Neuroprotection of Thioredoxin1 in the Brain.

Thioredoxin1 (Trx1) is a ubiquitous antioxidant protein that regulates the cell's redox status. Trx1's thiol redox activity protects neurons from various physiological processes that cause neuronal damage and neurodegeneration, including oxidative stress, apoptosis, and inflammation. Several studies have found that direct or indirect Trx1 regulation has neuroprotective effects in the brain, protecting against, preventing, or delaying neurodegenerative processes or brain traumas. This review focuses on the term neuroprotection, Trx1 localization, and expression in the brain, as well as its modulation concerning its neuroprotective effect in both animal and clinical models of ischemia, hypoxia, hemorrhage, traumatic brain injury, epilepsy, Alzheimer's disease, and Parkinson's disease.

The effect of thioredoxin-1 in a rat model of traumatic brain injury depending on diurnal variation.

INTRODUCTION: Traumatic brain injury (TBI) is a public health concern with limited treatment options because it causes a cascade of side effects that are the leading cause of hospital death. Thioredoxin is an enzyme with neuroprotective properties such as antioxidant, antiapoptotic, immune response modulator, and neurogenic, among others; it has been considered a therapeutic target for treating many disorders. METHODS: The controlled cortical impact (CCI) model was used to assess the effect of recombinant human thioredoxin 1 (rhTrx1) (1 µg/2 µL, intracortical) on rats subjected to TBI at two different times of the light-dark cycle (01:00 and 13:00 h). We analyzed the food intake, body weight loss, motor coordination, pain perception, and histology in specific hippocampus (CA1, CA2, CA3, and Dental Gyrus) and striatum (caudate-putamen) areas. RESULTS: Body weight loss, reduced food intake, spontaneous pain, motor impairment, and neuronal damage in specific hippocampus and striatum regions are more evident in rats subjected to TBI in the light phase than in the dark phase of the cycle and in groups that did not receive rhTrx1 or minocycline (as positive control). Three days after TBI, there is a recovery in body weight, food intake, motor impairment, and pain, which is more pronounced in the rats subjected to TBI at the dark phase of the cycle and those that received rhTrx1 or minocycline. CONCLUSIONS: Knowing the time of day a TBI occurs in connection to the neuroprotective mechanisms of the immune response in diurnal variation and the usage of the Trx1 protein might have a beneficial therapeutic impact in promoting quick recovery after a TBI.

Experimental Verification of Inferred Regulatory Interactions of EARLY FLOWERING 3 ( GmELF3-1 ) in Glycine max.

Understanding the roles of evening complex (EC) genes in the circadian clock of plants can inform how diurnal transcriptional loops in the clock gene network function to regulate key physiological and developmental events, including flowering transition. Gene regulatory interactions among soybean's circadian clock and flowering genes were inferred using time-series RNA-seq data and the network inference algorithmic package CausNet. In this study, we seek to clarify the inferred regulatory interactions of the EC gene GmELF3-1. A gene expression analysis using soybean protoplasts as a transient model indicated regulatory roles of GmELF3-1 in expression of selected flowering genes.

Activation of dopamine D2 receptors attenuates neuroinflammation and ameliorates the memory impairment induced by rapid eye movement sleep deprivation in a murine model.

The proinflammatory state, which may be induced by sleep deprivation, seems to be a determining factor in the development of neurodegenerative processes. Investigations of mechanisms that help to mitigate the inflammatory effects of sleep disorders are important. A new proposal involves the neurotransmitter dopamine, which may modulate the progression of the immune response by activating receptors expressed on immune cells. This study aimed to determine whether dopamine D2 receptor (D2DR) activation attenuates the proinflammatory response derived from rapid eye movement (REM) sleep deprivation in mice. REM sleep deprivation (RSD) was induced in 2-month-old male CD1 mice using the multiple platform model for three consecutive days; during this period, the D2DR receptor agonist quinpirole (QUIN) was administered (2 mg/kg/day i.p.). Proinflammatory cytokine levels were assessed in serum and homogenates of the brain cortex, hippocampus, and striatum using ELISAs. Long-term memory deficits were identified using the Morris water maze (MWM) and novel object recognition (NOR) tests. Animals were trained until learning criteria were achieved; then, they were subjected to RSD and treated with QUIN for 3 days. Memory evocation was determined afterward. Moreover, we found RSD induced anhedonia, as measured by the sucrose consumption test, which is commonly related to the dopaminergic system. Our data revealed increased levels of proinflammatory cytokines (TNFα and IL-1ß) in both the hippocampus and serum from RSD mice. However, QUIN attenuated the increased levels of these cytokines. Furthermore, RSD caused a long-term memory evocation deficit in both the MWM and NOR tests. In contrast, QUIN coadministration during the RSD period significantly improved the performance of the animals. On the other hand, QUIN prevented the anhedonic condition induced by RSD. Based on our results, D2DR receptor activation protects against memory impairment induced by disturbed REM sleep by inhibiting neuroinflammation.

Control of pH-Responsiveness in Graphene Oxide Grafted with Poly-DEAEMA via Tailored Functionalization.

Polymer-grafted nanomaterials based on carbon allotropes and their derivatives (graphene oxide (GO), etc.) are typically prepared by successive reaction stages that depend upon the initial functionalities in the nanostructure and the polymerization type needed for grafting. However, due to the multiple variables involved in the functionalization steps, it is commonly difficult to predict the properties in the final product and to correlate the material history with its final performance. In this work, we explored the steps needed to graft the carboxylic acid moieties in GO (COOH@GO) with a pH-sensitive polymer, poly[2-(diethylamino)ethyl methacrylate] (poly[DEAEMA]), varying the reactant ratios at each stage prior to polymerization. We studied the combinatorial relationship between these variables and the behavior of the novel grafted material GO-g-poly[DEAEMA], in terms of swelling ratio vs. pH (%Q) in solid specimens and potentiometric response vs. Log[H+] in a solid-state sensor format. We first introduced N-hydroxysuccinimide (NHS)-ester moieties at the -COOH groups (GO-g-NHS) by a classical activation with N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (EDC). Then, we substituted the NHS-ester groups by polymerizable amide-linked acrylic moieties using 2-aminoethyl methacrylate (AEMA) at different ratios to finally introduce the polymer chains via radical polymerization in an excess of DEAEMA monomer. We found correlated trends in swelling pH range, interval of maximum and minimum swelling values, response in potentiometry and potentiometric linear range vs. Log[H+] and could establish their relationship with the combinatorial stoichiometries in synthetic stages.

Spinal TASK-1 and TASK-3 modulate inflammatory and neuropathic pain.

This study assessed the participation of spinal TWIK-related acid-sensitive K+ channels 1 and 3 (TASK-1 and TASK-3) in inflammatory (formalin test) and neuropathic (spinal nerve ligation, SNL) pain in rats. Intrathecal pre-treatment (-10 min) with the TASK-1 blocker ML365 or TASK-3 blocker PK-THPP, but not vehicle, enhanced in a dose-dependent manner 1% formalin-induced acute and long-lasting secondary mechanical allodynia and mechanical hyperalgesia in rats. In contrast, intrathecal pre-treatment with terbinafine, an activator of TASK-3, reduced formalin-induced flinching and allodynia/hyperalgesia. Both blockers and terbinafine had similar effects on female and male rats. In addition, intrathecal injection of ML365 or PK-THPP blocked the terbinafine-induced antiallodynic effect in neuropathic rats, but they did not modify baseline withdrawal threshold in naïve or sham-operated rats. TASK-1 and TASK-3 mRNA and protein were expressed in L4 and L5 dorsal root ganglia (DRG) and dorsal and ventral spinal cord of naïve animals. Interestingly, formalin injection increased TASK-1 expression in ipsilateral L5 DRG, but not in the spinal cord. Moreover, formalin injection transiently enhanced TASK-3 expression in ipsilateral L5 DRG and dorsal spinal cord. In contrast, SNL down-regulated TASK-3 expression in the ipsilateral L4 and L5 DRG but not in dorsal or ventral spinal cord, while SNL did not modify TASK-1 expression at any tissue. The pharmacological and molecular results suggest that TASK-1 and TASK-3 have a relevant antinociceptive role in inflammatory and neuropathic pain.

Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting mechanical hypersensitivity.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity. MATERIALS AND METHODS: Formalin (1%)-induced chronic hypersensitivity was determined by the application of von Frey filaments to ipsilateral and contralateral paws and through pharmacological testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting. RESULTS: Formalin (1%) injection produced acute flinching behavior (1 h) as well as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment (10 min before) or posttreatment (6 days later) with A-967079 (1-100 µM) partially prevented and reversed, respectively, in a dose-dependent manner, long-lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin. Likewise, intrathecal pretreatment or posttreatment with A-967079 partially prevented and reversed, respectively, formalin-induced long-lasting hypersensitivity. A-967079 (100 µM) completely abolished the pro-nociceptive effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased TRPA1 protein expression in the DRG and spinal cord. CONCLUSION: Results indicate that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin-induced long-lasting secondary nociceptive hypersensitivity.

Hiperplasia adrenal congénita. Presentación de caso / Congenital adrenal hyperplasia. Case presentation

Fundamento: La hiperplasia adrenal congénita es el desorden adrenal más común en niños, causa frecuente de seudohermafroditismo femenino y de ambigüedad sexual. La deficiencia de la enzima 21 hidroxilasa es la causa más común, ocurre entre un 90 y 95 % de los casos. La incidencia de la enfermedad es de 1:14 000 nacimientos. La determinación de hormona 17 hidroxiprogesterona al quinto día de nacido, facilita el diagnóstico y el adecuado tratamiento. Presentación de caso: Se describe el diagnóstico de un recién nacido femenino, de nueve días, con antecedentes prenatales de alto riesgo obstétrico, sin manifestaciones clínicas de pérdida adrenal, al examen físico discreto grado de virilización (moderada hipertrofia del clítoris) y niveles elevados de 17 hidroxiprogesterona, al cual se le realizó confirmatorio de 17 hidroxiprogesterona en suero a los nueve días, resultó positivo y ante los antecedentes prenatales, se decidió su diagnóstico y tratamiento oportuno. Conclusiones: Se realizó el diagnóstico de una hiperplasia adrenal congénita, en recién nacido femenino de nueve días, se brindó asesoría a sus familiares, se indicó tratamiento médico con hidrocortisona y fluorhidrocortizona, se le siguió por consulta del programa de hiperplasia adrenal congénita y se realizó estudio molecular para precisar déficit enzimático.

Background: Adrenal hyperplasia, congenital is the most common adrenal disorder in children, a frequent cause of femenine pseudohermaphroditism and sexual ambiguity. The deficiency of the 21 hydroxylase enzyme is the most common cause, occurs between 90 and 95 % of the cases. The incidence of the disease is at about 1:14 000 births. The determination of hormone 17 hydroxyprogesterone on the fifth day of birth facilitates diagnosis and adequate treatment. Case report: We describe the diagnosis of a 9 days old femenine infant with a prenatal history of high obstetric risk, with no clinical manifestations of adrenal loss, a discrete physical examination of virilization (moderate clitoris hypertrophy) and elevated levels of 17 hydroxyprogesterone, which was confirmed with serum hydroxyprogesterone at 9 days, was positive and before the prenatal history, the diagnosis and timely treatment was decided. Conclusion: Adrenal hyperplasia, congenital was diagnosed in a 9-day-old femenine newborn, counseling was given to her relatives, medical treatment with hydrocortisone and fluorhydrocortisone was indicated, followed by consult with the adrenal hyperplasia, congenital program and molecular study was made to determine enzymatic deficit.

Hiperplasia adrenal congénita. Presentación de caso / Congenital adrenal hyperplasia. Case presentation

La hiperplasia adrenal congénita es el desorden adrenal más común en niños, causa frecuente de seudohermafroditismo femenino y de ambigüedad sexual. La deficiencia de la enzima 21 hidroxilasa es la causa más común, ocurre entre un 90 y 95 % de los casos. La incidencia de la enfermedad es de 1:14 000 nacimientos. La determinación de hormona 17 hidroxiprogesterona al quinto día de nacido, facilita el diagnóstico y el adecuado tratamiento. Presentación de caso: Se describe el diagnóstico de un recién nacido femenino, de nueve días, con antecedentes prenatales de alto riesgo obstétrico, sin manifestaciones clínicas de pérdida adrenal, al examen físico discreto grado de virilización (moderada hipertrofia del clítoris) y niveles elevados de 17 hidroxiprogesterona, al cual se le realizó confirmatorio de 17 hidroxiprogesterona en suero a los nueve días, resultó positivo y ante los antecedentes prenatales, se decidió su diagnóstico y tratamiento oportuno. Conclusiones: Se realizó el diagnóstico de una hiperplasia adrenal congénita, en recién nacido femenino de nueve días, se brindó asesoría a sus familiares, se indicó tratamiento médico con hidrocortisona y fluorhidrocortizona, se le siguió por consulta del programa de hiperplasia adrenal congénita y se realizó estudio molecular para precisar déficit enzimático(AU)

Adrenal hyperplasia, congenital is the most common adrenal disorder in children, a frequent cause of femenine pseudohermaphroditism and sexual ambiguity. The deficiency of the 21 hydroxylase enzyme is the most common cause, occurs between 90 and 95 % of the cases. The incidence of the disease is at about 1:14 000 births. The determination of hormone 17 hydroxyprogesterone on the fifth day of birth facilitates diagnosis and adequate treatment. Case report: We describe the diagnosis of a 9 days old femenine infant with a prenatal history of high obstetric risk, with no clinical manifestations of adrenal loss, a discrete physical examination of virilization (moderate clitoris hypertrophy) and elevated levels of 17 hydroxyprogesterone, which was confirmed with serum hydroxyprogesterone at 9 days, was positive and before the prenatal history, the diagnosis and timely treatment was decided. Conclusion: Adrenal hyperplasia, congenital was diagnosed in a 9-day-old femenine newborn, counseling was given to her relatives, medical treatment with hydrocortisone and fluorhydrocortisone was indicated, followed by consult with the adrenal hyperplasia, congenital program and molecular study was made to determine enzymatic deficit(AU)

Características clínico-epidemiológicas de los pacientes menores de 15 años con diagnóstico de hipertensión arterial / Clinical-epidemiological characteristics of patients younger than 15 years with arterial hypertension diagnosis

La hipertensión arterial es una enfermedad multifactorial, con incremento de la incidencia y prevalencia en niños en los últimos años por lo que se considera un problema de salud. Objetivo: Describir las características clínico-epidemiológicas del paciente pediátrico con diagnóstico de hipertensión arterial. Metodología: Se realizó un estudio transversal en el que se incluyeron solo los 70 pacientes con diagnóstico de hipertensión arterial primaria atendidos en la consulta de cardiología del Hospital Pediátrico José Martí de Sancti Spíritus, en el periodo de enero a diciembre de 2009. Las variables utilizadas fueron la edad, el sexo, color de la piel, valoración nutricional, frecuencia cardiaca, antecedentes familiares y personales, y tipo de hipertensión arterial. Resultados: Predominó el sexo masculino (81,2 porciento), también la raza blanca (80 porciento) y los pacientes mayores de 10 años (78,5 porciento). El 84,2 porciento de los pacientes tenía antecedentes familiares de primera línea con hipertensión arterial. La frecuencia cardiaca estuvo elevada en el 75,7 porciento de los pacientes; la hipertensión arterial esencial se diagnosticó en el 97,1 porciento de los casos. Conclusiones: Predominaron los mayores de 10 años, masculinos, blancos y obesos. La taquicardia y los antecedentes familiares de hipertensión arterial estuvieron directamente relacionados al grupo estudio. Predominó la hipertensión arterial primaria.(AU)

Background: arterial hypertension is a multifactorial disease, with an increase of the incidence and prevalence in children in the last years for what it is considered a health problem. Objective: to describe the pediatric patient's clinical- epidemiological characteristics with arterial hypertension diagnosis. Methodology: a cross- sectional study was carried out where 70 patients with primary arterial hypertension treated in Jose Martí Cardiology Pediatric Hospital of Sancti Spíritus, from January to December 2009 were included. The variables used were: age, sex, skin color, nutritional valuation, heart frequency, family and personal history and type of arterial hypertension. Results: there was a predominance of male (81.2 percent), also white (80 percent) and patients older than 10 years (78.5 percent). 84.2 percent of patients had a first-line hypertension family history. Heart rate was elevated in 75.7 percent of patients; essential hypertension was diagnosed in 97.1 percent of cases. Conclusions: male, white, obese patients older than 10 years predominated. Tachycardia and family history of hypertension were directly related to the study group. Primary arterial hypertension predominated.

Características clínico-epidemiológicas de los pacientes menores de 15 años con diagnóstico de hipertensión arterial / Clinical-epidemiological characteristics of patients younger than 15 years with arterial hypertension diagnosis

Fundamento: La hipertensión arterial es una enfermedad multifactorial, con incremento de la incidencia y prevalencia en niños en los últimos años por lo que se considera un problema de salud. Objetivo: Describir las características clínico-epidemiológicas del paciente pediátrico con diagnóstico de hipertensión arterial. Metodología: Se realizó un estudio transversal en el que se incluyeron solo los 70 pacientes con diagnóstico de hipertensión arterial primaria atendidos en la consulta de cardiología del Hospital Pediátrico José Martí de Sancti Spíritus, en el periodo de enero a diciembre de 2009. Las variables utilizadas fueron la edad, el sexo, color de la piel, valoración nutricional, frecuencia cardiaca, antecedentes familiares y personales, y tipo de hipertensión arterial. Resultados: Predominó el sexo masculino (81,2 %), también la raza blanca (80 %) y los pacientes mayores de 10 años (78,5 %). El 84,2 % de los pacientes tenía antecedentes familiares de primera línea con hipertensión arterial. La frecuencia cardiaca estuvo elevada en el 75,7 % de los pacientes; la hipertensión arterial esencial se diagnosticó en el 97,1 % de los casos. Conclusiones: Predominaron los mayores de 10 años, masculinos, blancos y obesos. La taquicardia y los antecedentes familiares de hipertensión arterial estuvieron directamente relacionados al grupo estudio. Predominó la hipertensión arterial primaria.

Background: arterial hypertension is a multifactorial disease, with an increase of the incidence and prevalence in children in the last years for what it is considered a health problem. Objective: to describe the pediatric patient's clinical- epidemiological characteristics with arterial hypertension diagnosis. Methodology: a cross- sectional study was carried out where 70 patients with primary arterial hypertension treated in Jose Martí Cardiology Pediatric Hospital of Sancti Spíritus, from January to December 2009 were included. The variables used were: age, sex, skin color, nutritional valuation, heart frequency, family and personal history and type of arterial hypertension. Results: there was a predominance of male (81.2 %), also white (80%) and patients older than 10 years (78.5 %). 84.2 % of patients had a first-line hypertension family history. Heart rate was elevated in 75.7 % of patients; essential hypertension was diagnosed in 97.1 % of cases. Conclusions: male, white, obese patients older than 10 years predominated. Tachycardia and family history of hypertension were directly related to the study group. Primary arterial hypertension predominated.

New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing.

Scorpion venoms are a rich source of K(+) channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an α-helical segment to the C-terminal strand of a double- or triple-stranded ß-sheet, conforming a cystine-stabilized α/ß scaffold (CSα/ß). Here we show that two K(+) channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CSα/ß scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds.