scholarly journals Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter, Stress Hormone, and Male Sex Hormone Systems

2019 ◽  
Author(s):  
Mariam Bonyadi Camacho ◽  
Warut D. Vijitbenjaronk ◽  
Thomas J Anastasio
Keyword(s):  
Antidepressant Treatment ◽  
Chronic Administration ◽  
Sex Hormone ◽  
Model Parameters ◽  
Depression Treatment ◽  
Stress Hormone ◽  
Large Sets ◽  
Effective Combination ◽  
Male Sex ◽  
Monoaminergic Neurotransmitter

AbstractSecond-line depression treatment involves augmentation with one (rarely two) additional drugs, of chronic administration of a selective serotonin reuptake inhibitor (SSRI), which is the first-line depression treatment. Unfortunately, many depressed patients still fail to respond even after months to years of searching to find an effective combination. To aid in the identification of potentially affective antidepressant combinations, we created a computational model of the monoaminergic neurotransmitter (serotonin, norepinephrine, and dopamine), stress-hormone (cortisol), and male sex-hormone (testosterone) systems. The model was trained via machine learning to represent a broad set of empirical observations. Neuroadaptation to chronic drug administration was simulated through incremental adjustments in model parameters that corresponded to key regulatory components of the neurotransmitter and neurohormone systems. Analysis revealed that neuroadaptation in the model depended on all of the regulatory components in complicated ways, and did not reveal any one or a few specific components that could be targeted in the design of combination antidepressant treatment. We used large sets of neuroadapted states of the model to screen 74 different drug and hormone combinations and identified several combinations that could potentially be therapeutic for a higher proportion of male patients than SSRIs by themselves.

scholarly journals Computational Analysis of Therapeutic Neuroadaptation to Chronic Antidepressant in a Model of the Monoaminergic Neurotransmitter and Stress Hormone Systems

2019 ◽  
Author(s):  
Mariam Bonyadi Camacho ◽  
Warut D. Vijitbenjaronk ◽  
Thomas J Anastasio
Keyword(s):  
Clinical Judgment ◽  
Computational Analysis ◽  
Antidepressant Drugs ◽  
Chronic Administration ◽  
Trial And Error ◽  
Stress Hormone ◽  
Treatment Resistant ◽  
Potential Explanation ◽  
System Components ◽  
Monoaminergic Neurotransmitter

AbstractThe clinical practice of selective serotonin reuptake inhibitor (SSRI) augmentation relies heavily on clinical judgment and trial-and-error. Unfortunately, the drug combinations prescribed today fail to provide relief for all treatment-resistant depressed patients. In order to identify potentially more effective treatments, we developed a computational model of the monoaminergic neurotransmitter and stress-steroid systems that neuroadapts to chronic administration of combinations of antidepressant drugs and hormones by adjusting the strengths of its transmitter-system components (TSCs). We used the model to screen 60 chronically administered drug/hormone pairs and triples, and identified as potentially therapeutic those combinations that raised the monoamines (serotonin, norepinephrine, and dopamine) but lowered cortisol following neuroadaptation in the model. We also evaluated the contributions of individual and pairs of TSCs to therapeutic neuroadaptation with chronic SSRI using sensitivity, correlation, and linear temporal-logic analyses. All three approaches found that therapeutic neuroadaptation to chronic SSRI is an overdetermined process that depends on multiple TSCs, providing a potential explanation for the clinical finding that no single antidepressant regimen alleviates depressive symptoms in all patients.

scholarly journals Regulatory Role of Sex Hormones in Cardiovascular Calcification

2021 ◽  
Vol 22 (9) ◽  
pp. 4620
Author(s):  
Holly J. Woodward ◽  
Dongxing Zhu ◽  
Patrick W. F. Hadoke ◽  
Victoria E. MacRae
Keyword(s):  
Cardiovascular Disease ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Aortic Stenosis ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Increased Risk ◽  
Male Sex ◽  
Primary Male

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

Experimental Data on the Function of the Interstitium of the Gonads: Experiments with Cockerels

1947 ◽  
Vol s3-88 (2) ◽  
pp. 135-150
Author(s):  
J. W. SLUITER ◽  
G. J. VAN OORDT
Keyword(s):  
Experimental Data ◽  
Connective Tissue ◽  
Leydig Cells ◽  
Cell Types ◽  
Sex Hormone ◽  
Secretory Cells ◽  
Secretory Function ◽  
Glandular Cells ◽  
Male Sex ◽  
Secondary Function

