with a sparse random pooling scheme and conventional group test decoding algorithms both for exact and inexact recovery. RESULTS: Our simulations showed that significant reduction in per case test numbers (or expansion in total test numbers preserving the number of actual tests conducted) for very sparse prevalence regimes is available. Currently proposed COVID-19 group testing schemes offer a gain up to 15X-20X scale-up. There is a good probability that the required scale up to achieve massive scale testing might be greater in certain scenarios. We investigated if further improvement is available, especially in sparse prevalence occurrence where outbreaks are needed to be avoided by population scans. CONCLUSION: Our simulations show that sparse random pooling can provide improved efficiency gains compared to conventional group testing or Reed-Solomon error correcting codes. Therefore, we propose that special designs for different scenarios could be available and it is possible to scale up testing capabilities significantly.


Assuntos
Infecções por Coronavirus/diagnóstico , Programas de Rastreamento/métodos , Pneumonia Viral/diagnóstico , Algoritmos , Simulação por Computador , Humanos , Pandemias , Distribuição Aleatória
20.
Nat Commun ; 11(1): 3520, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665551

RESUMO

PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure. Herein, we demonstrate that while PRDM15 is largely dispensable for mouse adult somatic cell homeostasis in vivo, it plays a critical role in B-cell lymphomagenesis. Mechanistically, PRDM15 regulates a transcriptional program that sustains the activity of the PI3K/AKT/mTOR pathway and glycolysis in B-cell lymphomas. Abrogation of PRDM15 induces a metabolic crisis and selective death of lymphoma cells. Collectively, our data demonstrate that PRDM15 fuels the metabolic requirement of B-cell lymphomas and validate it as an attractive and previously unrecognized target in oncology.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Imunoprecipitação da Cromatina , Biologia Computacional , Proteínas de Ligação a DNA/genética , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Humanos , Linfoma/genética , Linfoma/metabolismo , Camundongos , Camundongos SCID , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Distribuição Aleatória , Fatores de Transcrição/genética , Transcriptoma/genética
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