Green biorefinery - Industrial implementation.

Oil refineries currently generate a multitude of products for almost every sphere of life at very high efficiency. However, fossil raw materials are just available in limited quantities. The development of comparable BIOREFINERIES is necessary to make a variety of competitive biological products regarding their equivalent products based on fossil raw materials. The product range of a biorefinery comprises products that can be manufactured on the basis of crude oil, as well as such products that cannot be produced on the basis of crude oil (Kamm, Gruber, & Kamm, 2011). GREEN BIOREFINERIES [GBR's] are complex systems of sustainable, environment- and resource-friendly technologies for a comprehensive material and energy use or recovery of renewable raw materials in form of green and waste biomasses from a sustainable land use as target (Kamm et al., 2009; Digman, Runge, Shinners, & Hatfield, 2013).

Biorefineries--multi product processes.

The development of biorefineries represents the key for access to an integrated production of food, feed, chemicals, materials, goods, and fuels of the future [1]. Biorefineries combine the necessary technologies of the biogenic raw materials with those of intermediates and final products. The main focus is directed at the precursors carbohydrates, lignin, oils, and proteins and the combination between biotechnological and chemical conversion of substances. Currently the lignocellulosic feedstock biorefinery, green biorefinery, whole corn biorefinery, and the so-called two-platform concept are favored in research, development, and industrial implementation.

Chemical and biochemical generation of carbohydrates from lignocellulose-feedstock (Lupinus nootkatensis)--quantification of glucose.

Different chemical and enzymatic methods were applied for the hydrolysis of main stems from Lupinus nootkatensis (harvest November 2002). The whole process (all steps) is based on the lignocellulose-feedstock biorefinery regime. The acid hydrolysis of L. was performed with concentrated hydrochloric acid; advantages in this process are exothermic hydrolysis and the possibility of acid recovery. Enzymatic hydrolysis achieved high yields of fermentable carbohydrates (regarding to input cellulose) with high selectivity. However, this way requires the generation of cellulose from L. by chemical pulping. Monosaccharide derivatives thus obtained were identified by their GC retention times and the corresponding MS fragmentation. Hexamethyldisilazane was used as derivatization reagent to prepare the trimethylsilyl derivatives of the carbohydrates and of the degradations products of cellulose from the different fractions. The glucose content was quantified by GC peak integration with respect to an internal standard.

Polycarnitine--a new biomaterial.

The natural product L-carnitine is--due to its biotechnological accessibility and specific properties--on the way to becoming an attractive biobased bulk product. L-carnitine is a natural betaine with vitamin properties. Carnitine is an essential part of the fatty acid metabolism of human beings and animals. Carnitine was first isolated in 1905 from meat extract and important recent developments include the biosyntheses of L-carnitine from L-lysine or gamma-butyrobetaine. Our synthesis routes are designed to maintain the primary structure and specific properties of carnitine, such as hydrophilicity and "stiffening" effects for polymeric structures and applications. L-carnitine is converted via lactonization or olefinization into polymerizable basic molecules. The properties and the applications of carnitine polymers are described.

Principles of biorefineries.

Sustainable economic growth requires safe, sustainable resources for industrial production. For the future re-arrangement of a substantial economy to biological raw materials, completely new approaches in research and development, production and economy are necessary. Biorefineries combine the necessary technologies between biological raw materials and industrial intermediates and final products. The principal goal in the development of biorefineries is defined by the following: (biomass) feedstock-mix + process-mix --> product-mix. Here, particularly the combination between biotechnological and chemical conversion of substances will play an important role. Currently the "whole-crop biorefinery", "green biorefinery" and "lignocellulose-feedstock biorefinery" systems are favored in research and development.

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Separation, identification, and quantification of amino acids in L-lysine fermentation potato juices by gas chromatography-mass spectrometry.

The amino acid composition of L-lysine fermentation juices from potatoes and cane molasses from a green biorefinery has been determined by gas chromatography-mass spectrometry. N-Methyl-N-tert(butyldimethylsilyl)tri-fluoroacetamide (MTBSTFA) was used as derivatization reagent to prepare the t-butyldimethylsilyl derivatives of the amino acids present in the juices. The amino acids in these derivatives were identified from both their EI and CI mass spectra and their retention times in the gas chromatogram, and they were quantified employing the GC response signals relative to cycloleucine as internal standard.

The mammographer's role in addressing special needs.

Many mammography patients have special needs related to their age, sex, surgical status or a physical or mental condition. This article describes some of the accommodations mammographers can make to ensure excellent imaging and quality care for their patients with special needs.

