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1.
Environ Toxicol Pharmacol ; 102: 104241, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37562547

RESUMO

The use of in vivo models to assess nephrotoxicity has faced ethical limitations. A viable alternative is the ex vivo model that combines the 3 R principles with the preservation of tissue histology. Here, we established a gentamicin nephrotoxicity model using pigs` kidney explants and investigated the effect of phytic acid (IP6) against gentamicin- induced nephrotoxicity. A total of 360 kidney explants were divided into control, gentamicin (10 mM), IP6 (5 mM), and gentamicin+IP6 groups. The activity of gammaglutamyltransferase (GGT), creatinine levels, histological assessment, oxidative stress, and inflammatory cytokine expression were analyzed. Exposure to gentamicin induced an increase in GGT activity, creatinine levels, lesion score, lipoperoxidation and IL-8 expression. Explants exposed to IP6 remained like the control. The addition of IP6 to gentamicin prevented tissue damage, increasing the antioxidant status and gene expression of IL-10. This model proved to be an adequate experimental approach for identifying nephrotoxins and potential products to modulate the toxicity.


Assuntos
Nefropatias , Insuficiência Renal , Animais , Suínos , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Ácido Fítico/metabolismo , Creatinina , Rim , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Gentamicinas/toxicidade , Estresse Oxidativo , Nefropatias/patologia
2.
Toxicon ; 220: 106944, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36272502

RESUMO

Deoxynivalenol (DON), a mycotoxin produced mainly by Fusarium graminearum and F. culmorum commonly contaminates food commodities across the globe. Due to this, exposure to DON might pose potential health hazards to humans and animals. Biological factors like sex and age can influence the toxicity of DON. However, in toxicological studies involving DON, the sex and age-dependent response has been often overlooked. Thereby, the objective of this study was to evaluate if sex differences are evident in DON's systemic effects in peripubertal rats. Juvenile animals (n = 24) with 28 days postnatal day were randomly assigned to two experimental groups: Control group (n = 12, 6 females and 6 males, mycotoxin-free diet) and DON group (n = 12, 6 females and 6 males, diet containing 10 mg DON/kg of feed). During 28 days of treatment, the animals were weighed weekly and body weight gain and food intake were calculated for each week. After the experimental period, blood samples, intestine, liver, and kidney were collected and destined for biochemical, hematological, histopathological, and oxidative stress analyses. Greater anorectic responses were seen in males, while only females showed increased levels of creatinine and triglycerides. Regardless of sex, DON induces an increased number of white blood cells, particularly lymphocytes and a significant reduction in the levels of hemoglobin, hematocrit, mean corpuscular hemoglobin, and neutrophils. In males and females fed a DON-contaminated diet, histological lesions were observed in the intestine, liver, and kidney. Ingestion of DON induced a significant increase in the antioxidant potential in the intestine, liver, and kidney. However, this effect was not able to prevent oxidative stress in the renal tissue. Taken together, our results showed a sex-related response in food intake, weight gain, and biochemical parameters in rats exposed to DON during the juvenile and peripubertal periods. In addition, we have verified that oxidative stress is an important mechanism in the nephrotoxicity of DON.


Assuntos
Micotoxinas , Tricotecenos , Humanos , Animais , Feminino , Ratos , Masculino , Micotoxinas/toxicidade , Dieta , Anorexia/induzido quimicamente , Ração Animal/análise , Contaminação de Alimentos/análise
3.
Eur Phys J C Part Fields ; 82(2): 121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210938

RESUMO

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example.

