A1 Noradrenergic Neurons Lesions Reduce Natriuresis and Hypertensive Responses to Hypernatremia in Rats

Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280-340 g) received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL-1) or free saporin (sham, 0.021 ng.nL-1) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg-1, b.wt., for longer than 1 min). In the sham-group (n = 8), HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline). Ten min after HS infusion, the pressor responses of the anti-DβH-saporin-treated rats (n = 11)were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group), and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg). Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05). In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DβH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid. © 2013 da Silva et al.

Different tools for estimating cardiovascular risk in Brazilian postmenopausal women

Objective: To compare estimation of cardiovascular risk using the Framinghan Risk Score (FRS) and the presence of the metabolic syndrome (MetS) in postmenopausal women to prevent primary cardiovascular disease (CVD). Methods: This cross-sectional study included 497 Brazilian women (aged 45 years and amenorrhea >12months). Cardiovascular risk was calculated using the FRS that includes age, total cholesterol, HDL, systolic blood pressure and smoking status. Women showing three or more of the following criteria were diagnosed with MetS: waist circumference (WC) >88cm, blood pressure 130/85mmHg, triglycerides 150mg/dl, HDL<50mg/dl and glucose 100mg/dl. For statistical analysis, the Chi-square, Fisher's exact, and logistic regression (odds ratio-OR) were used. Results: The mean age was 55.3±7.0 years and time since menopause 7.2±5.9 years. Based on FRS, 72.4% of women were classified as low-risk, 16.5% moderate risk and 11.1% a high-risk. MetS was identified in 40% of the women, and 46.2% were considered of moderate risk for CVD, while 84.9% of those without MetS were classified as low-risk (p<0.001). The risk for CVD increased significantly with age at menopause (OR1.10; 95% CI, 1.04-1.17), time since menopause (OR1.13; 95% CI, 1.08-1.18), elevated triglycerides (OR1.03; 95% CI, 1.0-1.10) and presence of MetS (OR1.72; 95% CI 1.48-1.84). Conclusions: By using only FRS to estimate cardiovascular risk, a substantial number of postmenopausal women showing evidence of MetS were not identified, even though women with MetS are at higher risk of CVD. © 2013 Informa UK Ltd.

Influence of experimental canine ehrlichiosis on the E-ADA activity and purine levels in serum and possible functional correlations with pathogenesis

The aim of this study was to evaluate adenosine deaminase activity and purines levels in serum of dogs experimentally infected by Ehrlichia canis. Banked serum samples of dogs divided into two groups with five animals each: healthy animals and animals infected by E. canis. The concentration of purines (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine, inosine, hypoxanthine, xanthine and uric acid), and adenosine deaminase (E-ADA) activity in sera were evaluated. Samples were collected on days 12 and 30 post-infection (PI). The E-ADA activity showed a significant reduction on day 12 PI, and increased on day 30 PI in dogs infected with E. canis. On day 12, an increase in seric concentration of ATP, ADP and adenosine was verified, and different levels of hypoxanthine, xanthine and uric acid had a drastic reduction in infected compared healthy dogs (P< 0.05). However, on day 30 PI, the levels of seric ADP and AMP decreased, unlike the concentration of xanthine and uric acid that increased significantly in infected dogs (P< 0.05). Therefore, the activity of E-ADA and purine levels are altered in experimental canine ehrlichiosis, probably with the purpose of modulating the pathogenesis of the disease related to immune response, oxidative stress and coagulation disorders in acute phase. © 2013 Elsevier B.V.

An HPLC-UV method for the quantification of zidovudine in rat plasma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência do hormônio tireoidiano e da restrição alimentar sobre dano de DNA em animais obesos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito de diferentes doses de hormônios tireoidianos sobre a expressão gênica e protéica de proteínas relacionadas ao trânsito de cálcio em animais obesos e obesos submetidos à restrição alimentar

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Inter-relação da leptina e dos hormônios tireoidianos na perda de peso de ratos obesos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo clínico e molecular da relação entre câncer de mama e doenças tireoidianas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Inter-relação da modulação gênica entre triidotironina(T3) e estradiol(E2) em cultura primária de adrenocarcinoma de mama

