RESUMO
Background: Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results: Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (ß adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion: These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.(AU)
Assuntos
Animais , Masculino , Camundongos , Pneumonia/fisiopatologia , Atropina/farmacologia , Venenos de Escorpião/intoxicação , 1-Propanol/farmacologia , Venenos de Escorpião , Acetilcolina , CitocinasRESUMO
Coronary heart disease (CHD) is one of the major causes of human death. The most successful therapeutic approach available is based on the reduction of low density-lipoprotein cholesterol (LDL-C). However, it is believed that the next paradigm in CHD treatment will rely on increased HDL-C levels. One of the most promising strategies for this goal is the inhibition of cholesteryl ester transfer protein (CETP). In the present work, robust classical 2D QSAR (r(2)=0.76, q(2)=0.72) and hologram QSAR (r(2)=0.88, q(2)=0.70) models were developed for a series of 85 CETP inhibitors (N-N-disubstituted trifluoro-3-amino-2-propanol derivatives). These models are complementary in nature and highlight important structural features for the design of novel CETP inhibitors with improved potency.
Assuntos
1-Propanol/farmacologia , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Ésteres do Colesterol/metabolismo , Relação Quantitativa Estrutura-Atividade , 1-Propanol/química , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: To monitor the stiffening rate of demineralized dentin matrix at the early stages after exposure to different neat solvents. METHODS: Dentin beams approximately 0.8x0.7x8.0 mm were obtained from human third molars. After covering their ends with resin composite, the middle exposed length of 4.0mm (gauge-length) was demineralized in 0.5 M EDTA (pH 7.0) for 7 days. The specimens were gripped by a testing machine, pre-loaded to 10 g and cyclically stressed in tension to 5% strain, for 30 repeated cycles (total 20 min) at 0.6 mm/min while immersed in water (control). Then, water was replaced by either 100% acetone, methanol, ethanol, propanol, HEMA or air and the specimens subjected to the same cyclic protocol. The maximum apparent modulus of elasticity (E(Max)) was calculated for every cycle, plotted as a function of time and subjected to regression analysis. Stiffening rate was calculated as changes in E (min). Regression analysis examined the relationship between E and time for each solvent. Data were analyzed by one-way ANOVA and Student-Newman-Keuls test at alpha=0.05. RESULTS: Regression analysis showed that E increased significantly with time in all water-free solvents (R2=0.8-0.99). Stiffening rate was higher for acetone (0.9 MPa/min) and ethanol (0.8 MPa/min), intermediate for air (0.7 MPa/min), methanol (0.6 MPa/min) and propanol (0.5 MPa/min), lower for HEMA (0.2 MPa/min) and practically none for water (0.07 MPa/min) with p<0.05. CONCLUSIONS: The solvent-induced stiffening rate of demineralized dentin matrix is both time and solvent-dependent. The ability of solvents to promptly stiffen the demineralized dentin matrix may be important in maintaining the resin-infiltrated matrix expanded during the solvent evaporation stage of resin bonding.
Assuntos
Solubilidade da Dentina , Dentina/efeitos dos fármacos , Solventes/farmacologia , Desmineralização do Dente/patologia , 1-Propanol/farmacologia , Acetona/farmacologia , Ar , Análise de Variância , Colágeno/química , Análise do Estresse Dentário , Elasticidade/efeitos dos fármacos , Etanol/farmacologia , Humanos , Metacrilatos/farmacologia , Metanol/farmacologia , Análise de Regressão , Estatísticas não Paramétricas , Resistência à Tração/efeitos dos fármacos , Fatores de TempoRESUMO
Ethanol is the major product of yeast sugar fermentation and yet, at certain concentrations, it is very toxic to yeast cells. The major targets for ethanol's toxicity are the plasma membrane and the cytosolic enzymes: ethanol alters membrane organization and permeability and inactivates and unfolds globular cytosolic enzymes. The effects of ethanol on the plasma membrane are attenuated by the presence of trehalose, a disaccharide of glucose that is accumulated simultaneously with urea. The data presented in this paper show that trehalose is not effective at protecting yeast cytosolic inorganic pyrophosphatase against the inactivation of its catalytic activity promoted by alcohols. In contrast, 1 M trehalose increased the toxicity of alcohols against pyrophosphatase by at least 34%. On the other hand, 1.5 M urea attenuated the inactivation of pyrophosphatase promoted by alcohols by approximately 50%. Here we propose that, in the presence of alcohols, urea functions as a molecular filter, enriching the vicinity of the protein with water and excluding alcohol molecules. Conversely, trehalose tends to increase the interaction of alcohols with protein molecules, by withdrawing water, leading to a stronger inactivation promoted for a given concentration of alcohol in the bulk solution on pyrophosphatase activity.
Assuntos
Etanol/metabolismo , Etanol/farmacologia , Pirofosfatases/antagonistas & inibidores , Pirofosfatases/metabolismo , Ureia/metabolismo , Ureia/farmacologia , Leveduras/enzimologia , 1-Propanol/farmacologia , Catálise/efeitos dos fármacos , Etanol/antagonistas & inibidores , Fermentação , Cinética , Metanol/farmacologia , Pirofosfatases/química , Trealose/metabolismoRESUMO
BACKGROUND: Several methods are used to study heart rate variability, but they have limitations, which might be overcome by the use of a three-dimensional return map. OBJECTIVES: To evaluate the performance of three-dimensional return map-derived indices to detect (1) sympathetic and parasympathetic modulation to the sinus node and (2) autonomic dysfunction in diabetic patients. METHODS: Six healthy subjects underwent partial and total pharmacological autonomic blockade in a protocol that incorporated vagal and sympathetic predominance. Twenty-two patients with type 2 diabetes mellitus and 12 normal controls participated in the subsequent validation experiment. Three-dimensional return maps were constructed by plotting RRn intervals versus the difference between adjacent RR intervals [(RRn+1)-(RRn)] versus the number of counts, and four derived indices (P1, P2, P3, MN) were created for quantification. RESULTS: Both indices P1 and MN were significantly increased after sympathetic blockade with propranolol, while all indices except P1 were modified after parasympathetic blockade (P < 0.05). During the validation experiments, P1 and MN detected differences between normal controls, and diabetic patients with and without autonomic neuropathy. The overall accuracy of most three-dimensional indices to detect autonomic dysfunction, estimated by the area under the ROC curve, was significantly better than traditional time domain indices. Three-dimensional return map-derived indices also showed adequate reproducibility on two different recording days (intra-class correlation coefficients of 0.69 to 0.82; P < 0.001). CONCLUSIONS: Three-dimensional return map-derived indices are reproducible, quantify parasympathetic as well as sympathetic modulation to the sinus node, and are capable of detecting autonomic dysfunction in diabetic patients.
Assuntos
Vias Autônomas/fisiopatologia , Circulação Sanguínea/fisiologia , Neuropatias Diabéticas/fisiopatologia , Testes de Função Cardíaca/métodos , Frequência Cardíaca/fisiologia , Coração/fisiologia , Nó Sinoatrial/fisiologia , 1-Propanol/farmacologia , Adulto , Atropina/farmacologia , Vias Autônomas/efeitos dos fármacos , Neuropatias Diabéticas/patologia , Coração/inervação , Testes de Função Cardíaca/instrumentação , Humanos , Nó Sinoatrial/efeitos dos fármacosRESUMO
The addition of a precursor of the enol form of isobutanal to neutrophils results in formation of triplet acetone, as attested to by emission from appropriate acceptors and cell damage (Nascimento et al., 1986 Biochim. Biophys. Acta 888, 337-342). The present study confirms the formation of triplet acetone by detection of the direct emission (lambda max 430 nm) and differentiates between effects produced by triplet acetone and by the enol substrate itself. Thus, triplet acetone: (1) enhances the release of ribonucleic acid; (2) promotes lipid peroxidation (N3(-)-inhibitable formation of thiobarbituric acid reactive products and concomitant light emission peaking at 480-500 nm); (3) increases myeloperoxidase activity, presumable as a result of damage and consequent increased exposure of the enzyme. On the other hand, the enol greatly enhances the release of protein(s) into the medium. These results confirm the utility of the neutrophil as a model system for the study of chemiexcitation processes induced at the cellular level. They also provide the first demonstration that an excited species formed at the cellular level may induce release of nucleic acids, thus reflecting the occurrence of deleterious processes in situ.