Neonatal tactile stimulation reverses alterations in fine structure of small, but not large myelinated fibers, from the optic nerve of iron-deficient rats: A size-based selectivity.

Iron is the most common micronutrient deficiency in the world and it is most prevalent in young children, exposing their developing brain to inadequate iron levels. The damage related to neuroanatomical parameters is not reversed after iron treatment. However, evidence suggest that tactile stimulation (TS) may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Recently, we shown that neonatal iron deficient rats achieved some remedial effect by exposing them to TS treatment early in life, reinforcing the fact that the TS approach is a positive enriching experience, therefore, here we ask whether exposure to TS treatment, could also be employed to prevent fine structural changes in the fibers from optic nerve of rats maintained on an iron-deficient diet during brain development. To elucidate the protective effect of tactile stimulation, our methods resulted in 10,859 analyzed fibers, divided into small and large fibers. We found that iron deficiency led to a decreased axon, fiber and myelin size of small fibers, however, TS completely reversed the iron-decifiency-induced alteration on those fiber measurements. Large fibers were disproportionately affected by iron deficiency and there was no remediating effect due to tactile stimulation treatment. The present study adds new information regarding different alterations between small and large fibers due to diet and TS, which suggest a size-based selectivity. These results emphasize the concept that compromised brain development can be mitigated at an early age by environmental factors, such as tactile stimulation.

The study of the use of a latex biomembrane and conjunctival autograft in rabbit conjunctiva wound healing.

RESUMO Objetivo: Estudar o uso da biomembrana de látex e o transplante conjuntival autólogo na cicatrização conjuntival em coelhos. Métodos: Em nove coelhos albinos, neo-zelandeses, machos foram removidas áreas retangulares idênticas, do quadrante supero nasal, adjacente ao limbo, de ambos os olhos. As áreas desnudas da camada esclerótica nos olhos direitos foram recobertas com biomembrana de látex e a dos olhos esquerdos com enxerto conjuntival autólogo. Os animais foram sacrificados em grupos de três, aos 7, 14 e 21 dias após a cirurgia. Os tecidos do local cirúrgico, incluindo a córnea, foram fixados em formaldeído, antes de serem processados em parafina e corados com hematoxilina e eosina. A natureza e a intensidade da resposta inflamatória e o padrão de epitelização da superfície conjuntival foram avaliados sob microscopia óptica, em seções histológicas longitudinais, passando pelo centro dos espécimes anatômicos. Resultados: Até o décimo quarto dia pós-operatório, o grupo que recebeu a biomembrana apresentou reação inflamatória mais intensa do que o grupo com auto enxerto conjuntival. Aos 14 dias, os olhos com biomembrana apresentavam-se menos inflamados e com estroma mais espesso do que aos 7 dias. Aos 21 dias, a reparação conjuntival de ambos os grupos apresentavam características semelhantes. Conclusão: Apesar de apresentar uma cicatrização mais lenta, a biomembrana de látex se mostrou tão eficaz quanto o auto enxerto conjuntival na reconstrução da superfície ocular após três semanas de cicatrização pós-operatória. Devido as suas baixas toxicidade e alergenicidade, este material parece ser uma opção terapêutica promissora na reconstrução da conjuntiva.ABSTRACT Purpose: To study a latex biomembrane and conjunctival autograft with regard to the promotion of conjunctival healing in rabbits. METHODS: The study included nine male albino rabbits. In these rabbits, a rectangular area of the conjunctiva was surgically removed from the superonasal quadrant adjacent to the limbus in both eyes. The bare area of the sclerotic coat of the right eye was reconstructed with a latex biomembrane, and the corresponding site of the left eye was reconstructed with a conjunctival autograft. The animals were killed in groups of three at 7, 14, and 21 days after surgery. The tissues from the surgical site, including the cornea, were fixed in formaldehyde, and were then processed in paraffin and stained with hematoxylin and eosin. The nature and intensity of the inflammatory response and the epithelial pattern at the conjunctival surface were evaluated under optical microscopy with longitudinal histological sections through the center of the anatomical specimens. RESULTS: Until the 14th postoperative day, the inflammatory reaction was greater in the biomembrane group than in the conjunctival autograft group. In the latex biomembrane group, inflammation was less intense and the stroma was thicker on the 14th postoperative day than on the 7th postoperative day. After three weeks, conjunctival healing in both groups showed similar characteristics. CONCLUSION: Although healing was slower with a latex biomembrane, tissue reconstitution was almost the same as that with a conjunctival autograft by three weeks. A latex biomembrane is as effective as a conjunctival autograft for the reconstruction of the ocular surface. Owing to the lack of toxicity and allergenicity, a latex biomembrane appears to be a promising therapeutic option for conjunctival reconstruction.

The study of the use of a latex biomembrane and conjunctival autograft in rabbit conjunctiva wound healing / Estudo do implante de biomembrana de látex e auto-enxerto conjuntival em cicatrização de ferida conjuntiva de coelho

RESUMO Objetivo: Estudar o uso da biomembrana de látex e o transplante conjuntival autólogo na cicatrização conjuntival em coelhos. Métodos: Em nove coelhos albinos, neo-zelandeses, machos foram removidas áreas retangulares idênticas, do quadrante supero nasal, adjacente ao limbo, de ambos os olhos. As áreas desnudas da camada esclerótica nos olhos direitos foram recobertas com biomembrana de látex e a dos olhos esquerdos com enxerto conjuntival autólogo. Os animais foram sacrificados em grupos de três, aos 7, 14 e 21 dias após a cirurgia. Os tecidos do local cirúrgico, incluindo a córnea, foram fixados em formaldeído, antes de serem processados em parafina e corados com hematoxilina e eosina. A natureza e a intensidade da resposta inflamatória e o padrão de epitelização da superfície conjuntival foram avaliados sob microscopia óptica, em seções histológicas longitudinais, passando pelo centro dos espécimes anatômicos. Resultados: Até o décimo quarto dia pós-operatório, o grupo que recebeu a biomembrana apresentou reação inflamatória mais intensa do que o grupo com auto enxerto conjuntival. Aos 14 dias, os olhos com biomembrana apresentavam-se menos inflamados e com estroma mais espesso do que aos 7 dias. Aos 21 dias, a reparação conjuntival de ambos os grupos apresentavam características semelhantes. Conclusão: Apesar de apresentar uma cicatrização mais lenta, a biomembrana de látex se mostrou tão eficaz quanto o auto enxerto conjuntival na reconstrução da superfície ocular após três semanas de cicatrização pós-operatória. Devido as suas baixas toxicidade e alergenicidade, este material parece ser uma opção terapêutica promissora na reconstrução da conjuntiva.

ABSTRACT Purpose: To study a latex biomembrane and conjunctival autograft with regard to the promotion of conjunctival healing in rabbits. Methods: The study included nine male albino rabbits. In these rabbits, a rectangular area of the conjunctiva was surgically removed from the superonasal quadrant adjacent to the limbus in both eyes. The bare area of the sclerotic coat of the right eye was reconstructed with a latex biomembrane, and the corresponding site of the left eye was reconstructed with a conjunctival autograft. The animals were killed in groups of three at 7, 14, and 21 days after surgery. The tissues from the surgical site, including the cornea, were fixed in formaldehyde, and were then processed in paraffin and stained with hematoxylin and eosin. The nature and intensity of the inflammatory response and the epithelial pattern at the conjunctival surface were evaluated under optical microscopy with longitudinal histological sections through the center of the anatomical specimens. Results: Until the 14th postoperative day, the inflammatory reaction was greater in the biomembrane group than in the conjunctival autograft group. In the latex biomembrane group, inflammation was less intense and the stroma was thicker on the 14th postoperative day than on the 7th postoperative day. After three weeks, conjunctival healing in both groups showed similar characteristics. Conclusion: Although healing was slower with a latex biomembrane, tissue reconstitution was almost the same as that with a conjunctival autograft by three weeks. A latex biomembrane is as effective as a conjunctival autograft for the reconstruction of the ocular surface. Owing to the lack of toxicity and allergenicity, a latex biomembrane appears to be a promising therapeutic option for conjunctival reconstruction.

Environmental enrichment protects spatial learning and hippocampal neurons from the long-lasting effects of protein malnutrition early in life.

As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development.

Tactile stimulation partially prevents neurodevelopmental changes in visual tract caused by early iron deficiency.

Iron deficiency has a critical impact on maturational mechanisms of the brain and the damage related to neuroanatomical parameters is not satisfactorily reversed after iron replacement. However, emerging evidence suggest that enriched early experience may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Given the fact that tactile stimulation (TS) treatment has been previously shown to be an effective therapeutic approach and with potential application to humans, here we ask whether exposure to TS treatment, from postnatal day (P) 1 to P32 for 3min/day, could also be employed to prevent neuroanatomical changes in the optic nerve of rats maintained on an iron-deficient diet during brain development. We found that iron deficiency changed astrocyte, oligodendrocyte, damaged fiber, and myelinated fiber density, however, TS reversed the iron-deficiency-induced alteration in oligodendrocyte, damaged fiber and myelinated fiber density, but failed to reverse astrocyte density. Our results suggest that early iron deficiency may act by disrupting the timing of key steps in visual system development thereby modifying the normal progression of optic nerve maturation. However, optic nerve development is sensitive to enriching experiences, and in the current study we show that this sensitivity can be used to prevent damage from postnatal iron deficiency during the critical period.

Tactile stimulation during development alters the neuroanatomical organization of the optic nerve in normal rats.

This study was designed to investigate the progressive effect of tactile stimulation in the cytoarchitecture of the optic nerve of normal rats during early postnatal development. We used 36 male pups which were randomly assigned to either the tactile-stimulated group (TS-stimulation for 3 min, once a day, from postnatal day (P) 1 to 32) or the non-tactile-stimulated (NTS) group. Morphological analysis were performed to evaluate the alterations caused by tactile stimulation, and morphometric analysis were carried out to determine whether the observed changes in optic nerve cytoarchitecture were significantly different between groups and at three different ages (P18, P22, and P32), thereby covering the entire progression of development of the optic nerve from its start to its completion. The rats of both groups presented similar increase in body weight. The morphometric analysis revealed no difference in the astrocyte density between age-matched groups; however, the oligodendrocyte density of TS group was higher compared to the NTS at P22, and P32, but not at P18. The optic nerve of TS group showed an increase of blood vessels and a reduction of damage fiber density when compared to the age-matched pups of NTS. Taken together, these findings support the view that tactile stimulation, an enriching experience, can positively affects the neuroanatomy of the brain, modifying its cellular components by progressive morphological and morphometric changes.

Assessments of Motor Abnormalities on the Grid-Walking and Foot-Fault Tests From Undernutrition in Wistar Rats.

This study was designed to verify whether different lactation conditions influenced nervous system development. The authors used motor tasks to verify changes in exploratory activity and muscle strength of weaned rats from different litter sizes and evaluated the applicability of the grid-walking test for assessing motor abnormalities caused by undernutrition. Alterations in litter size during the suckling period perturbed the nutritional status of pups, which exhibited body weight differences between the groups. Large-litter (L) pups showed significant delays in achieving developmental milestones and neurological reflexes compared to the small-litter (S) and medium-litter (M) pups. The S, M, and L group pups exhibited similar exploratory responses and muscle strength. In the grid-walking and foot-fault tests, the L group pups traveled shorter distances and, consequently, had less footsteps. However, the percentages of foot faults in the L group were higher than S and M groups. These results reflect delayed maturation of structures responsible for sensorimotor responses, such as the cerebellum, because much cerebellar maturation takes place postnatally. This is the first study to report that early undernutrition in pups resulted in suboptimal performances on the grid-walking and foot-fault tests and that the former test was sensitive to alterations caused by nutritional deficiency.

Effects of environmental enrichment on blood vessels in the optic tract of malnourished rats: A morphological and morphometric analysis.

OBJECTIVES: This study aimed to compare the effects of environmental enrichment in nourished (on a diet containing 16% protein) and malnourished (on a diet containing 6% protein) rats during the critical period of brain development, specifically focusing on the optic nerve. METHODS: By means of morphologic and morphometric assessment of the optic nerve, we analyzed the changes caused by diet and stimulation (environmental enrichment) on postnatal day 35, a time point ideal for such morphological analysis since developmental processes are considered complete at this age. RESULTS: Malnourished animals presented low body and brain weights and high body-to-brain weight ratio compared to well-nourished rats. Furthermore, malnourished animals showed morphological changes in the optic nerve such as edema and vacuolization characterized by increased interstitial space. The malnourished-stimulated group presented lesions characteristic of early protein malnutrition but were milder than lesions exhibited by malnourished-non-stimulated group. The morphometric analysis revealed no difference in glial cell density between groups, but there was significantly higher blood vessel density in the stimulated rats, independent of their nutritional condition. DISCUSSION: Our data indicate that protein malnutrition imposed during the critical period of brain development alters the cytoarchitecture of the optic nerve. In addition, we affirm that a 1-hour exposure to an enriched environment everyday was sufficient for tissue preservation in rats maintained on a low-protein diet. This protective effect might be related to angiogenesis, as confirmed by the increased vascular density observed in morphometric analyses.

Environmental enrichment reverses reduction in glucocorticoid receptor expression in the hippocampus of and improves behavioral responses of anxiety in early malnourished rats.

We compared glucocorticoid receptor (GR) gene expression in the hippocampus of rats subjected to a low protein, "malnourished" diet (M; 6% protein) or a control, "well-nourished" diet (W; 16% protein), exposed to different environmental stimulation (environmental enrichment, E; no enrichment, N) between postnatal day 8 (P8) and P35. Rats were tested on the elevated plus maze (EPM) on P36. Male Wistar rats were split into two groups at birth according to diet (M or W) and subdivided according to environmental stimulation (E or N). GR expression was determined using real-time polymerase chain reaction and GR immunohistochemistry in the hippocampus. Our results showed that MN rats spent more time and made more entries into the open arms of the EPM compared to W rats. On the other hand, ME rats spent a similar percentage of time, and made a similar number of entries, in the open arms as WN rats. Following the EPM test, GR mRNA expression in the hippocampus was different in MN rats compared to W rats; expression was also different between M and ME rats; mRNA and expression of GR receptors in WN rats was similar to that observed in WE rats. These data also show that the effects of malnutrition on risk assessment in the EPM were reversed by E. Early malnutrition may alter GR expression in the hippocampus and environmental enrichment may exert a neuroprotective effect on malnutrition-induced brain injury.

The morphological and developmental changes of the anterior commissure of male Wistar rats submitted to protein malnutrition in the postnatal period.

The aim of this project was to study the effects of protein malnutrition in the anterior commissure of male albino Wistar rats, submitted to diets with different levels of protein to evaluate the possible morphological and developmental changes of the myelinated nervous fibers and glial cells of this important neural structure during the postnatal period until 120 days of age. In this study the animals (dams and pups) were divided into three groups: the control group which received a commercial diet from the laboratory (22% protein); the nourished group which received a diet of 16% of protein (casein); and the malnourished group which received a diet of 6% of protein (casein). Rat pups were fed by lactating females during the lactation period. After weaning the pups received the same diet until 120 days of age. The results obtained showed that the malnourished animals presented less body and brain growth and important morphological changes in the anterior commissure such as the retard in the myelination, damaged myelinic nervous fibers, and the increase of the interstitial space characterizing edema and vacuolization. The current study shows that the effects of protein malnutrition in the anterior commissure cause a bigger alteration in the posterior limb of the referred commissure, indicating that it is more vulnerable to malnutrition and more susceptible to damages of the anterior limb.

Sciatic nerve regeneration in rats by a nerve conduit engineering with a membrane derived from natural latex.

PURPOSE: To evaluate the capacity of natural latex membrane to accelerate and improve the regeneration quality of the of rat sciatic nerves. METHODS: Forty male adult Wistar rats were used, anesthetized and operated to cut the sciatic nerve and receive an autograft or a conduit made with a membrane derived from natural latex (Hevea brasiliensis). Four or eight weeks after surgery, to investigate motor nerve recovery, we analyzed the neurological function by walking pattern (footprints analysis and computerized treadmill), electrophysiological evaluation and histological analysis of regenerated nerve (autologous nerve graft or tissue cables between the nerve stumps), and anterior tibial and gastrocnemius muscles. RESULTS: All functional and morphological analysis showed that the rats transplanted with latex conduit had a better neurological recovery than those operated with autologous nerve: quality of footprints, performance on treadmill (p<0.01), electrophysiological response (p<0.05), and quality of histological aspects on neural regeneration. CONCLUSION: The data reported showed behavioral and functional recovery in rats implanted with latex conduit for sciatic nerve repair, supporting a complete morphological and physiological regeneration of the nerve.

Sciatic nerve regeneration in rats by a nerve conduit engineering with a membrane derived from natural latex / Regeneração do nervo ciático em ratos através de um conduto confeccionado com uma membrana de látex natural

PURPOSE: To evaluate the capacity of natural latex membrane to accelerate and improve the regeneration quality of the of rat sciatic nerves. METHODS: Forty male adult Wistar rats were used, anesthetized and operated to cut the sciatic nerve and receive an autograft or a conduit made with a membrane derived from natural latex (Hevea brasiliensis). Four or eight weeks after surgery, to investigate motor nerve recovery, we analyzed the neurological function by walking pattern (footprints analysis and computerized treadmill), electrophysiological evaluation and histological analysis of regenerated nerve (autologous nerve graft or tissue cables between the nerve stumps), and anterior tibial and gastrocnemius muscles. RESULTS: All functional and morphological analysis showed that the rats transplanted with latex conduit had a better neurological recovery than those operated with autologous nerve: quality of footprints, performance on treadmill (p<0.01), electrophysiological response (p<0.05), and quality of histological aspects on neural regeneration. CONCLUSION: The data reported showed behavioral and functional recovery in rats implanted with latex conduit for sciatic nerve repair, supporting a complete morphological and physiological regeneration of the nerve.

OBJETIVO: Avaliar a capacidade de uma membrana de látex natural em acelerar e melhorar a qualidade da regeneração do nervo ciático seccionado de ratos. MÉTODOS: Foram utilizados 40 ratos machos adultos da linhagem Wistar, anestesiados e operados com autoenxerto ou com interposição de um tubo confeccionado com uma membrana derivada do latex natural (Havea brasiliensis). Quatro ou oito semanas após a cirurgia, para investigar a recuperação motora do nervo, foram analisadas a função neurológica através do padrão da marcha (análise das pegadas e esteira computadorizada), avaliação eletrofisiológica e análise histológica do nervo regenerado (enxerto de nervo autólogo ou formação de nervo novo entre os cotos nervosos) e músculos gastrocnêmio e tibial anterior. RESULTADOS: Todas as análises morfológicas e funcionais demonstraram que os ratos transplantados com o conduto de látex tiveram recuperação melhor do que aqueles operados com nervo autólogo: qualidade das pegadas impressas, desempenho em esteira (p<0,01), resposta eletrofisiológica (p<0,05), e qualidade histológica da regeneração nervosa. CONCLUSÃO: Os dados apresentados demonstraram recuperação comportamental e funcional nos ratos implantados com o conduto de látex para a reparação do nervo ciático por meio de uma completa regeneração morfológica e fisiológica do nervo.

0.1T magnetic resonance image in the study of experimental hydrocephalus in rats. Accuracy of the method in the measurements of the ventricular size.

PURPOSE: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to measure the ventricular size in experimental hydrocephalus in pup rats. METHODS: Wistar rats were subjected to hydrocephalus by intracisternal injection of 20% kaolin (n=13). Ten rats remained uninjected to be used as controls. At the endpoint of experiment animals were submitted to MRI of brain and killed. The ventricular size was assessed using three measures: ventricular ratio (VR), the cortical thickness (Cx) and the ventricles area (VA), performed on photographs of anatomical sections and MRI. RESULTS: The images obtained through MR present enough quality to show the lateral ventricular cavities but not to demonstrate the difference between the cortex and the white matter, as well as the details of the deep structures of the brain. There were no statistically differences between the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992, respectively). There was difference between VA measured on anatomical sections and MRI (p<0.0001). CONCLUSION: The parameters obtained through 1.0T MRI were sufficient in quality to individualize the ventricular cavities and the cerebral cortex, and to calculate the ventricular ratio in hydrocephalus rats when compared to their respective anatomic slice.

0.1T magnetic resonance image in the study of experimental hydrocephalus in rats. Accuracy of the method in the measurements of the ventricular size / Imagem de ressonância magnética de 1,0T no estudo da hidrocefalia experimental em ratos. Avaliação do método de medição do tamanho ventricular

PURPOSE: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to measure the ventricular size in experimental hydrocephalus in pup rats. METHODS: Wistar rats were subjected to hydrocephalus by intracisternal injection of 20% kaolin (n=13). Ten rats remained uninjected to be used as controls. At the endpoint of experiment animals were submitted to MRI of brain and killed. The ventricular size was assessed using three measures: ventricular ratio (VR), the cortical thickness (Cx) and the ventricles area (VA), performed on photographs of anatomical sections and MRI. RESULTS: The images obtained through MR present enough quality to show the lateral ventricular cavities but not to demonstrate the difference between the cortex and the white matter, as well as the details of the deep structures of the brain. There were no statistically differences between the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992, respectively). There was difference between VA measured on anatomical sections and MRI (p<0.0001). CONCLUSION: The parameters obtained through 1.0T MRI were sufficient in quality to individualize the ventricular cavities and the cerebral cortex, and to calculate the ventricular ratio in hydrocephalus rats when compared to their respective anatomic slice.

OBJETIVO: Investigar a fidelidade das Imagens de Ressonância Magnética de 1,0T no estudo do tamanho ventricular na hidrocefalia experimental em ratos jovens. MÉTODOS: Ratos Wistar foram submetidos à hidrocefalia através da injeção intracisternal de caulim 20%. Dez animais permaneceram sem injeção para uso como controles. Ao final do experimento, os animais foram submetidos à Ressonância magnética de encéfalo e sacrificados. O tamanho ventricular foi avaliado por três medidas: razão ventricular (VR), espessura cortical (Cx) e área ventricular (VA), tomadas em fotografias das secções anatômicas e nas imagens de ressonância magnética (RM). RESULTADOS: As imagens por RM apresentaram qualidade suficiente para individualizar os ventriculos laterais, mas a distinção entre córtex e substância branca, bem como detalhamento das estruturas profundas do encéfalo não foram possíveis. Quando comparadas as medidas em seções anatômicas e RM, não houve diferença estatística entre as médias de razão ventricular e espessura cortical (p=0,9946 e p=0,5992, respectivamente). Houve diferença da área ventricular comparando-se as secções anatômicas e ressonância magnética (p<0,0001). CONCLUSÃO: Os parâmetros obtidos através de imagens da ressonância magnética de 1,0T foram suficientes para individualizar as cavidades ventriculares e o córtex cerebral, e para calcular o tamanho ventricular em ratos hidrocefálicos quando comparados aos seus respectivos cortes anatômicos.

Oral treatment with Hev b 13 prevents experimental arthritis in mice.

Hev b 13 is an allergenic esterase obtained from the rubber tree Hevea brasiliensis, which has been shown recently to induce human monocytes to release interleukin (IL)-10 in vitro, and to exert a potent anti-inflammatory effect in vivo. Moreover, Hev b 13 has been shown to reduce clinical signs of inflammation and also histological damage to the distal colon of mice with 2,4,6-trinitrobenze sulphonic acid (TNBS)-induced colitis after its oral administration. The aim of this study was to investigate the effect of Hev b 13 on human mononuclear cells, as well as its therapeutic use in the methylated bovine serum albumin (mBSA) model of antigen-induced arthritis. Five days before the intra-articular challenge, and daily thereafter for 8 days, Hev b 13 was administered by oral gavage. In mice treated with a dose of 0·5 mg/kg of Hev b 13, the severity of oedema, leucocyte infiltration, pannus formation and cartilage erosion were reduced significantly. These findings underscore the anti-inflammatory activity suggested previously for Hev b 13, an activity speculated to be related to its interaction with monocytes/macrophages and the consequent stimulation of IL-10 release and reduction of tumour necrosis factor (TNF) release. The study also opens a wide range of possible applications in the field of immune-mediated inflammatory diseases.

Changes caused by hydrocephalus, induced by kaolin, in the corpus callosum of adult dogs.

PURPOSE: To analyze the ventricular enlargement and myelination of the corpus callosum in adult dogs after four and eight weeks of kaolin-induction of hydrocephalus. METHODS: 36 dogs were randomly divided into 3 groups: 1 - without hydrocephalus, 2 - kaolin-induction of hydrocephalus until the fourth week, and 3 - kaolin-induction of hydrocephalus until the eighth week. Ventricular ratios and volumes were calculated using magnetic resonance images, and myelination of the corpus callosum were histologically evaluated using solocromo-cianin stain. RESULTS: Radiological hydrocephalus was observed in 93.75% and overall mortality was 38.4%. Ventricular volumes and ratios were higher in groups 2 and 3 compared to group 1 and similar when measures in the fourth and eighth weeks were compared in the group 3. Indices of luminescence in the knee and in the splenium of the corpus callosum were higher in group 2 than in group 1 indicating that there was loss of myelin in group 2, and similar in groups 1 and 3, showing a tendency to remyelination after 8 weeks. CONCLUSION: The corpus callosum of dogs with kaolin-induced hydrocephalus responds with demyelination of the knee and splenium by the fourth week with a tendency to remyelination by the eighth week.

Changes caused by hidrocephalus, induced by kaolin, in the corpus callosum of adult dogs / Alterações causadas pela hidrocefalia, induzida por caulim, no corpo caloso de cães adultos

PURPOSE: To analyze the ventricular enlargement and myelination of the corpus callosum in adult dogs after four and eight weeks of kaolin-induction of hydrocephalus. METHODS: 36 dogs were randomly divided into 3 groups: 1 - without hydrocephalus, 2 - kaolin-induction of hydrocephalus until the fourth week, and 3 - kaolin-induction of hydrocephalus until the eighth week. Ventricular ratios and volumes were calculated using magnetic resonance images, and myelination of the corpus callosum were histologically evaluated using solocromo-cianin stain. RESULTS: Radiological hydrocephalus was observed in 93.75 percent and overall mortality was 38.4 percent. Ventricular volumes and ratios were higher in groups 2 and 3 compared to group 1 and similar when measures in the fourth and eighth weeks were compared in the group 3. Indices of luminescence in the knee and in the splenium of the corpus callosum were higher in group 2 than in group 1 indicating that there was loss of myelin in group 2, and similar in groups 1 and 3, showing a tendency to remyelination after 8 weeks. CONCLUSION: The corpus callosum of dogs with kaolin-induced hydrocephalus responds with demyelination of the knee and splenium by the fourth week with a tendency to remyelination by the eighth week.

OBJETIVO: Analisar a dilatação ventricular e a mielinização do corpo caloso em cães adultos após quatro e oito semanas da indução de hidrocefalia por caulin. MÉTODOS: 36 cães foram aleatoriamente divididos em 3 grupos: 1- sem hidrocefalia, 2- quatro semanas de hidrocefalia induzida por caulin, 3- oito semanas de hidrocefalia induzida por caulin. As razões e volumes ventriculares foram calculados utilizando imagens de ressonância magnética, e, a mielinização do corpo caloso por estudo histológico (coloração com solocromo- cianina). RESULTADOS: Hidrocefalia foi observada radiologicamente em 93,75 por cento e a mortalidade global foi de 38,4 por cento. Os volumes e as razões ventriculares foram maiores nos grupos 2 e 3 em relação ao grupo 1 e semelhantes nas quarta e oitava semanas no grupo 3. Índices de luminescência no joelho e no esplênio do corpo caloso foram maiores no grupo 2 em relação ao grupo 1, indicando que houve perda de mielina no grupo 2, e semelhantes nos grupos 1 e 3, mostrando uma tendência à remielinização em torno de 8 semanas. CONCLUSÃO: O corpo caloso de cães com hidrocefalia induzida por caulin responde com desmielinização no joelho e esplênio em torno de quatro semanas com tendência à remielinização em torno da oitava semana.