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo da eficiência reprodutiva de búfalos (Bubalus bubalis) na Amazônia Oriental

Foram avaliados os dados de 1983 a 2005 de cinco rebanhos bubalinos das raças Jafarabadi, Murrah, Mediterrâneo, Carabao e Tipo Baio, bem como seus mestiços. Estudaram-se as características reprodutivas: Idade à Primeira Cria (IPC), Intervalo de Partos (IDP), Eficiência Reprodutiva (ER), Fertilidade Real Adaptada (FRA), Produtividade ao Primeiro Parto Adaptada (PPPA) e Produtividade Acumulada Adaptada (PACA). A média geral encontrada, não ajustada, para IPC foi de 1052,52 ± 120,45 dias (34,7 meses), com valor mínimo e máximo de 737 e 1271 dias, respectivamente, com um coeficiente de variação de 10,32%. O grau de sangue da fêmea e o ano do parto apresentaram efeito significativo (P<0,0001) sobre a idade ao primeiro parto. Para o IEP, a média geral encontrada, não ajustada, foi de 399,69 ± 23,78 dias ou 13,17 meses com um coeficiente de variação de 5,88%. Não foi observada influência significativa das fontes de variação (grau de sangue da fêmea, ano do parto e estação do parto) nos interpartos. A média geral encontrada, não ajustada, para ER, foi de 91,09 ± 1,89% com um coeficiente de variação de 2,05%. Não foi observada influência significativa das fontes de variação (grau de sangue da fêmea, ano do parto e estação do parto) na ER do rebanho. A FRA média encontrada, não ajustada, foi 29,30 ± 4,40 quilogramas de bezerro parido por ano, com valor mínimo e máximo de 0,99 e 44,27 quilogramas de bezerro parido por ano, respectivamente, com um coeficiente de variação de 11,89%. Dentre os fatores que afetam a FRA do rebanho estudado, o grau de sangue da fêmea e o ano do parto mostraram influência significativa (P<0,0001) constituindo-se, portanto, como fontes de variação para essa característica. Para a PPPA, a média geral encontrada, não ajustada, foi de 33,75 ± 6,89 quilogramas, com valor mínimo e máximo de 10 e 62 quilogramas, respectivamente, com um coeficiente de variação de 10,20%. Dentre os fatores que afetaram a PPPA do rebanho estudado, somente o ano do parto mostrou influência significativa (P<0,0001) constituindo-se, portanto, como fonte de variação para essa característica. No que diz respeito a PACA, a média geral encontrada, não ajustada, foi de 22,86 ± 6,55 quilogramas de bezerro parido por ano, com valor mínimo e máximo de 2,08 e 55,35 quilogramas de bezerro parido por ano, respectivamente, com um coeficiente de variação de 6,55%. Dentre os fatores que afetaram a PACA do rebanho estudado, o grau de sangue da fêmea e o ano do parto mostraram influência significativa (P<0,0001) constituindo-se, portanto, como fontes de variação para essa característica. Os parâmetros reprodutivos avaliados neste estudo mostraram-se dentro de uma variação compatível com a observada na literatura pertinente. De maneira geral, verificou-se influência do ano de parto, grau de sangue e grau de sangue da fêmea sobre as características estudadas, o que indica que tais efeitos devem ser levados em consideração na avaliação e seleção dos animais. Os índices produtivos utilizados mostraram-se de grande valia para a seleção, devendo ser melhor estudadas suas interações para com o desempenho geral do rebanho.

Hipotireoidismo em cães: aspectos gerais

Hypothyroidism is a common endocrine disorder in dogs caused by insufficient production and secretion of thyroid hormones. Most affected dogs have primary hypothyroidism that results from lymphocytic thyroiditis, idiopathic thyroid atrophy, or more rarely, neoplastic destruction. Secondary hypothyroidism resulting from inadequate secretion of thyrotropin (thyroid-stimulating hormone –TSH) from the pituitary gland is less commonly recognized. Tertiary hypothyroidism resulting from a deficiency of hypothalamic thyrotropin-releasing hormone (TRH) has not been documented in dogs. The diagnosis of hypothyroidism in dogs is made on the basis of clinical findings, results of routine laboratory and thyroid gland function tests and response to thyroid hormone replacement. Unfortunately, these tests have high sensitivity, but low specificity, for use in the diagnosis of hypothyroidism. Thyroid hormone supplementation is indicated for the treatment of confirmed hypothyroidism and for the diagnoses of the disease through clinical response to trial therapy

Endocrine and paracrine regulation of zebrafish spermatogenesis: the Sertoli cell perspective

Spermatogonial stem cells (SSCs) either self-renew or differentiate into spermatogonia that further develop into spermatozoa. Self-renewal occurs when residing in a specific micro-environment (niche) while displacement from the niche would tip the signalling balance towards differentiation. Considering the cystic type of spermatogenesis in fish, the SSC candidates are single type A undifferentiated (A(und)) spermatogonia, enveloped by mostly one niche-forming Sertoli cell. When going through a self-renewal cell cycle, the resulting new single type Aund spermatogonium would have to recruit another Sertoli cell to expand the niche space, while a differentiating germ cell cyle would result in a pair of spermatogonia that remain in contact with their cyst-forming Sertoli cells. In zebrafish, thyroid hormone stimulates the proliferation of Sertoli cells and of type Aund spermatogonia, involving Igf3, a new member of the Igf family. In cystic spermatogenesis, type Aund spermatogonia usually do not leave the niche, so that supposedly the signalling in the niche changes when switching from self-renewal to differentiation. and rzAmh inhibited differentiation of type A(und) spermatogonia as well as Fsh-stimulated steroidogenesis. Thus, for Fsh to efficiently stimulate testis functions, Amh bioactivity should be dampened. We also discovered that Fsh increased Sertoli cell Igf3 gene and protein expression; rzIgf3 stimulated spermatogonial proliferation and Fsh-stimulated spermatogenesis was significantly impaired by inhibiting Igf receptor signaling. We propose that in zebrafish, Fsh is the major regulator of testis functions and, supported by other endocrine systems (e.g. thyroid hormone), regulates Leydig cell steroidogenesis as well as Sertoli cell number and growth factor production to promote spermatogenesis.

Triiodothyronine and breast cancer

The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

Production of autoantibodies associated with polyclonal activation in Yersinia enterocolitica 0:8-infected mice

Polyclonal lymphocyte stimulation is one of the immunomodulatory mechanisms induced by arthritogenic pathogens. In this study we examined the polyclonal activation potential of a virulent strain of Y. enterocolitica serotype O:8 (WA 2707+) and its plasmidless isogenic pair (WA 2707-). SPF Swiss mice were infected intragastrically and spleen cells were obtained on days 7, 14, 21, 28, 35 and 42 after infection. The number of cells secreting nonspecific immunoglobulins of IgG, IgM and IgA isotypes was determined by the ELISPOT technique. The presence of serum-specific antibodies was investigated by ELISA and the presence of autoantibodies by dot-blot assay. Although the patterns of infection of the two bacterial strains were almost the same, only the animals infected with the virulent strain presented clinical anomalies. Neither arthritic nor inflammatory signs were observed in the joints of the infected animals. The greatest activation observed was that of the nonspecific IgM-secreting cells, and their peak of secretion occurred between the 28th and the 42nd day after infection, for both strains of Y. enterocolitica O:8. Only the animals infected with the virulent strain (WA 2707+) produced IgG-specific antibodies in the serum, from the 28th day after infection. The serum of animals infected with either strain showed reactivity to all the autologous constituents tested, mainly on the 28th and 42nd day after infection. It was concluded that infection of mice with either the virulent strain of Y. enterocolitica O:8 or with its plasmidless isogenic pair resulted in the polyclonal activation of the splenic B lymphocytes including some autoreactive clones.

Triiodothyronine Acutely Stimulates Glucose Transport into L6 Muscle Cells Without Increasing Surface GLUT4, GLUT1, or GLUT3

Background: Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T-3) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T-3 and insulin action. Methods: Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T3, Tx plus insulin, and Tx plus insulin and T-3. Results: Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T-3 treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T-3 treatment; however, in these cells glucose transport was not stimulated by T-3. In wild-type L6 cells, although T-3 treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T-3 stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T-3 plus insulin. Conclusions: These data reveal that T-3 rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T-3 effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT.