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Pregnancy outcomes following gestational exposure to papaverine: An observational comparative study.British Journal of Clinical Pharmacology Oct 2021Papaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to... (Observational Study)
Observational Study
AIMS
Papaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to examine whether first trimester exposure to papaverine is associated with increased risk for major malformation and whether gestational exposure at any stage is associated with increased risk for preterm delivery, lower birthweight, small for gestational age, caesarean section (CS), lower Apgar score and perinatal death.
METHODS
A retrospective comparative study consisted of pregnant women treated with papaverine between February 2010 and October 2019 at a large tertiary center. The control group comprised of livebirth deliveries randomly selected from the institutional obstetric database.
RESULTS
The study group consisted of 498 pregnancies, which resulted in 537/544 (98.7%) live births, of whom 46/537 (8.6%) were exposed during the first trimester. The control group consisted of 498 pregnancies and 514 live births. Rate of major malformations did not differ between study group (2/46, 4.3%) and control (25/315, 4.9%, P = .67). Papaverine exposure was associated with higher rate of preterm delivery (22.3 vs. 10.3%, P < .001), CS (35.9 vs. 24.1%, P < .001) and lower birth weight (3207 vs. 3246 g, P = .02). Adjustment for treatment indication demonstrated that these remained significant only when given for obstetrical/surgical aetiologies. Comparable rates were observed for the remaining outcomes.
CONCLUSIONS
Short-term gestational exposure to papaverine adjusted for indication was not associated with preterm deliveries, CS, lower birthweight, small for gestational age or perinatal death. Rate of major malformations among 46 first trimester exposures was comparable to controls.
Topics: Cesarean Section; Female; Gestational Age; Humans; Papaverine; Pregnancy; Pregnancy Outcome; Premature Birth; Retrospective Studies
PubMed: 33675044
DOI: 10.1111/bcp.14809 -
Saudi Journal of Gastroenterology :... 2021Drotaverine and Mebeverine are used for alleviating the pain of IBS, but the evidence for their efficacy is scarce. In this randomised control study, we evaluated and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Drotaverine and Mebeverine are used for alleviating the pain of IBS, but the evidence for their efficacy is scarce. In this randomised control study, we evaluated and compared their efficacy in improving severity, frequency of pain and its associated symptoms.
METHODS
Patients fulfilling the ROME III criteria of IBS were evaluated in this randomised control trial during 4 weeks of treatment. Group A (n = 100) received 80 mg Drotaverine and Group B (n = 100) received 135 mg Mebeverine three times a day, 1 hour before meals. Primary outcome measure was, the reduction in severity of pain (>30% reduction) assessed by VAS (0 to 10 scale) & PSS (patient symptoms scores).
RESULTS
The pain severity score fell from 6.02 to 4.8 on day 3 in Group A as compared to decrease from 6.72 to 6.62 in Group B (p < 0.01). This significant reduction in pain severity was observed till the end of the study, reducing from 6.02 to 1.78 (74% reduction) in Group A compared to 6.72 to 3.62 (46.1% reduction) in Group B (p < 0.05). There was a significant reduction in pain frequency, straining on stool, a change in one score in Bristol stool chart (BSC), achievement of complete spontaneous smooth bowel movement in Group A, compared to Group B patients. A significant improvement in Patient's evaluation of Global Assessment of Symptoms (p < 0.05) and Patient Assessment of Constipation - Quality Of Life (PAC-QOL) (p < 0.01) was observed in Group A compared to Group B.
CONCLUSION
Drotaverine was significantly superior in efficacy as compared to Mebeverine in alleviating pain severity (starting from day 3), frequency and stools-elated symptoms of IBS.
Topics: Double-Blind Method; Humans; Irritable Bowel Syndrome; Papaverine; Phenethylamines; Quality of Life; Treatment Outcome
PubMed: 33642357
DOI: 10.4103/sjg.SJG_266_20 -
Scientific Data Feb 2021SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden. We applied...
SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden. We applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. The primary screen identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 in vitro. These compounds were tested in an eight-point dose response screen using the same image-based cytopathicity readout. For the 67 most active molecules, cytotoxicity data were generated to confirm activity against SARS-CoV-2. We verified the ability of known inhibitors camostat, nafamostat, lopinavir, mefloquine, papaverine and cetylpyridinium to reduce the cytopathic effects of SARS-CoV-2, providing confidence in the validity of the assay. The high-content screening data are suitable for reanalysis across numerous drug classes and indications and may yield additional insights into SARS-CoV-2 mechanisms and potential therapeutic strategies.
Topics: Antiviral Agents; Benzamidines; COVID-19; Caco-2 Cells; Cetylpyridinium; Drug Evaluation, Preclinical; Drug Repositioning; Esters; Guanidines; Humans; Lopinavir; Mefloquine; Papaverine; SARS-CoV-2
PubMed: 33637768
DOI: 10.1038/s41597-021-00848-4 -
Acta Cirurgica Brasileira 2021This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.
PURPOSE
This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.
METHODS
Thirty Wistar rats (Rattus norvegicus albinos) were divided into five groups (according to the grafting material and time to euthanasia): (1) autograft - 14 days (control), (2) autograft - 28 days (control), (3) MSC + PRP - 14 days, (4) MSC + PRP + papaverine - 14 days and (5) MSC + PRP + papaverine - 28 days. After euthanasia, the graft was removed and histological slides were prepared. They were assessed by a blinded pathologist using a previously published histological scale as parameter.
RESULTS
There was some degree of neoformed bone trabeculae (NBT) in 93.3% of the samples, as well as osteoblastic activity (OA). The autograft groups (14 and 28 days) had higher levels in the formation of bone trabeculae. Nonparametric data were analyzed using the Wilcoxon-Mann-Whitney test and proved not to be statistically significant at p < 0.05.
CONCLUSIONS
Experimental parietal bone reconstruction, combining MSC, PRP and papaverine presented regeneration in all groups with no significant difference among them.
Topics: Animals; Bone Regeneration; Mesenchymal Stem Cells; Parietal Bone; Platelet-Rich Plasma; Rats; Rats, Wistar
PubMed: 33503214
DOI: 10.1590/ACB351201 -
Iranian Journal of Allergy, Asthma, and... Aug 2020This study was conducted to evaluate the possible mechanisms of the relaxant effects of hydroalcoholic extract of Plantago major (P. major) on tracheal smooth muscle...
This study was conducted to evaluate the possible mechanisms of the relaxant effects of hydroalcoholic extract of Plantago major (P. major) on tracheal smooth muscle (TSM) in rats. The effects of cumulative concentrations of P. major (5, 10, 20 and 40 mg/mL) and theophylline (0.2, 0.4, 0.6 and 0.8 mM) were evaluated on pre-contracted TSM with 10 μΜ methacholine or 60 mM KCl. To determine the possible mechanisms, the relaxant effect of the plant was also examined on incubated TSM with atropine, indomethacin, chlorpheniramine, glibenclamide, diltiazem, papaverine, and propranolol. The results indicated concentration-dependent relaxant effects for P. major in non-incubated TSM contracted by methacholine or KCl. There was no statistically significant difference in the relaxant effects of P. major between non-incubated and incubated tissues with indomethacin, papaverine, and propranolol. However, the relaxant effects of P. major in incubated tissues with atropine (p<0.01 to p<0.001), chlorpheniramine (p<0.05 to p<0.001), glibenclamide (p<0.05), or diltiazem (p<0.01) were significantly lower than non-incubated TSM. P. major indicated relatively potent relaxant effects which were lower than those of theophylline. Muscarinic and histamine (H1) receptors inhibition, as well as calcium channel blocking and potassium channel opening effects are suggested to contribute to the TSM relaxant effect of the plant.
Topics: Animals; Bronchodilator Agents; Dose-Response Relationship, Drug; Histamine H1 Antagonists; Muscarinic Antagonists; Muscle Relaxation; Muscle, Smooth; Plant Extracts; Plantago; Rats; Receptors, Histamine H1; Receptors, Muscarinic; Trachea
PubMed: 33463105
DOI: 10.18502/ijaai.v19i4.4113 -
Journal of the American Heart... Feb 2021
Topics: Aged; Coronary Stenosis; Coronary Vessels; Female; Fractional Flow Reserve, Myocardial; Humans; Hyperemia; Injections, Intra-Arterial; Male; Middle Aged; Papaverine; Vascular Resistance; Vasodilator Agents
PubMed: 33459027
DOI: 10.1161/JAHA.120.018562 -
Surgical Neurology International 2020Permanent hearing loss after posterior fossa microvascular decompression (MVD) for typical trigeminal neuralgia (TTN) is one of the possible complications of this...
Microvascular decompression for typical trigeminal neuralgia: Personal experience with intraoperative neuromonitoring with level-specific-CE-Chirp® brainstem auditory evoked potentials in preventing possible hearing loss.
BACKGROUND
Permanent hearing loss after posterior fossa microvascular decompression (MVD) for typical trigeminal neuralgia (TTN) is one of the possible complications of this procedure. Intraoperative brainstem auditory evoked potentials (BAEPs) are used for monitoring the function of cochlear nerve during cerebellopontine angle (CPA) microsurgery. Level-specific (LS)-CE-Chirp® BAEPs are the most recent evolution of classical click BAEP, performed both in clinical studies and during intraoperative neuromonitoring (IONM) of acoustic pathways during several neurosurgical procedures.
