Pancreatic Antioxidative Defense and Heat Shock Proteins Prevent Islet of Langerhans Cell Death After Chronic Oral Exposure to Cadmium LOAEL Dose.

Cadmium, a hazardous environmental contaminant, is associated with metabolic disease development. The dose with the lowest observable adverse effect level (LOAEL) has not been studied, focusing on its effect on the pancreas. We aimed to evaluate the pancreatic redox balance and heat shock protein (HSP) expression in islets of Langerhans of male Wistar rats chronically exposed to Cd LOAEL doses, linked to their survival. Male Wistar rats were separated into control and cadmium groups (drinking water with 32.5 ppm CdCl2). At 2, 3, and 4 months, glucose, insulin, and cadmium were measured in serum; cadmium and insulin were quantified in isolated islets of Langerhans; and redox balance was analyzed in the pancreas. Immunoreactivity analysis of p-HSF1, HSP70, HSP90, caspase 3 and 9, and cell survival was performed. The results showed that cadmium exposure causes a serum increase and accumulation of the metal in the pancreas and islets of Langerhans, hyperglycemia, and hyperinsulinemia, associated with high insulin production. Cd-exposed groups presented high levels of reactive oxygen species and lipid peroxidation. An augment in MT and GSH concentrations with the increased enzymatic activity of the glutathione system, catalase, and superoxide dismutase maintained a favorable redox environment. Additionally, islets of Langerhans showed a high immunoreactivity of HSPs and minimal immunoreactivity to caspase associated with a high survival rate of Langerhans islet cells. In conclusion, antioxidative and HSP pancreatic defense avoids cell death associated with Cd accumulation in chronic conditions; however, this could provoke oversynthesis and insulin release, which is a sign of insulin resistance.

[Clinician and researcher at the time. Is it possible?] / Clínico e investigador a la vez, ¿se puede?

Research in clinical practice arises as a constant need for improvement to provide better care to patients, train better human resources and make a daily reflection on the amount of scientific information we receive every day. We want to reflect on how the Centro de Adiestramiento en Investigación Clínica (CAIC) from our healthcare activity changed our practice.

La investigación en la práctica clínica surge como una necesidad constante de mejora, a fin de dar una atención de mayor calidad a los pacientes, formar recursos humanos más preparados y hacer una reflexión diaria ante la cantidad de información científica que recibimos todos los días. Queremos hacer una reflexión de como el Centro de Adiestramiento en Investigación Clínica (CAIC) desde nuestra actividad asistencial cambió nuestra práctica.

Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration.

Metabolic diseases are a worldwide health problem. Insulin resistance (IR) is their distinctive hallmark. For their study, animal models that provide reliable information are necessary, permitting the analysis of the cluster of abnormalities that conform to it, its progression, and time-dependent molecular modifications. We aimed to develop an IR model by exogenous insulin administration. The effective dose of insulin glargine to generate hyperinsulinemia but without hypoglycemia was established. Then, two groups (control and insulin) of male Wistar rats of 100 g weight were formed. The selected dose (4 U/kg) was administered for 15, 30, 45, and 60 days. Zoometry, a glucose tolerance test, insulin response, IR, and the serum lipid profile were assessed. We evaluated insulin signaling, glycogenesis and lipogenesis, redox balance, and inflammation in the liver. Results showed an impairment of glucose tolerance, dyslipidemia, hyperinsulinemia, and peripheral and time-dependent selective IR. At the hepatic level, insulin signaling was impaired, resulting in reduced hepatic glycogen levels and triglyceride accumulation, an increase in the ROS level with MAPK-ERK1/2 response, and mild pro-oxidative microenvironmental sustained by MT, GSH, and GR activity. Hepatic IR coincides with additions in MAPK-p38, NF-κB, and zoometric changes. In conclusion, daily insulin glargine administration generated a progressive IR model. At the hepatic level, the IR was combined with oxidative conditions but without inflammation.

Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes.

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.

Pancreas-Liver-Adipose Axis: Target of Environmental Cadmium Exposure Linked to Metabolic Diseases.

Cadmium has been well recognized as a critical toxic agent in acute and chronic poisoning cases in occupational and nonoccupational settings and environmental exposure situations. Cadmium is released into the environment after natural and anthropogenic activities, particularly in contaminated and industrial areas, causing food pollution. In the body, cadmium has no biological activity, but it accumulates primarily in the liver and kidney, which are considered the main targets of its toxicity, through oxidative stress and inflammation. However, in the last few years, this metal has been linked to metabolic diseases. The pancreas-liver-adipose axis is largely affected by cadmium accumulation. Therefore, this review aims to collect bibliographic information that establishes the basis for understanding the molecular and cellular mechanisms linked to cadmium with carbohydrate, lipids, and endocrine impairments that contribute to developing insulin resistance, metabolic syndrome, prediabetes, and diabetes.

ROS and ERK Pathway Mechanistic Approach on Hepatic Insulin Resistance After Chronic Oral Exposure to Cadmium NOAEL Dose.

Cadmium is a critical toxic agent in occupational and non-occupational settings and acute and chronic environmental exposure situations that have recently been associated with metabolic disease development. Until now, the no observed adverse effect level (NOAEL) of cadmium has not been studied regarding insulin resistance development. Therefore, we aimed to monitor whether chronic oral exposure to cadmium NOAEL dose induces insulin resistance in Wistar rats and investigate if oxidative stress and/or inflammation are related. Male Wistar rats were separated into control (standard normocalorie diet + water free of cadmium) and cadmium groups (standard normocalorie diet + drinking water with 15 ppm CdCl2). At 15, 30, and 60 days, oral glucose tolerance, insulin response, and insulin resistance were analyzed using mathematical models. In the liver glycogen, triglyceride, pro- and anti-inflammatory cytokines, cadmium, zinc, metallothioneins, and redox balance were quantified. Immunoreactivity analysis of proteins involved in metabolic and mitogenic insulin signaling was performed. The results showed that a cadmium NOAEL dose after 15 days of exposure causes ROS and mitogenic arm of insulin signaling to increase while hepatic glycogen diminishes. At 30 days, Cd accumulation accentuated ROS production, hepatic triglyceride overaccumulation, and mitogenic signals that develop insulin resistance. Finally, inflammation and lipid peroxidation appear after 60 days of Cd exposure, while lipids and carbohydrate homeostasis deteriorate. In conclusion, environmental exposure to cadmium NAOEL dose causes hepatic Cd accumulation and ROS overproduction that chronically declines the antioxidant defense, deteriorates metabolic homeostasis associated with the mitogenic pathway of insulin signaling, and induces insulin resistance.

Prophylactic Zinc Administration Combined with Swimming Exercise Prevents Cognitive-Emotional Disturbances and Tissue Injury following a Transient Hypoxic-Ischemic Insult in the Rat.

Exercise performance and zinc administration individually yield a protective effect on various neurodegenerative models, including ischemic brain injury. Therefore, this work was aimed at evaluating the combined effect of subacute prophylactic zinc administration and swimming exercise in a transient cerebral ischemia model. The prophylactic zinc administration (2.5 mg/kg of body weight) was provided every 24 h for four days before a 30 min common carotid artery occlusion (CCAO), and 24 h after reperfusion, the rats were subjected to swimming exercise in the Morris Water Maze (MWM). Learning was evaluated daily for five days, and memory on day 12 postreperfusion; anxiety or depression-like behavior was measured by the elevated plus maze and the motor activity by open-field test. Nitrites, lipid peroxidation, and the activity of superoxide dismutase (SOD) and catalase (CAT) were assessed in the temporoparietal cortex and hippocampus. The three nitric oxide (NO) synthase isoforms, chemokines, and their receptor levels were measured by ELISA. Nissl staining evaluated hippocampus cytoarchitecture and Iba-1 immunohistochemistry activated the microglia. Swimming exercise alone could not prevent ischemic damage but, combined with prophylactic zinc administration, reversed the cognitive deficit, decreased NOS and chemokine levels, prevented tissue damage, and increased Iba-1 (+) cell number. These results suggest that the subacute prophylactic zinc administration combined with swimming exercise, but not the individual treatment, prevents the ischemic damage on day 12 postreperfusion in the transient ischemia model.

