RESUMO
Temporomandibular joint (TMJ) disorder caused by occlusal trauma is one of the most controversial topics in dentistry. Experimental traumatic occlusion (ETO) induced by metal crowns cemented to mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-α, IL-1ß, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28 d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1ß and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization.
Assuntos
Oclusão Dentária Traumática , Animais , Oclusão Dentária Traumática/metabolismo , Neuroglia/metabolismo , Dor , Ratos , Articulação Temporomandibular/metabolismo , Gânglio Trigeminal/metabolismoRESUMO
PURPOSE: Pain is considered a stressful experience, related to real or possible tissue damage with emotional, sensory, social and cognitive components. The aim of the study was to evaluate and compare, using a digital algometer, the pressure pain threshold of temporal and masseter muscles of children and adolescents with and without intellectual disability. METHODS: A cross-sectional study was conducted. Data regarding gender and age were collected from the caregiver of children and adolescents with and without intellectual disability. The evaluations followed this sequence: pressure pain threshold of the masseter and temporal muscles, evaluation of pain on touch using the visual analog scale and signs and symptoms of Temporomandibular disorder. The χ2 test, the Kolgomorov-Smirnov test, Student t test and Mann-Whitney test were performed. The significance level was set at 5%. RESULTS: Two homogeneous groups by gender (P = 0.258) and age (P = 0.727) were evaluated, of which 25 children and adolescents presented intellectual disability and another 25 did not have intellectual disability. No significant difference was observed between groups on the pressure pain threshold of the masseter and temporal muscles, nor pressure average or exam time (P > 0.05). Regarding Temporomandibular dysfunction, no difference in signs or symptoms frequency was found (P > 0.05). However, the range of maximum mouth opening was smaller in the intellectual disability group (P = 0.006). CONCLUSION: Children and adolescents with intellectual disability and preserved basic functionalities do not present alterations in pain perception when evaluated with computerized pressure algometer and visual analog scale. They present similar threshold of pain to pressure as those reported by normative children and adolescents. These results emphasize the importance to treat these children and adolescents with intellectual disability with respect to their pain threshold.
Assuntos
Deficiência Intelectual , Limiar da Dor , Adolescente , Criança , Estudos Transversais , Humanos , Deficiência Intelectual/complicações , Músculo Masseter , Músculos da Mastigação , Projetos PilotoRESUMO
To understand the production factors that affect conclusive parameters of sow herd performance can improve the use of the resources and profitability of farm. The objective of this study was to identify associations and quantify the effects of a set of factors related to piglet weight at weaning (PWW), kilograms of piglets weaned per sow per year (kgPWSY) and sow feed conversion (SFC). Data from 150 farms were collected, for a total study population of 135 168 sows, including gilt replacement, breeding (mating), gestation and farrowing/lactation phases. A questionnaire focusing on reproductive performance, management, facilities, feeding, health and biosafety was administered. Multiple linear regression models were used to assess associations among factors with each of the three dependent variables. Increased duration of lactation was positively associated with PWW, kgPWSY and SFC. The increase in the number of live born pigs per litter was positively associated with kgPWSY and with SFC. Farms with higher PWW had farrowing room humidifiers, did not surgically castrate male piglets and used quaternary ammonia compounds for farrowing room disinfection. Farms with higher kgPWSY used lined ceilings in farrowing rooms and winter feeds with higher CP percentages in gestation; they also had more farrowings per sow per year. Sow feed conversion was worse in farms with partly slatted floors during gestation, in farms feeding lactating sows six times a day or ad libitum and farms with a higher sow-handler ratio. This study indicates that farms can increase PWW and kgPWSY and improve the SFC by changing one or more management, biosafety and feeding practices or facilities as well as by focusing on improving several performance parameters, particularly increasing the duration of lactation and the number of live born pigs per litter.
Assuntos
Peso Corporal , Suínos/fisiologia , Animais , Metabolismo Energético , Feminino , Lactação , Tamanho da Ninhada de Vivíparos , Reprodução , DesmameRESUMO
New therapeutic approaches are necessary to control strongyloidiasis due to the side effects of, and resistance to, currently available drugs thiabendazole, albendazole, and ivermectin. This study examined the anthelmintic properties of extracts and isolated compounds from Siparuna guianensis against Strongyloides venezuelensis eggs and larvae, using the egg hatching test (EHT) and larval motility test (LMT). Albendazole (0.025 mg/ml) and ivermectin (0.316 mg/ml) were used as the positive controls for the EHT and LMT assays, respectively. Strongyloides venezuelensis eggs or larvae (±50 specimens) were treated with ethanol extract (0.05-1.0 mg/ml), ethyl acetate and aqueous fractions (0.05-0.8 mg/ml), essential oil (0.2-1.0 mg/ml) and α-bisabolol (0.2-1.0 mg/ml) from S. guianensis, and analysed by optical microscopy after 48 h (EHT), or after 24, 48 and 72 h (LMT). All the tested compounds exhibited ovicidal activity equivalent to the positive control and changed the morphology of the eggs. The S. guianensis ethanol extract and aqueous fraction were as effective as the positive control. Phytochemical analysis of the ethanol extract and fractions revealed the presence of phenolic compounds, tannins and flavonoids. Therefore, S. guianensis is effective against S. venezuelensis eggs and larvae in vitro, and can be considered as a potential alternative treatment for strongyloidiasis.
Assuntos
Anti-Helmínticos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Strongyloides/efeitos dos fármacos , Traqueófitas/química , Animais , Anti-Helmínticos/química , Larva/efeitos dos fármacos , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/farmacologia , Óleos Voláteis/química , Óvulo/efeitos dos fármacos , Extratos Vegetais/químicaRESUMO
BACKGROUND AND OBJECTIVE: Soluble epoxide hydrolase (sEH) is an enzyme in the arachidonate cascade which converts epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 enzymes, to dihydroxy-eicosatrienoic acids. In the last 20 years with the development of inhibitors to sEH it has been possible to increase the levels of EETs and other EpFAs in in vivo models. Recently, studies have shown that EETs play a key role in blocking inflammation in a bone resorption process, but the mechanism is not clear. In the current study we used the sEH inhibitor (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea [TPPU]) to investigate the immunomodulatory effects in a mouse periodontitis model. MATERIAL AND METHODS: Mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 6) that were treated orally, daily for 15 days, with 1 mg/kg of TPPU. Then, the mice were killed and their jaws were analyzed for bone resorption using morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or western blotting. RESULTS: Infected mice treated with TPPU showed lower bone resorption than infected mice without treatment. Interestingly, infected mice showed increased expression of sEH; however, mice treated with TPPU had a reduction in expression of sEH. Besides, several proinflammatory cytokines and molecular markers were downregulated in the gingival tissue in the group treated with 1 mg/kg of TPPU. CONCLUSION: The sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model.
Assuntos
Reabsorção Óssea/imunologia , Reabsorção Óssea/prevenção & controle , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/antagonistas & inibidores , Epóxido Hidrolases/fisiologia , Imunomodulação/efeitos dos fármacos , Periodontite/imunologia , Periodontite/metabolismo , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Administração Oral , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Epóxido Hidrolases/metabolismo , Gengiva/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Compostos de Fenilureia/administração & dosagem , Piperidinas/administração & dosagemRESUMO
In the present work we propose a novel treatment to investigate ballistic electron transport under mechanical strain in a 1-D molecular bridge composed of alternating simple and triple bonds (polyyne) connected between two Single-Wall Carbon Nanotube (SWCNT) electrodes. Calculations with the DFT-NEGF methodology were performed in order to analyze this system at low values of mechanical strain (compression and distension) and at equilibrium length in the presence of bias voltages applied along the longitudinal direction. The results show that, while the mechanical strain displaces the energy levels and changes the band gap in the nanotube caps, the applied bias breaks the degeneracy in the nanotube cap states and defines the electrical conductance along the system. The analysis of the PDOS suggests that the main contribution to the electrical current comes from the superposition of the nanotube cap states, which is in agreement with the transmission calculation, and this device can be employed as a transistor observed in the I-V curve.
RESUMO
Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.
Assuntos
Melatonina/farmacologia , Atividade Motora/fisiologia , Fármacos Neuroprotetores/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Compressão da Medula Espinal/tratamento farmacológico , Animais , Modelos Animais de Doenças , Masculino , Melatonina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia , Compressão da Medula Espinal/patologia , Fatores de TempoRESUMO
Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.
Assuntos
Animais , Masculino , Ratos , Melatonina/farmacologia , Atividade Motora/fisiologia , Fármacos Neuroprotetores/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Compressão da Medula Espinal/tratamento farmacológico , Modelos Animais de Doenças , Melatonina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia , Compressão da Medula Espinal/patologia , Fatores de TempoRESUMO
As it is the case in all animal food production systems, it is often necessary to treat farmed fish for diseases and parasites. Quite frequently, fish farmers still rely on the aggressive use of copper to control bacterial infections and infestations by ecto-parasites, and to manage the spread of diseases. The susceptibility of the neotropical fish Rhamdia quelen to copper was here evaluated at different waterborne copper concentrations (2, 7 or 11 µg Cu L(-1)) for 96 h, through a multi biomarkers approach. Liver histopathological findings revealed leukocyte infiltration, hepatocyte vacuolization and areas of necrosis, causing raised levels of lesions upon exposure to 7 and 11 µg Cu L(-1). Decreased occurrence of free melano-macrophages and increased densities of melano-macrophage centers were noted upon exposure to 11 µg Cu L(-1). Gills showed damages on their secondary lamellae already at 2 µg Cu L(-1); hypertrophy and loss of the microridges of pavement cells at 7 and 11 µg L(-1), and increased in chloride cell (CC) apical surface area (4.9-fold) and in CC density (1.5-fold) at 11 µg Cu L(-1). In the liver, catalase (CAT), glutathione peroxidase activities (GPx) and glutathione concentration (GSH) remained unchanged, compared to the control group. However, there was inhibition of 7-ethoxyresorufin-O-deethylase (EROD) at all copper concentrations tested. Glutathione reductase activity (GR) was reduced and levels of lipid peroxidation (LPO) were increased at 11 µg Cu L(-1). Glutathione S-transferase activity (GST) at 7 µg Cu L(-1) and superoxide dismutase activity (SOD) at both 7 and 11 µg Cu L(-1) were reduced. However, copper exposure did not alter brain and muscle acetylcholinesterase (AChE) activity. Osmoregulatory function was also disturbed, in agreement with the above-mentioned changes noted in the gills, as detected by plasma osmolality reduction in the group exposed to 11 µg Cu L(-1), and plasma chloride reduction at 2 µg Cu L(-1). These concentrations also, coherently, lead to inhibition of branchial carbonic anhydrase activity. In the kidney, increased carbonic anhydrase activity was measured in the groups exposed to 2 and 7 µg Cu L(-1). When these effects are compared to data available in the literature for other freshwater fish, also for 96 h of exposure, R. quelen appears as a relatively sensitive species. In addition, the concentrations employed here were quite low in comparison to levels used for disease control in real culture practices (ranging from 4 µg Cu L(-1) used against bacteria to 6000 µg Cu L(-1) against fungal infections). We can conclude that the concentrations frequently employed in aquaculture are in fact not safe enough for this species. Such data are essential for the questioning and establishment of new policies to the sector.
Assuntos
Peixes-Gato/fisiologia , Cobre/toxicidade , Água Doce , Fígado/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Citocromo P-450 CYP1A1/metabolismo , Ativação Enzimática/efeitos dos fármacos , Enzimas/metabolismo , Pesqueiros , Brânquias/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacosRESUMO
7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson's disease.
Assuntos
Antidiscinéticos/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Indazóis/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Levodopa/farmacologia , Masculino , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacosRESUMO
7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson’s disease.
Assuntos
Animais , Masculino , Ratos , Antidiscinéticos/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Indazóis/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Levodopa/farmacologia , Ratos Wistar , Substância Negra/efeitos dos fármacosRESUMO
OBJECTIVES: Nitric oxide (NO) is a diffusible intracellular messenger that is present in saliva. Chronic treatment with isoproterenol, a beta receptor agonist, stimulates the release of NO from acinar cells and induces salivary gland hypertrophy. The aim of this study was to investigate the effect of NO synthesis inhibitors and isoproterenol on rat salivary glands. We analyzed salivary gland weight and the number of ducts per unit area (0.5mm(2)) by NADPH-diaphorase histochemistry (to identify the presence of the enzyme NO synthase-NOS) and haematoxylin-and-eosin (HE). METHODS: For 8 days male Wistar rats received daily single intraperitoneal injections of saline or a NOS inhibitor (40mg/kg N(omega)-nitro-L-arginine L-NOARG or N(omega)-nitro-l-arginine methyl ester L-NAME). This was followed, 30min later, by subcutaneous injection of isoproterenol (2 or 5mg/kg) or saline. RESULTS: Isoproterenol increased parotid and submandibular gland weights. Isoproterenol (2mg/kg) induced a decrease of ducts per unit area inversely correlated to the weight of the parotid gland. This effect was augmented by L-NAME. In the submandibular gland L-NAME attenuated isoproterenol (2mg/kg) weight increase. In the submandibular gland isoproterenol and NOS inhibitors induced an increase in ducts per unit area (HE and NADPH-diaphorase). No effect was observed in the sublingual gland. CONCLUSION: To our knowledge this is the first description of isoproterenol and NOS inhibitors increasing duct density in the submandibular gland. Our results corroborate the hypothesis that NO plays different roles in parotid and submandibular glands.
Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Isoproterenol/administração & dosagem , Nitroarginina/administração & dosagem , Ductos Salivares/efeitos dos fármacos , Animais , Inibidores Enzimáticos/administração & dosagem , Injeções Intraperitoneais , Injeções Subcutâneas , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Glândula Parótida/citologia , Glândula Parótida/efeitos dos fármacos , Glândula Parótida/metabolismo , Ratos , Ratos Endogâmicos BB , Ductos Salivares/metabolismo , Glândula Sublingual/citologia , Glândula Sublingual/efeitos dos fármacos , Glândula Sublingual/metabolismo , Glândula Submandibular/citologia , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/metabolismoRESUMO
RATIONALE: Catalepsy is a preclinical test that predicts extrapyramidal symptoms in humans. It models symptoms of acute extrapyramidal side effects induced at the beginning of antipsychotic treatment. Nitric oxide (NO) plays a role in a series of neurobiological functions underlying behavior. For example, inhibition of NO synthesis disrupts rodent exploratory behavior and induces catalepsy. Although several effects mediated by NO involve the activation of soluble guanylyl cyclase (sGC), the transduction mechanism of the catalepsy-inducing effect of NO has not yet been investigated. OBJECTIVES: The study was designed to test if intracerebroventricular (i.c.v.) microinjection of NO-sensitive inhibitors of sGC (NO-sGC) induces catalepsy in mice similar to that induced by NO synthase (NOS) inhibitors. Exploratory behavior was tested in the open field. In addition, the effects of a NOS inhibitor on oxidative metabolites of NO were measured in the striatum. MATERIALS AND METHODS: Drug effects were examined in the hanging-bar test after the following i.c.v. treatments: oxadiazolo-quinoxalin (ODQ, 30-300 nmol) or methylene blue (MB, 3-100 nmol), selective and nonselective sGC inhibitors, respectively, or 7-nitroindazole (7-NI, 3-90 nmol) and G-nitro-L: -arginine methyl ester (L: -NAME, 3-90 nmol), selective and nonselective neuronal NOS inhibitors. To test if the effects were related to interference with the NO system, additional groups received 7-NI (30 nmol), ODQ (100 nmol), or L-NAME (90 nmol) preceded by L: -arginine (L: -arg, 30-100 nmol, i.c.v. 30 min before). A possible interference of ODQ and 7-NI on exploratory behavior was tested in an open field. The concentration of nitrites and nitrates (NO( x )) in striatum homogenates was measured by the Griess reaction. RESULTS: Both NO-sGC and NOS inhibitors induced catalepsy in mice that lasted for at least 2 h. The range of effective doses of these drugs, however, was limited, and the dose-effect curves had an inverted U shape. The cataleptic effect induced by L: -NAME was inversely correlated with NO( x ) products in the striatum. The cataleptic effect of 7-NI and ODQ was prevented by pretreatment with L: -arginine. No drug changed exploratory behavior in the open field. CONCLUSION: This study showed that pharmacological disruption of the endogenous NO-sGC signaling in the central nervous system induces long-lasting catalepsy in mice. Moreover, the cataleptic effect of NOS inhibition correlates with the decrease in NO( x ) products formation in the striatum. The results give further support to the hypothesis that NO plays a role in motor behavior control mediated, at least in part, by cyclic guanosine monophosphate production in the striatum.
Assuntos
Catalepsia/induzido quimicamente , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Animais , Arginina/administração & dosagem , Arginina/farmacologia , Comportamento Animal/efeitos dos fármacos , Catalepsia/metabolismo , Catalepsia/prevenção & controle , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Indazóis/administração & dosagem , Indazóis/farmacologia , Injeções Intraventriculares , Masculino , Azul de Metileno/administração & dosagem , Azul de Metileno/farmacologia , Camundongos , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Oxidiazóis/administração & dosagem , Oxidiazóis/farmacologia , Quinoxalinas/administração & dosagem , Quinoxalinas/farmacologia , Transdução de Sinais , Guanilil Ciclase Solúvel , Fatores de TempoRESUMO
Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential for the study of cellular mechanisms of primary injury and repair after traumatic SC injury.
Assuntos
Comportamento Animal/fisiologia , Desempenho Psicomotor/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Laminectomia , Masculino , Exame Neurológico/métodos , Prognóstico , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential...
Assuntos
Animais , Masculino , Ratos , Comportamento Animal/fisiologia , Desempenho Psicomotor/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Modelos Animais de Doenças , Laminectomia , Exame Neurológico/métodos , Prognóstico , Ratos Wistar , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de TempoRESUMO
The objective of the present study was to propose an orthosis of light material that would be functional for the animal and that would maintain only the ankle joint immobilized. Male Wistar rats (3 to 4 months old, 250-300 g) were divided into 2 groups (N = 6): control and immobilized for 7 days. Rats were anesthetized with sodium pentobarbital (40 mg/kg weight) and the left hindlimb was immobilized with the orthoses composed of acrylic resin model, abdominal belt and lateral supports. The following analyses were performed: glycogen content of the soleus, extensor digitorum longus, white gastrocnemius, red gastrocnemius, and tibialis anterior muscles by the phenol sulfuric method, and the weight, fiber area and intramuscular connective tissue of the soleus by the planimetric system. Data were analyzed statistically by the Kolmogorov-Smirnov, Student t and Wilcoxon tests. Immobilization decreased glycogen in all muscles (P < 0.05; soleus: 31.6%, white gastrocnemius: 56.6%, red gastrocnemius: 39%, extensor digitorum longus: 41.7%, tibialis anterior: 45.2%) in addition to reducing soleus weight by 34% (P < 0.05). Furthermore, immobilization promoted reduction of the fiber area (43%, P < 0.05) and increased the connective tissue (200%, P < 0.05). The orthosis model was efficient comparing with another alternative immobilization model, like plaster casts, in promoting skeletal muscle alterations, indicating that it could be used as a new model in other studies related to muscle disuse.
Assuntos
Resinas Acrílicas , Elevação dos Membros Posteriores/métodos , Aparelhos Ortopédicos , Articulações Tarsianas , Animais , Glicogênio/análise , Elevação dos Membros Posteriores/instrumentação , Masculino , Músculo Esquelético/química , Ratos , Ratos WistarRESUMO
The objective of the present study was to propose an orthosis of light material that would be functional for the animal and that would maintain only the ankle joint immobilized. Male Wistar rats (3 to 4 months old, 250-300 g) were divided into 2 groups (N = 6): control and immobilized for 7 days. Rats were anesthetized with sodium pentobarbital (40 mg/kg weight) and the left hindlimb was immobilized with the orthoses composed of acrylic resin model, abdominal belt and lateral supports. The following analyses were performed: glycogen content of the soleus, extensor digitorum longus, white gastrocnemius, red gastrocnemius, and tibialis anterior muscles by the phenol sulfuric method, and the weight, fiber area and intramuscular connective tissue of the soleus by the planimetric system. Data were analyzed statistically by the Kolmogorov-Smirnov, Student t and Wilcoxon tests. Immobilization decreased glycogen in all muscles (P < 0.05; soleus: 31.6 percent, white gastrocnemius: 56.6 percent, red gastrocnemius: 39 percent, extensor digitorum longus: 41.7 percent, tibialis anterior: 45.2 percent) in addition to reducing soleus weight by 34 percent (P < 0.05). Furthermore, immobilization promoted reduction of the fiber area (43 percent, P < 0.05) and increased the connective tissue (200 percent, P < 0.05). The orthosis model was efficient comparing with another alternative immobilization model, like plaster casts, in promoting skeletal muscle alterations, indicating that it could be used as a new model in other studies related to muscle disuse.
Assuntos
Animais , Masculino , Ratos , Resinas Acrílicas , Elevação dos Membros Posteriores/métodos , Aparelhos Ortopédicos , Articulações Tarsianas , Glicogênio/análogos & derivados , Elevação dos Membros Posteriores/instrumentação , Músculo Esquelético/química , Ratos WistarRESUMO
RATIONALE: Systemic injections of nitric oxide synthase (NOS) inhibitors have been shown to decrease exploratory behavior in rats. This effect may be related to motor impairments since these drugs can induce catalepsy in rodents. OBJECTIVE: To compare the effects of two NOS inhibitors in tests aimed to investigate exploratory behavior and to assess motor control. METHODS: The acute effects of the NOS inhibitors NG-nitro- L-arginine ( L-NOARG, 10-80 mg/kg IP) and 7-nitroindazole (7-NIO, 3-30 mg/kg IP) on exploratory activity were analyzed in an open field arena. Drug effects on catalepsy were examined in the hanging-bar and wire-ring test. Footprint pattern after treatment with the two NOS inhibitors was evaluated and the results compared with those obtained with the dopamine D2 receptor antagonist haloperidol (1-2 mg/kg IP). Sub-chronic (twice a day for 4 days) effects of L-NOARG (40 mg/kg) or 7-NIO (30 mg/kg) were also tested in the open field arena and catalepsy test. RESULTS: L-NOARG and 7-NIO decreased locomotion and rearing in the open field arena. Both drugs induced catalepsy in the hanging-bar test but did not change footprint pattern. The cataleptic effect of L-NOARG in the hanging bar and wire-ring tests were highly correlated ( r=0.927). The exploratory and cataleptic effects of L-NOARG and 7-NIO provided evidence for tolerance after sub-chronic treatment. CONCLUSION: These results confirm that inhibition of neuronal NO formation induces impairment of exploratory behavior. This effect does not seem to involve aspects evaluated by footprint analysis, such as weight support, trunk stability and foot placement. They could, however, be related to drug-induced catalepsy.
Assuntos
Inibidores Enzimáticos/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Indazóis/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Animais , Catalepsia/induzido quimicamente , Relação Dose-Resposta a Droga , Masculino , CamundongosRESUMO
OBJECTIVE: Insulin inhibition of insulin secretion has been described in normal lean subjects. In this study, we examined whether this phenomenon also occurs in the morbidly obese who often have severe peripheral insulin resistance. SUBJECTS: Twelve obese patients, normotolerant to glucose (8 F/4 M, body mass index (BMI)=54.8+/-2.5 kg/m(2), 39 y) and 16 lean control subjects (10 F/6 M, BMI=22.0+/-0.5 kg/m(2), 31 y). DESIGN AND MEASUREMENTS: An experimental study using various parameters, including an euglycemic hyperinsulinemic clamp (280 pmol/min/m(2) of body surface), an oral glucose tolerance test (OGTT), electrical bioimpedance and indirect calorimetry. RESULTS: The obese subjects were insulin resistant (M=19.8+/-1.6 vs 48.7+/-2.6 micromol/min kg FFM, P<0.0001) and hyperinsulinemic in the fasted state and after glucose ingestion. Fasting plasma C-peptide levels (obese 1425+/-131 pmol/l vs lean 550+/-63 pmol/l; P<0.0001) decreased less during the clamp in the obese groups (-16.9+/-6.9% vs -43.0+/-5.6% relative to fasting values; P=0.007). In the lean group, the C-peptide decrease during the clamp (percentage variation) was related to insulin sensitivity, M/FFM (r=0.56, P=0.03), even after adjustment for the clamp glucose variation. CONCLUSION: We conclude that, in lean subjects, insulin inhibits its own secretion, and this may be related to insulin sensibility. This response is blunted in morbidly obese patients and may have a role in the pathogenesis of fasting hyperinsulinemia in these patients.
Assuntos
Peptídeo C/sangue , Hiperinsulinismo/etiologia , Resistência à Insulina/fisiologia , Insulina/sangue , Obesidade Mórbida/sangue , Adulto , Composição Corporal , Índice de Massa Corporal , Calorimetria Indireta , Estudos de Casos e Controles , Impedância Elétrica , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Hiperinsulinismo/sangue , Masculino , Obesidade Mórbida/fisiopatologiaRESUMO
A novel triterpene, viburgenin (1), has been isolated from an extract of the ripe fruit rinds of Rudgea viburnioides, together with the known saponins, arjunglucoside I and trachelosperosides B-1 and E-1, and the triterpenes trachelosperogenin B (2) and arjungenin. Compound 2 was previously obtained as a product from enzymatic hydrolysis, and it is reported for the first time as a natural product. The structure of compound 1 was determined as 2alpha,3beta, 19alpha,23,24-pentahydroxyurs-12-ene by extensive use of 1D and 2D NMR spectroscopic methods. Compound 1 exhibited moderate antifungal activity against Cladosporium cladosporioides.