Safety of herbal medicinal products: Echinacea and selected alkylamides do not induce CYP3A4 mRNA expression

Copyright © 2011 Maryam Modarai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A major safety concern with the use of herbal medicinal products (HMP) is their interactions with conventional medicines, which are often mediated via the cytochrome P450 (CYP) system. Echinacea is a widely used over-the-counter HMP, with proven immunomodulatory properties. Its increasing use makes research into its safety an urgent concern. Previously, we showed that Echinacea extracts and its alkylamides (thought to be important for Echinacea's immunomodulatory activity) mildly inhibit the enzymatic activity of the main drug metabolising CYP isoforms, but to this date, there is insufficient work on its ability to alter CYP expression levels. We now report for the first time the effect of a commercial Echinacea extract (Echinaforce) and four Echinacea alkylamides on the transcription of the major drug metabolizing enzyme CYP3A4. HepG2 cells were exposed for 96 h to clinically relevant concentrations of Echinaforce (22, 11.6 and 1.16g mL-1) or the alkylamides (1.62 and 44 nM). CYP3A4 mRNA levels were quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Neither Echinaforce nor the alkylamides produced any significant changes in the steady-state CYP3A4 mRNA levels, under these conditions. In contrast, treatment with 50M rifampicin resulted in a 3.8-fold up-regulation over the vehicle control. We conclude that Echinaforce is unlikely to affect CYP3A4 transcriptional levels, even at concentrations which can inhibit the enzymatic activity of CYP3A4. Overall, our data provides further evidence for the lack of interactions between Echinacea and conventional drugs.Bioforce, Switzerland and the Maplethorpe Trust (University of London)

The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. BecauseALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA)signaling, we studied RA signaling in normal and malignant colonic SCs.Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonicSCs dysregulation of RA signaling contributes to SC overpopulation and colorectalcancer (CRC) development.Methods: We analyzed normal and malignant colonic tissues and CRC cell linesto see if retinoid receptors (RXR &RAR) are exclusively expressed in ALDH+ SCs,and if RA signaling changes during CRC development. We determined whether RAsignaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation,and population size.Results: RXR &RAR were expressed in ALDH+ colonic SCs, but not in MCM2+proliferative cells. Western blotting/immunostaining of CRCs revealed that RAsignaling components become overexpressed in parallel with ALDH overexpression,which coincides with the known overpopulation of ALDH+ SCs that occurs during,and drives, CRC development. Treatment of SCs with all-trans retinoic acid (ATRA)decreased proliferation, sphere formation and ALDH+ SC population size, and induceddifferentiation along the neuroendocrine cell (NEC) lineage.Conclusions: Retinoid signaling, by regulating ALDH+ colonic CSCs, decreases SCproliferation, sphere formation, and population size, and increases SC differentiation toNECs. Dysregulation of RA signaling in colonic SCs likely contributes to overpopulationof ALDH+ SCs and CRC growth.Implications: That retinoid receptors RXR and RAR are selectively expressed inALDH+ SCs indicates RA signaling mainly occurs via ALDH+ SCs, which provides amechanism to selectively target CSCs. © 2018 Impact Journals LLC. All rights reserved

Outcomes following colectomy for Clostridium difficile colitis

AbstractIntroductionClostridium difficile associated diarrhoea has become an important health problem in UK hospitals but surgical intervention is rarely required. There is little evidence regarding best practice for patients requiring surgical intervention. The aim of this multicentre study was to review our experience in patients requiring surgery for C. difficile colitis.MethodsPatients who underwent surgery for C. difficile colitis in 5 hospitals in Southeast England over a 7-year period (1 teaching hospital and 4 district general hospitals) were identified from histopathology databases. Data were collected regarding the presentation, indication for surgery and post-operative outcomes.Results15 patients (9 males; mean age=71 years (range 35–84 years)) underwent surgery. 46% of patients (n=7) contracted C. difficile during their hospital admission for other medical reasons and 73% of patients were initially admitted under other medical specialties. Diagnosis was only made preoperatively in 8 patients (53%). Indications for surgery were peritonitis and systemic toxicity (n=12), failure of medical management (n=2) and unresolving large bowel dilatation (n=1). 12 patients underwent total colectomy and the rest underwent segmental resection. All patients were admitted to the intensive care unit post operatively with a mean stay of 6 days. 2 patients needed a second look laparotomy. Mortality rate was 67% (n=10), with all but 1 patient dying within the 30-day mortality period. The mean length of hospital stay of survivors was 30 days (range 17–72).ConclusionsSurgical intervention for C. difficile colitis remains uncommon. Total colectomy and end ileostomy is the procedure of choice. The outlook for patients requiring surgery remains poor

Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on Radiation Safety

Funding Information: On behalf of the Public and Community Oversight Group (PCOG) of the Health Protection Research Unit in Chemical and Radiation Threats and Hazards: Ian Wright; John Phipps; Colette Kelly; Robert Goundry; Eve Smyth; Andrew Wood; Paul Dale (also of the Scottish Environment Protection Agency). On behalf of the Society and College of Radiographers Patient Advisory Group: Lynda Johnson; Philip Plant; Michelle Carmichael – Specialist Senior Staff Nurse Guy's and St Thomas’ NHS Foundation trust.Peer reviewe

Leukocytes and the Natural History of Deep Vein Thrombosis Current Concepts and Future Directions

Observational studies have shown that inflammatory cells accumulate within the thrombus and surrounding vein wall during the natural history of venous thrombosis. More recent studies have begun to unravel the mechanisms that regulate this interaction and have confirmed that thrombosis and inflammation are intimately linked. This review outlines our current knowledge of the complex relationship between inflammatory cell activity and venous thrombosis and highlights new areas of research in this field. A better understanding of this relationship could lead to the development of novel therapeutic targets that inhibit thrombus formation or promote its resolution.</jats:p

An alternative surgical approach to subclavian and innominate stenosis: a case series

We report three cases of symptomatic stenosis of the great vessels or supra-aortic trunks successfully treated surgically with aorto-subclavian and aorto-innominate bypass. Two were performed via manubriotomy and a third case via standard median sternotomy because of concomitant coronary revascularisation. There was complete symptomatic relief on follow-up, and radiological imaging confirmed good flow in the grafts and post-stenotic arteries