Communicating with mammography patients.

This article examines the barriers that prevent many women from undergoing mammography and strategies that can help them overcome those barriers. It also describes techniques for effective, individualized patient communication and education. Mammographers will learn how to ask the right questions, listen effectively for stated and unstated messages and determine which methods to use when communicating with different patients.

Qualitative and quantitative analysis of carbohydrates in green juices (wild mix grass and alfalfa) from a green biorefinery by gas chromatography/mass spectrometry.

Green juices from biorefinery original raw material (wild mix grass and alfalfa after wet fractionation and protein separation) have been investigated by gas chromatography/mass spectrometry. The carbohydrates, involved in the green juices, were derivatized and identified by both their retention times in the gas chromatogram and EI mass spectra compared to those of pure reference compounds. Additionally, chemical ionization mass spectra were recorded for better characterizing the carbohydrates present. The carbohydrates which could thus be identified, were quantified by response signals with respect to that of the internal standard beta-phenyl-D-glucopyranoside.

Breast procedures and imaging techniques.

A variety of image-guided procedures and new imaging techniques are being used to supplement film-screen mammography and surgical biopsy in detection and evaluation of breast cancer. This article describes and evaluates several of these techniques, including image-guided needle procedures, galactography, magnetic resonance imaging and spectroscopy and positron emission mammography. Studies suggest these procedures may lead to more accurate characterization of breast masses and less surgery for breast cancer patients.

Current techniques in sentinel node mapping.

The prognosis for patients with breast cancer or melanoma largely depends on the involvement of nearby lymph nodes. This article examines techniques used to identify and assess sentinel nodes--those that drain the cancerous area. Such techniques may permit more conservative, node-sparing treatment. Studies evaluating the use of both radiopharmaceuticals and colored dyes are described.

Clinical pharmacokinetics of mycophenolate mofetil.

The pharmacokinetics of the immunosuppressant mycophenolate mofetil have been investigated in healthy volunteers and mainly in recipients of renal allografts. Following oral administration, mycophenolate mofetil was rapidly and completely absorbed, and underwent extensive presystemic de-esterification. Systemic plasma clearance of intravenous mycophenolate mofetil was around 10 L/min in healthy individuals, and plasma mycophenolate mofetil concentrations fell below the quantitation limit (0.4 mg/L) within 10 minutes of the cessation of infusion. Similar plasma mycophenolate mofetil concentrations were seen after intravenous administration in patients with severe renal or hepatic impairment, implying that the de-esterification process had not been substantially affected. Mycophenolic acid, the active immunosuppressant species, is glucuronidated to a stable phenolic glucuronide (MPAG) which is not pharmacologically active. Over 90% of the administered dose is eventually excreted in the urine, mostly as MPAG. The magnitude of the MPAG renal clearance indicates that active tubular secretion of MPAG must occur. At clinically relevant concentrations, mycophenolic acid and MPAG are about 97% and 82% bound to albumin, respectively. MPAG at high (but clinically realisable) concentrations reduced the plasma binding of mycophenolic acid. The mean maximum plasma mycophenolic acid concentration (Cmax) after a mycophenolate mofetil 1 g dose in healthy individuals was around 25 mg/L, occurred at 0.8 hours postdose, decayed with a mean apparent half-life (t1/2) of around 16 hours, and generated a mean total area under the plasma concentration-time curve (AUC infinity) of around 64 mg.h/L. Intra- and interindividual coefficients of variation for the AUC infinity of the drug were estimated to be 25% and 10%, respectively. Intravenous and oral administration of mycophenolate mofetil showed statistically equivalent MPA AUC infinity values in healthy individuals. Compared with mycophenolic acid, MPAG showed a roughly similar Cmax about 1 hour after mycophenolic acid Cmax, with a similar t1/2 and an AUC infinity about 5-fold larger than that for mycophenolic acid. Secondary mycophenolic acid peaks represent a significant enterohepatic cycling process. Since MPAG was the sole material excreted in bile, entrohepatic cycling must involve colonic bacterial deconjugation of MPAG. An oral cholestyramine interaction study showed that the mean contribution of entrohepatic cycling to the AUC infinity of mycophenolic acid was around 40% with a range of 10 to 60%. The pharmacokinetics of patients with renal transplants (after 3 months or more) compared with those of healthy individuals were similar after oral mycophenolate mofetil. Immediately post-transplant, the mean Cmax and AUC infinity of mycophenolic acid were 30 to 50% of those in the 3-month post-transplant patients. These parameters rose slowly over the 3-month interval. Slow metabolic changes, rather than poor absorption, seem responsible for this nonstationarity, since intravenous and oral administration of mycophenolate mofetil in the immediate post-transplant period generated comparable MPA AUC infinity values. Renal impairment had no major effect on the pharmacokinetic of mycophenolic acid after single doses of mycophenolate mofetil, but there was a progressive decrease in MPAG clearance as glomerular filtration rate (GFR) declined. Compared to individuals with a normal GFR, patients with severe renal impairment (GFR 1.5 L/h/1.73m2) showed 3-to 6-fold higher MPAG AUC values. In rental transplant recipients during acute renal impairment in the early post-transplant period, the plasma MPA concentrations were comparable to those in patients without renal failure, whereas plasma MPAG concentrations were 2- to 3-fold higher. Haemodialysis had no major effect on plasma mycophenolic acid or MPAG. Dosage adjustments appear to not be necessary either in renal impairment or during dialysis. (ABSTRACT TRUN

