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INTRODUCTION: Obesity has emerged as one of the main public health problems. This condition triggers a series of hormonal and metabolic changes related to a low-grade chronic inflammatory condition. The trypsin inhibitor purified from tamarind (TTIp) seeds is a promising anti-inflammatory molecule, but its safety needs to be evaluated. This study aimed to evaluate TTIp bioactive dose effects on organs involved in its metabolism (liver and pancreas) and affected tissues (small intestine and perirenal adipose tissue) in an obesity model. METHODS: Three groups of adult male Wistar rats were used (n = 5). Two of these groups had diet-induced obesity, and a third group was eutrophic. TTIp was administered by gavage in one of the obese groups for 10 days, while the remaining groups received a vehicle. The chromatographic profile and the inhibition assay corroded the purification of the inhibitor. Physical and behavioral changes, liver enzymes, and stereological and histopathological analyses of tissues were evaluated. RESULTS: TTIp did not cause visible signs of toxicity, nor caused changes in liver enzymes, the liver, and pancreatic tissues. TTIp did not cause changes in the intestinal mucosa, showing improvement in the villi's histopathological characteristics compared to the group of animals with obesity without treatment with TTIp (p = 0.004). The analysis of perirenal adipose tissue showed that the average sectional area of animals with obesity that received TTIp did not differ from the control. There was a difference between the high glycemic load diet group and the group treated with the inhibitor (351.8 ± 55.5) (p = 0.016). In addition, the group that received TTIp had no inflammatory infiltrates. CONCLUSION: Based on histological and stereological analysis, the use of TTIp is potentially safe and anti-inflammatory in the evaluated obesity model and can be investigated as a possible adjuvant in obesity therapy.
Assuntos
Tamarindus , Tecido Adiposo , Animais , Anti-Inflamatórios/uso terapêutico , Dieta Hiperlipídica , Mucosa Intestinal , Obesidade/tratamento farmacológico , Obesidade/etiologia , Ratos , Ratos WistarRESUMO
: The increasing prevalence of obesity and, consequently, chronic inflammation and its complications has increased the search for new treatment methods. The effect of the purified tamarind seed trypsin inhibitor (TTIp) on metabolic alterations in Wistar rats with obesity and dyslipidemia was evaluated. Three groups of animals with obesity and dyslipidemia were formed, consuming a high glycemic index and glycemic load (HGLI) diet, for 10 days: Obese/HGLI diet; Obese/standard diet; Obese/HGLI diet + TTIp (730 µg/kg); and one eutrophic group of animals was fed a standard diet. Rats were evaluated daily for food intake and weight gain. On the 11th day, animals were anesthetized and sacrificed for blood and visceral adipose tissue collection. TTIp treated animals presented significantly lower food intake than the untreated group (p = 0.0065), TG (76.20 ± 18.73 mg/dL) and VLDL-C (15.24 ± 3.75 mg/dL). Plasma concentrations and TNF-α mRNA expression in visceral adipose tissue also decreased in obese animals treated with TTIp (p < 0.05 and p = 0.025, respectively) with a negative immunostaining. We conclude that TTIp presented anti-TNF-α activity and an improved lipid profile of Wistar rats with dyslipidemia and obesity induced by a high glycemic index and load diet regardless of PPAR-γ induction.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Dislipidemias/tratamento farmacológico , Obesidade/complicações , PPAR gama/metabolismo , Peptídeos/farmacologia , Proteínas de Plantas/farmacologia , Tamarindus/química , Animais , Glicemia/efeitos dos fármacos , Dislipidemias/etiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Lipídeos/sangue , Masculino , Peptídeos/química , Proteínas de Plantas/química , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/sangueRESUMO
A well-developed visual system can provide significant sensory information to guide motor behavior, especially in fruit-eating bats, which usually use echolocation to navigate at high speed through cluttered environments during foraging. Relatively few studies have been performed to elucidate the organization of the visual system in bats. The present work provides an extensive morphological description of the retinal projections in the subcortical visual nuclei in the flat-faced fruit-eating bat (Artibeus planirostris) using anterograde transport of the eye-injected cholera toxin B subunit (CTb), followed by morphometrical and stereological analyses. Regarding the cytoarchitecture, the dorsal lateral geniculate nucleus (dLGN) was homogeneous, with no evident lamination. However, the retinal projection contained two layers that had significantly different marking intensities and a massive contralateral input. The superior colliculus (SC) was identified as a laminar structure composed of seven layers, and the retinal input was only observed on the contralateral side, targeting two most superficial layers. The medial pretectal nucleus (MPT), olivary pretectal nucleus (OPT), anterior pretectal nucleus (APT), posterior pretectal nucleus (PPT) and nucleus of the optic tract (NOT) were comprised the pretectal nuclear complex (PNT). Only the APT lacked a retinal input, which was predominantly contralateral in all other nuclei. Our results showed the morphometrical and stereological features of a bat species for the first time.
RESUMO
In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN, classically known as the master circadian clock, generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity. Strategies on the use of time by animals can provide important clues about how some species are adapted to competitive process in nature. Few studies have provided information about temporal niche in bats with special attention on the neural substrate underlies circadian rhythms. The aim of this study was to investigate these circadian centers with respect to their cytoarchitecture, chemical content and retinal projections in the flat-faced fruit-eating bat (Artibeus planirostris), a chiropteran endemic to South America. Unlike other species of phyllostomid bats, the flat-faced fruit-eating bat's peak of activity occurs 5 h after sunset. This raises several questions about the structure and function of the SCN and IGL in this species. We carried out a mapping of the retinal projections and cytoarchitectural study of the nuclei using qualitative and quantitative approaches. Based on relative optical density findings, the SCN and IGL of the flat-faced fruit-eating bat receive bilaterally symmetric retinal innervation. The SCN contains vasopressin (VP) and vasoactive intestinal polypeptide (VIP) neurons with neuropeptide Y (NPY), serotonin (5-HT) and glutamic acid decarboxylase (GAD) immunopositive fibers/terminals and is marked by intense glial fibrillary acidic protein (GFAP) immunoreactivity. The IGL contains NPY perikarya as well as GAD and 5-HT immunopositive terminals and is characterized by dense GFAP immunostaining. In addition, stereological tools were combined with Nissl stained sections to estimate the volumes of the circadian centers. Taken together, the present results in the flat-faced fruit-eating bat reveal some differences compared to other bat species which might explain the divergence in the hourly activity among bats in order to reduce the competitive potential and resource partitioning in nature.
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Foram avaliados, por meio da tomografia computadorizada, 19 cães com mastocitomas tratados com quimioterapia. Aspectos como contorno, atenuação, realce pós-contraste e presença de clivagem com estruturas adjacentes foram avaliados. Aplicaram-se os critérios RECIST e a mensuração volumétrica das lesões para se avaliar a resposta ao tratamento. Quanto à atenuação, os mastocitomas se mostraram como lesões homogêneas ou heterogêneas, com tendência a limites definidos e contornos regulares e apresentaram realce moderado após administração do contraste iodado intravenoso. Os métodos RECIST e a mensuração volumétrica apresentaram uma excelente concordância na classificação da resposta terapêutica, fornecendo um bom parâmetro da resposta ao tratamento instituído. O exame de tomografia computadorizada se mostrou útil na delimitação do tumor e importante ferramenta no planejamento das margens cirúrgicas. (AU)
Nineteen dogs with mast cell tumors treated with chemotherapy were evaluated by computed tomography (CT). Were evaluated aspects related to contours, attenuation, post-contrast enhancement and presence of cleavage with adjacent structures. The RECIST criteria and volumetric measurement of lesions were performed to assess the response to treatment. The mast cell tumors presented a homogeneous or heterogeneous attenuation, presented more frequently a well delineated and regular contours and moderate enhancement after intravenous administration of the iodinated contrast media. The methods RECIST and volumetric measurements showed an excellent agreement to the classification of therapeutic response, providing a good parameter of the response to treatment. The CT examination proved to be useful in the delimitation of the tumor and an important tool for planning of surgical margins. (AU)
Assuntos
Animais , Cães , Tratamento Farmacológico/veterinária , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/veterinária , Mastocitoma/veterinária , Diagnóstico por Imagem/veterinária , Tomografia Computadorizada Espiral/veterináriaRESUMO
Foram avaliados, por meio da tomografia computadorizada, 19 cães com mastocitomas tratados com quimioterapia. Aspectos como contorno, atenuação, realce pós-contraste e presença de clivagem com estruturas adjacentes foram avaliados. Aplicaram-se os critérios RECIST e a mensuração volumétrica das lesões para se avaliar a resposta ao tratamento. Quanto à atenuação, os mastocitomas se mostraram como lesões homogêneas ou heterogêneas, com tendência a limites definidos e contornos regulares e apresentaram realce moderado após administração do contraste iodado intravenoso. Os métodos RECIST e a mensuração volumétrica apresentaram uma excelente concordância na classificação da resposta terapêutica, fornecendo um bom parâmetro da resposta ao tratamento instituído. O exame de tomografia computadorizada se mostrou útil na delimitação do tumor e importante ferramenta no planejamento das margens cirúrgicas.
