scholarly journals Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

2014 ◽  
Vol 306 (2) ◽  
pp. L170-L182 ◽  
Author(s):  
Anna A. Shvedova ◽  
Naveena Yanamala ◽  
Elena R. Kisin ◽  
Alexey V. Tkach ◽  
Ashley R. Murray ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Inhalation Exposure ◽  
Geometric Feature ◽  
Width Ratio ◽  
Long Term Effects ◽  
Genotoxic Effects ◽  
Pulmonary Exposure ◽  
Pharyngeal Aspiration

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

scholarly journals Metformin decreases hyaluronan synthesis by vascular smooth muscle cells

2019 ◽  
Vol 68 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Annele Sainio ◽  
Piia Takabe ◽  
Sanna Oikari ◽  
Henriikka Salomäki-Myftari ◽  
Markku Koulu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Response To Treatment ◽  
Long Term Effects

Metformin is the first-line drug in the treatment of type 2 diabetes worldwide based on its effectiveness and cardiovascular safety. Currently metformin is increasingly used during pregnancy in women with gestational diabetes mellitus, even if the long-term effects of metformin on offspring are not exactly known. We have previously shown that high glucose concentration increases hyaluronan (HA) production of cultured human vascular smooth muscle cells (VSMC) via stimulating the expression of hyaluronan synthase 2 (HAS2). This offers a potential mechanism whereby hyperglycemia leads to vascular macroangiopathy. In this study, we examined whether gestational metformin use affects HA content in the aortic wall of mouse offspring in vivo. We also examined the effect of metformin on HA synthesis by cultured human VSMCs in vitro. We found that gestational metformin use significantly decreased HA content in the intima-media of mouse offspring aortas. In accordance with this, the synthesis of HA by VSMCs was also significantly decreased in response to treatment with metformin. This decrease in HA synthesis was shown to be due to the reduction of both the expression of HAS2 and the amount of HAS substrates, particularly UDP-N-acetylglucosamine. As shown here, gestational metformin use is capable to program reduced HA content in the vascular wall of the offspring strongly supporting the idea, that metformin possesses long-term vasculoprotective effects.

scholarly journals In Vivo Delivery of Recombinant Viruses to the Fetal Murine Cochlea: Transduction Characteristics and Long-Term Effects on Auditory Function

2006 ◽  
Vol 14 (3) ◽  
pp. 328-335 ◽  
Author(s):  
Jeffrey C. Bedrosian ◽  
Michael Anne Gratton ◽  
John V. Brigande ◽  
Waixing Tang ◽  
Jessica Landau ◽  
...  
Keyword(s):  
Auditory Function ◽  
Long Term Effects ◽  
Recombinant Viruses ◽  
In Vivo Delivery

scholarly journals Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity

2019 ◽  
Vol 20 (12) ◽  
pp. 3012 ◽  
Author(s):  
Beatriz Vidal-Villegas ◽  
Johnny Di Pierdomenico ◽  
Juan A Miralles de Imperial-Ollero ◽  
Arturo Ortín-Martínez ◽  
Francisco M Nadal-Nicolás ◽  
...  
Keyword(s):  
Intravitreal Injection ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Retinal Ganglion ◽  
Long Term Effects ◽  
Pou Domain ◽  
Short And Long Term ◽  
Sd Oct

We studied short- and long-term effects of intravitreal injection of N-methyl-d-aspartate (NMDA) on melanopsin-containing (m+) and non-melanopsin-containing (Brn3a+) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using Spectral Domain-Optical Coherence Tomography (SD-OCT). Ex vivo analyses were done at 3, 7, or 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for brain-specific homeobox/POU domain protein 3A (Brn3a) and melanopsin (m), the total number of Brn3a+RGCs and m+RGCs were quantified, and their topography represented. In control retinas, the mean total numbers of Brn3a+RGCs and m+RGCs were 78,903 ± 3572 and 2358 ± 144 (mean ± SD; n = 10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 49%, 28%, 24%, and 19%, at 3, 7, 14 days, and 15 months, respectively. There was no further loss between 7 days and 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3 and 7 days, and were back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induced within a week a rapid loss of 72% of Brn3a+RGCs, a transient downregulation of melanopsin expression (but not m+RGC death), and a thinning of the inner retinal layers.

