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Foods (Basel, Switzerland) Apr 2023Morphine and codeine are the two principal opiates found in the opium poppy ( L.) and are therapeutically used for pain management. Poppy seeds with low opiates are...
Morphine and codeine are the two principal opiates found in the opium poppy ( L.) and are therapeutically used for pain management. Poppy seeds with low opiates are primarily used for culinary purposes due to their nutritional and sensory attributes. Intentional adulteration of poppy seeds is common, often combined with immature, less expensive, exhausted, or substituted with morphologically similar seeds, viz., amaranth, quinoa, and sesame. For a safer food supply chain, preventive measures must be implemented to mitigate contamination or adulteration. Moreover, the simultaneous analysis of and its adulterants is largely unknown. Pre- and post-processing further complicate the alkaloid content and may pose a significant health hazard. To address these issues, two independent methods were investigated with eight botanically verified and fifteen commercial samples. Microscopical features were established for the authenticity of raw poppy seeds. Morphine, codeine, and thebaine quantities ranged from 0.8-223, 0.2-386, and 0.1-176 mg/kg, respectively, using LC-QToF. In most cases, conventional opiates have a higher content than papaverine and noscapine. The analytical methodology provided a chemical profile of 47 compounds that can be effectively applied to distinguish poppy seeds from their adulterants and may serve as an effective tool to combat ongoing adulteration.
PubMed: 37048333
DOI: 10.3390/foods12071510 -
Phytotherapy Research : PTR May 2023In the search for compounds that inhibit the SARS-CoV-2 after the onset of the COVID-19 pandemic, isoquinoline-containing alkaloids have been identified as compounds... (Review)
Review
Dual action anti-inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti-SARS-CoV-2 agents: A combined pharmacological and medicinal chemistry perspective.
In the search for compounds that inhibit the SARS-CoV-2 after the onset of the COVID-19 pandemic, isoquinoline-containing alkaloids have been identified as compounds with high potential to fight the disease. In addition to having strong antiviral activities, most of these alkaloids have significant anti-inflammatory effects which are often manifested through the inhibition of a promising host-based anti-COVID-19 target, the p38 MAPK signaling pathway. In the present review, our pharmacological and medicinal chemistry evaluation resulted in highlighting the potential of anti-SARS-CoV-2 isoquinoline-based alkaloids for the treatment of COVID-19 patients. Considering critical parameters of the antiviral and anti-inflammatory activities, mechanism of action, as well as toxicity/safety profile, we introduce the alkaloids emetine, cephaeline, and papaverine as high-potential therapeutic agents for use in the treatment of COVID-19. Although preclinical studies confirm that some isoquinoline-based alkaloids reviewed in this study have a high potential to inhibit the SARS-CoV-2, their entry into drug regimens of COVID-19 patients requires further clinical trial studies and toxicity evaluation.
Topics: Humans; Chemistry, Pharmaceutical; SARS-CoV-2; Pandemics; COVID-19; Isoquinolines; Alkaloids; Anti-Inflammatory Agents; Antiviral Agents
PubMed: 37039761
DOI: 10.1002/ptr.7833 -
The Journal of Sexual Medicine May 2023Structural alterations of the penis, including cavernosal apoptosis and fibrosis, induce venous leakage into the corpus cavernosum or cavernosal veno-occlusive...
Chronic treatment with a combination of hepatocyte growth factor and JNK inhibitor ameliorates cavernosal veno-occlusive dysfunction: a rat model of cavernous nerve injury.
BACKGROUND
Structural alterations of the penis, including cavernosal apoptosis and fibrosis, induce venous leakage into the corpus cavernosum or cavernosal veno-occlusive dysfunction, a key pathophysiology associated with erectile dysfunction after radical prostatectomy. We hypothesized that the effect of JNK inhibitors on reducing apoptosis and hepatocyte growth factor (HGF) on inducing tissue regeneration could be another treatment mechanism of erectile dysfunction after radical prostatectomy.
AIM
To investigate whether JNK inhibition combined with intracavernosal administration of HGF can completely preserve cavernosal veno-occlusive function (CVOF) in a rat model of erectile dysfunction induced via bilateral cavernosal nerve crush injury (CNCI).
METHODS
A total of 42 male Sprague-Dawley rats were randomly assigned to sham control (group S), CNCI (group I), and CNCI treated with a combination of JNK inhibitor and HGF (group J + H) for 5 weeks after surgery.
OUTCOMES
Rats in each group were evaluated via dynamic infusion cavernosometry (DIC), caspase-3 activity assay, Masson trichrome staining, immunohistochemical staining of α-smooth muscle actin, and immunoblotting at 5 weeks after surgery.
RESULTS
Regarding CVOF, group I showed decreased papaverine response, increased maintenance, and drop rates of DIC when compared with group S. Group J + H showed significant improvement in the 3 DIC parameters vs group I. No differences in the 3 DIC parameters were found between group J + H and group S. Regarding the structural integrity of the corpus cavernosum, group I showed increased caspase-3 activity, decreased smooth muscle (SM):collagen ratio, decreased SM content, decreased protein expression of PECAM-1, and decreased phosphorylation of c-Jun and c-Met. Group J + H showed significant attenuation in histologic and molecular derangement as compared with group I. There were no differences in caspase-3 activity, SM content, SM:collagen ratio, PECAM-1 protein expression, c-Jun phosphorylation, and c-Met phosphorylation between groups J + H and S.
CLINICAL IMPLICATIONS
Our results suggest that antiapoptotic and regenerative therapy for the corpus cavernosum is a potential mechanism of penile rehabilitation after radical prostatectomy.
STRENGTHS AND LIMITATIONS
This study provides evidence that combination treatment of JNK inhibitor and HGF preserves erectile function by restoring corporal SM and endothelium. However, additional human studies are needed to confirm the clinical effect.
CONCLUSION
Chronic treatment with JNK inhibitor and HGF may preserve CVOF to levels comparable to sham control by preserving the structural integrity of the corpus cavernosum and so represents a potential therapeutic option for preventing the development of cavernosal veno-occlusive dysfunction.
Topics: Animals; Humans; Male; Rats; Caspase 3; Disease Models, Animal; Erectile Dysfunction; Hepatocyte Growth Factor; Penile Erection; Penis; Platelet Endothelial Cell Adhesion Molecule-1; Rats, Sprague-Dawley; Trauma, Nervous System
PubMed: 37037785
DOI: 10.1093/jsxmed/qdad046 -
Journal of Clinical Neuroscience :... Jun 2023Vasospasm after resection of skull base tumors is a rare complication that often produces relevant ischemic sequelae. This review of the literature reports a number of... (Review)
Review
Diluted intracisternal papaverine for microvascular protection of cranial nerves during vestibular schwannoma and cerebello-pontine angle surgery. Commentary and review of the literature.
Vasospasm after resection of skull base tumors is a rare complication that often produces relevant ischemic sequelae. This review of the literature reports a number of published experiences that can help determine the potential causes of vasospasm after cerebello-pontine angle (CPA) tumor and -in particular-vestibular schwannoma (VS) resection, the ways to prevent it, and the methods to obtain the correct diagnosis. The cause appears to be multifactorial and the surgical approach may contribute to the pathogenesis of vasospasm. Neurosurgeons must pay attention to detect possible vasospasm at an early stage of cerebello-pontine. Cerebral blood flow measurement and transcranial Doppler are useful monitoring tools. Intra-operative prevention of vasospasm during CPA tumor resection with papaverine hydrochloride (PPV) seems to play a relevant role. In particular, PPV is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. There is large uncertainty about intracisternal PPV dose-related efficacy and side effects. Dilution of PPV in saline prior to application is recommended to avoid complications. In our experience, in line with the literature, we use a pure PPV without excipients 60 mg/2 ml diluted in 20 cc of 0,9% saline solution (0,3%) to prevent Hearing Loss during Posterior Fossa Microvascular Decompression for Typical Trigeminal Neuralgia and other cranial nerves potentially involved during VS and other CPA tumor resection. The aim of this commentary is to analyze and discuss the role of diluted intracisternal PPV for microvascular protection of cranial nerves during CPA tumor surgery.
Topics: Humans; Papaverine; Neuroma, Acoustic; Vasodilator Agents; Cranial Nerves; Hearing Loss; Brain Stem Neoplasms; Cerebellopontine Angle
PubMed: 37037167
DOI: 10.1016/j.jocn.2023.03.012 -
General Thoracic and Cardiovascular... Oct 2023There is controversy regarding which internal thoracic artery (ITA) should be anastomosed to the left anterior descending artery (LAD). Here, we propose an optimal graft...
Blood flow characteristics of the bilateral internal thoracic artery: implications of optimal graft configuration for coronary artery bypass grafting to maximize blood supply.
PURPOSE
There is controversy regarding which internal thoracic artery (ITA) should be anastomosed to the left anterior descending artery (LAD). Here, we propose an optimal graft design based on measurement of blood flow in the ITA.
METHODS
Sixty-one patients (53 men, median age 68 [62-75] years) undergoing first elective coronary artery bypass grafting were enrolled. Fifty-seven left ITAs (LITAs) and 28 right ITAs (RITAs) were harvested in either a semi-skeletonized manner using a harmonic scalpel covered with papaverine-soaked gauze (group-A, n = 45) or a fully skeletonized manner using electrocautery with intraluminal papaverine injection (group-B, n = 41). Free flow of 33 ITAs was measured after pharmacological dilatation and in situ ITA-LAD flow was measured in 59 patients by transit-time flowmetry.
RESULTS
RITA and LITA free flow were 147.0 [87.8-213.0] mL/min and 108.0 [90.0-144.0] mL/min, respectively (P = 0.199). The group-B had significantly higher ITA free flow (135.0 [102.0-171.0] mL/min) than group-A (63.0 [36.0-96.0] mL/min, P = 0.009). In 13 patients with bilateral ITA harvesting, free flow of the RITA (138.0 [79.5-204.0] mL/min) was also significantly higher than the LITA (102.0 [81.0-138.0] mL/min, P = 0.046). There was no significant difference between RITA and LITA flow anastomosed to the LAD. The group-B had significantly higher ITA-LAD flow (56.5 [32.3-73.6] mL/min) than group-A (40.9 [20.1-53.7] mL/min, P = 0.023).
CONCLUSION
RITA provides significantly higher free flow than LITA but similar blood flow to the LAD. Full skeletonization with intraluminal papaverine injection maximizes both free flow and ITA-LAD flow.
Topics: Male; Humans; Aged; Mammary Arteries; Papaverine; Vascular Patency; Coronary Artery Bypass; Coronary Vessels
PubMed: 36995639
DOI: 10.1007/s11748-023-01930-x -
Molecular Pharmaceutics Apr 2023The purpose of the present study was to evaluate whether the population balance model (PBM) could be a suitable model for the precipitation of weak base and zwitterionic...
The purpose of the present study was to evaluate whether the population balance model (PBM) could be a suitable model for the precipitation of weak base and zwitterionic drugs in the gastrointestinal pH environment. Five poorly soluble drugs were used as model drugs (dipyridamole, haloperidol, papaverine, phenazopyridine, and tosufloxacin). PBM consists of the equations for primary nucleation, secondary nucleation, and particle growth. Each equation has two empirical parameters. The pH shift (pH-dumping) precipitation test (pH 3.0 to 6.5) was used to determine the model parameters for each drug. It was difficult to determine all six parameters by simultaneously fitting them to the precipitation profiles. Therefore, the number of model parameters was reduced from six to three by neglecting the secondary nucleation process and applying a common exponent number for the particle growth equation. Despite reducing the parameter number, PBM appropriately described the precipitation profiles in the pH shift tests. The constructed PBM model was then used to predict the precipitation profiles in an artificial stomach-intestine transfer (ASIT) test. PBM appropriately predicted the precipitation profiles in the ASIT test. These results suggested that PBM can be a suitable model to represent the precipitation of weak base and zwitterionic drugs in the gastrointestinal pH environment for biopharmaceutics modeling and simulation.
Topics: Solubility; Administration, Oral; Gastrointestinal Tract; Stomach; Computer Simulation; Hydrogen-Ion Concentration; Models, Biological; Chemical Precipitation; Intestinal Absorption
PubMed: 36929729
DOI: 10.1021/acs.molpharmaceut.3c00088 -
African Health Sciences Sep 2022Drotaverine, a spasmolytic, has been found to have potential to achieve a reduction in the duration of labour and prevent prolonged labour. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Drotaverine, a spasmolytic, has been found to have potential to achieve a reduction in the duration of labour and prevent prolonged labour.
OBJECTIVE
To compare the effects of intravenous drotaverine hydrochloride with placebo for shortening the duration of active phase of labour in primigravidas.
METHODS
A double-blind, placebo-controlled randomized trial of 246 primigravidas in active phase of labour at term was conducted. They were randomly (1:1 ratio) administered intravenous 2 ml (40mg) of drotaverine hydrochloride or 2 ml of Vitamin B complex as placebo. The primary outcome measure was the duration of active phase of labour. The secondary outcome measures were cervical dilatation rate, oxytocin augmentation rate, incidence of prolonged labour, labour pain scores, mode of delivery, maternal and neonatal outcomes.
RESULTS
The mean duration of active phase of labour (hour) was significantly lower in the drotaverine group compared to the control (drotaverine; 6.22 ± 2.41 vs placebo; 8.33 ± 3.56; p <0.001). Also, the cervical dilatation rate (cm/hr) was significantly faster in the drotaverine arm (drotaverine; 1.68 ± 1.02 versus placebo; 1.06 ± 0.53, p <0.001). There was a significantly higher probability of faster delivery among women who were given drotaverine (log-rank test, p < 0.001). The oxytocin augmentation rate, incidence of prolonged labour, labour pain scores, mode of delivery, maternal and neonatal outcomes were not significantly different among the groups.
CONCLUSIONS
Drotaverine hydrochloride is effective in shortening the duration of active phase of labour without adverse maternal and neonatal outcomes. However, more evidence is needed to explore its role in active phase of labour among primigravid women. Trial registration number: PACTR201810902005232.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Oxytocin; Labor Pain; Labor, Obstetric; Papaverine; Double-Blind Method
PubMed: 36910347
DOI: 10.4314/ahs.v22i3.13 -
Journal of Diabetes and Its... Apr 2023The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation...
AIMS
The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts.
METHODS
HSV grafts (n = 10) obtained from patients undergoing CABG were incubated with 30 mM glucose and/or 10 μM pioglitazone or 0.1 % DMSO for 24 h after endothelium removal. ROS levels were examined by chemiluminescence assay, MMP-2,-9,-14, TIMP-2, and α-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, prostaglandin F and papaverine was assessed in HSVs.
RESULTS
HG induced superoxide anion (SA) (123 %) and other ROS levels (159 %), up-regulated MMP-2 expression (180 %)/activity (79 %), MMP-14 expression (24 %) and MMP-9 activity while down-regulating TIMP-2 expression (27 %). HG elevated total MMP-2/TIMP-2 ratio (483 %) and MMP-14/TIMP-2 ratio (78 %). However, HG plus pioglitazone inhibited SA (30 %) and other ROS levels (29 %), down-regulated MMP-2 expression (76 %)/activity (83 %), MMP-14 expression (38 %) and MMP-9 activity, while reversing TIMP-2 expression (44 %). HG plus pioglitazone decreased total MMP-2/TIMP-2 ratio (91 %) and MMP-14/TIMP-2 ratio (59 %). HG impaired contractions to all agents but pioglitazone improved them.
CONCLUSIONS
Pioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG.
Topics: Humans; Glucose; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Oxidative Stress; Pioglitazone; Reactive Oxygen Species; Saphenous Vein; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Inflammation
PubMed: 36905721
DOI: 10.1016/j.jdiacomp.2023.108421 -
Analytical Methods : Advancing Methods... Mar 2023The design of experiments (DoE) method was employed to optimize the adsorption processes of seven psychoactive substances in magnetic solid phase extraction....
The design of experiments (DoE) method was employed to optimize the adsorption processes of seven psychoactive substances in magnetic solid phase extraction. FeO/GO/ZIF-8 was utilized as an adsorbent for the efficient extraction of psychoactive substances from environmental water samples. The analytes were ephedrine, methylephedrine, amphetamine, methamphetamine, morphine, papaverine, and thebaine, which were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Plackett-Burman design was employed to identify the significant factors responsible for adsorption, and Box-Behnken design was used for further optimization to obtain the optimum values for each variable. The predicted and experimental values were found to be in good agreement. The coefficient of determination () values of 0.9500-0.9976 indicated that the model was significant. The linear ranges were 1-100 ng mL, and the correlation coefficient was good ( ≥ 0.995). The EF with values of about 2.5 was obtained with recoveries in the range of 74.92-94.47%. The limits of detection (LOD) and limits of quantification (LOQ) were 0.086-0.353 ng mL and 0.286-1.175 ng mL, respectively. The intra-day and inter-day RSDs were in the range of 0.17-1.87% and 0.06-2.21%, respectively. By using the DoE method, the errors associated with inferring the influence and interaction between various factors can be reduced. The combination of MSPE and DoE improves the recovery, precision, and simultaneous detectability of the target analytes. It has a high potential for psychoactive substance analysis in environmental water.
Topics: Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Central Nervous System Agents; Water; Amphetamine
PubMed: 36896683
DOI: 10.1039/d3ay00059a -
Scientific Reports Feb 2023In this paper, we present the results of toxicological analyses of preserved brain tissue and bone samples from the remains of the seventeenth century patients of the...
In this paper, we present the results of toxicological analyses of preserved brain tissue and bone samples from the remains of the seventeenth century patients of the Ospedale Maggiore, the main hospital in Milan and one of the most innovative hospitals in Europe from the Renaissance period. Beneath it, the crypt functioned as the burial place for the deceased of the hospital. In this multidisciplinary study of the remains, toxicological analyses in particular were performed with HPLC-MS/MS on different biological samples from nine individuals. Anthropological, paleopathological, histological, radiological examinations and radiocarbon dating were also carried out. As a result, archeotoxicological analyses revealed the presence of codeine, morphine, noscapine and papaverine, derived from Papaver somniferum, a plant present in the hospital pharmacopeia used as a narcotic, analgesic, astringent, coagulant, and antitussive agent. Such analyses have shed light on the pharmacological therapies administered to the patients near the time of death and have implemented our knowledge of medical treatment and drug administration in the 1600's.
Topics: Humans; Papaver; Tandem Mass Spectrometry; Brain; Italy; Hospitals; Narcotics
PubMed: 36854677
DOI: 10.1038/s41598-023-27953-1