RESUMO
The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.
Assuntos
Neoplasias da Mama , Canais de Cálcio Tipo T , Humanos , Feminino , Cálcio/metabolismo , Canais de Cálcio Tipo T/metabolismoRESUMO
The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.
RESUMO
The dopaminergic system plays an essential role in maintaining homeostasis between the central nervous system (CNS) and the immune system. Previous studies have associated imbalances in the dopaminergic system to the pathogenesis of multiple sclerosis (MS). Here, we examined the protein levels of dopaminergic receptors (D1R and D2R) in different phases of the experimental autoimmune encephalomyelitis (EAE) model. We also investigated if the treatment with pramipexole (PPX)-a dopamine D2/D3 receptor-preferring agonist-would be able to prevent EAE-induced motor and mood dysfunction, as well as its underlying mechanisms of action. We report that D2R immunocontent is upregulated in the spinal cord of EAE mice 14 days post-induction. Moreover, D1R and D2R immunocontents in lymph nodes and the oxidative damage in the spinal cord and striatum of EAE animals were significantly increased during the chronic phase. Also, during the pre-symptomatic phase, axonal damage in the spinal cord of EAE mice could already be found. Surprisingly, therapeutic treatment with PPX failed to inhibit the progression of EAE. Of note, PPX treatment inhibited EAE-induced depressive-like while failed to inhibit anhedonic-like behaviors. We observed that PPX treatment downregulated IL-1ß levels and increased BNDF content in the spinal cord after EAE induction. Herein, we show that a D2/D3 receptor-preferred agonist mitigated EAE-induced depressive-like behavior, which could serve as a new possibility for further clinical trials on treating depressive symptoms in MS patients. Thus, we infer that D2R participates in the crosstalk between CNS and immune system during autoimmune and neuroinflammatory response induced by EAE, mainly in the acute and chronic phase of the disease.
Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Anedonia/efeitos dos fármacos , Anedonia/fisiologia , Animais , Axônios/patologia , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Corpo Estriado/metabolismo , Depressão/etiologia , Depressão/prevenção & controle , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/psicologia , Feminino , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Estresse Oxidativo , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/genética , Pramipexol/farmacologia , Pramipexol/uso terapêutico , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D3/agonistas , Método Simples-Cego , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
The objective was to evaluate the available published data on sinonasal melanoma and analyse its clinical features, treatment modalities, and prognostic factors. An electronic search was undertaken in March 2018 in multiple databases. Eligibility criteria included publications with sufficient clinical, histological, and immunohistochemical information to confirm the diagnosis. Seventy-three publications (439 cases) were included. The lesion was more prevalent in females than in males. There was a higher prevalence in the seventh and eighth decades of life. The lesions mainly presented as epistaxis and commonly involved the nasal cavity. Age (>67.6 years; P=0.0012), primary location (middle turbinate; P=0.0112), disease stage (advanced disease stage; P=0.0026), treatment (radiotherapy; P=0.0111), recurrence (recurrence presented; P=0.0137), and distant metastasis (distant metastasis presented; P=0.0011) were independently associated with a lower survival rate. Recurrence was significantly correlated with age (>67.6 years; P=0.0021), sex (males tended to present a higher recurrence rate than females; P=0.0051), disease stage (stages III and IV presented a higher recurrence rate than stages I and II; P=0.0331), and histological type (amelanotic lesions presented a higher index of recurrence than melanotic lesions; P=0.0095). In conclusion, sinonasal melanoma is a neoplasm with a poor prognosis, presenting a 30.69% possibility of survival after 5 years.