IncFIB plasmids carrying the resistance gene blaCTX-M-15 in ESBL-producing Escherichia coli clones from pediatric patients.

INTRODUCTION: The emergence of extended-spectrum ß-lactamases (ESBLs)-producing Escherichia coli clones are a public health concern worldwide. Scarce information does exist about the spread of ESBLs-producing E. coli in pediatric patients from developing countries. METHODOLOGY: E. coli strains were analyzed by multilocus-sequence-typing, pulsed-field-gel-electrophoresis and phylogenetic group. The antimicrobial-resistance genes were detected by PCR, and plasmid content by the PCR-based replicon-typing. Horizontal transfer was tested by conjugation and the location of the blaCTX-M-15 gene by Southern blot hybridization. RESULTS: Thirty-two cefotaxime-resistant E. coli were recovered. Eleven of them were ESBL-producing isolates, which were well characterized and ascribed to seven sequence types and five phylogroups. The ESBL CTX-M-15 was the most prevalent enzyme (9 of 11). Plasmids of variable sizes (40-220 kb) were visualized, and the incompatibility (Inc) group FIB plasmid-replicon was detected in the ESBL strains and transferred by conjugation in 45.45% of them. Plasmid-borne toxin-antitoxin systems were the most frequently detected systems, strongly associated to IncF plasmids. The CTX-M-15-encoding gene was located on IncFIB plasmids. CONCLUSIONS: Even though a small number of ESBL-producing strains was recovered, we evidenced that IncFIB plasmids carry the blaCTX-M-15 gene, highlighting the role of IncF-type plasmids in facilitating the spread and maintenance of ESBL-encoding genes, which further favors the rapid increase of the antimicrobial resistance dissemination in disease-causing E. coli strains in pediatric patients.

Clinical monitored in subjects metabolically healthy and unhealthy before and during a SARS-CoV-2 infection- A cross-sectional study in Mexican population.

The COVID-19 disease has forced us to consider the physiologic role of obesity and metabolically healthy and unhealthy status in response to SARS-CoV-2 infection. Hematological, coagulation, biochemical, and immunoinflammatory changes have been informed with a disparity in morbidity and mortality. Therefore, we aimed to investigate the influence of metabolic health on clinical features in a cross-sectional study in Mexican subjects with and without SARS-CoV-2 infection in non-severe stages after a rigorous classification of obese and non-obese subjects who were metabolically healthy and unhealthy. Four groups were formed: 1) metabolically healthy with normal BMI (MHN); 2) metabolically unhealthy with normal BMI (MUN); 3) metabolically healthy obese (MHO); 4) metabolically unhealthy obese (MUO). Serum proinflammatory (TNF-α, MCP-1, IL-1ß, and IL-6) and anti-inflammatory (TGF-ß, IL-1Ra, IL-4, and IL-10) cytokines, hematological parameters, coagulation, and acute phase components were evaluated. Our results showed that MHO people live with inflammaging. Meanwhile, MUN and MUO subjects develop metaflammation. Both inflammaging and metaflammation cause imperceptible modifications on hematological parameters, mainly in leukocyte populations and platelets, as well as acute phase and coagulation components. The statistical analysis revealed that many clinical features are dependent on metabolic health. In conclusion, MHO subjects seem to be transitioning from metabolically healthy to unhealthy, which is accelerated in acute processes, such as SARS-CoV-2 infection. Meanwhile, metabolically unhealthy subjects independently of BMI have a deteriorating immunometabolic status associated with a hyperinflammatory state leading to multi-organ dysfunction, treatment complications, and severe COVID-19 disease.

Effects of chronic taurine administration on healthy pregnant rats and the consequences on the offspring: Datasets for motor tests and oxidative stress.

We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Sprague Dawley rats (SD). At embryonic day 15 (E15), healthy pregnant SD rats were given taurine treatment (50 mg/L drinking water) and then to their male offspring until they reached the age of eight months. We quantify, in the offspring, the concentration of nitric oxide (NO) through the Griess colorimetric reaction [1] and malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) by the Gérard-Monnier technique [2]. The assessment ages for NO and MDA + 4-HDA were at postnatal day 15 (PND15), 1, 3, and 8 months of age. The body weight was measured along with the integral motor behavior in the perinatal stage through the surface righting reflex test at PND5, cliff aversion test at PND9, grip strength test at PND 11, and front limb and hindlimb suspension tests at PND13. The tests were performed accordingly with [3]. The data obtained showed that SD rats with the taurine administration performed poorly in the motor tests compared with the untreated healthy rats. The taurine-treated rats also showed increased lipid peroxidation preferentially in cerebral regions involved in motor activity, such as the medulla oblongata, the subcortical nuclei, and the cerebral cortex. However, the taurine treatment only increased NO concentration in the evaluated cerebral regions at older ages. At E15, taurine plays a pivotal role in the excitatory/inhibitory neuromodulation, presumably by acting as an excitatory neurotransmitter during the GABA-switch [4]. The increase in the taurine concentration during the embryonic period might cause excitotoxicity in healthy brains, which might lead to impairments in the motor development of the offspring. Therefore, the present datasets can be valuable for researchers who attempt to use the taurine supplement on healthy animal models at gestational stages; and explore the relation with taurine intake during pregnancy in human patients. These datasets are related to the article "Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative stress and promoting myelination" [5].

Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production.

CONTEXT: The chronic exposure to Cadmium (Cd) constitute an risk to develop hypertension and cardiovascular diseases associated with the increase of oxidative stress. OBJECTIVE: In this study, we investigate the role of metabolic changes produced by exposure to Cd on the endothelial dysfunction via oxidative stress. METHODS: Male Wistar rats were exposed to Cd (32.5-ppm) for 2-months. The zoometry and blood pressure were evaluated, also glucose and lipids profiles in serum and vascular reactivity evaluated in isolated aorta rings. RESULTS: Rats exposed to Cd showed an increase of blood pressure and biochemical parameters similar to metabolic syndrome. Additionally, rats exposed to Cd showed a reduced relaxation in aortic rings, which was reversed after the addition of SOD and apocynin an inhibitor of NADPH. CONCLUSION: The Cd-exposition induced hypertension and endothelial injury by that modifying the vascular relaxation and develop oxidative stress via NADPH oxidase, superoxide and loss nitric oxide bioavailability.

Neuroplasticity and inflammatory alterations in the nucleus accumbens are corrected after risperidone treatment in a schizophrenia-related developmental model in rats.

Increased dopaminergic activity in the striatum underlies the neurobiology of psychotic symptoms in schizophrenia (SZ). Beyond the impaired connectivity among the limbic system, the excess of dopamine could lead to inflammation and oxidative/nitrosative stress. It has been suggested that atypical antipsychotic drugs attenuate psychosis not only due to their modulatory activity on the dopaminergic/serotonergic neurotransmission but also due to their anti-inflammatory/antioxidant effects. In such a manner, we assessed the effects of the atypical antipsychotic risperidone (RISP) on the structural neuroplasticity and biochemistry of the striatum in adult rats with neonatal ventral hippocampus lesion (NVHL), which is a developmental SZ-related model. RISP administration (0.25 mg/kg, i.p.) ameliorated the neuronal atrophy and the impairments in the morphology of the dendritic spines in the spiny projection neurons (SPNs) of the ventral striatum (nucleus accumbens: NAcc) in the NVHL rats. Also, RISP treatment normalized the pro-inflammatory pathways and induced the antioxidant activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in this model. Our results point to the neurotrophic, anti-inflammatory, and antioxidant effects of RISP, together with its canonical antipsychotic mechanism, to enhance striatum function in animals with NVHL.

Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative stress and promoting myelination.

