Influence of magnesium substitution on a collagen-apatite biomaterial on the production of a calcifying matrix by human osteoblasts

The induction of a calcifying matrix is of great interest in the restoration of bone defects. In a previous in vitro study we demonstrated that a collagen sponge constituted of type I collagen fibrils, chondroitin sulfates, and hydroxyapatite crystals induces an earlier and a more abundant synthesis of a new extracellular calcifying matrix than do other biomaterials such as collagen or hydroxyapatite alone. Bone mineral contains various amounts of magnesium ions, either adsorbed at the surface of apatite crystals or incorporated inside the crystal structure. Magnesium is known to reduce the degradation rate of tricalcium phosphate ceramics and to influence the crystallization of mineral substance. Thus we evaluated two sponges modified with different substituted apatites. The substituted low magnesium-containing apatite sample decreased the osteoinductive properties of the sponge whereas the substituted high magnesium-containing apatite sample had a toxic effect on bone cells and prevented the formation of any extracellular matrix. Such a toxic effect can be explained by the presence of large numbers of magnesium ions released into the culture medium even though at physiological level magnesium is able to promote bone mineralization and to control the growth of hydroxyapatite crystals. Thus collagen sponges containing hydroxyapatite remain one of the most appropriately evaluated biomaterials used for the restoration of periodontal pockets and bone defects.     

Rivastigmine. A review of its use in Alzheimer's disease

Rivastigmine (SDZ ENA 713) is a carbamylating, long-acting reversible and noncompetitive carbamate acetylcholinesterase inhibitor that is indicated as an oral treatment for patients with mild to moderately severe Alzheimer's disease. The drug has been evaluated for this use in 3 well designed, adequately powered, phase II/III, 26-week clinical trials that included a total of 1479 rivastigmine and 647 placebo recipients. Most of these patients had concomitant disorders that were being treated with numerous other drugs. Individual and pooled results of these trials indicate that rivastigmine 6 to 12 mg/day usually produces cognitive, global and functional changes that indicate significantly less deterioration than was observed with placebo in patients with mild to moderately severe Alzheimer's disease. Individual results of the 2 pivotal trials and pooled analysis also show that, compared with placebo recipients, significantly more rivastigmine 6 to 12 mg/day recipients respond to therapy. Indeed, after 26 weeks of therapy in the 2 pivotal trials, significantly more rivastigmine 6 to 12 mg/day than placebo recipients achieved clinically meaningful improvements as defined by 3 separate response criteria. The lower dosage range of 1 to 4 mg/day was not as effective as 6 to 12 mg/day, as measured using these criteria and other efficacy parameters. Rivastigmine causes adverse events that are generally those expected from an acetylcholinesterase inhibitor. They are usually mild to moderate, of short duration and responsive to dosage reduction. Unpublished data from 3989 patients indicate that rivastigmine and placebo were associated with similar incidences of serious adverse events and changes in laboratory parameters, ECG and cardiorespiratory vital signs. The most common events were gastrointestinal, central and peripheral nervous system and whole body adverse events. However, compared with placebo, rivastigmine more commonly caused adverse events resulting in treatment withdrawal. These events were most frequently gastrointestinal and were more common in women. CONCLUSION: Rivastigmine is a useful option for the treatment of patients with mild to moderately severe Alzheimer's disease. Although only short term (6- month) comparisons with placebo are available, given the lack of established treatment options it should be considered for first-line use in this population.     

The characterization of a subgenomic RNA and in vitro translation products of oat chlorotic stunt virus

Apoptosis has classically been viewed as a process not involving mitochondria, whereas the implication of mitochondrial dysfunction in necrosis has been recognized for several decades. Recently, it has become clear that apoptosis implies a disruption of mitochondrial membrane intregrity that is decisive for the cell death process. Cytofluorometric methods assessing the mitochondrial membrane function and structure can be employed to demonstrate that, at least in most models of apoptosis, mitochondrial changes precede caspase and nuclease activation. Moreover, pharmacological and genetic experiments suggest that the loss of mitochondrial membrane integrity is a critical event of the apoptotic process, beyond or at the point of no return of programmed cell death. Inhibitors of the mitochondrial megachannel (= permeability transition pore) can prevent both the mitochondrial and the post-mitochondrial manifestations of apoptosis.     

Pharmacotherapeutic compass 1998

The Central Medical Pharmaceutical Committee of the Health Insurance Council informs the medical profession annually about the effects of drugs through the Pharmacotherapeutical Compass. The 1998 edition now contains a chapter on pharmacokinetics as well. Compared with previous editions the main alterations of the contents concern an introduction and advice on the antidepressants, two protocols with respect to the medical treatment of patients suffering from epilepsy, advice with respect to oral drugs for the treatment of inflammatory bowel disease, an introduction and advice regarding the treatment of allergic rhinitis, the treatment of patients suffering from AIDS with antiretroviral drugs, the treatment of genital herpes, the taking of insulin lispro by patients with diabetes and the taking of bisphosphonates to prevent or to treat osteoporosis. Two corrections to the 1998 edition are given.     

Cerebral vasculitis associated with chronic mucocutaneous candidiasis

Proton nuclear magnetic resonance (1H NMR) was used to study the in vivo metabolism of Trypanosoma cruzi, the pathogen causing American trypanosomiasis (Chagas' disease). Three clones were isolated from a strain of T. cruzi (Bolivia strain), The clones I, II and III and the original strain were characterized according to the spectra of their metabolic pathways to test the hypothesis that clonal evolution of T. cruzi has a major impact on biologically relevant properties of this parasite. T. cruzi (Bolivia strain) excreted acetate, alanine, glycerol, and succinate as major end products, in the proportion 6:4:2:2. Comparing the spectra of T. cruzi clones with the original Bolivia strain revealed both quantitative, as well as qualitative differences in the metabolites excreted: the clones I and II, as opposed to the Bolivia strain and clone III, excreted significant quantities of ethanol.     

Determination of the survival of Trypanosoma evansi in equine blood, using the microhematocrit method

The microhaematocrit (MH) technique was used to study the survival of Trypanosoma evansi in blood from two herds of naturally-infected horses. A comparison was made between samples treated with ethylenediaminetetraacetic acid and sodium citrate (alone or with 1% glucose), and sent to the laboratory packed in ice. In general, the number of samples yielding positive results by the MH technique showed the least variation during the first 24-36 h after sample collection. Survival varied with the anticoagulant used, but it declined rapidly from 48 h after collection, although live parasites were still observed in up to 10% of samples until the seventh day. On the basis of the results obtained, the authors recommend the use of sodium citrate in treating equine blood samples for the parasitological diagnosis of T. evansi.     

Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells

Taxoids and other microtubule-damaging drugs are known to induce Bcl2 phosphorylation at the G2-M phase of the cell cycle, with concomitant apoptosis in malignant cells derived from a variety of human malignancies, including leukemia, lymphoma, and breast and prostate cancer. We have investigated the ability of another antineoplastic drug, dolastatin 10, in inducing Bcl2 phosphorylation and apoptosis. We also investigated the effects of a phosphatase inhibitor okadaic acid in the regulation of Bcl2 phosphorylation, cell cycle arrest, and programmed cell death. Moreover, site-directed mutagenesis studies were performed to determine the specific serine residue(s) responsible for drug-induced Bcl2 phosphorylation. Our results indicate that these antimicrotubule agents or okadaic acid can induce posttranslational modification (phosphorylation) of Bcl2 protein at multiple serine residues. Interestingly, mutation of a serine residue at position 70 to alanine can significantly decrease drug-induced posttranslational modification (phosphorylation) of Bcl2 protein. Apparently, Ser70 seems to be a critical site for drug-induced posttranslational modification (phosphorylation) of the Bcl2 protein.