Pharmacokinetics of oral mycophenolate mofetil in volunteer subjects with varying degrees of hepatic oxidative impairment.

Eighteen patients with compensated alcoholic cirrhosis participated in a single-dose pharmacokinetic study of oral mycophenolate mofetil (MMF). Participants were divided into groups of 6 patients each with mild, moderate, or severe hepatic oxidative impairment as defined by the aminopyrine breath test (APBT). Clinically, hepatic disease was of mild or moderate severity. Six healthy volunteers were included as control subjects. Plasma and urine samples were collected over 96 hours and assayed for the active metabolite mycophenolic aced (MPA) and the glucuronide conjugate, MPAG. Plasma protein binding of MPA also was determined in 6 unrelated patients with cirrhosis. Cirrhosis did not grossly affect plasma pharmacokinetics or plasma binding of MPA. Maximum plasma concentrations (C(max)) and area under the curve (AUC) of MPA and MPAG consistently decreased, increased, and then decreased as oxidative impairment declined from normal to severe. Patients with cirrhosis had comparable or greater recovery of administered drug substance in urine than controls, showing that cirrhosis did not affect the extent of MMF absorption. Urine clearance of MPAG was two times higher in the group with severe impairment than in the other groups. Creatinine clearance was similar in all groups. These results suggest progressive impairment of hepatic glucuronidation of MPA and induction of renal glucuronidation in patients with severe hepatic oxidative impairment.

Prevention of stroke with ticlopidine: who benefits most? TASS Baseline and Angiographic Data Subgroup.

We examined the baseline characteristics of patients in the Ticlopidine Aspirin Stroke Study (TASS) to determine if the effects of the two treatments in preventing stroke differed in various subgroups. Patients with the following characteristics did less well on aspirin: elevated creatinine, hypertension or diabetes requiring treatment, or treatment with anticoagulant or antiplatelet drugs prior to their qualifying TIA or stroke. Women and patients with vertebrobasilar symptoms did particularly well on ticlopidine. We performed arteriography in 1,188 patients with carotid qualifying events. The frequency of stroke in patients with abnormal arteriograms ipsilateral to their symptoms was slightly higher than in those with normal carotid arteries. Ticlopidine was more effective in patients without carotid stenosis. Ticlopidine is more effective than aspirin in preventing strokes in patients having warning TIAs. The patients who benefit most from ticlopidine may be women, those who have vertebrobasilar symptoms, those with cerebral ischemic symptoms while on aspirin or anticoagulant therapy, and patients with diffuse atherosclerotic disease rather than high-grade carotid stenosis.

A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group.

We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.

Design features of a controlled clinical trial to assess the effect of a calcium entry blocker upon the progression of coronary artery disease.

This report presents the design and methodological features of a double-blind, randomized, placebo-controlled, trial in 383 patients with coronary artery disease. The study's principal objective is to determine whether chronic treatment with a calcium entry blocker can retard the progression of coronary artery disease. The study population consists of patients with coronary artery disease and a baseline coronary arteriogram that qualifies them as being at high risk for disease progression. After satisfying all entry criteria, patients were randomized to receive either the calcium entry blocker nicardipine or placebo. All indicated concomitant medications except calcium entry blockers are permitted. Patients are being followed clinically for 24 months before undergoing a second coronary arteriogram. The effect of the treatments on a variety of clinical and angiographic parameters will be determined.