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EClinicalMedicine Sep 2021Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are...
BACKGROUND
Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear.
METHODS
The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742.
FINDINGS
Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control.
INTERPRETATION
The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin.
FUNDING
none.
PubMed: 34611615
DOI: 10.1016/j.eclinm.2021.101080 -
International Journal of Molecular... Sep 2021The paucity of currently available therapies for glioblastoma multiforme requires novel approaches to the treatment of this brain tumour. Disrupting cyclic...
The paucity of currently available therapies for glioblastoma multiforme requires novel approaches to the treatment of this brain tumour. Disrupting cyclic nucleotide-signalling through phosphodiesterase (PDE) inhibition may be a promising way of suppressing glioblastoma growth. Here, we examined the effects of 28 PDE inhibitors, covering all the major PDE classes, on the proliferation of the human U87MG, A172 and T98G glioblastoma cells. The PDE10A inhibitors PF-2545920, PQ10 and papaverine, the PDE3/4 inhibitor trequinsin and the putative PDE5 inhibitor MY-5445 potently decreased glioblastoma cell proliferation. The synergistic suppression of glioblastoma cell proliferation was achieved by combining PF-2545920 and MY-5445. Furthermore, a co-incubation with drugs that block the activity of the multidrug resistance-associated protein 1 (MRP1) augmented these effects. In particular, a combination comprising the MRP1 inhibitor reversan, PF-2545920 and MY-5445, all at low micromolar concentrations, afforded nearly complete inhibition of glioblastoma cell growth. Thus, the potent suppression of glioblastoma cell viability may be achieved by combining MRP1 inhibitors with PDE inhibitors at a lower toxicity than that of the standard chemotherapeutic agents, thereby providing a new combination therapy for this challenging malignancy.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclic AMP; Cyclic GMP; Drug Synergism; Glioblastoma; Humans; Multidrug Resistance-Associated Proteins; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Pyrazoles; Quinolines
PubMed: 34575827
DOI: 10.3390/ijms22189665 -
International Heart Journal Sep 2021Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is... (Observational Study)
Observational Study
Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms, 424 ± 41 ms, and 483 ± 54 ms, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.
Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Case-Control Studies; Coronary Angiography; Coronary Stenosis; Drug Therapy, Combination; Electrocardiography; Female; Fractional Flow Reserve, Myocardial; Hemodynamics; Humans; Hyperemia; Incidence; Long QT Syndrome; Male; Middle Aged; Nicorandil; Papaverine; Retrospective Studies; Safety; Tachycardia, Ventricular; Treatment Outcome; Vasodilator Agents
PubMed: 34544970
DOI: 10.1536/ihj.21-010 -
BMC Research Notes Sep 2021Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In...
OBJECTIVE
Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In this study, both species were evaluated for their alkaloid content and antimicrobial activities.
RESULTS
Alkaloids were extracted and isolated by preparative thin-layer chromatography (TLC). Identification was carried out by comparing spectral data (UV and H-NMR) and TLC Rf values with those of authentic samples. Two alkaloids, proapaorphine-type mecambrine and aporphine-type roemerine were isolated from P. decaisnei. Two benzylisoquinoline type alkaloids papaverine (major alkaloid) and palaudine as well as aporphine-type N-methylasimilobine have been obtained in P. glaucum. Both P. glaucum and P. decaisnei extracts revealed strong antimicrobial activity on Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212. Collectively these results indicate that P. glaucum and P. decaisnei are promising sources of alkaloids that could further be investigated for medicinal purposes.
Topics: Alkaloids; Anti-Infective Agents; Chromatography, Thin Layer; Papaver; Plant Extracts
PubMed: 34496958
DOI: 10.1186/s13104-021-05762-x -
F1000Research 2021Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral...
Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.
Topics: Anesthesia, General; Endovascular Procedures; Humans; Retrospective Studies; Treatment Outcome; United States; Vasodilator Agents; Vasospasm, Intracranial
PubMed: 34394915
DOI: 10.12688/f1000research.52324.2 -
Sexual Medicine Oct 2021The use of current available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been...
INTRODUCTION
The use of current available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been used as a new tool in medicine to improve these limitations and new medications potentially to alleviate and cure ED.
AIM
To review the currently literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and to identify gaps for future research.
METHODS
A comprehensive literature review was conducted via Google Scholar, Science Direct, and PubMed on English publications using different keywords such as "erectile dysfunction", "emerging treatments", "nanotechnology", and "herbal medicine". The retrieved papers were organized into groups according to the sections covered in this review paper.
MAIN OUTCOMES MEASURES
We reviewed novel ED treatments such as nanotechnological phosphodiesterase inhibitors, papaverine hydrochloride, sialorphin, adipose tissue-derived stem cells, sonic hedgehog, and herbal medicine.
RESULTS
Numerous preclinical studies have addressed novel phosphodiesterase 5 inhibitors nanoparticle, and their recent delivery systems. Nitric oxide, sialorphin, sonic hedgehog, and herbal medicine loaded nanoparticles and nano adipose tissue-derived stem cells as a potential new treatment for ED. In addition, papaverine-containing nanoparticles have been reported. A limited number of randomized clinical studies have determined the mechanism of these treatments.
CONCLUSION
A literature review on the application of nanotechnology in ED therapy was successfully conducted. New nano medications are promising to treat ED. However, further studies are warranted to further assess their efficacy and safety. Masuku NP, Unuofin JO, Lebelo SL. Advances in Nanoparticle Delivery System for Erectile Dysfunction: An Updated Review. Sex Med 2021;9:100420.
PubMed: 34388420
DOI: 10.1016/j.esxm.2021.100420 -
Foods (Basel, Switzerland) Jul 2021In recent years, health authorities have become increasingly concerned about preventing consumer exposure to opium alkaloids present in L. poppy seeds. In this study, a...
Mesostructured Silica-Coated Magnetic Nanoparticles to Extract Six Opium Alkaloids in Poppy Seeds Prior to Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Analysis.
In recent years, health authorities have become increasingly concerned about preventing consumer exposure to opium alkaloids present in L. poppy seeds. In this study, a simple, rapid and efficient method has been optimised to determine all main opioids in poppy seeds (morphine, codeine, thebaine, papaverine, noscapine and oripavine) by UHPLC-QqQ-MS/MS. For this purpose, solid-liquid extraction (SLE) of samples was optimised and six magnetic adsorbent materials with a core of FeO coated with amorphous and mesostructured silica, both functionalised with octadecyl-silane or octyl-silane were characterised and evaluated for magnetic solid-phase extraction (MSPE). The material with the best results was non-functionalised mesostructured silica and, with it, the MSPE procedure was optimised. This method was validated and used to quantify six opioids in 14 edible seed samples (eleven poppy seeds and three seed mixes). Considerable amounts were found (1.5-249.0 mg/kg morphine, <0.2 µg/kg-45.8 mg/kg codeine, <2.4 µg/kg-136.2 mg/kg thebaine, <0.2 µg/kg-27.1 mg/kg papaverine, <0.2 µg/kg-108.7 mg/kg noscapine and <240 µg/kg-33.4 mg/kg oripavine), exceeding maximum limits established in some EU countries and the reference level of morphine in the EU. Furthermore, in some commercial samples for human consumption, inadequate labelling was found because significant amounts of alkaloids were detected even though L. seeds were declared on the product label.
PubMed: 34359458
DOI: 10.3390/foods10071587 -
International Journal of Molecular... Jul 2021Despite the obvious benefits of using ureteral stents to drain the ureters, there is also a risk of complications from 80-90%. The presence of a foreign body in the...
Despite the obvious benefits of using ureteral stents to drain the ureters, there is also a risk of complications from 80-90%. The presence of a foreign body in the human body causes disturbances in its proper functioning. It can lead to biofilm formation on the stent surface, which may favor the development of urinary tract infections or the formation of encrustation, as well as stent fragmentation, complicating its subsequent removal. In this work, the effect of the polymeric coating containing the active substance-papaverine hydrochloride on the functional properties of ureteral stents significant for clinical practice were assessed. Methods: The most commonly clinically used polyurethane ureteral Double-J stent was selected for the study. Using the dip-coating method, the surface of the stent was coated with a poly(D,L-lactide-glycolide) (PLGA) coating containing the papaverine hydrochloride (PAP). In particular, strength properties, retention strength of the stent ends, dynamic frictional force, and the fluoroscopic visibility of the stent during X-ray imaging were determined. Results: The analysis of the test results indicates the usefulness of a biodegradable polymer coating containing the active substance for the modification of the surface of polyurethane ureteral stents. The stents coated with PLGA+PAP coating compared to polyurethane stents are characterized by more favorable strength properties, the smaller value of the dynamic frictional force, without reducing the fluoroscopic visibility.
Topics: Absorbable Implants; Biocompatible Materials; Drug-Eluting Stents; Humans; Papaverine; Polylactic Acid-Polyglycolic Acid Copolymer; Polyurethanes; Ureteral Obstruction
PubMed: 34299324
DOI: 10.3390/ijms22147705 -
IUCrJ Jul 2021The bacterial CYP105 family is involved in secondary metabolite biosynthetic pathways and plays essential roles in the biotransformation of xenobiotics. This study...
The bacterial CYP105 family is involved in secondary metabolite biosynthetic pathways and plays essential roles in the biotransformation of xenobiotics. This study investigates the newly identified HO-mediated CYP105D18 from as the first bacterial CYP for N-oxidation. The catalytic efficiency of CYP105D18 for papaverine N-oxidation was 1.43 s µ . The heme oxidation rate () was low (<0.3 min) in the presence of 200 m HO. This high HO tolerance capacity of CYP105D18 led to higher turnover prior to heme oxidation. Additionally, the high-resolution papaverine complexed structure and substrate-free structure of CYP105D18 were determined. Structural analysis and activity assay results revealed that CYP105D18 had a strong substrate preference for papaverine because of its bendable structure. These findings establish a basis for biotechnological applications of CYP105D18 in the pharmaceutical and medicinal industries.
PubMed: 34258016
DOI: 10.1107/S2052252521005522 -
Journal of Interventional Cardiology 2021To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR).
BACKGROUND
To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR).
METHODS
This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement.
RESULTS
One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, =0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, < 0.0001).
CONCLUSION
IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.
Topics: Aged; Cardiac Catheterization; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Female; Humans; Male; Microcirculation; Operative Time; Prospective Studies; Reproducibility of Results; Severity of Illness Index; Vascular Resistance; Work Simplification
PubMed: 34149324
DOI: 10.1155/2021/9971874