| 1. |
- Johansson, Inger, 1962, et al.
(författare)
-
Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells.
- 2008
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:5, s. 2191-9
-
Tidskriftsartikel (refereegranskat)abstract
- Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.
|
|
| 2. |
- Åberg, N David, 1970, et al.
(författare)
-
Peripheral infusion of insulin-like growth factor-I increases the number of newborn oligodendrocytes in the cerebral cortex of adult hypophysectomized rats.
- 2007
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:8, s. 3765-72
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that recombinant human (rh) IGF-I induces cell proliferation and neurogenesis in the hippocampus of hypophysectomized rats. In the current investigation, we determined the effects of rhIGF-I on proliferation and differentiation in the cerebral cortex. Adult hypophysectomized rats were injected with bromodeoxyuridine (BrdU) to label newborn cells (once a day for the first 5 d), and rhIGF-I was administered peripherally for 6 or 20 d. In the cerebral cortex, the number of BrdU-labeled cells increased after 20 d but not after 6 d of rhIGF-I infusion. This suggests that rhIGF-I enhances the survival of newborn cells in the cerebral cortex. Using BrdU labeling combined with the oligodendrocyte-specific markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase, we demonstrated an increase in oligodendrogenesis in the cerebral cortex. The total amount of myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase was also increased on Western blots of homogenates of the cerebral cortex, confirming the immunohistochemical findings. Also, we observed an increase in the number of capillary-associated BrdU-positive cells, although total capillary area was not increased. rhIGF-I treatment did not affect cortical astrogliogenesis and neurogenesis was not observed. The ability of rhIGF-I to induce cortical oligodendrogenesis may have implications for the regenerative potential of the cortex.
|
|
| 3. |
- Arcopinto, M., et al.
(författare)
-
Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the TOSCA. GHD Study
- 2017
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD. One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6 +/- 1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6 +/- 1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay. GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p=.008 and -24%, p=.015, respectively), lower LV end-systolic wall stress (-21%, p=.03), higher RV performance (+18% in RV area change, p=.03), lower estimated systolic pulmonary artery pressure (-11%, p=.04), higher peak VO2 (+20%, p=.001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p=.002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (beta = -1.92, SE = 1.67, p=.03), VE/VCO2 slope (beta = 2.23, SE = 1.20, p=.02) and NT-proBNP (beta = 2.48, SE = 1.02, p=.016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p<.001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF. GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality.
|
|
| 4. |
|
|
| 5. |
- Baldanzi, Gianluca, et al.
(författare)
-
Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.
- 2002
-
Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 159:6, s. 1029-37
-
Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is an acyl-peptide gastric hormone acting on the pituitary and hypothalamus to stimulate growth hormone (GH) release, adiposity, and appetite. Ghrelin endocrine activities are entirely dependent on its acylation and are mediated by GH secretagogue (GHS) receptor (GHSR)-1a, a G protein-coupled receptor mostly expressed in the pituitary and hypothalamus, previously identified as the receptor for a group of synthetic molecules featuring GH secretagogue (GHS) activity. Des-acyl ghrelin, which is far more abundant than ghrelin, does not bind GHSR-1a, is devoid of any endocrine activity, and its function is currently unknown. Ghrelin, which is expressed in heart, albeit at a much lower level than in the stomach, also exerts a cardio protective effect through an unknown mechanism, independent of GH release. Here we show that both ghrelin and des-acyl ghrelin inhibit apoptosis of primary adult and H9c2 cardiomyocytes and endothelial cells in vitro through activation of extracellular signal-regulated kinase-1/2 and Akt serine kinases. In addition, ghrelin and des-acyl ghrelin recognize common high affinity binding sites on H9c2 cardiomyocytes, which do not express GHSR-1a. Finally, both MK-0677 and hexarelin, a nonpeptidyl and a peptidyl synthetic GHS, respectively, recognize the common ghrelin and des-acyl ghrelin binding sites, inhibit cell death, and activate MAPK and Akt.These findings provide the first evidence that, independent of its acylation, ghrelin gene product may act as a survival factor directly on the cardiovascular system through binding to a novel, yet to be identified receptor, which is distinct from GHSR-1a.
|
|
| 6. |
- Barlind, Anna, 1978, et al.
(författare)
-
Decreased cytogenesis in the granule cell layer of the hippocampus and impaired place learning after irradiation of the young mouse brain evaluated using the IntelliCage platform.
- 2010
-
Ingår i: Experimental brain research. - : Springer Science and Business Media LLC. - 1432-1106 .- 0014-4819. ; 201:4, s. 781-787
-
Tidskriftsartikel (refereegranskat)abstract
- Radiation therapy is used to treat malignant tumors in the brain and central nervous system involvement of leukemia and lymphomas in children. However, ionizing radiation causes a number of adverse long-term side effects in the brain, including cognitive impairment. Hippocampal neurogenesis is important for place learning and has been shown to be decreased by irradiation (IR) in rats and mice. In the present study, 10-day-old male mice received 6-Gy IR to the brain on postnatal day 10. We used BrdU labeling of the granule cell layer (GCL) of the hippocampus to evaluate cell proliferation and survival. An unbiased, automated platform for monitoring of behavior in a group housing environment (IntelliCage) was used to evaluate place learning 2 months after IR. We show that cranial IR impaired place learning and reduced BrdU labeling by 50% in the GCL. Cranial IR also reduced whole body weight gain 5%. We conclude that this experimental paradigm provides a novel and time-saving model to detect differences in place learning in mice subjected to IR. This method of detecting behavioral differences can be used for further studies of adverse effects of IR on hippocampal neurogenesis and possible new strategies to ameliorate the negative effects of IR on cognition.
|
|
| 7. |
- Barlind, Anna, 1978, et al.
(författare)
-
The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus.
- 2010
-
Ingår i: Growth hormone & IGF research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 20:1, s. 49-54
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Radiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model. DESIGN: In the present study, 10-day-old male mice received 6Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100mug/kg/day) for 28days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten. RESULTS: Our results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls. CONCLUSION: The increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.
|
|
| 8. |
- Bollano, Entela, 1970, et al.
(författare)
-
Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene.
- 2000
-
Ingår i: Endocrinology. - 0013-7227. ; 141:6, s. 2229-35
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
|
|
| 9. |
- Bossone, Eduardo, et al.
(författare)
-
The T.O.S.CA. Project: research, education and care.
- 2011
-
Ingår i: Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo. - 1122-0643. ; 76:4, s. 198-203
-
Tidskriftsartikel (refereegranskat)abstract
- Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "GAP" has been revealed between the "real world care" and the "optimal care" of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF "metabolic pathophysiological model" and to improve the quality of care of HF patients through research and continuing medical education.
|
|
| 10. |
- Cittadini, Antonio, et al.
(författare)
-
Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure.
- 2003
-
Ingår i: Cardiovascular research. - 0008-6363. ; 58:3, s. 555-64
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the effects of aldosterone receptor blockade in postinfarction heart failure. METHODS: Eighty-seven rats with moderate myocardial infarction were randomized to receive either no drug or canrenone, the active metabolite of spironolactone, 20 mg/kg/day, or ramipril, 1 mg/kg/day, or a combination of the two drugs. Treatment was initiated 1 month after coronary ligation and lasted 4 weeks. Echocardiography was performed at baseline and after 4 weeks. LV catheterization, isolated heart studies, morphometric histology, myocardial norepinephrine and SERCA-2 mRNA were assessed at the end of the treatment period. RESULTS: Infarct sizes were 33+/-3, 32+/-3, 34+/-3, and 34+/-4% in the placebo, canrenone, ramipril, and combination groups, respectively. Canrenone attenuated LV remodeling, improved LV systolic and diastolic function, and markedly reduced interstitial and perivascular fibrosis. These effects were increased by concomitant ramipril therapy. Moreover, myocardial norepinephrine content was decreased while ventricular fibrillation threshold significantly augmented by canrenone. SERCA-2 levels remained unchanged. CONCLUSIONS: Canrenone attenuated LV dilation and interstitial remodeling, and improved LV filling dynamics and systolic function in the rat model of postinfarction heart failure. Addition of ramipril conferred further cardioprotection. Canrenone also reduced myocardial norepinephrine content and increased ventricular fibrillation threshold. The data provide a potential explanation for the decreased sudden death observed in the RALES study.The mechanisms of action of aldosterone inhibition are still poorly understood, despite its proven efficacy in heart failure. Rats with postinfarction heart failure were randomized to receive for 1 month either no drug or canrenone, or ramipril, or a combination of canrenone and ramipril. Canrenone treatment was associated with a significant attenuation of LV dilation, better LV diastolic and systolic dynamics, and a marked reduction of reactive fibrosis. These effects were enhanced by concomitant ramipril therapy. Moreover, canrenone increased ventricular fibrillation threshold and reduced myocardial norepinephrine content. The data may explain the reduced mortality demonstrated by the RALES.
|
|
