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Annals of Cardiac Anaesthesia 2021
Topics: Administration, Topical; Hemodynamics; Humans; Mammary Arteries; Papaverine; Stellate Ganglion
PubMed: 33938858
DOI: 10.4103/aca.ACA_171_20 -
Annals of Cardiac Anaesthesia 2021
Topics: Administration, Topical; Coronary Artery Bypass; Humans; Mammary Arteries; Papaverine; Stellate Ganglion
PubMed: 33938857
DOI: 10.4103/aca.ACA_118_20 -
Cancers Apr 2021Hypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting...
BACKGROUND
Hypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting mitochondrial oxidative metabolism is an emerging concept in translational cancer research aimed at reducing hypoxia. We have shown that the U.S. Food and Drug Administration (FDA)-approved drug papaverine and its novel derivative SMV-32 are potent mitochondrial complex I inhibitors.
METHODS
We used a dynamic in vivo luciferase reporter system, pODD-Luc, to evaluate the impact of pharmacological manipulation of mitochondrial metabolism on the levels of tumor hypoxia in transplanted mouse tumors. We also imaged canine patients with blood oxygen level-dependent (BOLD) MRI at baseline and one hour after a dose of 1 or 2 mg/kg papaverine.
RESULTS
We showed that the pharmacological suppression of mitochondrial oxygen consumption (OCR) in tumor-bearing mice increases tumor oxygenation, while the stimulation of mitochondrial OCR decreases tumor oxygenation. In parallel experiments in a small series of spontaneous canine sarcomas treated at The Ohio State University (OSU) Veterinary Medical Center, we observed a significant increase in BOLD signals indicative of an increase in tumor oxygenation of up to 10-50 mm HgO.
CONCLUSION
In both transplanted murine tumors and spontaneous canine tumors we found that decreasing mitochondrial metabolism can decrease tumor hypoxia, potentially offering a therapeutic advantage.
PubMed: 33916656
DOI: 10.3390/cancers13071696 -
Biomolecules & Therapeutics May 2021Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia...
Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons's disease, which is aggravated by systemic inflammation.
PubMed: 33911050
DOI: 10.4062/biomolther.2021.039 -
Frontiers in Pharmacology 2021The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal...
The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal relaxant effect and possible mechanism(s) of the essential oil of (TS Oil) in isolated guinea pig tracheal tissues. The essential oil was obtained from the fresh erial parts of , and its phyto-components were identified by GC-MS analysis. Guinea pig tracheal preparations were used for testing the tracheal relaxant effect of TS Oil with the determination of the mechanism(s) involved in this relaxation. GC-MS findings reveal that terpenes, fragrance constituents, saponins, and higher fatty acids are present in TS Oil. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 µM) and K (80 mM)-induced contractions in a pattern similar to that of dicyclomine. TS Oil, at 0.3 mg/ml, shifted parallel CCh-curves towards the right, followed by a non-parallel shift at higher concentration (1 mg/ml), thus suppressing maximum response in the same manner as produced by dicyclomine. Pretreatment of tissues with TS Oil (1 and 3 mg/ml) also produced a rightward shift of Ca concentration-response curves (CRCs) in the same manner as caused by verapamil. Further, TS Oil at low concentrations (0.3 and 1 mg/ml) shifted isoprenaline-induced inhibitory CRCs towards the left and increased cAMP levels in isolated tracheal homogenates similar to papaverine, a phosphodiesterase (PDE) inhibitor. In the antimicrobial assay performed by the agar well diffusion method, TS Oil was found most active against and where the zone of inhibition measured was 28 mm. Additionally, there was little difference between standard strains of gram-positive and gram-negative bacteria. However, methicillin-resistant (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm). From these results, it can be concluded that the essential oil of has the potential to produce antimicrobial effects while causing tracheal relaxation mediated possibly by anticholinergic effects, Ca channel blockade, and PDE inhibition whereas additional mechanism(s) cannot be ruled out.
PubMed: 33883992
DOI: 10.3389/fphar.2021.615228 -
Indian Journal of Urology : IJU :... 2021Drug-induced priapism is well known and papaverine is the most common drug known to cause priapism. Drotaverine, an analog of papaverine, is used extensively to treat...
Drug-induced priapism is well known and papaverine is the most common drug known to cause priapism. Drotaverine, an analog of papaverine, is used extensively to treat Colicky pain. We report the first case of drotaverine.induced priapism.
PubMed: 33850364
DOI: 10.4103/iju.IJU_240_20 -
Journal of Cosmetic Dermatology Oct 2021The incidence of hyaluronic acid (HA) embolism has increased markedly in recent years. HA embolism can lead to serious complications such as blindness, eye and eyelid...
BACKGROUND
The incidence of hyaluronic acid (HA) embolism has increased markedly in recent years. HA embolism can lead to serious complications such as blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment of HA embolism with intra-arterial thrombolytic therapy (IATT).
METHODS
In the present study, we enrolled 45 patients with decreased visual acuity, including 40 patients with symptoms of vision loss and eight patients with symptoms of intracranial embolism. The patients underwent emergency IATT via hyaluronidase and papaverine injections, followed by conventional sequential therapy.
RESULTS
In the 45 patients with symptoms of vision loss, 16 (36%) exhibited improvements in final visual acuity, even when the clinical application of the thrombolytic treatments was performed beyond the recommended window for optimal treatment. The facial skin necrosis of all patients was restored to near normal appearance. Notably, for eight patients with suspected symptoms of intracranial infarction we performed cerebral angiography and IATT, and in two patients obtained partial recanalization of the obstruction, the symptoms of heavy headache and binocular distension pain were improved in one patient with intracranial embolism after IATT treatment.
CONCLUSION
Our results indicate that IATT is feasible for patients with vision loss induced by HA embolism. IATT combined with conventional sequential therapy was beneficial in the recovery from other serious HA embolism complications. Nevertheless, the underlying pathophysiological mechanism needs to be clarified in future animal experiments.
Topics: Animals; Blindness; Dermal Fillers; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Thrombolytic Therapy
PubMed: 33825341
DOI: 10.1111/jocd.14111 -
Medicines (Basel, Switzerland) Mar 2021High mobility group box 1 (HMGB1)-receptor for advanced glycation endo-products (RAGE) axis serves as a key player in linking inflammation and carcinogenesis. Recently,...
High mobility group box 1 (HMGB1)-receptor for advanced glycation endo-products (RAGE) axis serves as a key player in linking inflammation and carcinogenesis. Recently, papaverine was revealed to suppress the HMGB1-RAGE inflammatory signaling pathway and cancer cell proliferation. Therefore, a dual suppressor targeting this axis is expected to become a new type of therapeutic agent to treat cancer. Papaverine 3D pharmacophore mimetic compounds were selected by the LigandScout software from our in-house, anti-cancer chemical library and assessed for their anti-inflammatory activities by a HMGB1-RAGE-mediated interleukin-6 production assay using macrophage-like RAW264.7 cells. Molecular-biological analyses, such as Western blotting, were performed to clarify the mechanism of action. A unique 6-methoxy-3-hydroxy-styrylchromone was found to possess potent anti-inflammatory and anti-cancer activities via the suppression of the HMGB1-RAGE-extracellular signal-regulated kinase 1/2 signaling pathway. Furthermore, the 3D pharmacophore-activity relationship analyses revealed that the hydroxyl group at the C4' position of the benzene ring in a 3-styryl moiety was significant in its dual suppressive effects. These findings indicated that this compound may provide a valuable scaffold for the development of a new type of anti-cancer drug possessing anti-inflammatory activity and as a tool for understanding the link between inflammation and carcinogenesis.
PubMed: 33805209
DOI: 10.3390/medicines8040017 -
Journal of Assisted Reproduction and... Jun 2021The aim of this study was to examine the ability and safety of papaverine supplementation for in vitro sperm motility enhancement. In addition, sperm motility...
PURPOSE
The aim of this study was to examine the ability and safety of papaverine supplementation for in vitro sperm motility enhancement. In addition, sperm motility enhancement of papaverine was compared to pentoxifylline and theophylline. The post-thaw spermatozoa were used as an asthenozoospermia model.
METHODS
Post thaw sperm suspensions were divided into two groups: papaverine (100 μmol/L) and control, and each was investigated in two subgroups of 30- and 60-min exposure times. Detailed motility parameters were detected using a computerized sperm motility analyzer. Acrosomal status, viability, apoptosis, and DNA fragmentation were evaluated by flow cytometry. Furthermore, the motility-enhancing capacity of papaverine, pentoxifylline, and theophylline was compared.
RESULTS
Cryopreservation impaired sperm parameters dramatically but no significant changes occurred in acrosomal status and apoptosis. Supplementation of papaverine enhanced motility parameters consistently at all exposure intervals, significantly. However, viability was lower at the 60th minute compared to the 30th minute (p=0.019). Papaverine did not alter any acrosomal or apoptotic markers at any time points. All of the compounds compared in this study increased the motility parameters, where theophylline supplementation provided significantly better improvement in total motility compared to papaverine and pentoxifylline.
CONCLUSION
Our results suggest that in vitro papaverine treatment for 30 min adequately improves motility of post-thaw sperm, without leading to acrosome reaction, DNA damage, and viability loss. Theophylline's potency on increasing the ratio of total motile spermatozoa was found significantly superior than the two tested compounds. Prospective clinical studies with embryo production, pregnancy, and live birth data should be undertaken.
Topics: Acrosome Reaction; Animals; Asthenozoospermia; Cryopreservation; Female; Fertilization in Vitro; Humans; Male; Papaverine; Pregnancy; Semen Preservation; Sperm Motility; Spermatozoa
PubMed: 33772411
DOI: 10.1007/s10815-021-02160-x -
Archives of Medical Science : AMS 2022Autologous saphenous vein (SV) and internal mammary artery (IMA) are used as bypass conduits during coronary artery bypass graft surgery. Vasospasm of the arterial and...
INTRODUCTION
Autologous saphenous vein (SV) and internal mammary artery (IMA) are used as bypass conduits during coronary artery bypass graft surgery. Vasospasm of the arterial and venous grafts may constitute a significant clinical problem. Pretreatment with a vasodilator drug of the graft or intraluminal injection before implantation may be used for spasm prophylaxis. This study was designed to assess the vasoactive effects and time-dependent changes of botulinum toxin A (BTX-A) and papaverine pretreatment on vasospasm of human SV and IMA grafts. Also, histomorphology of the vessels was assessed.
MATERIAL AND METHODS
SV and IMA segments were suspended in organ baths, and isometric contraction responses to 2 different concentrations of 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) were recorded after incubation with 2 different concentrations of BTX-A and papaverine at 2 time points (0 h and 2 h).
RESULTS
The results revealed the following: 1) incubation with BTX-A and papaverine relaxes both SV and IMA rings contracted with 5-HT and ET-1; 2) the duration of the relaxant effect of BTX-A lasts longer than papaverine; and 3) no apparent histomorphological changes were observed in the grafts under light microscopy.
CONCLUSIONS
This study demonstrates that in human SV and IMA grafts, pretreatment with both BTX-A and papaverine are safe and have a potent inhibitory effect depending on the vessel and vasoconstrictor agent. The long-lasting vasodilatory effect of BTX-A on vascular smooth muscle may provide promising results in the prevention of venous and arterial graft spasm.
PubMed: 36457963
DOI: 10.5114/aoms/110157