Nineteen dogs with mast cell tumors treated with chemotherapy were evaluated by computed tomography (CT). Were evaluated aspects related to contours, attenuation, post-contrast enhancement and presence of cleavage with adjacent structures. The RECIST criteria and volumetric measurement of lesions were performed to assess the response to treatment. The mast cell tumors presented a homogeneous or heterogeneous attenuation, presented more frequently a well delineated and regular contours and moderate enhancement after intravenous administration of the iodinated contrast media. The methods RECIST and volumetric measurements showed an excellent agreement to the classification of therapeutic response, providing a good parameter of the response to treatment. The CT examination proved to be useful in the delimitation of the tumor and an important tool for planning of surgical margins.
Assuntos
Animais , Cães , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Diagnóstico por Imagem/veterinária , Mastocitoma/veterinária , Tratamento Farmacológico/veterinária , Tomografia Computadorizada Espiral/veterináriaRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A) . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat) in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week) extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.
Assuntos
Esclerose Lateral Amiotrófica/mortalidade , Antioxidantes/uso terapêutico , Óxidos N-Cíclicos/uso terapêutico , Neurônios Motores/efeitos dos fármacos , Mutação/genética , Fármacos Neuroprotetores/uso terapêutico , Superóxido Dismutase/fisiologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Masculino , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Estresse Oxidativo/efeitos dos fármacos , Dobramento de Proteína , Ratos , Ratos Transgênicos , Marcadores de Spin , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Superóxido Dismutase-1 , Taxa de SobrevidaRESUMO
BACKGROUND/AIMS: Pharmacological antihypertensive therapies decrease both wall hypertrophy and collagen, but are unable to diminish the elastic content in the thoracic aorta. We investigated the effects of exercise training on aortic structure and function. METHODS: Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), submitted to low-intensity training (T) or kept sedentary (S), were subjected to haemodynamic analyses. The thoracic aorta was processed for real-time PCR, light (morphometric/stereological evaluations) and electron microscopy. RESULTS: SHR(S) versus WKY(S) exhibited a higher heart rate, pressure and pulse pressure, increased α-actin, elastin and collagen mRNA expression, augmented wall volume and cross-sectional area (marked elastin/collagen content). In the SHR, training reduced pressure and heart rate, with slight reduction in pulse pressure. SHR(T) aortas exhibited small morphometric changes, reduced α-actin, elastin and collagen mRNA expression, normalization of increased elastic content, reduction in collagen/connective tissue and a decrease in smooth muscle cell volume (p < 0.05 for all comparisons). SHR(T) aortas showed improved circumferential orientation of smooth muscle cells and prevention of rupture/duplication of internal elastic lamina. No effects were observed in trained WKY aortas. CONCLUSIONS: Training effectively corrects elastic, collagen and smooth muscle content in SHR aortas. These changes, by reducing aortic pulsatility, facilitate a buffering function and reduce the cardiovascular risk.
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Aorta Torácica/fisiologia , Elasticidade/fisiologia , Hipertensão/fisiopatologia , Condicionamento Físico Animal/fisiologia , Actinas/genética , Actinas/metabolismo , Animais , Aorta Torácica/ultraestrutura , Pressão Sanguínea/fisiologia , Colágeno/genética , Colágeno/metabolismo , Elastina/genética , Elastina/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Miócitos de Músculo Liso/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Comportamento SedentárioRESUMO
OBJECTIVE: The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. METHODS: Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. RESULTS: Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. CONCLUSION: We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments.