Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism.

Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As ß-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves ß-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 µM), in the presence or absence of α-tocopherol (40 µM). After 24 or 48 h, membrane integrity and DNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. The involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2',7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary ß-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with α-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesterone-treated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic ß-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone.

Sulfato de condroitina e hialuronato de sódio no tratamento da doença articular degenerativa em cães: estudo histológico da cartilagem articular e membrana sinovial / Chondroitin sulfate and sodium hyaluronate in the treatment of the degenerative joint disease in dogs: histological features of articular cartilage and synovium

Quinze cães, sem raça definida, de ambos os sexos, de peso entre 18 e 25kg, foram submetidos à secção artroscópica do ligamento cruzado cranial (LCCr) para indução da doença articular degenerativa (DAD). Após três semanas de instabilidade articular, o LCCr foi substituído pela fáscia lata segundo a técnica de Schwalder (1989) e os animais foram distribuídos em três grupos de cinco. Os animais do grupo I, controle, não receberam tratamento medicamentoso; os do grupo II, 24mg/animal de sulfato de condroitina, por via IM, de cinco em cinco dias, totalizando seis aplicações; e os do grupo III foram tratados com hialuronato de sódio na dose de 20mg/animal, por via IV, de cinco em cinco dias num total de três administrações. Ao final de 90 dias, os animais foram eutanasiados e procedeu-se à colheita e ao processamento histológico da membrana sinovial e da cartilagem articular para avaliações morfológica e morfométrica. No grupo I foram observadas alterações degenerativas de DAD mais acentuadas que nos demais grupos, como redução do número de condrócitos, presença de pânus, fibrilações, fissuras, erosões e irregularidades na superfície articular. No grupo II observou-se elevação do número de condrócitos com aumento da atividade de síntese da matriz e redução das lesões na superfície da cartilagem. No grupo III houve aumento do número de condrócitos que eram, muitas vezes, morfologicamente inviáveis. Todos os grupos apresentaram proliferação da membrana sinovial e presença de infiltrado linfoplasmocitário na subíntima e na perivascular. Nos grupos I e III, a proliferação da membrana sinovial era exuberante com formação de pânus, presença de sinoviócitos achatados ou ausência de sinóvia com tecido de granulação. Os resultados sugerem que o sulfato de condroitina estimulou a cartilagem articular, diminuindo ou retardando as alterações da DAD e o hialuronato de sódio não interferiu no processo degenerativo da cartilagem articular. Não foi constatada ...

Fifteen mongrel dogs, both genders, weighting from 18 to 25kg were used and Degenerative Joint Disease (DJD) was induced through cranial cruciate ligament (CCrL) artroscopical section. After three weeks, CCrL was reconstructed by Schawalder's (1989) technique. Then, dogs were distributed in three groups and the following protocols were used: group I, control, no other treatment but the CCrL reconstruction; group II received chondroitin sulfate 24mg per animal every five days, intramuscularly, in a total of six injections; and group III received sodium hyaluronate 20mg per animal every five days, intravenously, in a total of three injections. Clinical observation was done until 90 days after treatments. By that time, the articular cartilage and synovium were collected and their morphology was evaluated. In group I, the degenerative alterations of the DJD were the most intense. Thus, decrease of chondrocytes number, pannus, fibrillations, grooves, erosion, and irregular articular surface were observed on the cartilage. In group II, raise of chondrocytes number was observed, with increase of synthesis activity of matrix and decrease of lesions on the articular surface. There was an increase of chondrocytes in group III, but the cells were morphologically unviable. All the groups showed proliferation of the synovial membrane, with limpho-plasma cells infiltrated in subintim and perivascular. In groups I and III, the proliferation of synovium was abundant, with formation of pannus, flattened synoviocytes or synovium absent with granulation tissue. Those results suggest that the chondroitin sulfate stimulated the articular cartilage; decreasing or delaying the alterations of DJD, as well as, the sodium hyaluronate did not interfere on degenerative process in articular cartilage. No favorable action of these drugs in the synovial membrane was verified.

Effects of chondroitin sulfate and sodium hyaluronate on chondrocytes and extracellular matrix of articular cartilage in dogs with degenerative joint disease / Efeitos do sulfato de condroitina e do hialuronato de sódio nos condrócitos e na matriz extracelular na cartilagem articular de cães com doença articular degenerativa

Samples of articular cartilage of femur, tibia and patella of 15 dogs with experimentally induced degenerative joint disease (DJD) were microscopically analyzed. Animals were distributed into three groups (n=5): the control group received no medication; the second group was treated with chondroitin sulfate and the third received sodium hyaluronate. Samples were processed and stained with HE and toluidine blue for morphological evaluation. The metabolic and proliferative activity of the chondrocytes was evaluated by the measurement of nucleolar organizer regions (NORs) after impregnation by silver nitrate. Significant differences were not observed (P>0.05) in the morphology among the groups, however, the group treated with sodium hyaluronate had a higher score suggesting a trend to a greater severity of the lesions. Significant differences were not observed (P>0.05) in the measurement of NORs, cells and NORs/cells among the groups. Although differences were not significant, sodium hyaluronate group showed higher NOR and cell counts which suggested an increase of the proliferation rate of chondrocytes. In addition, a higher NOR/cell ratio in the group treated with chondroitin sulfate suggested that this drug may have stimulated the metabolic activity of the chondrocytes, minimizing the lesions resulting from DJD.

Foram utilizadas amostras de cartilagem articular do fêmur, tíbia e patela de 15 cães com doença articular degenerativa (DAD), induzida experimentalmente. Foram constituídos três grupos de cinco animais: grupo 1 - controle, não medicado; grupo 2 - tratado com sulfato de condroitina e grupo 3 - tratado com hialuronato de sódio. As amostras foram processadas e coradas pelas técnicas de HE e de azul de toluidina para avaliação das alterações morfológicas, e impregnadas pelo nitrato de prata para análise da atividade metabólica e/ou proliferativa dos condrócitos, por meio da visualização e quantificação de regiões organizadoras do nucléolo (NORs). Não foram notadas diferenças significativas (P<0,05) na avaliação morfológica entre os grupos. O grupo tratado com hialuronato obteve maior escore sugerindo maior gravidade das lesões. Não foram observadas diferenças significativas (P>0,05) na contagem de NORs, células e NORs/célula entre os grupos. As maiores contagens de NORs e de células no grupo tratado com hialuronato de sódio sugeriram aumento da taxa de proliferação dos condrócitos. A maior relação de NORs/célula obtida no grupo tratado com sulfato de condroitina sugere que essa droga estimula a atividade metabólica do condrócito, minimizando as lesões ocorridas durante a DAD.

Histomorfometria e histoquímica da tuba uterina e do útero de ratas púberes e pré-púberes induzidas ao hipertireoidismo / Histomorphometry and histochemistry of the uterine tubes and uterus of puberal and prepuberal rats induced for hyperthyroidism

Foram estudadas a histomorfometria e a atividade secretória das tubas uterinas e do útero de 38 ratas Wistar púberes, distribuídas em quatro grupos: (1) eutireóideo em proestro-estro, (2) hipertireóideo em proestro-estro, (3) eutireóideo em metaestro-diestro e (4) hipertireóideo em metaestro-diestro. Posteriormente, foram utilizadas outras 24 ratas Wistar pré-púberes, com 12 dias de idade, distribuídas em dois grupos: (1) hipertireóideo (n=12) e (2) eutireóideo (n=12). O útero e as tubas uterinas foram colhidos para avaliação histomorfométrica e histoquímica. A altura do epitélio da ampola, tanto no proestro-estro quanto no metaestro-diestro, elevou-se com a administração de tiroxina, tornando-se semelhante à do istmo. O hipertireoidismo aumentou a secreção PAS positiva e de mucossubstâncias ácidas do infundíbulo na fase estrogênica, igualando-a à do istmo. A parede uterina apresentou-se mais espessa na fase estrogênica, resultado da ação conjunta da tiroxina no endométrio e no miométrio. A atividade secretória e a composição do colágeno uterino não diferiram entre tratamentos. Nas ratas pré-púberes, o hipertireoidismo aumentou a espessura do miométrio e da parede uterina, mas não alterou a tuba uterina. O hipertireoidismo em ratas pré-púberes induz modificações significativas somente no útero; após a maturidade sexual, as modificações ocorrem no útero e na tuba uterina em intensidade variável e dependentes da fase do ciclo estral.

Resposta da paratireóide de ratas às variações do cálcio e fósforo plasmáticos no hipertireoidismo e hipogonadismo / Response of parathyroid to the plasmatic of calcium and phosphorus variations in hyperthyroidism and hypogonadism in the rat

Foram estudadas 84 paratireóides de ratas Wistar com cinco meses de idade, castradas ou não, e mantidas em hipertireoidismo por períodos de 30, 60 e 90 dias. Dois grupos eutireóideos, um castrado e o outro não, foram mantidos nas mesmas condições e serviram de controle. Ao final de cada período, foram colhidos o plasma, para determinação da concentração de T4 livre, o cálcio e o fósforo e as paratireóides, para análise morfológica e determinação da porcentagem de núcleo, citoplasma e estroma. Aos 90 dias houve reversão da hipocalcemia observada aos 60 dias nos animais eutireóideos castrados e não castrados, graças à hipertrofia da paratireóide. O mesmo não ocorreu com os grupos hipertireóideos que apresentaram hipocalcemia e hiperfosfatemia progressivas e não compensadas até os 90 dias. Na castração há pronta reversão da hipocalcemia em resposta ao aumento da atividade funcional da paratireóide. No estado hipertireóideo com gônadas funcionais, apesar da hipertrofia da paratireóide, não há retorno à isocalcemia e isofosfatemia. Na associação hipertireoidismo-castração, a paratireóide não responde satisfatoriamente à hipocalcemia e hiperfosfatemia intensas e progressivas.

Histomorfometria e histoquímica dos ovários, tubas e útero de ratas hipotireóideas em metaestro-diestro / Histomorphometry and histochemistry of the ovaries, oviduct and uterus in hypothyroid rats in the metaestrus-diestrus

A foliculogênese ovariana foi estudada em ratas adultas Wistar, hipotireóideas na fase de metaestro-diestro. O hipotireoidismo foi induzido pela administração oral e diária de propiltiouracil (1mg/animal). As ratas eutireóideas receberam placebo. Após 120 dias de tratamento, foi colhido o plasma para dosagem de tiroxina livre, progesterona e estradiol após o que foram sacrificadas para colheita dos ovários, tubas e útero, para avaliação histomorfométrica e histoquímica. O hipotireoidismo reduziu significativamente o peso dos ovários e o número de folículos secundários e terciários e de corpos lúteos sem, no entanto, alterar a porcentagem de folículos atrésicos e o número de folículos primários e pré-ovulatórios. As células da granulosa dos folículos secundários das ratas hipotireóideas apresentavam núcleo pequeno com significativa redução do número de regiões organizadoras de nucléolo (NORs). Essas mudanças não alteraram os valores periféricos de estradiol e de progesterona. Houve redução significativa da espessura do endométrio, do número de glândulas endometriais e da altura do epitélio do infundíbulo.

Avaliaçäo radiológica e artroscópica e histologia da membrana sinovial do joelho de cäes tratados com associaçäo de sulfato de condroitina e hialuronato de sódio, após doença articular degenerativa induzida experimentalmente / Radiological, arthroscopical evaluation and synovial membrane histology of the knee of dogs treated with chondroitin sulphate- sodium hialuronate association after experimental degenerative joint disease

O presente trabalho objetivou avaliar a associaçäo de hialuronato de sódio e sulfato de condroitina no tratamento da doença articular degenerativa (DAD) em cäes. Dez cäes sem raça definida foram submetidos à secçäo artroscópica do ligamento cruzado cranial visando o desenvolvimento da DAD. Após 21 dias, foi substituído cirurgicamente o ligamento cruzado cranial em todos os animais e iniciado o tratamento com associaçäo de hialuronato de sódio e sulfato de condroitina em cinco cäes, sendo os remanescentes utilizados como grupo-controle. Avaliaçöes artroscópica e radiológica do membro posterior esquerdo foram realizadas antes da secçäo do ligamento, no dia da sua substituiçäo e 90 dias após a cirurgia. Histologicamente, o efeito da associaçäo de hialuronato de sódio e sulfato de condroitina foi mais evidente na membrana sinovial, observando-se regeneraçäo da camada íntima e diminuiçäo da infiltraçäo linfoplasmocitária na sub-íntima. Artroscópica e macroscopicamente näo houve prevençäo das lesöes cartilaginosas decorrentes da DAD.

A fase estrogênica altera a resposta do osso e do metabolismo mineral de ratas com hipertireoidismo? / Does the estrogenic phase modify the bone and mineral metabolism response in rats under hyperthyroidism?

The effect of the estrogenic phase in the bone and in the mineral metabolism was studied in Wistar adult female rats kept under euthyroidism or hyperthyroidism for 60 days. The rats were divided, according to the stage of the estrous cycle, into four groups: 1) euthyroid (proestrus-estrus), 2) euthyroid (metaestrus-diestrus), 3) hyperthyroid (proestrus-estrus), and 4) hyperthyroid (metaestrus-diestrus). After 60 days the blood plasma was collected and the concentrations of free T4, estradiol, progesterone, calcium, phosphorus, and of alkaline phosphatase were determined. The bones (femur and tibia) were analysed microscopically. Despite of the functional state of the thyroid, the levels of estrogen were significantly higher in the proestrus-estrus. The estrogenic phase increased the plasmatic concentration of calcium significantly in the euthyroid rats but it did not alter the levels of phosphorus and alkaline phosphatase. In the hyperthyroid state no significant differences in the plasmatic concentrations of calcium, phosphorus and alkaline phosphatase throughout the cycle were found. The phases of the cycle did not also influence the bone morphology in the euthyroid and hyperthyroid states. It was concluded that the estrogenic phase increases the plasmatic concentration of calcium, even without altering the bone morphology of the euthyroid rats. In addition the estrogenic phase does not increase the plasmatic calcium and it does not modify the response of the bone as well as of the mineral metabolism under effect of the hyperthyroidism.

Antioxidant dietary deficiency induces caspase activation in chick skeletal muscle cells

Apoptosis and necrosis are two distinct forms of cell death that can occur in response to different agents and stress conditions. In order to verify if the oxidative stress induced by dietary selenium and vitamin E deficiencies can lead muscle cells to apoptosis, one-day-old chicks were reared using diets differing in their vitamin E (0 or 10 IU/kg) and selenium (0 or 0.15 ppm) supplementation. Chick skeletal muscle tissue was obtained from 28-day-old animals and used to verify apoptosis occurrence based on caspase activity detection and DNA fragmentation. Antioxidant deficiency significantly increased caspase-like activity assessed by the hydrolysis of fluorogenic peptide substrates (Abz-peptidyl-EDDnp) at lambdaexc = 320 nm and lambdaem = 420 nm. Proteolytic activation was not accompanied by typical internucleosomal DNA fragmentation detected by field inversion gel electrophoresis. Although the general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-fmk) (0 to 80 muM) did not block caspase-like activity when preincubated for 30 min with muscle homogenates, the hydrolyzed substrates presented the same cleavage profile in HPLC (at the aspartic acid residue) when incubated with the purified recombinant enzyme caspase-3. These data indicate that oxidative stress causes caspase-like activation in muscle cells and suggest that cell death associated with exudative diathesis (dietary deficiency of selenium and vitamin E) can follow the apoptotic pathway

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 æg/ml) on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates) reduced (1.2 to 3.0 times) the catalytic efficiency of kallikrein (in a nanomolar range) on the hydrolysis of plasminogen (0.3 to 1.8 æM) and increased (1.9 to 7.7 times) the enzyme efficiency in factor XII (0.1 to 10 æM) activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times) kallikrein inhibition by antithrombin (1.4 æM), while chondroitin 4- and 6-sulfates reduced it (1.3 times). Heparin and heparan sulfate increased (1.4 times) the enzyme inhibition by the C1-inhibitor (150 nM)

Antioxidant dietary deficiency induces caspase activation in chick skeletal muscle cells.

Apoptosis and necrosis are two distinct forms of cell death that can occur in response to different agents and stress conditions. In order to verify if the oxidative stress induced by dietary selenium and vitamin E deficiencies can lead muscle cells to apoptosis, one-day-old chicks were reared using diets differing in their vitamin E (0 or 10 IU/kg) and selenium (0 or 0.15 ppm) supplementation. Chick skeletal muscle tissue was obtained from 28-day-old animals and used to verify apoptosis occurrence based on caspase activity detection and DNA fragmentation. Antioxidant deficiency significantly increased caspase-like activity assessed by the hydrolysis of fluorogenic peptide substrates (Abz-peptidyl-EDDnp) at lambda exc = 320 nm and lambda em = 420 nm. Proteolytic activation was not accompanied by typical internucleosomal DNA fragmentation detected by field inversion gel electrophoresis. Although the general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-fmk) (0 to 80 muM) did not block caspase-like activity when preincubated for 30 min with muscle homogenates, the hydrolyzed substrates presented the same cleavage profile in HPLC (at the aspartic acid residue) when incubated with the purified recombinant enzyme caspase-3. These data indicate that oxidative stress causes caspase-like activation in muscle cells and suggest that cell death associated with exudative diathesis (dietary deficiency of selenium and vitamin E) can follow the apoptotic pathway.

Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors.

Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 micro/ml) on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates) reduced (1.2 to 3.0 times) the catalytic efficiency of kallikrein (in a nanomolar range) on the hydrolysis of plasminogen (0.3 to 1.8 microM) and increased (1.9 to 7.7 times) the enzyme efficiency in factor XII (0.1 to 10 microM) activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times) kallikrein inhibition by antithrombin (1.4 microM), while chondroitin 4- and 6-sulfates reduced it (1.3 times). Heparin and heparan sulfate increased (1.4 times) the enzyme inhibition by the C1-inhibitor (150 nM).

Morfologia e histoquímica da pele de ratas hipotireóideas castradas e näo castradas / Morfology and histochemistry of the skin in hypothyroid castrated and intact rats

Foram estudadas as alteraçöes cutâneas de ratas Wistar adultas castradas e näo castradas, mantidas em estado hipotireóideo por 120 dias. Dois grupos eutireóideos, um castrado e outro näo castrado, serviram de controle. Secçöes da pele abdominal ventral e torácica dorsal foram coradas pelas técnicas de HE, PAS, azul de alcian (alcian blue), picro-sirius red-luz polarizada e Verhoeff. Adelgaçamento da epiderme, atrofia de glândulas sebáceas, reduçäo parcial ou total de fibras elásticas e do colágeno do tipo III da derme caracterizaram tanto o hipotireoidismo quanto a castraçäo. Retardo no crescimento dos folículos pilosos e hiperceratose foram vistos apenas na deficiência dos hormônios tireoidianos, independente do estado funcional das gônadas. A associaçäo hipotireoidismo e castraçäo caracterizou-se por adelgaçamento da epiderme da regiäo abdominal ventral e espessamento e aumento da celularidade na regiäo torácica dorsal, com derme adelgaçada e desprovida de fibras elásticas e de colágeno do tipo III. Conclui-se que a deficiência dos hormônios sexuais ou tireoidianos altera todos os componentes da pele e que as lesöes säo agravadas na associaçäo hipotireoidismo-castraçäo

Quantificaçäo das regiöes organizadoras de nucléolo (NORs) como parâmetro para avaliar a proliferaçäo das células da granulosa / Quantification of the nucleolar organizer regions (NORs) as a parameter to measure proliferation of granulosa cells

The goal of this study was to determine whether the quantification of the nucleolar organizer regions (AgNORs) is a useful parameter for evaluation of the proliferative potential of non-neoplastic granulosa cells in ovarian follicles at different stages of development. Seven ovaries from six-month-old rats, all of which in metestrus-diestrus, were studied. The number of AgNORs from 60 granulosa cell nuclei was quantified in secondary follicles with two to three layers of cells and in follicles with more than five layers of granulosa cells. Follicles with two to three layers had larger AgNORs in lower numbers, whereas more developed secondary follicles the AgNORs were predominantly smaller, scattered throughout the nucleus, and in significantly higher numbers. In conclusion, quantification of the nucleolar organizer regions is an appropriate parameter for differentiation of the proliferative potential of non-neoplastic granulosa cells

Mapping of human plasma kallikrein active site by design of peptides based on modifications of a Kazal-type inhibitor reactive site.

Human plasma kallikrein (huPK) is a proteinase that participates in several biological processes. Although various inhibitors control its activity, members of the Kazal family have not been identified as huPK inhibitors. In order to map the enzyme active site, we synthesized peptides based on the reactive site (PRILSPV) of a natural Kazal-type inhibitor found in Cayman plasma, which is not an huPK inhibitor. As expected, the leader peptide (Abz-SAPRILSPVQ-EDDnp) was not cleaved by huPK. Modifications to the leader peptide at P'1, P'3 and P'4 positions were made according to the sequence of a phage display-generated recombinant Kazal inhibitor (PYTLKWV) that presented huPK-binding ability. Novel peptides were identified as substrates for huPK and related enzymes. Both porcine pancreatic and human plasma kallikreins cleaved peptides at Arg or Lys bonds, whereas human pancreatic kallikrein cleaved bonds involving Arg or a pair of hydrophobic amino acid residues. Peptide hydrolysis by pancreatic kallikrein was not significantly altered by amino acid replacements. The peptide Abz-SAPRILSWVQ-EDDnp was the best substrate and a competitive inhibitor for huPK, indicating that Trp residue at the P'4 position is important for enzyme action.

Pododermatite de contato em frangos de corte / Contact pododermatitis in broilers

Occurrence of contact pododermatitis in broilers in the State of Minas Gerais, Brazil, is reported. Lesions in the footpad were detected as early as 13 days of age and progressed to ulceration. Histologically, primarily inflammatory and degenerative changes mostly at the epidermal-dermal junction were observed. Retrospective evaluation indicated that pododermatitis in these cases were associated with exposure to high litter moisture during the first days of life

Influência do hipogonadismo na histomorfometria e funçäo tireoidiana de ratas hipotireóideas / Influence of hypogonadism on the morphology and function of the thyroid from hypothyroid rats

Foram investigadas a morfologia e a funçäo tireoidiana de ratas Wistar, adultas, castradas e näo castradas e mantidas em estado hipotireóideo pela administraçäo diária de propiltiouracil por 120 dias. Ratas eutireóideas castradas e näo castradas serviram de controle. As tireóides, colhidas ao final do experimento, foram pesadas, processadas histologicamente e submetidas à análise morfométrica, pela qual foi determinada a proporçäo dos componentes glandulares (epitélio folicular, colóide e estroma). No plasma sangüíneo, colhido também ao final do período experimental, foram determinadas as concentraçöes de T3 total, T4 livre e TSH. O peso e a histomorfometria da tireóide näo sofreu influência da castraçäo e o aumento do componente epitelial e decréscimo da quantidade de colóide só foram detectados no hipotireoidismo. No estado eutireóideo a deficiência dos esteróides sexuais levou ao aumento dos valores de T4 livre e T3 total e no hipotireoidismo, exacerbou a queda de T3 total, mas näo a de T4 livre. Os valores de TSH näo se alteraram em nenhum dos estados funcionais da glândula ou das gônadas. Conclui-se que o hipogonadismo näo modifica a hiperplasia glandular e a queda dos níveis plasmáticos de tiroxina livre induzidos pelo propiltiouracil, mas altera profundamente o comportamento da triiodotironina total de acordo com o estado funcional da tireóide, tudo sem alterar os valores plasmáticos de TSH

