scholarly journals Long-term cardiovascular re-programming by short-term perinatal exposure to nicotine‘s main metabolite cotinine

2017 ◽  
Author(s):  
Stefano Bastianini ◽  
Viviana Lo Martire ◽  
Alessandro Silvani ◽  
Giovanna Zoccoli ◽  
Chiara Berteotti ◽  
...  

AbstractBackgroundCotinine - a nicotine by-product and biomarker of passive perinatal tobacco smoke exposure - is historically considered to lack significant health effects. We challenged this notion and sought “proof-of-concept” evidence of the adverse developmental potential of exposure to this substance at real-life levels.MethodsPregnant C57 mice drank nicotine or cotinine-laced water for 6wks from conception (NPRE = 2% saccharin+100μg nicotine/ml; CPRE = 2% saccharin + 10μg cotinine/ml) or for 3wks after birth (CPOST = 2% saccharin + 30μg cotinine/ml). Controls drank 2% saccharin (CTRL). At 17±1weeks male pups (CTRL n=6; CPOST n=6; CPRE n=8; NPRE n=9) were instrumented for EEG and blood pressure (BP) telemetry. We evaluated (i) cardiovascular control during sleep (at rest / during stress); (ii) arterial reactivity ex vivo; (iii) expression of genes involved in arterial constriction/dilation.ResultsBlood cotinine levels (ELISA) recapitulated passive smoker mothers-infants. Pups exposed only to cotinine exhibited (i) mild bradycardia - hypotension at rest (p<0.001); (ii) attenuated (CPRE, p<0.0001) or reverse (CPOST; p<0.0001) BP reactivity to asphyxia; (iii) pronounced adrenergic hypo-contractility (p<0.0003), low Protein Kinase C (p<0.001) and elevated adrenergic receptor mRNA (p<0.05) (all drug-treated arteries). NPRE pups also exhibited endothelium-mediated dysfunction.ConclusionsCotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion to cotinine. Low-level exposure to this metabolite may pose unrecognized perinatal risks. Adults must avoid inadvertently exposing a fetus or infant to cotinine as well as nicotine.

2015 ◽  
Vol 63 (S 01) ◽  
Author(s):  
W. Sommer ◽  
M. Avsar ◽  
J. Salman ◽  
C. Kühn ◽  
I. Tudorache ◽  
...  

1970 ◽  
Vol 8 (1) ◽  
pp. 103-109
Author(s):  
Галина Радчук

Статтю  присвячено  проблемі  теоретичного  обґрунтування  діалогу  як  механізму  аксіогенезу  особистості в освітньому процесі та виокремлення сутнісних аспектів діалогізації освітнього середовища  вищої школи. Обґрунтовано, що провідними цілями сучасної вищої освіти в контексті її гуманітаризації є  загальнокультурні орієнтири, які дозволяють замінити власне  когнітивний  підхід на смислотворчий, де і  викладач, і студент є активними суб’єктами освітнього діалогу. Показано, що освітній діалог виступає  зовнішньою   спонукою   внутрішнього   ініціювання   особистісно-професійного   становлення   майбутнього  фахівця,  становлення  його  ціннісно-смислової  сфери,  а  рівень  діалогізації  освітнього  середовища  може  слугувати  мірилом  реалізації  особистісно-розвивального  потенціалу  освіти.  На  підставі  емпіричного  дослідження   визначено,  що  у   реальному   освітньому   процесі  найбільшою   перешкодою  у   діалогізації  освітнього   середовища   є      догматичність,   формалізованість   освітнього   процесу   та   закритість,  стереотипність рольової поведінки викладачів та студентів.  The  article  is  focused  on  theoretical  argumentation  of the  dialogue  as  a  mechanism  for  personality  axiogenesis in  educational process and separation of essential dialogue aspects in higher educational environment.  The author argues that general cultural orientations are main goals of modern higher education in the context of its  humanization. This allows to replace the actual cognitive approach with sense creation one, where both teacher and  student are active subjects of educational dialogue. It is shown that educational dialogue is an external stimulus of  internal initiation of personal and professional formation in future specialists, as well as formation of their value- semantic sphere. The level of dialogue in educational environment can serve as a measure of implementation of  personality and developmental potential in education. On the basis of empirical research it is determined that  dogmatism,  formalization  of  educational  process,  and  closeness,  stereotyped  role  of  teachers’  and  students’  behavior  are  the  greatest  obstacles  for  educational  environment  becoming  more  dialogue  driven  in  real-life  educational process.


2018 ◽  
Vol 60 (3) ◽  
Author(s):  
Bruno Lumbroso ◽  
Marco Rispoli ◽  
M. Cristina Savastano
Keyword(s):  

Author(s):  
Fatima Aerts-Kaya

: In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of Hematopoietic Stem Cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs will enable the development of better protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment potential and a better understanding of the effects of the external influences in and on the hematopoietic niche that may affect HSC function. During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on HSC potential, provide a better understanding of the true impact of certain treatments in the absence of confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence or loss of cell viability. This review summarizes some of available strategies that may be used to protect HSCs from culture-induced stress conditions.


2019 ◽  
Vol 316 (5) ◽  
pp. R584-R593 ◽  
Author(s):  
Sebastien Preau ◽  
Michael Ambler ◽  
Anna Sigurta ◽  
Anna Kleyman ◽  
Alex Dyson ◽  
...  

An impaired capacity of muscle to regenerate after critical illness results in long-term functional disability. We previously described in a long-term rat peritonitis model that gastrocnemius displays near-normal histology whereas soleus demonstrates a necrotizing phenotype. We thus investigated the link between the necrotizing phenotype of critical illness myopathy and proteasome activity in these two limb muscles. We studied male Wistar rats that underwent an intraperitoneal injection of the fungal cell wall constituent zymosan or n-saline as a sham-treated control. Rats ( n = 74) were killed at 2, 7, and 14 days postintervention with gastrocnemius and soleus muscle removed and studied ex vivo. Zymosan-treated animals displayed an initial reduction of body weight but a persistent decrease in mass of both lower hindlimb muscles. Zymosan increased chymotrypsin- and trypsin-like proteasome activities in gastrocnemius at days 2 and 7 but in soleus at day 2 only. Activated caspases-3 and -9, polyubiquitin proteins, and 14-kDa fragments of myofibrillar actin (proteasome substrates) remained persistently increased from day 2 to day 14 in soleus but not in gastrocnemius. These results suggest that a relative proteasome deficiency in soleus is associated with a necrotizing phenotype during long-term critical illness. Rescuing proteasome clearance may offer a potential therapeutic option to prevent long-term functional disability in critically ill patients.


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