High-effective biosynthesis of baccatin â ¢ by using the alternative acetyl substrate, N-acetyl-d-glucosamine.

AIMS: Paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA (17 709 677·4 USD mol-1 ), which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production. METHODS AND RESULTS: In this study, a substrate spectrum with 14 kinds of representative acetyl-donor substitutes predicted by computer-aided methods was tested in a 10-deacetylbaccatin Ⅲ-10-O-acetyltransferase (DBAT) heterogeneous-expressed open-whole-cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl-donor compounds based on this substrate spectrum. N-acetyl-d-glucosamine (30·95 USD mol-1 , about 572 202-fold cheaper than acetyl-CoA) is selected as a suitable substitute under the rule. The yield when using N-acetyl-d-glucosamine as acetyl donor in open-whole-cell catalytic system was 2·13-fold of that when using acetyl-CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl-CoA. CONCLUSION: The success of open-whole-cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N-acetyl-d-glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ. SIGNIFICANCE AND IMPACT OF THE STUDY: All these findings provided a potential acetyl-donor substitute for acetyl-CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi-synthesis.

Comparative study of gene expression during tooth eruption and orthodontic tooth movement in mice.

OBJECTIVE: The aim of this study was to understand tooth eruption by comparing the gene expression during tooth eruption and orthodontic tooth movement (OTM). MATERIALS AND METHODS: Orthodontic force was applied on maxillary molars for 2, 4, 7 and 14 days to study tooth movement. Mice at PN 0, 7, 10, 15 and 21 were fixed to observe tooth eruption. Comparative study of two procedures was assessed by haematoxylin and eosin, tartrate-resistant acid phosphatase staining and in situ hybridization for matrix metalloproteinase (Mmp)2, 13, bone sialoprotein (Bsp) and osteocalcin (Ocn). RESULTS: Tartrate-resistant acid phosphatase activity and expression of Mmp2, 13 were obviously detectable in the compression region during OTM. They were also identified in the occlusal and apical region of alveolar bone during tooth eruption. Strong expression of Bsp and Ocn was detectable at the tension side during OTM. These genes were also expressed in the inner lateral region of alveolar bone adjacent to the tooth, but absent in the inner surface of the occlusal and root apical regions during tooth eruption. CONCLUSION: The process of alveolar bone metabolism during developmental eruption and OTM shares the same mechanism. Internal force, as the orthodontic force for OTM, may be initiating factor for tooth eruption.

Dosing in obesity: a simple solution to a big problem.

The global epidemic of obesity has led to an increased prevalence of chronic diseases and need for pharmacological intervention. However, little is known about the influence of obesity on the drug exposure profile, resulting in few clear dosing guidelines for the obese. Here we present a semi-mechanistic model for lean body weight (LBW) that we believe is sufficiently robust to quantify the influence of body composition on drug clearance, and is therefore an ideal metric for adjusting chronic dosing in the obese.

Factors predictive of intravenous fluid administration errors in Australian surgical care wards.

BACKGROUND: Intravenous (IV) fluid administration is an integral component of clinical care. Errors in administration can cause detrimental patient outcomes and increase healthcare costs, although little is known about medication administration errors associated with continuous IV infusions. OBJECTIVES: (1) To ascertain the prevalence of medication administration errors for continuous IV infusions and identify the variables that caused them. (2) To quantify the probability of errors by fitting a logistic regression model to the data. METHODS: A prospective study was conducted on three surgical wards at a teaching hospital in Australia. All study participants received continuous infusions of IV fluids. Parenteral nutrition and non-electrolyte containing intermittent drug infusions (such as antibiotics) were excluded. Medication administration errors and contributing variables were documented using a direct observational approach. RESULTS: Six hundred and eighty seven observations were made, with 124 (18.0%) having at least one medication administration error. The most common error observed was wrong administration rate. The median deviation from the prescribed rate was -47 ml/h (interquartile range -75 to +33.8 ml/h). Errors were more likely to occur if an IV infusion control device was not used and as the duration of the infusion increased. CONCLUSIONS: Administration errors involving continuous IV infusions occur frequently. They could be reduced by more common use of IV infusion control devices and regular checking of administration rates.

Blood transfusion and autologous donation: a survey of post-surgical patients, interest group members and the public.

Before planned surgery, patients may choose autologous donation in order to avoid the small, but potential, risks of receiving an allogeneic blood transfusion. This study examined the perceived risks of allogeneic blood transfusions, preferences and willingness to pay for autologous donation and the desired role in the decision-making process in three populations: post-surgical patients, special interest group members and the general public. Quantitative and qualitative data were collected from 206 respondents with the help of computer-assisted semi-structured telephone interviews. Thirty-three per cent of the sample voiced concerns about receiving allogeneic blood transfusions. The risks of hepatitis C virus, human immunodeficiency virus, variant Creutzfeldt-Jakob disease and a haemolytic reaction were perceived as being low, but were rated as numerically higher than those of other life events that have equal probability. Autologous donation was perceived as removing all the risks associated with transfusion, and respondents were willing to pay a median $976 AUD ($664 US) to use this technique. Over 80% of respondents preferred to be involved in making the decision about whether to use autologous donation. Even though autologous donation is not 'risk-free' and the blood supply is very safe, people overestimate the associated risks and have a preference for their own blood. Decision aids presenting balanced information on the advantages and disadvantages of both allogeneic and autologous blood may be required.

Time-domain transillumination of biological tissues with terahertz pulses.

We present time-domain transmission imaging of an opaque structure in pork-fat tissue obtained with a terahertz (THz) field sampling technique. Compared with imaging with near-infrared pulses, the terahertz sampling technique shows significantly enhanced contrast, as a result of low scattering. For enhanced spatial resolution, we show mid-infrared THz imaging of onion cells. Water absorption of THz pulse in muscle tissues is discussed.

Use of the organic crystal DAST for terahertz beam applications.

We report the use of the organic crystal DAST as a freely propagating electromagnetic-wave sensor at terahertz (THz) frequency. We also report the result of using a DAST crystal as a mid-IR THz emitter. Compared with the optical rectification from our best ZnTe emitter, that obtained by use of DAST demonstrates a sixfold enhancement of radiation at 7-20 THz.

Optical phonon dynamics of GaAs studied with time-resolved terahertz spectroscopy.

We investigate the reflection near the reststrahlen band of the optical phonon in bulk GaAs in the time domain, using time-resolved terahertz spectroscopy. We find that the dynamics of the reflection measured for GaAs differs strongly from the reflection dynamics that would be expected for a TO phonon with a frequency-independent dephasing time.