Histomorfometria e funçäo tireoidiana no ciclo estral da rata / Histomorphometric and functional studies of the rat thyroid throughout the estrous cycle

The influence of the estrous cycle on the thyroid gland was studied. Twenty one five-to-seven-month-old Wistar female rats were divided according to the stage of the estrous cycle in two groups: metaestrus-diestrus and proestrus-estrus. After gross inspection, the thyroids were weighed, sampled, and processed for staining with hematoxilyn-eosin. Seric concentrations of total T4, free T4, total T3, TSH, progesterone, and estradiol were measured. The values of estradiol were significantly higher in the proestrus-estrus stage. However, no significant differences in the plasmatic concentrations of progesterone, free T4, total T4 and TSH throughout the cycle were found. The results of the morphometric study of the thyroid did not indicate any significant differences between the groups. These findings suggest that there is no thyreotrophic effect of estrogen during the estrous cycle in rats

Toxina T-2 e alteraçöes do crescimento endocondral em frangos de corte / T-2 toxin and disturbed endochondral bone growth in broiler chicken

Foi testada a habilidade da toxina T-2, produzida por Fusarium sporotrichioides Sherb e veiculada por milho experimentalmente contaminado, em induzir alteraçöes da placa epifisária proximal do tibiotarso de frangos de corte. Pintos de um dia, todos machos e da linhagem Hubbard, foram alimentados com raçäo básica a base de milho e soja, na qual todo o milho foi substituído por milho contaminado, contendo exclusivamente T-2 na quantidade de 2,64mg/Kg. Um outro grupo alimentado com milho näo contaminado serviu como testemunha e ambos foram observados por três períodos (7, 14 e 21 dias). Independente do período e da quantidade de T-2 ingerida (0,3 a 1,9mg/Kg), o tibiotarso dos animais tratados mostrou maturaçäo e diferenciçäo defectivas de condrócitos, lesöes vasculares e penetraçäo vascular de cartilagem, todas similares às da discondroplasia tibial. Conclui-se que a toxina T-2 oriunda de Fusarium sporotrichioides Sherb é capaz de induzir lesöes básicas e iniciais da discondroplasia tibial em frangos de corte

Proliferative and inflammatory changes in the urinary bladder of female rats naturally infected with Trichosomoides crassicauda: report of 48 cases

O presente trabalho teve o objetivo de descrever as alteraçöes encontradas na bexiga de ratas naturalmente parasitadas com Trichosomoides crassicauda. Foram estudadas em 48 ratas Wistar com idade entre 5 e 8 meses. A necropsia, foram detectados urólitos em sete animais (14,6(porcento)). Dentre as parasitadas, somente três ratas (6,3(porcento)) näo apresentavam alteraçäo histológica, três (6,3(porcento)) apresentavam papilomas e urólitos, quatro (8,3(porcento)) tinham urólitos com hiperplasia epitelial variando de moderada a intensa e 38 ratas restantes (79,2(porcento)) apresentavam grau variável de hiperplasia epitelial e inflamaçäo sem urolitíase. Näo se pôde concluir se a irritaçäo do epitélio desencadeada pelo parasita apresenta algum papel na induçäo de papiloma. No entanto, a ausência de papiloma em animais sem urolitíase sugere uma relaçäo direta entre urólitos e papilomas