Chronic effect of vagotomy in the morphometry of the myenteric plexus of rats' duodenum / Efeito crônico da vagotomia sobre a morfometria do plexo mioentérico do duodeno de ratos

BACKGROUND: The gastrointestinal disorders have been associated with morphological alterations in the myenteric nervous plexus. AIM: To evaluate, through morphometric studies, the chronic effects of the subdiaphragmatic trunk vagotomy on the nervous plexus. METHODS: Fifteen male exemplars of Wistar Rattus novergicus weighing about 150g, distributed into three groups, have been used: control (n=5), Sham (n=5) and vagotomized (n=5). The animals were sacrificed after 30 and 90 days post surgery. Fragments of duodenum were fixed in Bouin solution, embedded into paraffin and stained with HE and PAS. Morphometric analysis was performed by a Carl Zeiss KM 450 image system. The following aspects were observed: the density of nervous cells per linear micrometer (µm) (ND); the area of perikarya (µm²) (NA); the number of satellite cells per µm (SCD); and the number of satellite cells per neuron (SC/N). The averages were compared with the help of "software" program Sigma Plus through two way - ANOVA and Tuckey post-test. RESULTS: Denervation increased SC/N (p<0,05) and NA (p<0,05), in a time-dependent denervation way (p<0,05). However ND and SCD, decreased, which significantly with the animal's age (p<0,001). CONCLUSION: Vagotomy altered the myenteric plexus morphology in a time-dependent way.

RACIONAL: As disfunções gastrintestinais têm sido associadas à alterações morfológicas no plexo nervoso mioentérico. OBJETIVO: Avaliar através do estudo morfométrico, os efeitos crônicos da vagotomia troncular subdiafragmática sobre esse plexo nervoso. MÉTODOS: Foram utilizados 15 exemplares machos de Rattus novergicus da variedade Wistar, com cerca de 150 g, distribuídos nos grupos controle (n=5), Sham (n=5) e vagotomizados (n=5). Os animais foram sacrificados depois de 30 e 90 dias após as operações. Em seguida, fragmentos do duodeno foram fixados em solução de Bouin, incluídos em parafina e corados por HE e PAS. A análise morfométrica foi realizada por meio do sistema de análise de imagem Carl Zeiss KM 450. Foram observados: a densidade de células nervosas por micrômetro linear (µm); a área dos pericários (µm²); o número de células satélites por µm; e o número de células satélites por neurônio. As médias foram comparadas com o auxílio do programa de "software" Sigma Plus através do Two way - ANOVA e do pós-teste de Tukey. RESULTADOS: A desnervação aumentou o número de células satélites por neurônios (p<0,05) e a área média dos pericários (p<0,05), de maneira dependente do tempo de desnervação (p<0,05), mas diminuiu significativamente a densidade de neurônios (p<0,05) e de células satélites (p<0,05) em função da idade (p<0,001). CONCLUSÃO: A vagotomia alterou a morfologia do plexo mioentérico de maneira dependente do tempo.

Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis.

Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile's method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex.

Auditory evoked potential in handled and non-handled irondeficient rats

Iron deficiency alters metabolism, neurotransmission, glial integrity and the cortical myelin layer, besides increasing myelinization time. Environmental stimulation (handling) improves morphological, biochemical, electrophysiological and behavioral aspects of both well-nourished and malnourished animals. The objective of the present study was to determine the effects of an irondeficient diet and of handling on the brainstem auditory evoked potential (BAEP) of rats during development. Ninety-six male rats were divided since birth into Well-nourished (W, 35 mg iron/kg) and Anemic (A, 4 mg iron/kg) groups, and subdivided into Handling (H) and No Handling (NH). Body weight, hemoglobin (Hb), hematocrit (Ht), latencies of waves I, II, III IV, I-IV interpeak interval, and response threshold to auditory stimuli were evaluated at 18, 22, and 32 days. W animals presented higher Hb and Ht levels than A animals at 18, 22 and 32 days. The animals presented longer latencies of waves I, II, III and IV and I-IV interpeak interval of BAEP at 18 than at 22 and 32 days, and AH18 rats presented longer latencies of waves I and II than AH22 and AH32 rats, and longer wave I latency than WH18 animals. Iron deficiency increased the latencies of BAEP waves, suggesting damage to the myelin layer, especially during the early development, and the effects of handling were more evident along time in anemic animals.(AU)