Analysis of Safety Concerns on Herbal Products with Assumed Phytoestrogenic Activity

Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of products with assumed phytoestrogenic activity is not fully understood. This study aimed to identify plant species with assumed phytoestrogenic activity, review existing literature on their use and safety, and critically evaluate adverse reaction (AR) reports of single-herb, multi-herb, and mixed-multiple products, as submitted to the Netherlands Pharmacovigilance Centre Lareb and to VigiBase of the World Health Organization (WHO). In the Lareb database, the most commonly reported plant species to cause ARs (total of 67 reports) were Actaea racemosa L. (black cohosh) (47.8%), Humulus lupulus L. (hops) (32.8%), and Glycine max (L.) Merr. (soybean) (22.4%). In the VigiBase database (total of 21,944 reports), the top three consisted of Glycine max (L.) Merr. (71.4%), Actaea racemosa L. (11.6%), and Vitex agnus-castus L. (chaste tree) (6.4%). In the scoping review (total of 73 articles), Actaea racemosa L. (30.1%), Glycine max (L.) Merr. (28.8%), and Trifolium pratense L. (13.7%) were the most frequently mentioned plant species. ARs were most frequently reported in the system organ classes "gastrointestinal disorders", "skin and subcutaneous tissue disorders", "reproductive system and breast disorders", and "general disorders and administration site conditions". Furthermore, from the scoping review, it appeared that the use of products with assumed phytoestrogenic activity was associated with postmenopausal bleeding. It was concluded that, while the potential benefits of products with assumed phytoestrogenic activity have been extensively pursued, the potential occurrence of ARs after using these products is less well understood. This study highlights the need for further investigation and careful monitoring of these products to better understand their effects and ensure the safety and well-being of individuals using them. </p

Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge-eating disorder

Binge-eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg–1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior

Electronic interactions in Dirac fluids visualized by nano-terahertz spacetime mapping

Ultraclean graphene at charge neutrality hosts a quantum critical Dirac fluid of interacting electrons and holes. Interactions profoundly affect the charge dynamics of graphene, which is encoded in the properties of its collective modes: surface plasmon polaritons (SPPs). The group velocity and lifetime of SPPs have a direct correspondence with the reactive and dissipative parts of the tera-Hertz (THz) conductivity of the Dirac fluid. We succeeded in tracking the propagation of SPPs over sub-micron distances at femto-second (fs) time scales. Our experiments uncovered prominent departures from the predictions of the conventional Fermi-liquid theory. The deviations are particularly strong when the densities of electrons and holes are approximately equal. Our imaging methodology can be used to probe the electromagnetics of quantum materials other than graphene in order to provide fs-scale diagnostics under near-equilibrium conditions

A Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93759/1/j.1600-6143.2012.04253.x.pd

Long-Lived Phonon Polaritons in Hyperbolic Materials

Natural hyperbolic materials with dielectric permittivities of opposite signs along different principal axes can confine long-wavelength electromagnetic waves down to the nanoscale, well below the diffraction limit. Confined electromagnetic waves coupled to phonons in hyperbolic dielectrics including hexagonal boron nitride (hBN) and α-MoO3 are referred to as hyperbolic phonon polaritons (HPPs). HPP dissipation at ambient conditions is substantial, and its fundamental limits remain unexplored. Here, we exploit cryogenic nanoinfrared imaging to investigate propagating HPPs in isotopically pure hBN and naturally abundant α-MoO3 crystals. Close to liquid-nitrogen temperatures, losses for HPPs in isotopic hBN drop significantly, resulting in propagation lengths in excess of 8 μm, with lifetimes exceeding 5 ps, thereby surpassing prior reports on such highly confined polaritonic modes. Our nanoscale, temperature-dependent imaging reveals the relevance of acoustic phonons in HPP damping and will be instrumental in mitigating such losses for miniaturized mid-infrared technologies operating at liquid-nitrogen temperatures.Research at Columbia is supported by Vannevar Bush Faculty Fellowship ONR-VB: N00014-19-1-2630. We thank A. Sternbach and S. Zhang for helpful discussions. Exfoliation and transfer of hBN onto desired substrates and electron beam lithography of gold disks were performed by J.T.M. and supported by the National Science Foundation (DMR1904793). Additional structure fabrication was supported by the Center on Precision-Assembled Quantum Materials, funded through the U.S. National Science Foundation (NSF) Materials Research Science and Engineering Centers (award no. DMR-2011738). Initial simulations and experimental design from Vanderbilt were provided by J.D.C. in collaboration with the Columbia team (D.N.B. and G.N.) and was supported by the Office of Naval Research (N00014-18-1-2107). The hBN phonon band structure calculation was performed by R.C. and L.A. and supported by the Spanish MINECO/FEDER grant (MAT2015-71035- R). Cryogenics nano-optics experiments at Columbia were solely supported as part of Programmable Quantum Materials, an Energy Frontier Research Center funded by the U.S. Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES), under award no. DE-SC0019443. D.N.B is the Gordon and Betty Moore Foundation’s EPiQS Initiative Investigator no. 9455.Peer reviewe