METHODS
Since February 2016, we routinely use LS-CE-Chirp® BAEPs for monitoring the function of cochlear nerve during CPA surgery, including MVD for trigeminal neuralgia. From September 2011 to December 2018, 71 MVDs for TTN were performed in our department, 47 without IONM of acoustic pathways (Group A), and, from February 2016, 24 with LS-CE-Chirp BAEP (Group B).
RESULTS
Two patients of Group A developed a permanent ipsilateral anacusia after MVD. In Group B, we did not observe any permanent acoustic deficit after surgery. In one case of Group B, during arachnoid dissection, intraoperative LS-CE-Chirp BAEP showed a temporary lag of V wave, resolved in 5 min after application of intracisternal diluted papaverine (0.3% solution without excipients).
CONCLUSION
MVD is widely considered a definitive surgical procedure in the management of TTN. Even though posterior fossa MVD is a safe procedure, serious complications might occur. In particular, the use of IONM of acoustic pathways during MVD for TTN might contribute to prevention of postoperative hearing loss.
PubMed: 33408922
DOI: 10.25259/SNI_702_2020 -
Molecules (Basel, Switzerland) Nov 2020Cancer is one of the leading causes of death worldwide. Although several potential therapeutic agents have been developed to efficiently treat cancer, some side effects...
Cancer is one of the leading causes of death worldwide. Although several potential therapeutic agents have been developed to efficiently treat cancer, some side effects can occur simultaneously. Papaverine, a non-narcotic opium alkaloid, is a potential anticancer drug that showed selective antitumor activity in various tumor cells. Recent studies have demonstrated that metal complexes improve the biological activity of the parent bioactive ligands. Based on those facts, herein we describe the synthesis of novel papaverine-vanadium(III), ruthenium(III) and gold(III) metal complexes aiming at enhancing the biological activity of papaverine drug. The structures of the synthesized complexes were characterized by various spectroscopic methods (IR, UV-Vis, NMR, TGA, XRD, SEM). The anticancer activity of synthesized metal complexes was evaluated in vitro against two types of cancer cell lines: human breast cancer MCF-7 cells and hepatocellular carcinoma HepG-2 cells. The results revealed that papaverine-Au(III) complex, among the synthesized complexes, possess potential antimicrobial and anticancer activities. Interestingly, the anticancer activity of papaverine-Au(III) complex against the examined cancer cell lines was higher than that of the papaverine alone, which indicates that Au-metal complexation improved the anticancer activity of the parent drug. Additionally, the Au complex showed anticancer activity against the breast cancer MCF-7 cells better than that of cisplatin. The biocompatibility experiments showed that Au complex is less toxic than the papaverine drug alone with IC ≈ 111 µg/mL. These results indicate that papaverine-Au(III) complex is a promising anticancer complex-drug which would make it a suitable candidate for further in vivo investigations.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Chemistry Techniques, Synthetic; Coordination Complexes; Humans; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Nanostructures; Papaverine; Structure-Activity Relationship
PubMed: 33233775
DOI: 10.3390/molecules25225447 -
Frontiers in Chemistry 2020The opium alkaloids (morphine, codeine, thebaine, noscapine, and papaverine) have been detected on poppy seeds; they are widely used by the food industry for decoration...
The opium alkaloids (morphine, codeine, thebaine, noscapine, and papaverine) have been detected on poppy seeds; they are widely used by the food industry for decoration and flavor but can introduce opium alkaloids into the food chain. Of the opium alkaloids found on poppy seeds, morphine, and codeine are the most pharmacologically active and have been detected in biological matrices collected in workplace and roadside drug testing resulting in positive opiate results. The European Food Safety Authority introduced an acute reference dose of 10 μg morphine/kg of body weight as a safe level for morphine in food products. In this work, it was found that in harvested poppy seeds, and thermally processed poppy seeds (with and without a food matrix), if used in normal levels would not exceed the recommended acute reference dose. It was also shown that the levels of all alkaloids reduce when thermally processed, in comparison with harvested, untreated seeds.
PubMed: 33195013
DOI: 10.3389/fchem.2020.00737 -
Brazilian Journal of Cardiovascular... Oct 2020To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside.
OBJECTIVE
To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside.
METHODS
Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis.
RESULTS
Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups.
CONCLUSION
The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.
Topics: Diltiazem; Humans; Mammary Arteries; Nitroprusside; Papaverine; Vasodilator Agents
PubMed: 33118726
DOI: 10.21470/1678-9741-2019-0251