scholarly journals The Type 5 Phosphodiesterase Inhibitor Tadalafil Influences Salivary Cortisol, Testosterone, and Dehydroepiandrosterone Sulphate Responses to Maximal Exercise in Healthy Men

2008 ◽  
Vol 93 (9) ◽  
pp. 3510-3514 ◽  
Author(s):  
Luigi Di Luigi ◽  
Carlo Baldari ◽  
Paolo Sgrò ◽  
Gian Pietro Emerenziani ◽  
Maria Chiara Gallotta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hpa Axis ◽  
Exercise Test ◽  
Salivary Cortisol ◽  
Maximal Exercise ◽  
Biological Activities ◽  
Dehydroepiandrosterone Sulphate ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Related Stress ◽  
Phosphodiesterase Type

Context: Physical exercise-related stress activates hypothalamus-pituitary-adrenal (HPA) axis; nitric oxide is one of the mediators of the HPA axis response to stress, and phosphodiesterase type 5 inhibitors influences nitric oxide-linked biological activities. Objective: The objective of the study was to investigate whether a single oral long half-life phosphodiesterase type 5 inhibitor (tadalafil) administration influences the HPA axis response to exercise-related stress. Design: This was a double-blind, cross-over trial. Participants: Participants included nine healthy male athletes. Interventions: All subjects performed a maximal exercise test in normoxia, after which they received a single oral administration of tadalafil or placebo. Then after a 2-wk washout period, they were crossed over and repeated the exercise test. Each subject was his own control. Salivary collections, for steroid evaluations [cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone] and respective ratio calculation (DHEAS to cortisol, testosterone to cortisol, testosterone to DHEAS), were performed before each exercise (Pre-Ex), immediately after (Post-Ex), and at 30 min during recovery. Results: As expected, mean salivary cortisol concentration increased immediately after exercise after both tadalafil and placebo (P = 0.014 and P =0.036 vs. Pre-Ex, respectively); however, the cortisol increase was significantly higher after tadalafil administration (P = 0.034 vs. placebo). Furthermore, an increased salivary testosterone after exercise was observed only after tadalafil administration (P = 0.029 vs. Pre-Ex). No effects of either exercise and/or tadalafil administration on salivary DHEAS concentrations were observed. DHEAS to cortisol and testosterone to cortisol ratios significantly decreased after exercise after tadalafil administration (P = 0.037, and P = 0.02 vs. placebo, respectively). Conclusion: Tadalafil administration amplified the salivary cortisol and testosterone responses to a maximal exercise-related stress in healthy trained humans.

Challenges in Endpoint Development for Pulmonary Hypertension Trials in Children

2014 ◽  
Vol 13 (3) ◽  
pp. 125-128 ◽  
Author(s):  
Dunbar Ivy
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Drug Approval ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Hypoxemic Respiratory Failure ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type

There are currently 12 medications approved for use in the treatment of pulmonary arterial hypertension (PAH) in adults. These include endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclins. However, in children there are no approved targeted PAH medications, with the exception of inhaled nitric oxide for treatment of hypoxemic respiratory failure in neonates. This review will address some of the challenges in the development of treatments for children, including lessons from recent trials, endpoints for clinical trials, and challenges with drug approval in children.

scholarly journals Phosphodiesterase-5 Inhibitors: Action on the Signaling Pathways of Neuroinflammation, Neurodegeneration, and Cognition

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Christina Alves Peixoto ◽  
Ana Karolina Santana Nunes ◽  
Ana Garcia-Osta
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Signaling Pathways ◽  
Therapeutic Strategy ◽  
Memory Loss ◽  
Present Knowledge ◽  
Protein Kinase G ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Phosphodiesterase Type ◽  
Phosphodiesterase 5

Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and memory loss diseases. Mechanistically, PDE5-Is produce an anti-inflammatory and neuroprotection effect by increasing expression of nitric oxide synthases and accumulation of cGMP and activating protein kinase G (PKG), the signaling pathway of which is thought to play an important role in the development of several neurodiseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). The aim of this paper was to review present knowledge of the signaling pathways that underlie the use of PDE5-Is in neuroinflammation, neurogenesis, learning, and memory.

Repurposing cilostazol for Raynaud's phenomenon

2020 ◽  
Vol 27 ◽  
Author(s):  
Nehme El-Hachem ◽  
Manal M. Fardoun ◽  
Hasan Slika ◽  
Elias Baydoun ◽  
Ali H. Eid
Keyword(s):  
Color Change ◽  
Angiotensin Receptor Blockers ◽  
Raynaud’S Phenomenon ◽  
Blood Perfusion ◽  
Raynaud's Phenomenon ◽  
Channel Blockers ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Receptor Blockers ◽  
Phosphodiesterase Type ◽  
Food And Drugs Administration

: Raynaud's Phenomenon (RP) results from exaggerated cold-induced vasoconstriction. RP patients suffer from vasospastic attacks and compromised digital blood perfusion leading to triple color change at the level the fingers. Severe RP may cause ulcers and threaten tissue viability. Many drugs have been used to alleviate the symptoms of RP. These include calcium-channel blockers, cGMP-specific phosphodiesterase type 5 inhibitors, prostacyclin analogs, and angiotensin receptor blockers. Despite their variety, these drugs do not treat RP but rather alleviate its symptoms. To date, no drug for RP has been yet approved by U.S Food and Drugs Administration. Cilostazol is a selective inhibitor of phosphodiesteraseIII, originally prescribed to treat intermittent claudication. Owing to its antiplatelet and vasodilating properties, cilostazol is being repurposed as a potential drug for RP. This review focuses on the different lines of action of action of cilostazol serving to enhance blood perfusion in RP patients.

scholarly journals Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eleonora Iob ◽  
Jessie R. Baldwin ◽  
Robert Plomin ◽  
Andrew Steptoe
Keyword(s):  
Depressive Symptoms ◽  
Hpa Axis ◽  
Salivary Cortisol ◽  
Adverse Childhood Experiences ◽  
Emotional Abuse ◽  
Early Adulthood ◽  
Cumulative Exposure ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Cortisol Levels

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

scholarly journals Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2351 ◽  
Author(s):  
Daniel Cervantes-García ◽  
Armida I. Bahena-Delgado ◽  
Mariela Jiménez ◽  
Laura E. Córdova-Dávalos ◽  
Vanessa Ruiz-Esparza Palacios ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Intestinal Inflammation ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
Lipid Hydroperoxide ◽  
Neutrophil Infiltration ◽  
Clinical Problem ◽  
Intestinal Damage ◽  
Nsaid Enteropathy ◽  
Anti Inflammatory

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.

Sign in / Sign up

Export Citation Format

Share Document