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Steroid responsiveness

Guillermo de Anda-Jáuregui, Kai Guo, Brett A McGregor, Junguk Hur
The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs)...
2018: Frontiers in Physiology
Salvatore Sutti, Frank Tacke
Drug-induced liver injury (DILI) remains a clinical challenge due to the poorly predictable outcomes. Accordingly, considerable efforts have been devoted to unravel the risk factors responsible for DILI worsening toward acute liver failure (ALF), liver transplantation (LT), and/or death. From a pathogenic point of view, exhaustion of drug metabolizing pathways, cell death mechanisms, activation of local immune cells, such as Kupffer cells, and recruitment of inflammatory leukocytes including monocytes and lymphocytes are key drivers of DILI progression...
March 15, 2018: Clinical Science (1979-)
Hannah Major-Monfried, Anne S Renteria, Attaphol Pawarode, Pavan Reddy, Francis Ayuk, Ernst Holler, Yvonne A Efebera, William J Hogan, Matthias Wölfl, Muna Qayed, Elizabeth O Hexner, Kitsada Wudhikarn, Rainer Ordemann, Rachel Young, Jay Shah, Matthew J Hartwell, Mohammed Chaudhry, Mina Aziz, Aaron Etra, Gregory A Yanik, Nicolaus Kröger, Daniela Weber, Yi-Bin Chen, Ryotaro Nakamura, Wolf Rösler, Carrie L Kitko, Andrew C Harris, Michael Pulsipher, Ran Reshef, Steven Kowalyk, George Morales, Ivan Torres, Umut Özbek, James L M Ferrara, John E Levine
Acute graft versus host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after one week of therapy often guides further treatment decisions, but long term outcomes vary widely between centers and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken after one week of systemic treatment for GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into test (n=236) and two validation cohorts separated in time (n = 142 and 129, respectively)...
March 15, 2018: Blood
Carolyn M Bauer, Loreto A Correa, Luis A Ebensperger, L Michael Romero
The Common Degu (Octodon degus) is a small rodent endemic to central Chile. It has become an important model for comparative vertebrate endocrinology because of several uncommon life-history features - it is diurnal, shows a high degree of sociality, practices plural breeding with multiple females sharing natal burrows, practices communal parental care, and can easily be studied in the laboratory and the field. Many studies have exploited these features to make contributions to comparative endocrinology. This review summarizes contributions in four major areas...
March 12, 2018: General and Comparative Endocrinology
Emanuele F Osimo, Rudolf N Cardinal, Peter B Jones, Golam M Khandaker
Low-grade inflammation is a risk factor for depression, psychosis and other major psychiatric disorders. It is associated with poor response to antidepressant and antipsychotics, and could potentially be a treatment target. However, there is limited data on the prevalence of low-grade inflammation in major psychiatric disorders, and on the characteristics of patients who show evidence of inflammation. We examined the prevalence of low-grade inflammation and associated socio-demographic and clinical factors in acute psychiatric inpatients...
March 1, 2018: Psychoneuroendocrinology
Inger Sundström-Poromaa
From a psychological perspective, the menstrual cycle has been a research topic for more than 50 years. The most recent menstrual cycle research has been driven by an increased interest in sex differences in neuroscience, and the urge to understand sex disparities in prevalence, clinical presentation, and treatment response in psychiatric or neurologic disorders. Indeed, the menstrual cycle is an excellent model of ovarian steroid influence on emotion, behavior, and cognition. This review summarizes the emotion-related and cognitive findings of methodologically sound menstrual cycle studies...
2018: Vitamins and Hormones
Laura J Mosher, Sean C Godar, Marc Morissette, Kenneth M McFarlin, Simona Scheggi, Carla Gambarana, Stephen C Fowler, Thérèse Di Paolo, Marco Bortolato
The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses...
