Relationship between inflammation and oxidative stress and its effect on multiple sclerosis / Relación entre inflamación y estrés oxidativo y su efecto sobre la esclerosis múltiple

Introduction: This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune disease. Development: The oxidative stress concept has been defined by an imbalance between oxidants and antioxidants in favor of the oxidants. There is necessary to do physiological functions, like the respiration chain, but in certain conditions, the production of reactive species overpassed the antioxidant systems, which could cause tissue damage. On the other hand, it is well established that inflammation is a complex reaction in the vascularized connective tissue in response to diverse stimuli. However, an unregulated prolonged inflammatory process also can induce tissue damage. Conclusion: Both inflammation and oxidative stress are interrelated since one could promote the other, leading to a toxic feedback system, which contributes to the inflammatory and demyelination process in MS.(AU)

Introducción: Este trabajo destaca la relación de la inflamación y el estrés oxidativo como mecanismos de daño de la esclerosis múltiple, considerada enfermedad inflamatoria y autoinmune. Desarrollo: El concepto de estrés oxidativo se ha definido por un desequilibrio entre oxidantes y antioxidantes a favor de los oxidantes. Es necesario para realizar funciones fisiológicas, como la cadena respiratoria, pero en ciertas condiciones la producción de especies reactivas sobrepasaba los sistemas antioxidantes, lo que podría causar daño tisular. Por otro lado, está establecido que la inflamación es una reacción compleja en el tejido conectivo vascularizado en respuesta a diversos estímulos, pero un proceso inflamatorio prolongado no regulado también puede inducir daño tisular. Conclusión: Tanto la inflamación como el estrés oxidativo están interrelacionados entre sí, ya que uno de ellos podría promover al otro, dando lugar a un sistema de retroalimentación tóxico, que contribuye al desarrollo del proceso inflamatorio y desmielinizante en la esclerosis múltiple.(AU)

Relationship between inflammation and oxidative stress and its effect on multiple sclerosis.

INTRODUCTION: This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune disease. DEVELOPMENT: The oxidative stress concept has been defined by an imbalance between oxidants and antioxidants in favor of the oxidants. There is necessary to do physiological functions, like the respiration chain, but in certain conditions, the production of reactive species overpassed the antioxidant systems, which could cause tissue damage. On the other hand, it is well established that inflammation is a complex reaction in the vascularized connective tissue in response to diverse stimuli. However, an unregulated prolonged inflammatory process also can induce tissue damage. CONCLUSION: Both inflammation and oxidative stress are interrelated since one could promote the other, leading to a toxic feedback system, which contributes to the inflammatory and demyelination process in MS.

Mn-porphyrins in a four-helix bundle participate in photo-induced electron transfer with a bacterial reaction center.

Hybrid complexes incorporating synthetic Mn-porphyrins into an artificial four-helix bundle domain of bacterial reaction centers created a system to investigate new electron transfer pathways. The reactions were initiated by illumination of the bacterial reaction centers, whose primary photochemistry involves electron transfer from the bacteriochlorophyll dimer through a series of electron acceptors to the quinone electron acceptors. Porphyrins with diphenyl, dimesityl, or fluorinated substituents were synthesized containing either Mn or Zn. Electrochemical measurements revealed potentials for Mn(III)/Mn(II) transitions that are ~ 0.4 V higher for the fluorinated Mn-porphyrins than the diphenyl and dimesityl Mn-porphyrins. The synthetic porphyrins were introduced into the proteins by binding to a four-helix bundle domain that was genetically fused to the reaction center. Light excitation of the bacteriochlorophyll dimer of the reaction center resulted in new derivative signals, in the 400 to 450 nm region of light-minus-dark spectra, that are consistent with oxidation of the fluorinated Mn(II) porphyrins and reduction of the diphenyl and dimesityl Mn(III) porphyrins. These features recovered in the dark and were not observed in the Zn(II) porphyrins. The amplitudes of the signals were dependent upon the oxidation/reduction midpoint potentials of the bacteriochlorophyll dimer. These results are interpreted as photo-induced charge-separation processes resulting in redox changes of the Mn-porphyrins, demonstrating the utility of the hybrid artificial reaction center system to establish design guidelines for novel electron transfer reactions.

Association between genetic variations at 8q24 and prostate cancer risk in Mexican Men.

BACKGROUND: Variants of 8q24 locus have been associated with prostate cancer (PCa) susceptibility. This study aims to analyze the genetic basis of PCa susceptibility in Mexican men by analyzing SNPs in the 8q24 locus for the first time. METHODS: A case-control study was performed in 875 men recruited from the Mexican Social Security Institute, 326 patients with PCa, and 549 non-PCa patients (88 with benign prostatic hyperplasia BPH and 461 healthy controls). The 8q24 locus SNPs: rs16901979, rs16983267, rs1447295, and rs7837328 were genotyped by allelic discrimination assays using TaqMan probes. Statistical analysis was performed using Epi Info statistical 7.0 and SNPstats softwares. RESULTS: All genotype frequencies were in Hardy-Weinberg Equilibrium. No differences were observed in genotype distribution between PCa and non-PCa patients for rs6983267. Under different inheritance models, the rs16901979, rs1447295, and rs7837328 SNPs were associated with PCa (OR = 2.8, 1.8, and 1.72, respectively; Pc < 0.001) when comparing PCa patients against controls. This association remains between PCa and BPH patients under different models (OR = 8.5, 2.2, and 1.9, respectively; Pc < 0.001). There were no significant differences in allele and genotype distribution among BPH patients and controls. The combined effect of the alleles CGAA for the SNPs rs16901979, rs6983267, rs1447295, and rs7837328 showed significant differences between PCa patients and controls (OR = 2.9, 95% CI = 1.48-5.83, Pc = 0.008). Four 8q24 variants were not associated with D'Amico score, age at diagnosis, and bone metastases. CONCLUSIONS: Our study provides the first confirmation that variants rs16901979, rs1447295, and 7837328 at 8q24 locus are associated with PCa susceptibility in Mexican men.

Estudio comparativo de melatonina contra los tratamientos inmunomoduladores (interferón beta y acetato de glatirámero) en un modelo murino de esclerosis múltiple / A comparative study of melatonin and immunomodulatory therapy with interferon beta and glatiramer acetate in a mouse model of multiple sclerosis

Introducción: La esclerosis múltiple (EM) es una enfermedad crónica desmielinizante autoinmune del sistema nervioso central (SNC) que produce neuroinflamación; un modelo es la encefalitis autoinmune experimental (EAE). La EM ha sido tratada con interferón beta (IFN-β) y acetato de glatirámero (AG). Se ha descrito que la melatonina (MLT) modula la respuesta del sistema inmune. El objetivo de este estudio fue observar el efecto de la administración de MLT contra los tratamientos de primera línea utilizados en la EM (IFN-β y AG).MétodosSe indujo EAE a ratas macho Sprague Dawley y se les administró IFN-β, AG o MLT. Se colectó líquido cefalorraquídeo (LCR) y se midieron citocinas proinflamatorias por multiplex, además del registro de la evaluación neurológica de la EAE.ResultadosTodos los animales inmunizados establecieron la EAE. Se evaluó el primer ciclo de recaída-remisión, observando que IFN-β y AG tienen mejores resultados que MLT en la evaluación clínica. La concentración en el LCR tanto de IL-1β como de IL-12p70 no se vio modificada por el modelo o por los tratamientos administrados. EL TNF-α se vio disminuido en el LCR por el IFN-β y la MLT bajo el modelo de EM.ConclusionesEs necesario realizar estudios posteriores para evaluar los mecanismos moleculares involucrados en el comportamiento de la MLT en la EAE, así como la cuantificación de otras citocinas en diferentes matrices biológicas para poder considerar la MLT como un agente antiinflamatorio regulador de la EM. (AU)

Introduction: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA).MethodsEAE was induced in male Sprague-Dawley rats; the animals subsequently received either IFN-β, GA, or MLT. Cerebrospinal fluid (CSF) samples were analysed by multiplex assay to determine the levels of proinflammatory cytokines. The neurological evaluation of EAE was also recorded.ResultsAll immunised animals developed EAE. We evaluated the first relapse-remission cycle, observing that IFN-β and GA had better results than MLT in the clinical evaluation. Neither EAE nor any of the treatments administered modified CSF IL-1β and IL-12p70 concentrations. However, IFN-β and MLT did decrease CSF TNF-α concentrations.ConclusionsFurther studies are needed to evaluate the molecular mechanisms involved in the behaviour of MLT in EAE, and to quantify other cytokines in different biological media in order for MLT to be considered an anti-inflammatory agent capable of regulating MS. (AU)

A comparative study of melatonin and immunomodulatory therapy with interferon beta and glatiramer acetate in a mouse model of multiple sclerosis. / Estudio comparativo de melatonina contra los tratamientos inmunomoduladores (interferón beta y acetato de glatirámero) en un modelo murino de esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-ß) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-ß and GA). METHODS: EAE was induced in male Sprague-Dawley rats; the animals subsequently received either IFN-ß, GA, or MLT. Cerebrospinal fluid (CSF) samples were analysed by multiplex assay to determine the levels of proinflammatory cytokines. The neurological evaluation of EAE was also recorded. RESULTS: All immunised animals developed EAE. We evaluated the first relapse-remission cycle, observing that IFN-ß and GA had better results than MLT in the clinical evaluation. Neither EAE nor any of the treatments administered modified CSF IL-1ß and IL-12p70 concentrations. However, IFN-ß and MLT did decrease CSF TNF-α concentrations. CONCLUSIONS: Further studies are needed to evaluate the molecular mechanisms involved in the behaviour of MLT in EAE, and to quantify other cytokines in different biological media in order for MLT to be considered an anti-inflammatory agent capable of regulating MS.

The potential of Dicyphus hesperus as a biological control agent of potato psyllid and sweetpotato whitefly in tomato.

The potential of the mirid predator Dicyphus hesperus Knight (Heteroptera: Miridae) as a biological control agent of the sweetpotato whitefly, Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) and the potato psyllid, Bactericera cockerelli Sulcer (Hemiptera: Psyllidae) in tomato was investigated in two experiments. The first experiment focused on the study of the life history traits of D. hesperus when fed on nymphs of the potato psyllid compared with the factitious prey Ephestia kuehniella Zeller (Lepidoptera: Pyrallidae) eggs. Although reproductive and development rates were higher on E. kuehniella eggs, the predator exhibited a good intrinsic rate of natural increase (rm) when feeding on B. cockerelli nymphs (rm: B. cockerelli 0.069 ± 0.0001; E. kuehniella 0.078 ± 0.0001), thus reflecting good potential as a biocontrol agent of this pest. The second experiment focused on the efficacy of D. hesperus as a biocontrol agent of the potato psyllid and the sweetpotato whitefly in a tomato greenhouse. Prey species were offered individually or together in a series of five treatments in greenhouse cages. Results showed that the predator was able to establish and suppress populations of both pests inhabiting tomato plants when pests occurred alone or together. Thus, D. hesperus was demonstrated to be a suitable biocontrol agent of these two important pests that could be used in tomato greenhouses.

Hopf bifurcation stability in Hopfield neural networks.

In this paper we consider a simple discrete Hopfield neural network model and analyze local stability using the associated characteristic model. In order to study the dynamic behavior of the quasi-periodic orbit, the Hopf bifurcation must be determined. For the case of two neurons, we find one necessary condition that yields the Hopf bifurcation. In addition, we determine the stability and direction of the Hopf bifurcation by applying normal form theory and the center manifold theorem. An example is given and a numerical simulation is performed to illustrate the results. We analyze the influence of bias weights on the stability of the quasi-periodic orbit and study the phase-locking phenomena for certain experimental results with Arnold Tongues in a particular weight configuration.

Size and dry weight of main zooplankton species in Bariri reservoir (SP, Brazil).