4.
Toxicon ; 203: 12-21, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600911

RESUMO

The deterioration of food and feed stuffs and toxic intestinal effects due to fungal colonization and concomitant production of mycotoxins is an increasing concern. The development of fungi resistance to many commonly used chemical preservatives adds further alarm. Therefore, effective detoxification methods would be useful in counteracting this problem. Biotransformation/adsorption of mycotoxins by lactic acid bacteria and their metabolites is a promising approach to minimize the deleterious effects of mycotoxins. The objective of the present study was to evaluate the beneficial effects of Lactobacillus plantarum metabolites in reducing deoxynivalenol intestinal toxicity. To achieve this aim, histological, morphometrical and oxidative stress analyses were performed in the intestinal mucosa of piglets exposed to deoxynivalenol alone or associated with two strains (SN1 and SN2) of L. plantarum subsp. plantarum metabolites. Metabolites were obtained after dichloromethane (D) or ethyl acetate (A) extraction. Jejunal explants were exposed to the following treatments for 2 and 4 h a) culture medium (control group); b) deoxynivalenol (DON, 10 µM); c) L. plantarum metabolites DSN1; d) L. plantarum metabolites DSN1+DON; e) L. plantarum metabolites DSN2; f) L. plantarum metabolites DSN2+DON; g) L. plantarum metabolites ASN1; h) L. plantarum metabolites ASN1+DON; i) L. plantarum metabolites ASN2; j) L. plantarum metabolites ASN2+DON. The metabolites were incubated 1 h previously to DON challenge (one and 3 h of exposure). Histological assessment showed DON-treated explants with villi fusion and atrophy, multifocal apical necrosis and cuboid or flattened enterocytes with 2 and 4 h of exposure, while LP metabolites groups individually or associated with DON remained like control. The density of goblet cells in villi and crypts was reduced in DON explants compared to control group with 2 and 4 h of exposure; on the other hand, a significant increase in this parameter was achieved in LP metabolites groups compared to DON. Morphometric evaluation showed no difference in villi height or crypts depth in any treated explants. Overall, oxidative stress response assessments showed that explants exposed to SN1 extracted with dichloromethane and ethyl acetate, and SN2 extracted with dichloromethane reduced superoxide anion production. In conclusion, L. plantarum metabolites induced beneficial effects in intestinal mucosa, reducing the toxic effects of DON on intestinal morphology and oxidative response.


Assuntos
Lactobacillus plantarum , Micotoxinas , Tricotecenos , Animais , Jejuno , Suínos , Tricotecenos/toxicidade
5.
J Phys Chem C Nanomater Interfaces ; 125(11): 6387-6400, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33868543

RESUMO

Ternary lanthanide indium oxides LnInO3 (Ln = La, Pr, Nd, Sm) were synthesized by high-temperature solid-state reaction and characterized by X-ray powder diffraction. Rietveld refinement of the powder patterns showed the LnInO3 materials to be orthorhombic perovskites belonging to the space group Pnma, based on almost-regular InO6 octahedra and highly distorted LnO12 polyhedra. Experimental structural data were compared with results from density functional theory (DFT) calculations employing a hybrid Hamiltonian. Valence region X-ray photoelectron and K-shell X-ray emission and absorption spectra of the LnInO3 compounds were simulated with the aid of the DFT calculations. Photoionization of lanthanide 4f orbitals gives rise to a complex final-state multiplet structure in the valence region for the 4f n compounds PrInO3, NdInO3, and SmInO3, and the overall photoemission spectral profiles were shown to be a superposition of final-state 4f n-1 terms onto the cross-section weighted partial densities of states from the other orbitals. The occupied 4f states are stabilized in moving across the series Pr-Nd-Sm. Band gaps were measured using diffuse reflectance spectroscopy. These results demonstrated that the band gap of LaInO3 is 4.32 eV, in agreement with DFT calculations. This is significantly larger than a band gap of 2.2 eV first proposed in 1967 and based on the idea that In 4d states lie above the top of the O 2p valence band. However, both DFT and X-ray spectroscopy show that In 4d is a shallow core level located well below the bottom of the valence band. Band gaps greater than 4 eV were observed for NdInO3 and SmInO3, but a lower gap of 3.6 eV for PrInO3 was shown to arise from the occupied Pr 4f states lying above the main O 2p valence band.

6.
Prog Brain Res ; 228: 221-39, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27590971

RESUMO

Brain-computer interfaces (BCIs) are often based on the control of sensorimotor processes, yet sensorimotor processes are impaired in patients suffering from amyotrophic lateral sclerosis (ALS). We devised a new paradigm that targets higher-level cognitive processes to transmit information from the user to the BCI. We instructed five ALS patients and twelve healthy subjects to either activate self-referential memories or to focus on a process without mnemonic content while recording a high-density electroencephalogram (EEG). Both tasks are designed to modulate activity in the default mode network (DMN) without involving sensorimotor pathways. We find that the two tasks can be distinguished after only one experimental session from the average of the combined bandpower modulations in the theta- (4-7Hz) and alpha-range (8-13Hz), with an average accuracy of 62.5% and 60.8% for healthy subjects and ALS patients, respectively. The spatial weights of the decoding algorithm show a preference for the parietal area, consistent with modulation of neural activity in primary nodes of the DMN.