February 16, 2018: Psychoneuroendocrinology
Carmen J Zamora-Sánchez, Aylin Del Moral-Morales, Ana M Hernández-Vega, Valeria Hansberg-Pastor, Ivan Salido-Guadarrama, Mauricio Rodríguez-Dorantes, Ignacio Camacho-Arroyo
Glioblastomas (GBM) are the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F). 3α-THP modified the expression of 137 genes, while F changed 90. Besides, both steroids regulated the expression of 69 genes...
March 15, 2018: International Journal of Molecular Sciences
Do-Hwan Lim, Seungjae Lee, Jee Yun Han, Min-Seok Choi, Jae-Sang Hong, Youngmo Seong, Young-Soo Kwon, Young Sik Lee
The steroid hormone ecdysone has a central role in the developmental transitions of insects through its control of responsive protein-coding and microRNA (miRNA) gene expression. However, the complete regulatory network controlling the expression of these genes remains to be elucidated. In this study, we performed cross-linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 (Ago1) protein, the core effector of the miRNA pathway, in Drosophila S2 cells. We found that regulatory interactions between miRNAs and their cognate targets were substantially altered by Ago1 in response to ecdysone signaling...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jee Hee Son, Sook Young Park, Yong Se Cho, Bo Young Chung, Hye One Kim, Chun Wook Park
Corticosteroids are potent anti-inflammatory and anti-allergic agents used in the treatment of various inflammatory diseases, including allergic disease. They are frequently considered the therapy-of-choice for many skin diseases. However, allergic reactions caused by corticosteroids have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 32-year-old woman with triamcinolone-induced immediate hypersensitivity reaction, in which the patient had a positive prick test result with triamcinolone...
March 19, 2018: Journal of Korean Medical Science
Holger Joswig, Armin Neff, Christina Ruppert, Gerhard Hildebrandt, Martin Nikolaus Stienen
BACKGROUND: The predictive value of short-term arm pain relief after 'indirect' cervical epidural steroid injection (ESI) for the 1-month treatment response has been previously demonstrated. It remained to be answered whether the long-term response could be estimated by the early post-interventional pain course as well. METHODS: Prospective observational study, following a cohort of n = 45 patients for a period of 24 months after 'indirect' ESI for radiculopathy secondary to a single-level cervical disk herniation (CDH)...
March 14, 2018: Acta Neurochirurgica
M G Carta, A Preti, H S Akiskal
Human population is increasing in immense cities with millions of inhabitants, in which life is expected to run 24 hours a day for seven days a week (24/7). Noise and light pollution are the most reported consequences, with a profound impact on sleep patterns and circadian biorhythms. Disruption of sleep and biorhythms has severe consequences on many metabolic pathways. Suppression of melatonin incretion at night and the subsequent effect on DNA methylation may increase the risk of prostate and breast cancer...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
Carla A Piccinato, Rosa M Neme, Natália Torres, Elivane da Silva Victor, Heloísa F Brudniewski, Júlio C Rosa E Silva, Rui A Ferriani
The cellular function in endometriosis lesions depends on a highly estrogenic milieu. Lately, it is becoming evident that, besides the circulating levels of estrogens, the balance of synthesis versus inactivation (metabolism) of estrogens by intralesion steroid-metabolizing enzymes also determines the local net estrogen availability. In order to extend the knowledge of the role of estrogen-metabolizing enzymes in endometriosis, we investigated the gene and protein expression of a key uridine diphospho-glucuronosyltransferase (UGT) for estrogen glucuronidation, UGT1A1, in eutopic endometrial samples obtained from nonaffected and endometriosis-affected women and also from endometriotic lesions...
January 1, 2018: Reproductive Sciences
Jeffery M Vahrenkamp, Chieh-Hsiang Yang, Adriana C Rodriguez, Aliyah Almomen, Kristofer C Berrett, Alexis N Trujillo, Katrin P Guillen, Bryan E Welm, Elke A Jarboe, Margit M Janat-Amsbury, Jason Gertz
Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other's function. Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia...
March 13, 2018: Cell Reports
Sean A McGhee
PURPOSE OF REVIEW: Although biologic therapies can provide outstanding efficacy in the management of lung disease, especially asthma, most of these agents have been approved only for adults. Recent findings provide new strategies for using these agents in children. RECENT FINDINGS: Extensive evidence has consistently demonstrated the efficacy and safety of biologic therapy for asthma. In addition, some studies have documented potentially important secondary effects, such as improving response to respiratory virus infection in asthmatic patients...
March 13, 2018: Current Opinion in Pediatrics
Neal Bhatia, Leon Kircik
Optimizing combinations for psoriasis means asking patients to take control of their disease. It means balancing potency of steroids for the short-run to put out the fire and bring relief and maintaining the clearance for the long-run to reduce recurrence potential. Successful combinations are built on tolerability, ease of application, and the efficacy demonstrated by the synergy of the sum of the parts over being used separately. <p><em>J Drugs Dermatol. 2018;17(3):342-346.</em></p>...
March 1, 2018: Journal of Drugs in Dermatology: JDD
Logan W Thomas, Ashley Elsensohn, Terese Bergheim, Jessica Shiu, Anand Ganesan
IMPORTANCE: Intramuscular (IM) steroids can be used to treat a wide variety of dermatologic diseases. Although seemingly effective and safe, this form of corticosteroid therapy may be underused amongst dermatologists. OBJECTIVE: The objective of this review is to determine the evidence regarding the efficacy and side effect profile of intramuscular triamcinolone in the treatment of dermatologic disease. EVIDENCE REVIEW: A PubMed search engine was used for this study...
March 1, 2018: Journal of Drugs in Dermatology: JDD
Eva Nüsken, Jörg Dötsch, Lutz T Weber, Kai-Dietrich Nüsken
Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life...
2018: Frontiers in Pediatrics
Natalia Pascuali, Leopoldina Scotti, Mariana Di Pietro, Gonzalo Oubiña, Diana Bas, María May, Antonio Gómez Muñoz, Patricia S Cuasnicú, Débora J Cohen, Marta Tesone, Dalhia Abramovich, Fernanda Parborell
STUDY QUESTION: Is ceramide-1-phosphate (C1P) an ovarian protective agent during alkylating chemotherapy? SUMMARY ANSWER: Local administration of C1P drastically reduces ovarian damage induced by cyclophosphamide (Cy) via protection of follicular reserve, restoration of hormone levels, inhibition of apoptosis and improvement of stromal vasculature, while protecting fertility, oocyte quality and uterine morphology. WHAT IS KNOWN ALREADY: Cancer-directed therapies cause accelerated loss of ovarian reserve and lead to premature ovarian failure (POF)...
March 9, 2018: Human Reproduction
Daniela A Braun, Jillian K Warejko, Shazia Ashraf, Weizhen Tan, Ankana Daga, Ronen Schneider, Tobias Hermle, Tilman Jobst-Schwan, Eugen Widmeier, Amar J Majmundar, Makiko Nakayama, David Schapiro, Jia Rao, Johanna Magdalena Schmidt, Charlotte A Hoogstraten, Hannah Hugo, Sevcan A Bakkaloglu, Jameela A Kari, Sherif El Desoky, Ghaleb Daouk, Shrikant Mane, Richard P Lifton, Shirlee Shril, Friedhelm Hildebrandt
Background: Nephrotic syndrome (NS), a chronic kidney disease, is characterized by significant loss of protein in the urine causing hypoalbuminemia and edema. In general, ∼15% of childhood-onset cases do not respond to steroid therapy and are classified as steroid-resistant NS (SRNS). In ∼30% of cases with SRNS, a causative mutation can be detected in one of 44 monogenic SRNS genes. The gene LAMA5 encodes laminin-α5, an essential component of the glomerular basement membrane. Mice with a hypomorphic mutation in the orthologous gene Lama5 develop proteinuria and hematuria...
March 9, 2018: Nephrology, Dialysis, Transplantation
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