In order to generate a database for secondary production studies in the São Paulo State (Brazil) reservoirs, the size and dry weight of 13 sooplankton species from Bariri reservoir (middle Tietê River) were determined. Diameter and dry weight of eggs from some cladoceran and copepod species were also determined. Sizes varied from 108.6 microm (Keratella tropica) to 2488.6 microm (females of Argyrodiaptomus azevedoi), while dry weights varied between 0.025 microg (K. tropica) and 51.250 microg (females of A. azevedoi). Egg diameters varied between 75.0 microm (Mesocyclops ogunnus) and 171.8 microm (Ceriodaphnia silvestrii), while egg dry-weights varied between 0.074 microg (Acanthocyclops robustus) and 0.865 microg (Bosmina hagmanni). Size and dry weight distribution of the zooplanktonic organisms was not linear in the bariri reservoir.

Size and dry weight of main zooplankton species in Bariri reservoir (SP, Brazil)

In order to generate a database for secondary production studies in the São Paulo State (Brazil) reservoirs, the size and dry weight of 13 zooplankton species from Bariri reservoir (middle Tietê River) were determined. Diameter and dry weight of eggs from some cladoceran and copepod species were also determined. Sizes varied from 108.6 mm (Keratella tropica) to 2488.6 µm (females of Argyrodiaptomus azevedoi), while dry weights varied between 0.025 µg (K. tropica) and 51.250 µg (females of A. azevedoi). Egg diameters varied between 75.0 µm (Mesocyclops ogunnus) and 171.8 µm (Ceriodaphnia silvestrii), while egg dry-weights varied between 0.074 µg (Acanthocyclops robustus) and 0.865 µg (Bosmina hagmanni). Size and dry weight distribution of the zooplanktonic organisms was not linear in the Bariri reservoir.

Com a finalidade de gerar uma base de dados para o estudo da produção secundária nos reservatórios do Estado de São Paulo, foram determinados o comprimento e o peso seco de indivíduos de 13 espécies do zooplâncton do reservatório Bariri (médio rio Tietê). Também foram determinados o diâmetro e o peso seco dos ovos de algumas espécies de cladóceros e copépodos. Os comprimentos variaram entre 108,6 µm (Keratella tropica) e 2488,6 µm (fêmeas de Argyrodiaptomus azevedoi), e os valores de pesos secos variaram entre 0,025 µg (K. tropica) e 51,250 µg (fêmeas de A. azevedoi). Os diâmetros dos ovos variaram entre 75,0 µm (Mesocyclops ogunnus) e 171,8 µm (Ceriodaphnia silvestrii) e os pesos secos variaram entre 0,074 µg (Acanthocyclops robustus) e 0,865 µg (Bosmina hagmanni). A distribuição do comprimento e do peso seco dos organismos não foi do tipo linear no reservatório Bariri.

[Artificial nutrition in acute pancreatitis]. / Soporte nutricional en la pancreatitis aguda.

Metabolic changes that occur in acute pancreatitis result, as with other critically ill patients, in a metabolic stress situation that many times requires the application of a specialized nutritional support. Patients presenting the highest severity indexes (defined as Ranson's index = 3 or an APACHE II = 10) are candidates to receive nutritional support. Enteral nutrition must be the first route to consider for nutrients supply and must be maintained except for patients that have intolerance or develop pain, ascites, or increased serum amylase levels. Transpyloric enteral nutrition, through a naso-jejunal tube or by means of a jejunostomy catheter, is a safe access in severe acute pancreatitis, and it may even be accompanied by advantages in the patients' clinical course as compared with parenteral nutrition. The indication for parenteral nutrition would be conditioned by the inability to obtain an appropriate enteral (jejunal) approach, intolerance to enteral nutrition, or disease exacerbation after the onset of enteral nutrition support. With current data, no recommendations can be established in relation to the ideal characteristics that nutrients composition received by acute pancreatitis patients should meet.

Measurements of manganese with respect to calcium in histological enamel cross sections: toward a new manganese biomarker.

Airborne Mn may become an important route of exposure if the use of Mn-containing gasoline additives becomes more widespread. We report on the measurement of manganese and calcium in histological cross sections of shed deciduous tooth enamel of three human subjects. The goal of this research was to measure Mn in tooth enamel for use as a biomarker in assessing manganese exposure in cross-sectional and longitudinal studies. The histological locations can be time-specific (analogous to examining growth rings in trees). This technique, which may identify critical windows of exposure, can be important for evaluating potential vulnerability of the fetus and neonate to inhaled or ingested Mn.

Modeling DNA hydration: comparison of calculated and experimental hydration properties of nuclic acid bases.

Hydration properties of individual nucleic acid bases were calculated and compared with the available experimental data. Three sets of classical potential functions (PF) used in simulations of nucleic acid hydration were juxtaposed: (i) the PF developed by Poltev and Malenkov (PM), (ii) the PF of Weiner and Kollman (WK), which together with Jorgensen's TIP3P water model are widely used in the AMBER program, and (iii) OPLS (optimized potentials for liquid simulations) developed by Jorgensen (J). The global minima of interaction energy of single water molecules with all the natural nucleic acid bases correspond to the formation of two water-base hydrogen bonds (water bridging of two hydrophilic atoms of the base). The energy values of these minima calculated via PM potentials are in somewhat better conformity with mass-spectrometric data than the values calculated via WK PF. OPLS gave much weaker water-base interactions for all compounds considered, thus these PF were not used in further computations. Monte Carlo simulations of the hydration of 9-methyladenine, 1-methyluracil and 1-methylthymine were performed in systems with 400 water molecules and periodic boundary conditions. Results of simulations with PM potentials give better agreement with experimental data on hydration energies than WK PF. Computations with PM PF of the hydration energy of keto and enol tautomers of 9-methylguanine can account for the shift in the tautomeric equilibrium of guanine in aqueous media to a dominance of the keto form in spite of nearly equal intrinsic stability of keto and enol tautomers. The results of guanine hydration computations are discussed in relation to mechanisms of base mispairing errors in nucleic acid biosynthesis. The data presented in this paper along with previous results on simulation of hydration shell structures in DNA duplex grooves provide ample evidence for the advantages of PM PF in studies of nucleic-acid hydration.

[The possible role of rare tautomers of DNA bases in mutagenesis: study of the effect of hydration on tautomeric equilibrium by the Monte-Carlo method]. / O vozmozhnoi roli redkikh tautomerov osnovanii DNK v mutageneze: izuchenie vliianiia gidratatsii na tautomernoe v ravnovesie metodom Monte-Karlo.

Monte Carlo simulation of hydration of keto and enol tautomers of 9-methylguanine (G) and 1-methyluracil (U) has been performed in relation to a possible role of tautomer transitions of DNA bases in mutagenesis. The comparison of the simulation results with published experimental data and results of quantum mechanical computations leads us to conclusion about difference in the origins of keto-form prevalence in water solutions of G and U. Such a reason for uracil (thymine) is a greater intrinsic stability of keto tautomer while the more preferable hydration of keto form of G is the reason of its predominance. As a consequence, during biosynthesis less hydrophylic environment (as compared to water solution) can be a reason for guanine transition into enol form and can result in mispair formation. Such a mutation mechanism is of a minor probability through thymine (uracil) tautomerization.

Natural phillipsite as a matrix for a slow-release formulation of oxamyl.

The performance of phillipsite as a matrix for slow-release formulation of oxamyl [N,N-dimethyl-2-methylcarbamoyl-oxymino-2-(methylthio)acetamide] was tested. The adsorption kinetics followed a first-order law, and the adsorption isotherm fitted well in a two-surface Langmuir model, suggesting a double mechanism of interaction between oxamyl and the sorbent. The sorption mechanism, studied by FTIR, provided two fractions of oxamyl. The first one is sorbed on the mineral surface, linked by H-bonding, and the second one is constituted by a multilayer of oxamyl molecules linked by a water bridge between them. The release kinetics of oxamyl from a substratum zeolite-oxamyl also follows a first-order law, with two stages that correspond to both fractions of oxamyl previously detected.