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Nuclear factor kappa B activation by muscarinic receptors in astroglial cells: Effect of ethanol

Activation of muscarinic receptors leads to proliferation of astroglial cells and this effect is inhibited by ethanol. Among the intracellular pathways involved in the mitogenic action of muscarinic agonists, activation of the atypical protein kinase Czeta (PKC zeta) appears to be of most importance, and is also affected by low ethanol concentrations. PKC has been reported to activate nuclear factor kappaB (NF-kappaB), a transcription factor that has been shown to play an important role in cell proliferation. The aim of this study was, therefore, to determine whether muscarinic receptors would activate NF-kappaB in astroglial cells, whether such activation would play a role in the mitogenic action of muscarinic agonists, and whether it would represent a possible target for ethanol. Carbachol activated NF-kappaB in human 1321N1 astrocytoma cells, as evidenced by translocation of the p65 subunit of NF-kappaB to the nucleus, phosphorylation and degradation of IkappaBalpha in the cytosol, and increase NF-kappaB binding to DNA. Carbachol also induced translocation of p65 to the nucleus in primary rat astrocytes. Carbachol-induced NF-kappaB activation was mediated by the M3 subtype of muscarinic receptors and appeared to involve Ca2+ mobilization and activation of PKC E and PKC, but not P13-kinase and mitogen-activated protein kinase. The NF-kappaB peptide inhibitor SN50, but not the inactive peptide SN50M, strongly inhibited carbachol-induced astrocytoma cells proliferation and p65 translocation to the nucleus. Increased DNA synthesis was also antagonized by the IkappaBalpha kinase inhibitor BAY 11-7082. Ethanol (25-100 mM) inhibited the translocation of p65 and the binding of NF-kappaB to DNA in both 1321 NI astrocytoma cells and primary rat cortical astrocytes. Together, these results suggest that activation of NF-kappaB by muscarinic receptors in astroglial cells is important for carbachol-induced DNA synthesis and that ethanol-mediated inhibition of cell proliferation may be due in part to inhibition of NF-kappaB activation. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved

Nuclear factor κB activation by muscarinic receptors in astroglial cells: Effect of ethanol

Activation of muscarinic receptors leads to proliferation of astroglial cells and this effect is inhibited by ethanol. Among the intracellular pathways involved in the mitogenic action of muscarinic agonists, activation of the atypical protein kinase C ζ (PKC ζ) appears to be of most importance, and is also affected by low ethanol concentrations. PKC ζ has been reported to activate nuclear factor κB (NF-κB), a transcription factor that has been shown to play an important role in cell proliferation. The aim of this study was, therefore, to determine whether muscarinic receptors would activate NF-κB in astroglial cells, whether such activation would play a role in the mitogenic action of muscarinic agonists, and whether it would represent a possible target for ethanol. Carbachol activated NF-κB in human 1321N1 astrocytoma cells, as evidenced by translocation of the p65 subunit of NF-κB to the nucleus, phosphorylation and degradation of IκBα in the cytosol, and increase NF-κB binding to DNA. Carbachol also induced translocation of p65 to the nucleus in primary rat astrocytes. Carbachol-induced NF-κB activation was mediated by the M3 subtype of muscarinic receptors and appeared to involve Ca2+ mobilization and activation of PKC ε and PKC ζ, but not PI3-kinase and mitogen-activated protein kinase. The NF-κB peptide inhibitor SN50, but not the inactive peptide SN50M, strongly inhibited carbachol-induced astrocytoma cells proliferation and p65 translocation to the nucleus. Increased DNA synthesis was also antagonized by the IκBα kinase inhibitor BAY 11-7082. Ethanol (25-100 mM) inhibited the translocation of p65 and the binding of NF-κB to DNA in both 1321N1 astrocytoma cells and primary rat cortical astrocytes. Together, these results suggest that activation of NF-κB by muscarinic receptors in astroglial cells is important for carbachol-induced DNA synthesis and that ethanol-mediated inhibition of cell proliferation may be due in part to inhibition of NF-κB activation. © 2003 IBRO. Published by Elsevier Ltd. All rights reserved

Potential role of NF-kB in muscarinic receptor-induced astroglial cell proliferation.

These results show that in human astrocytoma cells carbachol activates NF-kB and that this activation may be involved in the mitogenic action of acetylcholine in these cells