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PURPOSE: NAFLD is a hepatic component of type 2 diabetes mellitus (T2D), in which impaired hepatic glucose production plays an important role. Inhibitors of sodium glucose transporter 2 (SGLT2) reduce glycemia and exert beneficial effects on diabetic complications. Recently, dual SGLT1/2 inhibition has been proposed to be more effective in reducing glycemia. We hypothesized that improving hepatic glucose metabolism induced by SGLT1/2 inhibition could be accompanied by beneficial effects on NAFLD progression. METHODS: Glycemic homeostasis, hepatic glucose production and NAFLD features were investigated in obese T2D mice, treated with SGLT1/2 inhibitor phlorizin for 1 week. RESULTS: T2D increased glycemia; insulinemia; hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) and glucose transporter 2 (Slc2a2 gene); hepatocyte nuclear factors 1A/4A/3B-binding activity in Slc2a2; endogenous glucose production; liver weight, plasma transaminase concentration as well as hepatic inflammation markers, and induced histological signals of non-alcoholic steatohepatitis (NASH, according to NASH-CRN Pathology Committee System). Phlorizin treatment restored all these parameters (mean NASH score reduced from 5.25 to 2.75 P<0.001); however, plasma transaminase concentration was partially reverted and some hepatic inflammation markers remained unaltered. CONCLUSION: NAFLD accompanies altered hepatic glucose metabolism in T2D mice and that greatly ameliorated through short-term treatment with the dual SGLT1/2 inhibitor. This suggests that altered hepatic glucose metabolism participates in T2D-related NAFLD and highlights the pharmacological inhibition of SGLTs as a useful approach not only for controlling glycemia but also for mitigating development and/or progression of NAFLD.
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Hypothyroidism and thyrotoxicosis produce adverse effects in male reproduction by unknown mechanisms. We investigated whether triiodothyronine (T3) modulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) synthesis/secretion, by inducing different thyroid states. In hypothyroidism, the content of Lhb and Fshb mRNAs was increased, while their association to ribosomes and the protein content were reduced and the serum LH and FSH concentrations were augmented and decreased, respectively. Thyrotoxicosis reduced Lhb mRNA and LH serum concentration, and increased Lhb mRNA translational rate. The Fshb mRNA content and its association to ribosomes were also increased, whereas FSH serum concentrations were comparable to euthyroid levels. Acute T3 treatment decreased the total content of Lhb and Fshb mRNAs, and increased their association to ribosomes, as well as the LHB and FSHB contents in secretory granules. This study shows that T3 acts on gonadotrophs, resulting in direct effects on LH and FSH synthesis/secretion of male rats, suggesting that some reproductive disorders observed in men may be associated with thyroid hormone imbalances.
Assuntos
Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Tri-Iodotironina/farmacologia , Animais , Expressão Gênica/efeitos dos fármacos , Hipotireoidismo/genética , Hipotireoidismo/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , TireoidectomiaRESUMO
Thousands of people die every year from burn injuries. The aim of this study is to evaluate the feasibility of high intensity femtosecond lasers as an auxiliary treatment of skin burns. We used an in vivo animal model and monitored the healing process using 4 different imaging modalities: histology, Optical Coherence Tomography (OCT), Second Harmonic Generation (SHG), and Fourier Transform Infrared (FTIR) spectroscopy. 3 dorsal areas of 20 anesthetized Wistar rats were burned by water vapor exposure and subsequently treated either by classical surgical debridement, by laser ablation, or left without treatment. Skin burn tissues were non-invasively characterized by OCT images and biopsied for further histopathology analysis, SHG imaging and FTIR spectroscopy at 3, 5, 7 and 14 days after burn. The laser protocol was found as efficient as the classical treatment for promoting the healing process. The study concludes to the validation of femtosecond ultra-short pulses laser treatment for skinburns, with the advantage of minimizing operatory trauma.
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Rapid actions of T3 on TSH synthesis in posttranscriptional steps, such as polyadenylation and translation rate, have already been described. The focus of this paper was to characterize rapid actions of T3 on TSH secretion and the involvement of actin and microtubule cytoskeleton in this process. For that, sham-operated (SO) and thyroidectomized (Tx) rats were subjected to acute or chronic treatment with T3. We observed a disarrangement in microtubule and actin cytoskeletons and an increase in Tshb mRNA levels in Tx rats, whereas the total TSH protein content was reduced in the pituitary gland as a whole, but increased in the secretory granules close to the plasma membrane of thyrotrophs, as well as in the extracellular space. The acute T3 dose promoted a rapid increase and redistribution of TSH secretory granules throughout the cytoplasm, as well as a rearrangement in actin and microtubule cytoskeletons. The T3 chronic treatment outcome reinforces the acute effects observed and, additionally, evinces an increase in the α-tubulin content and a rearrangement in microtubule cytoskeleton. Thus, T3 is able to rapidly suppress TSH secretion and, in parallel, to promote a rearrangement in actin and microtubules assembly throughout the pituitary gland, effects that seem to be independent from each other.
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Citoesqueleto/fisiologia , Vesículas Secretórias/fisiologia , Tireotrofos/citologia , Tireotropina/metabolismo , Tri-Iodotironina/farmacologia , Actinas/metabolismo , Animais , Masculino , Ratos , Ratos Wistar , Tireoidectomia , Tireotrofos/metabolismo , Tireotropina Subunidade beta/genética , Tireotropina Subunidade beta/metabolismoRESUMO
Glutamine is the most important donor of NH(3) in kidney playing an important role in acid-base buffering system. Besides this effect, glutamine presents many other relevant functions in the whole body, such as a precursor of arginine in adult and neonates. In addition to these effects, some studies have shown that glutamine can potentiate renal disease. In the present study, the effect of short-term treatment (15 days) with glutamine on control and diabetic rats was investigated. Using biochemical, histological and molecular biology analysis from control and diabetic rats we verified that glutamine supplementation increase in pro-inflammatory interleukins (IL)-1beta and IL-6 content in renal cortex and induce alteration in glomerular characteristics. This study showed that short-term treatment with glutamine in association with increased glucose levels could cause important alterations in glomerular morphology that may result in fast progression of kidney failure.
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Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Glutamina/toxicidade , Rim/patologia , Animais , Glicemia/análise , Contraindicações , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Suplementos Nutricionais/toxicidade , Regulação da Expressão Gênica , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/patologia , Glutamina/sangue , Glicosúria/induzido quimicamente , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Rim/metabolismo , Córtex Renal/metabolismo , Córtex Renal/patologia , Glomérulos Renais/patologia , Masculino , Nitrogênio/metabolismo , Ratos , Ratos Wistar , Esclerose/induzido quimicamente , Esclerose/patologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: We investigated factors that may be involved in the reduced leukocyte migration observed in intrauterine undernourished rats. METHODS: Male Wistar rat offspring (8-9 wk of age) of dams fed during pregnancy with 50% less food than control dams were used to measure L-selectin expression (by flow cytometry), bone marrow cell count, blood cell count, laminin and type IV collagen in the basal membrane of venules of the spermatic fascia (by immunohistochemistry), total protein level and serum albumin, and the production of leukotriene B4 after stimulation with tumor necrosis factor-alpha and corticosterone plasma levels (by enzyme-linked immunosorbent assay). RESULTS: Hypocellularity in bone marrow and peripheral blood and reduced L-selectin expression were found in the undernourished rat offspring (UR) compared with nourished offspring (NR; P < 0.05). Type IV collagen in the basal membrane of the venules of the spermatic fascia was less in UR than in NR (P < 0.05). The total protein levels and serum albumin did not differ between the two groups. Leukotriene B4 production after stimulation with tumor necrosis factor-alpha was lower in UR (P < 0.05). These differences could not be attributed to circulating glucocorticoids levels, which were not different in the NR and UR groups. CONCLUSION: Our data suggest that all observed differences contribute to reduced leukocyte migration in undernourishment.
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Membrana Basal , Movimento Celular/fisiologia , Doenças Fetais/fisiopatologia , Inflamação/imunologia , Leucócitos/fisiologia , Desnutrição/fisiopatologia , Fenômenos Fisiológicos da Nutrição Pré-Natal , Animais , Membrana Basal/citologia , Membrana Basal/imunologia , Células da Medula Óssea/fisiologia , Colágeno Tipo IV/fisiologia , Corticosterona/sangue , Feminino , Doenças Fetais/imunologia , Doenças Fetais/metabolismo , Citometria de Fluxo , Imuno-Histoquímica , Selectina L/metabolismo , Laminina/metabolismo , Leucócitos/imunologia , Leucotrieno B4 , Masculino , Desnutrição/imunologia , Desnutrição/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Aleatória , Ratos , Ratos Wistar , Albumina Sérica/análiseRESUMO
A mammal's endometrium is deeply remodeled while receiving and implanting an embryo. In addition to cell proliferation and growth, endometrial remodeling also comprises synthesis and degradation of several molecular components of the extracellular matrix. All of these events are orchestrated by a precise sequence of ovarian hormones and influenced by several types of cytokines. As we have previously reported, an intriguing and rapid increase in collagen fibril diameter occurs in the decidualized areas of the endometrium, surrounding the implantation crypt, whereas collagen fibrils situated far from the embryo remain unchanged. Collagen fibrilogenesis is a complex molecular process coordinated by a number of factors, such as the types and amounts of glycosaminoglycans and proteoglycans associated with collagen molecules. Collagen genetic type, mechanical stress, aging, and other factors not yet identified also contribute to this development. A recent study suggests that thick fibrils from mouse decidua are formed, at least in part, by aggregation of thin fibrils existing in the stroma before the onset of decidualization. In the present ultrastructural study using single and double immunogold localization, we showed that both thin and thick collagen fibrils present in the mouse pregnant endometrium endometrium are heterotypic structures formed at least by type I, type III, and type V collagens. However, type V collagen predominates in the thick collagen fibrils, whereas it is almost absent of the thin collagen fibrils. The putative role of type V homotrimer in the rapid increase of the diameter of collagen fibrils of the mouse decidua is discussed.
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Colágeno Tipo III/ultraestrutura , Colágeno Tipo I/ultraestrutura , Colágeno Tipo V/ultraestrutura , Decídua/ultraestrutura , Colágenos Fibrilares/ultraestrutura , Animais , Feminino , Colágenos Fibrilares/classificação , Imuno-Histoquímica/métodos , Camundongos , GravidezRESUMO
We use the optical path difference (OPD) technique to quantify the organization of collagen fibers during skin repair of full-thickness burns following low-intensity polarized laser therapy with two different polarization incidence vectors. Three burns are cryogenerated on the back of rats. Lesion L(parallel) is irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction. Lesion L(perpendicular) is irradiated using the electric field vector of the polarized laser radiation aligned perpendicularly to the aforementioned orientation. Lesion C is untreated. A healthy area labeled H is also evaluated. The tissue samples are collected and processed for polarized light microscopy. The overall finding is that the OPD for collagen fibers depends on the electric field vector of the incident polarized laser radiation. No significant differences in OPDs are observed between L(parallel) and H in the center, sides, and edges of the lesion. Lesions irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction show higher birefringence, indicating that collagen bundles in these lesions are more organized.