Assuntos
Melanoma , Recidiva Local de Neoplasia , Feminino , Humanos , Masculino , Cavidade Nasal , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
O objetivo do presente experimento foi avaliar efeito do estresse e da dificuldade de inseminação (DifIA) sobre a taxa de concepção (TC) de vacas (n=93) e novilhas (n= 72) Nelore submetidas à IATF. No D9, anotou-se nota de temperamento (NTe) e tempo da saída do brete (TSB) de todos os animais e coletou-se sangue das novilhas. No dia da IATF (D11), anotou-se NTe, TSB, DifIA e tempo de IA. A TC foi 36% para vacas e 46% para novilhas (P>0,05). Não foi observado efeito de Nte sobre TC (P>0,05). Porém, houve tendência para maior (P<0,10) TC nos animais que não apresentaram dificuldade de inseminação (DifIA1; TP=42%) em comparação aos animais com moderada ou alta dificuldade (DifIA2+DifIA3; TP=27%). Foi observado menor (P<0,05) tempo de IA para animais DifIA1 (17:31±06:02s) que animais DifIA2-3 (30:10±15:45s). Novilhas com maiores (P<0,05) níveis de cortisol apresentaram maior NTe (P<0,05). Entretanto, TC (59%) das novilhas menos reativas (cortisol=4,12±1,12ng/mL; NTe=3,2±0,6) não diferiu da TC (41%; P>0,05) das mais agitadas (cortisol=7,76±1,33ng/mL; NTe=3,82±0,79). Concluiu-se que avaliações de temperamento se relacionaram com nível de estresse, embora esses parâmetros não tenham afetado a TC deste trabalho. A maior dificuldade e/ou tempo necessário para se completar a IA demonstrou ser um potencial fator para a redução da fertilidade na IATF.(AU)
The objective was to evaluate the influence of stress and difficulty of insemination (DifIA) on conception rate (CR) of Nellore cows (n= 93) and heifers (n= 72) in Timed-AI. On D9, temperament (NTe) and time for chute exit (TSB) were recorded for all animals, and blood samples were colected from heifers. On the day of Timed-AI (D11), NTe, TSB, DifIA and time for AI were recorded. For cows, CR was 36% and for heifers 46% (P> 0.05). No effect (P> 0.05) of NTe was observed on CR. However, a tendency (P< 0,10) for higher CR was observed in animals with no difficulty for insemination (DifIA1; CR=42%) compared to animals that presented moderate or high difficulty (DifIA2+DifIA3, CR=27%). Time required for AI was lower (P< 0.05) in animals DifIA1 (17:31±06:02sec) than in animals DifIA2-3 (30:10±15:45sec). Heifers with greater (P< 0.05) cortisol levels presented higher Nte (P< 0.05). However, CR (59%) of less reactive heifers (cortisol=4,12±1,12ng/mL; NTe=3,2±0,6) did not differ from CR (41%; P> 0.05) of stressed animals (cortisol=7,76±1,33ng/mL; NTe=3,82±0,79). It was concluded that assessments of temperament were related to stress level, although these parameters did not affect the CR of this study. However, the higher difficulty and/or time to complete AI showed to be a potential factor for reducing fertility after timed-AI.(AU)
Assuntos
Animais , Feminino , Bovinos , Estresse Fisiológico , Hidrocortisona/sangue , Inseminação Artificial/métodos , Inseminação Artificial/veterinária , FertilidadeRESUMO
O objetivo do presente experimento foi avaliar efeito do estresse e da dificuldade de inseminação (DifIA) sobre a taxa de concepção (TC) de vacas (n=93) e novilhas (n= 72) Nelore submetidas à IATF. No D9, anotou-se nota de temperamento (NTe) e tempo da saída do brete (TSB) de todos os animais e coletou-se sangue das novilhas. No dia da IATF (D11), anotou-se NTe, TSB, DifIA e tempo de IA. A TC foi 36% para vacas e 46% para novilhas (P>0,05). Não foi observado efeito de Nte sobre TC (P>0,05). Porém, houve tendência para maior (P<0,10) TC nos animais que não apresentaram dificuldade de inseminação (DifIA1; TP=42%) em comparação aos animais com moderada ou alta dificuldade (DifIA2+DifIA3; TP=27%). Foi observado menor (P<0,05) tempo de IA para animais DifIA1 (17:31±06:02s) que animais DifIA2-3 (30:10±15:45s). Novilhas com maiores (P<0,05) níveis de cortisol apresentaram maior NTe (P<0,05). Entretanto, TC (59%) das novilhas menos reativas (cortisol=4,12±1,12ng/mL; NTe=3,2±0,6) não diferiu da TC (41%; P>0,05) das mais agitadas (cortisol=7,76±1,33ng/mL; NTe=3,82±0,79). Concluiu-se que avaliações de temperamento se relacionaram com nível de estresse, embora esses parâmetros não tenham afetado a TC deste trabalho. A maior dificuldade e/ou tempo necessário para se completar a IA demonstrou ser um potencial fator para a redução da fertilidade na IATF.(AU)
The objective was to evaluate the influence of stress and difficulty of insemination (DifIA) on conception rate (CR) of Nellore cows (n= 93) and heifers (n= 72) in Timed-AI. On D9, temperament (NTe) and time for chute exit (TSB) were recorded for all animals, and blood samples were colected from heifers. On the day of Timed-AI (D11), NTe, TSB, DifIA and time for AI were recorded. For cows, CR was 36% and for heifers 46% (P> 0.05). No effect (P> 0.05) of NTe was observed on CR. However, a tendency (P< 0,10) for higher CR was observed in animals with no difficulty for insemination (DifIA1; CR=42%) compared to animals that presented moderate or high difficulty (DifIA2+DifIA3, CR=27%). Time required for AI was lower (P< 0.05) in animals DifIA1 (17:31±06:02sec) than in animals DifIA2-3 (30:10±15:45sec). Heifers with greater (P< 0.05) cortisol levels presented higher Nte (P< 0.05). However, CR (59%) of less reactive heifers (cortisol=4,12±1,12ng/mL; NTe=3,2±0,6) did not differ from CR (41%; P> 0.05) of stressed animals (cortisol=7,76±1,33ng/mL; NTe=3,82±0,79). It was concluded that assessments of temperament were related to stress level, although these parameters did not affect the CR of this study. However, the higher difficulty and/or time to complete AI showed to be a potential factor for reducing fertility after timed-AI.(AU)
Assuntos
Animais , Feminino , Bovinos , Estresse Fisiológico , Hidrocortisona/sangue , Inseminação Artificial/métodos , Inseminação Artificial/veterinária , FertilidadeRESUMO
Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Canais de Sódio Disparados por Voltagem/metabolismo , Feminino , Humanos , Invasividade Neoplásica , Metástase NeoplásicaRESUMO
We investigated the effects of physical exercise (PE) on locomotor activity and anxiety-like behavior in Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) male rats. Rats received either four weeks of forced training, 5days/week, on a treadmill (experiment 1) or were given 21days of free access to running wheels (experiment 2). We also tested the effects of social isolation (SI) (seven days of isolation - experiment 3) on behavior. In experiment 1, 20% of LEW rats and 63% of SHR rats completed the training protocol. PE significantly increased central and peripheral locomotion in the open field (OF) and entries into the open arms in the elevated plus-maze (EPM) in both strains. In experiment 2, the distance traveled by SHR rats on running wheels was significantly higher compared with LEW rats. PE on running wheels also increased the time spent in the center of the OF in SHR rats only. In experiment 3, SI decreased central and peripheral locomotion in the OF in both strains. In summary, forced PE on a treadmill reduced anxiety-like behavior and increased locomotion in male rats of both strains, whereas voluntary PE on running wheels decreased anxiety-like behavior in SHR rats only. SI decreased locomotion in both strains in the OF. This study suggests that spontaneous activity levels are genotype-dependent and the effects of PE depend on the type of exercise performed.
Assuntos
Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Atividade Motora/fisiologia , Condicionamento Físico Animal/fisiologia , Isolamento Social , Agressão/fisiologia , Agressão/psicologia , Animais , Ansiedade/psicologia , Masculino , Condicionamento Físico Animal/psicologia , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos SHR , Ratos EndogâmicosRESUMO
This study aimed to evaluate Himatanthus drasticus latex in a mice wound healing experimental model. Animals were divided into four groups (n=7) according to the treatments: GI - saline 0.9% (control), GII - mineral oil (vehicle), GIII - H. drasticus commercial latex (HdCL) and GIV - H. drasticus mixed isolated fraction (MIF, 1 mg/mL). The treatments were applied topically once daily, 50 µL for 14 consecutive days. Macroscopic lesions were evaluated, considering parameters such as swelling, redness, granulation tissue and reepithelialization. VEGF+, CD68+ expressions and mast cells (Toluidin blue stain) were evaluated. HdCL induced higher contraction and exuberant granulation tissue (P > 0.05). HdCL showed a mild inflammatory process while MIF induced intense infiltrate inflammatory predominantly by lymphocytes, vascular congestion, bleeding and did not presented full reepithelialization. Reorganization of collagen fibers (red picrosirius stain) was observed. CD68+ expression and mast cells were presented as moderate, intense and mild in GI, GIII and GIV, respectively. Neovascularization occurred in all groups, while VEGF+ expression was intense in MIF in relation to HdCL. We concluded that HdCL presents wound healing potential, through modulation of mast cells, CD68+ and VEGF+ expressions that can be associated to triterpenes presence according MIF isolated from HdCL.(AU)
Objetivou-se avaliar o látex de Himatanthus drasticus em feridas induzidas experimentalmente em camundongos. Os animais foram divididos em quatro grupos (n=7): GI - salina 0,9% (controle), GII - óleo mineral (veículo), GIII - látex comercial de H. drasticus (HdCL) e GIV - fração isolada mista de H. drasticus (MIF, 1mg/mL). Os tratamentos foram aplicados topicamente uma vez ao dia (50µL), durante 14 dias consecutivos. Lesões macroscópicas, as expressões de VEGF+, CD68+ e a participação dos mastócitos (coloração azul de toluidina) foram avaliadas. HdCL induziu maior contração e tecido de granulação exuberante (P >0,05). HdCL induziu leve processo inflamatório enquanto MIF promoveu intenso infiltrado inflamatório predominantemente linfocítico, congestão vascular, hemorragia e reepitelização parcial. Observou-se reorganização das fibras colágenas (coloração picrosírius). A expressão de CD68+ e os mastócitos apresentaram-se moderados, intensos e leves em GI, GIII e GIV, respectivamente. A neovascularização foi observada em todos os grupos, enquanto a expressão de VEGF+ foi mais intensa em MIF em relação a HdCL. Conclui-se que HdCL apresenta potencial de cicatrização por meio da modulação dos mastócitos e das expressões de CD68+ e VEGF+, o que pode estar associado à presença de triterpenos de acordo com MIF isolada de HdCL.(AU)
Assuntos
Animais , Camundongos , Indutores da Angiogênese/análise , Apocynaceae/química , Glicoproteínas , Mastócitos , Fator A de Crescimento do Endotélio Vascular/análise , Cicatrização/efeitos dos fármacos , Látex/químicaRESUMO
This study aimed to evaluate Himatanthus drasticus latex in a mice wound healing experimental model. Animals were divided into four groups (n=7) according to the treatments: GI - saline 0.9% (control), GII - mineral oil (vehicle), GIII - H. drasticus commercial latex (HdCL) and GIV - H. drasticus mixed isolated fraction (MIF, 1 mg/mL). The treatments were applied topically once daily, 50 µL for 14 consecutive days. Macroscopic lesions were evaluated, considering parameters such as swelling, redness, granulation tissue and reepithelialization. VEGF+, CD68+ expressions and mast cells (Toluidin blue stain) were evaluated. HdCL induced higher contraction and exuberant granulation tissue (P > 0.05). HdCL showed a mild inflammatory process while MIF induced intense infiltrate inflammatory predominantly by lymphocytes, vascular congestion, bleeding and did not presented full reepithelialization. Reorganization of collagen fibers (red picrosirius stain) was observed. CD68+ expression and mast cells were presented as moderate, intense and mild in GI, GIII and GIV, respectively. Neovascularization occurred in all groups, while VEGF+ expression was intense in MIF in relation to HdCL. We concluded that HdCL presents wound healing potential, through modulation of mast cells, CD68+ and VEGF+ expressions that can be associated to triterpenes presence according MIF isolated from HdCL.(AU)
Objetivou-se avaliar o látex de Himatanthus drasticus em feridas induzidas experimentalmente em camundongos. Os animais foram divididos em quatro grupos (n=7): GI - salina 0,9% (controle), GII - óleo mineral (veículo), GIII - látex comercial de H. drasticus (HdCL) e GIV - fração isolada mista de H. drasticus (MIF, 1mg/mL). Os tratamentos foram aplicados topicamente uma vez ao dia (50µL), durante 14 dias consecutivos. Lesões macroscópicas, as expressões de VEGF+, CD68+ e a participação dos mastócitos (coloração azul de toluidina) foram avaliadas. HdCL induziu maior contração e tecido de granulação exuberante (P >0,05). HdCL induziu leve processo inflamatório enquanto MIF promoveu intenso infiltrado inflamatório predominantemente linfocítico, congestão vascular, hemorragia e reepitelização parcial. Observou-se reorganização das fibras colágenas (coloração picrosírius). A expressão de CD68+ e os mastócitos apresentaram-se moderados, intensos e leves em GI, GIII e GIV, respectivamente. A neovascularização foi observada em todos os grupos, enquanto a expressão de VEGF+ foi mais intensa em MIF em relação a HdCL. Conclui-se que HdCL apresenta potencial de cicatrização por meio da modulação dos mastócitos e das expressões de CD68+ e VEGF+, o que pode estar associado à presença de triterpenos de acordo com MIF isolada de HdCL.(AU)
Assuntos
Animais , Camundongos , Apocynaceae/química , Cicatrização , Indutores da Angiogênese/análise , Mastócitos , Fator A de Crescimento do Endotélio Vascular/análise , Glicoproteínas , Látex/químicaRESUMO
Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.
Assuntos
Síndrome do Nevo Basocelular/complicações , Síndrome do Nevo Basocelular/genética , Carcinoma Basocelular/complicações , Carcinoma Basocelular/genética , Mutação da Fase de Leitura , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/genética , Neoplasias Orbitárias/etiologia , Receptores de Superfície Celular/genética , Teratoma/etiologia , Adolescente , Síndrome do Nevo Basocelular/diagnóstico , Encéfalo/patologia , Carcinoma Basocelular/diagnóstico , Análise Mutacional de DNA , Mutação em Linhagem Germinativa , Síndrome do Hamartoma Múltiplo/diagnóstico , Humanos , Masculino , Neoplasias Orbitárias/congênito , Neoplasias Orbitárias/diagnóstico , Receptores Patched , Receptor Patched-1 , Radiografia Panorâmica , Teratoma/congênito , Teratoma/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The aim of this study was to analyse the visual perceptions of different experts with respect to multilocular radiolucent lesions in circumstances when the diagnosis is either known or unknown. METHODS: 6 radiographs of ameloblastomas (AMELs), keratocystic odontogenic tumours (KOTs), central giant cell lesions (CGCLs) and myxomas (MIXs) were analysed by 16 dental experts [stomatologists/oral surgeons (SS) and dental radiologists (R)]. They delimited the lesions prior to having knowledge of the diagnosis (T1) and after 30 days, when they were aware of the histopathological results (T2). For each image, the following morphometric parameters were calculated: area (A), perimeter (P) and shape factor (SF); after image subtraction procedures (T1 - T2), the exclusive area (EA) of the non-overlapping delimited region was also calculated. RESULTS: For both groups, the T2 area was larger than the T1, although the EA of the SS group was higher than that of the R group independently of the type of lesion. The SF from the SS group was greater than that from the R group, and at T2 the SF values were higher for both groups. AMELs and MIXs showed larger SF and A values; the SS group tended to have the greatest changes in the delimitations of the lesions at T2. CONCLUSIONS: The methodology allowed us to quantify differences in the spatial perceptions of professionals. The knowledge of the diagnosis and the expertise of examiners influenced the examiner's perception of the limits of the lesions independently of the actual biological behaviour of the lesion.
Assuntos
Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/patologia , Invasividade Neoplásica/patologia , Percepção Visual , Ameloblastoma/diagnóstico por imagem , Análise de Variância , Tumores de Células Gigantes/diagnóstico por imagem , Humanos , Mixoma/diagnóstico por imagem , Variações Dependentes do Observador , Tumores Odontogênicos/diagnóstico por imagem , Intensificação de Imagem Radiográfica , Estatísticas não Paramétricas , Técnica de SubtraçãoRESUMO
Ursolic acid, a constituent from Rosmarinus officinalis, is a triterpenoid compound which has been extensively known for its anticancer and antioxidant properties. In the present study, we investigated the antidepressant-like effect of ursolic acid isolated from this plant in two predictive tests of antidepressant property, the tail suspension test (TST) and the forced swimming test (FST) in mice. Furthermore, the involvement of dopaminergic system in its antidepressant-like effect was investigated in the TST. Ursolic acid reduced the immobility time in the TST (0.01 and 0.1mg/kg, p.o.) and in the FST (10mg/kg, p.o.), similar to fluoxetine (10mg/kg, p.o.), imipramine (1mg/kg, p.o.) and bupropion (10mg/kg, p.o.). The effect of ursolic acid (0.1mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with SCH23390 (0.05mg/kg, s.c., a dopamine D(1) receptor antagonist) and sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist). The administration of a sub-effective dose of ursolic acid (0.001mg/kg, p.o.) in combination with sub-effective doses of SKF38393 (0.1mg/kg, s.c., a dopamine D(1) receptor agonist), apomorphine (0.5µg/kg, i.p., a preferential dopamine D(2) receptor agonist) or bupropion (1mg/kg, i.p., a dual dopamine/noradrenaline reuptake inhibitor) reduced the immobility time in the TST as compared with either drug alone. Ursolic acid and dopaminergic agents alone or in combination did not cause significant alterations in the locomotor and exploratory activities. These results indicate that the antidepressant-like effect of ursolic acid in the TST is likely mediated by an interaction with the dopaminergic system, through the activation of dopamine D(1) and D(2) receptors.
Assuntos
Antidepressivos/farmacologia , Dopamina/fisiologia , Rosmarinus/química , Triterpenos/farmacologia , Animais , Antidepressivos/isolamento & purificação , Comportamento Animal , Masculino , Camundongos , Natação , Triterpenos/isolamento & purificação , Ácido UrsólicoRESUMO
Folic acid (folate) is a vitamin of the B-complex group that is essential for cell replication. Folate is a major determinant of one-carbon metabolism, in which S-adenosylmethionine donates methyl groups that are crucial for neurological function. Many roles for folic acid have been reported, including neuroprotective and antidepressant properties. On the other hand, increased concentrations of corticoids have proven neurotoxic effects and hypersecretion of glucocorticoids has been linked to different mood disorders. The purpose of this study was to investigate the potential protective effect of folic acid on dexamethasone-induced cellular death in SH-SY5Y neuroblastoma cell line and the possible intracellular signaling pathway involved in such effect. Exposure to 1 mM dexamethasone for 48 h caused a significant reduction of cell viability measured as 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction. Exposure of SH-SY5Y cells for 72 h to increasing concentrations of folate (1-300 µM) was not cytotoxic. However, pretreatment with folate (10-300 µM) reduced dexamethasone-induced toxicity in a significant manner. To explore the putative intracellular signaling pathways implicated in the protective effect of folate we used different protein kinase inhibitors. The protective effect of folic acid on dexamethasone-induced neurotoxicity was reversed by the phosphatidylinositol-3 kinase/Akt (PI3K/Akt, LY294002), Ca²âº/Calmodulin-dependent protein kinase II (CaMKII, KN-93), and protein kinase A (PKA, H-89) inhibitors, but not the mitogen-activated protein/extracellular signal-regulated kinase (MEK1/2, PD98059) and protein kinase C (PKC, chelerythrine) inhibitors. In conclusion, the results of this study show that folic acid can protect against dexamethasone-induced neurotoxicity and its protective mechanism is related to a signaling pathway that involves PI3K/Akt, CaMKII, and PKA.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Dexametasona/toxicidade , Ácido Fólico/farmacologia , Glucocorticoides/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Hemoperitoneum due to spontaneous rupture of a hepatic hemangioma is a rare and serious clinical event with a high mortality rate. CASE REPORT: 25-year-old woman under hormonal treatment for pregnancy with abdominal pain with distension followed by vomits, palpable epigastric mass and paleness of the skin and mucosas. Computed tomography of the abdomen without oral and venous contrast showed a heterogeneous and capsulated tumor of the liver. Exploratory laparotomy was carried out that revealed a large tumor occupying the gastro-hepatic site with partial rupture of the tumor's capsule with bleeding. Because of the close relationship between the tumor and the retro-hepatic inferior vena cava, the partial resection of the tumor was realized. The patient had a good post-operative evolution. The study of the tumor revealed hepatic hemangioma. CONCLUSION: Hepatic Hemangiomas may evolve to spontaneous rupture leading to hemorrhagic acute abdomen. Surgery is mandatory and the resection of the Hemangioma will depend on the clinical condition of the patient and on the relationship of the tumor with the vascular structures of the liver. Partial resection is a safe choice that saves lives in urgency situations, as the one described herein.
Assuntos
Hemangioma Cavernoso/diagnóstico , Hemoperitônio/etiologia , Hemoperitônio/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Hemangioma Cavernoso/complicações , Hemangioma Cavernoso/cirurgia , Hemoperitônio/diagnóstico , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/cirurgia , Ruptura Espontânea , Resultado do TratamentoRESUMO
Epidemiological and experimental studies have associated development of metabolic syndrome with stressful events (nutritional, hormonal, or environmental) in early life. This phenomenon is known as programing and changes in adipokines levels in early life, especially leptin, seem to be involved with its development. We have shown that neonatal hyperleptinemia on lactation programs for leptin resistance, hyperthyroidism, and higher corticosterone and catecholamines levels with cardiovascular consequences. In the present study, we evaluated the effect of hyperleptinemia during lactation on the glucose and lipid metabolism and liver morphology of adult rats, which were saline or leptin-treated (8 microg/100 g of body weight) daily, for the first 10 days of life. Leptin group had lower body mass during treatment, but higher body mass and hyperleptinemia at adulthood, without difference in fat mass. We showed that the probable source of hyperleptinemia is the higher leptin content in the subcutaneous adipose tissue. The programed rats showed hyperinsulinemia and hypoadiponectinemia with higher expression of the hypothalamic Suppressor of Cytokine Signaling 3 (SOCS3), suggesting insulin resistance. Besides, they presented higher liver glycogen and hypertriglyceridemia. We also observed liver microsteatosis in the leptin-programed adult rats. Our data show that neonatal hyperleptinemia alters glucose metabolism, which seems to be partially compensated by the hyperinsulinemia. However, changes in the lipid metabolism are not compensated. It is probable that these changes induced by neonatal hyperleptinemia result from a selective tissue specific resistance both to insulin and leptin at adulthood, and the increase of SOCS3 may play an important role in this process.
