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Background:Dapsone (4,4'-diamino-diphenyl sulfone) is a synthetic derivative of sulfones, with the antimicrobial activity described since 1937. It is also a drug traditionally used in dermatological therapies due to its anti-inflammatory effect. In recent years its antioxidant, antiexcitotoxic, and antiapoptotic effects have been described in different ischemic damage models, traumatic damage, and models of neurodegenerative diseases, such as Parkinson's (PD) and Alzheimer's diseases (AD). Finally, dapsone has proven to be a safe and effective drug as a protector against heart, renal and pulmonary cells damage; that is why it is now employed in clinical trials with patients as a neuroprotective therapy by regulating the main mechanisms of damage that lead to cell death.Objective:To provide a descriptive review of the evidence demonstrating the safety and therapeutic benefit of dapsone treatment, evaluated in animal studies and various human clinical trials.Methods:We conducted a review of PubMed databases looking for scientific research in animals and humans, oriented to demonstrate the effect of dapsone on regulating and reducing the main mechanisms of damage that lead to cell death.Conclusion:The evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

Introduction A first manic episode after 50 years of age is uncommon. Late Onset Mania might be indicative of abnormalities in white matter, probably related to vascular, degenerative, or inflammatory processes. Objective To determine if patients with late onset mania have reduced white matter integrity according to Magnetic Resonance Diffusion Tensor Imaging (DTI) and structural MRI. Methods Twenty-two patients with late onset mania (>50 years old) and 22 age-paired healthy subjects were included in the study. Fractional anisotropy (FA) was used as a quantitative measure of white matter integrity. Fazekas scale was assessed also to measure white matter abnormalities in the FLAIR sequence. The Frontal Assessment Battery, COGNISTAT and Trail making test A and B were used as cognitive measurements. Results According to DTI, commissural connections (left corpus callosum), and limbic connections (right and left uncinate fasciculus) were different between the patients and the comparison group. Fractional anisotropy values in the left corpus callosum showed significant correlations with neuropsychological measures, and with the Fazekas scale score. According to Fazekas scale, a pathological score in the FLAIR sequence was significantly more frequent in the patients as compared to the comparison group. Conclusions Patients with first episode mania in late life have relevant white matter abnormalities not explained by age, affecting interhemispheric and fronto-limbic networks probably related to executive functioning and emotional processing, at the level of the corpus callosum and the uncinate fasciculus. The etiology of this white matter loss of integrity in patients with late-onset mania is yet to be explored.

Background Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, an NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI. Methods To produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25 mm and 12.5 mm. Nociceptive behaviour, was evaluated with the use of von Frey filaments for 31 days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15 days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25-50 mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue. Results Acute treatment with amantadine reduced nociceptive behaviour. Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine. Conclusions Data from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated with N-methyl-D-aspartate receptors activation. Significance This study suggests that acute treatment with amantadine decreases hypersensitivity threshold and frequency of hypersensitivity response in a dose-dependent manner, in rats with SCI, by decreasing oxidative stress. Since amantadine is an easily accessible drug and has fewer adverse effects than current treatments for hypersensitivity threshold and frequency of hypersensitivity response, amantadine could represent a safe and effective therapy for the treatment of neuropathic pain. However, further research is required to provide evidence of the effectiveness and feasibility.

Background Excessive occlusal forces and occlusal trauma have been implicated as co-destructive factors for periodontitis in animal models. The objective of this study was to assess the association between occlusal trauma and periodontitis. Methods A total of 167 cases and 205 controls were included for analysis. Occlusal trauma was the exposures of interest and was registered for cases and controls. Additional clinical co-variables were registered as well for further analysis. The association of the exposure and periodontitis was determined by the odds ratio and logistic regression analysis adjusted for confounders. Results Amalgam restorations, pathogenic occlusion and occlusal trauma were more frequent in cases as compared to controls (P ≤ 0.05). The distribution of pathogenic occlusion and occlusal trauma was similar according to the stage and class of periodontitis. Logistic regression analysis showed a significant association for cigarette smoking, systemic conditions, amalgam restorations, pathogenic occlusion, and occlusal trauma with periodontitis (P ≤ 0.05). After adjusting for confounding variables in the model, amalgam restorations and occlusal trauma remained strongly associated with periodontitis (P ≤ 0.05). Conclusions Occlusal trauma is strongly associated with periodontitis. Additional long-term prospective studies are necessary to further understand the impact of the occlusal condition and periodontitis.

The use of the medicinal plant Ginkgo biloba has increased worldwide. However, G. biloba is capable of assimilating both essential and toxic metals, and the ingestion of contaminated products can cause damage to health. The aim of this study was to investigate the safety of manganese (Mn), copper (Cu), lead (Pb), arsenic (As), and cadmium (Cd) in 26 items containing Ginkgo biloba (pharmaceutical herbal products, dietary supplements, and traditional herbal remedies) purchased in the metropolitan area of Mexico City. Metal analysis was performed using a graphite furnace atomic absorption spectrometer. All of the products were contaminated with Pb, 54% of them with As, and 81% with Cd. The lowest values of Pb, As, and Cd were detected in pharmaceutical herbal products &gt, dietary supplements &gt, traditional herbal remedies. The daily intake dose (DID) of pharmaceutical herbal products was within the established limits for the five metals. Dietary supplements and traditional herbal remedies exceeded the DID limits for Pb. The hazard quotients estimation and non-carcinogenic cumulative hazard estimation index for Mn, As, and Cd indicated no human health risk. Our results suggest that products containing G. biloba for sale in Mexico are not a health risk.

Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation-dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, were included in the analysis by linear regression. Overall, CYP variants showed no effect on CLZ pharmacokinetics. The rs2069514 variant in homozygous genotype (also known as CYP1A2*1C/*1C) was associated with CLZ adverse reactions in Mexican patients with refractory psychosis (OR = 3.55 CI95 = 1.041-12.269, p = .043) and demonstrated that this effect is doubled by concomitant alcohol consumption (OR = 7.9 CI95 = 1.473-42.369, p = .016). Clinicians should be aware of this information before starting CLZ use, when treating patients with refractory psychosis, who are alcohol drinkers and carriers of this genetic variant in order to prevent CLZ-related adverse reactions. Nevertheless, our findings should be replicated in larger samples.

Las características geográficas de la Amazonía colombiana, sumadas a las dificultades de acceso al territorio y la baja presencia gubernamental, han creado un escenario en el que resulta posible el desarrollo de economías ilícitas, que en muchas ocasiones son fuente de financiación de agrupaciones criminales. En este orden de ideas, en este artículo se caracteriza la dimensión de la minería aurífera en la región, sus impactos en materia ambiental y social, y su relación con los cultivos de uso ilícito. Todo esto, a partir del análisis de bases de datos oficiales, revisión de la producción científica existente, entrevistas semiestructuradas a mineros y cocaleros que se realizaron en el marco de un estudio de caso en San José del Fragua, Caquetá y derechos de petición a las autoridades ambientales.

Background: For more than seven decades, ultrasound has been used as an imaging and diagnostic tool. Today, new technologies, such as focused ultrasound (FUS) neuromodulation, have revealed some innovative, potential applications. However, those applications have been barely studied to deal with neuropathic pain (NP), a cluster of chronic pain syndromes with a restricted response to conventional pharmaceuticals. Objective: To analyze the therapeutic potential of low-intensity (LIFUS) and high-intensity (HIFUS) FUS for managing NP. Methods: We performed a narrative review, including clinical and experimental ultrasound neuromodulation studies published in three main database repositories. Discussion: Evidence shows that FUS may influence several mechanisms relevant for neuropathic pain management such as modulation of ion channels, glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival, nerve regeneration, and remyelination. Some experimental models have shown that LIFUS may reduce allodynia after peripheral nerve damage. At the same time, a few clinical studies support its beneficial effect on reducing pain in nerve compression syndromes. In turn, Thalamic HIFUS ablation can reduce NP from several etiologies with minor side-effects, but some neurological sequelae might be permanent. HIFUS is also useful in lowering non-neuropathic pain in several disorders. Conclusion: Although an emerging set of studies brings new evidence on the therapeutic potential of both LIFUS and HIFUS for managing NP with minor side-effects, we need more controlled clinical trials to conclude about its safety and efficacy.

Understanding the impact of a publication by using bibliometric indices becomes an essential activity not only for universities and research institutes but also for individual academicians. This paper aims to provide a brief review of the current bibliometric tools used by authors and editors and proposes an algorithm to assess the relevance of the most common bibliometric tools to help the researchers select the fittest journal and know the trends of published submissions by using self-evaluation. We present a narrative review answering at least two related consecutive questions triggered by the topics mentioned above. How prestigious is a journal based on its most recent bibliometrics, so authors may choose it to submit their next manuscript? And, how can they self-evaluate/understand the impact of their whole publishing scientific life? We presented the main relevant definitions of each bibliometrics and grouped them in those oriented to evaluated journals or individuals. Also, we share with our readers our algorithm to assess journals before manuscript submission. Since there is a journal performance market and an article performance market, each one with its patterns, an integrative use of these metrics, rather than just the impact factor alone, might represent the fairest and most legitimate approach to assess the influence and importance of an acceptable research issue, and not only a sound journal in their respective disciplines.

Background Mexico City has air, water and food pollution problems; however, human exposure to cadmium and its sources have not been described. Objectives To determine the blood cadmium (BCd) level and its main exposure sources among males aged 40 years or older living in different areas of Mexico City. Methods After receiving informed consent, we interviewed 702 males aged ≥40 years to collect data on their sociodemographic characteristics, lifetime occupation, smoking history, and dietary habits, using a validated questionnaire. The BCd level (μg/L) was determined by atomic absorption spectrophotometry. Results The BCd mean level ± SD was 2.61 ± 0.82 μg/L, and 20% of men reported a potential cadmium occupational exposure. After adjusting for age and other potential confounders, the main determinants of the BCd level were the current smoking status at interview, with low (β≤8.5packs/year vs. non-smoker = 0.46; 95% CI: 0.28–0.64 μg/L; p 8.5 packs/year vs. non-smoker = 0.71; 95% CI: 0.56–0.87 μg/L; p 1–3servings/month vs. No = 0.14, 95% CI: 0.01–0.26 μg/L; p Conclusions The BCd levels observed in this population are high and only similar to those observed in workers from a sanitary landfill area in Southern Thailand. Potential environmental Cd exposure sources, such as industrial activity and previous land use, in the West and Center areas of the city should be explored in detail, especially in vulnerable population groups, such as children.

Objective Brain metabolic processes are not fully characterized in the kainic acid (KA)-induced Status Epilepticus (KASE). Thus, we evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an experimental strategy to evaluate in vivo, in a non-invasive way, the glucose consumption in several brain regions, in a semi-quantitative study to compare and to correlate with data from electroencephalography and histology studies. Methods. Sixteen male Wistar rats underwent FDG-PET scans at basal state and after KA injection. FDG-PET images were normalized to an MRI-based atlas and segmented to locate regions. Standardized uptake values (SUV) were obtained at several time points. EEGs and cell viability by histological analysis, were also evaluated. Results FDG-PET data showed changes in regions such as: amygdala, hippocampus, accumbens, entorhinal cortex, motor cortex and hypothalamus. Remarkably, hippocampal hypermetabolism was found (mean SUV = 2.66 ± 0.057) 2 h after KA administration, while hypometabolism at 24 h (mean SUV = 1.83 ± 0.056) vs basal values (mean SUV = 2.19 ± 0.057). EEG showed increased spectral power values 2 h post-KA administration. Hippocampal viable-cell counting 24 h after KA was decreased, while Fluoro-Jade B-positive cells were increased, as compared to control rats, coinciding with the hypometabolism detected in the same region by semi-quantitative FDG-PET at 24 h after KASE. Conclusions PET is suitable to measure metabolic brain changes in the rat model of status epilepticus induced by KA (KASE) at the first 24 h, compared to that of EEG; PET data may also be sensitive to cell viability.