The taiep rat undergoes hypomyelination and progressive demyelination caused by an abnormal microtubule accumulation in oligodendrocytes, which elicits neuroinflammation and motor behavior dysfunction. Based on taurine antioxidant and proliferative actions, this work explored whether its sustained administration from the embryonic age to adulthood could prevent neuroinflammation, stimulate cell proliferation, promote myelination, and relieve motor impairment. Taurine (50 mg/L of drinking water = 50 ppm) was given to taiep pregnant rats on gestational day 15 and afterward to the male offspring until eight months of age. We measured the levels of nitric oxide (NO), malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), CXCL1, CXCR2 receptor, growth factors (BNDF and FGF2), cell proliferation, and myelin content over time. Integral motor behavior was also evaluated. Our results showed that taurine administration significantly decreased NO and MDA + 4-HDA levels, increased cell proliferation, and promoted myelination in an age- and brain region-dependent fashion compared with untreated taiep rats. Taurine effect on chemokines and growth factors was also variable. Taurine improved vestibular reflexes and limb muscular strength in perinatal rats and fine movements and immobility episodes in adult rats. These results show that chronic taurine administration partially alleviates the taiep neuropathology.

Taurine Increases Zinc Preconditioning-Induced Prevention of Nitrosative Stress, Metabolic Alterations, and Motor Deficits in Young Rats following Intrauterine Ischemia.

Oxygen deprivation in newborns leads to hypoxic-ischemic encephalopathy, whose hallmarks are oxidative/nitrosative stress, energetic metabolism alterations, nutrient deficiency, and motor behavior disability. Zinc and taurine are known to protect against hypoxic-ischemic brain damage in adults and neonates. However, the combined effect of prophylactic zinc administration and therapeutic taurine treatment on intrauterine ischemia- (IUI-) induced cerebral damage remains unknown. The present work evaluated this issue in male pups subjected to transient IUI (10 min) at E17 and whose mothers received zinc from E1 to E16 and taurine from E17 to postnatal day 15 (PND15) via drinking water. We assessed motor alterations, nitrosative stress, lipid peroxidation, and the antioxidant system comprised of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Enzymes of neuronal energetic pathways, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), were also evaluated. The hierarchization score of the protective effect of pharmacological strategies (HSPEPS) was used to select the most effective treatment. Compared with the IUI group, zinc, alone or combined with taurine, improved motor behavior and reduced nitrosative stress by increasing SOD, CAT, and GPx activities and decreasing the GSSG/GSH ratio in the cerebral cortex and hippocampus. Taurine alone increased the AST/ALT, LDH/ALT, and AST/LDH ratios in the cerebral cortex, showing improvement of the neural bioenergetics system. This result suggests that taurine improves pyruvate, lactate, and glutamate metabolism, thus decreasing IUI-caused cerebral damage and relieving motor behavior impairment. Our results showed that taurine alone or in combination with zinc provides neuroprotection in the IUI rat model.

Sodium metavanadate treatment improves glycogen levels in multiple tissues in a model of metabolic syndrome caused by chronic cadmium exposure in Wistar rats.

Cadmium, one of the more hazardous environmental contaminants, has been proposed as a metabolic disruptor. Vanadium has emerged as a possible treatment for metabolic diseases. Both metals are important in public health. We aimed to investigate whether vanadium treatment is effective against metabolic disturbances caused by chronic exposure to the lowest-observable adverse effect level of cadmium. Male Wistar rats were exposed to cadmium (32.5 ppm) in drinking water for 3 months. Metabolic complications such as overweight, visceral adipose gain, hyperglycemia, impaired glucose tolerance, and dyslipidemia were detected, and low glycogen levels and steatosis were observed in the tissues. Then, the control and treated animals were subdivided and treated with a solution of 5 µM NaVO3/kg/twice a week for 2 months. The control-NaVO3 group did not show zoometric or metabolic changes. A strong interaction of NaVO3 treatment over cadmium metabolic disruption was observed. The vanadium accumulation diminished cadmium concentration in tissues. Also, vanadium interaction improved glucose homeostasis. The major effect was observed on glycogen synthesis, which was fully recovered in all tissues analyzed. Additionally, vanadium treatment prevented overweight and visceral fat accumulation, improving BMI and the percentage of fat. However, NaVO3 treatment did not have an effect on dyslipidemia or steatosis. In conclusion, this work shows that vanadium administration has a strong effect against metabolic disturbances caused by chronic cadmium exposure, observing powerful interaction on glucose homeostasis.