Assuntos
Fígado Gorduroso/metabolismo , Lactação , Leptina/biossíntese , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Modelos Animais de Doenças , Fígado Gorduroso/fisiopatologia , Feminino , Glucose/metabolismo , Humanos , Lactação/metabolismo , Leptina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculos/efeitos dos fármacos , Músculos/metabolismo , Ratos , Ratos WistarRESUMO
Realizou-se um estudo para caracterizar a situação epidemiológica da brucelose bovina no Estado do Tocantins, entre fevereiro de 2002 e agosto de 2003. O Estado foi dividido em seis áreas com características produtivas homogêneas (circuitos produtores). Para cada área, foi calculada uma amostragem simples aleatória de 300 propriedades, com o objetivo de estimar a prevalência de focos de brucelose além da prevalência de fêmeas bovinas adultas soropositivas. Para isso, foram amostradas de 10 a 15 vacas com idade superior a dois anos em cada propriedade. Um total de 20.908 soros foi obtido de 1.842 propriedades. A prevalência de focos de brucelose foi de 21,2 por cento [19,3-23,1 por cento] e a prevalência de fêmeas bovinas adultas soropositivas de 4,4 por cento [3,6-5,3 por cento] para o Estado. Quando se considerou o circuito produtor, observou-se que os circuitos 1, 2, 3 e 5 tiveram prevalência de focos significativamente maior que os circuitos 4 e 6. Os resultados da prevalência nos circuitos 1, 2, 3 e 5 foram de: 16,0 por cento [12,1-20,6 por cento], 37,6 por cento [32,1-43,4 por cento], 26,4 por cento [21,5-31,7 por cento] e 29,3 por cento [24,3-34,7 por cento], respectivamente. Nos circuitos 4 e 6, foram de 5,8 por cento [3,5-9,1 por cento] e 8,6 por cento [5,7-12,2 por cento], respectivamente. Em cada propriedade, foi aplicado um questionário epidemiológico, com o objetivo de avaliar o grau de associação de possíveis fatores de risco com a doença. Os fatores de risco (odds ratio, OR) associados à condição de foco de brucelose foram: rebanho com mais de 120 vacas (OR= 2,0) e abate de reprodutores na propriedade (OR= 1,52). Vacinação contra brucelose (OR= 0,37), presença de piquete de parição (OR= 0,72) e exploração de leite (OR= 0,63) apresentaram-se como fatores de proteção.
A study was carried out to characterize the epidemiological situation of brucellosis in the State of Tocantins from February 2002 to August 2003. The State was divided into six regions with a homogeneous productive system. For each region, a simple random sample was calculated to estimate the prevalence both in farms and cows older than two-year. To achieve this, from 10 to 15 adult cows (older than two-year) were sampled. A total of 20,908 sera from 1,842 farms were obtained. For the whole State of Tocantins, the prevalence of positive farms (or farms with at least one positive animal) was 21.2 percent [19.3-23.1 percent]. When the production regions were considered, the prevalences for the regions 1, 2, 3, and 5 were: 16.0 percent [12.1-20.6 percent], 37.6 percent [32.1-43.4 percent], 26.4 percent [21.5-31.7 percent], and 29.3 percent [24.3-34.7 percent], respectively. In the regions 4 and 6, the prevalences were 5.8 percent [3.5-9.1 percent] and 8.6 percent [5.7-12.2 percent], respectively. In each visited farm, a questionnaire was applied, in order to evaluate the association between with possible risk factors and the brucellosis. The risk factors (odds ratio, OR) associated with the infected herds were number of cows above 120 (OR= 2.0) and slaughtering of breeding animals in the farm (OR= 1.52). Vaccinating against brucellosis (OR= 0.37), presence of birth pen (OR= 0.72), and dairy farm (OR= 0.63) presented as protective factors.
Assuntos
Animais , Bovinos , Brucella/isolamento & purificação , Brucelose Bovina/epidemiologia , Brucelose Bovina/imunologia , Vacina contra Brucelose/administração & dosagem , Brasil/epidemiologia , Controle de Doenças Transmissíveis/métodos , Inseminação Artificial/métodos , Fatores de Risco , Rosa BengalaRESUMO
Realizou-se um estudo para caracterizar a situação epidemiológica da brucelose bovina no Estado do Tocantins, entre fevereiro de 2002 e agosto de 2003. O Estado foi dividido em seis áreas com características produtivas homogêneas (circuitos produtores). Para cada área, foi calculada uma amostragem simples aleatória de 300 propriedades, com o objetivo de estimar a prevalência de focos de brucelose além da prevalência de fêmeas bovinas adultas soropositivas. Para isso, foram amostradas de 10 a 15 vacas com idade superior a dois anos em cada propriedade. Um total de 20.908 soros foi obtido de 1.842 propriedades. A prevalência de focos de brucelose foi de 21,2 por cento [19,3-23,1 por cento] e a prevalência de fêmeas bovinas adultas soropositivas de 4,4 por cento [3,6-5,3 por cento] para o Estado. Quando se considerou o circuito produtor, observou-se que os circuitos 1, 2, 3 e 5 tiveram prevalência de focos significativamente maior que os circuitos 4 e 6. Os resultados da prevalência nos circuitos 1, 2, 3 e 5 foram de: 16,0 por cento [12,1-20,6 por cento], 37,6 por cento [32,1-43,4 por cento], 26,4 por cento [21,5-31,7 por cento] e 29,3 por cento [24,3-34,7 por cento], respectivamente. Nos circuitos 4 e 6, foram de 5,8 por cento [3,5-9,1 por cento] e 8,6 por cento [5,7-12,2 por cento], respectivamente. Em cada propriedade, foi aplicado um questionário epidemiológico, com o objetivo de avaliar o grau de associação de possíveis fatores de risco com a doença. Os fatores de risco (odds ratio, OR) associados à condição de foco de brucelose foram: rebanho com mais de 120 vacas (OR= 2,0) e abate de reprodutores na propriedade (OR= 1,52). Vacinação contra brucelose (OR= 0,37), presença de piquete de parição (OR= 0,72) e exploração de leite (OR= 0,63) apresentaram-se como fatores de proteção.(AU)
A study was carried out to characterize the epidemiological situation of brucellosis in the State of Tocantins from February 2002 to August 2003. The State was divided into six regions with a homogeneous productive system. For each region, a simple random sample was calculated to estimate the prevalence both in farms and cows older than two-year. To achieve this, from 10 to 15 adult cows (older than two-year) were sampled. A total of 20,908 sera from 1,842 farms were obtained. For the whole State of Tocantins, the prevalence of positive farms (or farms with at least one positive animal) was 21.2 percent [19.3-23.1 percent]. When the production regions were considered, the prevalences for the regions 1, 2, 3, and 5 were: 16.0 percent [12.1-20.6 percent], 37.6 percent [32.1-43.4 percent], 26.4 percent [21.5-31.7 percent], and 29.3 percent [24.3-34.7 percent], respectively. In the regions 4 and 6, the prevalences were 5.8 percent [3.5-9.1 percent] and 8.6 percent [5.7-12.2 percent], respectively. In each visited farm, a questionnaire was applied, in order to evaluate the association between with possible risk factors and the brucellosis. The risk factors (odds ratio, OR) associated with the infected herds were number of cows above 120 (OR= 2.0) and slaughtering of breeding animals in the farm (OR= 1.52). Vaccinating against brucellosis (OR= 0.37), presence of birth pen (OR= 0.72), and dairy farm (OR= 0.63) presented as protective factors.(AU)
Assuntos
Animais , Bovinos , Brucelose Bovina/epidemiologia , Brucelose Bovina/imunologia , Brucella/isolamento & purificação , Vacina contra Brucelose/administração & dosagem , Controle de Doenças Transmissíveis/métodos , Brasil/epidemiologia , Fatores de Risco , Rosa Bengala , Inseminação Artificial/métodosRESUMO
The subcapsular hematoma of the liver (SHL) are the results of injuries such as liver needle biopsy, liver trauma, pregnancy illnesses, parasitic diseases and others. The approach of these lesions depends on the various clinical presentations of subcapsular hematoma of the liver because it may be small with minimal clinical repercussion, managed only by ultrasound observation. In some situations the SHL may present large dimensions with hemodinamic instability. A case of subcapsular hematoma of the liver secondary to anesthetic intercostal blockade to control the postoperative pain after cholecystectomy is reported. A 34-year-old woman was submitted to intercostal anesthetic blockade after cholecystectomy for treatment of cholelithiasis. The blockade evolved with pain in right flank followed of mucocutaneous pallor and fall of the haematocrit and hemoglobin levels. At relaparotomy, subcapsular hematoma of the liver was proven and tamponed with compresses. The patient had good postoperative evolution being discharged from hospital, after removing the compresses. In conclusion, the intercostal anesthesic blockade, as any other medical procedure, is not exempt of complications. Therefore, it must be carried through in well selected cases; Anyway nowadays, there are efficient drugs for the control of postoperative pain.
Assuntos
Anestésicos Locais/efeitos adversos , Bupivacaína/efeitos adversos , Colecistectomia Laparoscópica , Hematoma/etiologia , Injeções Intralesionais/efeitos adversos , Nervos Intercostais , Hepatopatias/etiologia , Dor Pós-Operatória/tratamento farmacológico , Adulto , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Colecistectomia Laparoscópica/métodos , Colelitíase/cirurgia , Feminino , Hematoma/terapia , Humanos , Hepatopatias/terapia , Resultado do TratamentoRESUMO
Meckel's diverticulum (MD) is a congenital disorder that results from an incomplete obliteration of the vitelline duct. MD may give rise to bleeding, intestinal obstruction and inflammation; however its perforation by a foreign body is an extremely rare life-threatening complication. We report on a 52 years-old Brazilian Amazon man presenting symptoms and signs of acute abdomen with an initial suspicion of acute appendicitis. However, the right diagnosis was made only during exploratory laparotomy when the appendix was found to be normal, whereas MD was found to be inflamed and perforated by a chicken bone. The patient was treated successfully with resection of a segment of the ileum, including the perforated diverticulum, and had an uncomplicated postoperative course.