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In eukaryotic cells, the endoplasmic reticulum (ER) is the principal site for the folding and maturation of transmembrane, secretory and ER-resident proteins. Functions of the ER are affected by various intracellular and extracellular stimuli, which include inhibition of glycosylation, reduction of disulfide bonds, calcium depletion from the ER lumen, impairment of protein transport to the Golgi, and expression of mutated proteins in the ER. Under ER stress, unfolded/misfolded proteins accumulate in the ER lumen, which induces conflicting cellular activities: survival and apoptosis. To cope with this stress, cells activate intracellular signalling pathways, such as the unfolded protein response (UPR) and the ER-associated degradation (ERAD). However, under conditions of severe ER stress or when the UPR has been compromised, the cell may be incapable of maintaining ER homeostasis, which may eventually activate programmed cell death (PCD) pathways. Clinical data support the potential of drugs that inhibit the normal functions and homeostasis of the ER and the proteasome in treatment of malignancies like cancer. It is therefore reasonable to assume that manipulation of ER stress might enhance the efficacy of chemotherapeutic drugs and provide new anticancer targets like the ER and the proteasome.

Hurler syndrome (MPS 1H) is the severe form of mucopolysaccharidosis type 1 (MPS 1). Haematopoietic cell transplantation (HCT) is the treatment of choice, but carries a high incidence of graft failure and morbidity. The use of enzyme replacement therapy (ERT) might improve the clinical signs and symptoms before HCT, resulting in less transplantation-related complications. Moreover, clearance of glycosaminoglycans (GAG's) from the bone marrow might improve engraftment. Twenty-two patients with MPS 1H received one or more HCT procedures in combination with ERT. One patient with severe cardiomyopathy improved significantly after ERT. All children were in a relatively good clinical condition before HCT. Of patients 59, 82 and 86% were alive and engrafted after one, two and three HCT procedures, respectively. Two patients died after repetitive HCT. No serious ERT-infusion-related toxicity occurred. ERT with HCT was well tolerated. Neither a positive nor a negative effect on the number of patients who are alive and engrafted after receiving ERT before HCT as compared to a historic cohort was noted. However, patients in a poor clinical condition before HCT might benefit from ERT.

The use of catheters is often complicated by infection, mainly due to Staphylococcus epidermidis. Recently, a novel poly(vinylpyrrolidone)-grafted silicone elastomer catheter (SEpvp) was introduced. Less bacteria adhered to SEpvp than to conventional SE catheters in vitro. The frequency of S. epidermidis infection associated with SEpvp and SE was assessed in a rabbit model. Unexpectedly, abscesses were induced by the injection of low numbers of S. epidermidis along subcutaneously inserted SEpvp. No abscesses were seen around SE, even when very high numbers of S. epidermidis were injected. This bioincompatibility reaction observed around the SEpvp was independent of the host, bacterial strain, and method of inoculation. Abscesses were also induced by nonviable S. epidermidis and by bacterial cell wall components. Because these incompatibility reactions were not observed in the absence of bacteria, biocompatibility testing should include experiments in which the inflammatory effects of the combination of catheter and (non)viable bacteria are tested., (Copyright 2000 John Wiley & Sons, Inc.)

Biomaterial surfaces may be modified to reduce bacterial adhesion. The susceptibility in mice to Staphylococcus epidermidis infection in tissue surrounding the commonly used catheter materials-silicon elastomer (SE), polyamide (PA), and their surface-modified polyvinylpyrrolidone (PVP)-grafted derivatives, SE-PVP and PA-PVP, respectively-was assessed. Abscesses developed around SE-PVP. Around SE, PA, and PA-PVP catheters, no signs of infection were observed, although mice carrying PA-PVP developed septicemia after 14-21 days. S. epidermidis was cultured from the tissue surrounding PA-PVP segments. Cells around PA-PVP segments containing large numbers of bacteria were identified as macrophages by use of immunohistochemistry and electron microscopy. This persistence of intracellular bacteria was also observed around SE-PVP, SE, and PA catheters, although to a lesser extent. The cytokine profiles around the 4 materials were different. Implanted biomaterial induces an inflammatory response favorable to the persistence of S. epidermidis. Intracellular persistence of bacteria inside macrophages may be a pivotal process in the pathogenesis of biomaterial-associated infection.

Survival of Staphylococcus epidermidis inside macrophages has been recognized as a pivotal process in the pathogenesis of biomaterial-associated infection (BAI). Interferon (IFN)-gamma is a potent activator of macrophages. This study examined whether subcutaneous injections of IFN-gamma can reverse macrophage deactivation induced by implanted biomaterials. Mice received subcutaneous implants combined with an injection of 106 S. epidermidis to induce an experimental BAI. Subsequently, 3 groups of mice received subcutaneous injections of 25,000 IU IFN-gamma 3 times weekly, 10,000 IU IFN-gamma 3 times in 2 weeks, or saline 3 times weekly (saline control), respectively. A fourth group received no injections (control). Segments and tissues of the IFN-gamma-treated mice were significantly less (P<.05) culture positive than those of the control groups. Histologically, the high numbers of intracellularly persisting gram-positive cocci observed in the control mice were absent in the IFN-gamma-treated mice. These data indicate that IFN-gamma protects against experimental BAI.

Biowaste or the organic fraction of domestic waste, for instance kitchen, fruit and garden waste, is collected selectively in several European communities. The complementary fraction is called the dry or non recyclable fraction. A Dutch study reported that 92% of the participants that have a weekly collection service of both fractions (biowaste and non recyclable fraction) and 80% of the participants in the alternating collection program (one week biowaste and the next week non recyclable fraction) are pleased with separate collection of biowaste. Dominating problems that arise in case of alternating collection are a repulsive odor and an infestation with flies and maggots. By expanding the definition of biowaste to include non recyclable or soiled paper like dirty newspapers, table napkins and paper handkerchiefs, most of these problems can be overcome without changing the way compostable waste is collected and processed. The expanded definition of biowaste was used in this paper. Over a 12 month period a quality survey of the collected biowaste was conducted by the composting facility Intercompost, Hoeselt, Belgium. A special aspect was the fact that in one participating community baby diapers were included in the soiled paper fraction; this is called "biowaste+". The biowaste+ had a 10% non recyclable paper fraction opposed to only 1-2% of non recyclable paper present in the conventional biowaste. Baby diapers were a rather notable part (more than 80%) of this non recyclable paper fraction of biowaste+ and as a consequence might contribute to a large extent to improve the collection and treatment of biowaste. It was demonstrated that rural districts yielded about 35% more biowaste than more urban districts; resp. +/- 122 kg biowaste/capita. year versus +/- 90 kg biowaste/capita. year. In Hoeselt the biowaste+ yield was about 130 kg/capita.year. Biowaste+ is also separately collected in another Belgium community, namely Brecht. The purity level of the biowaste+ and the amount of non recyclable paper (including diapers) were comparable with the results of Hoeselt. In Hoeselt the biowaste+ fraction is composted aerobically. In Brecht on the other hand, the biowaste+ is processed using the Dry Anaerobic Composting process (DRANCO). The latter process is discussed in more detail. The biological start-up of the dry anaerobic composting installation at Brecht, Belgium, is reported. The reactor has a total volume of 808 m3 and a design capacity of 730 m3. After 2 months of start up, the fermentor was at full loading rate, i.e. 8 kg bVS/m3 reactor.day and the installation was working at full capacity, i.e. 40 ton/day.(ABSTRACT TRUNCATED AT 400 WORDS)