Assuntos
Esclerose Lateral Amiotrófica/reabilitação , Interfaces Cérebro-Computador , Cognição/fisiologia , Neurorretroalimentação/métodos , Lobo Parietal/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Ritmo alfa/fisiologia , Mapeamento Encefálico , Eletroencefalografia , Eletromiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neurorretroalimentação/instrumentação , Análise de Componente Principal , Ritmo Teta/fisiologia , Interface Usuário-Computador , Adulto Jovem
7.
Plant Cell Environ ; 39(9): 2064-73, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27144906

RESUMO

Assessment of yield performance under fluctuating environmental conditions is a major aim of crop breeders. Unfortunately, results from controlled-environment evaluations of complex agronomic traits rarely translate to field performance. A major cause is that crops grown over their complete lifecycle in a greenhouse or growth chamber are generally constricted in their root growth, which influences their response to important abiotic constraints like water or nutrient availability. To overcome this poor transferability, we established a plant growth system comprising large refuse containers (120 L 'wheelie bins') that allow detailed phenotyping of small field-crop populations under semi-controlled growth conditions. Diverse winter oilseed rape cultivars were grown at field densities throughout the crop lifecycle, in different experiments over 2 years, to compare seed yields from individual containers to plot yields from multi-environment field trials. We found that we were able to predict yields in the field with high accuracy from container-grown plants. The container system proved suitable for detailed studies of stress response physiology and performance in pre-breeding populations. Investment in automated large-container systems may help breeders improve field transferability of greenhouse experiments, enabling screening of pre-breeding materials for abiotic stress response traits with a positive influence on yield.


Assuntos
Biomassa , Produtos Agrícolas/crescimento & desenvolvimento , Projetos de Pesquisa , Brassica napus , Secas , Fertilizantes , Nitrogênio , Estresse Fisiológico
8.
Neuroscience ; 314: 134-44, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26642808

RESUMO

Fibroblast growth factors (FGFs) regulate development and maintenance, and reduce vulnerability of neurons. FGF-2 is essential for survival of midbrain dopaminergic (DA) neurons and is responsible for their dysplasia and disease-related degeneration. We previously reported that FGF-2 is involved in adequate forebrain (FB) target innervation by these neurons in an organotypic co-culture model. It remains unclear, how this ex-vivo phenotype relates to the in vivo situation, and which FGF-related signaling pathway is involved in this process. Here, we demonstrate that lack of FGF-2 results in an increased volume of the striatal target area in mice. We further add evidence that the low molecular weight (LMW) FGF-2 isoform is responsible for this phenotype, as this isoform is predominantly expressed in the embryonic ventral midbrain (VM) as well as in postnatal striatum (STR) and known to act via canonical transmembrane FGF receptor (FGFR) activation. Additionally, we confirm that the phenotype with an enlarged FB-target area by DA neurons can be mimicked in an ex-vivo explant model by inhibiting the canonical FGFR signaling, which resulted in decreased extracellular signal-regulated kinase (ERK) activation, while AKT activation remained unchanged.


Assuntos
Corpo Estriado/citologia , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/citologia , Fator 2 de Crescimento de Fibroblastos/fisiologia , Substância Negra/citologia , Substância Negra/metabolismo , Animais , Corpo Estriado/embriologia , Neurônios Dopaminérgicos/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vias Neurais/citologia , Vias Neurais/embriologia , Vias Neurais/metabolismo , Prosencéfalo , Isoformas de Proteínas/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Substância Negra/embriologia , Tirosina 3-Mono-Oxigenase/metabolismo
9.
Braz. j. med. biol. res ; 48(4): 321-331, 4/2015. graf
Artigo em Inglês | LILACS | ID: lil-744363

RESUMO

It is currently accepted that superoxide anion (O2•−) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO2), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO2 is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO2. The KO2-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO2 induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO2 also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO2-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO2 is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.


Assuntos
Animais , Masculino , Camundongos , /efeitos dos fármacos , Hiperalgesia/induzido quimicamente , Inflamação/induzido quimicamente , Dor Nociceptiva/induzido quimicamente , Superóxidos/farmacologia , Analgésicos Opioides/uso terapêutico , Antioxidantes/uso terapêutico , /uso terapêutico , /genética , Edema/induzido quimicamente , Membro Posterior , Temperatura Alta , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Dor Nociceptiva/tratamento farmacológico , Medição da Dor/métodos , Peroxidase/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos
10.
Braz J Med Biol Res ; 48(4): 321-31, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25714890

RESUMO

It is currently accepted that superoxide anion (O2•-) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO2), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO2 is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO2. The KO2-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO2 induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO2 also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO2-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO2 is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.


Assuntos
Ciclo-Oxigenase 2/efeitos dos fármacos , Hiperalgesia/induzido quimicamente , Inflamação/induzido quimicamente , Dor Nociceptiva/induzido quimicamente , Superóxidos/farmacologia , Analgésicos Opioides/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Edema/induzido quimicamente , Membro Posterior , Temperatura Alta , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Dor Nociceptiva/tratamento farmacológico , Medição da Dor/métodos , Peroxidase/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Pele/efeitos dos fármacos , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos
11.
Neuroscience ; 286: 293-307, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25499314

RESUMO

Fibroblast growth factor-2 (FGF-2) is a potent neurotrophic factor promoting survival of dopaminergic (DA) neurons in vitro and in vivo. FGF-2 is expressed in different isoforms representing distinct translation products from a single mRNA. For this study, we focused on the high molecular weight (HMW) isoform, which, after non-viral plasmid-based overexpression in embryonic day 12 (E12) rat ventral mesencephalon (VM)-derived cells, revealed increased numbers of tyrosine hydroxylase-positive (TH(+)) cells in a 'colayer' cell culture model. To determine the therapeutic potential of VM cells producing FGF-2-HMW as their 'own' neurotrophic factor, we transplanted cell suspensions obtained from such in vitro modified and differentiated cell cultures into the 6-hydroxydopamine (6-OHDA) hemiparkinsonian rat model. Animals, having received either non-transfected cells, empty-control transfected, or FGF-2-HMW-plasmid transfected cells, were analyzed in two different transplantation paradigms each using 172,000 or 520,000 cells, respectively. The behavioral performances in the amphetamine- and apomorphine-induced rotational test as well as in the cylinder test were evaluated for up to thirteen weeks post transplantation (postTX). Finally, the integration of the grafted cells into the host striatum was analyzed by immunohistochemical measurements. Those analyses revealed improvements of behavioral deficits in all five groups receiving DA neuron grafts, except for amphetamine-induced rotation of the FGF-2-HMW small graft group. Altogether, genetic modification with the FGF-2-HMW-plasmid did not further improve functional recovery compared to the control groups and had no influence on either the number of surviving DA neurons or on the density of outgrowing TH(+) fibers.


Assuntos
Neurônios Dopaminérgicos/citologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Mesencéfalo/citologia , Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Células Cultivadas , Feminino , Atividade Motora , Oxidopamina , Isoformas de Proteínas , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase
12.
Braz J Med Biol Res ; 46(7): 601-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23903682

RESUMO

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.


Assuntos
Hiperalgesia/metabolismo , Interleucinas/metabolismo , Dor Nociceptiva/fisiopatologia , Medição da Dor/métodos , Receptores de Interleucina/deficiência , Transdução de Sinais , Ácido Acético , Animais , Benzoquinonas , Homozigoto , Temperatura Alta , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Camundongos , Camundongos Endogâmicos BALB C , Atividade Motora/fisiologia , Nociceptividade/fisiologia , Dor Nociceptiva/induzido quimicamente , Ovalbumina/imunologia , Teste de Desempenho do Rota-Rod
13.
Braz. j. med. biol. res ; 46(7): 601-606, ago. 2013. graf
Artigo em Inglês | LILACS | ID: lil-682395

RESUMO

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.


