scholarly journals Estradiol and GH cells: Immunohistomorphometric study in an animal model of andropause

2012 ◽  
Vol 64 (2) ◽  
pp. 451-457 ◽  
Author(s):  
Verica Milosevic ◽  
Svetlana Trifunovic ◽  
B. Filipovic ◽  
Branka Sosic-Jurjevic ◽  
Jasmina Pantelic ◽  
...  

Andropause, the culminating phase of ageing in males is characterized by the decline of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis that is responsible for somatic development. Estrogens on the other hand, assume a relevant somatic role, as well as the one in the pituitary. They are particularly interesting because of their therapeutic uses in certain common ageing-associated diseases. The aim of the present study was to examine the effects of subcutaneous treatment with estradiol, dipropionate on the immunohistomorphometric features of GH cells, in an animal model of the andropause. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and estradiol dipropionate-treated orchidectomized (Orx+Edp) groups. Estradiol dipropionate (0.625 mg/kg/day) was administered subcutaneously for three weeks while the SO and Orx groups received the vehicle alone. GH cells were identified by the peroxidase-antiperoxidase (PAP) immunohistochemical procedure. In the Orx+Edp group, GH cell volumes as well as the relative volume densities were significantly (p<0.05) decreased, by 27.4% and by 61.1%, respectively, in comparison with the same parameters of SO animals. Compared to the Orx animals, the cell volumes and relative volume densities of GH cells in Orx+Edp group were also significantly (p<0.05) decreased, by 23.2% and by 64.1%, respectively. It can be concluded that chronic estradiol dipropionate application in an animal in the andropause results in the suppression of immunohistochemical and morphometric parameters of pituitary GH cells.

2014 ◽  
Vol 64 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Vladimir Ajdžanović ◽  
Ivana Medigović ◽  
Jasmina Živanović ◽  
Branka Šošić-Jurjević ◽  
Svetlana Trifunović ◽  
...  

Abstract Somatopause, the complex aspect of andropause, is recognizable by reduced growth hormone - GH/insulin-like growth factor 1 axis function in the ageing male. Soy isoflavones (usually genistein and daidzein), which are known for their beneficial effects in the treatment of ageing symptoms, are active in the pituitary, as well. The immunohistomorphometric and -fluorescent characteristics of pituitary growth hormone secreting cells, in an animal model of andropause, were examined after a treatment with genistein or daidzein. Andropausal Wistar rats were divided into sham operated, orchidectomized and genistein or daidzein treated orchidectomized groups. Genistein or daidzein (30 mg/kg/day) were administered subcutaneously for three weeks, while sham operated and orchidectomized groups received the vehicle alone. Growth hormone secreting cells were identified by the peroxidase-antiperoxidase immuno-histochemical, and immuno-fluorescent procedure. The main characteristic of growth hormone secreting cells in soy isoflavones treated groups is a weaker immuno-histochemical staining and immuno-fluorescent signal compared to sham operated and orchidectomized groups. The growth hormone secreting cell volume in orchidectomized +genistein or +daidzein groups is by 13.8% and 11.9% (p<0.05) smaller respectively, in comparison with the orchidectomized group. In orchidectomized +genistein or +daidzein groups, the growth hormone secreting cells relative volume density is by 62.5% and 61.0% lower (p<0.05) respectively than for the sham operated group, and decreased by 65.4% and 64.0% (p<0.05) respectively, compared to the orchidectomized group. It can be concluded that chronic genistein or daidzein treatment, in an animal model of andropause, attenuates immunohistomorphometric and -fluorescent characteristics of growth hormone secreting cells.


2020 ◽  
Vol 19 (7) ◽  
pp. 503-508
Author(s):  
Maiko Hayashida ◽  
Sadayuki Hashioka ◽  
Kenji Hayashida ◽  
Shoko Miura ◽  
Keiko Tsuchie ◽  
...  

Background: Fibroblast growth factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and pro-differentiation of neurons. Method: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. Results: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of unconjugated bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 at serum levels in all the rats studied. Conclusion: Since it is known that FGF2 regulates dopaminergic neurons and have anti-neuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which disbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.


1996 ◽  
Vol 30 (4) ◽  
pp. 337-346 ◽  
Author(s):  
S. W. Y. Chan ◽  
P. C. Reade

Wistar Shionogi rats of the ( od/od) substrain with the osteogenic disorder are unable to synthesize L-ascorbic acid ( L-AA) and appear to be an appropriate animal model for studying the effect of L-AA in carcinogenesis. To determine the minimal L-AA requirements of these animals for prolonged survival in a satisfactory physical condition during experimentation, four concentrations of L-AA (0.33 g/l, 0.67 g/l, 1.67 g/l and 3.33 g/l) were administered via drinking water to four groups of animals ( n=2). Their water intake per cage was recorded three times weekly and the plasma L-AA levels were determined at the start, after 2, 4, 8 and 12 weeks and at the termination of the experiment. To simulate the procedures to be undertaken in oral mucosal carcinogenesis experiments, the animals were gently restrained and a designated amount of sterile NaCl was applied to the palatal mucosa three times a week for 26 weeks. The L-AA supplement group with the lowest concentration (0.33 g/l L-AA) achieved mean plasma levels of 7 ± 1.38 μM, approximately one-eighth that of the normal level (mean plasma L-AA level in outbred Wistar rats was found to be 58 ± 3 μM) whilst those in the higher supplement group (3.33 g/l L-AA) achieved a mean of 18 ± 1.25 μM. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA deficiency during this period.


1989 ◽  
Vol 30 (2) ◽  
pp. 217-222 ◽  
Author(s):  
H. S. Thomsen ◽  
S. Larsen ◽  
L. Hemmingsen ◽  
J. Holm ◽  
P. Skaarup

Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy.


2019 ◽  
Vol 8 (8) ◽  
pp. 1117 ◽  
Author(s):  
Gaetano Scaramuzzo ◽  
Ludovic Broche ◽  
Mariangela Pellegrini ◽  
Liisa Porra ◽  
Savino Derosa ◽  
...  

Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH2O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 ± 2.0 at PEEP 12 to 7.6 ± 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 ± 52 at PEEP 12 to 146.4 ± 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S136-S136
Author(s):  
Camila Loureiro ◽  
Fachim Helene Aparecida ◽  
Corsi-Zuelli Fabiana ◽  
Shuhama Rosana ◽  
Joca Sâmia Regiane Lourenço ◽  
...  

Abstract Background Early-life stress is a key risk for psychiatric disorders that may produce changes in the neurodevelopment. N-methyl-d-aspartate receptor (NMDAR) have been associated with the pathophysiology of schizophrenia and evidence supports that epigenetic changes in NMDAR imply deficiencies in excitatory neurotransmission suggest its role in the neurobiology of psychoses (Uno and Coyle, 2019; Fachim et al., 2019; Gulchina et al., 2017). Aims: Although previous studies have shown abnormalities in the glutamatergic system in animal model of schizophrenia, it is not known if there are equivalent mRNA/protein alterations and DNA methylation changes in the brains of rats reared in isolation. Thus, in order to improve the knowledge of glutamatergic system role in psychosis, we investigated the NR1 and NR2 mRNA/protein and the DNA methylation levels of Grin1, Grin2a and Grin2b promoter region in the prefrontal cortex (PFC) and hippocampus (HIPPO) of male Wistar rats after isolation rearing. Furthermore, because the Parvalbumin (PV) deficit is the most consistent finding across animal models and schizophrenia itself, we also evaluated the expression of PV and other related GABAergic genes (REL and GAD1) in the brain of rats undergoing social isolation rearing as a validation of this animal model. We hypothesized that isolation rearing reduces mRNA and protein expressions of NMDAR subunits and cause DNA methylation changes. Methods Wistar rats were kept isolated or grouped (n=10/group) from weaning (21 days after birth) to 10 weeks and then exposed to the Open Field Test to assess locomotion. Afterwards the behavioural tests, the tissues were dissected for RNA/DNA extraction and NMDAR subunits were analysed using qRT-PCR, ELISA and pyrosequencing. Data were analysed by parametric tests. Results Isolated-reared animals presented: (i) decreased mRNA levels of Grin1 (p=0.011), Grin2a (p=0.039) and Grin2b (p=0.037) in the PFC followed by reduction in the GABAergic markers; (ii) increased NR1 protein levels in the HIPPO (p=0.001); (iii) hypermethylation of Grin1 at CpG5 in the PFC (p=0.047) and Grin2b CpG4 in the HIPPO when compared to grouped (p=0.024). Moreover, isolated and grouped animals presented a negative correlation between Grin1 mRNA and Grin1 methylation levels at CpG5 in the PFC (r: -0.577; p=0.010) and isolated rats presented a negative correlation between Grin2b methylation at CpG4 and NR2 protein levels in the HIPPO (r: -0.753; p=0.012). Discussion This study supports the hypothesis that the NMDAR methylation changes found in the brain tissues may underlie the NMDAR mRNA/protein expression alterations caused by the isolation period. These results highlighted the importance of the environmental influence during the development that may lead to cognitive impairments in adulthood. Moreover, we demonstrated that the social isolation rearing during 10 weeks causes long-lasting behavioral changes that may be more associated with late stages of schizophrenia. Our study contributes to the identification of the epigenetic mechanisms involved in the neuropathophysiology of schizophrenia, which can bring new pharmacotherapeutic strategies and to identify biomarkers that can improve the early interventions in schizophrenia patients. Finally, our data thus reinforce the validity of rats reared in social isolation after weaning in modelling aspects of schizophrenia, highlighting the glutamatergic and GABAergic features involved principally in the cognitive impairments related to prefrontal cortex.


Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 1 ◽  
Author(s):  
Josephine Schlosser ◽  
Lisa Dähnert ◽  
Paul Dremsek ◽  
Kerstin Tauscher ◽  
Christine Fast ◽  
...  

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but autochthonous cases of zoonotic genotype 3 (HEV-3) infection also occur in industrialized countries. In contrast to swine, rats, and rabbits, natural HEV infections in mice have not yet been demonstrated. The pig represents a well-established large animal model for HEV-3 infection, but a suitable small animal model mimicking natural HEV-3 infection is currently missing. Therefore, we experimentally inoculated C57BL/6 mice (wild-type, IFNAR−/−, CD4−/−, CD8−/−) and BALB/c nude (nu/nu) mice, Wistar rats, and European rabbits with a wild boar-derived HEV-3 strain and monitored virus replication and shedding, as well as humoral immune responses. HEV RNA and anti-HEV antibodies were detected in one and two out of eight of the rats and all rabbits inoculated, respectively, but not in any of the mouse strains tested. Remarkably, immunosuppressive dexamethasone treatment of rats did not enhance their susceptibility to HEV infection. In rabbits, immunization with recombinant HEV-3 and ratHEV capsid proteins induced protection against HEV-3 challenge. In conclusion, the rabbit model for HEV-3 infection may serve as a suitable alternative to the non-human primate and swine models, and as an appropriate basis for vaccine evaluation studies.


2005 ◽  
Vol 48 (spe2) ◽  
pp. 89-96 ◽  
Author(s):  
Simone Odília Fernandes Diniz ◽  
Cristiano Ferrari Siqueira ◽  
David Lee Nelson ◽  
Josep Martin-Comin ◽  
Valbert Nascimento Cardoso

The aim of this work was to prepare a kit of 99mTc-ceftizoxime (99mTc-CFT), with stability and biological activity preserved, able to identify a septic focus (E. coli) in the experimental infection model in rats. The preparation of the CFT kit involved the use of lyophilized solutions containing the antibiotic ceftizoxime and the sodium dithionite reducing agent (6.0 mg/mL). After lyophilization, the kit was reconstituted with 1.0 mL of sodium 99mTc-pertechnetate solution (Na99mTcO4-) with an activity of 370 MBq. The solution was boiled for 10 min and filtered through a cellulose ester filter. The labeling efficiency was on the order of 92%, remaining stable for six hours and the kit remained stable for two months. The biological activity of the 99mTc-CFT was evaluated by diffusion in agar impregnated with E.coli and S. aureus. Seven Wistar rats, weighing from 200 to 250 g, were used for the development of the septic focus. After 24 hours from the induction of the infectious site (E.coli), the animals were anesthetized and 0.1 mL of 99mTc-CFT (37 MBq) was injected into the tail veins of the animals. The images were obtained with a gamma camera one, two and six hours after injection and the regions of interest (ROIs) were calculated. The diameters of the inhibition halos for 99mTc-CFT were 27.16 ± 0.23 and 27.17 ± 0.20 for S.aureus and E.coli, respectively, while those for the unlabeled CFT were 30.4 ± 0.33 and 29.43 ± 0.26, respectively. The results for the biodistribution of 99mTc-CFT in infected animals furnished a ratio of 1.97 ± 0.31, 2.10 ± 0.42 and 2.01 ± 0.42 for cpm-target/cpm-no target for the one, two and six-hour periods, respectively. The images showed a clear uptake of labeled antibiotic (99mTc-CFT) by the infectious site during the experiment. The results attest to the viability of producing a kit with 99m technetium-labeled ceftizoxime for the investigation of infectious processes.


Author(s):  
ELAHE KARIMI ◽  
SHAHRYAR ABBASI ◽  
ALI AIDY ◽  
HORI GHANEIALVAR ◽  
SHAHRAM MOHAMMADPOUR ◽  
...  

Objective: The aim of this study was to evaluate the effect of thymol and thymol nano polymer on the blood biochemical parameters and anti-diabetic activity in Streptozotocin (STZ)-induced diabetic rats. Methods: The synthesized nano polymer (NP) was characterized by using different spectroscopy methods, such as IR, HNMR and CNMR. Loading and releasing of thymol were investigated by HPLC. Eleven groups of the Streptozotocin-induced diabetic and normal rats (overall 110 males) were tested through various biochemical factors such as: serum glucose, insulin, liver function-related enzymes including ALT, AST, ALP and bilirubin by ELISA kit methods. Results: It has shown that thymol nano polymer is desirable for transferring drug. The amount of thymol loaded on NP estimated at 43±2.5 %. Then, 65% of the loaded drug was released. LD50 for thymol and thymol nano polymer were 435 and 583 mg/kg, respectively. thymol nano polymer at doses of 30, 60 and 90 mg/kg, in a dose-dependent manner, reduced blood glucose, increased insulin levels, and controlled liver enzymes ALT, AST, ALP and bilirubin in the STZ-induced diabetic rats. Conclusion: The use of thymol nano polymer appears to be a new aspect concerning to protect diabetes-induced damage in the animal model.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Danielle dos Santos Tavares Pereira ◽  
Maria Helena Madruga Lima-Ribeiro ◽  
Nicodemos Teles de Pontes-Filho ◽  
Ana Maria dos Anjos Carneiro-Leão ◽  
Maria Tereza dos Santos Correia

Thermal lesions were produced in 12 male Wistar rats, positioning a massive aluminum bar 10 mm in diameter (51 g), preheated to 99°C ± 2°C/10 min. on the back of each animal for 15 sec. After 7, 14, 21, and 28 days, animals were euthanized. The edema intensity was mild, with no bubble and formation of a thick and dry crust from the 3rd day. The percentage of tissue shrinkage at 28 days was 66.67 ± 1.66%. There was no sign of infection, bleeding, or secretion. Within 28 days reepithelialization was incomplete, with fibroblastic proliferation and moderate fibrosis and presence of modeled dense collagen fibers. It is concluded that the model established is applicable in obtaining deep second-degree thermal burns in order to evaluate the healing action of therapeutic agents of topical use.


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