Pediatric tuberculosis in Mexico and the COVID-19 phenomenon: Past and present.

In endemic regions, tuberculosis in children constitutes a bigger fraction of total cases as compared to those in low endemic regions, regardless of the implications, this phenomenon has been historically neglected. Pediatric tuberculosis has an insidious onset and quickly develops into disseminated disease and the young are at a special risk for dissemination. Some studies suggest that measures to contain adult tuberculosis are not enough to manage tuberculosis in children, meaning that pediatric tuberculosis needs dedicated attention. Children are harder to diagnose than adults, because collecting samples is difficult, and their bacterial yield is low. In endemic countries, such as Mexico, where contact with Mycobacterium tuberculosis is common, immunological tests are inconsistent, especially in immunocompromised children. With the disruption of Mexican healthcare services by the COVID-19 pandemic, there is an uncertainty of how the situation has evolved, current data about tuberculosis indicates a drop in the national report of cases: 15.4 per 100,000 persons in 2021, compared with pre-COVID 2019 17.7 per 100,000 persons, a small increase in mortality: 1.7 per 100,000 in 2021 compared with 2019 1.6 per 100,000, a drop in treatment success: 80.4% in 2021 compared with 85.4% in 2019, and a decrease in national vaccination rates: an estimate of 86.6% children between 1 and 2 years-old were vaccinated in 2021 compared with 97.3% reported national rate in 2018-2019. There is a need for new research on regions with high tuberculosis incidence, to clarify the current situation of pediatric tuberculosis and improve epidemiological surveillance.

Repurposing Simvastatin in Parkinson's Disease Model: Protection Is throughout Modulation of the Neuro-Inflammatory Response in the Substantia nigra.

Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.

Effects of postnatal exposure to cadmium on male sexual incentive motivation and copulatory behavior: Estrogen and androgen receptors expression in adult brain rat.

There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1-56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -ß), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.

Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence.

BACKGROUND AND OBJECTIVE: One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. METHODS: A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. RESULTS: A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). CONCLUSIONS: OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar.

Impact of a One-Stop Hematuria Clinic on Overall Survival and Bladder Tumor Recurrence

Background and Objective: One-stop clinics have emerged as a tool to optimize the therapeutic management of cancer patients. The main purpose of this study was to assess the role of the one-stop hematuria clinic (OSHC), as compared to a conventional clinic (CC), on the overall and disease-free survival of patients with bladder cancer. Methods: A five-year follow-up retrospective and single-center study was conducted in patients with primary bladder tumor diagnosed between 2006 and 2015. The primary outcomes were five-year overall survival and one-year relapse rate. Results: A total of 394 patients (160 in OSHC and 234 in CC) were included. No differences were observed in terms of age, sex, smoking habit or risk group between the OSHC and CC groups. The average times from first symptom to diagnosis (24.9 ± 29.1 vs. 100.7 ± 93.6 days) and from first symptom to treatment (70.2 ± 34.0 vs. 155.0 ± 102.9 days) were significantly lower in the OSHC group than in the CC group (p < 0.001 each). There was no significant difference in the five-year survival rate between OSHC and CC (103/160 vs. 150/234, respectively; p = 0.951), although the proportion of relapses during the first year was significantly lower in the OSHC group (35/139, 25.2%) than in the CC one (74/195, 38.0%; p = 0.02). Conclusions: OSHC significantly reduced the diagnosis and treatment times. The early-relapse rate was significantly lower in the OSHC group, although the five-year survival rate was similar (AU)

Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury.

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride. Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury. The aim of this study was to analyze the role of α2-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage. The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours, 3 days, and 20 days after ferrous chloride-induced cortical injury: saline, clonidine, efaroxan (a selective antagonist of α2-adrenergic receptors) and clonidine + efaroxan. The sensorimotor score, the immunohistochemical staining for α2A-adrenergic receptors, and norepinephrine levels were evaluated. Eight hours post-injury, the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased, and these effects were maintained 3 days post-injury. However, 20 days later, clonidine administration diminished norepinephrine levels in the pons compared with the sham group. This effect was accompanied by sensorimotor deficits. These effects were blocked by efaroxan. In conclusion, an increase in α2-adrenergic receptor levels was observed after injury. Clonidine restores motor deficits in rats recovering from cortical injury, an effect that was prevented by efaroxan. The underlying mechanisms involve the stimulation of hypersensitive α2-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α2 receptor agonists might restore deficits or impede rehabilitation in patients with brain injury, and therefore pharmacological therapies need to be prescribed cautiously to these patients.

Non-pancreatic Pseudocyst Presenting as a Giant Retroperitoneal Mass.

OBJECTIVE: To assess the non-pancreatic retroperitoneal pseudocyst in the differenctial diagnosis of retroperitoneal cystic masses. METHODS: To report a case. RESULTS: We present a case of a 50-year-old woman with symptoms of pain and a palpable abdominal mass. In imaging studies a 13-cm retroperitoneal cystic mass with left ureterohydronephrosis was observed. Surgical excision of the mass was performed with pathological diagnosis of non-pancreatic retroperitoneal pseudocyst. CONCLUSION: Non-pancreatic retroperitoneal pseudocyst is an entity with a very low incidence, benign, usually asymptomatic. It can grow compressing on adjacent structures. The definitive diagnosis is histopathological and the treatment is surgical. It's important to carry out complete exeresis to avoid recurrences.

Relevance of biometals during neuronal differentiation and myelination: in vitro and in vivo studies.

Biometals are essential during the development of the central nervous system (CNS) since they participate in the organization and regulation of multiple processes related with the proper organization and functioning of brain structures. Neuronal differentiation is a specialized and complex process that occurs actively from embryonic development to the first years of life and is even maintained in specific areas of the mammalian adult brain. In this review, we focus on describing the cellular and molecular mechanisms of trace biometals such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) on neuronal specialization, comprising from brain uptake to effects on synaptogenesis, axonal outgrowth, myelination, and cellular and neurochemical phenotype determination. We highlight the relevance of biometals in the proper brain functioning by discussing some of the potentially detrimental effects when biometal dyshomeostasis occurs in the brain. Finally, future directions are proposed for exploring the relevance of biometals in brain function using pharmacological, molecular, and analytical approaches.

[Usefulness of contrast enhanced ultrasound for evaluation of cystic renal masses.] / Utilidad de la ecografía con contraste en el estudio de las lesiones renales quísticas.

OBJECTIVE: Contrast enhanced ultrasound(CE) consists of the intravenous injection of gasmicrobubbles and their detection within the kidney in differentphases. CE is more accurate than contrast enhancedtomography for detection of septa and wall thicknessvascularization in cystic renal lesions. The purposes ofthis study are to confirm the usefulness of this tool in thecharacterization of complex cystic renal masses and toassess its histological correlation. MATERIALS AND METHODS: Retrospective observationalstudy of 78 patients with complex or indeterminatecystic renal masses who underwent a CE betweenJanuary 2015 - January 2020. RESULTS: Lesions with high suspicion of malignancy(Bosniak III and IV) were identified in 35 patients(45%). A surgical approach was taken in 23 (30%): 18patients with histology of renal cell carcinoma, and onlyin 4 the histology was benign. CE involved a change intherapeutic management due to better definition of thelesion in 48 patients (61.5%). CE has a sensitivity 100%,specificity 91.5%, PPV 81.8%, NPV 100%, and CE hadan important confidence level showed by the area underthe ROC curve (AUC = 0.968). CONCLUSIONS: CE is a useful tool in the characterizationof complex cystic renal lesions. It allows abetter definition of the Bosniak classification for thoseindeterminate or doubtful cases on CT that couldgenerate a change in the therapeutic attitude in manycases. It has a good image - histology relation.

