Co-pyrolysis of chicken manure with tree bark for reduced biochar toxicity and enhanced plant growth in Arabidopsis thaliana.

Co-pyrolysis of chicken manure with tree bark was investigated to mitigate salinity and potentially toxic element (PTE) concentrations of chicken manure-derived biochar. The effect of tree bark addition (0, 25, 50, 75 and 100 wt%) on the biochar composition, surface functional groups, PTEs and polycyclic aromatic hydrocarbons (PAH) concentration in the biochar was evaluated. Biochar-induced toxicity was assessed using an in-house plant growth assay with Arabidopsis thaliana. This study shows that PTE concentrations can be controlled through co-pyrolysis. More than 50 wt% of tree bark must be added to chicken manure to reduce the concentrations below the European Biochar Certificate-AGRO (EBC-AGRO) threshold. However, the amount of PAH does not show a trend with tree bark addition. Furthermore, co-pyrolysis biochar promotes plant growth at different application concentrations, whereas pure application of 100 wt% tree bark or chicken manure biochar results in decreased growth compared to the reference. In addition, increased plant stress was observed for 100 wt% chicken manure biochar. These data indicate that co-pyrolysis of chicken manure and tree bark produces EBC-AGRO-compliant biochar with the potential to stimulate plant growth. Further studies need to assess the effect of these biochars in long-term growth experiments.

Observational survey of NSAID-related upper gastro-intestinal adverse events in Belgium.

OBJECTIVES: To evaluate the impact of NSAID use on current routine upper GI endoscopy (UGIE) and to compare the lesions found in NSAID users and non-users. METHODS: Participating gastroenterologists consecutively documented outpatients with and without suspicion of bleeding, referred for upper gastrointestinal endoscopy. Patient characteristics, presence of risk factors, NSAID use and endoscopic findings were reported on standard data collection forms. MAIN RESULTS: A total of 2685 non-bleeding and 159 bleeding patients were enrolled within a time period of 2 months. NSAID therapy was present in 20% of the non-bleeding patients and at least 9% of referrals for endoscopy were directly related to suspected NSAID adverse events. Nearly half of acute bleeding patients (42%) were NSAID users, including aspirin for cardioprevention. Warning digestive symptoms prior to acute bleeding were frequently absent (56%). Oesophagitis was the main endoscopic diagnosis (51% of patients). Gastroduodenal (GD) ulcer was significantly more frequent in NSAID users, whereas oesophagitis and bleeding oesophageal varices were more frequent among non-users. Analysis of odds ratio's demonstrated NSAID use to significantly increase the risk for gastric ulcer in the whole patient group (OR = 2.73; 95% confidence interval (CI): 1.98-3.77; p < 0.001) and, in addition, for duodenal ulcer in the elderly (> 65 y) subgroup (OR = 2.91; 95% CI: 1.52-5.59; p < 0.05). CONCLUSIONS: This survey confirms the high incidence of GD ulcers in NSAID users and the risk for serious gastrointestinal complications, often occurring without warning symptoms. It underlines the impact of NSAID use on the routine endoscopy load, the necessity of careful selection of patients for NSAID prescriptions and the need for gastropreventive measures, particularly in elderly patients and patients associating multiple risk factors.

Pricing and reimbursement of pharmaceuticals in Belgium.

The Belgian healthcare system has a tradition of access and equity at affordable prices. As in other countries, the system becomes pressured by increasing healthcare costs. This paper describes the actual situation in Belgium with special focus on pharmaceutical products and the potential role of pharmacoeconomics in decision making on price and reimbursement. Nearly all people in Belgium are covered by compulsory health insurance. The system is paid for by social security, the patients and the federal and regional authorities. The part of the consumption of pharmaceuticals that is charged to insurance was about 62.1 billion Belgian francs (BeF), i.e. about 50% of the pharmaceutical market in 1994. Price setting in Belgium has been rather low due to the positive reimbursement list, where the price of a new drug is compared to existing drugs in a comparable therapeutic class (so-called reimbursement criteria). The expenditure on pharmaceuticals is increasing faster than global funding for public health. In order to control drug budgets, different cost-containment measures have been or are being taken, i.e. a mix of price, reimbursement and volume controls. These cost-containment measures are not necessarily in accordance with a health economic approach. This paper suggests the scope for better implementation of pharmacoeconomic evaluation, which can lead to more flexible reimbursement systems in specific indications. Therefore, a formal recognition of the role of objective economic evaluations is needed for both hospital and ambulatory care. This process should be proceeded by improving the understanding and robustness of pharmacoeconomic evaluations.

Inhibition of steroid-protein interactions by dicyclohexane derivatives.

Sixteen dicyclohexane derivatives including the parent compound d,1-3,4-bis (4-oxocyclohexyl)-hexane (PRDX) have been synthesized and studied for putative interference with androgen binding to transport proteins, metabolizing enzymes, and receptors from rat tissues. Several of these analogues inhibited competitively the binding of dihydrotestosterone to ABP, the epididymal androgen transport protein. One compound had an affinity for ABP as high as Kd = 70 nM. Some dicyclohexanes also inhibited the aromatase enzyme which catalyses conversion of androgens into estrogens, as well as the NADPH-dependent, particulate form of 3 alpha(beta)-hydroxysteroid dehydrogenase, the enzyme that converts dihydrotestosterone into 5 alpha-androstanediol. For both enzymes the inhibition potency Ki of PRDX was about equal to the Km of the substrate. All of these interactions were specific in that they were modulated by single substitutions on the dicyclohexane molecule and they did not occur with other steroid binding proteins such as 5 alpha-reductase and the intracellular androgen receptor. A conformational study showed that dicyclohexanes can assume a 'steroidoid' conformation that differs from the crystal structure and which could account for the specific interactions with the steroid binding sites described here.

Hematuria as presenting sign in Wissler-Fanconi syndrome.

We describe a case of persistent microscopic hematuria as initial finding in incomplete Still's disease or Wissler-Fanconi syndrome. Renal biopsy findings were compatible with intravascular coagulation. Wissler-Fanconi syndrome and the associated renal abnormalities are briefly reviewed.

In vivo stimulation and inhibition of granulopoiesis: the effect of an inflammatory reaction on murine diffusion chamber granulopoiesis.

Humoral factors influencing granulopoiesis have been evaluated using diffusion chambers (DC) implanted in the peritoneal cavity of mice challenged by an aseptic abscess produced by the subcutaneous implantation of copper rods. This resulted in an increase in peripheral blood neutrophils and an increase in tibial granulocytic elements. When DC loaded with bone-marrow cells were implanted into mice stimulated the day before by an aseptic abscess significantly more CFU-s, CFU-c, proliferative and non-proliferative granulocytes were produced, as compared to DC implanted into control hosts. When DC were implanted 4-6 d after the induction of inflammation in mice a significant depression of DC granulopoiesis was observed. Levels of serum and DC fluid CSF and serum inhibitors of in vitro colony growth showed no correlation with DC myelopoiesis. The data show that mice undergoing an inflammatory reaction elaborate first humoral substance(s) enhancing CFU-s and granulocytic growth in DC and next inhibitory factor(s) of DC granulopoiesis.

Comparative toxicity of detorubicin and doxorubicin, free and DNA-bound, for hemopoietic stem cells.

We compared the toxicity of detorubicin (DET) and of doxorubicin (DOX) on the hematopoietic stem cells in C57BL6J mice by means of the CFUS and CFUC assays. On an equimolar basis DET appears to be less toxic than DOX for both the pluripotent stem cells and the granulocytic progenitor cells. Moreover, the administration of these anthracyclines as DNA complexes leads to a decreased toxicity to the pluripotent stem cells, while no such attenuated toxic effect is observed in committed stem cells.

The diffusion chamber technique as an in vivo assay in mice for the effectiveness of antitumor agents.

The diffusion chamber (DC) technique has been applied to the culture of L1210 cells in view of determining their sensitivity to chemotherapic agents. The surviving fraction of L1210 cells cultivated in DC's 4 d after i.v. injection of the host mice with 10 mg/kg of daunorubicin or daunorubicin-DNA was 40% and 9% respectively. The results suggest that the DC technique could be a useful in vivo predictive test for cancer chemotherapy.

Effects of daunorubicin and doxorubicin, free and associated with DNA, on hemopoietic stem cells.

We have compared daunorubicin (DNR)-DNA with free DNR and doxorubicin (DOX)-DNA with free DOX for their effects in vivo in mice on pluripotent stem cells and granulocytic committed stem cells. Dose-survival, time-survival, and recovery curves were obtained after one i.v. injection of either drug. The dose-survival curves of colony-forming units-spleen (CFU-S) and colony-forming units-committed stem cells (CFU-C) were exponential in shape with both agents. DNR-DNA appeared more toxic to the hemopoietic precursor cells than did free DNR. In contrast, DOX-DNA was less toxic toward CFU-S and as toxic as DOX toward CFU-C. Time-survival curves indicated a minimum level of CFU-S and CFU-C at about 33 hr. After that, the recovery of CFU-S was rapid for DNR-treated mice but remained below 50% of the controls on Day 12 for the DNR-DNA-treated group. In mice previously given injections of DOX or DOX-DNA, the recovery of the CFU-S was more protracted in time with a better recovery in mice treated with DOX-DNA. Both DNR and DNR-DNA induced an initial CFU-C decrease followed by a rapid but transient rise with a maximum on Day 4 after chemotherapy. On Day 12, the CFU-C recovery was still incomplete in both DNR- and DNR-DNA-treated mice. In the groups treated with DOX, the CFU-C recovery was more important after DOX-DNA complex than after free DOX. The results are discussed in view of the "lysosomotropic chemotherapy" hypothesis.

Comparative study in mice of the toxicity, pharmacology, and therapeutic activity of daunorubicin-DNA and doxorubicin-DNA complexes.

We have compared the toxicologic, pharmacologic, and therapeutic properties of the DNA complexes of daunorubicin and doxorubicin, after intravenous (IV) administration into mice. The overall toxicity of doxorubicin is significantly reduced after IV injection as a DNA complex while daunorubicin-DNA is as toxic as free daunorubicin. On hemopoietic stem cells, daunorubicin-DNA was found to be more cytotoxic than daunorubicin, while the opposite was observed with doxorubicin and doxorubicin-DNA. Both complexes are more effective than the corresponding free drugs on the L1210 murine leukemia, when given IV at equitoxic doses. The tissue uptake in mice, after IV administration, is generally lower when the drugs are given bound to DNA. The stability of the two DNA complexes is very different in the bloodstream: daunorubicin-DNA behaves more like a prodrug of daunorubicin, while doxorubicin-DNA, remaining stable in the bloodstream, meets much more the requirements of an ideal drug-macromoleculare carrier entity.