Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine.

Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.

A new Monte Carlo code for light transport in biological tissue.

The aim of this work was to develop an event-by-event Monte Carlo code for light transport (called MCLTmx) to identify and quantify ballistic, diffuse, and absorbed photons, as well as their interaction coordinates inside the biological tissue. The mean free path length was computed between two interactions for scattering or absorption processes, and if necessary scatter angles were calculated, until the photon disappeared or went out of region of interest. A three-layer array (air-tissue-air) was used, forming a semi-infinite sandwich. The light source was placed at (0,0,0), emitting towards (0,0,1). The input data were: refractive indices, target thickness (0.02, 0.05, 0.1, 0.5, and 1 cm), number of particle histories, and λ from which the code calculated: anisotropy, scattering, and absorption coefficients. Validation presents differences less than 0.1% compared with that reported in the literature. The MCLTmx code discriminates between ballistic and diffuse photons, and inside of biological tissue, it calculates: specular reflection, diffuse reflection, ballistics transmission, diffuse transmission and absorption, and all parameters dependent on wavelength and thickness. The MCLTmx code can be useful for light transport inside any medium by changing the parameters that describe the new medium: anisotropy, dispersion and attenuation coefficients, and refractive indices for specific wavelength.

67Ga as a biosensor of iron needs in different organs: Study performed on male and female rats subjected to iron deficiency and exercise.

The aim of the present study was to determine the iron needs in different organs and tissues using 67Ga as a biosensor in males and females rats subjected to iron deficiency (ID) and voluntary exercise (EX). 67Ga citrate was injected i.p. to female and male Wistar rats (n=5/sex/group). Groups: Control (sedentary conditions), Control+EX, ID and ID+EX. To determine the 67Ga uptake, samples from the following regions of interest (ROIs) were extracted 12h post-injection: blood, liver, gonads, bone marrow, heart, adrenal glands, skeletal muscle, stomach, kidney, eyeball, sciatic nerve, small intestine and peritoneum. The total 67Ga uptake was 412% higher in ID subjects than in control subjects, being 1011% higher in ID-males than ID-females. In ID-females, the ROIs with the greater 67Ga uptake were blood, kidney and bone marrow, while in ID-males they were sciatic nerve, eyeball and adrenals, which demonstrates that the biodistribution differed between sexes in sedentary conditions but when subjected to EX, the biodistribution was similar in each sex group although females had a greater 67Ga uptake. In ID+EX subjects, the ROIs that showed the highest uptake were sciatic nerve, eyeball and adrenal glands. Using 67Ga as a biosensor, it is possible to identify the needs of iron that each organ requires to perform their functions in normal physiological conditions. In addition, a higher or lower 67Ga uptake in a specific organ may indicate its malfunction or show damage.

An iron-deficient diet during development induces oxidative stress in relation to age and gender in Wistar rats

Iron is a trace element and a structural part of antioxidant enzymes, and its requirements vary according to age and gender. We hypothesized that iron deficiency (ID) leads to an increase in free radicals which mainly affect the brain, and the severity of damage would therefore be dependent on age and gender. Two groups of Wistar rats were evaluated evolutionarily: 100 rats (50 males; 50 females) with ID diet and 100 rats (50 males; 50 females) with standard diet. Both groups were offspring from mothers who were previously under the same dietary intervention. The ages studied roughly correspond to stages of human development: birth (0 postnatal day "PND" in rats), childhood (21 PND), early adolescence (42 PND), late adolescence (56 PND), and adulthood (70 PND). The following biomarkers in the brain, blood, and liver were analyzed: lipid peroxidation products (LPO), protein carbonyl content and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. It was demonstrated that ID subjects are born with high levels of LPO in the brain and low antioxidant activity, the damage being more severe in males. After birth, antioxidant defense focuses on the central level (brain) in ID females and on the peripheral level (blood and liver) in ID males. In two critical stages of development, birth and late adolescence, antioxidant protection is insufficient to counteract oxidative damage in ID subjects. Moreover, we observed that the variability of results in the literature on oxidative stress and ID comes from gender and age of the subjects under study. With this, we can establish patterns and exact moments to carry out studies or treatments (AU)

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Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model.

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.

An iron-deficient diet during development induces oxidative stress in relation to age and gender in Wistar rats.

