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Introduction: It has been demonstrated the dysregulation of the cardiac endocannabinoid system in cardiovascular diseases. Thus, the modulation of this system through the administration of phytocannabinoids present in medicinal cannabis oil (CO) emerges as a promising therapeutic approach. Furthermore, phytocannabinoids exhibit potent antioxidant properties, making them highly desirable in the treatment of cardiac pathologies, such as hypertension-induced cardiac hypertrophy (CH). Objective: To evaluate the effect of CO treatment on hypertrophy and mitochondrial status in spontaneously hypertensive rat (SHR) hearts. Methods: Three-month-old male SHR were randomly assigned to CO or olive oil (vehicle) oral treatment for 1 month. We evaluated cardiac mass and histology, mitochondrial dynamics, membrane potential, area and density, myocardial reactive oxygen species (ROS) production, superoxide dismutase (SOD), and citrate synthase (CS) activity and expression. Data are presented as mean ± SEM (n) and compared by t-test, or two-way ANOVA and Bonferroni post hoc test were used as appropriate. p < 0.05 was considered statistically significant. Results: CH was reduced by CO treatment, as indicated by the left ventricular weight/tibia length ratio, left ventricular mass index, myocyte cross-sectional area, and left ventricle collagen volume fraction. The ejection fraction was preserved in the CO-treated group despite the persistence of elevated systolic blood pressure and the reduction in CH. Mitochondrial membrane potential was improved and mitochondrial biogenesis, dynamics, area, and density were all increased by treatment. Moreover, the activity and expression of the CS were enhanced by treatment, whereas ROS production was decreased and the antioxidant activity of SOD increased by CO administration. Conclusion: Based on the mentioned results, we propose that 1-month oral treatment with CO is effective to reduce hypertrophy, improve the mitochondrial pool and increase the antioxidant capacity in SHR hearts.
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The Bengal tiger (Panthera tigris tigris) is a species belonging to the Felidae family. In Argentina, tigers are currently only found in captivity. The longevity of individual animals in human-controlled environments depends on proper management and practices that prioritize animal welfare. Regular veterinary care is essential to maintain optimal health conditions. Professionals must have a comprehensive understanding of the anatomy and physiology of tigers to effectively perform medical procedures and administer treatments. The study described in the text focuses on the trajectory and distribution of nerves in the pelvic limb of a Bengal tiger specimen, providing detailed dissection findings. The results revealed that the lumbosacral plexus is formed from the ventral rami of the LIV, LV, LVI, LVII, SI, SII and SIII nerves. Among the observations to highlight is the great development of the nerves N. cutaneus femoris lateralis and N. cutaneus femoris caudalis some differences were observed in the distribution of the N. femoralis and N. obturatorius; the N. ischiadicus, together with its division into the fibularis communis and tibialis nerves, showed the same configuration observed in other cats. Finally, it was observed that the nerves N. gluteus cranialis and N. gluteus caudalis also originated from the truncus lumbosacralis. The similarities and differences with studies carried out on other cats are relevant and provide anatomical data for medical procedures in the Bengal tiger.
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Tigres , Humanos , Animais , Membro Posterior , Extremidade Inferior , Plexo Lombossacral/anatomia & histologiaRESUMO
This study is based on the premise that the application of chemical synthesis strategies to structurally modify commercial drugs by complexation with biometals is a valid procedure to improve their biological effects. Our purpose is to synthesize a compound with greater efficacy than the original drug, able to enhance its antihypertensive and cardiac pharmacological activity. Herein, the structure of the coordination compound of Zn(II) and the antihypertensive drug olmesartan, [Zn(Olme)(H2O)2] (ZnOlme), is presented. After 8 weeks of treatment in SHR male rats, ZnOlme displayed a better blood pressure-lowering activity compared with olmesartan, with a noticeable effect even in the first weeks of treatment, while ZnCl2 showed similar results than the control. ZnOlme also reduced left ventricle (LV) weight and left ventricle/tibia length ratio (LV/TL), posterior wall thickness (PWT), and intraventricular septum in diastole (IVSd) suggesting its potential to prevent LV hypertrophy. Besides, ZnOlme reduced interstitial fibrosis (contents of collagen types I and III, responsible for giving rigidity and promoting vascular elasticity, respectively). The recovery of heart function was also evidenced by fractional shortening (diastolic left ventricular/systolic left ventricular) diameter determinations. Furthermore, ZnOlme increased the antioxidant capacity and prevented cardiac oxidative stress: it enhanced the reduction of reactive oxygen species generation, exerted a significant decrease in lipid peroxidation and enhanced glutathione contents in heart tissues compared to the control, Zn, and olmesartan treatments. Our results demonstrate that continuous oral administration of ZnOlme causes a better antihypertensive effect and grants enhancement of cardioprotection through antioxidant activity, in combination with hemodynamic improvement.
