Continuous fermentation of wheat-supplemented lignocellulose hydrolysate with different types of cell retention.

Medium supplementation and process alternatives for fuel ethanol production from dilute acid lignocellulose hydrolysate were investigated. Dilute acid lignocellulose hydrolysate supplemented with enzymatically hydrolysed wheat flour could sustain continuous anaerobic cultivation of Saccharomyces cerevisiae ATCC 96581 if further supplemented with ammonium sulphate and biotin. This medium composition allowed for a hexose utilisation of 73% and an ethanol production of 36 mmol l(-1) h(-1) in chemostat cultivation at dilution rate 0.

Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered.

Objective: To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans.

Methods: In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 microl) were collected by means of a finger prick and dried on filter paper.

CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir.

CYP3A is the main enzyme subfamily involved in the metabolism of the HIV protease-inhibitor saquinavir. We hypothesized that individuals homozygous for CYP3A5*1 might have a higher oral clearance of saquinavir, compared with subjects lacking functional CYP3A5 alleles. A single-dose pharmacokinetic trial of saquinavir soft gel capsules, 1,200 mg, was performed in 16 black Tanzanian healthy volunteers with two functional CYP3A5 alleles (*1/*1) and in 18 volunteers without functional CYP3A5 alleles (both alleles being either *3, *6, or *7).

Pharmacokinetics of quinine and its metabolites in pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria.

Objectives: The study was conducted in New Halfa teaching hospital, eastern Sudan to investigate the pharmacokinetics of quinine in pregnant Sudanese women.

Methods: Sixteen (eight pregnant and eight non-pregnant) Sudanese women infected with Plasmodium falciparum malaria were given a single dose of quinine hydrochloride (10 mg/kg body weight) as intravenous infusion over 2 h. The women were treated with intramuscular artemether.

Industrial biotechnology for the production of bio-based chemicals--a cradle-to-grave perspective.

Shifting the resource base for chemical production from fossil feedstocks to renewable raw materials provides exciting possibilities for the use of industrial biotechnology-based process tools. This review gives an indication of the current developments in the transition to bio-based production, with a focus on the production of chemicals, and points out some of the challenges that exist in the large-scale implementation of industrial biotechnology. Furthermore, the importance of evaluating the environmental impact of bio-based products with respect to their entire life cycle is highlighted, demonstrating that the choice of the raw material often turns out to be an important parameter influencing the life cycle performance.

Increase in exhaled nitric oxide and protective role of the nitric oxide system in experimental pulmonary embolism.

Background And Purpose: Pulmonary embolism (PE) represents a real diagnostic challenge. PE is associated with pulmonary hypertension due to pulmonary vascular obstruction and vasoconstriction. We recently reported that pulmonary gas embolism transiently increases exhaled nitric oxide (FENO), but it is not known whether solid emboli may alter FENO, and whether an intact endogenous NO synthesis has a beneficial effect in experimental solid pulmonary embolism.

Assessing health worker performance in malaria case management of underfives at health facilities in a rural Tanzanian district.

Objective: To study the quality of malaria case management of underfives at health facilities in a rural district, 2 years after the Tanzanian malaria treatment policy change in 2001.

Methods: Consultations of 117 sick underfives by 12 health workers at 8 health facilities in Mkuranga District, Tanzania were observed using checklists for history taking, counselling and prescription. Diagnoses and treatment were recorded.

Influence of cultivation conditions on mechanical and morphological properties of bacterial cellulose tubes.

Bacterial cellulose (BC) was deposited in tubular form by fermenting Acetobacter xylinum on top of silicone tubes as an oxygenated support and by blowing different concentrations of oxygen, that is, 21% (air), 35%, 50%, and 100%. Mechanical properties such as burst pressure and tensile properties were evaluated for all tubes. The burst pressure of the tubes increased with an increase in oxygen ratio and reached a top value of 880 mmHg at 100% oxygen.

Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve-induced release of nitric oxide from the rabbit corpus cavernosum.

Background And Purpose: Nitrergic neurons are important for erectile responses in the corpus cavernosum and impaired signalling results in erectile dysfunction, today treated successfully by oral administration of the selective phosphodiesterase 5 (PDE 5) inhibitors sildenafil, tadalafil and vardenafil. Although the importance of nitrergic neurons in urogenital function has become evident, it has not been investigated if the PDE 5 inhibitors affect the nerve-induced release of nitric oxide (NO). In a previous study we found that the soluble guanylate cyclase (sGC)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway might modulate nerve-induced release of NO in isolated cavernous tissue.

Levels of linkage disequilibrium in a wild bird population.

Population-based mapping approaches are attractive for tracing the genetic background to phenotypic traits in wild species, given that it is often difficult to gather extensive and well-defined pedigrees needed for quantitative trait locus analysis. However, the feasibility of association or hitch-hiking mapping is dependent on the degree of linkage disequilibrium (LD) in the population, on which there is yet limited information for wild species. Here we use single nucleotide polymorphism (SNP) markers from 23 genes in a recently established linkage map of the Z chromosome of the collared flycatcher, to study the extent of LD in a natural bird population.

Cross-fostering reveals seasonal changes in the relative fitness of two competing species of flycatchers.

Spatial and temporal heterogeneity in relative fitness of competing species is a key factor affecting the structure of communities. However, it is not intuitive why species that are ecologically similar should differ in their response to environmental changes. Here we show that two sympatric flycatchers differ in reproductive strategy and in sensitivity to harsh environment.

Improved yields of full-length functional human FGF1 can be achieved using the methylotrophic yeast Pichia pastoris.

We have produced human fibroblast growth factor 1 (hFGF1) in the methylotrophic yeast Pichia pastoris in order to obtain the large amounts of active protein required for subsequent functional and structural characterization. Four constructs were made to examine both intracellular and secreted expression, with variations in the location of the His6 tag at either end of the peptide. hFGF1 could be produced from all four constructs in shake flasks, but production was optimized by growing only the highest-yielding of these strains, which produced hFGF1 intracellularly, under tightly controlled conditions in a 3 L fermentor.

Time-dependent alterations in ethanol intake in male wistar rats exposed to short and prolonged daily maternal separation in a 4-bottle free-choice paradigm.

Background: Previous studies have shown that maternal separation can be used in animal studies of early environmental influence on adult ethanol intake. These studies have shown that short daily separations result in low ethanol intake, whereas prolonged separations relate to an enhanced risk for a high ethanol intake. The aim of the present study was to further examine the long-term effects of early-life events on ethanol intake.

Improved efficacy with amodiaquine instead of chloroquine in sulfadoxine/pyrimethamine combination treatment of falciparum malaria in Uganda: experience with fixed-dose formulation.

Amodiaquine (AQ) is an affordable compound, chemically related to chloroquine (CQ) but often effective against CQ resistant Plasmodium falciparum. In Uganda, a pre-packed fixed-dose combination of CQ plus sulfadoxine/pyrimethamine (CQ+SP) called Homapak is used in the home based management of fever program (HBM). We performed a single blind randomized trial to determine the efficacy of AQ+SP in comparison with the fixed-dose CQ+SP (Homapak) in the treatment of uncomplicated falciparum malaria in Ugandan children aged 6 months to 5 years.

Workplace NO and NO2 during combined treatment of infants with nasal CPAP and NO.

Objective: To determine the workplace concentrations of NO and NO(2) in and around a paediatric incubator during inhaled NO (iNO) treatment and during an accidental emptying of NO cylinders into room air.

Design: We simulated iNO-nasal CPAP treatment in order to assess the impact on the occupational environment. Furthermore, two full NO cylinders for therapy, 1,000 ppm, 20 litres, 150 bar and 400 ppm, 10 litres, 150 bar, were emptied as rapidly as possible into an intensive care unit (ICU) room.

Eukaryotic expression: developments for structural proteomics.

The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high-throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and transient expression in mammalian cells.

Comparison between effects of intravenous and nebulized histamine in guinea pigs: correlation between changes in respiratory mechanics and exhaled nitric oxide.

Nitric oxide (NO) is a marker of airway inflammation in humans, despite not having effects on basal bronchial tone. Inhibition of NO synthesis can lead to enhanced airway reactivity in humans and it is therefore of importance to understand how bronchial provocation can affect endogenous NO. Presently, we have studied the role of exhaled nitric oxide in airway reactivity by measuring changes in pulmonary mechanics in response to histamine in anaesthetized guinea pigs.

Long-term follow-up of Swedish children vaccinated with acellular pertussis vaccines at 3, 5, and 12 months of age indicates the need for a booster dose at 5 to 7 years of age.

Objectives: The purpose of this work was to evaluate the long-term effectiveness of vaccination with acellular pertussis vaccines at 3, 5, and 12 months of age.

Methods: Clinical follow-up of reported culture- and polymerase chain reaction-confirmed cases of pertussis was initiated during October 1997 in most of Sweden (except Gothenburg and environs). The study population included 90% of Swedish children born during 1996 or later (ie, who received diphtheria-tetanus-acellular pertussis vaccines at 3, 5, and 12 months of age) and children who had participated in a large pertussis vaccine trial in 1993-1996.

Generation of NO by probiotic bacteria in the gastrointestinal tract.

Probiotic bacteria elicit a number of beneficial effects in the gut but the mechanisms for these health promoting effects are not entirely understood. Recent in vitro data suggest that lactobacilli can utilise nitrate and nitrite to generate nitric oxide, a gas with immunomodulating and antibacterial properties. Here we further characterised intestinal NO generation by bacteria.

Sternal stability at different negative pressures during vacuum-assisted closure therapy.

Background: Vacuum-assisted closure (VAC) is a widely used therapy in patients with poststernotomy mediastinitis. The aim of this study was to evaluate sternal stability during VAC application at seven negative pressures (-50 to -200 mm Hg) in a porcine wound model.

Methods: Six pigs underwent median sternotomy and 2 steel wires were fixed at each sternal side and connected to a traction device.

Pharmacokinetic interactions between chloroquine, sulfadoxine and pyrimethamine and their bioequivalence in a generic fixed-dose combination in healthy volunteers in Uganda.

Background: A pre-packaged fixed-dose formulation of chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P) combination (Homapak) is widely used for the treatment of falciparum malaria in Ugandan children. It is however a product whose pharmacokinetics and interactions have not been studied.

Objectives: To explore possible pharmacokinetic interactions between CQ and S/P during co-administration, and to determine their bioavailability in the locally made Homapak compared to the Good Manufacturing Practice (GMP) made formulations.

Genetic and environmental variation in immune response of collared flycatcher nestlings.

This paper aims at partitioning genetic and environmental contribution to the phenotypic variance in nestling immune function measured with the hypersensitivity test after inoculation with phytohaemagglutinin. A cross-fostering experiment with artificial enlargement of some broods was conducted. Variation in nestling immune response was related to their common origin, which suggests heritable component of cell-mediated immunity.

CYP3A5 genotype has significant effect on quinine 3-hydroxylation in Tanzanians, who have lower total CYP3A activity than a Swedish population.

Objectives: To study the correlation between CYP3A5 genotype and quinine 3-hydroxylation in black Tanzanian and Swedish Caucasians as well as to investigate the interethnic differences in CYP3A activity between the two populations.

Methods: Tanzanian (n=144) and Swedish (n=136) healthy study participants were given a single oral 250 mg dose of quinine hydrochloride and a 16-h post-dose blood sample was collected. The metabolic ratio of quinine/3-hydroxyquinine was determined in plasma by high-performance liquid chromatography.