Accidental venous port placement via the persistent left superior vena cava: Two case reports.

BACKGROUND: Breast cancer poses a great threat to females worldwide. There are various therapies available to cure this common disease, such as surgery, chemotherapy, radiotherapy, and immunotherapy. Implantable venous access ports (IVAP, referred to as PORT) have been widely used for breast cancer chemotherapy. Venous malformations are possible conditions encountered during PORT implantation. Persistent left superior vena cava (PLSVC) is a common superior vena cava malformation. Most patients have normal right superior vena cava without affecting hemodynamics, so patients often have no obvious symptoms. CASE SUMMARY: We incidentally found that two patients had PLSVC while a PORT was implanted via the internal jugular vein. Due to chemotherapy for breast cancer, PORT was successfully implanted under the guidance of ultrasound into these 2 patients. Positive chest X-ray examination after the operation showed that the catheter ran beside the left mediastinum and the end was located in the seventh thoracic vertebra. The patients had no catheter-related complications and successfully completed the course of chemotherapy. Ultrasonography found that the ratio of PORT outer diameter to PLSVC inner diameter was less than 0.45, which was in line with the recommendations of relevant literature and operating guidelines. The purpose of this article is to introduce two rare cases and review the relevant literature. CONCLUSION: Correct assessment of PLSVC status and ultrasound-guided PORT placement generally does not affect breast cancer patients chemotherapy.

CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Genetic polymorphisms of VKORC1 and CYP2C9 are known to influence warfarin dosage. * Recent studies among Caucasians showed that polymorphisms of CYP4F2 also play a role in warfarin pharmacogenetics. * The contribution of CYP4F2 variants to the variability inwarfarin dose requirement in Chinese subjects remains to be investigated. WHAT THIS STUDY ADDS * This research was to study the effect of CYP4F2 variants on warfarin requirements in the Han Chinese population. * This study developed a multiple regression model including CYP2C9, VKORC1 3673G>A, CYP4F2 genotypes and age, weight, combination use of amiodarone which could explain 56.1% of the individual variability in warfarin dose CYP4F2 could explain 4% of the variance in warfarin dose. * We found that one novel genotypic polymorphism 5417G>T for Asp36Tyr, which was identified as an important marker of warfarin resistance, was absent in the Han Chinese population in our study. AIMS The objective of this study was to assess the effect of the CYP4F2 on the daily stable warfarin dose requirement in Han Chinese patients with mechanical heart valve replacement (MHVR). METHODS From March 2007 to November 2008, 222 Han Chinese MHVR patients were recruited in our study. VKORC1 3673G>A, 5417G>T, CYP2C9*3 and CYP4F2 rs2108622 were genotyped by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Polymorphisms of VKORC1 9041G>A were detected by direct sequencing. Multiple linear regression analysis was used to investigate the contribution of CYP4F2. RESULTS The CYP4F2 rs2108622 CT/TT group took a significantly higher stable warfarin dose (3.2 mg day(-1)) than the CC group (2.9 mg day(-1), 95% CI 0.2, 1.0, P= 0.033). The multiple linear regression model included VKORC1 3673G>A, CYP2C9, CYP4F2 genotypes and clinical characteristics. The model could explain 56.1% of the variance in stable warfarin dose in Han Chinese patients with MHVR. CYP4F2 contributed about 4% to the variance in the warfarin dose. There was no variation in the SNPs of VKORC1 5417G>T. CONCLUSION CYP4F2 is a minor significant factor of individual variability in the stable warfarin dose in Han Chinese patients with MHVR. The effect of CYP2C9 and VKORC1 genotypes on variability in the stable warfarin dose had also been confirmed.

Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb (Rhei Rhizoma et Radix) is used for the treatment of digestive diseases in traditional medicinal practice in China. Recent studies also support its beneficial activities in alleviating ulcerative colitis (UC). AIM OF THE STUDY: This study aimed to characterize the oral pharmacokinetics of rhubarb anthraquinones, the main bioactive components of this herb, in the experimental chronic colitis rat model induced by dextran sulfate sodium (DSS) and to identify the factors causing the pharmacokinetic alterations. MATERIALS AND METHODS: Rats received drinking water (normal group) or 5% DSS for the first 7 days and 3% DSS for additional 14 days (UC group). On day 21 both groups received an oral dose of the rhubarb extract (equivalent to 5.0g crude drug/kg body weight). Plasma anthraquinone aglycones levels were determined directly by an LC-MS/MS method and the total of each anthraquinone (aglycone+conjugates) was quantified after ß-glucuronidases hydrolysis. RESULTS: Rhubarb anthraquinones predominantly existed as conjugates in plasma samples from both groups and only free aloe-emodin, rhein and emodin were detected. Compared to the normal rats, both Cmax and AUC of the three free anthraquinones were increased, while the systemic exposure (AUC) of the total (aglycone+conjugates) of most anthraquinones decreased by UC accompanied by the disappearance of multiple-peak phenomenon in the plasma concentration-time profiles. Gut bacteria from UC rats exhibited a decreased activity in hydrolyzing anthraquinone glycosides to form respective aglycone and there were significant decreases in microbial ß-glucosidases and ß-glucuronidases activities. Moreover, the intestinal microsomes from UC rats catalyzed glucuronidation of free anthraquinones with higher activities, while the activities of hepatic microsomes were comparable to normal rats. CONCLUSIONS: The decreases of ß-glucuronidases activity in DSS-induced chronic rat colitis should mainly account for the decreases in systemic exposure and abrogation of enterohepatic recirculation of most rhubarb anthraquinones after oral intake.

Pharmacokinetic evidence on the contribution of intestinal bacterial conversion to beneficial effects of astragaloside IV, a marker compound of astragali radix, in traditional oral use of the herb.

Astragaloside IV (AIV) is the most abundant saponin and a marker compound in Astragali Radix, a Chinese herb notable for its anti-aging and immune-enhancing effects. The present study investigated the role of intestinal bacterial conversion in the in vivo fate of AIV administered through a traditional oral route for the first time. When incubated anaerobically with rat intestinal bacteria, AIV generated five metabolites with three [monoglycosides brachyoside B and cyclogaleginoside B, the aglycone cycloastragenol (CA)] via stepwise deglycosylation and two from further epimerization (CA-iso) and dehydrogenation (CA-2H). Hydrolytic removal of C-6 glucose was a rate-limiting step for formations of CA and its derivatives. When AIV was orally administered to the rat, CA and CA-iso presented as the main components in plasma following AIV, and the AUC(0-∞) were 88.60 ± 9.66 (CA), 179.06 ± 28.53 (CA-iso) and 452.28 ± 43.33 nM·h (AIV). CA-2H was the predominant form in feces but was not detected in urine or plasma. This agreed well with in vitro data including rapid hepatic metabolism of CA-2H to form CA and CA-iso and reversible conversions between CA-2H and CA/CA-iso by intestinal bacteria. These findings support a crucial role of gut bacterial conversion of AIV in the traditional application of Astragali herb and warrant further investigational emphasis on CA and CA-iso.

In vitro pharmacokinetic characterization of mulberroside A, the main polyhydroxylated stilbene in mulberry (Morus alba L.), and its bacterial metabolite oxyresveratrol in traditional oral use.

Mulberroside A (MulA) is one of the main bioactive constituents in mulberry (Morus alba L.). This study examined the determining factors for previously reported oral pharmacokinetic profiles of MulA and its bacterial metabolite oxyresveratrol (OXY) on in vitro models. When incubated anaerobically with intestinal bacteria, MulA underwent rapid deglycosylation and generated two monoglucosides and its aglycone OXY sequentially. MulA exhibited a poor permeability and predominantly traversed Caco-2 cells via passive diffusion; yet, the permeation of OXY across Caco-2 cells was much more rapid and involved efflux (both p-glycoprotein and MRPs)-mediated mechanisms. Moreover, OXY underwent extensive hepatic glucuronidation; yet, the parent MulA was kept intact in liver subcellular preparations. There was insignificant species difference in intestinal bacterial conversion of MulA and the extent of OXY hepatic glucuronidation between humans and rats, while OXY exhibited a distinct positional preference of glucuronidation in the two species. Overall, these findings revealed a key role of intestinal bacterial conversion in absorption and systemic exposure of MulA and its resultant bacterial metabolite OXY in oral route in humans and rats and warranted further investigational emphasis on OXY and its hepatic metabolites for understanding the benefits of mulberry.