Assuntos
Animais , Camundongos , Hiperalgesia/metabolismo , Interleucinas/metabolismo , Dor Nociceptiva/fisiopatologia , Medição da Dor/métodos , Receptores de Interleucina/deficiência , Transdução de Sinais , Ácido Acético , Benzoquinonas , Homozigoto , Temperatura Alta , Camundongos Endogâmicos BALB C , Atividade Motora/fisiologia , Nociceptividade/fisiologia , Dor Nociceptiva/induzido quimicamente , Ovalbumina/imunologia , Teste de Desempenho do Rota-Rod
14.
Lupus ; 20(13): 1356-64, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21868433

RESUMO

The aims of the present study were to report the frequency of metabolic syndrome in systemic lupus erythematosus (SLE); to verify differences in inflammatory biomarkers and oxidative stress in SLE patients with or without metabolic syndrome; and to assess which metabolic syndrome components are associated with oxidative stress and disease activity. The study included 58 SLE patients and 105 controls. SLE patients were divided in two groups, with and without metabolic syndrome. 41.4% patients met the criteria for metabolic syndrome compared with 10.5% controls. Patients with SLE and metabolic syndrome had significantly raised serum uric acid, C-reactive protein (CRP), lipid hydroperoxides, and protein oxidation when compared with patients with SLE without metabolic syndrome. Lipid hydroperoxides were correlated with CRP, whereas protein oxidation was associated with waist circumference and uric acid. There was a positive association between serum C3 and C4 and glucose and between C3 and CRP. SLE disease activity index (SLEDAI) scores were positively correlated with body mass index (BMI) and waist circumference (WC). In conclusion, SLE patients have a high prevalence of metabolic syndrome and this syndrome directly contributes to increase inflammatory status and oxidative stress. Inflammatory processes, being overweight/obese, and uric acid may favor oxidative stress increases in patients with SLE and metabolic syndrome. C3 and C4 may have a positive acute-phase protein behavior in patients with SLE.


Assuntos
Biomarcadores/metabolismo , Inflamação , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Síndrome Metabólica/sangue , Síndrome Metabólica/imunologia , Estresse Oxidativo , Proteínas de Fase Aguda/metabolismo , Adulto , Proteína C-Reativa/metabolismo , Comorbidade , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Peroxidação de Lipídeos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade , Sobrepeso , Fatores de Risco , Ácido Úrico/sangue
15.
Eur Radiol ; 19(2): 324-32, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18726597

RESUMO

The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL(CO)) (R= -0.531, P<0.0001) and moderately with forced vital capacity (FVC) (R= -0.483, P=0.0008). There was close correlation between CAD and the readers (EoILD vs. CAD: R=0.716, P<0.0001; EoRet vs. CAD: R=0.69, P<0.0001). Subgroup analysis including patients with minimal EoGGO (<15%) strengthened the correlations between CAD and the readers, readers and PFT, and CAD and PFT. EoILD by readers correlated strongly with DL(CO) (R= -0.705, P<0.0001) and moderately with FVC (R= -0.559, P=0.0002). EoRet correlated closely with DL(CO) and moderately with FVC (DL(CO): R= -0.663; FVC: R = -0.436; P

Assuntos
Doenças do Colágeno/diagnóstico , Doenças do Colágeno/metabolismo , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/metabolismo , Doenças Vasculares/diagnóstico , Doenças Vasculares/metabolismo , Idoso , Estudos de Coortes , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise de Regressão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
16.
Z Geburtshilfe Neonatol ; 211(2): 45-53, 2007 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-17486524

RESUMO

There has been a controversial discussion for decades about the significance of low blood pressure during pregnancy. This review should answer the question, whether low blood pressure itself or the decrease in blood pressure on standing have a negative effect on pregnant women. In addition, we will focus on physiologic and pathophysiologic pregnancy related mechanisms of changes in blood pressure. Subjective symptoms occur more frequently with low blood pressure, however, they disappear at the end of pregnancy. Physiologically, blood pressure decreases towards midpregnancy and rises to preconceptional values at term. Birthweight was directly related to the magnitude and direction of the pressor response on standing in late pregnancy but not to the low blood pressure at rest itself. There is no causal association between low blood pressure and poor perinatal outcomes. It is only an accompanied symptom for other risks in pregnancy. There is a direct relationship between the change in mean arterial blood pressure in standing position and birthweight during late pregnancy. Patients whose pressure falls on standing have the lightest babies.


Assuntos
Hipotensão Ortostática/etiologia , Hipotensão/etiologia , Animais , Peso ao Nascer/fisiologia , Sistema Cardiovascular/fisiopatologia , Feminino , Idade Gestacional , Humanos , Hipotensão/diagnóstico , Hipotensão/fisiopatologia , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/fisiopatologia , Recém-Nascido , Gravidez , Resultado da Gravidez , Ratos , Valores de Referência , Fatores de Risco , Resistência Vascular/fisiologia
17.
Arch Orthop Trauma Surg ; 121(1-2): 75-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11195125

RESUMO

In a cross-sectional study, 46 male patients with paralysis after spinal cord injury (average age 32 years; injuries sustained from 1 to 26 years ago; 33 Frankel A, 13 Frankel B, C, D) were examined clinically and by dual-energy X-ray absorptiometry (DEXA). Their bone mineral density (BMD) values were compared with age-related controls and correlated to clinical parameters. BMD was reduced in the proximal femur (p < 0.05) and the distal forearm (p < 0.05), but not in the lumbar spine. Demineralisation was influenced in the proximal femur (Z-score -2.95) by immobilisation after surgical treatment. Patients suffering from complete lesions had significantly lower BMD in the lumbar spine (-1.47) compared with patients with incomplete lesions (+0.02). BMD was not significantly influenced by the level of the lesion and the ambulatory status. Long-term monitoring showed significant demineralisation in the proximal femur (r = -0.36) and the distal forearm (r = -0.4), but not in the lumbar spine (r = -0.21). By correlating BMD with clinical parameters, it can be deduced that, firstly, immobilisation after surgical treatment should be reduced to a minimum; secondly, that every effort must be expended to prevent turning an incomplete into a complete lesion; and finally, that rehabilitation treatment should be lifelong.


Assuntos
Absorciometria de Fóton , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Quadriplegia/complicações , Traumatismos da Medula Espinal/complicações , Adulto , Densidade Óssea , Estudos de Casos e Controles , Estudos Transversais , Fêmur/diagnóstico por imagem , Antebraço/diagnóstico por imagem , Humanos , Imobilização/efeitos adversos , Vértebras Lombares/diagnóstico por imagem , Masculino , Osteoporose/prevenção & controle , Cintilografia , Fatores de Risco , Traumatismos da Medula Espinal/classificação
18.
Ultraschall Med ; 21(1): 26-31, 2000 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-10746281

RESUMO

AIM: To evaluate a novel 3D power Doppler ultrasound-technique (3D PDUS) in the diagnosis and documentation of tumours of the floor of the mouth. METHOD: 22 patients with tumours of the floor of the mouth (2 T1-, 5 T2-, 6 T3- and 9 T4-carcinomas) prospectively underwent conventional grey-scale ultrasound combined with power Doppler ultrasound and 3D PDUS (3-Scape). All examinations were performed with the "Sonoline Elegra Advanced" in combination with a 7.5 MHz transducer. Two independent observers compared the results regarding clear tumour margins, midline crossing, infiltration of the mylohyoid muscle, infrahyoidal tumour, contact to the mandible, contact to major vessels (such as the lingual, submental and/or facial artery), intra- and peritumoural vascularisation and judged the value of the 3D reconstruction method for documentation purpose. RESULTS: All parameters relevant for therapy could be gathered from the 3D data (agreement: 98.2%) almost without loss of information; results of both observers were identical (kappa value: 1.0). In the comparison to conventional ultrasound, 3D PDUS also allows for the reconstruction of axial images of the floor of the mouth similar to CT-images, and a 3D image of tumour vascularisation can be obtained. Acquisition and reconstruction of the 3D data only takes a couple of minutes. CONCLUSIONS: "3-Scape" is a novel easy-to-perform method allowing the complete acquisition of 3D data of the entire floor of the mouth, and providing the possibility to digitally store and/or transfer examination results without loss of information. Reconstruction of ultrasound-images in any desirable plane and/or as a 3D presentation is possible. Thus, in the future, additional software will facilitate the determination of the volume and the degree of vascularisation of tumours.


