Toenail infection by Cladophialophora boppii.

Cladophialophora boppii is a black yeast-like fungus that up to now has been only rarely described as a cause of human infection and whose role as a pathogen was not established despite its repeated isolation and genetic identification in these reports. Here we report the first case of a verified toenail infection caused by this fungus in a woman without any systemic disease or evidence of immunodeficiency. Identical dark molds were isolated from the same toenail at three points of time. Species identification was performed by scrutinizing the isolates morphologic, physiologic and genetic characteristics which resulted in their identification as Cladophialophora boppii. Oral treatment with terbinafin plus topical ciclopiroxolamine was effective.

Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease.

Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Objectives were to determine the clinical response after EN addition and the plasma degradation of LD and 3-O-methyldopa [3-OMD]. Not optimum treated hospitalised patients with Parkinson's disease received the same LD dosage on the first day only with carbidopa (CD) and on the second day with CD and EN (t.i.d.) within a standardised setting. We scored motor symptoms and measured LD- and 3-OMD levels on both days at fixed moments. Motor impairment significant better improved probably due to significant higher maximum concentrations [C(max)] and computed area under the curve values of LD levels during the LD/CD/EN condition. Time to C(max) of LD was significantly delayed after the first two LD/CD/EN intakes. An impact of EN on 3-OMD levels appeared. A possibly augmented LD absorption and a prolonged LD metabolism after EN supplementation may contribute to a more continuous LD delivery to the brain.

[Indirect costs in idiopathic Parkinson's disease]. / Die indirekten Kosten des idiopathischen Parkinson-Syndroms.

The economic impact of parkinsonism has been getting more significant due to the increasing prevalence of Parkinson's disease and the modern therapies available nowadays. The present study is supposed to update the existing databases and to provide a sound foundation for rational decision-making in the health care sector. It does not only focus on the direct costs of this disease incurred by 75 patients over a longer period, but also and for the first time, takes a look on the indirect cost as well. The study shows that the expenses for PD-related house rebuilding and early retirement make up for a substantial share among the indirect costs. In the overall analysis, the ratio between both, direct and indirect costs appear to be relatively balanced with slight domination of the direct costs.

[Analysis of direct costs in therapy of Parkinson disease]. / Analyse der direkten Kosten in der Parkinson-Therapie.

The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.

Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wild-type p53.

Hypericin and tamoxifen are experimental agents for the adjuvant chemotherapy of malignant glioma. We report that hypericin and tamoxifen induce apoptosis of 7 human malignant glioma cell lines in a concentration- and time-dependent manner. Illumination is essential for the cytotoxicity of hypericin but not tamoxifen. Apoptosis is unaffected by inhibitors of RNA and protein synthesis or free radical scavengers, does not require wild-type p53 activity, and occurs in glioma cells expressing high levels of bcl-2. There is no correlation between hypericin and tamoxifen-induced cytotoxicity and inhibition of protein kinase C (PKC). Ectopic expression of a murine bcl-2 transgene provides modest protection from tamoxifen but does not affect hypericin toxicity. Hypericin and tamoxifen do not modulate glioma cell killing induced by tumor necrosis factor-alpha (TNF-alpha) or CD95 ligand. Both drugs augment the acute cytotoxicity of various cancer chemotherapy drugs but fail to shift their EC50 values in modified colony formation assays. These data do not provide further supportive evidence how to enhance the limited efficacy of tamoxifen treatment for human malignant glioma. However, hypericin is a promising agent for the treatment of malignant glioma if local photodynamic activation of hypericin in the glioma tissue can be achieved.

Cooperative interception of neuronal apoptosis by BCL-2 and BAG-1 expression: prevention of caspase activation and reduced production of reactive oxygen species.

Neuronally differentiated PC12 cells undergo synchronous apoptosis when deprived of nerve growth factor (NGF). Here we show that NGF withdrawal induces actinomycin D- and cycloheximide-sensitive caspase (ICE-like) activity. The peptide inhibitor of caspase activity, N-acetyl-Asp-Glu-Val-Asp-aldehyde, was more potent than acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone in preventing NGF withdrawal-induced apoptosis, suggesting an important role for caspase-3 (CPP32)-like proteases. We observed a peak of reactive oxygen species (ROS) 6 h after NGF withdrawal. ROS appear to be required for apoptosis, because cell death is prevented by the free radical spin trap, N-tert-butyl-alpha-phenylnitrone, and the antioxidant, N-acetylcysteine. ROS production was blocked by actinomycin D, cycloheximide, and caspase protease inhibitors, suggesting that ROS generation is downstream of new mRNA and protein synthesis and activation of caspases. Forced expression of either BCL-2 or the BCL-2-binding protein BAG-1 blocked NGF withdrawal-induced apoptosis, activation of caspases, and ROS generation, showing that they function upstream of caspases. Coexpression of BCL-2 and BAG-1 was more protective than expression of either protein alone.

NADPH-diaphorase reactivity in the Mauthner cells of the swordtail fish, Xiphophorus helleri.

The presence of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHDH) in fixed tissue was histochemically demonstrated in the Mauthner cells of the teleost fish Xiphophorus helleri. This is the first detection of the enzyme in these giant neurons (which are restricted to fishes and amphibians) of a gnathostomate vertebrate. NADPHDH reactivity in fixed tissue is thought to reflect the activity of nitric oxide synthase. Thus, nitric oxide, a gaseous intercellular messenger, is probably synthesized in the Mauthner cells.