scholarly journals Long-Term Exposure to Temozolomide Affects Locomotor Activity and Cartilage Structure of Elderly Experimental Rats

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 541
Author(s):  
Anastasia V. Suhovskih ◽  
Olga P. Molodykh ◽  
Victor S. Ushakov ◽  
Maxim O. Politko ◽  
Dmitry K. Sokolov ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Wistar Rats ◽  
Life Quality ◽  
Epiphyseal Cartilage ◽  
Knee Joints ◽  
Malignant Tumours ◽  
Long Term Effects ◽  
Long Term Treatment ◽  
And Cartilage

Chemotherapy with temozolomide (TMZ) is an essential part of anticancer therapy of various malignant tumours; however, its long-term effects on patients’ health and life quality need to be further investigated. Here, we studied the effects of TMZ and/or companion drug dexamethasone (DXM) on the locomotor activity and cartilage structure of elderly Wistar rats (n = 40). Long-term TMZ treatment selectively inhibited the horizontal, but not vertical locomotor activity of the rats (6.7-fold, p < 0.01) and resulted in delamination of the superficial epiphyseal cartilage of the femoral epiphysis of knee joints, a 2-fold decrease in mean thickness of epiphyseal cartilage (p < 0.001), and changes in the proliferative and maturation cartilage zones ratio. The simultaneous use of DXM attenuated TMZ-induced changes in cartilage thickness and integrity and compensated the decrease in horizontal locomotor activity of experimental animals. Nevertheless, combined TMZ/DXM treatment still significantly affected the structure of proximal tibial, but not distal femoral epiphysis of knee joints of the rats. These changes were accompanied by the increased content of total glycosaminoglycans (GAGs) and their partial re-localisation from chondrocytes into tissue matrix, as well as the decrease in sulfated GAGs content in both compartments. Taken together, the results demonstrate that long-term treatment with TMZ results in a significant decrease in locomotor activity of elderly Wistar rats and the reorganisation of their knee joint cartilage structure, while DXM treatment attenuates those effects. So, use of DXM or chondroprotective drugs might be beneficial to maintain quality of life for TMZ-treated cancer patients.

Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles

1987 ◽  
Vol 112 (2) ◽  
pp. 275-282 ◽  
Author(s):  
E. van Leengoed ◽  
E. Kerker ◽  
H. H. Swanson
Keyword(s):  
Wistar Rats ◽  
Post Partum ◽  
Rapid Onset ◽  
Maternal Behaviour ◽  
Cerebral Ventricles ◽  
Long Term Effects ◽  
Nesting Material ◽  
The Right ◽  
Oxytocin Antagonist

ABSTRACT Endogenous oxytocin released into the brain at parturition may stimulate the onset of maternal behaviour. In this study an attempt was made to block spontaneous maternal behaviour following natural delivery in Wistar rats by the injection of an antagonist of oxytocin into the cerebral ventricles. The analogue antagonist, d(CH2)5-8-ornithine-vasotocin, was administered by injection into a chronically implanted cannula in the right lateral ventricle at hourly intervals, beginning immediately after the expulsion of the first pup. The antagonist did not interfere with the normal progress of parturition or birth-related behaviours. After delivery of the last pup, mothers rested for 40 min in the test cage with the pups having been removed. Four pups and standard nesting material were then presented. Latency to pup carrying and duration of pup manipulation, nest building, and time spent on the nest with the pups, as well as duration of autogrooming and general activity were determined. Saline-injected controls started gathering the pups immediately and usually showed all elements of maternal behaviour within 10 min. Antagonist-treated mothers showed a marked delay in the onset of pup grouping and other maternal behaviours. At the end of 1 h, two out of six mothers had not yet picked up a single infant. Pups left overnight with their mothers were gathered into the nest and suckled, and no long-term effects of the antagonist were evident on retesting. The effectiveness of oxytocin antagonist in suppressing the rapid onset of post-partum maternal behaviour supports the hypothesis that centrally released oxytocin is involved in this process. It is noteworthy that these effects were obtained in Wistar rats, a strain in which oxytocin has failed to accelerate responsiveness to pups in virgin females. J. Endocr. (1987) 112, 275–282

Aspects of Long-Term Treatment with Neuroleptics Historical and Literature Review—Personal Experience with Fluspirilene and Penfluridol

1975 ◽  
Vol 3 (2) ◽  
pp. 114-124 ◽  
Author(s):  
Lucian Floru
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Personal Experience ◽  
Term Treatment ◽  
Term Therapy ◽  
Tabular Form ◽  
Long Term Effects ◽  
Long Term Treatment ◽  
Long Term Therapy

The literature on neuroleptics with substance-specific long-term effects (fluspirilene, penfluridol) is reviewed in tabular form. This is followed by a report of personal investigations on 76 schizophrenics who were treated with fluspirilene initially within the hospital and later on an out-patient basis, on 86 patients who were treated with it exclusively at the out-patients' department, as well as on 123 schizophrenic psychoses treated with penfluridol in the out-patients' department. The side-effects caused by the two substances are compared. Pre-requisites for effective long-term therapy with a few complications are discussed.

An investigation into the effects of ketoconazole on testicular function in Wistar rats

1986 ◽  
Vol 111 (2) ◽  
pp. 246-251 ◽  
Author(s):  
A. I. Vawda ◽  
A. G. Davies
Keyword(s):  
Germ Cells ◽  
Wistar Rats ◽  
Term Treatment ◽  
Plasma Testosterone ◽  
Testicular Function ◽  
Sperm Number ◽  
Abnormal Sperm ◽  
Long Term Treatment ◽  
Sexually Mature

Abstract. Ketoconazole was administered orally to sexually mature Wistar rats and testicular function assessed. A single oral dose of 24 mg ketoconazole/kg body weight lowered plasma testosterone and DHT levels by 83 and 50%, respectively within 2 h, without altering gonadotrophin levels. Treatment for up to 7 days decreased epididvmal sperm number and motility and increased the proportion of abnormal sperm. The sperm appeared to be most affected 3 days after a single dose of ketoconazole and recovery had taken place by the seventh day. Daily treatment for up to 90 days also decreased sperm number and motility and increased the proportion of abnormal sperm, but did not affect testicular germ cells. No significant change was noted in the weights of the testis, epididymis, seminal vesicle and prostate; nor was there a change in testicular DNA, RNA and protein contents. Although fertility appeared to be impaired by long-term treatment, some of the treated rats mated successfully.

Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis

2007 ◽  
Vol 67 (3) ◽  
pp. 353-357 ◽  
Author(s):  
F Chopin ◽  
P Garnero ◽  
A le Henanff ◽  
F Debiais ◽  
A Daragon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Long Term Effects ◽  
Turnover Markers ◽  
And Cartilage ◽  
Cartilage Turnover

Long-term effects of chromium on morphological and immunological parameters of Wistar rats

2019 ◽  
Vol 133 ◽  
pp. 110748 ◽  
Author(s):  
A.V. Karaulov ◽  
E.A. Renieri ◽  
A.I. Smolyagin ◽  
I.V. Mikhaylova ◽  
A.A. Stadnikov ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Long Term Effects ◽  
Immunological Parameters

Slow-Release Terbutaline and Theophylline for the Long-Term Therapy of Children With Asthma: A Latin Square and Factorial Study of Drug Effects and Interactions

PEDIATRICS ◽  
1989 ◽  
Vol 84 (1) ◽  
pp. 119-125
Author(s):  
Olivia Kit Wun Chow ◽  
Kam Pui Fung
Keyword(s):  
Side Effects ◽  
Slow Release ◽  
Clinical Symptoms ◽  
Combined Therapy ◽  
Latin Square ◽  
Term Therapy ◽  
Long Term Effects ◽  
Long Term Treatment ◽  
Children With Asthma

To evaluate the long-term effects of slow-release formulations of theophylline and terbutaline on pulmonary function, clinical symptoms, and side effects, 24 children with stable and moderately severe perennial asthma participated in a prospective double-blind crossover study. The patients and the treatments were randomized according to the Latin square design to eliminate all possible period/climate biases throughout the protracted study period. The treatments consisted of terbutaline, 5 mg, theophylline, 200 mg, the combination, and placebo, given twice daily orally and crossing over every 28 days. The two drugs, administered alone or in combination, improved lung function and symptoms when compared with placebo. The interaction of theophylline and terbutaline was quantitatively shown by 2 x 2 factorial statistical design to be essentially additive rather than synergistic in the control of asthma. No increase in side effects was noted when the combined therapy was used. These findings suggest therapeutic advantages to combining submaximal oral doses of sustained-release theophylline and terbutaline for the long-term treatment of children with asthma.

Long-term effects of pre-pubertal fluoxetine on behaviour and monoaminergic stress response in stress-sensitive rats

2016 ◽  
Vol 29 (4) ◽  
pp. 222-235 ◽  
Author(s):  
Nico Johan Badenhorst ◽  
Linda Brand ◽  
Brian Herbert Harvey ◽  
Susanna Maria Ellis ◽  
Christiaan Beyers Brink
Keyword(s):  
Locomotor Activity ◽  
Stress Responses ◽  
Forced Swim Test ◽  
Early Adulthood ◽  
Plasma Corticosterone ◽  
Long Term Effects ◽  
Swim Stress ◽  
Term Outcome ◽  
Long Term Outcome

ObjectiveAlthough prescription rates of antidepressants for children and adolescents have increased, concerns have been raised regarding effects on neurodevelopment and long-term outcome. Using a genetic animal model of depression, this study investigated the long-term effects of pre-pubertal administration of fluoxetine (FLX) on depressive-like behaviour in early adulthood, as well as on central monoaminergic response to an acute stressor. We postulated that pre-pubertal FLX will have lasting effects on animal behaviour and monoaminergic stress responses in early adulthood.MethodsFlinders sensitive line (FSL) rats received 10 mg/kg/day FLX subcutaneously from postnatal day 21 (PnD21) to PnD34 (pre-pubertal). Thereafter, following normal housing, rats were either subjected to locomotor testing and the forced swim test (FST) on PnD60 (early adulthood), or underwent surgery for microdialysis, followed on PnD60 by exposure to acute swim stress and measurement of stressor-induced changes in plasma corticosterone and pre-frontal cortical monoamine concentrations.ResultsPre-pubertal FLX did not induce a late emergent effect on immobility in FSL rats on PnD60, whereas locomotor activity was significantly decreased. Acute swim stress on PnD60 significantly increased plasma corticosterone levels, and increased pre-frontal cortical norepinephrine (NE) and 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations. Pre-pubertal FLX significantly blunted the pre-frontal cortical NE and 5-HIAA response following swim stress on PnD60. Baseline dopamine levels were significantly enhanced by pre-pubertal FLX, but no further changes were induced by swim stress.ConclusionPre-pubertal FLX did not have lasting antidepressant-like behavioural effects in genetically susceptible, stress-sensitive FSL rats. However, such treatment reduced locomotor activity, abrogated noradrenergic and serotonergic stressor responses and elevated dopaminergic baseline levels in adulthood.

Putative Anti-Immobility Action of Acute Insulin Is Attributable to an Increase in Locomotor Activity in Healthy Wistar Rats

2021 ◽  
pp. 1-10
Author(s):  
Ana G. Gutiérrez-García ◽  
Carlos M. Contreras
Keyword(s):  
Locomotor Activity ◽  
Treatment Regimen ◽  
Wistar Rats ◽  
Day Treatment ◽  
Forced Swim Test ◽  
Diabetic Rats ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Immobility Time ◽  
Female Wistar Rats

<b><i>Background/Aims:</i></b> Anti-immobility actions of insulin in diabetic rats that are subjected to the forced swim test (FST) have been reported. In this test, low doses of antidepressants exert actions after long-term treatment, without affecting locomotor activity in healthy rats. Few studies have compared acute and chronic actions of insulin with antidepressants in healthy rats. <b><i>Methods:</i></b> We hypothesized that if insulin exerts a true anti-immobility action, then its effects must be comparable to fluoxetine in both a 1-day treatment regimen and a 21-day treatment regimen in healthy, gonadally intact female Wistar rats. <b><i>Results:</i></b> The results showed that low levels of glycemia were produced by all treatments, including fluoxetine, and glycemia was lower in proestrus-estrus than in diestrus-metestrus. None of the treatments or regimens produced actions on indicators of anxiety in the elevated plus maze. Insulin in the 1-day regimen increased the number of crossings and rearings in the open field test and caused a low cumulative immobility time in the FST. These actions disappeared in the 21-day regimen. Compared with the other treatments, fluoxetine treatment alone or combined with insulin produced a longer latency to the first period of immobility and a shorter immobility time in the chronic regimen in the FST, without affecting locomotor activity, and more pronounced actions were observed in proestrus-estrus (i.e., a true anti-immobility effect). <b><i>Conclusion:</i></b> These results indicate that insulin does not produce a true antidepressant action in healthy rats. The purported antidepressant effects that were observed were instead attributable to an increase in locomotor activity only in the 1-day regimen.

scholarly journals 66 Intra-articular lipopolysaccharide challenge has no long-term effects on inflammation and cartilage metabolism

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 41-41
Author(s):  
Amanda N Bradbery ◽  
Jessica L Leatherwood ◽  
Brittany L Silvers ◽  
Mattea L Much ◽  
Rafael E Martinez ◽  
...  
Keyword(s):  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Long Term Effects ◽  
Negative Effects ◽  
Cartilage Metabolism ◽  
Time Interaction ◽  
Stock Type ◽  
Lactated Ringer's Solution ◽  
And Cartilage

Abstract Intra-articular lipopolysaccharide is a common model to induce acute synovitis to investigate the effects of various therapeutic agents or nutraceuticals. The long-term effects of intra-articular lipopolysaccharide use in skeletally mature and immature horses has yet to be investigated; therefore, the objective of this study was to describe long-term effects of single-administration of intra-articular lipopolysaccharide on joint inflammation and cartilage metabolism. To test this objective, both radial carpal joints from 5 stock-type horses never exposed to lipopolysaccharide (CON; n = 10) were compared to radial carpal joints from 17 similar stock-type horses previously exposed to intra-articular lipopolysaccharide (INFL; n = 34). Joints within INFL were further categorized as the joint which received lipopolysaccharide (LPS; n = 17) and contralateral control which received iso-volumetric lactated Ringer’s solution (CONTRA; n = 17). A single synovial fluid sample from each joint was analyzed for prostaglandin E2 (PGE2), collagenase cleavage neopeptide (C2C), carboxypeptide of type II collagen (CPII), and chondroitin sulfate 846 (CS846). All data were analyzed using PROC MIXED of SAS with main effects of treatment (CON, INFL) and joint (CON, LPS, CONTRA). Time post-administration (1.5, 2, 6 yr) and age-at-administration (1, 3, 5, 7 yr) were included in the model within INFL joints (LPS, CONTRA). There was no influence of treatment on any biomarker (P &gt; 0.40). Similarly, inflammation and cartilage metabolism were not different between CON, CONTRA, and LPS joints (P &gt; 0.50). Within INFL, there was no influence of joint, age, or time post-administration for PGE2, CPII, or CS846 (P &gt; 0.10). A joint x time interaction was observed for catabolic C2C (P &lt; 0.01); however, where LPS was less than CONTRA 2 yr post-lipopolysaccharide administration and similarly when lipopolysaccharide was administered at 5 and 7 yr of age (P &lt; 0.01). These data indicate no long-term negative effects for the use of intra-articular lipopolysaccharide as an acute inflammatory model in skeletally mature and immature horses.

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