Cognitive and olfactory deficits in Machado-Joseph disease: A dopamine transporter study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative study of epidural xylazine or clonidine in horses

Objective To evaluate the cardiorespiratory and behavioural effects of epidural xylazine (XYL) or clonidine (CLO) in horses.Study design Blinded, randomized experimental study.Twelve healthy Arabian yearling horses weighing 117-204 kg were randomly allocated into two groups: XYL (n = 6) and CLO (n = 6).Methods An epidural catheter was inserted and a facial arterial catheter was placed and the next day the horses were restrained in stocks. Baseline values for heart (HR) and respiratory (RR) rates, arterial pressure and behavioural responses were evaluated before (TO) and 10, 20, 30, 45, 60, 90 and 120 minutes after epidural injection (T10-T120). The horses received 0.2 mg kg(-1) of XYL or 5 mu g kg(-1) CLO; adjusted to (3.4 + (body weight in kg x 0.013) mL with saline. Data were analysed by the Kolmogorov-Smirnov test, one-way ANOVA with repeated measures, and one-way ANOVA followed by a Student-Newman-Keuls test or Fisher's exact test, as necessary. Significance was set at p <= 0.05.Results Sedation and ataxia were seen at T10, persisting until T120 in four and three horses, respectively, in XYL and all horses in CLO respectively. Two XYL and one CLO horses became recumbent at T45 and T25 respectively. Penile prolapse occurred in four of five males at T30 and T45, in the XYL and CLO groups, respectively, resolving by T120. Tail relaxation was present from T10 to T120 in all horses in XYL and in four horses in CLO. Head drop was observed from T20 to T60 and from T10 to T120 in XYL and CLO respectively. Respiratory rate decreased significantly only at T45 in the CLO group. Heart rate and arterial blood pressure remained stable.Conclusions and clinical relevance Epidural CLO and XYL produce similar cardiorespiratory and behavioural changes but neither would be safe to use clinically at the doses used in this study.

Fetal and maternal lesions of cyanide dosing to pregnant goats

The present work evaluated the pathological effects in both dams and their fetuses of cyanide ingestion during pregnancy using goat as animal model. From the Day 24 of pregnancy, three pregnant goats were dosed by gavage with 3.0 mg KCN/kg bw/day, and two others received only tap water. All dams were euthanized and necropsied at Day 120 of pregnancy. The fetuses were examined carefully for gross abnormalities. Determinations of cyanide and thiocyanate were performed in maternal and fetal blood and in amniotic fluid. Samples of several organs were collected for histopathologic evaluation. No clinical changes were seen in any animal throughout the pregnancy. No malformations or dead fetuses were observed: however, placenta from one treated goat presented increased cotyledon surface area occupied by vascular lumina. Histological lesions in KCN-treated dams consisted of vacuolation of hepatocytes and thyroid follicular cells, increased number of vacuoles on thyroid follicular colloid. and spongiosis of cerebral, internal capsule, and cerebellar peduncles tracts. Fetuses from these mothers showed vacuolation of hepatocytes and thyroid follicular cells, and spheroids in the cerebellar white matter. Levels of cyanide and thiocyanate were higher in maternal than fetal blood, which suggests that these substances were largely but not freely transferred from mothers to fetuses. (C) 2009 Elsevier B.V. All rights reserved.

Acute, subchronic and chronic 2,4-dichlorophenoxyacetic acid (2,4-D) intoxication in rats

The acute, subchronic and chronic toxicities of 2,4- dichlorophenoxyacetic acid (2,4-D) were studied in rats. Animals were exposed acutely (600 mg/kg), subchronically (200 ppm for 30 d) and chronically (200 ppm for 180 d) to 2,4-D by the oral route. Clinical, laboratory and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased locomotor activity and induced ataxia, sedation, muscular weakness (mainly of the hind quarters) and gasping for breath; increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), amylase activities and creatinine levels; decreased total protein (TP) and glucose levels; and increased hematocrit values. Subchronic and chronic 2,4-D exposures did not induce overt clinical signs or symptoms of intoxication. However, subchronic herbicide exposure increased AST activity and albumin and hematocrit values, and chronic exposure increased AST, AP and LDH activities, decreased amylase and glucose levels, but did not change hematocrit values. Chromatographic analysis of the serum of chronically exposed rats showed the presence of the herbicide; the amount found (3.76 ± 1.16 mg/ml) suggested the absence of 2,4-D accumulation within the body. Although macroscopic or histopathological lesions were not observed in acutely, subchronically or chronically 2,4-D exposed rats, the laboratory data obtained suggest tissue injuries after dosing, since the results are considered early indicators of primarily hepatic and muscle tissue damage.

New approach of induction machine drive using an adaptive digital PID controller with gain planning based on artificial neural networks

The present work introduces a new strategy of induction machines speed adjustment using an adaptive PID (Proportional Integral Derivative) digital controller with gain planning based on the artificial neural networks. This digital controller uses an auxiliary variable to determine the ideal induction machine operating conditions and to establish the closed loop gain of the system. The auxiliary variable value can be estimated from the information stored in a general-purpose artificial neural network based on CMAC (Cerebellar Model Articulation Controller).

Injeção epidural de cetamina ou cetamina levógira no controle da dor pós-incisional, em eqüinos

The aim of this study was to evaluate the pre-emptive effect of epidural ketamine S (+) (SK) or racemic ketamine (RK) administration, in post-incisional pain in horses. Were used in a blinded, randomized experimental study, sixteen mixed breed mares, 6±2 years old, weighting 273.2±42.0 kg. An epidural catheter was inserted 24 hours before the trials. The thigh region was shaved bilaterally, and mechanical cutaneous sensibility was measured using von Frey filaments (T-30). Using the left side as the control one, local anesthesia was performed at the right side. Twenty-five minutes later, SK was injected in G1 or RK in G2 through the epidural catheter. Five minutes after the ketamine injection, a 10 cm skin incision was made on the right side, and then sutured. Mechanical post-incisional pain was measured using von Frey filaments, at 1, 3 and 5 cm around the incision at 15 minutes intervals, for 2 hours, then 4, 6 and 8 hours after suturing. No changes were observed in the heart and respiratory rate and rectal temperature among groups or times of each group. Hind limb ataxia was observed in 62.5% and 12.5% of G1 and G2 respectively. SK and RK reduced cutaneous sensibility in the right and the left sides to mechanical postincisional pain during all time of experiment. Epidural SK and RK produce similar post-incisional analgesic effects, did not interfere in the cardio-respiratory parameters. The SK induces more intense ataxia in mares and presents a larger analgesic potency in the first 60 minutes after the administration.

Experimental envenomation with Crotalus durissus terrificus venom in dogs treated with antiophidic serum - Part I: Clinical evaluation, hematology and myelogram

The present study aimed at evaluating clinical and laboratory aspects during experimental envenomation by Crotalus durissus terrificus in dogs treated with antiophidic serum. Twenty-one dogs were divided into three groups of seven animals each. Group I received 1mg/kg venom (sc); Group II received 1mg/kg venom (sc), 50mg antiophidic serum (iv), and fluid therapy including 0.9% NaCl solution (iv); and Group III received 1mg/kg venom (sc), 50mg antiophidic serum (iv), and fluid therapy including 0.9% NaCl solution containing sodium bicarbonate diluted to the dose of 4mEq/kg. The clinical signs of ataxia, sedation, flaccid paralysis, mydriasis, eyeball paralysis, mandible ptosis, sialorrhea, vomiting and diarrhea observed in the dogs were very similar to those observed in humans. The decrease in hemoglobin, hematocrit, erythrocyte, platelet and fibrinogen levels, prolongation of clotting time, prothrombin time (PT) and activated partial thromboplastin time (APTT), as well as hypocellularity in the bone marrow characterized anemia, thrombocytopenia and blood incoagulability, as well as hypofibrinogenemia and decreased bone-marrow activity. Important bleeding was not observed. Increased numbers of leukocytes and neutrophils and decreased numbers of lymphocytes and eosinophils characterized an acute inflammatory response and stress caused by generalized pain. The employed antiophidic serum was effective and all animals survived.

Pilomyxoid astrocytoma of the brainstem

A pilomyxoid astrocytoma is a recently described tumor that occurs predominantly in the hypothalamic-chiasmatic region and is rarely found elsewhere. It has similar features as pilocytic astrocytomas, but has distinct histological characteristics and a poorer prognosis. A pilomyxoid astrocytoma is an aggressive tumor, and increased awareness is necessary with a suspect case. We present the first case of a pilomyxoid astrocytoma of the brainstem described after the newest World Health Organization classification of central nervous system tumors. © F.O. Pereira et al., 2013. Licensee PAGEPress, Italy.

Hepatitis C Virus NS2 Protein Inhibits DNA Damage Pathway by Sequestering p53 to the Cytoplasm

Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality globally, and often leads to end-stage liver disease. The DNA damage checkpoint pathway induces cell cycle arrest for repairing DNA in response to DNA damage. HCV infection has been involved in this pathway. In this study, we assess the effects of HCV NS2 on DNA damage checkpoint pathway. We have observed that HCV NS2 induces ataxia-telangiectasia mutated checkpoint pathway by inducing Chk2, however, fails to activate the subsequent downstream pathway. Further study suggested that p53 is retained in the cytoplasm of HCV NS2 expressing cells, and p21 expression is not enhanced. We further observed that HCV NS2 expressing cells induce cyclin E expression and promote cell growth. Together these results suggested that HCV NS2 inhibits DNA damage response by altering the localization of p53, and may play a role in the pathogenesis of HCV infection. © 2013 Bitter et al.

The Edinger-Westphal nucleus II: Hypothalamic afferents in the rat

Numerous functions have been attributed to the Edinger-Westphal nucleus (EW), including those related to feeding behavior, pain control, alcohol consumption and the stress response. The EW is thought to consist of two parts: one controls accommodation, choroidal blood flow and pupillary constriction, primarily comprising cholinergic cells and projecting to the ciliary ganglion; and the other would be involved in the non-ocular functions mentioned above, comprising peptide-producing neurons and projecting to the brainstem, spinal cord and prosencephalic regions. Despite the fact that the EW is well known, its connections have yet to be described in detail. The aim of this work was to produce a map of the hypothalamic sources of afferents to the EW in the rat. We injected the retrograde tracer Fluoro-Gold into the EW, and using biotinylated dextran amine, injected into afferent sources as the anterograde control. We found retrogradely labeled cells in the following regions: subfornical organ, paraventricular hypothalamic nucleus, arcuate nucleus, lateral hypothalamic area, zona incerta, posterior hypothalamic nucleus, medial vestibular nucleus and cerebellar interpositus nucleus. After injecting BDA into the paraventricular hypothalamic nucleus, lateral hypothalamic area and posterior hypothalamic nucleus, we found anterogradely labeled fibers in close apposition to and potential synaptic contact with urocortin 1-immunoreactive cells in the EW. On the basis of our findings, we can suggest that the connections between the EW and the hypothalamic nuclei are involved in controlling stress responses and feeding behavior. © 2013 The Authors.

Exploring the multifactorial nature of autism through computational systems biology: Calcium and the Rho GTPase RAC1 under the spotlight

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca2+) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism. © 2013 Springer Science+Business Media New York.

Behavioral and Antinociceptive Effects of Alfentanil, Butorphanol, and Flunixin in Horses

To determine the behavioral and antinociceptive effects of narcotic and non-narcotic analgesics administered by intravenous injection in horses, 10 thoroughbred mares weighing between 450 and 550 kg and ranging in age from 8 to 13 years old were analyzed. The effects of alfentanil, butorphanol, flunixin, and saline solution on the general activity of the horses were investigated by measuring spontaneous locomotor activity (SLA) and head height (HH) in two behavior stalls. The antinociceptive effects of alfentanil (0.02 mg kg-1), butorphanol (0.1 mg kg-1), flunixin meglumine (0.5 mg kg-1), and saline were determined by measuring skin twitch reflex latency (STRL) after thermal cutaneous nociceptive stimulation. A paired Student t-test was used to compare SLA and HH between the groups of horses receiving different doses of the same drug at various time points. The Tukey test was used to compare the antinociceptive effect of the treatments. Differences were considered significant when P value was <.05. Horses treated with opioid analgesics demonstrated excitation, as shown by a significant increase in SLA at all doses tested and by neighing and demonstrating attentive attitudes with movement of the ears, stereotypical walking, and ataxia in most of the animals. HH was elevated only in animals treated with alfentanil. Antinociception was observed at 5 and 30 minutes after administration of alfentanil and butorphanol, respectively. Increased SLA was observed at 30 and 90 minutes after administration of alfentanil and butorphanol, respectively. We observed no effect on antinociception in horses given flunixin. In conclusion, this study suggests that alfentanil has a faster onset and a shorter duration than butorphanol; however, both drugs are able to stimulate the central nervous system. © 2013 Elsevier Inc. All rights reserved.

Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis

Distemper leukoencephalitis is a disease caused by the canine distemper virus (CDV) infection. It is a demyelinating disease affecting mainly the white matter of the cerebellum and areas adjacent to the fourth ventricle; the enzymes of the matrix metalloproteinases (MMPs) group, especially MMP-2 and MMP-9 have a key role in the myelin basic protein fragmentation and in demyelination, as well as in leukocyte traffic into the nervous milieu. To evaluate the involvement of MMPs during subacute distemper leukoencephalitis, we measured the levels of MMP-2 and MMP-9 by zymography in the cerebrospinal fluid (CSF) and in the cerebellum of 14 dogs naturally infected with CDV and 10 uninfected dogs. The infected dogs presented high levels of pro-MMP-2 in the CSF and elevated levels of pro-MMP-2 and pro-MMP-9 in the cerebellar tissue. Active MMP-2 was detected in the CSF of some infected dogs. As active MMP-2 and MMP-9 are required for cellular migration across the blood-brain barrier and any interference between MMPs and their inhibitors may result in an amplification of demyelination, this study gives additional support to the involvement of MMPs during subacute distemper leukoencephalitis and suggests that MMP-2 and MMP-9 may take part in the brain inflammatory changes of this disease. © 2013 Elsevier B.V.

Antinociceptive and Behavioral Effects of Methadone Alone or in Combination with Detomidine in Conscious Horses

The antinociceptive and behavioral effects of methadone (MET) alone or combined with detomidine (DET) were studied in horses. Intravenous treatments were randomly administered in a two-phase crossover study. In phase 1, six horses were treated with saline (control) or 0.2 or 0.5 mg/kg methadone (MET0.2; MET0.5, respectively). In phase 2, six horses were treated with 0.01 mg/kg DET alone or with DET combined with 0.2 mg/kg MET (DET/MET0.2). Thermal nociceptive threshold (TNT) and electrical nociceptive thresholds (ENT) were recorded by using a heat projection lamp and electrodes placed in the coronary band of the thoracic limbs, respectively. Spontaneous locomotor activity (SLA) was studied by movement sensors in the stall (phase 1). Chin-to-floor distance was assessed in phase 2. In phase 1, the TNT increased significantly for 30 minute after MET0.5 but not after saline or MET0.2. Hyperesthesia and ataxia were observed in 2 of 6 and 6 of 6 horses after MET0.2 and MET0.5, respectively. SLA increased significantly for 120 minutes after MET in a dose-dependent way, but not after placebo. In phase 2, DET and DET/MET0.2 significantly increased the TNT and ENT above baseline for 15 and 30 minutes, respectively; thresholds were significantly higher with DET/MET0.2 than with DET at the same times. Chin-to-floor distance decreased significantly from baseline for 30 minutes, and no excitatory behavior was observed in both treatments. Although the higher dose of MET induced short-acting antinociception, the associated adverse effects may contraindicate its clinical use. The lower dose of MET potentiated DET-induced antinociception without adverse effects, which might be useful under clinical circumstances. © 2013 Elsevier Inc. All rights reserved.

Morfometria do cerebelo de ratos machos UChA e UChB submetidos a separação materna neonatal (consumidores voluntários de etano)

Pós-graduação em Biologia Geral e Aplicada - IBB