Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st-12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th-9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 µg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-γ-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.

Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st–12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th–9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 µg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-?-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.

Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st–12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th–9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 µg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-?-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.

Assessing epidemiology of leprosy and socio-economic distribution of cases.

Leprosy still represents a serious health problem in a number of countries, including Brazil. Although leprosy has been associated with poverty for a long time, it is still difficult to accurately define this relationship. Here, we evaluated in an endemic municipality the progress from 1995 to 2015 of epidemiological indicators to establish if there were any strong associations between social indicators and the occurrence of leprosy. An ecological study was conducted using the SINAN database (Brazilian leprosy-national notifiable diseases information system) in combination with georeferencing of leprosy cases. The georeferencing used the ArcGis programme and occurrence of cases was evaluated in relation to the Health Vulnerability Index (HVI), an indicator that categorises socio-economic and sanitation factors. The data identified a marked decrease in the overall prevalence of leprosy, a reduction in the new case-detection rate and a reduction in the number of cases with grade 2 disabilities (albeit with transient peaks in 2007 and 2015). Logistic regression analysis showed association of detection rates with elevated HVI. Thus, while the epidemiological indicators point to the elimination of leprosy, there is evidence of hidden cases and an association between higher rates of leprosy detection and greater social vulnerability remain.

Wheat gluten intake increases weight gain and adiposity associated with reduced thermogenesis and energy expenditure in an animal model of obesity.

BACKGROUND/OBJECTIVES: The association between gluten and body weight is inconsistent. Previously, we showed that a gluten-free diet reduces weight gain without changing food intake in mice fed high-fat diets. In the present study, we investigated the effects of gluten intake on fat metabolism, thermogenesis and energy expenditure in mice fed a standard or high-fat diet. METHODS: Mice were fed four different experimental diets during 8 weeks: a control-standard diet (CD), a CD added with 4.5% of wheat gluten (CD-G), a high-fat diet (HFD) and a HFD added with 4.5% of wheat gluten (HFD-G). After 8 weeks, the mice received (99m)Tc-radiolabeled gluten orally to study gluten absorption and biodistribution or they underwent indirect calorimetry. After killing, subcutaneous and brown adipose tissues (SAT and BAT) were collected to assess thermogenesis-related protein expression. Lipid metabolism was studied in adipocyte cultures from the four groups. RESULTS: Despite having had the same energy intake, CD-G and HFD-G mice exhibited increased body weight and fat deposits compared with their respective controls. (99m)Tc-GLU or its peptides were detected in the blood, liver and visceral adipose tissue, suggesting that gluten can even reach extraintestinal organs. Uncoupling protein-1 expression was reduced in the BAT of HFD-G and in the SAT of CD-G and HFD-G mice. Indirect calorimetry showed lower oxygen volume consumption in CD-G and HFD-G groups compared with their controls. In HFD mice, daily energy expenditure was reduced with gluten intake. Gluten also reduced adiponectin, peroxisome proliferator-activated receptor (PPAR)-α and PPARγ and hormone-sensitive lipase in cultures of isolated adipocytes from HFD mice, whereas in the CD-G group, gluten intake increased interleukin-6 expression and tended to increase that of tumor necrosis factor. CONCLUSIONS: Wheat gluten promotes weight gain in animals on both HFD and CD, partly by reducing the thermogenic capacity of adipose tissues.

Morphometry and histomorphometry of the testis in crossbred pigs fed diets with different protein levels / Morfometria e histomorfometria do testículo em suínos híbridos recebendo dietas com diferentes níveis de proteína

Aiming to evaluate the effect of the diet protein content on testicular parameters in pigs, 21 non-gelded male Dalland pigs were used and randomly divided into three groups. Males belonging to groups G2 and G3 received a diet with crude protein levels of 15% below and above, respectively, in relation to G1 (control). At 210 days of age, animals were castrated, and testis and epididymis were collected for morphometric and histomorphometry analyses. No difference was observed in relation to the total length of seminiferous tubules (G1=3239.9±333,3m; G2=2989.4±171,7m and G3=3059.5±254.9m), population of Sertoli cell (G1=4.7±0.5x10(9); G2=4.3±0.3x10(9) and G3=4.7±0.5x10(9)), population (G1=31.6±5.58x10(9); G2=27.3±4.0x10(9) and G3=26.4±3.9x10(9)) and volume of Leydig cells (G1=1289.3±182.6µm³; G2=1179.1±85.4µm³ and G3=1133.3±37.8µm³) and sperm production (G1=5.9±0.9x10(9); G2=5.6±0.6x10(9) and G3=5.1±0.3x10(9)). Protein levels were sufficient to maintain spermatogenesis in different experimental groups. It can be concluded that the magnitude of variation in levels of protein used in different stages of development was not sufficient to promote significant changes in testicular development and spermatogenesis process in adult animals.

Avaliou-se o efeito do teor de proteína da dieta sobre características testiculares em suínos, utilizando-se 21 suínos da raça Dalland, distribuídos aleatoriamente em três grupos. Os animais do G2 e G3 receberam dieta com porcentagens de proteína bruta de 15% para mais e para menos, respectivamente, em relação ao G1 (controle). Aos 210 dias de idade, os animais foram orquiectomizados e os testículos e epidídimos foram coletados para análises morfométricas e histomorfométricas. Observou-se efeito significativo da porcentagem de proteína sobre o comprimento e a largura dos testículos, e nenhuma diferença foi identificada em relação ao comprimento total dos túbulos seminíferos (G1=3239,9±333,3m; G2=2989,4±171,7m e G3=3059,5±254,9m), à população de células de Sertoli (G1=4,7±0,5x10(9); G2=4,3±0,3 x10(9) e G3=4,7±0,5x10(9)), à população (G1=31,6±5,58x10(9); G2=27,3±4,0x10(9) e G3=26,4±3,9x10(9)) e ao volume das células de Leydig (G1=1289,3±182,6µm³; G2=1179,1±85,4µm³ e G3=1133,3±37,8µm³) e à produção espermática (G1=5,9±0,9 x10(9); G2=5,6±0,6x10(9) e G3=5,1±0,3x10(9)). Os percentuais de proteína foram suficientes para a manutenção da espermatogênese nos diferentes grupos. Pode-se concluir que a magnitude da variação dos níveis de proteína usada em diferentes fases do desenvolvimento não foi suficiente para promover alterações significativas no desenvolvimento testicular e no processo espermatogênico em animais adultos.

[Intraspinal syphilitic gumma causing spinal cord compression. Report of a case]. / Goma sifilítica intra-raquídea causando compressão medular. Relato de um caso.

A case of an syphilitic intraspinal gumma is reported. A 48 years-old woman developed severe spastic crural paraparesis of two months duration, associated with sensory and sphincteric disturbances. Myelography revealed an intraspinal tumor at T3 level. Surgical exploration by dorsal laminectomy showed a syphilitic gumma attached to the spinal cord. Clinical observations and laboratory studies are discussed. Revision and comments on previous reports are presented.