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Anti-Hipertensivos , Hipertensão , Ratos , Animais , Masculino , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Ratos Endogâmicos SHR , Pressão Sanguínea , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Zinco/farmacologia , Zinco/uso terapêuticoRESUMO
BACKGROUND: the antihypertensive drug α-methyldopa (MD) stands as one of the extensively used medications for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases. In this context, the synthesis of a Zn coordination complex [Zn(MD)(OH)(H2O)2]·H2O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD. METHODS: ZnMD was synthesized and physicochemically characterized. Fluorescence spectral studies were conducted to examine the binding of both, the ligand and the metal with bovine serum albumin (BSA). MD, ZnMD, and ZnCl2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and blood pressure and echocardiographic parameters were determined. Ex vivo assays were conducted to evaluate levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO). Cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes were also assessed. Furthermore, the expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis. RESULTS: The complex exhibited a moderate affinity for binding with BSA showing a spontaneous interaction (indicated by negative ΔG values) and moderate affinity (determined by affinity constant values). The binding process involved the formation of Van der Waals forces and hydrogen bonds. Upon treatment with MD and ZnMD, a reduction in the systolic blood pressure in SHR was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week of treatment, respectively). The ZnMD treatment prevented myocardial hypertrophy, improved the heart function and reduced the cardiac fibrosis, as evidenced by parameters such as left ventricular mass, fractional shortening, and histological studies. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulates negatively the oxidative damage by reducing levels of ROS and lipid peroxidation, as well as the cardiac NAD(P)H oxidase, and increasing SOD1 expression, while MD did not show significant effect. Moreover, cardiac nitric oxide levels were greater in the ZnMD therapy compared to MD treatment. CONCLUSION: Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction.
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Anti-Hipertensivos , Hipertensão , Ratos , Animais , Anti-Hipertensivos/uso terapêutico , Metildopa/farmacologia , Metildopa/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase-1 , Óxido Nítrico/metabolismo , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Ratos Endogâmicos SHR , Miócitos Cardíacos/metabolismo , Cardiomegalia , NADPH Oxidases , Zinco/farmacologia , Zinco/uso terapêuticoRESUMO
Hypertension is the most common cause of left ventricular hypertrophy, contributing to heart failure progression. Candesartan (Cand) is an angiotensin receptor antagonist widely used for hypertension treatment. Structural modifications were previously performed by our group using Zinc (ZnCand) as a strategy for improving its pharmacological properties. The measurements showed that ZnCand exerts a stronger interaction with the angiotensin II receptor, type 1 (AT1 receptor), reducing oxidative stress and intracellular calcium flux, a mechanism implied in cell contraction. These results were accompanied by the reduction of the contractile capacity of mesangial cells. In vivo experiments showed that the complex causes a significant decrease in systolic blood pressure after 8 weeks of treatment in spontaneously hypertensive rats (SHR). The reduction of heart hypertrophy was evidenced by echocardiography, the histologic cross-sectional area of cardiomyocytes, collagen content, the B-type natriuretic peptide (BNP) marker and connective tissue growth factor (CTGF) and the matrix metalloproteinase 2 (MMP-2) expression. Besides, the complex restored the redox status. In this study, we demonstrated that the complexation with Zn(II) improves the antihypertensive and cardiac effects of the parental drug.
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Anti-Hipertensivos , Hipertensão , Hipertrofia Ventricular Esquerda , Zinco , Animais , Ratos , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Pressão Sanguínea , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Metaloproteinase 2 da Matriz , Miócitos Cardíacos , Ratos Endogâmicos SHR , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Zinco/farmacologiaRESUMO
The main evolutionary milestone in the oviparity-viviparity transition is placentation. The placenta is an organ with great morphological diversity among eutherians. The expression of different glycosidic residues (Gr) in the near-term placenta constitutes its glycotype. In this study, the expression of different Gr was determined by lectin histochemistry in early, midterm, and near-term placentas of the plains viscacha (Lagostomus maximus), a caviomorph rodent with the highest poliovulatory rate and embryonic resorption rate among eutherians. Besides, a matrix with the expression of each Gr in the exchange trophoblast of viscacha and other eutherians was constructed to map and infer phylogenetic and evolutionary relationships. Between early, midterm, and near-term placentas, variations in the pattern expression of Gr were observed. The glycotype of the near-term placenta is composed of a high diversity of Gr. Reconstruction of the ancestral state for each Gr present in the near-term placenta showed a diverse scenario: some sugars were common to the species of Placentalia included in this study. In the analyzed species with synepitheliochorial and epitheliochorial placentas, no differential glycosylation patterns between them were observed. In species with invasive placentas, such as the endotheliochorial placentas of Carnivora, some common Gr were detected among them, while others were species-specific. In species with hemochorial placenta, the same Gr are shared. Particularly, in the viscacha greater differences with species of the Hominidae and even Muridae families were observed. Nevertheless, greater similarities with other caviomorph rodents were detected. Placental glycotype of each species constitutes an excellent tool to achieve phylogenetic and evolutionary inferences among eutherians.
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Placenta , Roedores , Gravidez , Feminino , Animais , Placenta/anatomia & histologia , Filogenia , Placentação , TrofoblastosRESUMO
Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms. In the heart two different NBC isoforms have been described: the electroneutral NBCn1 (1Na+:1 HCO 3 - ) and the electrogenic NBCe1 (1Na+:2 HCO 3 - ). NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). In addition to regulating the pH, the NBC is a source of sodium influx. It has been postulated that NBC could play a role in the development of hypertrophy. The aim of this research was to study the contribution of NBCe1 in heart electrophysiology and in the development of heart hypertrophy in an in vivo mouse model with overexpression of NBCe1. Heart NBCe1 overexpression was achieved by a recombinant cardiotropic adeno-associated virus (AAV9) and was evidenced by western-blot and qPCR. AAV9-mCherry was used as a transduction control. NBCe1 overexpression fails to increase heart growth. Patch clamp and electrocardiogram were performed. We observed a reduction on both, ventricular myocytes APD and electrocardiogram QT interval corrected by cardiac rate, emphasizing for the first time NBCe1 relevance for the electrical activity of the heart.
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Vascular mineralization is a hallmark of enzootic calcinosis. Histopathological, ultrastructural, and immunohistochemical investigations were performed on the external carotid arteries of seven sheep naturally poisoned by Nierembergia veitchii. Histologically, moderate to marked hyperplasia of the tunica intima was observed without mineralization. The tunica media exhibited mild to severe mineralization and osteochondroid metaplasia. Sheep with enzootic calcinosis showed arterial overexpression of osteopontin and tissue-nonspecific alkaline phosphatase and immunolabeling for osteonectin and osteocalcin in both intima and media layers of the tested arteries. The main ultrastructural finding in the tunica media was a marked phenotypic change of vascular smooth muscle cells from a contractile phenotype (VSMC-C) into a synthetic phenotype (VSMC-S). In the tunica media, VSMC-S produced matrix and extracellular vesicles, forming mineralizable granules associated with arterial mineralization. VSMC-S were also present in the tunica intima, but matrix and extracellular vesicles and mineralization were not observed. The absence of matrix and extracellular vesicles in the intimal hyperplasia, even in the presence of noncollagenous bone proteins, tissue-nonspecific alkaline phosphatase, and vitamin D receptors, reinforces the hypothesis that the presence of matrix and extracellular vesicles are crucial for the development of vascular mineralization in enzootic calcinosis. It is proposed that the two different VSMC-S phenotypes in calcinosis are due to the expression of at least two genetically different types of these cells induced by the action of 1,25(OH)2D3.
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Calcinose , Hiperplasia , Doenças dos Ovinos , Fosfatase Alcalina/metabolismo , Animais , Calcinose/veterinária , Células Cultivadas , Hiperplasia/patologia , Hiperplasia/veterinária , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Ovinos , Doenças dos Ovinos/patologiaRESUMO
Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergoes a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of changes in microglia during is of great relevance to understand age-related declines in cognitive and motor function. We have targeted the deleterious effects of aging by implementing IGF-1 gene transfer, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) RAd-IGF-1 or control injection on aged female rats and evaluated its effect on caudate-putamen unit (CPu) gene expression and inflammatory state. Our results demonstrate that IGF-1 overexpression modified aged microglia of the CPu towards an anti-inflammatory condition increasing the proportion of double immuno-positive Iba1+Arg1+ cells. We also observed that phosphorylation of Akt was increased in animals treated with RAd-IGF-1. Moreover, IGF-1 gene transfer was able to regulate CPu pro-inflammatory environment in female aged rats by down-regulating the expression of genes typically overexpressed during aging. RNA-Seq data analysis identified 97 down-modulated DEG in the IGF-1 group as compared to the DsRed one. Interestingly, 12 of these DEG are commonly overexpressed during aging, and 9 out of 12 are expressed in microglia/macrophages and are involved in different processes that lead to neuroinflammation and/or neuronal loss. Finally, we observed that IGF-1 overexpression led to an improvement in motor functions. Although further studies are necessary, with the present results, we conclude that IGF-1 gene transfer is modifying both the pro-inflammatory environment and activation of microglia/macrophages in CPu. In this regard, IGF-1 gene transfer could counteract the neuroinflammatory effects associated with aging and improve motor functions in senile animals.
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Fator de Crescimento Insulin-Like I , Putamen , Animais , Encéfalo/metabolismo , Feminino , Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Microglia/metabolismo , Putamen/metabolismo , RatosRESUMO
Prediabetic myocardium, induced by fructose-rich diet (FRD), is prone to increased sarcoplasmic reticulum (SR)-Ca2+ leak and arrhythmias due to increased activity of the Ca2+/calmodulin protein kinase II (CaMKII). However, little is known about the role of SR-mitochondria microdomains, mitochondrial structure, and mitochondrial metabolisms. To address this knowledge gap we measured SR-mitochondrial proximity, intracellular Ca2+, and mitochondrial metabolism in wild type (WT) and AC3-I transgenic mice, with myocardial-targeted CaMKII inhibition, fed with control diet (CD) or with FRD. Confocal images showed significantly increased spontaneous Ca2+ release events in FRD vs. CD WT cardiomyocytes. [3H]-Ryanodine binding assay revealed higher [3H]Ry binding in FRD than CD WT hearts. O2 consumption at State 4 and hydrogen peroxide (H2O2) production rate were increased, while respiratory control rate (RCR) and Ca2+ retention capacity (CRC) were decreased in FRD vs. CD WT isolated mitochondria. Transmission Electron Microscopy (TEM) images showed increased proximity at the SR-mitochondria microdomains, associated with increased tethering proteins, Mfn2, Grp75, and VDAC in FRD vs. CD WT. Mitochondria diameter was decrease and roundness and density were increased in FRD vs. CD WT specimens. The fission protein, Drp1 was significantly increased while the fusion protein, Opa1 was unchanged in FRD vs. CD WT hearts. These differences were prevented in AC3-I mice. We conclude that SR-mitochondria microdomains are subject to CaMKII-dependent remodeling, involving SR-Ca2+ leak and mitochondria fission, in prediabetic mice induced by FRD. We speculate that CaMKII hyperactivity induces SR-Ca2+ leak by RyR2 activation which in turn increases mitochondria Ca2+ content due to the enhanced SR-mitochondria tethering, decreasing CRC.
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Sinalização do Cálcio/fisiologia , Diabetes Mellitus/fisiopatologia , Mitocôndrias , Miocárdio , Retículo Sarcoplasmático , Animais , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Dieta , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Miocárdio/metabolismo , Miocárdio/patologia , Miocárdio/ultraestrutura , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Oxigênio/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/ultraestrutura , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
Five adult Saanen goats received a single oral dose of Heterophyllaea pustulata containing 42.25 µg/kg rubiadin (anthraquinone) and 3 adult goats were untreated controls. All goats were exposed to sunlight and sequential ear skin biopsies were collected before treatment and at 32 hours, 3 days, 8 days, and 15 days after treatment. Changes at 32 hours after dosing included epidermal spongiosis, single cell death and acantholysis, an increased BAX/BCL-2 protein ratio, and dermal edema. Lesions at day 3 included epidermal and adnexal necrosis, crust formation, and acanthosis. Acanthosis, hyperkeratosis, and dermal fibrosis and neovascularization were present at day 15. The pro-apoptotic (BAX)/anti-apoptotic (BCL-2) protein ratio increased at 32 hours, whereas epidermal and dermal PCNA immunolabeling increased between days 8 and 15 after treatment. The cutaneous lesions were consistent with sunlight-induced damage, and the occurrence in treated but not control goats indicates photosensitization.
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Doenças das Cabras , Transtornos de Fotossensibilidade , Animais , Doenças das Cabras/induzido quimicamente , Cabras , Transtornos de Fotossensibilidade/induzido quimicamente , Transtornos de Fotossensibilidade/veterinária , PeleRESUMO
Embryonic death followed by resorption is a conserved process in mammals. Among the polyovular species, Lagostomus maximus (plains viscacha) constitutes a model of early and physiological embryonic death, since out of a total of 10-12 implants, 8-10 are resorbed during early/intermediate gestation, surviving are only the most caudal implantations of each uterine horn. This regular reproductive event is unique to this species, but many characteristics of the implantations during the early gestation of L. maximus, when embryonic death processes begin are unknown. The aim of the present work was to analyze the implantation sites of this species using morphological, morphometric, histochemical, lectinhistochemical, and immunohistochemical techniques to infer the possible causes of this event. Macroscopically, the length and width of the implantation sites significantly increased in a craniocaudal direction. Histochemically, the implantation sites did not differ in the expression of glycoconjugates and glycosidic residues. Furthermore, no variations were observed in cell renewal, hormone receptor expression, and decidualization. Both the glandular and vascular areas of the implantation sites significantly increased in the craniocaudal axis. Some necrotic cells and an inflammatory response with a predominance of lymphocytes and fibrin were observed in the cranial and middle but not in the caudal implantation sites. We conclude that signs of embryonic death and resorption are already observed in the early gestation of L. maximus. Our results reaffirm the hypothesis that postulates the key potential role of uterine glands and blood vessels in the gestation of the species, with emphasis on embryonic death. This pattern of embryonic death in L. maximus makes this species an unconventional mammalian model, which adds to the peculiarities of polyovulation (200-800 oocytes/estrus) and hemochorial placentation.
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Eutérios , Roedores , Animais , Feminino , Hormônios , Placentação , Gravidez , ÚteroRESUMO
Previously, we have shown that an increased cGMP-activated protein Kinase (PKG) activity after phosphodiesterase 5 (PDE5) inhibition by Sildenafil (SIL), leads to myocardial Na+/H+ exchanger (NHE1) inhibition preserving its basal homeostatic function. Since NHE1 is hyperactive in the hypertrophied myocardium of spontaneous hypertensive rats (SHR), while its inhibition was shown to prevent and revert this pathology, the current study was aimed to evaluate the potential antihypertrophic effect of SIL on adult SHR myocardium. We initially tested the inhibitory capability of SIL on NHE1 in isolated cardiomyocytes of SHR by comparing H+ efflux during the recovery from an acid load. After confirmed that effect, eight-month-old SHR were chronically treated for one month with SIL through drinking water. Compared to their littermate controls, SIL-treated rats presented a decreased NHE1 activity, which correlated with a reduction in its phosphorylation level assigned to activation of a PKG-p38 MAP kinase-PP2A signaling pathway. Moreover, treated animals showed a decreased oxidative stress that appears to be a consequence of a decreased mitochondrial NHE1 phosphorylation. Treated SHR showed a significant reduction in the pro-hypertrophic phosphatase calcineurin, despite slight tendency to decrease hypertrophy was detected. When SIL treatment was prolonged to three months, a significant decrease in myocardial hypertrophy and interstitial fibrosis that correlated with a lower myocardial stiffness was observed. In conclusion, the current study provides evidence concerning the ability of SIL to revert established cardiac hypertrophy in SHR, a clinically relevant animal model that resembles human essential hypertension.
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Cardiomegalia/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Músculos Papilares/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Trocador 1 de Sódio-Hidrogênio/metabolismo , Animais , Cardiomegalia/enzimologia , Cardiomegalia/etiologia , Cardiomegalia/fisiopatologia , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Fibrose , Hipertensão/complicações , Masculino , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Músculos Papilares/enzimologia , Músculos Papilares/fisiopatologia , Fosforilação , Proteína Fosfatase 2/metabolismo , Ratos Endogâmicos SHR , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Physical training stimulates the development of physiologic cardiac hypertrophy (CH), being a key event in this process the inhibition of the Na+/H+ exchanger. However, the role of the sodium bicarbonate cotransporter (NBC) has not been explored yet under this circumstance. C57/Bl6 mice were allowed to voluntary exercise (wheel running) for five weeks. Cardiac mass was evaluated by echocardiography and histomorphometry detecting that training promoted the development of physiological CH (heart weight/tibia length ratio, mg/mm: 6.54 ± 0.20 vs 8.81 ± 0.24; interstitial collagen content, %: 3.14 ± 0.63 vs. 1.57 ± 0.27; and cross-sectional area of cardiomyocytes, µm2: 200.6 ± 8.92 vs. 281.9 ± 24.05; sedentary (Sed) and exercised (Ex) mice, respectively). The activity of the electrogenic isoform of the cardiac NBC (NBCe1) was estimated by recording intracellular pH under high potassium concentration and by measuring action potential duration (APD). NBCe1 activity was significantly increased in isolated cardiomyocytes of trained mice. Additionally, the APD was shorter and the alkalization due to high extracellular potassium-induced depolarization was greater in this group, indicating that the NBCe1 was hyperactive. These results are online with the observed myocardial up-regulation of the NBCe1 (Western Blot, %: 100 ± 13.86 vs. 202 ± 29.98; Sed vs. Ex, n = 6 each group). In addition, we detected a reduction in H2O2 production in the myocardium of trained mice. These results support that voluntary training induces the development of physiologic CH with up-regulation of the cardiac NBCe1 in mice. Furthermore, the improvement in the antioxidant capacity contributes to the beneficial cardiovascular consequences of physical training.
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Miocárdio/metabolismo , Condicionamento Físico Animal , Simportadores de Sódio-Bicarbonato/metabolismo , Animais , Cardiomegalia Induzida por Exercícios/fisiologia , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Isoformas de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para CimaRESUMO
Development of alternative therapies for treating functional deficits after different neurological damages is a challenge in neuroscience. Insulin-like growth factor-1 (IGF-1) is a potent neurotrophic factor exerting neuroprotective actions in brain and spinal cord. It is used to prevent or treat injuries of the central nervous system using different administration routes in different animal models. In this study, we evaluated whether intracisternal (IC) route for IGF-1 gene therapy may abrogate or at least reduce the structural and behavioral damages induced by the intraparenchymal injection of kainic acid (KA) into the rat spinal cord. Experimental (Rad-IGF-1) and control (Rad-DsRed-KA) rats were evaluated using a battery of motor and sensory tests before the injection of the recombinant adenovector (day -3), before KA injection (day 0) and at every post-injection (pi) time point (days 1, 2, 3 and 7 pi). Histopathological changes and neuronal and glial counting were assessed. Pretreatment using IC delivery of RAd-IGF-1 improved animal's general condition and motor and sensory functions as compared to Rad-DsRed-KA-injected rats. Besides, IC Rad-IGF-1 therapy abrogated later spinal cord damage and reduced the glial response induced by KA as observed in Rad-DsRed-KA rats. We conclude that the IC route for delivering RAd-IGF-1 prevents KA-induced excitotoxicity in the spinal cord.
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Ácido Caínico , Fármacos Neuroprotetores , Animais , Terapia Genética , Fator de Crescimento Insulin-Like I/genética , Ácido Caínico/toxicidade , Ratos , Ratos Sprague-Dawley , Medula EspinalRESUMO
The uterus is an organ with great plasticity due to the morphological and physiological changes it experiences during the estrous cycle and pregnancy. In mammals, pregnancy requires diverse sex hormones, growth factors and cytokines, among others, for promoting uterine remodeling to favor implantation, placentation, and embryo/fetus survival and growth. The hystricognathi rodent Lagostomus maximus (plains viscacha) has a high rate of embryonic resorption. The cranial and middle implants are reabsorbed 25-35 days after intercourse while the caudal embryos continue with their development until two precocial offspring are born. So far, no uterine studies of non-pregnant L. maximus females were performed to determine the possible existence of variations in the organ that could be related to the differential survival of the implants. We used ultrasonography, as well as morphological, morphometric, histochemical, lectinhistochemical, and immunohistochemical methods to study differences in the uterine glands (area), vasculature (area), and musculature (thickness) along the uterine horns in non-pregnant females. Along the uterus, all these structures were in more advanced developmental condition in the caudal region as compared to more anterior positions. These regional variations could be decisive in explaining the reason why only caudal implantations come to term. In contrast, no differences in the in the luminal and glandular epithelial cells, nor in the degree of cell proliferation and apoptosis, and hormonal receptor staining were found. These parameters could be related to implantation along the uterine horns, but not to the differential survival of the implants.
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Embrião de Mamíferos/anatomia & histologia , Músculos/anatomia & histologia , Roedores/embriologia , Útero/anatomia & histologia , Útero/irrigação sanguínea , Animais , Apoptose , Proliferação de Células , Feminino , Hormônios/metabolismo , Lectinas/metabolismo , Receptores de Superfície Celular/metabolismo , Roedores/anatomia & histologia , Útero/diagnóstico por imagemRESUMO
Several countries have established self-help cryonics groups whose mission is to cryopreserve human bodies or brains after legal death and ship them to cryonics organizations. The objective of this study was to report the first case of human brain cryopreservation in Argentina and complementary experiments in rats. After legal death, the body of a 78-year-old Caucasian woman was transported to a funeral home where her head was submitted to intracarotid perfusion with 5 L cold physiologic saline followed by the same volume of cold saline containing 13% dimethyl sulfoxide and 13% glycerol. The brain was removed, temporarily frozen at -80°C, and shipped to a U.S. cryostasis facility. Three groups of rats were intracardially perfused with fixative but not frozen (Reference group), vitrification solution VM1 (Control group), or the cryoprotection solution used in the patient (Experimental group). Control and Experimental brains were stored at -80°C and subsequently assessed by immunohistochemistry for the adult neuron marker (NeuN), the immature neuron marker doublecortin (DCX), the dopaminergic neuron marker tyrosine hydroxylase, and the presynaptic marker synaptophysin (SYN). The number of NeuN-positive neurons remained unchanged in the experimental brain cortex, whereas the number of immature DCX neurons in the hippocampus fell markedly in the cryoprotected brains. The results were highly variable for hypothalamic dopaminergic neurons. Confocal microscopy for SYN revealed that cryopreservation did not affect the synaptic network in the hippocampus. To our knowledge, this is the first report correlating a human cryoprotection procedure with results in complementary experiments in laboratory animals.
Assuntos
Encéfalo , Criopreservação , Modelos Animais , Idoso , Animais , Encéfalo/anatomia & histologia , Cadáver , Criopreservação/métodos , Crioprotetores , Proteína Duplacortina , Feminino , Congelamento , Hipocampo , Humanos , Ratos , Fixação de Tecidos , VitrificaçãoRESUMO
Meningiomas are one of the most common primary tumors of the canine central nervous system. They usually grow within the cranial cavity but occasionally they are found in the spinal cord. A case of a Boxer breed with a spinal cord transitional meningioma is reported. Two years history presenting progressive neurological signs is described. The MRI examination revealed a focal, intradural extramedullary lesion within the right side of the spinal canal, compromising the C1and C2 vertebral segments. Cytoreductive surgery with a dorsolateral laminectomy approach was performed to decompressthe spinal cord and to obtain a definitive diagnosis. Histopathological studies diagnosed a grade I transitional meningioma. Immunohistochemistry and immunofluorescence analysis detected positive cells to vimentin (VIM), pan-cytokeratin (pCk),neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and doublecortin (DXC). Although apparently benign, positivity to pCK and DXC suggest a possible transition into a malignant tumor. Although variations in the behavior, histology and the immunoreactive profile of these tumors are reported, the latter constitutes a good indicator for the diagnosis of the patient.(AU)
Assuntos
Animais , Masculino , Cães , Meningioma/patologia , Meningioma/veterinária , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/veterinária , Meningioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/veterináriaRESUMO
Meningiomas are one of the most common primary tumors of the canine central nervous system. They usually grow within the cranial cavity but occasionally they are found in the spinal cord. A case of a Boxer breed with a spinal cord transitional meningioma is reported. Two years history presenting progressive neurological signs is described. The MRI examination revealed a focal, intradural extramedullary lesion within the right side of the spinal canal, compromising the C1and C2 vertebral segments. Cytoreductive surgery with a dorsolateral laminectomy approach was performed to decompressthe spinal cord and to obtain a definitive diagnosis. Histopathological studies diagnosed a grade I transitional meningioma. Immunohistochemistry and immunofluorescence analysis detected positive cells to vimentin (VIM), pan-cytokeratin (pCk),neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and doublecortin (DXC). Although apparently benign, positivity to pCK and DXC suggest a possible transition into a malignant tumor. Although variations in the behavior, histology and the immunoreactive profile of these tumors are reported, the latter constitutes a good indicator for the diagnosis of the patient.
Assuntos
Masculino , Animais , Cães , Meningioma/diagnóstico por imagem , Meningioma/patologia , Meningioma/veterinária , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/veterinária , Imageamento por Ressonância Magnética/veterináriaRESUMO
Ventricular hypertrophy is a risk factors for arrhythmias, ischemia and sudden death. It involves cellular modifications leading to a pathological remodeling and is associated with heart failure. The activation of the G protein-coupled estrogen receptor (GPER) mediates beneficial actions in the cardiovascular system. Our goal was to prevent and regress the hypertrophy by the activation of GPER in neonatal cardiac myocytes (NRCM) and SHR male rats. Aldosterone increased the neonatal cardiomyocytes cell surface area after 48 h of incubation. The aldo-induced hypertrophy was blocked by the mineralocorticoid receptor (MR) inhibitor Eplererone or the reduction of MR expression by siRNA. The activation of GPER by the agonist G-1 totally prevented the increase surface area by Ald. The transfection of neonatal rat cardiac myocytes with a siRNA against GPER or the incubation with GPER blockers G-15 and G-36 inhibited the protection of G-1. The significant increase of cell surface area after 48 h of incubation with Ald was totally regressed in 24 h by the presence of G-1, indicating that the activation of GPER not only prevent the hypertrophy but also regress the hypertrophy when it is already established. In the in vivo model, G-1 or Vehicle was constantly infused via the minipump to SHR. The reduction of the hypertrophy by G-1 was evident by the cross-sectional area, BNP and ANP markers and by echocardiography. In this studied we demonstrated that the activation of GPER prevented and regressed the hypertrophy induced by Ald in NRCM and regressed hypertrophy in SHR rats.