RESUMO
OBJECTIVE: To establish the influence of overweight/obesity, medicated hypothyroidism, and medicated non-syndromic hypogrowth on maxillary and mandibular growth. MATERIALS AND METHODS: The relation between 10 craniofacial anthropometric measurements and hypothyroidism (n = 216), overweight/obesity (n = 108), and non-syndromic hypogrowth (n = 250) were evaluated in patients aged 1-19 years and a control group of healthy patients (n = 587). A subgroup analysis was performed at the peak growth in all groups. RESULTS: Patients with overweight/obesity and hypothyroidism showed increased craniofacial growth, while hypogrowth patients showed differences in zygomatic width and nasal base growth. Females with hypothyroidism and non-syndromic hypogrowth showed decreased head circumference at peak growth. Several anthropometric measurements were increased in patients with overweight/obesity, including head circumference. When all age groups were analyzed, overweight/obese and hypothyroidism patients showed increased zygomatic width while decreased hypogrowth. Overall, most craniofacial anthropometric measurements in overweight/obese patients were increased. Finally, the peak growth in males with hypothyroidism and subjects with non-syndromic hypogrowth was delayed compared to the control group (p < 0.05). CONCLUSIONS: Children and adolescents with overweight/obesity and endocrine disorders showed alterations in craniofacial growth. Clinicians must be aware that the growth peak in these patients may be delayed when planning maxillary and mandibular orthopedic treatment.
Assuntos
Hipotireoidismo , Sobrepeso , Masculino , Criança , Feminino , Humanos , Adolescente , Estudos Transversais , Colômbia , Obesidade/complicações , Hipotireoidismo/complicações , Índice de Massa CorporalRESUMO
PURPOSE: Recent evidences support a role of gut microbiota in influencing the efficacy of immune checkpoint inhibitors (ICI). The use of antibiotics (ATB) and other concomitant medications may impair the balance of microbiota and negatively affect the efficacy of immunotherapy. METHODS: Retrospective data analysis was performed on advanced cancer patients treated with ICI. Those receiving ATB within 4 weeks before or after initiating ICI were compared with those who did not. Likewise, those who received ATB (irrespective of time of onset) were compared with not exposed and was calculated the variable "ATB exposure" (AE) defined as the % "days of ATB/days of ICI". Use of proton pump inhibitors (PPIs), opioids and steroids was also evaluated. RESULTS: Of the 102 patients included, 60 (58.8%) received ATB during immunotherapy treatment (ATB+ group), and 33 (32.3%) received them between 4 weeks before or after starting ICI (ATB4+ group). Median AE of the ATB-treated patients was 11.1% (range 5.6-21.3). PFS and OS did not differ between ATB4+ and ATB4- group or between ATB+ group and not treated one. However, both PFS and OS were significantly lower in patients with a higher AE than the median one (3.1 vs. 8.2 months, p = 0.007; 9.4 vs. 17.8 months, p = 0.02, respectively). PPIs or steroids use did not affect clinical outcome of ICI but opioids use was significantly associated with lower PFS and OS (4.5 vs. 8.1 months, p = 0.010; 8.6 vs. 26.3 months, p < 0.001, respectively). CONCLUSIONS: Cumulative ATB use, rather than simple use in a defined time frame, may impair the efficacy of immunotherapy. Opioids use was also associated with poorer outcomes in patients treated with ICI.
Assuntos
Antibacterianos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Several physiological processes in the CNS are regulated by the endocannabinoid system (ECS). Cannabinoid receptors (CBr) and CBr agonists have been involved in the modulation of the N-methyl-D-aspartate receptor (NMDAr) activation. Glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids are endogenous metabolites produced and accumulated in the brain of children affected by severe organic acidemias (OAs) with neurodegeneration. Oxidative stress and excitotoxicity have been involved in the toxic pattern exerted by these organic acids. Studying the early pattern of toxicity exerted by these metabolites is crucial to explain the extent of damage that they can produce in the brain. Herein, we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) on early markers of GA-, 3-OHGA-, MMA- and PA-induced toxicity in brain synaptosomes from adult (90-day-old) and adolescent (30-day-old) rats. As pre-treatment, WIN exerted protective effects on the GA- and MMA-induced mitochondrial dysfunction, and prevented the reactive oxygen species (ROS) formation and lipid peroxidation induced by all metabolites. Our findings support a protective and modulatory role of cannabinoids in the early toxic events elicited by toxic metabolites involved in OAs.
Assuntos
Ácidos Acíclicos/metabolismo , Ácidos Acíclicos/toxicidade , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Benzoxazinas/farmacologia , Encefalopatias Metabólicas/metabolismo , Encéfalo/metabolismo , Agonistas de Receptores de Canabinoides/farmacologia , Glutaril-CoA Desidrogenase/deficiência , Morfolinas/farmacologia , Naftalenos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Glutaratos/metabolismo , Glutaratos/toxicidade , Glutaril-CoA Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ácido Metilmalônico/metabolismo , Ácido Metilmalônico/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Propionatos/metabolismo , Propionatos/toxicidade , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismoRESUMO
The brain of children affected by organic acidemias develop acute neurodegeneration linked to accumulation of endogenous toxic metabolites like glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids. Excitotoxic and oxidative events are involved in the toxic patterns elicited by these organic acids, although their single actions cannot explain the extent of brain damage observed in organic acidemias. The characterization of co-adjuvant factors involved in the magnification of early toxic processes evoked by these metabolites is essential to infer their actions in the human brain. Alterations in the kynurenine pathway (KP) - a metabolic route devoted to degrade tryptophan to form NAD(+) - produce increased levels of the excitotoxic metabolite quinolinic acid (QUIN), which has been involved in neurodegenerative disorders. Herein we investigated the effects of subtoxic concentrations of GA, 3-OHGA, MMA and PA, either alone or in combination with QUIN, on early toxic endpoints in rat brain synaptosomes. To establish specific mechanisms, we pre-incubated synaptosomes with different protective agents, including the endogenous N-methyl-d-aspartate (NMDA) receptor antagonist kynurenic acid (KA), the antioxidant S-allylcysteine (SAC) and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME). While the incubation of synaptosomes with toxic metabolites at subtoxic concentrations produced no effects, their co-incubation (QUIN+GA, +3-OHGA, +MMA or +PA) decreased the mitochondrial function and increased reactive oxygen species (ROS) formation and lipid peroxidation. For all cases, this effect was partially prevented by KA and l-NAME, and completely avoided by SAC. These findings suggest that early damaging events elicited by organic acids involved in metabolic acidemias can be magnified by toxic synergism with QUIN, and this process is mostly mediated by oxidative stress, and in a lesser extent by excitotoxicity and nitrosative stress. Therefore, QUIN can be hypothesized to contribute to the pathophysiology of brain degeneration in children with metabolic acidemias.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Encefalopatias Metabólicas/metabolismo , Encéfalo/metabolismo , Glutaratos/metabolismo , Glutaril-CoA Desidrogenase/deficiência , Ácido Quinolínico/metabolismo , Sinaptossomos/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Glutaratos/toxicidade , Glutaril-CoA Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ácido Metilmalônico/metabolismo , Ácido Metilmalônico/toxicidade , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Propionatos/metabolismo , Propionatos/toxicidade , Ácido Quinolínico/toxicidade , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sinaptossomos/efeitos dos fármacosRESUMO
The endocannabinoid system (ECS) is involved in a considerable number of physiological processes in the Central Nervous System. Recently, a modulatory role of cannabinoid receptors (CBr) and CBr agonists on the reduction of the N-methyl-d-aspartate receptor (NMDAr) activation has been demonstrated. Quinolinic acid (QUIN), an endogenous analog of glutamate and excitotoxic metabolite produced in the kynurenine pathway (KP), selectively activates NMDAr and has been shown to participate in different neurodegenerative disorders. Since the early pattern of toxicity exerted by this metabolite is relevant to explain the extent of damage that it can produce in the brain, in this work we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) and other agonists (anandamide or AEA, and CP 55,940 or CP) on early markers of QUIN-induced toxicity in rat striatal cultured cells and rat brain synaptosomes. WIN, AEA and CP exerted protective effects on the QUIN-induced loss of cell viability. WIN also preserved the immunofluorescent signals for neurons and CBr labeling that were decreased by QUIN. The QUIN-induced early mitochondrial dysfunction, lipid peroxidation and reactive oxygen species (ROS) formation were also partially or completely prevented by WIN pretreatment, but not when this CBr agonist was added simultaneously with QUIN to brain synaptosomes. These findings support a neuroprotective and modulatory role of cannabinoids in the early toxic events elicited by agents inducing excitotoxic processes.
