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Pharmacological Research: the Official Journal of the Italian Pharmacological Society

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https://www.readbyqxmd.com/read/30227261/preventing-childhood-and-lifelong-disability-maternal-dietary-supplementation-for-perinatal-brain-injury
#1
REVIEW
Oriana E F Shaw, Jerome Y Yager
The majority of brain injuries that lead to cerebral palsy, developmental disability, and mental health disorders have their onset in utero. These lifelong conditions come with great economic and emotional burden as they impact function in nearly all domains of affected individuals' lives. Unfortunately, current therapeutic options are limited. There remains a focus on rescue, rehabilitation, and regeneration after the injury has occurred, rather than aiming to prevent the initial injury. Prevention would imply treating the mother during pregnancy to alter the fetal environment and in turn, treat the fetus...
September 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30227260/improvement-of-glucocorticoid-impaired-thymus-function-by-dihydromyricetin-via-up-regulation-of-ppar%C3%AE-associated-fatty-acid-metabolism
#2
Ting Li, Fenggen Yan, Xiongyu Meng, Jingrong Wang, Richard Kin Ting Kam, Xing Zeng, Zhongqiu Liu, Hua Zhou, Fen Yang, Rutong Ren, Kangsheng Liao, Liang Liu
T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX...
September 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30223086/uncoupling-proteins-as-a-therapeutic-target-to-protect-the-diabetic-heart
#3
REVIEW
Phiwayinkosi V Dludla, Bongani B Nkambule, Luca Tiano, Johan Louw, Martin Jastroch, Sithandiwe E Mazibuko-Mbeje
Myocardial remodeling and dysfunction caused by accelerated oxidative damage is a widely reported phenomenon within a diabetic state. Altered myocardial substrate preference appears to be the major cause of enhanced oxidative stress-mediated cell injury within a diabetic heart. During this process, exacerbated free fatty acid flux causes an abnormal increase in mitochondrial membrane potential leading to the overproduction of free radical species and subsequent cell damage. Uncoupling proteins (UCPs) are expressed within the myocardium and can protect against free radical damage by modulating mitochondrial respiration, leading to reduced production of reactive oxygen species...
September 14, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30223085/evolutionary-considerations-on-5-ht-2-receptors
#4
REVIEW
Imane Moutkine, Emily Lauren Collins, Catherine Béchade, Luc Maroteaux
Serotonin is a neurotransmitter widely conserved from ancient organisms lacking nervous systems through man, and its presence precedes the appearance of nervous systems on both developmental and evolutionary time scales. Serotonin receptor subtypes diversified approximately at the time period during which vertebrates diverged from invertebrates. The biological and clinical importance of serotonin receptors, may benefit from studies on their evolution. Although potentially informative about their pathophysiological functions, reviews on this topic are sparse...
September 14, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30219582/regulation-of-endoplasmic-reticulum-mitochondria-contacts-by-parkin-via-mfn2
#5
Valentina Basso, Elena Marchesan, Caterina Peggion, Joy Chakraborty, Sophia von Stockum, Marta Giacomello, Denis Ottolini, Valentina Debattisti, Federico Caicci, Elisabetta Tasca, Valentina Pegoraro, Corrado Angelini, Angelo Antonini, Alessandro Bertoli, Marisa Brini, Elena Ziviani
Parkin, an E3 ubiquitin ligase and a Parkinson's disease (PD) related gene, translocates to impaired mitochondria and drives their elimination via autophagy, a process known as mitophagy. Mitochondrial pro-fusion protein Mitofusins (Mfn1 and Mfn2) were found to be a target for Parkin mediated ubiquitination. Mfns are transmembrane GTPase embedded in the outer membrane of mitochondria, which are required on adjacent mitochondria to mediate fusion. In mammals, Mfn2 also forms complexes that are capable of tethering mitochondria to endoplasmic reticulum (ER), a structural feature essential for mitochondrial energy metabolism, calcium (Ca2+ ) transfer between the organelles and Ca2+ dependent cell death...
September 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30219581/therapeutic-potential-of-curcumin-in-diabetic-complications
#6
REVIEW
Negin Parsamanesh, Maryam Moossavi, Afsane Bahrami, Alexandra E Butler, Amirhossein Sahebkar
Diabetes mellitus is an extremely prevalent endocrine disease and a major global public health concern. Diabetic complications, such as retinopathy, nephropathy, neuropathy and cardiovascular disease, are common and majorly impact a patient's quality of life. Curcumin, the major active component of turmeric, possesses extensive known pharmacological properties, including anti-inflammatory, antioxidant, and antitumor effects. Increasing evidence suggests that curcumin may offer protection against diabetic complications...
September 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30219580/phase-iia-trial-in-duchenne-muscular-dystrophy-shows-vamorolone-is-a-first-in-class-dissociative-steroidal-anti-inflammatory-drug
#7
Laurie S Conklin, Jesse M Damsker, Eric P Hoffman, William J Jusko, Panteleimon D Mavroudis, Benjamin D Schwartz, Laurel J Mengle-Gaw, Edward C Smith, Jean K Mah, Michela Guglieri, Yoram Nevo, Nancy Kuntz, Craig M McDonald, Mar Tulinius, Monique M Ryan, Richard Webster, Diana Castro, Richard S Finkel, Andrea L Smith, Lauren P Morgenroth, Adrienne Arrieta, Maya Shimony, Mark Jaros, Phil Shale, John M McCall, Yetrib Hathout, Kanneboyina Nagaraju, John van den Anker, Leanne M Ward, Alexandra Ahmet, Michaelyn R Cornish, Paula R Clemens
We report a first-in-patient study of vamorolone, a first-in-class dissociative steroidal anti-inflammatory drug, in Duchenne muscular dystrophy. This 2-week, open-label Phase IIa multiple ascending dose study (0.25, 0.75, 2.0, and 6.0 mg/kg/day) enrolled 48 boys with Duchenne muscular dystrophy (4 to <7 years), with outcomes including clinical safety, pharmacokinetics and pharmacodynamic biomarkers. The study design included pharmacodynamic biomarkers in three contexts of use: 1. Secondary outcomes for pharmacodynamic safety (insulin resistance, adrenal suppression, bone turnover); 2...
September 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30213564/clinical-utility-of-abcb1-genotyping-for-preventing-toxicity-in-treatment-with-irinotecan
#8
Sara Salvador-Martín, Xandra García-González, María I García, Carolina Blanco, Pilar García-Alfonso, Luis Robles, Cristina Grávalos, Vanessa Pachón, Federico Longo, Virginia Martínez, María Sanjurjo-Sáez, Luis A López-Fernández
Preventing severe irinotecan-induced adverse reactions would allow us to offer better treatment and improve patients' quality of life. Transporters, metabolizing enzymes, and genes involved in the folate pathway have been associated with irinotecan-induced toxicity. We analyzed 12 polymorphisms in UGT1A1, ABCB1, ABCG2, ABCC4, ABCC5, and MTHFR in 158 patients with metastatic colorectal cancer treated with irinotecan and studied the association with grade >2 adverse reactions (CTCAE). Among the most frequent ADRs, the SNPs rs1128503, rs2032582, and rs1045642 in ABCB1 and rs1801133 in MTHFR were associated with hematological toxicity and overall toxicity...
September 11, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30213563/liraglutide-and-cardiovascular-outcomes-in-a-real-world-type-2-diabetes-cohort
#9
Marco Mirani, Giuseppe Favacchio, Eliseo Serone, Giuseppe Lucisano, Maria Chiara Rossi, Cesare C Berra
In the last years, due to new regulatory guidelines requiring a stringent documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes, cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the knowledge about the safety profile of the new drugs, but they have intrinsic limits that make difficult their transferability to clinical practice. For this reason, real world evidence is considered an important complement to experimental data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the LEADER CVOT demonstrated superiority in reducing the risk of major CV events (MACEs) vs...
September 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30208338/serotonin-contribution-to-cardiac-valve-degeneration-new-insights-for-novel-therapies
#10
REVIEW
Estelle Ayme-Dietrich, Roland Lawson, Sylvia Da-Silva, Jean Philippe Mazzucotelli, Laurent Monassier
Heart valve disease (HVD) is a complex entity made by different pathological processes that ultimately lead to the abnormal structure and disorganization of extracellular matrix proteins resulting to dysfunction of the leaflets. At its final evolutionary step, treatments are limited to the percutaneous or surgical valve replacement, whatever the original cause of the degeneration. Understanding early molecular mechanisms that regulate valve interstitial cells remodeling and disease progression is challenging and could pave the way for future drugs aiming to prevent and/or reverse the process...
September 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30205140/treatment-duration-affects-cytoprotective-efficacy-of-positive-allosteric-modulation-of-%C3%AE-7-nachrs-after-focal-ischemia-in-rats
#11
Nikhil Gaidhani, Victor V Uteshev
To minimize irreversible brain injury after acute ischemic stroke (AIS), the time to treatment (i.e., treatment delay) should be minimized. However, thus far, all cytoprotective clinical trials have failed. Analysis of literature identified short treatment durations (≤72 h) as a common motif among completed cytoprotective clinical trials. Here, we argue that short cytoprotective regimens even if given early after AIS may only slow down the evolution of ischemic brain injury and fail to deliver sustained long-term solutions leading to relapses that may be misinterpreted for conceptual failure of cytoprotection...
September 8, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30196104/modulation-of-cellular-bioenergetics-by-co-releasing-molecules-and-no-donors-inhibits-the-interaction-of-cancer-cells-with-human-lung-microvascular-endothelial-cells
#12
Marta Stojak, Patrycja Kaczara, Roberto Motterlini, Stefan Chlopicki
Interactions between cancer cells and the endothelium play a crucial role during metastasis. Here we examined the effects of a carbon monoxide-releasing molecule (CORM-401) and a nitric oxide donor (PAPA NONOate) given alone or in combination on breast cancer cell adhesion and transmigration across the lung microvascular endothelium. We further explored whether the effects of CO and NO on cancer-endothelial cells interactions are linked with changes in cellular bioenergetics in breast cancer or endothelial cells...
September 6, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30196103/selective-serotonin-reuptake-inhibitors-affect-structure-function-and-metabolism-of-skeletal-muscle-a-systematic-review
#13
REVIEW
Diego Bulcão Visco, Raul Manhães-de-Castro, Wenicios Ferreira Chaves, Diego Cabral Lacerda, Sabrina da Conceição Pereira, Kelli Nogueira Ferraz-Pereira, Ana Elisa Toscano
Selective Serotonin Reuptake Inhibitors (SSRIs) may have side effects, such as stiffness, tremors and altered tonic activity, as well as an increased risk of developing insulin resistance and diabetes mellitus. However, little is known about the structural, functional and metabolic changes of skeletal muscle after administration of SSRIs. The aim of this systematic review was to explore and discuss the effects of SSRIs on skeletal muscle properties described in human and rodent studies. A systematic search of PUBMED, SCOPUS, and WEB OF SCIENCE was performed...
September 6, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30196102/resolving-neuroinflammation-the-therapeutic-potential-of-the-anti-malaria-drug-family-of-artemisinin
#14
REVIEW
Zhe Shi, Ying Chen, Cong Lu, Li-Ming Dong, Jing-Wei Lv, Qin-Hui Tuo, Li Qin, Shao-Wu Cheng, Lan-Lan Bu, Na Lin, Xiao-Xin Zhu, Duan-Fang Liao, Xin-Min Liu
Artemisinin (Qinghaosu) and its semi-synthetic derivatives have been demonstrated to alleviate neuroinflammatory response in the central nerve system (CNS). In this review, we summarized that artemisinins are capable to treat neuroinflammtion-related CNS diseases in both direct (via regulating inflammatory process in the CNS, exerting anti-oxidative stress and neuroprotective effect, and preventing Aβ accumulation) and indirect (via maintaining BBB integrity, suppressing systemic inflammation and alleviating intestinal inflammtion) manner...
September 6, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30189295/fenfluramine-induced-pvat-dependent-contraction-depends-on-norepinephrine-and-not-serotonin
#15
Ramya K Kumar, Emma S Darios, Robert Burnett, Janice M Thompson, Stephanie W Watts
Perivascular adipose tissue (PVAT) modulates vascular tone and altered PVAT function is observed in vascular diseases such as hypertension and atherosclerosis. We discovered that the PVAT surrounding rat thoracic aorta (RA) and the superior mesenteric artery (SMA) contain significant amounts of 5-hydroxytryptamine (5-HT). We hypothesized that the 5-HT contained within the PVAT is functional and vasoactive. Isolated tissue baths were used for isometric contractility studies and high performance liquid chromatography was used to quantitatively measure amines in the PVAT and release studies...
September 3, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30171902/neuronal-mechanisms-mediating-pathological-reward-related-behaviors-a-focus-on-silent-synapses-in-the-nucleus-accumbens
#16
REVIEW
Dillon S McDevitt, Nicholas M Graziane
The compulsive drive to seek drugs despite negative consequences relies heavily on drug-induced alterations that occur within the reward neurocircuit. These alterations include changes in neuromodulator and neurotransmitter systems that ultimately lock behaviors into an inflexible and permanent state. To provide clinicians with improved treatment options, researchers are trying to identify, as potential targets of therapeutic intervention, the neural mechanisms mediating an "addictive-like state"...
August 29, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30170190/therapeutic-implication-of-vascular-endothelial-growth-factor-receptor-1-vegfr-1-targeting-in-cancer-cells-and-tumor-microenvironment-by-competitive-and-non-competitive-inhibitors
#17
REVIEW
Pedro Miguel Lacal, Grazia Graziani
The vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF) ligands that is expressed in endothelial, myelomonocytic and tumor cells. VEGF-B and PlGF exclusively bind to VEGFR-1, whereas VEGF-A also binds to VEGFR-2. At variance with VEGFR-2, VEGFR-1 does not play a relevant role in physiological angiogenesis in the adult, while it is important in tumor-associated angiogenesis. VEGFR-1 and PlGF are expressed in a variety of tumors, promote invasiveness and contribute to resistance to anti-VEGF-A therapy...
August 28, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30170189/%C3%AE-9-tetrahydrocannabivarin-impairs-epithelial-calcium-transport-through-inhibition-of-trpv5-and-trpv6
#18
Annelies Janssens, Cristoforo Silvestri, Andrea Martella, Jo M Vanoevelen, Vincenzo Di Marzo, Thomas Voets
Compounds extracted from the cannabis plant, including the psychoactive Δ9 -tetrahydrocannabinol (THC) and related phytocannabinoids, evoke multiple diverse biological actions as ligands of the G protein-coupled cannabinoid receptors CB1 and CB2. In addition, there is increasing evidence that phytocannabinoids also have non-CB targets, including several ion channels of the transient receptor potential superfamily. We investigated the effects of six non-THC phytocannabinoids on the epithelial calcium channels TRPV5 and TRPV6, and found that one of them, Δ9 -tetrahydrocannabivarin (THCV), exerted a strong and concentration-dependent inhibitory effect on mammalian TRPV5 and TRPV6 and on the single zebrafish orthologue drTRPV5/6...
August 28, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30149054/novel-pharmacological-targets-for-calcific-aortic-valve-disease-prevention-and-treatments
#19
REVIEW
Veronika A Myasoedova, Alessio L Ravani, Beatrice Frigerio, Vincenza Valerio, Donato Moschetta, Paola Songia, Paolo Poggio
Calcific aortic valve disease (CAVD) is the most common valvular disorder in the elderly, with the incidence of 3% in general population of Western countries. The initial phase of CAVD is characterized by leaflet thickening and possible spotty calcification (i.e. aortic valve sclerosis (AVSc)), while advanced stages have leaflets structure degeneration (i.e. aortic valve stenosis (AS)). The pathological cellular and molecular mechanisms, involved in CAVD, are extracellular matrix degradation, aberrant matrix deposition, fibrosis, mineralization, inflammation, lipid accumulation, and neo-angiogenesis...
August 24, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30145328/immunomodulatory-effects-of-braf-and-mek-inhibitors-implications-for-melanoma-therapy
#20
REVIEW
Marvin Kuske, Dana Westphal, Rebekka Wehner, Marc Schmitz, Stefan Beissert, Christian Praetorius, Friedegund Meier
Targeted therapy with BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) provides rapid disease control with high response rates in patients with BRAF-mutant metastatic melanoma. However, the majority of patients develop resistance to therapy during the course of therapy. Immune checkpoint inhibitors show a slower onset of action with lower response rates, with responders showing sustained response. The combination of BRAFi/MEKi and immune checkpoint inhibitors combines the hope for a fast, reliable and lasting response to therapy...
August 23, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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