Stent thromboses due to multifactorial causes including hypercoagulable conditions and high on treatment platelet reactivity (HTPR), which means a low response to anti-platelet therapy, especially clopidogrel. Prasugrel is a third generation thienopyridine and inactive pro-drug requiring metabolic activation in vivo, which improves the rate of HTPR with clopidogrel. This drug is mostly effective, with a potent, fast, and consistent anti-platelet action, but rare cases of inadequate platelet inhibition with prasugrel have been reported. Here we describe the case of a 47-year-old man who presented with a recurrent acute myocardial infarction and ST during an intravascular ultrasound pullback and was resistant to prasugrel, was successfully treated with ticagrelor.
Activation, Metabolic ; Blood Platelets ; Humans ; Middle Aged ; Myocardial Infarction ; Prasugrel Hydrochloride* ; Stents* ; Thrombosis* ; Ultrasonography

The present study was designed to determine the intestinal bacterial metabolites of trollioside and isoquercetin and their antibacterial activities. A systematic in vitro biotransformation investigation on trollioside and isoquercetin, including metabolite identification, metabolic pathway deduction, and time course, was accomplished using a human intestinal bacterial model. The metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial activities of trollioside, isoquercetin, and their metabolites were evaluated using the broth microdilution method with berberine as a positive control, and their potency was measured as minimal inhibitory concentration (MIC). Our results indicated that trollioside and isoquercetin were metabolized by human intestinal flora through O-deglycosylation, yielding aglycones proglobeflowery acid and quercetin, respectively The antibacterial activities of both metabolites were more potent than that of their parent compounds. In conclusion, trollioside and isoquercetin are totally and rapidly transformed by human intestinal bacteria in vitro and the transformation favors the improvement of the antibacterial activities of the parent compounds.
Activation, Metabolic ; Anti-Bacterial Agents ; metabolism ; Bacteria ; metabolism ; Benzoates ; metabolism ; Biotransformation ; Gastrointestinal Microbiome ; Glucosides ; metabolism ; Humans ; Intestines ; microbiology ; Microbial Sensitivity Tests ; Models, Biological ; Quercetin ; analogs & derivatives ; metabolism

Among three representative species of Angelica found in Asian countries, including Korea, China, and Japan, Angelica acutiloba (AA) has been used as traditional herbal medicine with antitumor, anti-inflammatory, anti-obesity, and anti-diabetes activities. In this study, the potential genotoxicity and mutagenicity of the AA extract were examined in a battery of in vitro and in vivo tests (bacterial reverse mutation assay, in vitro chromosomal aberrations assay, and in vivo micronucleus assay) in accordance with the test guidelines for toxicity testing developed by the Organization for Economic Cooperation and Development. Upon testing in the bacterial mutation assay (Ames test) using five Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537, no significant increase the number of revertant colonies in the metabolic activation system and non-activation system was noted in the AA extract groups. Also, in the chromosome aberration test, the AA extract did not cause chromosomal aberration with or without metabolic activation by S9 mix. A bone marrow micronucleus test of mice demonstrated that the incidence of micronucleated polychromatic erythrocytes in the AA extract groups (500, 1000 and 2000 mg/kg BW) was equivalent to that of the negative control group. Based on these results from a standard battery of assays, the AA extract was concluded to have no genotoxic at the proper dose.
Activation, Metabolic ; Angelica* ; Animals ; Asian Continental Ancestry Group ; Bone Marrow ; China ; Chromosome Aberrations ; Erythrocytes ; Herbal Medicine ; Humans ; In Vitro Techniques* ; Incidence ; Japan ; Korea ; Medicine, Traditional ; Mice ; Micronucleus Tests ; Organisation for Economic Co-Operation and Development ; Salmonella typhimurium ; Toxicity Tests

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.
Activation, Metabolic ; Areca ; Asian Continental Ancestry Group ; Cytochrome P-450 Enzyme System ; Deglutition ; DNA ; DNA Damage ; Epithelium ; Female ; Fibroblasts ; Fibrosis ; Humans ; Incidence ; Lobeline* ; Male ; Mastication ; Mouth ; Mouth Neoplasms* ; Nicotine ; Nitrosamines ; Nuts ; Oral Submucous Fibrosis ; Prevalence* ; Reactive Oxygen Species ; Risk Factors ; RNA ; Tobacco ; Tobacco, Smokeless*

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.
Activation, Metabolic ; Areca ; Asian Continental Ancestry Group ; Cytochrome P-450 Enzyme System ; Deglutition ; DNA ; DNA Damage ; Epithelium ; Female ; Fibroblasts ; Fibrosis ; Humans ; Incidence ; Lobeline ; Male ; Mastication ; Mouth ; Mouth Neoplasms ; Nicotine ; Nitrosamines ; Nuts ; Oral Submucous Fibrosis ; Prevalence ; Reactive Oxygen Species ; Risk Factors ; RNA ; Tobacco ; Tobacco, Smokeless