Anticonvulsant activity of some vanilloid receptor agonists

Background: Vanilloid receptors 1 (VR 1), a group of transient receptor potential channels family was cloned in 1997. They were found to be a potential target for treatment of different acute and chronic pain disorder. Recently these receptors were reported to be involved in several  pathological conditions.Objectives: The present study aimed to investigate the potential  anticonvulsant activity of five vanilloidal agonists (capsaicin, nonivamide, zingerone, dehydrozingerone and 6-gingerol).Methods: Experimental animal model of pentylenetetrazole (PTZ) induced seizure was used to investigate the potential anticonvulsant activity of capsaicin, nonivamide, zingerone, dehydrozingerone and 6-gingerol.Results: The data obtained showed that, all tested compounds (capsaicin, nonivamide, zingerone, dehydrozingerone and 6-gingerol) possess dose dependant anticonvulsant activity.Conclusion: The five vanilloidal agonists; capsaicin, nonivamide,  zingerone, dehydrozingerone and 6-gingerol exhibit anticonvulsant activity and may find clinical applications.Key words: Anticonvulsant, vanilloid receptor agonists and  pentylenetetrazol

Anticonvulsant Activity of Capsicum Annum (Red Pepper) Fruit Extract using Pentylentetrazole and Maximum Electroshock Induced Seizure Tests in Rats

Background: Epilepsy is a disorder of brain function characterized by periodic and unpredictable occurrence of seizures that refers to as a transient alteration of behavior due to disordered, synchronous and rhythmic firing of populations of brain neurons. Modern drug therapy of epilepsy is complicated by side effects and inability to control seizures in some patients.Objectives: The present study was conducted to test the anticonvulsant activity of Capsicum annum fruit extract in rat models.Materials and Methods: The methanolic extract of Capsicum annum fruit was tested for its potential anticonvulsant activity using pentylentetrazole (PTZ) and maximum electroshock (MES) induced seizure models in rats. The simple activity meter was used to determine the sedative activity of Capsicum annum fruit extract. Thereafter, the protective index was calculated.Results: Results obtained showed that the extract at concentrations of 5, 9, 10, 20 and 40 mg/kg produced dose dependent anticonvulsant activity. Capsicum annum (40 mg/kg, i.p.) caused 100% protection from seizure induced by PTZ and sedation in 50% of rats (TD50). Fifty percent anticonvulsant activity was produced by 9mg/kg Capsicum annum. Moreover, the protective index was calculated to be more than four. When tested on seizure induced by MES, Capsicum annum extract at doses of 10, 20 and 40 mg\kg showed no seizure protection.Conclusion: It could be concluded that Capsicum annum fruit could be a source for potential antiepileptic agent(s). Further studies are needed to determine the active constituents responsible for the anticonvulsant activity as well as to elucidate their mechanism(s) of action.Key words: Epilepsy, Pentylenetetrazole, electroshock, Capsicum annum, Sudan

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy

Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin

Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand–receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour

Preparation, characterization and antibacterial effects of eco-friendly gold nanorods

Purpose: To synthesize and characterize eco-friendly gold nanorods (Au-NRs) and to assess their effects against two bacterial strains.Methods: Synthesis of eco-friendly gold nanorods was done from an aqueous solution of chloroauric acid and cetyltrimethylammonium bromide by mixing Olea europaea fruit and Acacia nilotica husk extracts with the latter as a reducing agent. The synthesis was monitored by ultraviolet–visible (UV) spectrophotmetry and a zetasizer, while the morphology of the resulting nanorods was assessed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) coupled with an energy-dispersive spectrophotometer (EDS). The effect of the prepared eco-nanorods on growth of Escherichia coli and Staphylococcus aureus bacteria were investigated by agar diffusion method.Results: The synthesized Au-NRs were mostly rod-shaped, with mean size of 96 nm. They exhibited a potent antibacterial activity against Gram-positive and  Gram-negative microorganisms (Escherichia coli and Staphylococcus aureus).Conclusion: The findings suggest that the nanoformulation of the biomaterial mix of Olea europaea fruit and Acacia nilotica husk extracts is a cost-effective, eco-friendly, and non-toxic synthesis of Au- NRs which has therpeautic potential.Keywords: Olea europaea, Acacia nilotica, Gold nanorods, Eco-friendly synthesis, Gram-positive and Gram-negative microorganism

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-β, TGF-β1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-β induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-β1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe