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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 -
Pharmaceutical Development and... Jun 2024Over the past decades, opium derivatives have been discovered as new anti-cancer agents. In our study, Fe3O4 superparamagnetic nanoparticles (SPIONs) decorated with...
Over the past decades, opium derivatives have been discovered as new anti-cancer agents. In our study, Fe3O4 superparamagnetic nanoparticles (SPIONs) decorated with chitosan were loaded with papaverine or noscapine to surmount dug delivery-related obstacles. Modifying the magnetic nanoparticles (MNP) surface with polymeric materials such as chitosan prevents oxidation and provides a site for drug linkage, which renders them a great drug carrier. The obtained systems were characterized by DLS (20- 40 nm were achieved for MNPs and medicine loaded MNPs),TEM (spherical with average size of 11-20 nm)FTIR, XRD, and VSM (71.3 - 42.8 emu/g). Contrary to noscapine, papaverine-magnetic nanoparticles (MNPs) attenuated 4T1 murine breast cancer cell proliferation (11.50 ± 1.74 µg/ml) effectively compared to the free drug (62.35 ± 2.88 µg/ml) while sparing L-929 fibroblast cells (138.14 ± 4.38 µg/ml). Furthermore, SPION and SPION-chitosan displayed no cytotoxic activity. Colony-formation assay confirmed the long-term cytotoxicity of nanostructures. Both developed formulations promoted ROS production accompanied by late apoptotic cell death. The biocompatible nanoparticle exerted an augmenting effect to deliver papaverine to metastatic breast cancer cells.
PubMed: 38932720
DOI: 10.1080/10837450.2024.2372568 -
RoFo : Fortschritte Auf Dem Gebiete Der... Nov 2023Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in...
BACKGROUND
Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in Germany.
METHODS
Retrospective analysis of the clinical and procedural data on endovascular spasm therapies (EST) documented anonymously in the DeGIR registry. We analysed: pre-interventional findings of CTP and consciousness; radiation dose applied, interventional-technical parameters (local medication, devices, angiographic result), post-interventional symptoms, complications and mortality.
RESULTS
3584 patients received a total of 7628 EST (median age/patient: 53 [range: 13-100, IQR: 44-60], 68.2 % women) in 91 (2018), 92 (2019), 100 (2020) and 98 (2021) centres; 5388 (70.6 %) anterior circulation and 378 (5 %) posterior circulation (both involved in 1862 cases [24.4 %]). EST was performed once in 2125 cases (27.9 %), with a mean of 2.1 EST/patient. In 7476 times, purely medicated EST were carried out (nimodipine: 6835, papaverine: 401, nitroglycerin: 62, other drug not specified: 239; combinations: 90). Microcatheter infusions were documented in 1132 times (14.8 %). Balloon angioplasty (BA) (additional) was performed in 756 EST (9.9 %), other mechanical recanalisations in 154 cases (2 %) and stenting in 176 of the EST (2.3 %). The median dose area product during ET was 4069 cGycm² (drug: 4002/[+]BA: 8003 [p < 0.001]). At least 1 complication occurred in 95 of all procedures (1.2 %) (drug: 1.1 %/[+]BA: 4.2 % [p < 0.001]). Mortality associated with EST was 0.2 % (n = 18). After EST, overall improvement or elimination of CVS was found in 94.2 % of cases (drug: 93.8 %/[+]BA: 98.1 % [p < 0.001]). In a comparison of the locally applied drugs, papaverine eliminated CVS more frequently than nimodipine (p = 0.001).
CONCLUSION
EST have a moderate radiation exposure and can be performed with few complications. Purely medicated EST are predominantly performed, especially with nimodipine. With (additional) BA, radiation exposure, complication rates and angiographic results are higher or better. When considering drug EST alone, there is evidence for an advantage of papaverine over nimodipine, but a different group size has to be taken into account. In the analysis of EST, the DeGIR registry data are suitable for answering more specific questions, especially due to the large number of cases; for this purpose, further subgroupings should be sought in the data documentation.
KEY POINTS
· In Germany, there are currently no guidelines for the endovascular treatment of cerebral vasospasm following spontaneous subarachnoid hemorrhage.. · In addition to oral nimodipine administration endovascular therapy is used to treat cerebral vasospasm in most hospitals.. · This is the first systematic evaluation of nationwide registry data on endovascular treatment of cerebral vasopasm in Germany.. · This real-world data shows that endovascular treatment for cerebral vasospasm has a moderate radiation exposure and can be performed with few complications overall. With (additional) balloon angioplasty, radiation exposure, complication rates and angiographic therapy results are higher or better..
CITATION FORMAT
· Neumann A, Weber W, Küchler J et al. Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. Fortschr Röntgenstr 2023; 195: 1018 - 1026.
Topics: Humans; Female; Male; Nimodipine; Papaverine; Vasodilator Agents; Vasospasm, Intracranial; Retrospective Studies; Routinely Collected Health Data; Subarachnoid Hemorrhage; Endovascular Procedures; Treatment Outcome
PubMed: 37467777
DOI: 10.1055/a-2102-0129 -
Journal of AOAC International Sep 2023Computationally designed molecular imprinted polymer (MIP) incorporation into electrochemical sensors has many advantages to the performance of the designed sensors. The...
Computer-Aided Design of Eco-Friendly Imprinted Polymer Decorated Sensors Augmented by Self-Validated Ensemble Modeling Designs for the Quantitation of Drotaverine Hydrochloride in Dosage Form and Human Plasma.
BACKGROUND
Computationally designed molecular imprinted polymer (MIP) incorporation into electrochemical sensors has many advantages to the performance of the designed sensors. The innovative self-validated ensemble modeling (SVEM) approach is a smart machine learning-based (ML) technique that enables the design of more accurate predictive models using smaller data sets.
OBJECTIVE
The novel SVEM experimental design methodology is exploited here exclusively to optimize the composition of four eco-friendly PVC membranes augmented by a computationally designed magnetic molecularly imprinted polymer to quantitatively determine drotaverine hydrochloride (DVN) in its combined dosage form and human plasma. Furthermore, the application of hybrid computational simulations such as molecular dynamics and quantum mechanical calculations (MD/QM) is a time-saving and eco-friendly provider for the tailored design of the MIP particles.
METHOD
Here, for the first time, the predictive power of ML is assembled with computational simulations to develop four PVC-based sensors decorated by computationally designed MIP particles using four different experimental designs known as central composite, SVEM-LASSO, SVEM-FWD, and SVEM-PFWD. The pioneering AGREE approach further assessed the greenness of the analytical methods, proving their eco-friendliness.
RESULTS
The proposed sensors showed decent Nernstian responses toward DVN in the range of 58.60-59.09 mV/decade with a linear quantitative range of 1 × 10-7 - 1 × 10-2 M and limits of detection in the range of 9.55 × 10-8 to 7.08 × 10-8 M. Moreover, the proposed sensors showed ultimate eco-friendliness and selectivity for their target in its combined dosage form and spiked human plasma.
CONCLUSIONS
The proposed sensors were validated in accordance with International Union of Pure and Applied Chemistry (IUPAC) recommendations, proving their sensitivity and selectivity for drotaverine determination in dosage form and human plasma.
HIGHLIGHTS
This work presents the first ever application of both the innovative SVEM designs and MD/QM simulations in the optimization and fabrication of drotaverine-sensitive and selective MIP-decorated PVC sensors.
Topics: Humans; Polymers; Papaverine; Computer-Aided Design
PubMed: 37140537
DOI: 10.1093/jaoacint/qsad049 -
Antibiotics (Basel, Switzerland) Feb 2024Rhodomyrtone has indisputable and undeniable potential as a new antibiotic for antibiotic-resistant Gram-positive bacteria. Therefore, the main objective of this study...
A Novel Antibiotic, Rhodomyrtone: Pharmacokinetic Studies in a Murine Model and Optimization and Validation of High-Performance Liquid Chromatographic Method for Plasma Analysis.
Rhodomyrtone has indisputable and undeniable potential as a new antibiotic for antibiotic-resistant Gram-positive bacteria. Therefore, the main objective of this study was to determine the pharmacokinetics profiles of orally administered rhodomyrtone in rats. A reverse-phase HPLC-UV method was developed, optimized and validated for the analysis of rhodomyrtone concentrations in rat plasma. The retention time of papaverine and rhodomyrtone was 3.928 and 5.937 min, with no interference with the excipients used. The lower limit of quantification (LLOQ) of rhodomyrtone in the plasma sample was 0.04 μg/mL, the accuracy of rhodomyrtone at the LLOQ level ranged from 93.64 to 106.36%, precision was 6.59%, 80-120% for accuracy and <20% CV for precision. The calibration curve was linear at concentrations ranging from 0.04 to 128 µg/mL with a correlation coefficient (r) value of equal to or greater than 0.999. Sprague Dawley rats received a single dose of rhodomyrtone at 50 and 100 mg/kg. Blood samples were collected from tail veins. The peak plasma concentration was observed at 2 h, and the area under the curve of rhodomyrtone at 50 mg/kg and 100 mg/kg was 3.41 ± 1.04 and 7.82 ± 1.53 μg·h/mL, respectively. The results demonstrated linear pharmacokinetics characteristics at the studied dosage range. The plasma concentration of rhodomyrtone was above the minimal inhibition concentrations of several common pathogenic bacteria of medical importance. The proposed HPLC-UV method is fast, cost-effective, reliable and reproducible, and it is proposed for the routine analysis of rhodomyrtone.
PubMed: 38391542
DOI: 10.3390/antibiotics13020156 -
World Journal of Clinical Cases Apr 2024Idiopathic mesenteric phlebosclerosis (IMP) is a rare type of ischemic colitis characterized by thickening of the wall of the right hemicolon and calcification,...
BACKGROUND
Idiopathic mesenteric phlebosclerosis (IMP) is a rare type of ischemic colitis characterized by thickening of the wall of the right hemicolon and calcification, sclerosis, and fibrosis of mesenteric veins. The diagnosis of IMP is based on typical clinical features and imaging findings. We report a case of IMP that was initially missed by the radiologist.
CASE SUMMARY
A 77-year-old woman was admitted to the hospital due to chronic diarrhea for over 2 months. She had been consuming Chinese patent medicines (CPM) containing fructus gardeniae for more than 15 years. Colonoscopy revealed an edematous mucosa, bluish-purple discoloration, erosions, and ulcerations throughout the colorectal area. Abdominal computed tomography (CT) showed diffuse mural thickening of the entire colorectum, with tortuous thread-like calcifications in the right hemicolon, left hemicolon, and rectum. Most of the calcifications were located in the mesenteric vein. The diagnosis of IMP was established based on medical history, colonoscopy, CT findings, and histopathological examination. The patient was treated conservatively with papaverine and rifaximin, and CPM was stopped. Her diarrhea symptoms improved, indicating the effectiveness of the treatment. Over the next several years, she took opium alkaloids for an extended period and did not require hospitalization for the aforementioned gastrointestinal disorder.
CONCLUSION
IMP is a rare gastrointestinal disease affecting Asian populations, possibly related to long-term herbal medicine intake. Accurate imaging analysis is crucial for diagnosis, but insufficient understanding of the disease can lead to misdiagnosis or missed diagnosis. Treatment strategies should be personalized.
PubMed: 38660081
DOI: 10.12998/wjcc.v12.i10.1810 -
Microbial Cell Factories Jun 2024Computational mining of useful enzymes and biosynthesis pathways is a powerful strategy for metabolic engineering. Through systematic exploration of all conceivable...
BACKGROUND
Computational mining of useful enzymes and biosynthesis pathways is a powerful strategy for metabolic engineering. Through systematic exploration of all conceivable combinations of enzyme reactions, including both known compounds and those inferred from the chemical structures of established reactions, we can uncover previously undiscovered enzymatic processes. The application of the novel alternative pathways enables us to improve microbial bioproduction by bypassing or reinforcing metabolic bottlenecks. Benzylisoquinoline alkaloids (BIAs) are a diverse group of plant-derived compounds with important pharmaceutical properties. BIA biosynthesis has developed into a prime example of metabolic engineering and microbial bioproduction. The early bottleneck of BIA production in Escherichia coli consists of 3,4-dihydroxyphenylacetaldehyde (DHPAA) production and conversion to tetrahydropapaveroline (THP). Previous studies have selected monoamine oxidase (MAO) and DHPAA synthase (DHPAAS) to produce DHPAA from dopamine and oxygen; however, both of these enzymes produce toxic hydrogen peroxide as a byproduct.
RESULTS
In the current study, in silico pathway design is applied to relieve the bottleneck of DHPAA production in the synthetic BIA pathway. Specifically, the cytochrome P450 enzyme, tyrosine N-monooxygenase (CYP79), is identified to bypass the established MAO- and DHPAAS-mediated pathways in an alternative arylacetaldoxime route to DHPAA with a peroxide-independent mechanism. The application of this pathway is proposed to result in less formation of toxic byproducts, leading to improved production of reticuline (up to 60 mg/L at the flask scale) when compared with that from the conventional MAO pathway.
CONCLUSIONS
This study showed improved reticuline production using the bypass pathway predicted by the M-path computational platform. Reticuline production in E. coli exceeded that of the conventional MAO-mediated pathway. The study provides a clear example of the integration of pathway mining and enzyme design in creating artificial metabolic pathways and suggests further potential applications of this strategy in metabolic engineering.
Topics: Metabolic Engineering; Benzylisoquinolines; Escherichia coli; Cytochrome P-450 Enzyme System; Biosynthetic Pathways; Computer Simulation; Tetrahydropapaveroline; 3,4-Dihydroxyphenylacetic Acid
PubMed: 38879464
DOI: 10.1186/s12934-024-02453-7 -
Saudi Pharmaceutical Journal : SPJ :... Apr 2024Total extract of () expressed potent bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of total extract ( using liquid-liquid technique...
Total extract of () expressed potent bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of total extract ( using liquid-liquid technique followed by bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl) soluble fraction. Phytochemical study of the CHCl fraction guided by bronchodilator activity led to the isolation of 7 active flavones of which compounds (Tephroapollin G), (Acetyltephroapollin C), (4''-Dehydroxytephroapollin E), and (Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds , , and lanceolatin A () behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G () selectively inhibited CCh-mediated contractions but was not found active against high K. -Tephroapollin F () and (-)-Pseudosemiglabrin () in contrast were significantly more potent to abolish CCh induced contraction when compared with high K similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca ion inhibitory activities of and were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca inhibitory effect of and - was confirmed by the rightward deflection of Ca concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds and at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the , CHCl and to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol .
PubMed: 38435847
DOI: 10.1016/j.jsps.2024.101992 -
Cardiovascular Revascularization... Mar 2024The aim of this study was to determine if postprocedural peripheral fractional flow reserve (pFFR) is associated with patency one year after drug-coated balloon (DCB)...
PURPOSE
The aim of this study was to determine if postprocedural peripheral fractional flow reserve (pFFR) is associated with patency one year after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) lesions.
MATERIALS AND METHODS
Forty-five consecutive patients having 49 de novo FP lesions were enrolled in this prospective, observational study conducted from April 2022 to Aug 2023. The pFFR was measured under hyperemic conditions after the administration of 30 mg of papaverine. The relationship between pFFR and restenosis 12 months after the procedure was determined using receiver operating characteristic (ROC) curve analysis.
RESULTS
The one-year follow-up was completed for 47 lesions (95.9 %). Restenosis was detected in 7 lesions (14.9 %). Postprocedural pFFR was significantly higher in the nonrestenosis group compared with the pFFR in the stenosis group (0.95 ± 0.054 vs. 0.88 ± 0.090, p = 0.010). The optimal pFFR cutoff value for predicting restenosis was 0.92 (sensitivity, 0.824; specificity, 0.600). The area under the curve for pFFR was numerically higher than the area under the curve for minimum lumen area (0.73 vs. 0.64, p = 0.22). Rates of freedom from restenosis at one year were significantly higher in the pFFR >0.92 group compared with the pFFR ≤0.92 group (p = 0.0042).
CONCLUSION
Postprocedural pFFR was associated with patency at one year after DCB angioplasty for FP lesions.
PubMed: 38641440
DOI: 10.1016/j.carrev.2024.03.029 -
Analytical and Bioanalytical Chemistry Jan 2024The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium...
Comparison of direct analysis in real-time mass spectrometry, atmospheric solids analysis probe-mass spectrometry, and ion mobility spectrometry for ensuring food safety by rapid screening of poppy seeds.
The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium alkaloids including morphine, codeine, thebaine, noscapine, and papaverine are found primarily in the latex produced by the plant. If the plant is allowed to fully mature, poppy seeds that do not contain the opium alkaloids will form within the pods and may be used in the food industry. It is possible for the seeds to become contaminated with alkaloids by the latex during harvesting, posing a potential health risk for consumers. In the USA, there have been more than 600 reported adverse events including 19 fatalities that may be linked to the consumption of a contaminated poppy-containing product such as home-brewed poppy seed tea. Unwashed poppy seeds and pods may be purchased over the Internet and shipped worldwide. The Forensic Chemistry Center, US Food and Drug Administration (FDA) has evaluated several mass spectrometers (MS) capable of rapid screening to be used for high-throughput analysis of samples such as poppy seeds. These include a direct analysis in real-time (DART) ambient ionization source coupled to a single-quadrupole MS, an atmospheric solids analysis probe (ASAP) ionization source coupled to the same MS, and ion mobility spectrometers (IMS). These instruments have been used to analyze 17 poppy seed samples for the presence of alkaloids, and the results were compared to data obtained using liquid chromatography with mass spectral detection (LC-MS/MS). Results from the 17 poppy seed samples indicate that the DART-MS, ASAP-MS, and IMS devices detect many of the same alkaloids confirmed during the LC-MS/MS analyses, although both the false-positive and false-negative rates are higher, possibly due to the non-homogeneity of the samples and the lack of chromatographic separation.
Topics: Papaver; Opium; Chromatography, Liquid; Ion Mobility Spectrometry; Latex; Tandem Mass Spectrometry; Morphine; Alkaloids; Seeds
PubMed: 37999721
DOI: 10.1007/s00216-023-05042-6