Iron is a trace element and a structural part of antioxidant enzymes, and its requirements vary according to age and gender. We hypothesized that iron deficiency (ID) leads to an increase in free radicals which mainly affect the brain, and the severity of damage would therefore be dependent on age and gender. Two groups of Wistar rats were evaluated evolutionarily: 100 rats (50 males; 50 females) with ID diet and 100 rats (50 males; 50 females) with standard diet. Both groups were offspring from mothers who were previously under the same dietary intervention. The ages studied roughly correspond to stages of human development: birth (0 postnatal day "PND" in rats), childhood (21 PND), early adolescence (42 PND), late adolescence (56 PND), and adulthood (70 PND). The following biomarkers in the brain, blood, and liver were analyzed: lipid peroxidation products (LPO), protein carbonyl content and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. It was demonstrated that ID subjects are born with high levels of LPO in the brain and low antioxidant activity, the damage being more severe in males. After birth, antioxidant defense focuses on the central level (brain) in ID females and on the peripheral level (blood and liver) in ID males. In two critical stages of development, birth and late adolescence, antioxidant protection is insufficient to counteract oxidative damage in ID subjects. Moreover, we observed that the variability of results in the literature on oxidative stress and ID comes from gender and age of the subjects under study. With this, we can establish patterns and exact moments to carry out studies or treatments.

Metals and nonsteroidal anti-inflammatory pharmaceuticals drugs present in water from Madín Reservoir (Mexico) induce oxidative stress in gill, blood, and muscle of common carp (Cyprinus carpio).

Many toxic xenobiotics that enter the aquatic environment exert their effects through redox cycling. Oxidative stress, which incorporates both oxidative damage and antioxidant defenses, is a common effect induced in organisms exposed to xenobiotics in their environment. The results of the present study aimed to determine the oxidative stress induced in the common carp Cyprinus carpio by contaminants [metals and nonsteroidal anti-inflammatory drugs (NSAIDs)] present in Madín Reservoir. Five sampling stations (SSs), considered to have the most problems due to discharges, were selected. Carp were exposed to water from each SS for 96 h, and the following biomarkers were evaluated in gill, blood, and muscle: hydroperoxide content, lipid peroxidation, protein carbonyl content, and the activity of antioxidant enzymes superoxide dismutase and catalase. Results show that contaminants (metals and NSAIDs) present in water from the different SSs induce oxidative stress. Thus, water in this reservoir is contaminated with xenobiotics that are hazardous to C. carpio, a species consumed by the local human population.

Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium.

Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system.

Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression.

In this study, we compared the depression-like symptoms induced by olfactory bulbectomy (OBX) in the two inbred Wistar and Long Evans rat strains. We also analyzed the self-regulated oral intake of nicotine in these strains and the effect of nicotine on the depression-like symptoms of olfactory bulbectomy. Furthermore, we compared the antidepressant-like effects of nicotine on Wistar rats to those of transcranial magnetic stimulation (TMS), which has emerged as a therapeutic alternative for depression management. Our results show that Wistar rats develop depression-like symptoms, demonstrated by the forced swim test (FST), 4 weeks after OBX. However, in bulbectomized Long Evans rats these symptoms cannot be assessed due to a higher degree of variability of the swimming behavior of this strain. These results suggest that there are some innate differences in susceptibility to stress between these two rat strains. In Wistar rats, voluntary oral nicotine intake (1.2 mg/(kg day) for 14 days) as well as nicotine administered as a single daily i.p. injection (1.5 mg/(kg day) for 14 days) decrease the depression-like symptoms of OBX. Daily transcranial magnetic stimulation (60 Hz and 0.7 mT for 2h/day for 14 days) also decreases depression-like symptoms but is less effective than nicotine. In conclusion, our results support the idea that there are possible innate differences for depression susceptibility and that nicotine and TMS may be useful in the treatment of this syndrome.

Voluntary oral nicotine intake in mice down-regulates GluR2 but does not modulate depression-like behaviors.