OBJETIVO: La ecografía con contraste(EC) consiste en la inyección intravenosa demicroburbujas de gas y su detección dentro del riñón endistintas fases. En las lesiones renales quísticas la EC esmás sensible que la tomografía con contraste para valorarla vascularización de septos y tabiques. Los objetivosde este trabajo son confirmar la utilidad de esta técnicaen la caracterización de las lesiones renales quísticascomplejas y estudiar su relación anatomo-patológica MATERIAL Y MÉTODOS: Estudio observacionalretrospectivo de 78 pacientes con masas renales quísticascomplejas o dudosas en los que se les realizó una ECentre enero 2015 ­ enero 2020. RESULTADOS: En 35 pacientes (45%) se identificaronlesiones con alta sospecha de malignidad (BosniakIII y IV). En 23 (30%) se tomó una actitud quirúrgica: 18con anatomía patológica de carcinoma de células renalesy 4 con anatomía patológica benigna. En 48 pacientes(61,5%) supuso un cambio de actitud terapéuticadebido a la mejor definición de la lesión. La EC presentóuna sensibilidad 100%, especificidad 91,5%, VPP 81,8%,VPN 100%, con un nivel confianza diagnóstica mostradopor el área bajo la curva ROC (AUC = 0,968).CONCLUSIÓN: La EC es una herramienta útil en lavaloración de quistes renales complejos. Permite unamejor definición de la clasificación Bosniak para aquelloscasos indeterminados o dudosos en TC, que implicóun cambio de actitud terapéutica en muchos casos. Además,presenta una buena relación imagen-histología.

Utilidad de la ecografía con contraste en el estudio de las lesiones renales quísticas / Usefulness of contrast enhanced ultrasound for evaluation of cystic renal masses

OBJETIVO: La ecografía con contraste (EC) consiste en la inyección intravenosa demicroburbujas de gas y su detección dentro del riñón endistintas fases. En las lesiones renales quísticas la EC esmás sensible que la tomografía con contraste para valorar la vascularización de septos y tabiques. Los objetivosde este trabajo son confirmar la utilidad de esta técnicaen la caracterización de las lesiones renales quísticascomplejas y estudiar su relación anatomo-patológicaMATERIAL Y MÉTODOS: Estudio observacionalretrospectivo de 78 pacientes con masas renales quísticas complejas o dudosas en los que se les realizó una ECentre enero 2015 – enero 2020.RESULTADOS: En 35 pacientes (45%) se identificaron lesiones con alta sospecha de malignidad (BosniakIII y IV). En 23 (30%) se tomó una actitud quirúrgica: 18con anatomía patológica de carcinoma de células renales y 4 con anatomía patológica benigna. En 48 pacientes (61,5%) supuso un cambio de actitud terapéuticadebido a la mejor definición de la lesión. La EC presentóuna sensibilidad 100%, especificidad 91,5%, VPP 81,8%,VPN 100%, con un nivel confianza diagnóstica mostradopor el área bajo la curva ROC (AUC = 0,968).CONCLUSIÓN: La EC es una herramienta útil en lavaloración de quistes renales complejos. Permite unamejor definición de la clasificación Bosniak para aquellos casos indeterminados o dudosos en TC, que implicóun cambio de actitud terapéutica en muchos casos. Además, presenta una buena relación imagen-histología. (AU)

OBJECTIVE: Contrast enhanced ultrasound (CE) consists of the intravenous injection of gasmicrobubbles and their detection within the kidney in different phases. CE is more accurate than contrast enhanced tomography for detection of septa and wall thicknessvascularization in cystic renal lesions. The purposes ofthis study are to confirm the usefulness of this tool in thecharacterization of complex cystic renal masses and toassess its histological correlation.MATERIALS AND METHODS: Retrospective observational study of 78 patients with complex or indeterminate cystic renal masses who underwent a CE betweenJanuary 2015 – January 2020.RESULTS: Lesions with high suspicion of malignancy (Bosniak III and IV) were identified in 35 patients(45%). A surgical approach was taken in 23 (30%): 18patients with histology of renal cell carcinoma, and onlyin 4 the histology was benign. CE involved a change intherapeutic management due to better definition of thelesion in 48 patients (61.5%). CE has a sensitivity 100%,specificity 91.5%, PPV 81.8%, NPV 100%, and CE hadan important confidence level showed by the area under the ROC curve (AUC = 0.968). CONCLUSIONS: CE is a useful tool in the characterization of complex cystic renal lesions. It allows abetter definition of the Bosniak classification for those indeterminate or doubtful cases on CT that couldgenerate a change in the therapeutic attitude in manycases. It has a good image – histology relation. (AU)

Characterization of pain-related behaviors, changes in bone microarchitecture and sensory innervation induced by chronic cadmium exposure in adult mice.

Because of the relative lack of understanding of the neurobiological mechanisms that drive toxic effects of cadmium in bone, the purpose of this study was to characterize a preclinical model of chronic cadmium exposure. Adult male C57BL/6 J mice were exposed to cadmium 25 mg/L (as CdCl2) in drinking water for 16 weeks. During this time, pain-related behaviors including hindpaw mechanical sensitivity and vertical rears were evaluated every four weeks. We assessed changes in bone microarchitecture at the femoral neck and L5 vertebra by microcomputed tomography and quantified the density of nerve fibers expressing PGP 9.5 (a pan-neuronal marker) and CGRP (a marker of sensory nerve fibers subfamily) at the femoral neck and glabrous skin of the hindpaw using immunohistochemistry. Cadmium exposure produced mechanical hypersensitivity in both hindpaws along with decreased rearing activity (surrogate for musculoskeletal-related pain) without affecting the horizontal activity (a measure of locomotor behavior) in comparison to the control group. Intraperitoneal acute treatment with morphine and gabapentin reversed pain-related behaviors in cadmium-exposed mice. Furthermore, exposure to cadmium resulted in significant trabecular bone deterioration at the femoral neck and L5 vertebra. We also observed a significant reduction in the density of both CGRP+ and PGP 9.5+ nerve fibers in the femoral neck, but not in the hindpaw glabrous skin, suggesting tissue-dependent neurotoxicity. This model may help in developing a mechanism-based understanding of the factors that generate and maintain musculoskeletal pain and bone loss caused by chronic cadmium exposure and in translating these findings into new therapies for treating cadmium-induced bone toxicity.

The C-terminal domain of the heavy chain of tetanus toxin prevents the oxidative and nitrosative stress induced by acute toxicity of 1-methyl-4-phenylpyridinium, a rat model of Parkinson's disease.

The recombinant carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts neuroprotective and neurorestorative effects on the dopaminergic system of animal models of Parkinson's disease (PD). The present study aimed to determine the effect of the Hc-TeTx fragment on the markers of oxidative stress and nitrosative stress generated by the acute toxicity of 1-methyl-4-phenylpyridinium (MPP+). For this purpose, the Hc-TeTx fragment was administered once a day in three 20 µg/kg consecutive injections into the grastrocnemius muscle of the rats, with an intra-striatal unilateral injection of 1 µL of MPP+ [10 µg/mL] then administered in order to cause a dopaminergic lesion. The results obtained show that the rats treated with Hc-TeTx plus MPP+ presented an increase in the expression of tyrosine hydroxylase (TH), a significantly greater decrease in the levels of the markers of oxidative stress, nitrosative stress, and neurodegeneration than that observed for the group injured with only MPP+. Moreover, it was observed that total superoxide dismutase (SOD) and copper/zinc SOD activity increased with the administration of Hc-TeTx. Finally, immunoreactivity levels were observed to decrease for the levels of 3-nitrotyrosine and the glial fibrillary acidic protein in the ipsilateral striatum of the rats treated with Hc-TeTx plus MPP+, in contrast with those lesioned with MPP+ alone. Our results demonstrate that the recombinant Hc-TeTx fragment may be a potent antioxidant and, therefore, could be suggested as a therapeutic tool against the dopaminergic neuronal impairment observed in the early stages of PD.

Captopril and losartan attenuate behavioural sensitization in mice chronically exposed to toluene.

Inhalants are consumed worldwide for recreational purposes. The main component found in many inhalants is toluene. One of the most deleterious behavioural effects caused by chronic exposure to inhalants is addiction. This response has been associated with activation of the mesolimbic dopaminergic pathway, and it is known that the renin angiotensin system plays a role in the modulation of this dopaminergic system. In the present work, we hypothesize that blockade of the RAS with angiotensin converting enzyme inhibitors or angiotensin II type 1 receptor blockers is able to attenuate the addictive response induced by toluene. We exposed mice to toluene for four weeks to induce locomotor sensitization. In the second phase of the work, captopril or losartan were administered for 20 days. Subsequently, the expression of behavioural sensitization was evaluated with a toluene challenge. To exclude false associations between the observed responses and treatments, motor coordination and blood pressure were analysed in animals treated with captopril or losartan. At the end of the behavioural studies, animal brains were harvested and Ang II/Ang-(1-7) and Ang-(1-7)/Ang II ratios were analysed in the nucleus accumbens (NAc) and prefrontal cortex (PFCx). The results showed that toluene induced behavioural sensitization, while captopril or losartan treatment attenuated the expression of this response. No significant differences were observed in motor coordination or blood pressure. Repeated toluene administration decreased Ang-(1-7)/Ang II ratio in the PFCx. On the other hand, treatment with captopril or losartan decreased the Ang II/Ang-(1-7) ratio and enhanced the Ang-(1-7)/Ang II ratio in the NAc. This work suggests that blockade of RAS attenuates the toluene-induced behavioural sensitization.

[Unusual presentation of metastasis of prostate carcinoma as a mediastinal mass: A case report and a brief review of the literature.] / Presentación inusual de metástasis de carcinoma prostático como masa mediastínica: descripción de un caso y breve revisión de la literatura.

OBJECTIVE: To assess the metastasic prostatecancer in the differenctial diagnosis of mediastinal masses. METHODS: To report a case. RESULTS: We present the case of a 78-year-old male patientwith a diagnosis of prostate cancer with a mediastinalmass compatible with prostate metastasis. CONCLUSION: Mediastinum is a very rare site for prostatecancer metastasis, but it must be considered in thedifferential diagnosis of mediastinal masses. Treatment isthe usual for metastatic prostate cancer.

OBJETIVO: Considerar el cáncer de próstatametastásico en el diagnóstico diferencial de masas mediastínicas. MÉTODOS: Presentación de un caso clínico. RESULTADOS: Se presenta el caso de un paciente varónde 78 años con diagnóstico de cáncer de próstata en elque se objetiva una masa mediastínica compatible conmetástasis prostática. CONCLUSIÓN: El mediastino es un lugar muy infrecuentede metástasis de cáncer de próstata, pero hay que considerarloen el diagnóstico diferencial de masas mediastínicas.El tratamiento es el estándar del cáncer de próstatametastásico.

Presentación inusual de metástasis de carcinoma prostático como masa mediastínica: descripción de un caso y breve revisión de la literatura / Unusual presentation of prostate carcinoma metastases as a mediastinal mass: description of a case and brief review of the literature

Objetivo: Considerar el cáncer de próstatametastásico en el diagnóstico diferencial de masas mediastínicas. Métodos: Presentación de un caso clínico.Resultados: Se presenta el caso de un paciente varónde 78 años con diagnóstico de cáncer de próstata en elque se objetiva una masa mediastínica compatible conmetástasis prostática. Conclusion: El mediastino es un lugar muy infrecuentede metástasis de cáncer de próstata, pero hay que considerarlo en el diagnóstico diferencial de masas mediastínicas. El tratamiento es el estándar del cáncer de próstatametastásico.(AU)