Assuntos
Neoplasias Bucais/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Documentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/irrigação sanguínea , Neoplasias Bucais/patologia , Invasividade Neoplásica , Estadiamento de Neoplasias , Variações Dependentes do Observador
19.
Zentralbl Gynakol ; 120(6): 293-300, 1998.
Artigo em Alemão | MEDLINE | ID: mdl-9659700

RESUMO

In a randomized, prospective study at the Dept. of Obstetrics and Gynecology of the University Hospital of Giessen 4 different ways of inducing abortions with prostaglandins were tested between the 15th and 24th week of gestation. The aim of the study was to determine the best approach to inducing abortion in order to minimize the psychological and physical stress to the patient. Subjects randomized to the first two groups got a single cervical installation of either 0.5 mg Dinoprostongel (Prepidil, N = 22) or 0.5 mg Sulprostongel (Nalador, N = 21). Six hours later, i.v. infusion with Sulproston (8.3 micrograms/min) was started and continued until the abortion was complete. Patients randomized to the third and fourth group received either 0.5 mg Dinoprostongel intracervically (N = 15) or 1 mg Gemeprost vaginal suppositories (Cergem, N = 21) every 6 hours until the cervix was 1-2 cm dilated. Subsequently the patients received an i.v. infusion with Sulproston until the abortion was complete. In the first group with intracervical application of Sulproston the total time until abortion was 17.8 h +/- 7.8 h. This was shorter than following a single application of Dinoprostongel (22.5 h +/- 14.7 h). Although there was a five hours difference, the between-group differences were not statistically different because of a wide range in values following Dinoproston treatment. This range could not be explained by the age of the mother, week of gestation or parity. In the group receiving multiple intracervical applications of Dinoproston the time till expulsion was twice as long as that after multiple vaginal suppositories of Gemeprost (33.8 h +/- 13.9 h vs. 15.6 +/- 6.0 h, p < 0.01). The time span until a cervical dilatation of 1-2 cm was 27.0 h +/- 13.7 h in the group with repeated Dinoproston application. This period of time was more than twice the time span seen in the group with repeated Gemeprost application (12.5 h +/- 4.2 h, p < 0.01). On the average four treatments with intracervical Dinoprostongel were required while the average with Gemeprost vaginal suppositories was two to achieve a cervical dilatation of 1-2 cm. Furthermore in 7 of 21 cases treatment with Gemeprost achieved the expulsion of the fetus without Sulproston infusion (11.4 h +/- 5.2 h). Comparing single versus repetitive prostaglandin application we could demonstrate that the duration of Sulproston infusion was cut in half after repeated therapy with Gemeprost. We conclude that repetitive application of Gemeprost vaginal suppositories decreases the time to abortion and subject discomfort tremendously. The application of Gemeprost suppositories provides the easiest and most efficient therapeutic approach for both patients and staff. Furthermore the regiment that provided the best results was also the most cost-effective (range 180,-DM to 317,- DM per case).


Assuntos
Abortivos não Esteroides/administração & dosagem , Aborto Eugênico , Aborto Induzido , Alprostadil/análogos & derivados , Dinoprostona/análogos & derivados , Dinoprostona/administração & dosagem , Abortivos não Esteroides/efeitos adversos , Administração Intravaginal , Adulto , Alprostadil/administração & dosagem , Alprostadil/efeitos adversos , Dinoprostona/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
20.
Eur J Pediatr ; 156(5): 389-91, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9177983

RESUMO

UNLABELLED: To compare the impact of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, uncomplicated hypertension in pregnancy (HIP), and no hypertension (controls) on neonatal morbidity and mortality, 108 infants were matched with respect to gestational age, date of birth, and gender. The HELLP group infants had more grade 3 and 4 respiratory distress syndromes (36%) than the HIP group (19%) or controls (11%). Cardiovascular instability (arterial hypotension, volume resuscitation) was significantly more common in HELLP neonates (20% and 31%) than in HIP infants (9% and 6%) or controls (3% and 9%). Both, HELLP and HIP infants showed a higher incidence of growth retardation than the controls. After 32 weeks of gestation the incidence of severe neonatal morbidity was not different. CONCLUSION: : Before 32 weeks of gestation both respiratory and cardiovascular morbidity and intra-uterine growth retardation associated with HIP is further aggravated by a maternal HELLP syndrome.


Assuntos
Síndrome HELLP , Hipertensão , Mortalidade Infantil , Complicações Hematológicas na Gravidez , Adulto , Peso ao Nascer , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Síndrome HELLP/sangue , Humanos , Hipertensão/sangue , Recém-Nascido , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez/sangue , História Reprodutiva , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia
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