Rosmarinus officinalis, conocido como aceite de romero, se utiliza en herbolaria tradicional. Estudios recientes han encontrado que algunos alcaloides aislados de la planta actúan como antidepresivos y antiinflamatorios, debido a su actividad inhibidora sobre la acetilcolinesterasa y la butirilcolinesterasa, por lo tanto, podrían actuar como tratamiento complementario para la enfermedad de Alzheimer, en la que se presenta una deficiencia de acetilcolina. Objetivo: evaluar el efecto del aceite de romero sobre el aprendizaje y la memoria, evaluado por medio del laberinto acuático de Morris en ratones. Material y métodos: se utilizaron 24 ratones macho de la cepa CD1, con 20-30g de peso. Se dividieron en cuatro grupos de tratamiento: 1. solución salina, vía intraperitoneal, 2. memantina (10μg/Kg), vía intraperitoneal, 3. aceite de romero (20 μg/Kg), vía inhalatoria y 4.aceite de romero (120 μg/Kg), vía oral. Se midió el tiempo que permaneció en cada cuadrante como una forma de evaluar el aprendizaje y la memoria, a través del reconocimiento del área. Resultados: se encontró que el grupo tratado con aceite de romero por vía oral consiguió un desempeño parecido al del grupo tratado con memantina, fármaco utilizado para tratar el Alzheimer, en cambio, el grupo tratado por vía inhalatoria no mostro diferencia significativa. Conclusiones: el presente estudio mostró que los ratones tratados con aceite de romero por vía oral presentan un mejor desempeño en el laberinto acuático de Morris, en comparación con los ratones tratados por vía inhalatoria y los controles, lo que indica que se mejora el aprendizaje y la memoria. Se concluye que el uso de este remedio etnobotánico podría aportar una opción al tratamiento de pacientes con Alzheimer.

Epilepsy is characterized by spontaneous recurrent seizures and temporal lobe epilepsy (TLE) is the most common serious neurological example of acquired and frequent epilepsy. Oxidative stress is recognized as playing a contributing role in several neurological disorders, and most recently have been implicated in acquired epilepsies. The MTs occur in several brain regions and may serve as neuroprotective proteins against reactive oxygen species causing oxidative damage and stress. The main aim of this work was to describe the immunohistochemical localization of MT in the specimens derived from the patients affected by TLE. Histopathological examination showed NeuN, GFAP and MT immunopositive cells that were analyzed for determinate in hippocampal and parietal cortex samples. An increase in the reactive gliosis associated with increased MT expression was observed in patients with TLE.

Background Context Traumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions. Purpose Injection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy. Study Design This is an in vivo animal study. Methods This study evaluates the use of such particles in rats after SCI by examining spared nervous tissue and the Basso, Beattie, and Bresnahan (BBB) scale to evaluate the functional outcome. Diffusive magnetic resonance imaging (MRI) was employed to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) as non-invasive biomarkers of damage after SCI. Results Fractional anisotropy decreased, whereas ADC increased in all groups after the lesion. There were significant differences in FA when compared with the SCI-PPy-I group versus the SCI group (p 2 =0.449, p 2 =0.395, p 2 =0.367, p 2 =0.421, p Conclusions The results suggested that PPy-I is neuroprotective as it decreased the amount of damaged tissue while improving the motor function. Non-invasive MRI proved to be useful in the characterization of SCI and recovery.

Purpose The aim of present study is to measure plasma clozapine (CLZ) and N-desmethyl clozapine (DMC) as biomarkers to correlate drug concentrations with the appearance of preclinical adverse hematic effects. Methods A high-performance liquid chromatographic method, using a diode-array (ultraviolet) detector, was validated to obtain reliable concentrations of CLZ and DMC, its main metabolite, in plasma of 41 schizophrenic patients taking CLZ. Blood neutrophils and leucocytes counting were concurrently assessed as a proxy to subclinical adverse reactions. Results The analytical method employed was linear, reproducible, and stable to measure concentrations of CLZ between 30 and 1000 ng/mL, while 12.5–560 ng/mL of the metabolite. The method allowed us to correlate CLZ plasma concentrations, the time taking CLZ and CLZ dose as determinants of neutrophils’ counting with a R2 = 0.447, using a multiple regression analysis model. Likewise, the correlation of leucocyte counting vs CLZ plasma levels and CLZ time, showed a R2 = 0.461. DMC correlated significantly with both neutrophils and leucocytes counting, but was excluded from the regression when CLZ concentration was included in the model. Finally, no other hematological adverse reactions were recorded. One patient presented a cardiovascular complication. The negative correlation between clozapine and neutrophil count observed in patients, suggest that CLZ itself, but not DMC, could be related to hematologic side-effects. Conclusion The findings of this study, demonstrate for the first time, that plasma levels of CLZ and time taking the drug are independent determinants of blood neutrophils and leucocytes, so the monitoring of plasma CLZ may be useful in the clinic practice to determine safe dosing of the drug.

Background Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. Aim To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. Methods A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. Results 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. Conclusions In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium.

Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke.

Lead exposure remains a significant environmental problem; lead is neurotoxic, especially in developing humans. In Mexico, lead in human blood is still a concern. Historically, much of the lead exposure is attributed to the use of handcrafted clay pottery for cooking, storing and serving food. However, experimental cause-and-effect demonstration is lacking. The present study explores this issue with a prospective experimental approach.We used handcrafted clay containers to prepare and store lemonade, which was supplied as drinking water to pregnant rats throughout the gestational period.We found that clay pots, jars, and mugs leached on average 200 µg/l lead, and exposure to the lemonade resulted in 2.5 µg/dl of lead in the pregnant rats' blood. Neonates also showed increased lead content in the hippocampus and cerebellum. Caspase-3 activity was found to be statistically increased in the hippocampus in prenatally exposed neonates, suggesting increased apoptosis in that brain region. Glazed ceramics are still an important source of lead exposure in Mexico, and our results confirm that pregnancy is a vulnerable period for brain development.

Manganese (Mn) is an essential nutrient for cellular function, but in high concentrations, it is neurotoxic. Environmental exposure to Mn has been associated with cognitive effects in children. This study aimed to assess the effect of environmental exposure to Mn on verbal memory and learning in schoolchildren residents from two municipalities in the state of Hidalgo, Mexico. Cross-sectional studies were conducted in 2006 and 2013 with a total of 265 schoolchildren of 7 to 11 years old. Children’s Auditory Verbal Learning Test-2 (CAVLT-2) was used to assess verbal memory and learning. Mn exposure tertiles were defined according to hair manganese (MnH) levels determined by atomic absorption spectrophotometry. Linear regression models were used to estimate the association between MnH levels and CAVLT-2 scores. The models were adjusted by potential confounders. The lowest and highest exposure tertiles were defined below and above MnH levels of ≤ 0.72 and ≥ 3.96 μg/g, respectively. Mn exposure was significantly associated with an average of 5- to 9-point decrease in learning curves and summary CAVLT-2 scores in the highest tertile. This study adds to the evidence of decreased verbal memory and learning in schoolchildren environmentally exposed to manganese.

Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.

Status epilepticus (SE) is a serious medical condition, as it may trigger epileptogenesis. SE produces continuous generalized seizures resulting in irreversible brain damage. Therefore, the use of neuroprotective agents to prevent cell damage, may reduce the impact of SE. The use of diazepam (DZP), has shown limited neuroprotective effect in SE patients. According to previous reports, dapsone (DDS) is able to reduce both cell damage and seizures, when administered 30 min before the onset of seizures. This study is aimed to evaluate the ability of DDS, alone or in combination with DZP starting their administration once the SE is onset to evaluate the control of seizures in rats. Results showed a reduced convulsive electrical activity after 30 min, 1 and 2 h after SE induced by kainic acid (KA) administration, in the animals treated with DZP alone or in combination with DDS. At 24 h, we observed electrical activity similar to baseline in all groups receiving treatment. The animals treated with DDS and DZP alone or in combination showed an increase in the number of viable pyramidal cells but only the combination showed a lower number of damaged pyramidal neurons of hippocampal CA3. In conclusion, DDS plus DZP was able to control SE and to prevent SE-induced damage, when administered in combination with DZP. As DDS is already in use for patients with leprosy, that combination may be a safe, good option for human cases of SE.

The effects caused by exposure to lead (Pb) are still considered as a relevant health risk despite public policies aimed to restricting the use of this element. The toxicity limit in the blood (10 μg/dL, established by the Center for Disease Control and Prevention) has been insufficient to prevent adverse effects and even lower values have been related to neurobehavioral dysfunctions in children. Currently, there is not a safe limit of exposure to Pb. A large body of evidence points to environmental pollutant exposure as the cause of predisposition to violent behavior, among others. Considering the evidence by our group and others, we propose that Pb exposure induces alterations in the brain vasculature, specifically in nitric oxide synthases (NOS), affecting in turn the serotonergic system and leading to heightened aggressive behavior in the exposed individuals. This review article describes the consequences of Pb exposure on the nitrergic and serotonergic systems as well as its relationship with aggressive behavior. In addition, it summarizes the available therapy to prevent damage in gestation and among infants.

After spinal cord injury (SCI), some self-destructive mechanisms start leading to irreversible neurological deficits. It is known that oxidative stress and apoptosis play a major role in increasing damage after SCI. Metallothioneins I and II (MT) are endogenous peptides with known antioxidant, neuroprotective capacities. Taking advantage of those capacities, we administered exogenous MT to rats after SCI in order to evaluate the protective effects of MT on the production of reactive oxygen species (ROS) and lipid peroxidation (LP), as markers of oxidative stress. The activities of caspases-9 and -3 and the number of annexin V and TUNEL-positive cells in the spinal cord tissue were also measured as markers of apoptosis. Rats were subjected to either sham surgery or SCI and received vehicle or two doses of MT (10 μg per rat) at 2 and 8 h after surgical procedure. The results showed a significant increase in levels of MT protein by effect of SCI and SCI plus treatment at 12 h, while at 24 h an increase of MT was observed only in the injury plus treatment group (p<0.05). ROS production was decreased by effect of MT in lesioned tissue; likewise, we observed diminished LP levels by MT effect both in the sham group and in the group with SCI. Also, the results showed an increase in the activity of caspase-9 due to SCI, without changes by effect of MT, as compared to the sham group. Caspase-3 activity was increased by SCI, and again, MT treatment reduced this effect only at 24 h after injury. Finally, the results of the number of cells positive to annexin V and TUNEL showed a reduction due to MT treatment both at 24 and 72 h after the injury. With the findings of this work, we conclude that exogenously administered MT has antioxidant and antiapoptotic effects after SCI.

Objectives The prevalence of stroke survivors with incomplete recovery in society has been estimated at 460/100,000 people, and one third of them require help in at least one daily activity. Two thirds of all deaths related to stroke in the world occur in low- and middle-income countries. The objective of the present work was to assess the reliability and validity of the previously translated Spanish Stroke-Specific Quality-of-Life (SSQOL) version 2.0 scales in Mexican stroke survivors. Methods An observational and cross-sectional pilot study was conducted. Thirty-one patients who suffered stroke up to 1 year prior to the present study were included. Patients were interviewed twice in a 7-day period; other indexes and scales were applied. The reliability was assessed by using Cronbach's alpha (internal consistency) and test-retest by using Spearman's rho scores; the acceptability was evaluated by the floor and ceiling effects. Results Ceiling and floor effects were observed for fewer than 20% of the patients. The overall internal consistency of the questionnaire was greater than 0.7 (Cronbach's α ), with only two domains (family roles and personality) having lower internal consistency values. The results displayed high test-retest reliability: all domains had Spearman's rho scores of over 0.8. The questionnaire has adequate construct validity. Conclusions Our preliminary results showed that the psychometric properties (acceptability and reliability) of the Spanish SSQOL questionnaire are good, encouraging, and comparable to those of other similar studies. This study is the first approach to validate the Spanish version of the SSQOL questionnaire in Mexican stroke survivors.

La lesión traumática de médula espinal (LTME) es un problema de salud que afecta a la población en edad económicamente activa (20 a 45 años) para la cual no se tiene un tratamiento eficaz. En este estudio se ha demostrado que el fenobarbital (FB) y dapsona (DDS) tienen efecto neuroprotector en modelos de infarto cerebral y de excitotoxicidad. Objetivo: evaluar el efecto terapéutico de FB administrado sólo o en combinación con la DDS durante la etapa aguda de la LTME, cuantificando la actividad de la caspasa3 y la recuperación funcional motora. Material y métodos: se utilizaron ratas hembras de 250 g, con laminectomía o LTME, tratadas con FB o DDS solos o en combinación y sacrificadas a 72 hs después del procedimiento quirúrgico para medir la actividad de caspasa-3. Además, se evaluó la recuperación motora durante 2 meses. Resultados: Los valores de la actividad de caspasa-3 mostraron un incremento por efecto de la lesión que disminuyó cuando ambos fármacos fueron administrados sólo o en combinación. Asimismo, los animales tratados con FB sólo o en combinación con DDS tuvieron el mejor desempeño funcional siendo la terapia combinada la más eficaz mostrando un incremento del 135 % respecto al grupo control. Conclusiones: se pudo demostrar que ambos fármacos ofrecen beneficio terapéutico al disminuir la apoptosis y promover la recuperación funcional de los animales, por lo que, los hallazgos de este estudio puede tener valor como estrategia farmacológica eficaz en la práctica clínica.

Introduction: Oestrogen deficiency produces oxidative stress (OS) and changes in hippocampal neurons and also reduces the density of dendritic spines (DS). These alterations affect the plastic response of the hippocampus. Oestrogen replacement therapy reverses these effects, but it remains to be seen whether the same changes are produced by tibolone (TB). The aim of this study was to test the neuroprotective effects of long-term oral TB treatment and its ability to reverse DS pruning in pyramidal neurons (PN) of hippocampal area CA1. Methods: Young Sprague-Dawley rats were distributed in 3 groups: a control group in proestrus (Pro) and two ovariectomised groups (Ovx), of which one was provided with a daily TB dose (1 mg/kg), OvxTB and the other with vehicle (OvxV), for 40 days in both cases. We analysed lipid peroxidation and DS density in 3 segments of apical dendrites from PNs in hippocampal area CA1. Results: TB did not reduce lipid peroxidation but it did reverse the spine pruning in CA1 pyramidal neurons of the hippocampus which had been caused by ovariectomy. Conclusions: Oestrogen replacement therapy for ovariectomy-induced oestrogen deficiency has a protective effect on synaptic plasticity in the hippocampus. Resumen: Introducción: El hipoestrogenismo produce estrés oxidativo (EO) y cambios en las neuronas del hipocampo (H) y reduce la densidad de las espinas dendríticas (ED). Estas alteraciones repercuten en la respuesta plástica del H. La terapia de sustitución intraperitoneal con estrógenos revierte estos efectos, pero no se sabe si ocurre lo mismo con la tibolona (TB). El objetivo fue comprobar los efectos neuroprotectivos de la TB administrada por vía oral a largo plazo y su capacidad para revertir la poda de ED de las neuronas piramidales (NP) del CA1 del H. Métodos: Ratas Sprague-Dawley jóvenes: distribuidas en 3 grupos: control en proestro (Pro) y 2 grupos ovariectomizados (Ovx), uno suplementado con dosis diaria de TB (1 mg/kg), OvxTB, y otro con vehículo (OvxV), por 40 días. Se analizaron la peroxidación de lípidos y la densidad de las ED en 3 segmentos de la dendrita apical de las NP del CA1 del H. Resultados: La TB no redujo la peroxidación de lípidos en el H, pero recuperó la poda de espinas en las NP del CA1 del H, producida por la ovariectomía. Conclusiones: La terapia de sustitución estrogénica en el hipoestrogenismo por ovariectomía tiene un efecto protector. Keywords: Oestrogen deficiency, Tibolone, Hippocampus, Area CA1, Morphology, Dendritic spines, Palabras clave: Hipoestrogenismo, Tibolona, Hipocampo, Área CA1, Morfología, Espinas dendríticas

Prenatal malnutrition (M) and lead intoxication (Pb) have adverse effects on neuronal development; one of the cellular mechanisms involved is a disruption of the pro- and anti-oxidant balance. In the developing brain, the vulnerability of neuronal membrane phospholipids is variable across the different brain areas. This study assesses the susceptibility of different brain regions to damage by quitar tissue oxidative stress and lead quitar concentrations to determine whether the combined effect of prenatal malnutrition (M) and lead (Pb) intoxication is worse than the effect of either of them individually.M was induced with an isocaloric and hypoproteinic (6% casein) diet 4 weeks before pregnancy. Intoxication was produced with lead acetate in drinking water, from the first gestational day. Both the M and Pb models were continued until the day of birth. Four brain regions (hippocampus, cortex, striatum, and cerebellum) were dissected out to analyze the lipid peroxidation (LP) levels in four groups: normally nourished (C); normally nourished but intoxicated with lead (CPb); malnourished (M); and M intoxicated with lead (MPb).Dam body and brain weights were significantly reduced in the fourth gestational week in the MPb group. Their pups had significantly lower body weights than those in the C and CPb groups. The PbM group exhibited significant increases of lead concentration and LP in all areas evaluated. A potentiation effect of Pb and M on LP was found in the cerebellum.This study provides information on how environmental conditions (intoxication and malnutrition) during the intrauterine period could differentially affect the development of neuronal plasticity and, in consequence, alter adult brain functions such as learning and memory.

INTRODUCTION A deeper understanding of supplementary bibliometrics beyond the impact factor might provide researchers with a better understanding of the citation process. This study presents a multivariate analysis of gastroenterology and hepatology journals to evaluate the predictive ability of seven bibliometrics in the Web of Science to calculate total cites over a 2-year period. METHODS Coincidentally, bibliometrics appearing during 2008, 2009, and 2010, with their corresponding cites in 2010, 2011, and 2012, were recorded from the Journal Citation Reports Science Edition. A linear mixed-effects design using random slopes and intercepts was performed on 51 out of 74 journals in the Gastroenterology and Hepatology category. RESULT There was a significant global effect size (R(2) = 0.992; P < 0.001), which yielded a total variance of 99.2%. The strongest predictors in the model were the Eigenfactor Score and Cited Half-life (P < 0.001), followed by the Number of Articles (P = 0.011) and the Immediacy Index (P = 0.021). The impact factor was not a significant predictor. CONCLUSION The Eigenfactor Score and Cited Half-life predictors might be the new standards to assess the influence and importance of scientific journals; this approach may help researchers select journals in which to publish their work.

