scholarly journals Cardiovascular Effects of Long-Term Central and Peripheral Administration of Urocortin, Corticotropin-Releasing Factor, and Adrenocorticotropin in Sheep

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5598-5604 ◽  
Author(s):  
R. S. Weisinger ◽  
J. R. Blair-West ◽  
P. Burns ◽  
D. A. Denton ◽  
B. Purcell ◽  
...  
Keyword(s):  
Stress Response ◽  
Arterial Pressure ◽  
Cardiovascular Effects ◽  
Corticotropin Releasing Factor ◽  
Central Administration ◽  
Long Term Effects ◽  
Cardiovascular Actions ◽  
Term Administration

Abstract The neuroendocrine hormones ACTH and corticotropin- releasing factor (CRF), which are involved in the stress response, have acute effects on arterial pressure. New evidence indicates that urocortin (UCN), the putative agonist for the CRF type 2 receptor, has selective cardiovascular actions. The responses to long-term infusions of these hormones, both peripherally and centrally, in conscious animals have not been studied. Knowledge of the long-term effects is important because they may differ considerably from their acute actions, and stress is frequently a chronic stimulus. The present experiments investigated the cardiovascular effects of CRF, UCN, and ACTH in conscious sheep. Infusions were made either into the lateral cerebral ventricles (icv) or iv over 4 d at 5 μg/h. UCN infused icv or iv caused a prolonged increase in heart rate (HR) (P < 0.01) and a small increase in mean arterial pressure (MAP) (P < 0.05). CRF infused icv or iv progressively increased MAP (P < 0.05) but had no effect on HR. Central administration of ACTH had no effect, whereas systemic infusion increased MAP and HR (P < 0.001). In conclusion, long-term administration of these three peptides associated with the stress response had prolonged, selective cardiovascular actions. The striking finding was the large and sustained increase in HR with icv and iv infusions of UCN. These responses are probably mediated by CRF type 2 receptors because they were not reproduced by infusions of CRF.

scholarly journals Regulation of corticotropin-releasing factor and its types 1 and 2 receptors by leptin in rats subjected to treadmill running-induced stress

2006 ◽  
Vol 191 (1) ◽  
pp. 179-188 ◽  
Author(s):  
Qingling Huang ◽  
Elena Timofeeva ◽  
Denis Richard
Keyword(s):  
De Novo ◽  
Third Ventricle ◽  
Corticotropin Releasing Factor ◽  
Treadmill Running ◽  
Hypothalamic Nucleus ◽  
Long Term Effects ◽  
Induced Stress

The present study was conducted to investigate the long-term effects of subchronic elevation of central leptin levels on the expression of corticotropin-releasing factor (CRF) and its types 1 and 2 receptors in the brain of rats subjected to treadmill running-induced stress. PBS or recombinant murine leptin was infused continuously for a period of 5 days into the third ventricle of rats with the aid of osmotic minipumps at a delivery rate of 2 μg/day. On the fifth day of infusion, rats were killed under resting conditions or after a session of treadmill running, which is known to induce a stress response in rats. Leptin treatment significantly decreased food intake, body weight, white adipose tissue weight, glucose and insulin plasma contents, and blunted the treadmill running-induced elevation in plasma levels of corticosterone. Leptin infusion prevented stress-induced de novo synthesis of CRF in the paraventricular hypothalamic nucleus (PVN), which was measured using the intronic probe for CRF heteronuclear RNA. The induction of the type 1 CRF receptor (CRF1R) in the PVN and supraoptic nucleus in running rats was also significantly blunted by leptin. In contrast, leptin treatment strongly increased the expression of type 2 CRF receptor (CRF2R) in the ventromedial hypothalamic nucleus (VMH). The present results suggest that subchronic elevation of central levels of leptin blunts treadmill running-induced activation of the hypothalamic–pituitary–adrenal axis through the inhibition of activation of the CRFergic PVN neurons, and potentially enhances the anorectic CRF effects via the stimulation of expression of CRF2R in the VMH.

scholarly journals Effect of ionizing radiation on human skeletal muscle precursor cells

2013 ◽  
Vol 47 (4) ◽  
pp. 376-381 ◽  
Author(s):  
Mihaela Jurdana ◽  
Maja Cemazar ◽  
Katarina Pegan ◽  
Tomaz Mars
Keyword(s):  
Skeletal Muscle ◽  
Stress Response ◽  
Ionizing Radiation ◽  
Human Skeletal Muscle ◽  
Long Term Effects ◽  
Post Irradiation ◽  
Acute Response ◽  
Proliferation Capacity ◽  
Myoblast Proliferation

Abstract Background. Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures. Materials and methods. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin - 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death. Results. Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70). Conclusions. Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions.