Repeated exposure to nicotine induces adaptive changes in the central nervous system including the mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). These modifications can modulate nicotine reward and reinforcement, but also anxiety and depression-related behaviors. The development of addiction-related phenotypes is known to be modulated by regulation of glutamate receptors, as well as activation of transcription factors including cAMP response element-binding protein (CREB), in the NAc. We investigated the effects of nicotine pre-exposure on nicotine preference and levels of GluR1/2 and CREB in the mesolimbic system in male mice C57BL/6J and BALB/c inbred mice. We also evaluated locomotor activity, anxiety-like and depression-like behaviors known to be affected by nicotine. There were few behavioral changes in mice subjected to chronic nicotine exposure, but there was a marked regulation of GluR2 in the mesolimbic system. Both treated and non-treated animals showed a significant preference for nicotine when facing a choice with a control solution. These results suggest that voluntary nicotine drinking induces nicotine preference in mice, but does not alter a number of affective behaviors. In addition, alterations in CREB and GluR1 levels are not sufficient to explain preference for nicotine in a 2-bottle choice paradigm.

Células epiteliales en la inmunidad del pulmón / Immunological role of lung epithelial cells

El sistema respiratorio se encuentra en contacto con patógenos, sin embargo, gracias a la respuesta inmune innata de este, solo en raras ocasiones se establece la enfermedad. Las células epiteliales del tracto respiratorio juegan un papel importante para evitar la colonización del pulmón por agentes infecciosos, identificando a los microorganismos a través de receptores especializados, como los Toll-like,. Las células epiteliales son capaces de secretar citocinas, péptidos antimicrobianos y otras moléculas proinflamatorias las cuales evitan el establecimiento de patógenos

[Cell immunity response in human pulmonary tuberculosis. Review]. / Respuesta de inmunidad celular en la tuberculosis pulmonar. Revisión.

Human pulmonary tuberculosis (TB) is a worldwide public health problem, which is caused by Mycobacterium tuberculosis. It is a fact that one third of the world's population is infected with this mycobacteria, however, only a minority of people infected by M. tuberculosis may develop a clinical disease. In general, about 90% have their bacilli under control in a latent state throughout their lives by means of their immune responses. About 5% will develop primary progressive TB and the remaining 5% will develop the disease in the later stages of their lives, which is known as reactivation or post-primary TB. In resistant individuals, control of the infection mainly requires development of a Th1 cell immunity response. This type of response involves participation of alveolar macrophages and T CD4+, CD8+ and T gammadelta lymphocytes, and production of cytokines such as IL-2, IFN-gamma, IL-12, IL-18 and TNF-alpha, as well as chemokines such as RANTES, MCP-1, MIP-1alpha and IL-8 which play an important role in the migration of different cell subpopulations to the infection site for the formation of granulome. In addition, the role of "natural killer" (NK) cells, along with epitelial cells, is essential as part of the innate immune response.

Respuesta de inmunidad celular en la tuberculosis pulmonar: revisión / Cell immunity response in human pulmonary tuberculosis: review

La tuberculosis (TBC) pulmonar humana, un problema de salud pública en el mundo, es una enfermedad infecciosa causada por Mycobacterium tuberculosis. Se conoce que una minoría de las personas que son infectadas por M. tuberculosis son capaces de progresar a enfermedad clínica. Se puede decir, en términos generales, que el 90 por ciento de las personas tendrán controlados los bacilos en estado latente para toda la vida, por medio de su sistema inmunológico. Un 5 por ciento presentará TBC primaria progresiva y el otro 5 por ciento presentará la enfermedad en estados tardíos de la vida, lo que se denomina TBC de reactivación o post-primaria. En los individuos resistentes, el control de la infección o de los bacilos tuberculosos que se encuentran en la región alveolar requiere principalmente del desarrollo de una respuesta de inmunidad celular (RIC) del tipo Th1. Este tipo de respuesta incluye la participación de los macrófagos alveolares, los linfocitos T CD4+ y CD8+, principalmente los linfocitos T gd y la producción de citocinas como: IL-2, IFN-g, IL-12, IL-18 y TNF-a. Aunado están las quimiocinas como RANTES, MCP-1, MIP-1a e IL-8 que juegan un papel muy importante en la migración de las diferentes subpoblaciones celulares al sitio de infección para la formación del granuloma. Además, es primordial el papel de las células "natural killer" (NK), y de las células epiteliales como parte de la respuesta de inmunidad innata