Objetive: To assess the metastasic prostatecancer in the differenctial diagnosis of mediastinal masses. Methods: To report a case. Results: We present the case of a 78-year-old male patient with a diagnosis of prostate cancer with a mediastinalmass compatible with prostate metastasis. Conclusion: Mediastinum is a very rare site for prostate cancer metastasis, but it must be considered in thedifferential diagnosis of mediastinal masses. Treatment isthe usual for metastatic prostate cancer.(AU)

The acute systemic toxicity of thallium in rats produces oxidative stress: attenuation by metallothionein and Prussian blue.

Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental contamination by Tl has been reported in several countries, urging the need for studies to determine the impact of endogenous and exogenous mechanisms preventing thallium toxicity. The cytoprotective effect of metallothionein (MT), a protein with high capacity to chelate metals, at two doses (100 and 600 µg/rat), was tested. Prussian blue (PB) (50 mg/kg) was administered alone or in combination with MT. A dose of Tl (16mg/kg) was injected i.p. to Wistar rats. Antidotes were administered twice daily, starting 24h after Tl injection, for 4 days. Tl concentrations diminished in most organs (p < 0.05) by effect of PB, alone or in combination with MT, whereas MT alone decreased Tl concentrations in testis, spleen, lung and liver. Likewise, brain thallium also diminished (p < 0.05) by effect of PB and MT alone or in combination in most of the regions analyzed (p < 0.05). The greatest diminution of Tl was achieved when the antidotes were combined. Plasma markers of renal damage increased after Tl administration, while PB and MT, either alone or in combination, prevented the raise of those markers. Only MT increased the levels of reduced glutathione (GSH) in the kidney. Finally, increased Nrf2 was observed in liver and kidney, after treatment with MT alone or in combination with PB. Results showed that MT alone or in combination with PB is cytoprotective after thallium exposure.

Glutamate, Glutamine, GABA and Oxidative Products in the Pons Following Cortical Injury and Their Role in Motor Functional Recovery.

Brain injury leads to an excitatory phase followed by an inhibitory phase in the brain. The clinical sequelae caused by cerebral injury seem to be a response to remote functional inhibition of cerebral nuclei located far from the motor cortex but anatomically related to the injury site. It appears that such functional inhibition is mediated by an increase in lipid peroxidation (LP). To test this hypothesis, we report data from 80 rats that were allocated to the following groups: the sham group (n = 40), in which rats received an intracortical infusion of artificial cerebrospinal fluid (CSF); the injury group (n = 20), in which rats received CSF containing ferrous chloride (FeCl2, 50 mM); and the recovery group (n = 20), in which rats were injured and allowed to recover. Beam-walking, sensorimotor and spontaneous motor activity tests were performed to evaluate motor performance after injury. Lipid fluorescent products (LFPs) were measured in the pons. The total pontine contents of glutamate (GLU), glutamine (GLN) and gamma-aminobutyric acid (GABA) were also measured. In injured rats, the motor deficits, LFPs and total GABA and GLN contents in the pons were increased, while the GLU level was decreased. In contrast, in recovering rats, none of the studied variables were significantly different from those in sham rats. Thus, motor impairment after cortical injury seems to be mediated by an inhibitory pontine response, and functional recovery may result from a pontine restoration of the GLN-GLU-GABA cycle, while LP may be a primary mechanism leading to remote pontine inhibition after cortical injury.

Antioxidant Effect of Hydroxytyrosol, Hydroxytyrosol Acetate and Nitrohydroxytyrosol in a Rat MPP+ Model of Parkinson's Disease.

3,4-Dihydroxyphenyl ethanol, known as hydroxytyrosol (HTy), is a phenylpropanoid found in diverse vegetable species. Several studies have demonstrated that HTy is a potent antioxidant. Thus, our study is aimed to evaluate the antioxidant effect of HTy and its derivatives, hydroxytyrosol acetate (HTyA) and nitrohydroxytyrosol (HTyN), in a model of oxidative stress induced by 1-methyl-4-phenylpyridinium (MPP+) in rats. Rats were administered intravenously (i.v.) in the tail with 1 mL saline solution or polyphenol compound (1.5 mg/kg) 5 min before intrastriatal infusion of 10 µg MPP+/8 µL. We found that rats injured with MPP+, pretreatment with HTy, HTyA or HTyN significantly decreased ipsilateral turns. This result was consistent with a significant preservation of striatal dopamine levels and decreased lipid fluorescence products (LFP), a marker of oxidative stress. Brain GSH/GSSG ratio, from rats pretreated with HTy or HTyN showed a significant preservation of that marker, decreased as a consequence of MPP+-induced oxidative damage. These results show an antioxidant effect of HTy, HTyA and HTyN in the MPP+ model of Parkinson's disease in the rat.

Chronic lead exposure alters photic entrainment of locomotor activity rhythm and neuronal photoactivation in the suprachiasmatic nucleus of the adult rat.

Chronic lead (Pb) exposure affects the circadian physiological processes regulated by suprachiasmatic nucleus (SCN), which is synchronized (entrainment) by light. Disorders in the entrainment capacity of an organism alter its performance to interact with the environment, thus affecting its health status. The objectives of the present study were to evaluate whether chronic early Pb exposure affects the entrainment of the circadian rhythm of locomotor activity by light and to explore the possible mechanisms involved. Adult male Wistar rats, control and chronically exposed to Pb (320 ppm) in drinking water from gestation to adult age, were used. Assessment of the metal level showed a significant increase of Pb in the blood, hypothalamus and prefrontal cortex of the experimental rats. Continuous registrations of locomotor activity (12 h:12 h light-dark cycle) depicted that Pb induces important delay of this activity when the light was turned off. The Pb exposed animals entrained faster with a photoperiod delay of 6 h, (lights on at 13:00 h), and maintained the significant delay in the onset of activity at lights out. In continuous darkness, the animals were exposed to a light pulse at circadian time 23. This resulted in a significant decrease of photo-stimulated neurons (immunoreactivity to c-Fos) in the SCN of the metal-exposed animals. These results show that chronic early Pb exposure alters the photic entrainment of the rhythm of locomotor activity, which is evidenced by a significant decrease in both the number of photo-stimulated neurons and neuronal population (Nissl stain) of the SCN.

Copper biodistribution after acute systemic administration of copper gluconate to rats.

Neurodegenerative disorders have been linked to the decrease of copper concentrations in different regions of the brain. Therefore, intake of micronutrient supplements could be a therapeutic alternative. Since the copper distribution profile has not been elucidated yet, the aim of this study was to characterize and to analyze the concentration profile of a single administration of copper gluconate to rats by two routes of administration. Male Wistar rats were divided into three groups. The control group received vehicle (n = 5), and the experimental groups received 79.5 mg/kg of copper orally (n = 4-6) or 0.64 mg/kg of copper intravenously. (n = 3-4). Blood, striatum, midbrain and liver samples were collected at different times. Copper concentrations were assessed using atomic absorption spectrophotometry. Copper concentration in samples from the control group were considered as baseline. The highest copper concentration in plasma was observed at 1.5 h after oral administration, while copper was quickly compartmentalized within the first hour after intravenous administration. The striatum evidenced a maximum metal concentration at 0.25 h for both routes of administration, however, the midbrain did not show any change. The highest concentration of the metal was held by the liver. The use of copper salts as replacement therapy should consider its rapid and discrete accumulation into the brain and the rapid and massive distribution of the metal into the liver for both oral and intravenous routes. Development of controlled-release pharmaceutical formulations may overcome the problems that the liver accumulation may imply, particularly, for hepatic copper toxicity.