Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

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.

Short-term and long-term effects of embryo culture in the surrogate sheep oviduct versus in vitro culture for different domestic species

2010 ◽  
Vol 73 (6) ◽  
pp. 748-757 ◽  
Author(s):  
G. Lazzari ◽  
S. Colleoni ◽  
I. Lagutina ◽  
G. Crotti ◽  
P. Turini ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Embryo Culture ◽  
Long Term Effects ◽  
Short Term ◽  
Domestic Species

scholarly journals Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

2020 ◽  
Vol 17 (8) ◽  
pp. 2654 ◽  
Author(s):  
Francesca Gorini ◽  
Elisa Bustaffa ◽  
Alessio Coi ◽  
Giorgio Iervasi ◽  
Fabrizio Bianchi
Keyword(s):  
Thyroid Dysfunction ◽  
Direct Action ◽  
Epidemiological Studies ◽  
In Vivo Studies ◽  
Original Research ◽  
Long Term Effects ◽  
Toxicological Studies

Bisphenols (BPs), and especially bisphenol A (BPA), are known endocrine disruptors (EDCs), capable of interfering with estrogen and androgen activities, as well as being suspected of other health outcomes. Given the crucial role of thyroid hormones and the increasing incidence of thyroid carcinoma in the last few decades, this review analyzes the effects of BPS on the thyroid, considering original research in vitro, in vivo, and in humans published from January 2000 to October 2019. Both in vitro and in vivo studies reported the ability of BPs to disrupt thyroid function through multiple mechanisms. The antagonism with thyroid receptors (TRs), which affects TR-mediated transcriptional activity, the direct action of BPs on gene expression at the thyroid and the pituitary level, the competitive binding with thyroid transport proteins, and the induction of toxicity in several cell lines are likely the main mechanisms leading to thyroid dysfunction. In humans, results are more contradictory, though some evidence suggests the potential of BPs in increasing the risk of thyroid nodules. A standardized methodology in toxicological studies and prospective epidemiological studies with individual exposure assessments are warranted to evaluate the pathophysiology resulting in the damage and to establish the temporal relationship between markers of exposure and long-term effects.

scholarly journals Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression—Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 688
Author(s):  
Adrian Tiron ◽  
Irina Ristescu ◽  
Paula A. Postu ◽  
Crina E. Tiron ◽  
Florin Zugun-Eloae ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Long Term Effects ◽  
Short Term ◽  
Bdnf Expression ◽  
In Vivo Models

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.

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
Keyword(s):  
Corticotropin Releasing Factor ◽  
Long Term Effects ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Short Term ◽  
Neural Lobe ◽  
Ether Anesthesia ◽  
Acth Release

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.

Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE2 but no change in mineralization

2001 ◽  
Vol 90 (5) ◽  
pp. 1849-1854 ◽  
Author(s):  
E. A. Nauman ◽  
R. L. Satcher ◽  
T. M. Keaveny ◽  
B. P. Halloran ◽  
D. D. Bikle
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Fluid Shear Stress ◽  
Bone Cells ◽  
Shear Stresses ◽  
Long Term Effects ◽  
Fluid Shear ◽  
Short Term

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.

scholarly journals Short-Term Studies of MDL 19,660-induced Canine Thrombocytopenia

1990 ◽  
Vol 18 (4) ◽  
pp. 651-660 ◽  
Author(s):  
John T. Yarrington ◽  
David E. Loudy ◽  
Jean Sprinkle-Cavallo ◽  
Robert Broersma ◽  
John P. Gibson
Keyword(s):  
Protective Effect ◽  
In Vitro Testing ◽  
Short Term ◽  
Drug Induced ◽  
Vacuolar Degeneration ◽  
Platelet Counts ◽  
Spontaneous Aggregation ◽  
Induced Aggregation

After 2 days of dosing, platelet counts progressively declined in dogs treated orally with 30 mg/kg/day of the antidepressant compound MDL 19,660 for 8 days. Accompanying the decrease in platelet counts was an increase in both large and vacuolated degenerating platelets. Upon cessation of dosing, the platelet counts returned to levels equal to or exceeding predosing levels within 4–7 days. Co-administration with aspirin, a known antiaggregating agent, had no protective effect on the drug-induced thrombocytopenia. In vitro testing of normal canine platelets in the presence of MDL 19,660 further revealed that spontaneous aggregation did not occur and that ADP-induced aggregation was inhibited. Drug-related platelet loss was also not prevented by the co-administration of prednisone, a steroid with immunosuppressive effects and inhibitory properties against reticuloendothelial cell phagocytosis of platelets. The results of the present investigation indicate that MDL 19,660 may produce in the dog a reversible thrombocytopenia in the form of vacuolar degeneration and subsequent destruction of the platelet by means other than aggregation or steroid-responsive mechanisms.

SUMBER-SUMBER RESILIENSI PADA REMAJA AKHIR YANG MENGALAMI KEKERASAN DARI ORANGTUA PADA MASA KANAK-KANAK

Psibernetika ◽  
2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Devina Calista ◽  
Garvin Garvin
Keyword(s):  
Late Adolescents ◽  
Long Term Effects ◽  
Short Term ◽  
Parental Affection ◽  
Resilience Factors ◽  
Childhood Violence ◽  
Past Experiences ◽  
The Impact ◽  
Depth Interviews

<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>

Sign in / Sign up

Export Citation Format

Share Document