27 research outputs found
Ancient Chinese methods are remarkably effective for the preparation of artemisinin-rich extracts of Qing Hao with potent antimalarial activity.
yesAncient Chinese herbal texts as far back as the 4th Century Zhou hou bei ji fang
describe methods for the use of Qing Hao (Artemisia annua) for the treatment of
intermittent fevers. Today, the A. annua constituent artemisinin is an important
antimalarial drug and the herb itself is being grown and used locally for malaria treatment
although this practice is controversial. Here we show that the ancient Chinese methods that
involved either soaking, (followed by wringing) or pounding, (followed by squeezing) the
fresh herb are more effective in producing artemisinin-rich extracts than the usual current
method of preparing herbal teas from the dried herb. The concentrations of artemisinin in
the extracts was up to 20-fold higher than that in a herbal tea prepared from the dried herb,
but the amount of total artemisinin extracted by the Chinese methods was much less than
that removed in the herbal tea. While both extracts exhibited potent in vitro activities
against Plasmodium falciparum, only the pounded juice contained sufficient artemisinin to
suppress parasitaemia in P. berghei infected mice. The implications of these results are
discussed in the context of malaria treatment using A. annua infusions
Biotransformation of Monoterpenoids by Suspension Cultures of Lavandula angustifolia
Abstract Callus and suspension cultures of Lavandula angustifolia Mill. (Lamiaceae) were established and the effect of different culture media on growth rate was investigated. Terpenoids added to suspension culture to investigate their biotransformation. All samples were analyzed by gas chromatography (GC) and GC-mass spectroscopy (MS). Octan-1-ol, citronellol, linalool, borneol and geraniol were biotransformed products of octanal, citronellal, linalyl acetate, bornyl acetate and geranyl acetate, respectively. Citronellol, linalool, borneol, and menthol didn't change by L. angustifolia suspension cultures. Blue pigment production by cultures of L. angustifolia was also studied. Ester hydrolysis and oxidation were the main reactions which occurred in biotransformation process, which may be attributed to the presence of related or bifunctional enzymes. This technique is a possible way of the production of expensive or rare compounds from cheap and plentiful substrates
Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.
Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14路2 per cent (646 of 4544) and the 30-day mortality rate was 1路8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7路61, 95 per cent c.i. 4路49 to 12路90; P < 0路001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0路65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
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Can ancient texts assist in the development of herbal treatments for malaria?
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Kinobead Profiling Reveals Reprogramming of BCR Signaling in Response to Therapy within Primary CLL Cells
PURPOSE: B-cell receptor (BCR) signaling is critical for the pathogenesis of chronic lymphocytic leukemia (CLL), promoting both malignant cell survival and disease progression. Although vital, understanding of the wider signaling network associated with malignant BCR stimulation is poor. This is relevant with respect to potential changes in response to therapy, particularly involving kinase inhibitors. In the current study, we describe a novel high-resolution approach to investigate BCR signaling in primary CLL cells and track the influence of therapy on signaling response. EXPERIMENTAL DESIGN: A kinobead/mass spectrometry鈥揵ased protocol was used to study BCR signaling in primary CLL cells. Longitudinal analysis of samples donated by clinical trial patients was used to investigate the impact of chemoimmunotherapy and ibrutinib on signaling following surface IgM engagement. Complementary Nanostring and immunoblotting analysis was used to verify our findings. RESULTS: Our protocol isolated a unique, patient-specific signature of over 30 kinases from BCR-stimulated CLL cells. This signature was associated with 13 distinct Kyoto Encyclopedia of Genes and Genomes pathways and showed significant change in cells from treatment-na茂ve patients compared with those from patients who had previously undergone therapy. This change was validated by longitudinal analysis of clinical trials samples where BCR-induced kinome responses in CLL cells altered between baseline and disease progression in patients failing chemoimmunotherapy and between baseline and treatment in patients taking ibrutinib. CONCLUSIONS: These data comprise the first comprehensive proteomic investigation of the BCR signaling response within CLL cells and reveal unique evidence that these cells undergo adaptive reprogramming of this signaling in response to therapy