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Queimaduras/patologia , Queimaduras/terapia , Cicatriz/fisiopatologia , Colágeno/ultraestrutura , Terapia com Luz de Baixa Intensidade/métodos , Pele/lesões , Pele/ultraestrutura , Birrefringência , Cor , Microscopia de Polarização/métodos , Pele/química , Resultado do Tratamento , Cicatrização/fisiologiaRESUMO
The digitalics (digoxin and digitoxin) have an estrogenic action, confirmed by the presence of gynecomastia observed in men who are users of steroids, and it is also confirmed by the increase of vaginal trophism in postmenopausal female users, although little is known about the endometrium. These effects might result from the similarity of the chemical structures between the digitalics and estrogens. This study evaluated 27 female mice. Twenty-four mice were oophorectomized and in three of them the ovaries were manipulated, but they were not extirpated. Forty days after the surgery each group of three animals received a medication with a specific drug (digoxin, digitoxin or estradiol) for 2 weeks. Twenty-four hours after the last medication, all the animals were hysterectomized and the wombs were processed, cut and put on laminae. By histomorphometry, we analysed the area of the transverse sections of the endometrium, the area of the endometrial glands and the height of the uterine epithelium. The respective averages and the standard deviations were calculated. The results showed that digoxin neither presented an estrogenic action (p > 0.05) nor raised the power of the estradiol action (p > 0.05). Digitoxin promoted an estrogenic action on the glandular area (p < 0.05), and also raised the power of the estradiol action on the transverse section of the endometrium and on the glandular area (p < 0.05).
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Antiarrítmicos/farmacologia , Digitoxina/farmacologia , Digoxina/farmacologia , Endométrio/efeitos dos fármacos , Estradiol/farmacologia , Animais , Endométrio/patologia , Feminino , Histocitoquímica , Processamento de Imagem Assistida por Computador , Camundongos , Ovariectomia , Distribuição AleatóriaRESUMO
OBJECTIVE: This study was carried out to investigate the influence of low-intensity polarized visible laser radiation on the acceleration of skin wound healing. BACKGROUND DATA: Low-level laser therapy (LLLT) at adequate wavelength, intensity, and dose can accelerate tissue repair. However, there is still unclear information about light characteristics, such as coherence and polarization. Some studies indicate that linearly polarized light can survive through long propagation distance in biological tissue. MATERIALS AND METHODS: Three burns about 6 mm in diameter were created on the back of rats with liquid N(2). Lesion "L(//)" was irradiated by He-Ne laser (lambda = 632.8 nm), D= 1.0 J/cm(2), with linear polarization parallel to the spinal column of the rat. Lesion "L(inverted v)" was irradiated using the same laser and dose, but the light polarization was aligned perpendicularly to the relative orientation. Lesion "C" was not irradiated in order to be considered as control. The animals were sacrificed at day 3-17 after lesion creation. Samples were collected and prepared for histological analysis. RESULTS: Histological analysis showed that the healing of irradiated wounds was faster than that of non-irradiated wounds. Moreover, it was observed that skin wound repair is dependent on polarization orientation with respect to a referential axis as the animal's spinal column. Consequently, "L(//)" was completely healed after 17 days, whereas "L (perpendicular) " showed a moderate degree of healing after the same period. CONCLUSIONS: These results indicate that the relative direction of the laser polarization plays an important role in the wound healing process when highly coherent He-Ne laser is used.
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Queimaduras/radioterapia , Terapia com Luz de Baixa Intensidade , Pele/efeitos da radiação , Cicatrização/efeitos da radiação , Animais , Queimaduras/patologia , Masculino , Ratos , Ratos Endogâmicos Lew , Pele/lesões , Pele/patologiaRESUMO
Doze ratos receberam 0,5 mg/kg de colchicina (CLC) por via endovenosa. Cada três animais foram sacrificados após 5h, 24h, 3 dias e 7 dias após a administraçäo de CLC. Noventa minutos antes do sacrifício, todos os animais receberam prolina triciada por via peritoneal. Os radioautogramas dos incisivos superiores foram submetidos a contagem e, posteriormente, foram analisados estatisticamente. Os resultados revelaram aumento na atividade secretora dos odontoblastos na porçäo mais incisal do dente, indicando um efeito estimulatório de CLC sobre a produçäo e secreçäo de colágeno após 3 dias de sua aplicaçäo
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Animais , Ratos , Colchicina , Colágeno , DentinogêneseRESUMO
Nesta revisäo foram apresentados conhecimentos recentes sobre o papel dos microtúbulos nos processos secretórios, dando especial ênfase á sua participaçäo na secreçäo do colágeno pelos odontoblastos. A utilizaçäo de drogas antimicrotubulares, como a colchicina, tem evidenciado a importância destes componentes citoplásmaticos na dentinogênese