Long-Term Effects of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Surgery on Type 2 Diabetes Mellitus in Morbidly Obese Subjects

2012 ◽  
Vol 256 (6) ◽  
pp. 1023-1029 ◽  
Author(s):  
Amanda Jiménez ◽  
Roser Casamitjana ◽  
Lílliam Flores ◽  
Judith Viaplana ◽  
Ricard Corcelles ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Morbidly Obese ◽  
Long Term Effects ◽  
Obese Subjects

Treatments for Pathological Gambling and Other Impulse Control Disorders

2007 ◽  
pp. 561-578 ◽  
Author(s):  
Jon E. Grant ◽  
Marc N. Potenza
Keyword(s):  
Pathological Gambling ◽  
Pharmacological Treatment ◽  
Impulse Control ◽  
Behavioral Therapy ◽  
Impulse Control Disorders ◽  
Long Term Effects ◽  
Drug Treatments

Several controlled outcome studies (Type 1 and Type 2) suggest that specific behavioral (e.g., cognitive-behavioral therapy [CBT]) and pharmacological (e.g., naltrexone, nalmefene, lithium) treatments significantly reduce the symptoms of pathological gambling in the short term compared with wait-list or placebo. Although long-term effects of manual-based CBT have been observed in several small studies, the long-term benefits of pharmacological treatment have not been adequately tested. No studies combining behavioral and pharmacological therapies have been published to date. Thus, the potential benefit of combining behavioral and drug treatments for pathological gambling remains to be investigated systematically. Although several studies (Type 1 and Type 2) suggest that CBT is effective for trichotillomania, pharmacological treatment studies for this disorder have shown mixed results. Similarly, controlled pharmacological studies (Type 1 and Type 2) of compulsive buying have demonstrated mixed results. Limited treatment studies exist for other impulse control disorders (kleptomania, intermittent explosive disorder), although various pharmacological and psychological treatments have shown promise in uncontrolled studies.

Metformin regulates TRPM6, a potential explanation for magnesium imbalance in type 2 diabetes patients

2020 ◽  
Vol 98 (6) ◽  
pp. 400-411 ◽  
Author(s):  
Hacene Bouras ◽  
Sara R. Roig ◽  
Steef Kurstjens ◽  
Cees J.J. Tack ◽  
Mohamed Kebieche ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Surface ◽  
Fine Tuning ◽  
Metformin Treatment ◽  
Long Term Effects ◽  
Short Term ◽  
Metformin Therapy ◽  
Diabetes Patients

Metformin therapy is associated with lower serum magnesium (Mg2+) levels in type 2 diabetes patients. The TRPM6 channel determines the fine-tuning of Mg2+ (re)absorption in intestine and kidney. Therefore, we aimed to investigate the short- and long-term effects of metformin on TRPM6. Patch clamp recordings and biotinylation assays were performed upon 1 h of incubation with metformin in TRPM6-transfected HEK293 cells. Additionally, 24 h of treatment of mDCT15 kidney and hCaco-2 colon cells with metformin was applied to measure the effects on endogenous TRPM6 expression by quantitative real-time PCR. To assess Mg2+ absorption, 25Mg2+ uptake measurements were performed using inductively coupled plasma mass spectrometry. Short-term effects of metformin significantly increased TRPM6 activity and its cell surface trafficking. In contrast, long-term effects significantly decreased TRPM6 mRNA expression and 25Mg2+ uptake. Metformin lowered TRPM6 mRNA levels independently of insulin- and AMPK-mediated pathways. Moreover, in type 2 diabetes patients, metformin therapy was associated with lower plasma Mg2+ concentrations and fractional excretion of Mg2+. Thereby, short-term metformin treatment increases TRPM6 activity explained by enhanced cell surface expression. Conversely, long-term metformin treatment results in downregulation of TRPM6 gene expression in intestine and kidney cells. This long-term effect translated in an inverse correlation between metformin and plasma Mg2+ concentration in type 2 diabetes patients.

scholarly journals Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes mellitus on hemodialysis

2016 ◽  
Vol 89 (6) ◽  
pp. 1380-1387 ◽  
Author(s):  
Vera Krane ◽  
Kay-Renke Schmidt ◽  
Lena J. Gutjahr-Lengsfeld ◽  
Johannes F.E. Mann ◽  
Winfried März ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Long Term Effects
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