Because we believe the journal selection before a manuscript submission deserves further investigation in each medical specialty, we aimed to evaluate the predictive ability of seven bibliometrics in the Radiology, Nuclear Medicine and Medical Imaging category of the Web of Knowledge to calculate total citations over a 7-year period. A linear mixed effects design using random slopes and intercepts were performed on bibliometrics corresponding to 124 journals from 2007 to 2011, with their corresponding citations from 2009 to 2013, which appeared in the Journal Citations Report Science Edition. The Eigenfactor Score, Article Influence Score, Cited Half-life, 5-years impact factor and Number of Articles are significant predictors of 2-year-ahead total citations (p ≤ 0.010 for all variables). The impact factor and Immediacy Index are not significant predictors. There was a significant global effect size (R2 = 0.934; p

Objective Stroke is the leading cause of disability and death in the world. Each year, 15 million people worldwide suffer strokes. This study aims to analyze the relationship between the economic consequences and the units of utility in Mexican acute ischemic stroke (AIS) survivors who attended the National Institute of Neurology and Neurosurgery in Mexico City and who were treated with dapsone (a neuroprotective drug) versus placebo in addition to conventional treatment. Methods This cost–utility analysis was done in the context of a clinical trial with a follow-up period of 3 months. In the clinical trial, dapsone efficacy versus placebo was measured in patients who presented with an AIS that also were receiving conventional therapy. Efficacy was also obtained from a published article that used dapsone to treat patients with AIS. A meta-analysis was conducted in order to obtain dapsone efficacy with a 95% confidence interval. The economic medical and nonmedical costs were calculated. The utility was evaluated using the Stroke Specific Quality of Life questionnaire, Spanish version. A Markov model was used. Key findings Twenty-nine patients with AIS were included, with an average age of 62.2 years (interval 23–90 years), and 62.1% were women. Dapsone cost–utility ratio was US$14612.79/quality-adjusted life year (QALY) versus placebo US$18631.84/QALY. The incremental cost-effectiveness ratio was US$49 700.05/QALY gained with dapsone. The sensitivity analysis of results was not sensitive to the variation of costs and/or QALYs. Conclusions The use of dapsone in AIS patients is a favourable option regarding cost–utility in comparison with placebo.

Object The object of this study was to determine the relationship between plasma taurine and subarachnoid hemorrhage (SAH) outcome. Methods Forty patients with SAH and mild neurological deficits were included in this prospective, blinded cohort study. Plasma taurine levels were measured using high-performance liquid chromatography on admission and were correlated with patient outcomes at discharge. Results Twenty-five percent of the patients ultimately had a poor outcome. Plasma taurine concentrations at admission were increased (2-fold) in SAH patients with a favorable outcome and were further increased (6-fold) in those who had a poor outcome. Increased taurine levels identified patients who would be discharged with a poor outcome, with sensitivity and specificity values of approximately 80% and 100%, respectively, and positive and negative predictive values of approximately 90%. Delayed cerebral vasospasm showed an OR of 27.9 (95% CI 1.090–714.9) for a poor outcome, whereas an increased taurine concentration had an OR of 105 for a poor outcome (95% CI 8.3–1328.0, p < 0.001). Conclusions Increased plasma taurine concentrations on admission predict a poor outcome in SAH.

Manganese (Mn) is an essential metal, but in excess it becomes neurotoxic. Children's developing nervous system may be especially vulnerable to the neurotoxic effects of overexposure to this metal. The aim of this study was to assess the effect of Mn exposure on verbal memory and learning in 7- to 11-year-old children. We tested 79 children living in the Molango Mn-mining district and 95 children from a non-exposed community in the same State of Mexico. The Children's Auditory Verbal Learning Test (CAVLT) was administered. Blood and hair samples were obtained to determine Mn concentrations using atomic absorption spectrophotometry. CAVLT performance was compared between the two groups and multilevel regression models were constructed to estimate the association between biomarkers of Mn exposure and the CAVLT scores. The exposed group presented higher hair and blood Mn (p

A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis.A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in TDuring the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χMRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.

Introduction:Cadmium (Cd) is a non-essential metal classified by IARC as a type 1 carcinogen. The main non-occupational exposure route is via inhalation of tobacco smoke or suspended particles. At ...

Almost a dozen diffusion tensor-imaging (DTI) variables have been used to evaluate brain tumours with scarce information about their diagnostic ability. We aimed to perform a comprehensive evaluation of tensor metrics reported in the last decade. Retrospective case control study performed in 14 patients with glioblastoma multiforme (GBM) and 28 controls. Conventional brain MR sequences and image postprocessing of DTI allowed the calculation of: MD, FA, p, q, L, Cl, Cp, Cs, RA, RD and AD, classified into five regions: normal appearance white matter (NAWM), immediate and distant oedema, enhancing rim and cystic cavity. ANOVA and AUROC analyses were performed. ANOVA depicted a significant difference among all metrics (p

Background: Stroke is the second leading cause of death in the world and the main cause of long-term disability in Western countries. Evaluating health-related quality of life (HRQOL) in patients who have survived a stroke provides a more complete picture of the effects of different interventions in a patient's condition. Dapsone has been shown to have neuroprotective effects during the acute phase of stroke. Objective: To evaluate HRQOL in patients who received dapsone versus placebo after stroke. Methods: This was an observational pilot study of 21 patients who randomly received dapsone or placebo during the acute phase of a stroke. HRQOL was evaluated with the Stroke-Specific Quality of Life (SSQOL) questionnaire 6 months after the stroke. Results: There was no significant difference in the total SSQOL score 6 months after a stroke between patients who received dapsone or placebo (3.41 vs 3.19; p = 0.434). Patients who received dapsone had higher mean values for 9 of the 12 domains of the SSQOL than patients who received placebo. However, the difference was not statistically significant. The highest score for the patients who received dapsone was in the self-care domain. Overall SSQOL scores were lower in women than in men (p < 0.01). Conclusion: SSQOL was slightly better for patients who received dapsone, showing a possible improvement in their functional level. More prospective, randomized, and placebo-controlled studies with a larger number of patients are needed to confirm these results.

Lead (Pb), a ubiquitous and potent neurotoxicant, induces several neurophysiological and behavioural changes, while Pb alters the function of multiple organs and systems, it primarily affects the central nervous system. In human adults, encephalopathy resulting from Pb intoxication is often characterized by sleeplessness, poor attention span, vomiting, convulsions and coma; in children, Pb-induced encephalopathy is associated with mental dullness, vomiting, irritability and anorexia; diminished cognitive function resulting in a mental deficit has been also observed during Prolonged exposure to Pb. Pb can produce oxidative stress, disrupt the blood-brain barrier and alter several Ca(2+)-dependent processes, including physiological processes that involve nitric oxide synthesis on central nervous system in development and adult animals. This review summarizes recent evidence showing that Pb can interfere with the production of nitric oxide and can disrupt the function of nitric oxide synthase. Lead interferes with nitric oxide-related physiological mechanisms, and Pb neurotoxicity may affect processes involved in learning and memory.

After spinal cord injury (SCI), a complex cascade of pathophysiological processes rapidly damages the nervous tissue. The initial damage spreads to the surrounding tissue by different mechanisms, including oxidative stress. We have recently reported that the induction of metallothionein (MT) protein is an endogenous rapid-response mechanism after SCI. Since the participation of MT in neuroprotective processes after SCI is still unknown, the aim of the present study was to evaluate the possible neuroprotective effect of exogenously administered MT-II during the acute phase after SCI in rats. Female Wistar rats weighing 200-250g were submitted to spinal cord contusion by means of a computer-controlled device (NYU impactor). Rats received several doses of MT-II (3.2, 10 and 100μg) at 2 and 8h after SCI. Results of the BBB scale were statistically analysed using an ANOVA of repeated-measures, followed by Tukey's test. Among the three doses tested, only 10 and 100μg were able to significantly increase (p

Neuroprotection refers to the protection of neurons from excitotoxicity, oxidative stress and apoptosis as principal mechanisms of cell loss in a variety of diseases of the central nervous system. Our interest in Parkinson’s disease (PD) treatment is focused on drugs with neuroprotective properties in preclinical experiments and evidence-based efficacy in human subjects. To this date, neuroprotection has never been solidly proven in clinical trials but recent adequate markers and/or strategies to study and promote this important goal are described. A myriad of compounds with protective properties in cell cultures and animal models yield to few treatments in clinical practice. At present, markers of neuronal vitality, disease modifying effects and long term clinical stability are the elements searched for in clinical trials. This review highlights new strategies to monitor patients with PD. Currently, neuroprotection in subjects has not been solidly achieved for selegiline and pramipexole; however, a recent rasagiline trial design is showing new indications of disease course modifying effects. In neurological practice, it is of utmost importance to take into account the potential neuroprotection exerted by a treatment in conjunction with its symptomatic efficacy.

After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4 0 -diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (BassoBeattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 6 1.12, whereas, in the dapsone-treated groups, it reached 13.6 6 1.04 and 12.9 6 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI. V V C 2011 Wiley-Liss, Inc.

Objective To evaluate the cost-effectiveness (CE) ratio of clomiphene citrate versus anastrozole in the induction of ovulation in infertile adult women attending a Mexican public hospital. Methods A CE study was conducted from a hospital perspective. A clinical pilot study was carried out at the La Raza hospital. Thirty patients with infertility due to anovulation were recruited and grouped as follows: group A was treated with clomiphene citrate and group B with anastrozole. Efficacy data and adverse events of both drugs were obtained from the above-described clinical pilot study with Mexican women patients and through a systematic review of published medical literature. Efficacy data were analysed using meta-analysis; direct and indirect costs were gathered and calculated by the micro-costing technique, and a 1-year time horizon was considered. The Monte Carlo Markov model was used, and quality-adjusted life years (QALYs) were used as the unit of effectiveness. Incremental and sensitivity analyses were performed and we investigated the effect of a 5% discount rate. Key findings The odds ratios from the meta-analysis were 0.86 for ovulation induction and 1.46 for pregnancy. The most cost-effective therapy was clomiphene citrate at US$405/QALY in comparison to US$457/QALY for anastrozole. The incremental cost was US$52/QALY. The result of the discount rate for the most cost-effective therapy projected for 5 years was US$1288. The sensitivity analysis did not show changes for the most cost-effective therapy when the effectiveness probabilities or the treatment costs were modified. Conclusion Conventional treatment with clomiphene citrate therapy has the highest cost-effectiveness for the population studied.

Background Excessive exposure to manganese (Mn), an essential trace element, has been shown to be neurotoxic, especially when inhaled. Few studies have examined potential effects of Mn on cognitive functions of environmentally exposed children. Objective This study was intended to estimate environmental exposure to Mn resulting from mining and processing and to explore its association with intellectual function of school-age children. Methods Children between 7 and 11 years of age from the Molango mining district in central Mexico (n = 79) and communities with similar socioeconomic conditions that were outside the mining district (n = 93) participated in the cross-sectional evaluation. The revised version of the Wechsler Intelligence Scale for Children adapted for the Mexican population was applied. Concentrations of Mn in blood (MnB) and hair (MnH) were used as biomarkers of exposure. Results Exposed children had significantly higher median values for MnH (12.6 μg/g) and MnB (9.5 μg/L) than did nonexposed children (0.6 μg/g and 8.0 μg/L, respectively). MnH was inversely associated with Verbal IQ [β = −0.29; 95% confidence interval (CI), −0.51 to −0.08], Performance IQ (β = −0.08; 95% CI, −0.32 to 0.16), and Total Scale IQ (β = −0.20; 95% CI, −0.42 to 0.02). MnB was inversely but nonsignificantly associated with Total and Verbal IQ score. Age and sex significantly modified associations of MnH, with the strongest inverse associations in young girls and little evidence of associations in boys at any age. Associations with MnB did not appear to be modified by sex but appeared to be limited to younger study participants. Conclusions The findings from this study suggest that airborne Mn environmental exposure is inversely associated with intellectual function in young school-age children.

Objective: Our purpose was to report the design and positioning accuracy testing of a stereotactic device designed for a linear accelerator to perform spinal radiosurgery in rats. Methods: To define the spatial and repositioning accuracy of the device, we measured the 3-dimensional (3D) translation of a paraspinal fiducial mark implanted by microsurgery in 5 Wistar rats during a sequence of setups and treatment simulations, thus obtaining final 3D translation vectors and maximum displacements. Results: For spatial accuracy, the differential coordinate translations were 0.8 ± 0.3, 0.6 ± 0.2 and 0.5 ± 0.1 mm in the x-, y- and z-directions, respectively. The median magnitude of the 3D vector was 1.3 mm (σ = 0.2 mm), with a maximum error of 2.2 mm. The differential coordinate translation for the repositioning accuracy showed values of 1.4 ± 0.3, 1.3 ± 0.3 and 0.8 ± 0.1 mm for the x-, y- and z-coordinates, resulting in a 3D displacement vector of 2.2 mm (σ = 0.2 mm) and a maximum displacement error of 3.6 mm. Conclusions: Using a linear accelerator, our novel stereotactic device provides accurate immobilization and repositioning of paraspinal structures under experimental conditions in rats.

This study examined the neuroprotective ability of tetrapeptide l-Asp-Ala-His-Lys (DAHK) in permanent middle cerebral artery occlusion in rats. One DAHK dose (16 mg/kg) or saline solution were i.v. administered 30 min after occlusion and neurological deficit was evaluated at 2, 24, 48, 72 and 96 h using Longa scoring scale. The striatum infarction area was evaluated until 96 h after occlusion in both groups after staining with hematoxylin–eosin. DAHK-treated group showed a significant (P

Although dapsone (4,4′-diaminodiphenylsulfone) has been described as a neuroprotective agent in occlusive focal ischemia in rats, its mechanism of action is still unknown. To explore this mechanism, oxidative, inflammatory and apoptotic processes were evaluated in the striatum of adult rats using a model of ischemia-reperfusion (I/R), either with or without dapsone treatment. Male Wistar rats were submitted to transient middle cerebral artery occlusion for 2 hr, followed by reperfusion. Rats were dosed either with dapsone (12.5 mg/kg i.p.) or vehicle 30 min before or 30 min after the ischemia onset. Lipid peroxidation (LP) and nitrotyrosine contents were measured 22 hr after reperfusion, and myeloperoxidase activity was evaluated 46 hr after I/R. Different markers for apoptosis and necrosis were also evaluated both at 24 and 72 hr after I/R experimental procedure. LP increased by 37% in ischemic animals vs controls, and this effect was reversed by dapsone treatments. A similar effect was observed regarding nitrotyrosine striatal contents. Myeloperoxidase activity, a marker of inflammatory response, increased 3.7-fold in ischemic animals vs. control rats, and dapsone treatment antagonized that effect. Although apoptosis was increased by the effect of ischemia at both evaluation times, dapsone antagonized that effect only at 72 hr after surgery. Dapsone antagonized all of the I/R end points measured, showing a remarkable ability to decrease markers of damage through antioxidant, antiinflammatory, and anti-apoptotic effects. © 2008 Wiley-Liss, Inc.

It has been shown that the steroid dehydroepiandrosterone (DHEA) interacts with dopamine (DA) and serotonin (5-HT) neurotransmitter systems, which are involved in the pathophysiology of neurological and psychiatric diseases such as Parkinson's disease as well as mood and psychotic disorders. To explore if DHEA modulates DA and 5-HT metabolism we analyzed the content of both neurotransmitters and their metabolites in the rat corpus striatum (CS) and nucleus accumbens (NAc) 2 h after steroid administration (30, 60 and 120 mg/kg i.p.). DHEA treatment significantly reduced DA turnover (up to 33%) in the CS, but increased 5-HT turnover (up to 76%) in both regions. Those effects could be relevant to mood and neurodegenerative disorders.

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

Monoamines such as norepinephrine (NE) and serotonin (5-HT) have shown to play an important role in motor recovery after brain injury. The effects elicited by these neurotransmitters have been reported as distal from the area directly affected. Remote changes may take place over minutes to weeks and play an important role in post-stroke recovery. However, the mechanisms involved in spontaneous recovery have not been thoroughly delineated. Therefore, we determined the NE and 5-HT content, in the pons and hippocampal dentate gyrus (DG) as well as motor deficit and spontaneous activity in rats after 3, 10 and 20 days cortical iron injection. Three days post-lesion the pontine NE content diminished, this effect was accompanied by deficient spontaneous activity and impaired sensorimotor evaluation. Ten and twenty days after lesion the NE levels were similar to those of control group, and animals also showed behavioral recovery. Monoamines content on DG 3 days post-lesion showed no differences as compared to controls. Interestingly, ten and twenty days after cortical injury, animals showed increased NE and 5-HT. These results suggest that behavioral recovery after brain damage involve changes on monoamines levels on DG, an important structure to plastic processes. In addition, the results herein support evidence to propose these neurotransmitters as key molecules to functional recovery in the central nervous system.

To determine existing correlates among diffusion tensor imaging (DTI)-derived metrics in healthy brains and brains with glioblastoma multiforme (GBM).Case-control study using DTI data from brain magnetic resonance imaging of 34 controls (mean, 41.47; SD, ± 21.94 years; range, 21-80 years) and 27 patients with GBM (mean, SD; 48.41 ± 15.18 years; range, 18-78 years). Image postprocessing using FSL software calculated eleven tensor metrics: fractional (FA) and relative anisotropy; pure isotropic (p) and anisotropic diffusions (q), total magnitude of diffusion (L); linear (Cl), planar (Cp) and spherical tensors (Cs); mean (MD), axial (AD) and radial diffusivities (RD). Partial correlation analyses (controlling the effect of age and gender) and multivariate Mancova were performed.There was a normal distribution for all metrics. Comparing healthy brains vs brains with GBM, there were significant very strong bivariate correlations only depicted in GBM: [FA↔Cl (+)], [FA↔q (+)], [p↔AD (+)], [AD↔MD (+)], and [MD↔RD (+)]. Among 56 pairs of bivariate correlations, only seven were significantly different. The diagnosis variable depicted a main effect [F-value (11, 23) = 11.842, P ≤ 0.001], with partial eta squared = 0.850, meaning a large effect size; age showed a similar result. The age also had a significant influence as a covariate [F (11, 23) = 10.523, P0.001], with a large effect size (partial eta squared = 0.834).DTI-derived metrics depict significant differences between healthy brains and brains with GBM, with specific magnitudes and correlations. This study provides reference data and makes a contribution to decrease the underlying empiricism in the use of DTI parameters in brain imaging.