1. The relative volumes of the testes and their components of 31 cockerels, 2-200 days old, were calculated and compared with the size of their increasing head appendages (Text-figs. 1a-d, 2); in addition, the effect of gestyl-administration on testes of cockerels of this age was investigated. 2. Several types of interstitial testis-cells could be distinguished morphologically and physiologically (Text-figs. 3-6 and Pl. 1); these cell-types were studied with different techniques and counted separately. 3. The main types of the interstitial cells are: (a) Lipoid cells, totally packed with lipoid globules. These cells, which are considered by many authors as fully developed Leydig cells, are not directly connected with the production of the male sex hormone; perhaps they have a secondary function in this respect, as cholesterolderivatives are stored in these cells (Pl. 1, Text-fig. 3a). (b) Secretory cells, characterized by the absence of lipoid vacuoles and the presence of numerous granular and filamentous mitochondria. These secretory cells, which produce the male sex hormone, can be divided into secretory cells A (Text-fig. 6a) without, and secretory cells B with, one large vacuole (Text-figs. 6b, 6c, 6d). 4. A considerable and partly intercellular storage of lipoids may take place at any age in the intertubular connective tissue (Text-figs. 3-4 and Pl. 1). 5. The number of the lipoid cells depends on the nutritive conditions of the animal and the development of its testes (Text-fig. 7). 6. In older cockerels most of the glandular cells lose their secretory function and pass over into lipoid storing cells. 7. Therefore we agree with Benoit, when he denies the occurrence of a ‘secretion de luxe’, but we cannot accept the presence of a ‘parenchyme de luxe’ in the testes of older cockerels.

Virtual screening attributes male biased COVID-19 mortality to predicted antiviral activity of female sex hormones

2021 ◽  
Vol 18 ◽  
Author(s):  
Galal Yahya ◽  
Basem Mansour ◽  
Kristina Keuper ◽  
Moataz Shaldam ◽  
Ahmed El-Baz
Keyword(s):  
Virtual Screening ◽  
Sex Hormones ◽  
Hospital Admissions ◽  
Epidemiological Data ◽  
Antiviral Effect ◽  
Sex Hormone ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Disaggregated Data ◽  
Male Sex

Background: Coronavirus disease-19 (COVID-19) is a newly emerged pandemic leading to a state of international alert with millions of infected individuals and thousands of deaths all over the world. Analysis of statistics and epidemiological data for the pandemic outcome pinpointed a puzzling influence of human sex on the heterogeneous outcome of COVID-19, where hospital admissions and mortality were higher among males than females. Two theories explained the observed male-biased COVID-19 mortality based on either dosage of immunoregulatory genes coded in X- chromosomes or on the abundance of the angiotensin-converting enzyme two (ACE2) receptors in males than females. Objective: In our study, we propose a third scenario through virtual screening of direct antiviral effects of sex hormones. Materials & Methods: Updated screening statistics from 47 countries displaying sex-disaggregated data on COVID-19 were employed and visualized in the form of heatmaps depicting sex difference effects on statistics of cases and deaths. Molecular docking and binding simulations of investigated sex steroids against COVID-19 specific proteins were investigated. Results: Analysis of COVID-19 sex-disaggregated data confirmed that male-biased mortality and computer-aided docking found unexpected female sex hormones biased binding against key targets implicated in the life cycle of COVID-19 compared to the male sex hormone testosterone. Other investigated steroids showed promising docking scores, while the male sex hormone exhibited the lowest affinity. Conclusion: Female sex hormones virtually exhibited direct COVID-19 effect. The proposed antiviral effect of sex hormones should be considered to explain the outcomes of mortality; moreover, the fluctuation of sex hormones influences sex and personal derived-differential response to COVID-19 infection.

Male Sex Hormone and Osteo-Arthrosis in Mice

1961 ◽  
Vol 43 (2) ◽  
pp. 243-248 ◽  
Author(s):  
Ruth Silberberg ◽  
Martin Silberberg
Keyword(s):  
Sex Hormone ◽  
Male Sex
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