Kidney Adaptations Prevent Loss of Trace Elements in Wistar Rats with Early Metabolic Syndrome.

Metabolic syndrome (MetS) represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance. These metabolic derangements present significant risk factors for chronic kidney disease that carries to loss of essential micronutrients, which accelerates comorbidity apparition. The work aimed was to evaluate the trace element homeostasis regarding morphological adaptations and renal function in MetS early-onset. Fifty male Wistar rats were divided into two groups: (a) control group and (b) hypercaloric diet group that developed MetS early-onset after 3 months. Classical zoometric parameters do not show changes; however, biochemical modifications were observed such as hyperglycemia, protein glycation, insulin resistance, dyslipidemia, hyperinsulinemia, and hypoadiponectinemia. MetS early-onset group observed renal structural modifications, but no functional changes. The structural modifications observed were minimal glomerular injury, glomerular basement membrane thickening, as well as mesangial and tubular cells that showed growth and proliferation. In serum and kidney (cortex and medulla), the concentrations of Zn, Fe, Cr, Mg, Mn, Cu, Co, and Ni were no differences between the experimental groups, but excretory fractions of these were lower in the hypercaloric diet group. In conclusion, MetS early-onset coexist renal structural modification and a hyperreabsorptive activity of essential trace elements that avoid its loss; thus, the excretory fraction of oligo-elements could be used a biomarker of early renal injury caused by metabolic diseases in the clinical practice.

Amphetamine sensitization alters hippocampal neuronal morphology and memory and learning behaviors.

It is known that continuous abuse of amphetamine (AMPH) results in alterations in neuronal structure and cognitive behaviors related to the reward system. However, the impact of AMPH abuse on the hippocampus remains unknown. The aim of this study was to determine the damage caused by AMPH in the hippocampus in an addiction model. We reproduced the AMPH sensitization model proposed by Robinson et al. in 1997 and performed the novel object recognition test (NORt) to evaluate learning and memory behaviors. After the NORt, we performed Golgi-Cox staining, a stereological cell count, immunohistochemistry to determine the presence of GFAP, CASP3, and MT-III, and evaluated oxidative stress in the hippocampus. We found that AMPH treatment generates impairment in short- and long-term memories and a decrease in neuronal density in the CA1 region of the hippocampus. The morphological test showed an increase in the total dendritic length, but a decrease in the number of mature spines in the CA1 region. GFAP labeling increased in the CA1 region and MT-III increased in the CA1 and CA3 regions. Finally, we found a decrease in Zn concentration in the hippocampus after AMPH treatment. An increase in the dopaminergic tone caused by AMPH sensitization generates oxidative stress, neuronal death, and morphological changes in the hippocampus that affect cognitive behaviors like short- and long-term memories.

Changes in nitric oxide, zinc and metallothionein levels in limbic regions at pre-pubertal and post-pubertal ages presented in an animal model of schizophrenia.

Recent data suggest that rats with neonatal ventral hippocampal lesion (NVHL) show changes related to inflammatory processes and oxidative stress at the prefrontal cortex (PFC) level at post-pubertal age. The NVHL model is considered an animal model in schizophrenia. Here we analyzed the levels of nitrite, zinc, and metallothionein (MT) in cortical and subcortical regions of NVHL rats at pre-pubertal and post-pubertal ages. Nitric oxide (NO) levels were evaluated through measurement of nitrite levels. The locomotor activity was also evaluated in a novel environment. Animals with NVHL showed an increase in locomotor activity only at post-pubertal age. Furthermore, at pre-pubertal age, NVHL rats showed an increase in NO levels in ventral and dorsal hippocampus, thalamus, Caudate-putamen (CPu) and brainstem, in zinc levels in ventral and dorsal hippocampus, and CPu, and the MT level also in the ventral hippocampus and occipital cortex. In addition, at pre-pubertal age, a reduction in MT levels was also found in the PFC, parietal and temporal cortices, the CPu and the cerebellum. However, after puberty, NVHL caused an increase in NO levels in the PFC, and also zinc levels in the PFC and occipital and parietal cortices, with a reduction in MT levels in the thalamus and NAcc. Our results show the changes of these three molecules over time, among lesion (PD7), pre-pubertal and post-pubertal ages. This suggests changes at pre-pubertal age directly related to the site of the lesion, while at post-pubertal age, our data highlight changes in the PFC, a region mainly involved in schizophrenia.

Síntomas del tracto urinario inferior como reflejo del ambiente laboral hospitalario en médicos residentes / Lower urinary tract symptoms in medical residents as reflection of a stressful work environment

OBJETIVO: Determinar si la presencia de síntomas del tracto urinario inferior moderados a severos en médicos residentes se asocian con la exposición a bullying laboral. MATERIAL Y MÉTODOS: Estudio transversal realizado en médicos residentes. Se definió síntomas del tracto urinario inferior moderados a severos como más de 8 puntos en el Índice Internacional de Síntomas Prostáticos. Los residentes se consideraron como expuestos a bullying si el puntaje total en la Escala de Conductas Negativas era mayor a 41 puntos. Se consideró como bullying percibido cualquier respuesta positiva en una pregunta específica para medir esta variable. Se realizó un análisis bivariado utilizando la Χ² para determinar diferencias estadísticas entre la presencia de síntomas del tracto urinario inferior y la exposición a ambos tipos de bullying. La magnitud y dirección de las asociaciones se establecieron calculando el Odds Ratio con un intervalo de confianza al 95%. RESULTADOS: Se incluyeron 209 residentes, 63% hombres; 68% refirieron algún síntoma del tracto urinario, de los cuales, 56% fueron leves, 10% moderados y 2% severos. La prevalencia de bullying fue de 42% y el bullying percibido se presentó en el 39%. Los residentes con ≥ 8 puntos en el Índice Internacional de Síntomas Prostáticos tuvieron mayor riesgo de estar expuestos a bullying (OR: 2,8, IC 95%: 1,1-6,7, p = 0,01) y bullying percibido (OR: 3,1 95% CI: 1,3-7,5, p 0,00). Ser mujer se asoció con mayor riesgo de presentar síntomas del tracto urinario inferior (OR: 2,8, IC 95%: 1,1-6,6, p = 0,01). CONCLUSIONES: Los médicos residentes con síntomas del tracto urinario moderados o severos pueden estar relacionados a bullying. Ser mujer se asocia a mayor riesgo de presentar STUI

OBJECTIVE: To determine if the presence of moderate to severe lower urinary tract symptoms in medical resident are associated with workplace bullying. MATERIAL AND METHODS: Cross-sectional study conducted in medical residents. Moderate to severe lower urinary tract symptoms were defined as greater than 8 points on the International Prostate Symptom Score. Residents were classified as bullied if their total score on the Negative Acts Questoinnarie-Revised, was above 41 points. Perceived bullying was considered as present when any positive answer was documented in a specific question to measure this variable. Bivariate analysis to determine statistical differences between presence of lower urinary tract symptoms and exposure to both types of bullying was performed using Χ². The magnitude and directions of all associations were determined by calculating the Odds Ratio with 95% level of confidence. RESULTS: 209 residents were included, 63% men; 68% reported at least one lower urinary tract symptom, of which, 56% were mild, 10% moderate and 2% severe. The prevalence of bullying was 42% while perceived bullying was present in 39%. Residents with ≥ 8 points on the International Prostate Symptom Score had higher risk of being exposed to bullying (OR: 2.8, 95% CI: 1.1-6.7, p = 0.01) and/or perceived bullying (OR: 3.1 95% CI: 1.3-7.5, p = 0.00). Female gender had greater risk than man for presenting lower urinary tract symptoms at basal state (OR: 2.8, 95% CI: 1.1-6.6, p = 0.01). CONCLUSIONS: Medical residents with moderate or severe urinary tract symptoms may be related to bullying. Being a woman is associated with an increased risk of developing LUTS