Assuntos
Encéfalo/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/farmacologia , Fármacos Atuantes sobre Aminoácidos Excitatórios/toxicidade , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ácido Quinolínico/toxicidade , Animais , Ácidos Araquidônicos/farmacologia , Benzoxazinas/farmacologia , Encéfalo/fisiopatologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Cicloexanóis/farmacologia , Endocanabinoides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Mitocôndrias/metabolismo , Morfolinas/farmacologia , Naftalenos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Estresse Oxidativo/fisiologia , Alcamidas Poli-Insaturadas/farmacologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de Canabinoides/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/fisiologiaRESUMO
Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.
Assuntos
Anticarcinógenos/farmacologia , Glutationa/metabolismo , Isotiocianatos/farmacologia , Ácido Quinolínico/metabolismo , Animais , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Doenças Neurodegenerativas/metabolismo , Ratos Wistar , SulfóxidosRESUMO
Dogs play an important role in infectious disease transmission as reservoir hosts of many zoonotic and wildlife pathogens. Nevertheless, unlike wildlife species involved in the life cycle of pathogens, whose health status might be a direct reflection of their fitness and competitive abilities, dog health condition could be sensitive to socio-economic factors impacting the well-being of their owners. Here, we compare several dog health indicators in three rural communities of Panama with different degrees of socio-economic deprivation. From a total of 78 individuals, we collected blood and fecal samples, and assessed their body condition. With the blood samples, we performed routine hematologic evaluation (complete blood counts) and measured cytokine levels (Interferon-γ and Interleukin-10) through enzyme-linked immunosorbent assays. With the fecal samples we diagnosed helminthiases. Dogs were also serologically tested for exposure to Trypanosoma cruzi and canine distemper virus, and molecular tests were done to assess T. cruzi infection status. We found significant differences between dog health measurements, pathogen prevalence, parasite richness, and economic status of the human communities where the dogs lived. We found dogs that were less healthy, more likely to be infected with zoonotic pathogens, and more likely to be seropositive to canine distemper virus in the communities with lower economic status. This study concludes that isolated communities of lower economic status in Panama may have less healthy dogs that could become major reservoirs in the transmission of diseases to humans and sympatric wildlife.
Assuntos
Doenças do Cão/epidemiologia , Cães , Nível de Saúde , Animais de Estimação/fisiologia , Animais , Análise Química do Sangue , Doença de Chagas/epidemiologia , Doença de Chagas/veterinária , Estudos Transversais , Cinomose/epidemiologia , Vírus da Cinomose Canina/imunologia , Fezes/parasitologia , Feminino , Helmintíase Animal/epidemiologia , Humanos , Masculino , Panamá/epidemiologia , População Rural , Fatores Socioeconômicos , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologiaRESUMO
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor involved in the orchestration of antioxidant responses. Although its pharmacological activation has been largely hypothesized as a promising tool to ameliorate the progression of neurodegenerative events, the actual knowledge about its modulation in neurotoxic paradigms remains scarce. In this study, we investigated the early profile of Nrf2 modulation in striatal slices of rodents incubated in the presence of the toxic kynurenine pathway metabolite, quinolinic acid (QUIN). Tissue slices from rats and mice were obtained and used throughout the experiments in order to compare inter-species responses. Nuclear Nrf2 protein levels and oxidative damage to lipids were compared. Time- and concentration-response curves of all markers were explored. Nrf2 nuclear activation was corroborated through phase 2 antioxidant protein expression. The effects of QUIN on Nrf2 modulation and oxidative stress were also compared between slices of wild-type (Nrf2(+/+)) and Nrf2 knock-out (Nrf2(-/-)) mice. The possible involvement of the N-methyl-d-aspartate receptor (NMDAr) in the Nrf2 modulation and lipid peroxidation was further explored in mice striatal slices. In rat striatal slices, QUIN stimulated the Nrf2 nuclear translocation. This effect was accompanied by augmented lipid peroxidation. In the mouse striatum, QUIN per se exerted an induction of Nrf2 factor only at 1h of incubation, and a concentration-response effect on lipid peroxidation after 3h of incubation. QUIN stimulated the striatal content of phase 2 enzymes. Nrf2(-/-) mice were slightly more responsive than Nrf2(+/+) mice to the QUIN-induced oxidative damage, and completely unresponsive to the NMDAr antagonist MK-801 when tested against QUIN. Findings of this study indicate that: (1) Nrf2 is modulated in rodent striatal tissue in response to QUIN; (2) Nrf2(-/-) striatal tissue was moderately more vulnerable to oxidative damage than the Wt condition; and (3) early Nrf2 up-regulation reflects a compensatory response to the QUIN-induced oxidative stress in course as part of a general defense system, whereas Nrf2 down-regulation might contribute to more intense oxidative cell damage.
Assuntos
Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Ácido Quinolínico/toxicidade , Animais , Feminino , Humanos , Cinurenina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos WistarRESUMO
There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 µg/2 µL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.
Assuntos
Antioxidantes/farmacologia , Corpo Estriado/efeitos dos fármacos , Modelos Animais , Oxidopamina/toxicidade , Spirulina , Animais , Corpo Estriado/microbiologia , Corpo Estriado/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Resultado do TratamentoRESUMO
Quinolinic acid (QA)-induced overactivation of N-methyl-d-aspartate receptors yields excitotoxicity, oxidative stress and mitochondrial dysfunction, which altogether contribute to trigger a wide variety of toxic pathways with biochemical, behavioral and neuropathological alterations similar to those observed in Huntington's disease. Noteworthy, in the brains of these patients, increased expression of heme oxygenase-1 (HO-1) levels can be found. It has been proposed that this enzyme can exert a dual role, as it can be either protective or deleterious to the CNS. While some evidence indicates that its overexpression affords cellular anti-oxidant protection due to decreased concentrations of its pro-oxidative substrate heme group, and increased bilirubin levels, other reports established that high HO-1 expression and activity may result in a pro-oxidizing atmosphere due to a release of Fe(2+). In this work, we examined the temporal evolution of oxidative damage to proteins, HO-1 expression, immunoreactivity, total activity, and cell death after 1, 3, 5 and 7 days of an intrastriatal QA infusion (240 nmol/µl). QA was found to induce cellular degeneration, increasing carbonylated proteins and generating a transitory response in HO-1 mRNA, protein content, and immunoreactivity and activity in nerve cells. In order to study the role of HO-1 in the QA-induced cellular death, the tin protoporphyrin IX (SnPP), a well-known HO inhibitor, was administered to rats (30 µmol/kg, i.p.). The administration of SnPP to animals treated with QA inhibited the HO activation, and exacerbated the striatal cell damage induced by QA. Our findings reveal a potential modulatory role of HO-1 in the toxic paradigm evoked by QA in rats. This evidence provides a valuable tool for further approaches on HO-1 regulation in neurotoxic paradigms.
Assuntos
Corpo Estriado/metabolismo , Heme Oxigenase-1/antagonistas & inibidores , Degeneração Neural/metabolismo , Estresse Oxidativo/fisiologia , Regulação para Cima/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Heme Oxigenase-1/metabolismo , Masculino , Metaloporfirinas/farmacologia , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Protoporfirinas/farmacologia , Ácido Quinolínico , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 µM) were tested in cerebellum and forebrain homogenates exposed to 5 µM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 µM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 µM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 µM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 µM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA, in addition to be a well-known antagonist acting on nicotinic and NMDA receptors, can be considered as a potential endogenous antioxidant.
Assuntos
Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Ácido Cinurênico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Células Cultivadas , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Compostos Ferrosos/antagonistas & inibidores , Compostos Ferrosos/farmacologia , Hidróxidos/metabolismo , Ácido Cinurênico/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microinjeções , Nitrocompostos/antagonistas & inibidores , Nitrocompostos/farmacologia , Oócitos/metabolismo , Propionatos/antagonistas & inibidores , Propionatos/farmacologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Xenopus laevisRESUMO
Class II skeletal malocclusion and respiratory disorders owing to the obstruction of the upper airway at early growth stages have been correlated. The retro/micrognathism can be treated with functional appliances. However, the effects of an early functional orthopedic treatment on the airway dimensions have not been evaluated before the growth peak. Therefore, the objective of this study was to evaluate the changes in the airway dimensions of class II retrognathic children who received treatment with either Klammt or Bionator on a pre-pubertal stage. The sample consisted of 50 lateral cephalograms of class II retrognathic patients in a pre-puberal stage, before and after the use of a Klammt or Bionator II treatment for 1 year. The data were evaluated by Student's t-test or Mann-Whitney test, and significance was set at 5% (P < 0·05). When the measurements before and after treatment were compared, a statistically significant increase in the airway dimensions was found at the space where the adenoid tissue was located. The only airway dimensions that increased after treatment with functional appliances were the ones located at the nasopharynx. The adenoid tissue is still in the peak of growing at the ages of the subjects included in this study. However, the measurements along the nasopharynx increased when compared with the initial ones. Still, similar retrospective and prospective studies are needed at older stages.
Assuntos
Aparelhos Ativadores , Mandíbula/patologia , Desenvolvimento Maxilofacial , Orofaringe/patologia , Retrognatismo/patologia , Retrognatismo/terapia , Cefalometria , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/crescimento & desenvolvimento , Mandíbula/fisiopatologia , Orofaringe/diagnóstico por imagem , Orofaringe/crescimento & desenvolvimento , Orofaringe/fisiopatologia , Radiografia , Reprodutibilidade dos Testes , Retrognatismo/diagnóstico por imagem , Retrognatismo/fisiopatologia , Estudos RetrospectivosRESUMO
The prevalence of canine trypanosomosis was investigated in two Chagas disease endemic rural communities located in the central region of Panama. Serologic tests for Trypanosoma cruzi infection revealed a prevalence of 11.1%. Hemocultures coupled with PCR analysis demonstrated a Trypanosoma rangeli infection rate of 5.1%. An overall trypanosome infection index of 16.2% (16/99) was detected in this canine population. One dog had a mixed infection of T. cruzi and T. rangeli. Six of the trypanosome-infected dogs belong to people who were diagnosed of Chagas disease. We conclude that dogs from this rural area of Panama are frequently infected with trypanosomes transmitted by the sylvatic vector, Rhodnius pallescens, and suggest that dogs are important in the peridomestic transmission cycle of trypanosomes as reservoirs and hosts. The epidemiological implications of these findings are discussed.
Assuntos
Reservatórios de Doenças/veterinária , Doenças do Cão/parasitologia , Trypanosoma cruzi/isolamento & purificação , Tripanossomíase/veterinária , Zoonoses/parasitologia , Animais , Anticorpos Antiprotozoários/sangue , Distribuição de Qui-Quadrado , Estudos Transversais , Reservatórios de Doenças/parasitologia , Doenças do Cão/epidemiologia , Doenças do Cão/transmissão , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Humanos , Masculino , Panamá/epidemiologia , População Rural , Estudos Soroepidemiológicos , Tripanossomíase/epidemiologia , Tripanossomíase/parasitologia , Tripanossomíase/transmissão , Zoonoses/epidemiologia , Zoonoses/transmissãoRESUMO
Multidetector computed tomography (MDCT) and advances in CT urography techniques have enabled vast improvements in the depiction of the ureter. Studies of the ureter can find a wide variety of conditions including congenital defects and anatomic variants (anomalies in the origin, distribution, and distal insertion of the ureter) as well as all benign and malignant causes of focal and diffuse wall thickening (inflammatory and infectious processes, and neoplasms, as well as iatrogenic thickening and postsurgical changes). Other benign processes like ureteral kinking and stenosis due to extrinsic compression of the iliac vessels are also well characterized by MDCT. The aim of this article is to show the spectrum of ureteral variants and disease apart from common entities related to stones.
Assuntos
Tomografia Computadorizada por Raios X , Doenças Ureterais/diagnóstico por imagem , Humanos , Urografia/métodosRESUMO
The aim of this study was to precise the relationships of the auriculotemporal nerve in the infratemporal and parotid regions. We realized micro-dissections of thirty-two infratemporal and parotid regions of human cadaver's formol-fixed. The pattern of origin was: one root: 15.4%, two roots: 73.1%, three roots: 11.5%. In all cases, the lateral root present the major diameter (2-2.5 mm). In those cases with two roots, these formed a neural loop round the middle meningeal artery in the 89.4% of the cases. The origin of the medial root was the posterior border of the inferior alveolar nerve. The median distance between the lateral root and the temporomandibular joint capsule was 1.5 mm, with asymmetric pattern: right: 2 mm (rank: 0-7 mm; ED: 1.90 mm); left: 1.25 mm (rank: 0-3 mm; ED: 0.88 mm). In 10 cases (31.3%) the lateral root was in direct contact with the articular capsule, with asymmetric pattern: left: 46.1%; right: 21%. The median distance between the superior aspect of the articular disk and the trunk of the auriculotemporal nerve in the posterior aspect of the temporomandibular joint was 10,5 mm (ED: 4.06 mm), with asymmetric pattern: right: 9 mm (rank: 5-18.0 mm; ED: 3.70 mm); left: 11.0 mm (rank: 3.0-20 mm; ED: 4.41 mm). We discussed the rol of this findings in the etiology of the Frey's syndrome.
Assuntos
Nervo Mandibular/anatomia & histologia , Sudorese Gustativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Nervo Mandibular/patologia , Pessoa de Meia-Idade , Glândula Parótida/anatomia & histologia , Sudorese Gustativa/patologia , Articulação Temporomandibular/anatomia & histologiaRESUMO
Huntington's disease (HD) is a demential, neurodegenerative inheritable disease affecting middle-aged patients. HD is characterized by uncontrolled choreiform movements, psychiatric symptoms and cognitive decline. Histopathological changes in HD brains reveal a considerable damage to basal ganglia, particularly affecting middle-sized spiny neurons from the caudate-putamen region. Neurochemical changes are specifically oriented to deplete GABAergic and cholinergic systems, while molecular alterations include an increased expression of CAG trinucleotide at exon 1 from the huntingtin (htt) gene, as well as aggregation of mutant htt. Although several hypotheses regarding the mechanisms by which neurotoxicity is triggered in HD brains have been suggested on the basis of experimental evidence, so far it remains not clear which of them are predominant or whether they are complementary. Recent experimental evidence through transgenic mice models reveal an interesting interaction between expanded CAG triplets, mutant htt, and the increase in toxic metabolites from the kynurenine pathway. Further evidence supports the assumption that different toxic mechanisms (i.e. excitotoxicity, energy metabolism impairment, inflammatory events, oxidative stress, etc.) are confluent and depend on each other. In this review we will briefly summarize some of those findings and propose a final integrative hypothesis for HD.
Assuntos
Doença de Huntington/metabolismo , Neurônios/metabolismo , Animais , Cálcio/metabolismo , Morte Celular , Modelos Animais de Doenças , Metabolismo Energético , Aminoácidos Excitatórios/metabolismo , Humanos , Doença de Huntington/induzido quimicamente , Doença de Huntington/genética , Doença de Huntington/patologia , Inflamação/metabolismo , Ácido Cinurênico/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Neurônios/patologia , Nitrocompostos , Estresse Oxidativo , Propionatos , Ácido Quinolínico , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Repetições de Trinucleotídeos , Triptofano/metabolismoRESUMO
Oxidative/nitrosative stress is involved in NMDA receptor-mediated excitotoxic brain damage produced by the glutamate analog quinolinic acid. The purpose of this work was to study a possible role of peroxynitrite, a reactive oxygen/nitrogen species, in the course of excitotoxic events evoked by quinolinic acid in the brain. The effects of Fe(TPPS) (5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III)), an iron porphyrinate and putative peroxynitrite decomposition catalyst, were tested on lipid peroxidation and mitochondrial function in brain synaptic vesicles exposed to quinolinic acid, as well as on peroxynitrite formation, nitric oxide synthase and superoxide dismutase activities, lipid peroxidation, caspase-3-like activation, DNA fragmentation, and GABA levels in striatal tissue from rats lesioned by quinolinic acid. Circling behavior was also evaluated. Increasing concentrations of Fe(TPPS) reduced lipid peroxidation and mitochondrial dysfunction induced by quinolinic acid (100 microM) in synaptic vesicles in a concentration-dependent manner (10-800 microM). In addition, Fe(TPPS) (10 mg/kg, i.p.) administered 2 h before the striatal lesions, prevented the formation of peroxynitrite, the increased nitric oxide synthase activity, the decreased superoxide dismutase activity and the increased lipid peroxidation induced by quinolinic acid (240 nmol/microl) 120 min after the toxin infusion. Enhanced caspase-3-like activity and DNA fragmentation were also reduced by the porphyrinate 24 h after the injection of the excitotoxin. Circling behavior from quinolinic acid-treated rats was abolished by Fe(TPPS) six days after quinolinic acid injection, while the striatal levels of GABA, measured one day later, were partially recovered. The protective effects that Fe(TPPS) exerted on quinolinic acid-induced lipid peroxidation and mitochondrial dysfunction in synaptic vesicles suggest a primary action of the porphyrinate as an antioxidant molecule. In vivo findings suggest that the early production of peroxynitrite, altogether with the enhanced risk of superoxide anion (O2*-) and nitric oxide formation (its precursors) induced by quinolinic acid in the striatum, are attenuated by Fe(TPPS) through a recovery in the basal activities of nitric oxide synthase and superoxide dismutase. The porphyrinate-mediated reduction in DNA fragmentation simultaneous to the decrease in caspase-3-like activation from quinolinic acid-lesioned rats suggests a prevention in the risk of peroxynitrite-mediated apoptotic events during the course of excitotoxic damage in the striatum. In summary, the protective effects that Fe(TPPS) exhibited both under in vitro and in vivo conditions support an active role of peroxynitrite and its precursors in the pattern of brain damage elicited by excitotoxic events in the experimental model of Huntington's disease. The neuroprotective mechanisms of Fe(TPPS) are discussed.
Assuntos
Lesões Encefálicas/metabolismo , Doença de Huntington/prevenção & controle , Ácido Peroxinitroso/metabolismo , Porfirinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Análise de Variância , Animais , Comportamento Animal , Southern Blotting/métodos , Lesões Encefálicas/complicações , Caspase 3 , Caspases/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletroforese em Gel de Ágar/métodos , Doença de Huntington/etiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Mitocôndrias/fisiologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Óxido Nítrico Sintase/metabolismo , Ácidos Quinolínicos/farmacologia , Ratos , Ratos Wistar , Teste de Desempenho do Rota-Rod/métodos , Superóxido Dismutase/metabolismo , Vesículas Sinápticas/metabolismo , Sinaptossomos/fisiologia , Tirosina/análogos & derivados , Tirosina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
We studied the effect of an acute infusion of quinolinic acid (QUIN) on in vivo hydroxyl radical (.OH) formation in the striatum of awake rats. Using the microdialysis technique, the generation of.OH was assessed through electrochemical detection of the salicylate hydroxylation product 2,3-dihydroxybenzoic acid (2,3-DHBA). The .OH extracellular levels increased up to 30 times over basal levels after QUIN infusion (240 nmol/microl), returning to the baseline 2 h later. This response was attenuated, but not abolished, by pretreatment with the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.) 60 min before QUIN infusion. The mitochondrial toxin 3-nitropropionic acid (3-NPA, 500 nmol/microl) had stronger effects than QUIN on .OH generation, as well as on other markers of oxidative stress explored as potential consequences of .OH increased levels. These results support the hypothesis that early .OH generation contributes to the pattern of toxicity elicited by QUIN. The partial protection by MK-801 suggests that QUIN neurotoxicity is not completely explained through NMDA receptor overactivation, but it may also involve intrinsic QUIN oxidative properties.
Assuntos
Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Radical Hidroxila/metabolismo , Ácido Quinolínico/administração & dosagem , Animais , Cromatografia Líquida de Alta Pressão , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hidroxibenzoatos/análise , Hidroxibenzoatos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microdiálise , Microinjeções , Fármacos Neuroprotetores/farmacologia , Nitrocompostos , Estresse Oxidativo , Perfusão , Propionatos/administração & dosagem , Ratos , Ratos Wistar , Ácido Salicílico/administração & dosagem , Ácido Salicílico/metabolismo , VigíliaRESUMO
The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.