Testicular oxytocin: effects of intratesticular oxytocin in the rat

1991 ◽  
Vol 130 (2) ◽  
pp. 231-NP ◽  
Author(s):  
H. D. Nicholson ◽  
S. E. F. Guldenaar ◽  
G. J. Boer ◽  
B. T. Pickering
Keyword(s):  
Leydig Cells ◽  
Light And Electron Microscopy ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Epididymal Sperm ◽  
Long Term Effects ◽  
Sperm Counts ◽  
Term Administration

ABSTRACT The long-term effects of oxytocin administration on the testis were studied using intratesticular implants. Adult male rats had an Accurel device containing 20 μg oxytocin (releasing approximately 200 ng/day) implanted into the parenchyma of each testis; control animals received empty devices. The animals were killed at weekly intervals for 4 weeks. Some animals were perfused and the testes processed for light and electron microscopy. Blood was collected from the remaining animals for the measurement of testosterone, dihydrotestosterone, LH, FSH and oxytocin; epididymal sperm counts were measured and the testes were extracted and radioimmunoassayed for testosterone, dihydrotestosterone and oxytocin. Long-term administration of oxytocin resulted in a significant reduction in testicular and plasma testosterone levels throughout the 4-week period examined and, after 14 days of treatment, lipid droplets were seen in the Leydig cells of treated but not control animals. Concentrations of dihydrotestosterone in the plasma and testes of the oxytocin-treated animals, however, were significantly elevated after 7 and 14 days and at no time fell below control values. Plasma FSH levels were also lower in the oxytocin-treated animals. Intratesticular oxytocin treatment did not affect LH or oxytocin concentrations in the plasma, epididymal sperm counts or the number of Leydig cells in the testis. Empty Accurel devices had no effect on testicular morphology. This study provides the first evidence that oxytocin in vivo can modify steroidogenesis in the testis. Journal of Endocrinology (1991) 130, 231–238

Long-term effects of a high-dose methamphetamine regimen on subsequent methamphetamine-induced dopamine release in vivo

2001 ◽  
Vol 892 (1) ◽  
pp. 122-129 ◽  
Author(s):  
K.E. Sabol ◽  
J.T. Roach ◽  
S.L. Broom ◽  
C. Ferreira ◽  
M.M. Preau
Keyword(s):  
Dopamine Release ◽  
High Dose ◽  
Long Term Effects

scholarly journals BDNF-induced TrkB activation down-regulates the K+–Cl− cotransporter KCC2 and impairs neuronal Cl− extrusion

2002 ◽  
Vol 159 (5) ◽  
pp. 747-752 ◽  
Author(s):  
Claudio Rivera ◽  
Hong Li ◽  
Judith Thomas-Crusells ◽  
Hannele Lahtinen ◽  
Tero Viitanen ◽  
...  
Keyword(s):  
Hippocampal Slice ◽  
Neuronal Excitability ◽  
Epileptic Activity ◽  
Signaling Cascades ◽  
Gabaergic Inhibition ◽  
Long Term Effects ◽  
Mouse Hippocampus

Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl− regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+–Cl− cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl− extrusion capacity. After kindling-induced seizures in vivo, the expression of KCC2 is down-regulated in the mouse hippocampus with a spatiotemporal profile complementary to the up-regulation of TrkB and BDNF. The present data demonstrate a novel mechanism whereby BDNF/TrkB signaling suppresses chloride-dependent fast GABAergic inhibition, which most likely contributes to the well-known role of TrkB-activated signaling cascades in the induction and establishment of epileptic activity.

scholarly journals Long-term nicotine exposure dampens LPS-induced nerve-mediated airway hyperreactivity in murine airways

2017 ◽  
Vol 313 (3) ◽  
pp. L516-L523 ◽  
Author(s):  
Yuan Xu ◽  
Lars-Olaf Cardell
Keyword(s):  
Airway Hyperreactivity ◽  
Nicotine Exposure ◽  
Long Term Effects ◽  
Contractile Responses ◽  
Neuronal Mechanisms ◽  
Airway Infections ◽  
Before And After

Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine’s effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg·kg−1·day−1) for 28 days. LPS (0.1 mg/ml, 20 µl) was administered intranasally for 3 consecutive days during the end of this period. Lung functions were measured with flexiVent. For the in vitro experiments, mice tracheae were organcultured with either nicotine (10 μM) or vehicle (DMSO, 0.1%) for 4 days. Contractile responses of the tracheal segments were measured in myographs following electric field stimulation (EFS; increasing frequencies of 0.2 to 12.8 Hz) before and after incubation with 10 µg/ml LPS for 1 h. Results showed that LPS induced AHR to methacholine in vivo and increased contractile responses to EFS in vitro. Interestingly, long-term nicotine exposure markedly dampened this LPS-induced AHR both in vitro and in vivo. Tetrodotoxin (TTX) inhibited LPS-induced AHR but did not further inhibit nicotine-suppressed AHR in vivo. In conclusion, long-term nicotine exposure dampened LPS-induced AHR. The effect of nicotine was mimicked by TTX, suggesting the involvement of neuronal mechanisms. This information might be used for evaluating the long-term effects of nicotine and further exploring of how tobacco products interact with bacterial airway infections.

scholarly journals Glyphosate Herbicide: Reproductive Outcomes and Multigenerational Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
María Mercedes Milesi ◽  
Virginia Lorenz ◽  
Milena Durando ◽  
María Florencia Rossetti ◽  
Jorgelina Varayoud
Keyword(s):  
Endocrine Function ◽  
Social Concern ◽  
Long Term Effects ◽  
Crop Varieties ◽  
Estrogenic Effects ◽  
Multigenerational Effects ◽  
Successive Generations

Glyphosate base herbicides (GBHs) are the most widely applied pesticides in the world and are mainly used in association with GBH-tolerant crop varieties. Indiscriminate and negligent use of GBHs has promoted the emergence of glyphosate resistant weeds, and consequently the rise in the use of these herbicides. Glyphosate, the active ingredient of all GBHs, is combined with other chemicals known as co-formulants that enhance the herbicide action. Nowadays, the safety of glyphosate and its formulations remain to be a controversial issue, as evidence is not conclusive whether the adverse effects are caused by GBH or glyphosate, and little is known about the contribution of co-formulants to the toxicity of herbicides. Currently, alarmingly increased levels of glyphosate have been detected in different environmental matrixes and in foodstuff, becoming an issue of social concern. Some in vitro and in vivo studies have shown that glyphosate and its formulations exhibit estrogen-like properties, and growing evidence has indicated they may disrupt normal endocrine function, with adverse consequences for reproductive health. Moreover, multigenerational effects have been reported and epigenetic mechanisms have been proved to be involved in the alterations induced by the herbicide. In this review, we provide an overview of: i) the routes and levels of human exposure to GBHs, ii) the potential estrogenic effects of glyphosate and GBHs in cell culture and animal models, iii) their long-term effects on female fertility and mechanisms of action, and iv) the consequences on health of successive generations.

Intervertebral Disc Function Is Restored in an In Vivo Model of Chronic Nucleus Pulposus Glycosaminoglycan Reduction

2008 ◽  
Author(s):  
John I. Boxberger ◽  
Joshua D. Auerbach ◽  
Sounok Sen ◽  
George R. Dodge ◽  
Dawn M. Elliott
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Lumbar Disc ◽  
Post Treatment ◽  
In Vivo Model ◽  
Long Term Effects ◽  
Early Human

Reduced nucleus pulposus glycosaminoglycan (GAG) content is one of the earliest clinically detectable changes during the course of intervertebral disc degeneration [1,2]. Depletion of nucleus GAG by small percentages consistent with this early loss has been experimentally linked to altered motion segment mechanical function, and thus, potentially increases the risk of damage accumulation directly due to elevated stresses and strains and through altered cellular function [3]. Recently, our laboratory has established an in vivo model in a rat lumbar disc which moderately decreases nucleus GAG to levels observed in early human degeneration. In this model, GAG loss is accompanied by a state of hypermobility at both 4 and 12 weeks post treatment [4], potentially making the disc susceptible to mechanical failure. The objective of this study was to determine the long term effects of nucleus GAG depletion and to determine if altered discs demonstrate hallmark features of disc degeneration. We hypothesized that GAG will remain depleted 24 weeks post treatment, potentially decreasing to lower levels, and further that geometrical and mechanical changes consistent with degeneration will be observed.

Sign in / Sign up

Export Citation Format

Share Document