Neuroprotective properties of valproate

Neuropsychiatric disturbances are extremely common in Alzheimer’s disease (AD), and represent integral features of the illness, as well as appropriate targets for therapy. We are interested in designing trials aimed at preventing or delaying the emergence of psychopathology in AD. For symptomatic treatment of agitation, mood stabilizers, particularly sodium valproate, have proved to be beneficial in some patients. Since these effects take several weeks to emerge, we considered that they might be dependent on potentially neuroprotective actions of valproate, such as inhibition of apoptosis and slowing of neurofibrillary tangle formation. In this article we present the rationale for testing the neuroprotective potential of valproate experimentally in mouse models of tauopathy and in a clinical trial of patients with AD who lack psychopathology at baseline. Together, these studies will provide important tests of the hypothesis that valproate, either through inhibition of tau phosphorylation or some other mechanism, is a useful therapeutic agent to modify disease progression in AD.     

Synthesis and anti-microbial activity of benzo-condensed heterocyclic derivatives

The synthesis of 2,4-dione derivatives of 1,5-benzodithiepine, 1,5-benzodiazepine and 1,5-benzothiazepine and the anti-microbial activity in vitro of these derivatives and of analogous of 1,5-benzodioxepine, 1,5-benzoxathiepine and 1,5-benzoxazepine, previously prepared, are reported. Some of these compounds showed a good activity against some Gram positive microorganisms and blastomycetes.     

Immunostaining for P-glycoprotein in the diagnosis of thyroid carcinomas.

The morphologic distinction between thyroid carcinoma and certain benign thyroid conditions can be difficult in selected cases. P-glycoprotein (Pgp), a glycoprotein associated with tumor multidrug resistance, has been reported to be expressed in thyroid carcinoma but not in benign thyroid conditions. To determine the specificity of immunostaining for Pgp in the diagnosis of thyroid carcinoma, we studied formalin-fixed, paraffin-embedded tissue from 69 cases of various thyroid lesions using a commercially available monoclonal antibody to Pgp (C219, Centocor, Malvern, PA) and an avidin-biotin-peroxidase complex technique. Positive reactivity was seen in 15 of 37 (41%) benign thyroid conditions and in 23 of 32 (72%) thyroid carcinomas. We conclude that immunostaining for Pgp is not specific in the diagnosis of thyroid carcinoma.     

Wilms' tumor in adults

A rare case of metastatic nephroblastoma on the right side in a 28-year-old female patient is presented. Complete remission was achieved by inductive chemotherapy with vincristine, Adriamycin, actinomycin D and cyclophosphamide and subsequent radical nephrectomy. There was no evidence of disease 24 months after the initial diagnosis had been made. The problems specific to the diagnosis and treatment of adult Wilms tumor are discussed. A chemotherapy regimen known to be successful in childhood Wilms tumor was shown to be equally effective in our adult patient.     

"Waste" follicular aspirate from fertility treatment--a potential source of human germline stem cells?

Fertility clinics worldwide routinely produce a large volume of 'waste' follicular aspirate, which is potentially an abundant source of immature ovarian follicles. Current attempts to cultivate these further in vitro to yield viable mature oocytes for fertility treatment have not yet achieved much success. Instead, recent lines of evidence have emerged that are suggestive of a potential stem cell niche within such immature ovarian follicles. The recent discovery of follicular renewal and putative germ-line stem cells within the postnatal mammalian ovary shook the foundations of reproductive biology by challenging the established dogma that mammalian females lose the capacity for germ cell renewal during fetal life, such that a fixed reserve of germ cells (oocytes) enclosed within follicles is endowed at birth. More intriguingly, another recent study in the Drosophila model provided compelling evidence that somatic progenies (nurse cells) of germ-line stem cells had the ability to revert back to the stem-cell-like state. This introduces the exciting possibility that within the mammalian ovarian follicle, similar somatic progenies of germ-line stem cells may also possess a greater intrinsic ability to revert back into functional stem cells. If this is the case, then a favored candidate would be the cumulus/granulosa of immature ovarian follicles, since such cells are true homologues of nurse cells found within the Drosophila ovary. The successful elucidation of a human germ-line stem cell niche within immature ovarian follicles is likely to have huge ramifications in stem cell biology and regenerative medicine.     

In Vitro and In Vivo Characterization of MEMS Microneedles

Transdermal drug delivery TDD systems have many advantages but are conventionally limited by the low permeability of skin. The idea of using microneedles to painlessly penetrate the topmost impermeable stratum corneum has previously been put forward. In this paper, the fabrication of solid and hollow silicon microneedles with straight side-walls and with the following dimensions: 20–100 m in diameter and 100–150 m in length is described. In vitro tests demonstrate that with prior solid microneedle application, transdermal drug transport is significantly increased by 10–20 times, with the degree of enhancement being related to needle diameter. In vivo tests in diabetic animals, however, were unable to demonstrate any delivery of insulin through the hollow microneedles. It is proposed that two factors, microneedle length and tip sharpness, have to be improved for systemic drug delivery to be seen in vivo.     

Altersspezifische Trends des risikoreichen Alkoholkonsums in Deutschland: Parallele oder unterschiedliche Verläufe?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Nach der Collectivity-of-Drinking-Cultures-Theorie von Skog finden Veränderungen des Alkoholkonsums in allen...