Long-term effects of hypothalamic paraventricular lesion on CRF content and stimulated ACTH secretion

1986 ◽  
Vol 250 (3) ◽  
pp. E319-E324 ◽  
Author(s):  
G. B. Makara ◽  
E. Stark ◽  
G. Kapocs ◽  
F. A. Antoni

The effect of short-term (1 wk) and long-term (6 wk) lesion of the paraventricular nucleus (PVN) on the hypothalamopituitary-adrenal axis was studied. Six weeks after PVN lesion there was no change in resting morning plasma ACTH and corticosterone levels. The increase of plasma ACTH levels that occurs 8 days after adrenalectomy was inhibited 6 wk after placing a lesion in the PVN. In contrast, 6 wk after PVN lesion the plasma ACTH response measured 3 min after laparatomy and intestinal traction under ether anesthesia was not significantly different from that in the controls. The responsiveness to corticotropin-releasing factor (CRF)-41 of anterior pituitary segments incubated in vitro increased slightly at 6 wk after PVN lesion. The amount of CRF-41-like immunoreactive material in the stalk-median eminence decreased to approximately 14% of the control, while that in neural lobe failed to change. We suggest that the ACTH hypersecretion after adrenalectomy is driven predominantly by CRF-and/or AVP-producing neurons in and around the PVN, whereas other sources of CRF-41, increased pituitary sensitivity or other hypothalamic factors, may restore stress-induced ACTH release in the absence of the region of the PVN.

Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.


2010 ◽  
Vol 73 (6) ◽  
pp. 748-757 ◽  
Author(s):  
G. Lazzari ◽  
S. Colleoni ◽  
I. Lagutina ◽  
G. Crotti ◽  
P. Turini ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 688
Author(s):  
Adrian Tiron ◽  
Irina Ristescu ◽  
Paula A. Postu ◽  
Crina E. Tiron ◽  
Florin Zugun-Eloae ◽  
...  

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1α, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.


1993 ◽  
Vol 265 (4) ◽  
pp. R840-R845 ◽  
Author(s):  
R. J. Kemppainen ◽  
T. P. Clark ◽  
J. L. Sartin ◽  
C. A. Zerbe

The relative abilities of the hypothalamic peptides corticotropin-releasing factor (CRF), arginine vasopressin (AVP), oxytocin (OT), and angiotensin II (ANG II) to stimulate adrenocorticotropic hormone (ACTH) secretion from cultured sheep anterior pituitary cells were studied. Incubation of cells with CRF, AVP, and OT, but not ANG II, was associated with increased ACTH secretion. CRF and AVP were equally effective in stimulating ACTH release at 0.1 nM, but larger doses of each resulted in distinctly different ACTH secretory patterns. The minimally effective dose of OT was 10 nM; greater doses of this peptide resulted in ACTH secretory responses similar to those measured after addition of AVP. Cotreatment with ANG II did not affect the ACTH-secretory response to CRF, AVP, or OT. These data confirm that AVP is a potent stimulus for ACTH secretion from sheep anterior pituitary in vitro and also show that CRF is effective in low concentrations in releasing ACTH. In contrast, the data do not support a regulatory role for ANG II in stimulating ACTH release directly from sheep corticotroph cells.


2001 ◽  
Vol 90 (5) ◽  
pp. 1849-1854 ◽  
Author(s):  
E. A. Nauman ◽  
R. L. Satcher ◽  
T. M. Keaveny ◽  
B. P. Halloran ◽  
D. D. Bikle

Although there is no consensus as to the precise nature of the mechanostimulatory signals imparted to the bone cells during remodeling, it has been postulated that deformation-induced fluid flow plays a role in the mechanotransduction pathway. In vitro, osteoblasts respond to fluid shear stress with an increase in PGE2production; however, the long-term effects of fluid shear stress on cell proliferation and differentiation have not been examined. The goal of this study was to apply continuous pulsatile fluid shear stresses to osteoblasts and determine whether the initial production of PGE2 is associated with long-term biochemical changes. The acute response of bone cells to a pulsatile fluid shear stress (0.6 ± 0.5 Pa, 3.0 Hz) was characterized by a transient fourfold increase in PGE2 production. After 7 days of static culture (0 dyn/cm2) or low (0.06 ± 0.05 Pa, 0.3 Hz) or high (0.6 ± 0.5 Pa, 3.0 Hz) levels of pulsatile fluid shear stress, the bone cells responded with an 83% average increase in cell number, but no statistical difference ( P > 0.53) between the groups was observed. Alkaline phosphatase activity per cell decreased in the static cultures but not in the low- or high-flow groups. Mineralization was also unaffected by the different levels of applied shear stress. Our results indicate that short-term changes in PGE2 levels caused by pulsatile fluid flow are not associated with long-term changes in proliferation or mineralization of bone cells.


Psibernetika ◽  
2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Devina Calista ◽  
Garvin Garvin

<p><em>Child abuse by parents is common in households. The impact of violence on children will bring short-term effects and long-term effects that can be attributed to their various emotional, behavioral and social problems in the future; especially in late adolescence that will enter adulthood. Resilience factors increase the likelihood that adolescents who are victims of childhood violence recover from their past experiences</em><em>,</em><em> become more powerful individuals and have a better life. The purpose of this study was to determine the source of resilience in late adolescents who experienced violence from parents in their childhood. This research uses qualitative research methods with in-depth interviews as a method of data collection. The result shows that the three research participants have the aspects of "I Have", "I Am", and "I Can"; a participant has "I Can" aspects as a source of resilience, and one other subject has no source of resilience. The study concluded that parental affection and acceptance of the past experience have role to the three sources of resilience (I Have, I Am, and I Can)</em></p><p><em> </em></p><p><strong><em>Keyword : </em></strong><em>Resilience, adolescence, violence, parents</em></p>


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 559-559
Author(s):  
Sara Freed ◽  
Briana Sprague ◽  
Lesley Ross

Abstract Interventions using exercise video games, or exergames, have shown short-term cognitive and physical benefits to older adults, though long-term effects are less promising. Enjoyment of exergames may promote exergame use after the intervention period, though little work has examined older adults’ views of exergames before and after gameplay experience. We invited 20 older adults between 65 and 84 years of age (M=73.30, SD=5.95) to play two Xbox Kinect games, Just Dance and Kinect Sports Rivals, for twenty minutes. In our presentation, we will present qualitative and quantitative findings of this pilot study, including findings that older adults reported that they were not likely to play similar exergames in the future and that they did not find the exergames to be more fun compared to other ways of exercising. We will discuss implications for game design and research relevant to game developers, manufacturers, and researchers. Part of a symposium sponsored by Technology and Aging Interest Group.


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