Inhibition of Lysophosphatidate Signaling by Lidocaine and Bupivacaine 

1997 ◽  
Vol 86 (5) ◽  
pp. 1112-1119 ◽  
Author(s):  
Gregor W. Nietgen ◽  
Carrie K. Chan ◽  
Marcel E. Durieux
Keyword(s):  
Wound Healing ◽  
Local Anesthetics ◽  
Xenopus Oocytes ◽  
Inhibitory Concentration ◽  
Angiotensin Ii Receptor ◽  
Activated Platelets ◽  
Surgical Wounds ◽  
Smooth Muscle Proliferation ◽  
Site Of Action ◽  
G Protein Coupled

Background Lidocaine and bupivacaine impair wound healing, but the mechanism of this side effect has not been determined. The phospholipid messenger lysophosphatidate is released from activated platelets and induces fibroblast and smooth muscle proliferation. Because it may play a role in wound healing, the authors studied the effects of local anesthetics on lysophosphatidate signaling in Xenopus oocytes. Methods Defolliculated Xenopus oocytes expressing endogenous G protein-coupled lysophosphatidate receptors were voltage clamped and studied in the presence or absence of lidocaine or bupivacaine. Lysophosphatidate-induced Ca(2+)-activated Cl- currents (IC1(Ca)) were measured. To determine the site of action of the local anesthetics on the signaling pathway, the authors studied 1) the effects of local anesthetics on signaling induced by intracellular injection of the second messenger inositoltrisphosphate, and 2) the effects of local anesthetics on functioning of recombinantly expressed angiotensin II receptor signaling through the same pathways as the lysophosphatidate receptor. Results Lysophosphatidate signaling was inhibited in the presence of local anesthetics. The half maximal inhibitory concentration (IC50S) for lidocaine and bupivacaine were 29.6 mM and 4.7 mM, respectively. Neither responses induced by inositoltrisphosphate injection nor angiotensin signaling were influenced by local anesthetics. Conclusions Lysophosphatidate signaling is inhibited by the extracellular application of lidocaine or bupivacaine. In contrast, inositoltrisphosphate or angiotensin signaling was not affected by local anesthetics. Therefore local anesthetics have a specific, extracellular effect on lysophosphatidate receptor functioning. As the local anesthetic concentrations used were similar to those observed after injection around surgical wounds, LP inhibition may play a role in the observed detrimental effects of local anesthetics on wound healing.

scholarly journals MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection

2019 ◽  
Vol 5 (1) ◽  
pp. eaav0216 ◽  
Author(s):  
Mohammad Arifuzzaman ◽  
Yuvon R. Mobley ◽  
Hae Woong Choi ◽  
Pradeep Bist ◽  
Cristina A. Salinas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wound Healing ◽  
Dendritic Cells ◽  
Mast Cells ◽  
Connective Tissue ◽  
Selective Activation ◽  
Adaptive Immune ◽  
Antigen Presenting ◽  
G Protein Coupled ◽  
Draining Lymph Nodes

Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, a peptide MC activator (MCA), enhances clearance ofStaphylococcus aureusfrom infected mouse skins and accelerates healing of dermonecrotic lesions. Mastoparan functions by activating connective tissue MCs (CTMCs) via the MRGPRX2 (Mas-related G protein-coupled receptor member X2) receptor. Peripheral CTMC activation, in turn, enhances recruitment of bacteria-clearing neutrophils and wound-healing CD301b+dendritic cells. Consistent with MCs playing a master coordinating role, MC activation also augmented migration of various antigen-presenting dendritic cells to draining lymph nodes, leading to stronger protection against a second infection challenge. MCAs therefore orchestrate both the innate and adaptive immune arms, which could potentially be applied to combat peripheral infections by a broad range of pathogens.

Platelet-Rich Plasma: Optimal Use in Surgical Wounds

2021 ◽  
Vol 33 (6) ◽  
pp. 219-221
Author(s):  
Laura Bolton
Keyword(s):  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Foot And Ankle ◽  
Activated Platelets ◽  
Surgical Wounds ◽  
Ankle Surgery ◽  
Surgical Incisions ◽  
Wound Pain ◽  
Acute Wound ◽  
Meta Analyses

Activated platelets release a rich broth of growth factors involved in wound healing. One way to deliver activated platelets to wounds is in the form of platelet-rich plasma (PRP) harvested by centrifuging the patient’s venous blood after activating the platelets with collagen or calcium chloride and/or autologous thrombin, then delicately removing the supernatant, called platelet-poor plasma (PPP). Platelet-rich plasma is usually injected into the lesion and/or applied topically, then sealed in or over the wound using a moisture-retentive dressing. Platelet-rich plasma (often with PPP) has been applied at different times, depths, and frequencies to chronic and acute wounds using various PRP doses and vehicles to achieve widely differing results. Meta-analyses have reported that PRP improved healing rates of open diabetic foot ulcers and venous ulcers1,2 and may reduce pain and surgical site infection (SSI) incidence in open and closed acute surgical wounds. However, inconsistency in study methods and outcome measures limited consistency of pain and SSI results.1 No consistent effect on healing or deep SSI rates was reported as a result of adding 1 intraoperative dose of PRP in the surgical site before closing elective foot and ankle surgery incisions of 250 patients as compared with 250 similar patients receiving the same procedure without PRP.3 After decades of research, ideal parameters of PRP delivery and use on each type of wound remain unclear for improving SSI, acute wound pain, and healing outcomes. This installment of the Evidence Corner reviews 2 surgical studies that may provide clues about optimal PRP use. One triple-blind randomized clinical trial (RCT) focused on irrigation of freshly closed carpal ligament surgical incisions with PRP as compared with PPP.4 Another non-blind RCT explored the effect of injecting PRP into open pilonidal sinus excisions 4 days and 12 days after surgery.5

Curcumin Loading on Alginate Nano-Micelle for Anti-Infection and Colonic Wound Healing

2021 ◽  
Vol 17 (6) ◽  
pp. 1160-1169
Author(s):  
Zhiyong Zhang ◽  
Xin Zhang
Keyword(s):  
Wound Healing ◽  
Inhibitory Concentration ◽  
Antibacterial Effects ◽  
Negative Effects ◽  
Collagen Concentration ◽  
Mtt Method ◽  
Physicochemical Studies ◽  
Colonic Wound ◽  
Healing Of Wounds ◽  
Hematoxylin And Eosin

Despite the antibacterial, and anti-inflammatory properties of curcumin (C), its effect on wound healing, especially in the colorectal, is ambiguous. Moreover, due to the hydrophobic properties of C, its use is limited. Therefore, to reduce the bioavailability challenge and improve the transfer to colon area, we designed a C-alginate-based nano-micelle (C-A-NM). After fabrication of C-A-NM (55.5 nm) and physicochemical studies with the TEM, DLS and XRD, the C release rate based on gastrointestinal state was evaluated. Furthermore, the effects of C-A-NM on the survival of HCT-8 cells at 24 and 48 hours by MTT method and its antibacterial effects were also evaluated. To explain the effects of wound healing in rats, in addition to colonoscopy on the 14th-day, the repaired tissue on the 7th and 14th days were examined by Hematoxylin and Eosin method. Also, for evaluating wound healing in the colon, the protein/collagen concentration, and TGFβ1/NFκB gene expression were determined. The results of C cumulative release showed that the NM allows the drug to be loaded in the colon in a favourable manner. Also, the toxicity outputs revealed that C-A-NM at a concentration of 7.5 mg had no negative effects on cell viability. While the activity of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, bacteria decreased based on the minimum inhibitory concentration value with 153, 245 and 319 (μg/mL). The use of C-A-NM not only increases protein and collagen in damaged sites, but also increases TGFβ1 expression in contrast to NFκB. Based on these results, and the results of histopathology and colonoscopy, it was found that C-A-NM accelerates the healing of damaged areas. Overall, the results show that the use of C-A-NM can significantly accelerate the healing of wounds in the gastrointestinal tract based on collagen induction and reduced bacterial activity.

scholarly journals REVIEW ON ANTIMICROBIAL AND ANTI ACNE POTENTIAL OF KAEMPFERIA SPP.

2021 ◽  
Vol 21 (no 1) ◽  
Author(s):  
Subhash Chandra Mishra ◽  
Shailesh Jain
Keyword(s):  
Drug Delivery ◽  
Health Care ◽  
Minimum Inhibitory Concentration ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Age Groups ◽  
Chebulagic Acid ◽  
Site Of Action ◽  
Novel Drug ◽  
Aromatic Oils

Acne is a general but somber skin disease, which affects approximately 80% adolescents and young adults in 11–30 age groups. 42.5 % of men and 50.9 % of women keep onto suffer from this disease into their twenties. Bacterial resistance is now at the alarming stage due to the irrational use of antibiotics. Hence, search for new lead molecule/bioactive and rational delivery of the existing drug (for better therapeutic effect) to the site of action is the need of the hour. Plants and plant-derived products have been an integral part of health care system since time immemorial. Therefore, plants that are currently used for the treatment of acne and those with a high potential are summarized in the present review. Most active plant extracts, namely, P. granatum, M. alba, A. anomala, and M. aquifolium exhibit minimum inhibitory concentration (MIC) in the range of 4–50 µg/mL against P. acnes, while aromatic oils of C. obovoides, C. natsudaidai, C. japonica, and C. nardus possess MICs 0.005–0.6 ?L/mL and phytomolecules such as rhodomyrtone, pulsaquinone, hydropulsaquinone, honokiol, magnolol, xanthohumollupulones, chebulagic acid and rhinacanthin-C show MIC in the range of 0.5–12.5 ?g/mL. Novel drug delivery tant plant leads in the treatment of acne have also been discussed.

Immunoglobulin G of systemic sclerosis patients programs a pro-inflammatory and profibrotic phenotype in monocyte-like THP-1 cells

Rheumatology ◽  
2020 ◽  
Author(s):  
Sripriya Murthy ◽  
Melanie Wannick ◽  
Georgios Eleftheriadis ◽  
Antje Müller ◽  
Jiao Luo ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Antagonistic Activity ◽  
G Protein Coupled Receptors ◽  
Endothelin Receptor ◽  
Angiotensin Ii Receptor ◽  
Monocytic Cells ◽  
Endothelin Receptor A ◽  
The Individual ◽  
G Protein Coupled ◽  
Individual Donor

Abstract Objectives Functional IgG autoantibodies against diverse G protein-coupled receptors, i.e. antibodies with agonistic or antagonistic activity at these receptors, are abundant in human serum. Their levels are altered in patients with SSc, and autoantibodies against angiotensin II receptor 1 (ATR1) and endothelin receptor A (ETA) have been suggested to drive SSc by inducing the chemokines CXCL8 and CCL18 in the blood. The objective of our study is to profile the effect of IgG in SSc (SSc-IgG) on the production of soluble mediators in monocytic cells. Methods Monocyte-like THP-1 cells were stimulated with SSc-IgG and their secretome was analysed. Furthermore, the significance of major pro-inflammatory pathways for the induction of CXCL8 and CCL18 in response to SSc-IgG was assessed by a pharmacological approach. Results Stimulation with SSc-IgG significantly alters the secretome of THP-1 cells towards a general pro-inflammatory and profibrotic phenotype, which includes an increase of CCL18 and CXCL8. The consequent expression profiles vary depending on the individual donor of the SSc-IgG. CCL18 and CXCL8 expression is thus regulated differentially, with AP-1 driving the induction of both CCL18 and CXCL8 and the TAK/IKK-β/NF-κB pathway and ERK1/2 driving that of CXCL8. Conclusions Our results suggest that SSc-IgG contributes to the generation of the pro-inflammatory/profibrotic tissue milieu characteristic of SSc by its induction of a respective phenotype in monocytes. Furthermore, our results highlight AP-1 as a critical regulator of gene transcription of CCL18 in monocytic cells and as a promising pharmacological therapeutic target for the treatment of SSc.

scholarly journals Blockade by local anesthetics of the potassium current induced by NIP-121, a novel potassium channel opener, in Xenopus oocytes.

1994 ◽  
Vol 64 ◽  
pp. 302
Author(s):  
Ikuo Yoneda ◽  
Hidenari Sakuta ◽  
Koichi Okamoto ◽  
Yasuhiro Watanabe
Keyword(s):  
Potassium Channel ◽  
Local Anesthetics ◽  
Potassium Current ◽  
Xenopus Oocytes ◽  
Potassium Channel Opener ◽  
Channel Opener

Inhibitory Effect of Glucocorticoids on Human-cloned 5-hydroxytryptamine3AReceptor Expressed in Xenopus  Oocytes

2004 ◽  
Vol 101 (3) ◽  
pp. 660-665 ◽  
Author(s):  
Takahiro Suzuki ◽  
Masahiro Sugimoto ◽  
Hideki Koyama ◽  
Takashi Mashimo ◽  
Ichiro Uchida
Keyword(s):  
Xenopus Oocytes ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Combined Effect ◽  
Induced Current ◽  
Direct Effects ◽  
Receptor Antagonists ◽  
Electrode Voltage ◽  
Direct Inhibitory Effect ◽  
Voltage Clamping

Background Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes. Methods Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current. Results Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 microm 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 microm. Methylprednisolone inhibited 2 microm 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor. Conclusion The glucocorticoids had a direct inhibitory effect on 5-HT3 receptors. The combined effect of glucocorticoids and the 5-HT3 receptor antagonists seems additive.

Effects of local anesthetics and related drugs on endogenous glibenclamide-sensitive K+ channels in Xenopus oocytes

1993 ◽  
Vol 247 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Ikuo Yoneda ◽  
Hidenari Sakuta ◽  
Koichi Okamoto ◽  
Yasuhiro Watanabe
Keyword(s):  
Local Anesthetics ◽  
Xenopus Oocytes ◽  
K Channels

SYNERGISTIC INHIBITION OF LYSOPHOSPHATIDATE SIGNALING IN XENOPUS OOCYTES BY CHARGED AND UNCHARGED LOCAL ANESTHETICS

1999 ◽  
Vol 88 (Supplement) ◽  
pp. 389S
Author(s):  
L.M. Sullivan ◽  
C.W. Honemann ◽  
J.A.M. Arledge ◽  
M.E. Durieux
Keyword(s):  
Local Anesthetics ◽  
Xenopus Oocytes ◽  
Synergistic Inhibition

4-Aminopyridine block of the noninactivating cloned K+ channel Kv1.5 expressed in Xenopus oocytes

1995 ◽  
Vol 269 (2) ◽  
pp. H556-H564 ◽  
Author(s):  
T. Yamane ◽  
T. Furukawa ◽  
M. Hiraoka
Keyword(s):  
Xenopus Oocytes ◽  
Inhibitory Concentration ◽  
External Solution ◽  
K Channel ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
External Application ◽  
Charged Form ◽  
Cytoplasmic Side ◽  
Voltage Clamp Method

The blocking action of 4-aminopyridine (4-AP) on the cloned K+ channel Kv1.5 expressed in Xenopus oocytes was studied using the two-microelectrode voltage-clamp method. Application of 4-AP to the bath solution reversibly suppressed the expressed current in a voltage- and concentration-dependent manner decreasing with membrane depolarization and with a half-maximal inhibitory concentration of 0.14 mM (at +40 mV). Both block and unblock occurred mainly during a depolarization when channels were activated. With successive depolarizations, 4-AP decreased not only the peak amplitudes of the current in successive pulses, but also the current during a depolarization. Upon washout of 4-AP, the current recovered with successive depolarizations, whereas no recovery of the current was noted in the absence of depolarizations. The extent of block markedly increased with alkalization of the external solution and decreased with acidification. External application of 4-amino-pyridine methiodide, a charged form of a quaternary 4-AP derivative, did not affect the current, but internal application markedly suppressed the current, indicating the drug gained access to the channel from the cytoplasmic side. These data suggest that 4-AP crosses the membrane in its uncharged form and acts from inside of the cell in its charged form, resulting in block of the channels with higher affinity to the open state.

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