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1.
J Appl Anim Welf Sci ; : 1-14, 2022 Oct 31.
Article in English | MEDLINE | ID: mdl-36317262

ABSTRACT

This study explored the demand for improved farm animal welfare (FAW) legislation in the BRIC countries and the USA. Results are discussed in comparison to Europe. Interviewees ranked their willingness to support or oppose introduction of more FAW-friendly laws in their country. A multinomial logistic regression was fit to the data (p < 0.001), with the parameters "country × gender" (p < 0.001) and "country × age" (p < 0.001) found significant. Americans, Russian women, and older Brazilian men are very supportive. The age effect is also felt in India, where older people are more supportive. Chinese, American men, and younger Indians are less supportive. Russian males are the group that oppose the most, followed by younger Brazilians and Indians. The law and its application vary a lot between countries. Nevertheless, the societal willingness to improve FAW legislation is high in all countries. The willingness is higher in Europe. The different cultural backgrounds, the socio-economic factors, and the social, economic, and environmental sustainability are enough reasons to create barriers to policy harmonization in the global trade of farm animal products.

2.
Med Oral Patol Oral Cir Bucal ; 26(3): e292-e298, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33247570

ABSTRACT

BACKGROUND: Among the oral potentially malignant disorders, leukoplakia stands out as the most prevalent. The purpose of this study was to analyse the clinical-pathological features of oral leukoplakia in groups of patients from three major pathology centers in two different regions of Brazil, in order to determine which factors would be associated to the clinical risk of malignant transformation. MATERIAL AND METHODS: A total of 148 patients was analyzed, and data regarding gender, age, site, classification of the clinical subtype, harmful habits such as use of tobacco and alcohol, time of evolution and presence of dysplasia were collected. The association between risk factors and malignant transformation was investigated using the chi-square test and Fischer's exact test for correlation of variables. A significance level of 5% (p≤0.05) was used. RESULTS: The mean age of the patients was 60 years, and 56% were female. Most of the lesions (34,5%) were located in the lateral and ventral regions of the tongue. Of the 148 patients, ninety had clinical follow-up. Malignant transformation occurred in 13 patients (8.8%), with an average of 44 months of follow up. CONCLUSIONS: Non-smoker, nonhomogeneous clinical presentation, location at the tongue, and the presence of high degree of dysplasia were statistically relevant factors associated with a higher risk of transformation transformation.


Subject(s)
Cell Transformation, Neoplastic , Leukoplakia, Oral , Brazil/epidemiology , Female , Humans , Leukoplakia, Oral/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors
4.
Neurol Sci ; 42(5): 1995-2003, 2021 May.
Article in English | MEDLINE | ID: mdl-32997282

ABSTRACT

BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. METHODS: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. RESULTS: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. CONCLUSIONS: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Fingolimod Hydrochloride/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Portugal/epidemiology , Retrospective Studies , Treatment Outcome
5.
Nat Commun ; 10(1): 5699, 2019 12 13.
Article in English | MEDLINE | ID: mdl-31836716

ABSTRACT

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.


Subject(s)
Atlases as Topic , Brain Mapping/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging , Animals , Cerebrospinal Fluid/diagnostic imaging , Cerebrospinal Fluid/physiology , Gray Matter/anatomy & histology , Gray Matter/diagnostic imaging , Gray Matter/physiology , Male , Models, Animal , Rats , Rats, Wistar , Software , White Matter/anatomy & histology , White Matter/diagnostic imaging , White Matter/physiology
6.
J Dev Orig Health Dis ; 9(5): 536-543, 2018 10.
Article in English | MEDLINE | ID: mdl-29900811

ABSTRACT

Animal evidence has suggested that maternal emotional and nutritional stress during pregnancy is associated with behavioral outcomes in offspring. The nature of the stresses applied may differ, but it is often assumed that the mother's hippocampus-hypothalamic-pituitary-adrenal (HHPA) axis response releases higher levels of glucocorticoid hormones. The bed nucleus of the stria terminalis (BNST) is in a pivotal position to regulate the HHPA axis and the stress response, and it has been implicated in anxiety behavior. In the current study, to search whether BNST structural changes and neurochemical alterations are associated with anxiety-related behavior in adult gestational protein-restricted offspring relative to an age-matched normal protein diet (NP) rats, we conduct behavioral tests and, BNST dendritic tree analysis by Sholl analysis, associated to immunoblotting-protein quantification [11ß-HSD2, GR, MR, AT1R, 5HT1A and 5HT2A, corticotrophin-releasing factor (CRH) and CRH1]. Dams were maintained either on isocaloric standard rodent chow [with NP content, 17% casein or low protein content (LP), 6% casein] chow throughout their entire pregnancy. Here, in rats subjected to gestational protein restriction, we found: (a) a significant reduction in dendritic length and impoverished dendritic arborization in BNST neurons; (b) an elevated plasmatic corticosterone levels; and (c) associated with enhanced anxiety-like behavior when compared with age-matched NP offspring. Moreover, altered protein (11ß-HSD2, GR, MR and type 1 CRH receptors) expressions may underlie the increase in anxiety-like behavior in LP offspring. This work represents the first demonstration that BNST developmental plasticity by maternal protein restriction, resulting in fine structural changes and neurochemical alterations that are associated with modified behavioral states.


Subject(s)
Anxiety , Diet, Protein-Restricted , Prenatal Exposure Delayed Effects , Septal Nuclei/embryology , Animals , Behavior, Animal , Body Weight , Female , Male , Maternal Nutritional Physiological Phenomena , Nutritional Status , Pregnancy , Rats , Rats, Wistar , Septal Nuclei/pathology
7.
Mol Psychiatry ; 23(10): 1998-2006, 2018 10.
Article in English | MEDLINE | ID: mdl-29203852

ABSTRACT

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.


Subject(s)
Brain/physiopathology , Stress, Psychological/diagnostic imaging , Stress, Psychological/physiopathology , Animals , Biomarkers , Connectome/methods , Disease Models, Animal , Disease Susceptibility/diagnostic imaging , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Neural Pathways/diagnostic imaging , Rats , Rats, Wistar , Thalamus/physiopathology , Ventral Tegmental Area/physiopathology
8.
Transplant Proc ; 49(6): 1280-1284, 2017.
Article in English | MEDLINE | ID: mdl-28735994

ABSTRACT

BACKGROUND: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. The standard surgery uses the recipient's iliac vessels for vascular anastomosis. Thrombosis and/or stenosis of the iliac vein, which are possible complications of multiple vascular access points for dialysis, can be detected intraoperatively, constituting a surgical challenge. An infrequently reported option is the use of the gonadal vein. OBJECTIVES: This study aims to evaluate the outcomes of venous anastomosis in the gonadal vein in patients with iliac vein thrombosis and/or stenosis submitted to kidney transplantation. METHODS: We reviewed the records of five adult recipients with iliac vein thrombosis and/or stenosis detected intraoperatively during emergency kidney transplantation with deceased donor due to vascular access failure from February 2013 to December 2014. Antithrombotic prophylaxis was not performed. We evaluated the postoperative complications, length of stay, early graft echo-Doppler, and renal function during the first year postoperatively. RESULTS: Delayed graft function occurred in three cases. Two patients developed postoperative infection requiring antibiotics. One patient required reoperation due to post-renal biopsy complications. The mean length of stay was 31.2 days and the mean serum creatinine levels at discharge, at 6 months, and at 12 months postoperatively were 1.42 mg/dL, 0.86 mg/dL, and 0.82 mg/dL, respectively. All patients had normal ultrasonography. There were no losses of graft or deaths during follow-up. CONCLUSION: Venous anastomosis using the gonadal vein in kidney transplantation for patients with iliac vein thrombosis and/or stenosis showed good clinical and surgical results, showing this method to be a viable alternative to venous drainage in these complex patients.


Subject(s)
Iliac Vein/surgery , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Kidney/surgery , Venous Thrombosis/surgery , Adult , Aged , Anastomosis, Surgical/methods , Constriction, Pathologic/surgery , Female , Gonads/blood supply , Gonads/surgery , Humans , Iliac Vein/pathology , Kidney/physiopathology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/pathology , Length of Stay , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Period , Renal Dialysis/adverse effects , Venous Thrombosis/etiology
9.
Prog Neurobiol ; 156: 149-163, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28528956

ABSTRACT

Interferon gamma (IFNγ) is a pro-inflammatory cytokine, first described as a secreted molecule capable of interfering with viral replication. Since then, numerous other important actions in the context of the immune response to invading pathogens (including those invading the brain) have been ascribed to this pleiotropic cytokine. Nevertheless, the precise role of IFNγ in neuropsychiatric and neurodegenerative disorders, and its possible contribution to the regulation of normal brain function, remains enigmatic. This review integrates and considers current knowledge about IFNγ actions with accumulating evidence of its importance on neurocytogenesis, synaptic plasticity and neurodegeneration within the framework of brain health and disease.


Subject(s)
Central Nervous System/metabolism , Interferon-gamma/metabolism , Neurodegenerative Diseases/pathology , Neuronal Plasticity/physiology , Animals , Central Nervous System/immunology , Cytokines/metabolism , Humans
10.
Plant Biol (Stuttg) ; 19(4): 650-659, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28403551

ABSTRACT

Although plant physiological responses to drought have been widely studied, the interaction between photoprotection, photorespiration and antioxidant metabolism in water-stressed plants is scarcely addressed. This study aimed to evaluate the physiological adjustments preserving photosynthesis and growth in two plant species with different tolerance to drought: Jatropha curcas and Ricinus communis. We measured stress indicators, gas exchange, photochemistry of PSII and PSI, antioxidant enzymes, cyclic electron flow and photorespiration. Physiological stress indicators associated with reduction in growth confirmed R. communis as sensitive and J. curcas as tolerant to drought. Drought induced loss of photosynthesis in R. communis, whereas J. curcas maintained higher leaf gas exchange and photochemistry under drought. In addition, J. curcas showed higher dissipation of excess energy and presented higher cyclic electron flow when exposed to drought. Although none of these mechanisms have been triggered in R. communis, this species showed increases in photorespiration. R. communis displayed loss of Rubisco content while the Rubisco relative abundance did not change in J. curcas under drought. Accordingly, the in vivo maximum Rubisco carboxylation rate (Vcmax ) and the maximum photosynthetic electron transport rate driving RuBP regeneration (Jmax ) were less affected in J. curcas. Both species displayed an efficient antioxidant mechanism by increasing activities of ascorbate peroxidase (APX) and superoxide dismutase (SOD). Overall, we suggest that the modulation of different photoprotective mechanisms is crucial to mitigate the effects caused by excess energy, maintaining photosynthetic apparatus efficiency and promoting the establishment of young plants of these two species under drought.


Subject(s)
Droughts , Jatropha/metabolism , Ricinus/metabolism , Ascorbate Peroxidases/metabolism , Electron Transport/genetics , Electron Transport/physiology , Jatropha/physiology , Photosynthesis/genetics , Photosynthesis/physiology , Plant Leaves/metabolism , Plant Leaves/physiology , Ribulose-Bisphosphate Carboxylase/metabolism , Ricinus/physiology , Water/metabolism
11.
Transplant Proc ; 48(1): 74-80, 2016.
Article in English | MEDLINE | ID: mdl-26915846

ABSTRACT

BACKGROUND: Transplant renal artery stenosis (TRAS), the most common vascular complication after transplant (Tx), leads to resistant hypertension, impaired renal function, and even loss of the graft. The purpose of the study was to investigate the prevalence and factors associated with TRAS in northeastern Brazil. METHODS: The study was conducted as a retrospective case-control study in a population of Tx recipients in a renal Tx center in northeastern Brazil. Demographic and clinical characteristics of the recipients and donors, data related to the surgery, laboratory data, and number of anti-hypertensive drugs were assessed. Statistical analysis was performed with the use of SPSS 17.0. RESULTS: A total of 494 of 529 recipients were assessed, of which 24 had TRAS. The prevalence of TRAS was 4.8%. Twelve patients (50%) were men with a mean age of 46.7 ± 13.5 years. The mean time of diagnosis was 89.9 days after Tx. The risk factors associated with TRAS were number of anti-hypertensive drugs ≥2 (odds ratio, 17.0; confidence interval, 4.1 to 70.4; P = .001) and grafting with 2 or more arteries (odds ratio, 8.9; confidence interval, 1.4 to 56.6; P = .021). There was a significant reduction in mean systolic blood pressure (147.1 ± 23.7 to 127.8 ± 15.2 mm Hg, P = .001) and diastolic blood pressure (86.6 ± 13.0 to 77.6 ± 9.4 mm Hg, P = .001) after TRAS repair and in serum creatinine (2.8 ± 2.4 to 1.9 ± 1.8 mg/dL, P = .04). CONCLUSIONS: Grafts with 2 or more arteries are associated with TRAS, as well as patients who use a higher number of anti-hypertensive drugs. TRAS repair was associated with improved blood pressure control and renal function.


Subject(s)
Graft Occlusion, Vascular/etiology , Kidney Transplantation/adverse effects , Renal Artery Obstruction/etiology , Adult , Antihypertensive Agents/therapeutic use , Blood Pressure , Brazil/epidemiology , Case-Control Studies , Female , Graft Occlusion, Vascular/epidemiology , Graft Occlusion, Vascular/physiopathology , Humans , Kidney/blood supply , Kidney/surgery , Kidney Transplantation/methods , Male , Middle Aged , Prevalence , Renal Artery/physiopathology , Renal Artery Obstruction/epidemiology , Renal Artery Obstruction/physiopathology , Renal Insufficiency/etiology , Retrospective Studies , Risk Factors , Treatment Outcome
12.
Transl Psychiatry ; 6: e707, 2016 Jan 05.
Article in English | MEDLINE | ID: mdl-26731444

ABSTRACT

Cognitive functioning can be differentially modulated by components of the immune system. Interferon-γ (IFNγ) is a pro-inflammatory cytokine whose production is altered in many conditions displaying some degree of cognitive deficits, although its role in cognitive functioning is still unclear. Here we show that the absence of IFNγ selectively enhances cognitive behaviours in tasks in which the hippocampus is implicated. Moreover, the absence of IFNγ leads to volumetric and cell density changes that are restricted to the dorsal part of the hippocampus. In the dorsal hippocampus, the absence of this pro-inflammatory cytokine leads to an increase in the numbers of newly born neurons in the subgranular zone of the dentate gyrus (DG), an adult neurogenic niche known to support learning and memory, and to an enlargement of the dendritic arborization of DG granule and cornu ammonis (CA)1 pyramidal neurons. Moreover, it also modestly impacts synaptic plasticity, by decreasing the paired-pulse facilitation in the Schaffer collateral to CA1 pyramidal cell synapses. Taken together, our results provide evidence that IFNγ is a negative regulator of hippocampal functioning, as its absence positively impacts on dorsal hippocampus structure, cell density, neuronal morphology and synaptic plasticity. Importantly, these neuroplastic changes are associated with improved performance in learning and memory tasks. Therefore, blockage of the IFNγ signalling may present as promising therapeutic targets for the treatment of inflammation-associated cognitive dysfunction.


Subject(s)
Cognition/physiology , Hippocampus/physiology , Interferon-gamma , Neuronal Plasticity/physiology , Animals , Female , Male , Mice , Mice, Inbred C57BL
13.
Int J Impot Res ; 28(1): 20-4, 2016.
Article in English | MEDLINE | ID: mdl-26510967

ABSTRACT

We studied the mechanisms involved in the human corpora cavernosa (HCC) relaxation induced by a new metal-based nitric oxide (NO) donor, the ruthenium complex cis-[Ru(bpy)2Imn(NO)](+3) (FOR0811). FOR0811 produced relaxation in phenylephrine (PE)-precontracted HCC with a maximal response that achieved 112.9 ± 10.6%. There was no difference between the maximal relaxation induced by FOR0811 when compared with sodium nitroprusside (SNP) (106.8 ± 7.3%), BAY41-2272 (107.6 ± 4.1%) or vardenafil (103.4 ± 3.8%), however, FOR0811 was less potent than SNP and vardenafil. L-N(G)-nitroarginine methyl ester (L-NAME), a NO synthase inhibitor, had no effect in the concentration-response curve elicited by FOR0811. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a heme-site inhibitor of soluble guanylyl cyclase (sGC) was able to either block or reverse the relaxation induced by FOR0811. On the other hand, the relaxation induced by FOR0811 was not affected by glibenclamide, a blocker of ATP-sensitive potassium channels. FOR0811 (10 µM) was able to increase cyclic guanosine monophosphate (cGMP) levels in corpora cavernosa strips. FOR0811 completely relaxes HCC by a sGC-cGMP-dependent mechanism and can be a lead compound in the development of new stable NO donors.


Subject(s)
Guanylate Cyclase/physiology , Muscle Relaxation , Nitric Oxide Donors/pharmacology , Penile Erection , Penis , Receptors, Cytoplasmic and Nuclear/physiology , Ruthenium Compounds/pharmacology , Cyclic GMP/physiology , Humans , Male , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Nitric Oxide/metabolism , Nitroprusside/pharmacology , Penile Erection/drug effects , Penile Erection/physiology , Penis/pathology , Penis/physiology , Penis/physiopathology , Research Design , Soluble Guanylyl Cyclase
14.
Mol Psychiatry ; 21(1): 80-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25754084

ABSTRACT

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.


Subject(s)
Brain/metabolism , Lipids , Stress, Psychological/metabolism , Animals , Chromatography, High Pressure Liquid , Chronic Disease , Disease Models, Animal , Hydrocortisone/blood , Male , Mass Spectrometry , Rats, Wistar , Real-Time Polymerase Chain Reaction , Uncertainty
15.
J Neurosci Res ; 93(6): 839-47, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25483118

ABSTRACT

For a number of decades, different fields of knowledge, including psychology, economics, and neurosciences, have focused their research efforts on a better understanding of the decision-making process. Making decisions based on the probability of future events is routine in everyday life; it occurs whenever individuals select an option from several alternatives, each one associated with a specific value. Sometimes subjects decide knowing the precise outcomes of each option, but commonly they have to decide without knowing the consequences (because either ambiguity or risk is involved). Stress has a broad impact on animal behaviors, affects brain regions involved in decision-making processes, and, when maladaptive, is a trigger for neuropsychiatric disorders. This Mini-Review provides a comprehensive overview on how stress impacts decision-making processes, particularly under uncertain conditions. Understanding this can prove to be useful for intervention related to impairments to decision-making processes that present in several stress-triggered neuropsychiatric disorders.


Subject(s)
Cognition Disorders/etiology , Decision Making/physiology , Stress, Psychological/complications , Uncertainty , Humans
16.
Brain Struct Funct ; 220(2): 1205-12, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24500370

ABSTRACT

Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.


Subject(s)
Hippocampus/pathology , Hippocampus/physiopathology , Stress, Psychological/pathology , Stress, Psychological/physiopathology , Animals , Atrophy , Behavior, Animal , CA1 Region, Hippocampal/pathology , CA1 Region, Hippocampal/physiopathology , CA3 Region, Hippocampal/metabolism , CA3 Region, Hippocampal/physiopathology , Chronic Disease , Cognition , Long-Term Potentiation , Male , Maze Learning , Memory , Rats, Wistar , Stress, Psychological/psychology , Time Factors
17.
Rev Neurol ; 59(9): 399-406, 2014 Nov 01.
Article in English, Spanish | MEDLINE | ID: mdl-25342053

ABSTRACT

INTRODUCTION: Studies have shown that natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). To date, no data are available in Portuguese patients. AIM: To determine the efficacy and safety of natalizumab in patients with RRMS in routine clinical practice in Portugal. PATIENTS AND METHODS: Clinical data for adult patients with RRMS treated with natalizumab at specialist neurology centres in Portugal were entered retrospectively into a database for analysis between October 2010 and February 2012. Changes in annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) scores and disability status were analysed. RESULTS: A total of 383 patients from 20 centres were included. Prior to starting natalizumab, the baseline median EDSS score was 4 and the mean ARR was 1.64. Most patients had previously received multiple sclerosis treatment (93.0%). Median natalizumab treatment duration was 12 months. Natalizumab treatment was associated with significant (p < 0.001) reductions from baseline in the mean ARR and EDSS scores in patients treated with natalizumab for >= 12 months (n = 288) and for >= 24 months (n = 160). Natalizumab was more effective in patients with less disability (EDSS < 3) and in those who had not previously received disease-modifying treatments. Two cases of progressive multifocal leukoencephalopathy were reported. No new unexpected adverse events occurred. CONCLUSION: Natalizumab is well tolerated, and is effective in reducing relapse rate and stabilising disease in patients with RRMS in the clinical practice setting in Portugal. Its efficacy persists with continued treatment, and it may be particularly effective in patients with less disability and without prior disease modifying therapy.


TITLE: Estudio retrospectivo de la eficacia y seguridad del natalizumab en el tratamiento de la esclerosis multiple en Portugal.Introduccion. Los estudios han demostrado que el natalizumab constituye un tratamiento eficaz contra la esclerosis multiple remitente recurrente (EMRR). Hasta la fecha, no habia datos de pacientes portugueses. Objetivo. Determinar la eficacia y la seguridad del natalizumab en pacientes con EMRR atendidos en la practica clinica ordinaria en Portugal. Pacientes y metodos. Los datos clinicos de adultos con EMRR tratados con natalizumab en centros especializados de neurologia en Portugal se introdujeron de forma retrospectiva en una base de datos para llevar a cabo un analisis entre octubre de 2010 y febrero de 2012. Se analizo el cambio en la tasa anualizada de brotes (TAB), en las puntuaciones de la escala ampliada de discapacidad (EDSS) y en el estado de discapacidad. Resultados. Se admitio un total de 383 pacientes atendidos en 20 centros. Antes de iniciar el tratamiento con natalizumab, la mediana inicial de la EDSS era de 4,0 y la TAB media, de 1,64. La mayor parte de los pacientes ya habia recibido tratamiento contra la esclerosis multiple (93,0%). La duracion media del tratamiento con natalizumab era de 12 meses. El tratamiento propicio reducciones significativas (p < 0,001) de los valores iniciales de la TAB media y de las puntuaciones EDSS en los tratados con el anticuerpo durante >= 12 meses (n = 288) y durante >= 24 meses (n = 160). El natalizumab resulto mas eficaz en los pacientes que presentaban un menor grado de discapacidad (EDSS < 3,0) y en los que no habian recibido ningun tratamiento modificador de la enfermedad. Se notificaron dos casos de leucoencefalopatia multifocal progresiva. No hubo efectos adversos inesperados. Conclusion. El natalizumab presenta una tolerabilidad satisfactoria y se muestra eficaz en la reduccion de las recidivas y la estabilizacion de la EMRR en el marco de la practica clinica ordinaria en Portugal. Conserva su eficacia con el tratamiento continuado y podria ser eficaz especialmente en los pacientes con menos discapacidad y en aquellos que no han recibido ningun tratamiento modificador de la enfermedad hasta el momento.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Disability Evaluation , Drug Hypersensitivity/epidemiology , Drug Hypersensitivity/etiology , Female , Humans , Infections/epidemiology , Leukoencephalopathy, Progressive Multifocal/epidemiology , Leukoencephalopathy, Progressive Multifocal/etiology , Male , Middle Aged , Multiple Sclerosis/epidemiology , Myocardial Infarction/chemically induced , Myocardial Infarction/epidemiology , Natalizumab , Portugal/epidemiology , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Young Adult
18.
Mol Psychiatry ; 19(7): 834-41, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24419043

ABSTRACT

Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-α-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.


Subject(s)
Astrocytes/pathology , Cognition/drug effects , Prefrontal Cortex/drug effects , 2-Aminoadipic Acid/administration & dosage , 2-Aminoadipic Acid/toxicity , Animals , Astrocytes/drug effects , Atrophy , Attention/drug effects , Cell Death , Dendrites/drug effects , Dendrites/pathology , Male , Memory, Short-Term/drug effects , Microinjections , Nerve Degeneration/chemically induced , Nerve Degeneration/pathology , Prefrontal Cortex/pathology , Rats , Reversal Learning/drug effects
19.
Minerva Ginecol ; 65(3): 297-302, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23689172

ABSTRACT

AIM: The aim of this paper was to compare the carotid intima-media thickness (IMT) in pre- and postmenopausal women and to evaluate the association between endogenous sex hormones, body fat distribution, and insulin resistance and the IMT. METHODS: This cross-sectional study included 145 women aged 45-65 yr, comprising 56 premenopausal (FSH<20IU/mL and regular menstrual cycles) and 89 postmenopausal (FSH>40IU/ml and amenorrheic). All patients were evaluated for lipid profile, estradiol and testosterone, insulin ratio (G/I), HOMA-IR, and ultrasound measurement of IMT. Each variable was assessed for correlation with IMT using the univariate model. RESULTS: No difference was observed in IMT between pre- and postmenopausal women. A positive and statistically significant correlation was found between IMT and FSH levels (rs=0.21, P<0.009) and HOMA (rs=0.16, P<0.04). A positive and statistically significant correlation was observed between testosterone and waist (rs=0.3, P<0.04). No correlation was found between IMT and time of menopause (r=0.02, P=0.19). CONCLUSION: Estradiol and testosterone are not associated with subclinical atherosclerosis in menopausal women. A positive correlation between IMT and FSH may reflect an association between low estrogen and IMT. Abdominal fat can be an important link between androgenic levels and cardiovascular risk.


Subject(s)
Abdominal Fat/metabolism , Atherosclerosis/pathology , Carotid Intima-Media Thickness , Postmenopause , Aged , Body Fat Distribution , Cross-Sectional Studies , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Insulin/metabolism , Insulin Resistance , Middle Aged , Premenopause , Testosterone/blood , Time Factors
20.
Int. j. morphol ; 31(1): 55-63, mar. 2013. ilus
Article in English | LILACS | ID: lil-676133

ABSTRACT

Body measurements in Portuguese Holstein-Friesian breed and its association with the dimensions of the cubicles were investigated. During a period of 5 months, body measurements and cubicles size data from 55 commercial Portuguese dairy herds were collected including in total 1054 individual cows. Data were analyzed using the general linear model and principal components. The most relevant body measurements were: height at withers (141.1±4.72 cm), height at rump (144.2±4.47 cm), length of trunk (170.8±8.31 cm), width of biiliac (55.9±4.17 cm) and perimeter of the thorax (206.8±10.43 cm). In general, the first class of parity showed significant different measures (P<0.001) associated with the development of animals. Head to head cubicle length and cubicle width were 223.0±11.0 cm and 113.0±5.0 cm respectively; whereas in cubicle against wall length was 227.0±18.0 cm and width 111.0±7.0 cm. The highest correlations were found for body measures between the different heights and between the height at chest and perimeter of the thorax. The analysis showed no relation between body measurements and dimensions of the cubicles. Principal component analysis of the different body measurements and cubicles dimensions expressed 51.4% of the total variability, in which the first factor represented 40.2% and the second factor 11.1%.


Fueron investigadas las medidas corporales en la raza Holstein-Friesian Portuguesa y su asociación con las dimensiones de los cubículos. Durante un período de 5 meses, se recogieron las medidas corporales y los datos de tamaño de cubículos de 55 explotaciones lecheras comerciales portuguesas incluyendo un total de 1054 animales. Los datos fueron analizados utilizando el modelo linear general y componentes principales. Las medidas del cuerpo más relevantes fueron: altura a la cruz (141,1±4,7 cm), altura a la grupa (144,2±4,5 cm), longitud del tronco (170,8±8,3 cm), ancho biisquiática (55,9±4,2 cm) y el perímetro del tórax (206,8±10,4 cm). En general, la primera paridad reveló diferencias (P<0,001), lo que se encuentra asociado con el desarrollo de los animales. La longitud y la ancho del cubículo cabeza con cabeza fue 223±11 cm y 113±5 cm respectivamente, mientras que en el cubículo frente a la pared, la longitud fue 227±18 cm y el ancho de 111±7 cm. Las medidas del cuerpo con las más altas correlaciones se observaron entre las diferentes alturas y entre la altura del pecho y el perímetro del tórax. El análisis no evidenció relación alguna entre las medidas del cuerpo y las dimensiones de los cubículos. El análisis de componentes principales de las medidas del cuerpo y de las diferentes dimensiones de los cubículos explican el 51,4% de la variabilidad total, en la que el primer factor representa el 40,2% y el segundo el 11,1%.


Subject(s)
Animals , Cattle , Cattle/anatomy & histology , Housing, Animal , Body Weights and Measures , Linear Models , Principal Component Analysis , Farms
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