scholarly journals Chronic Social Defeat During Adolescence Induces Short- and Long-Term Behavioral and Neuroendocrine Effects in Male Swiss-Webster Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Héctor Miguel Mancha-Gutiérrez ◽  
Erika Estrada-Camarena ◽  
Lilian Mayagoitia-Novales ◽  
Elena López-Pacheco ◽  
Carolina López-Rubalcava
Keyword(s):  
Early Adolescence ◽  
Cognitive Deficits ◽  
Early Adulthood ◽  
Social Defeat ◽  
Adolescent Male ◽  
Normal Brain ◽  
Dependent Manner ◽  
Barnes Maze ◽  
Short And Long Term

Chronic stress exposure during adolescence is a significant risk factor for the development of depression. Chronic social defeat (CSD) in rodents is an animal model of depression with excellent ethological, predictive, discriminative, and face validity. Because the CSD model has not been thoroughly examined as a model of stress-induced depression within the adolescence stage, the present study analyzed the short- and long-term behavioral and neuroendocrine effects of CSD during early adolescence. Therefore, adolescent male Swiss-Webster (SW) mice were exposed to the CSD model from postnatal day (PND) 28 to PND37. Twenty-four hours (mid-adolescence) or 4 weeks (early adulthood) later, mice were tested in two models of depression; the social interaction test (SIT) and forced swimming test (FST); cognitive deficits were evaluated in the Barnes maze (BM). Finally, corticosterone and testosterone content was measured before, during, and after CSD exposure, and serotonin transporter (SERT) autoradiography was studied after CSD in adolescent and adult mice. CSD during early adolescence induced enduring depression-like behaviors as inferred from increased social avoidance and immobility behavior in the SIT and FST, respectively, which correlated in an age-dependent manner with SERT binding in the hippocampus; CSD during early adolescence also induced long-lasting learning and memory impairments in the Barnes maze (BM). Finally, CSD during early adolescence increased serum corticosterone levels in mid-adolescence and early adulthood and delayed the expected increase in serum testosterone levels observed at this age. In conclusion: (1) CSD during early adolescence induced long-lasting depression-like behaviors, (2) sensitivity of SERT density during normal brain development was revealed, (3) CSD during early adolescence induced enduring cognitive deficits, and (4) results highlight the vulnerability of the adolescent brain to social stressors on the adrenal and gonadal axes, which emphasizes the importance of an adequate interaction between both axes during adolescence for normal development of brain and behavior.

scholarly journals Increased mortality risk associated with serum sodium variations and borderline hypo- and hypernatremia in hospitalized adults

2019 ◽  
Vol 35 (10) ◽  
pp. 1746-1752 ◽  
Author(s):  
Charat Thongprayoon ◽  
Wisit Cheungpasitporn ◽  
John Q Yap ◽  
Qi Qian
Keyword(s):  
Hospital Stay ◽  
Serum Sodium ◽  
Reference Range ◽  
Length Of Hospital Stay ◽  
Sodium Concentration ◽  
Dependent Manner ◽  
Short And Long Term ◽  
Dose Dependent ◽  
Long Term Mortality

Abstract Background This study aimed to evaluate short-term and long-term mortalities in a cohort of unselected hospitalized patients with serum sodium concentration ([Na+]) variations within and outside of reference range. Methods All adult patients admitted to the Mayo Clinic, Rochester, MN, USA from January 2011 to December 2013 (n = 147358) were retrospectively screened. Unique patients admitted during the study period were examined. The main exposure was serum [Na+] variation. Outcome measures were hospital and 1-year all-cause mortalities. Results A total of 60944 patients, mean age 63 ± 17 years, were studied. On admission, 17% (n = 10066) and 1.4% (n = 852) had hypo- and hypernatremia, respectively. During the hospital stay, 11044 and 4128 developed hypo- and hypernatremia, respectively, accounting for 52.3 and 82.9% of the total hypo- and hypernatremic patients. Serum [Na+] variations of ≥6 mEq/L occurred in 40.6% (n = 24 740) of the 60 944 patients and were significantly associated with hospital and 1-year mortalities after adjusting potential confounders (including demographics, comorbidities, estimated glomerular filtration rate, admission serum [Na+], number of [Na+] measurements and length of hospital stay). Adjusted odds ratios for hospital and 1-year mortalities increased with increasing [Na+] variations in a dose-dependent manner, from 1.47 to 5.48 (all 95% confidence intervals >1.0). Moreover, in fully adjusted models, [Na+] variations (≥6 mEq/L) within the reference range (135–145 mEq/L) or borderline hypo- or hypernatremia (133–137 and 143–147 mEq/L, respectively) compared with 138–142 mEq/L were associated with increased hospital and 1-year mortalities. Conclusion In hospitalized adults, [Na+] fluctuation (≥6 mEq/L) irrespective of admission [Na+] and borderline hypo- or hypernatremia are independent predictors of progressively increasing short- and long-term mortality burdens.

scholarly journals Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway

2008 ◽  
Vol 199 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Helena C Barbosa ◽  
Silvana Bordin ◽  
Gabriel Anhê ◽  
Shanta J Persaud ◽  
James Bowe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Islet Neogenesis ◽  
Rat Islets ◽  
Short Term Exposure ◽  
Cholinergic Pathway ◽  
M3 Receptor ◽  
Short And Long Term

Islet neogenesis associated protein (INGAP) increases islet mass and insulin secretion in neonatal and adult rat islets. In the present study, we measured the short- and long-term effects of INGAP-PP (a pentadecapeptide having the 104–118 amino acid sequence of INGAP) upon islet protein expression and phosphorylation of components of the PI3K, MAPK and cholinergic pathways, and on insulin secretion. Short-term exposure of neonatal islets to INGAP-PP (90 s, 5, 15, and 30 min) significantly increased Akt1-Ser473 and MAPK3/1-Thr202/Tyr204 phosphorylation and INGAP-PP also acutely increased insulin secretion from islets perifused with 2 and 20 mM glucose. Islets cultured for 4 days in the presence of INGAP-PP showed an increased expression of Akt1, Frap1, and Mapk1 mRNAs as well as of the muscarinic M3 receptor subtype, and phospholipase C (PLC)-β2 proteins. These islets also showed increased Akt1 and MAPK3/1 protein phosphorylation. Brief exposure of INGAP-PP-treated islets to carbachol (Cch) significantly increased P70S6K-Thr389 and MAPK3/1 phosphorylation and these islets released more insulin when challenged with Cch that was prevented by the M3 receptor antagonist 4-DAMP, in a concentration-dependent manner. In conclusion, these data indicate that short- and long-term exposure to INGAP-PP significantly affects the expression and the phosphorylation of proteins involved in islet PI3K and MAPK signaling pathways. The observations of INGAPP-PP-stimulated up-regulation of cholinergic M3 receptors and PLC-β2 proteins, enhanced P70S6K and MAPK3/1 phosphorylation and Cch-induced insulin secretion suggest a participation of the cholinergic pathway in INGAP-PP-mediated effects.

EXTH-60. PRECLINICAL STUDY OF PAMIPARIB, A CNS-PENETRANT PARP INHIBITOR, IN IDH1/2 MUTATED GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi176-vi177
Author(s):  
Christopher Hong ◽  
Ranjini Sundaram ◽  
Ranjit Bindra
Keyword(s):  
Cell Lines ◽  
Parp Inhibitor ◽  
Idh1 Mutation ◽  
In Vivo Studies ◽  
Pharmacokinetic Analysis ◽  
Normal Brain ◽  
Dependent Manner ◽  
Rat Glioma ◽  
Cns Penetration

Abstract Our group has demonstrated that IDH1/2 mutated gliomas harbor intrinsic homologous recombination (HR) defects mediated by the oncometabolite, 2-HG, rendering them sensitive to PARP inhibitors. Here, we studied the efficacy of pamiparib, a CNS-penetrant PARP inhibitor with potent PARP trapping ability, in combination with temozolomide (TMZ) and radiation therapy (RT) in IDH1/2 mutated gliomas. We also studied the pharmacokinetics of BGB290 to demonstrate CNS penetrance. We performed a series of DNA repair functional studies with in vitro short- and long-term viability assays, as well as in vivo studies utilizing an orthotopically injected rat glioma model with bioluminescence. Pharmacokinetics was measured with a previously validated LCMS/MS technique. Short-term and long-term viability assays in paired isogenic IDH1 wildtype and mutant cell lines showed the IDH1 mutation conferred enhanced sensitivity to pamiparib with several-fold decreases in IC50, as well as TMZ and RT as expected. Combination treatment with pamiparib and TMZ or RT also demonstrated synergistic interactions in these same cell lines, dependent upon IDH1 mutation status. An ELISA assay confirmed PARylation inhibition by pamiparib at the nanomolar range in a dose-dependent manner. Pharmacokinetic analysis demonstrated favorable CNS penetration with tumor:plasma ratios ( >0.20) observed with low (3 mg/kg) and high (6 mg/kg) doses of pamiparib, orally administered BID to rats harboring intrinsic rat glioma intracranial tumors. These levels persisted between 2 and 8 hours after last dosing. Pamiparib also selectively penetrated tumors over normal brain with normal brain:plasma ratios under 0.20. These data suggest pamiparib may selectively target IDH1/2 mutated gliomas and act synergistically with TMZ and RT to exploit intrinsic HR defects associated with these tumors. Pharmacokinetic analysis suggest favorable CNS penetration after standard bid oral administration. As such, these results lay the groundwork for study of pamiparib with TMZ and/or RT in patients with IDH1/2 mutated gliomas.

The Short- and Long-Term Effects of Adolescent Violent Victimization Experienced Within the Family and Community

2003 ◽  
Vol 18 (4) ◽  
pp. 445-459 ◽  
Author(s):  
Abigail A. Fagan
Keyword(s):  
Early Adulthood ◽  
Violent Victimization ◽  
Long Term Effects ◽  
Youth Survey ◽  
Criminal Involvement ◽  
The Family ◽  
Short And Long Term ◽  
Using Data ◽  
The Relationship

Adolescents face high rates of victimization, yet little is known regarding the criminal consequences of these experiences. Using data from the National Youth Survey, this investigation compared the relative and combined effects of adolescent violent victimization perpetrated by family and nonfamily members on self-reported criminal offending from adolescence to early adulthood. The results demonstrate that both types of violence have an immediate and sustained impact on criminal involvement, although the effect is somewhat stronger for nonfamily victimization, and for both types, the relationship tends to weaken over time. In addition, those experiencing both types of victimization report a higher frequency of offending compared to those experiencing only one type. The findings indicate the need for prevention programs aimed at decreasing the prevalence of adolescent victimization, as well as intervention efforts to help victims from becoming offenders.

Pubertal gynecomastia: years of progress – the Hacettepe experience

2017 ◽  
Vol 31 (3) ◽  
Author(s):  
Sinem Akgül ◽  
Orhan Derman ◽  
Nuray Kanbur
Keyword(s):  
Body Image ◽  
Psychological Distress ◽  
Review Article ◽  
Tamoxifen Treatment ◽  
Adolescent Male ◽  
Adolescent Medicine ◽  
Short And Long Term ◽  
Conducting Research ◽  
Pubertal Gynecomastia

Abstract Gynecomastia is defined as an enlargement of the male breast. Although it is commonly seen during puberty, it is often overlooked by many physicians. As adolescent medicine specialists, we believe there is a gap in the literature concerning both the etiology and maybe more importantly the care of these adolescents. Thus, we have been dedicated to conducting research on this topic. The aim of this review article was to evaluate the studies concerning pubertal gynecomastia that took place at the Division of Adolescent Medicine, Hacettepe University, published between the years 2003 and 2016. The review covers in detail both the short- and long-term effectivity and safety of tamoxifen used for the treatment of pubertal gynecomastia. As the exact basis for the pathogenesis of gynecomastia remains unknown, we also evaluate three studies that aimed to answer this question. We additionally review a study that aimed to assess the psychological distress and effect on body image that gynecomastia may have on the adolescent male. An important contribution this review article adds to the literature is as a conclusion to all the studies performed, we present the ‘Hacettepe indications for tamoxifen treatment for pubertal gynecomastia’. These indications will aid physicians when considering treating these patients.

scholarly journals Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

2020 ◽  
Vol 21 (3) ◽  
pp. 1148 ◽  
Author(s):  
Zuzana Nova ◽  
Henrieta Skovierova ◽  
Jan Strnadel ◽  
Erika Halasova ◽  
Andrea Calkovska
Keyword(s):  
Oxidative Stress ◽  
A549 Cells ◽  
Surfactant Proteins ◽  
Proper Function ◽  
Suitable Model ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
Short And Long Term

Alveolar epithelial type II (ATII) cells and their proper function are essential for maintaining lung integrity and homeostasis. However, they can be damaged by lipopolysaccharide (LPS) during Gram-negative bacterial infection. Thus, this study evaluated and compared the effects of LPS on short and long-term cultures of A549 cells by determining the cell viability, levels of oxidative stress and antimicrobial peptide cathelicidin LL-37 and changes in the expression of surfactant proteins (SPs). Moreover, we compared A549 cell response to LPS in the presence of different serum concentrations. Additionally, the effect of N-acetylcysteine (NAC) on LPS-induced oxidative stress as a possible treatment was determined. Our results indicate that A549 cells are relatively resistant to LPS and able to maintain integrity even at high LPS concentrations. Their response to endotoxin is partially dependent on serum concentration. NAC failed to lower LPS-induced oxidative stress in A549 cells. Finally, LPS modulates SP gene expression in A549 cells in a time dependent manner and differences between short and long-term cultures were present. Our results support the idea that long-term cultivation of A549 cells could promote a more ATII-like phenotype and thus could be a more suitable model for ATII cells, especially for in vitro studies dealing with surfactant production.

scholarly journals Disruption of fish gut microbiota composition and holobiont’s metabolome by cyanobacterial blooms

2021 ◽  
Author(s):  
Alison Gallet ◽  
Sébastien Halary ◽  
Charlotte Duval ◽  
Hélène Huet ◽  
Sébastien Duperron ◽  
...  
Keyword(s):  
Oxygen Depletion ◽  
Cyanobacterial Blooms ◽  
Dependent Manner ◽  
Microbiome Composition ◽  
Fish Gut ◽  
Short And Long Term ◽  
Metabolome Profiling ◽  
The Times ◽  
Dose Dependent

AbstractBackgroundCyanobacterial blooms are one of the most common stress encountered by metazoans living in freshwater lentic systems such as lakes and ponds. Blooms reportedly impair fish health, notably through oxygen depletion and production of bioactive compounds including cyanotoxins. However, in the times of the “microbiome revolution”, it is surprising that so little is still known regarding the influence of blooms on fish microbiota. In this study, an experimental approach is used to demonstrate that blooms affect fish microbiome composition and functions, as well as the metabolome of holobionts. To this end, the model teleost Oryzias latipes is exposed to simulated Microcystis aeruginosa blooms of various intensities in a microcosm setting, and the response of bacterial gut communities is evaluated in terms of composition, metagenome-encoded functions and metabolome profiling.ResultsThe gut bacterial community of O. latipes exhibits marked responses to the presence of M. aeruginosa blooms in a dose-dependent manner. Notably, abundant gut-associated Firmicutes almost disappear, while potential opportunists increase. The holobiont’s gut metabolome displays major changes, while functions encoded in the metagenome of bacterial partners are more marginally affected. Bacterial communities tend to return to original composition after the end of the bloom suggesting post-bloom resilience, and remain sensitive in case of a second bloom, reflecting a highly reactive gut community.ConclusionIn the context of increasingly frequent and intense blooms worldwide, results point to the relevance of accounting for short- and long-term microbiome-related effects in fish ecology, with potential outcomes relevant to conservation biology as well as aquaculture.

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