2,340 research outputs found
Wie der TI-92 Plus den Mathematikunterricht in der Sekundarstufe I verändern kann
Zitat aus der Einleitung des Textes:"Das SCHULZENTRUM FINDORFF (www.szfindorff.de) in Bremen ist ein Schulzentrum der Sekundarstufe I. Es beherbergt unter einem Dach alle Klassen von der fünften bis zur zehnten Jahrgangsstufe. Die fünfte und sechste Klasse bilden dabei die schulformunabhängige Orientierungsstufe, ab 7. Klasse sind die Schülerinnen und Schüler in Klassen der Hauptschule, der Realschule und des Gymnasiums aufgeteilt. Nachdem im Schuljahr 1995/96 eine Veränderung des naturwissenschaftlichen Unterricht ihren Anfang genommen hatte, sollte zwei Jahre später auch die Mathematik mit einbezogen werden. Im Schuljahr 1997/98 begann dann der veränderte Mathematikunterricht mit zwei Kollegen in zwei siebten Klassen des Gymnasiums. Seitdem werden alle Klassen des Gymnasiums nach diesem Modell unterrichtet. Hierfür wurden im weiteren Verlauf zusätzliche KollegInnen fortgebildet.
Entwicklung der Rechnerausstattung am SZ Findorff Äußeres Kennzeichen der Veränderung war die Einbeziehung des modernen Taschencomputers TI-92 von Texas Instruments in den Mathematikunterricht. Die Rechner werden den Schülerinnen und Schülern von der Schule zur Verfügung gestellt. Dies bedingt eine ausreichende Rechnerausstattung, so dass jeder Schülerin und jedem Schüler ein Rechner für den Unterricht zur Verfügung gestellt werden kann. Außerdem sollte jede Klasse am Gymnasium nach den neuen Prinzipien unterrichtet werden. Daher wurden weitere Kolleginnen und Kollegen schulintern im Unterrichten mit dem Rechner fortgebildet."</div
Peptides antimicrobiens naturels cutanés
Une des stratégies majeures mises en jeu par la peau pour se protéger des infections est de maintenir une barrière physique cutanée intacte. La désquamation, de même que la sécrétion de mucus, sont à l’origine d’un renouvellement permanent de la surface cutanée, qui s’accompagne d’une élimination des micro-organismes adhérant à cette surface. La découverte récente de peptides antibiotiques épithéliaux suggère qu’il existe, à côté de cette barrière physique, une barrière cutanée « chimique » constituée par des peptides antibiotiques capables de contrôler la croissance bactérienne au niveau des couches cutanées et, éventuellement, de lutter contre les infections.Human skin is always in contact with the environment and is covered with a characteristic microflora, but it is usually not infected. Although desquamation and secretion of mucus lead to a permanent renewal of these body surfaces and simultaneous elimination of microorganisms adhering to these layers, another reason for this natural resistance might be the existence of a “chemical barrier” consisting in constitutively and inducibly produced antimicrobial peptides and proteins (AMPs), which include some ß-defensins, RNase 7, the S100-protein psoriasin and the cathelicidin LL-37. Most of these AMPs can be induced in vitro in epithelial cells by proinflammatory cytokines or bacteria. In vivo, AMPs are mainly expressed in uppermost and differentiated parts of inflammatory lesions and wounds, but some are also focally expressed in skin in the absence of inflammation, suggesting that apart from inflammatory mediators, also non-inflammatory stimuli of endogenous and/or exogenous origin can stimulate AMP-synthesis. Increased levels of AMPs in psoriatic lesions may explain why psoriasis patients rarely suffer from skin infections. Further, an increased infection rate in atopic dermatitis patients could be the consequence of decreased levels of AMPs in atopic lesions. These observations may indicate an important role of the “chemical skin barrier” in prevention of skin infection and suggest that artificial stimulation of this system, without inflammation, would be beneficial as « immune stimulus »
Efficacy of Cyclooctadepsipeptides and Aminophenylamidines against Larval, Immature and Mature Adult Stages of a Parasitologically Characterized Trichurosis Model in Mice
The genus Trichuris includes parasites of major relevance in veterinary and
human medicine. Despite serious economic losses and enormous impact on public
health, treatment options against whipworms are very limited. Additionally,
there is an obvious lack of appropriately characterized experimental infection
models. Therefore, a detailed parasitological characterization of a Trichuris
muris isolate was performed in C57BL/10 mice. Subsequently, the in vivo
efficacies of the aminophenylamidines amidantel, deacylated amidantel (dAMD)
and tribendimidine as well as the cyclooctadepsipeptides emodepside and in
particular PF1022A were analyzed. This was performed using various
administration routes and treatment schemes targeting histotropic and further
developed larval as well as immature and mature adult stages. Duration of
prepatent period, time-dependent localization of larvae during period of
prepatency as well as the duration of patency of the infection were determined
before drugs were tested in the characterized trichurosis model. Amidantel
showed no effect against mature adult T. muris. Tribendimidine showed
significantly higher potency than dAMD after oral treatments (ED50 values of
6.5 vs. 15.1 mg/kg). However, the opposite was found for intraperitoneal
treatments (ED50 values of 15.3 vs. 8.3 mg/kg). When emodepside and PF1022A
were compared, the latter was significantly less effective against mature
adults following intraperitoneal (ED50 values of 6.1 vs. 55.7 mg/kg) or
subcutaneous (ED50 values of 15.2 vs. 225.7 mg/kg) administration. Only
minimal differences were observed following oral administration (ED50 values
of 2.7 vs. 5.2 mg/kg). Triple and most single oral doses with moderate to high
dosages of PF1022A showed complete efficacy against histotropic second stage
larvae (3 × 100 mg/kg or 1 × 250 mg/kg), further developed larvae (3 × 10
mg/kg or 1 × 100 mg/kg) and immature adults (3 × 10 mg/kg or 1×100 mg/kg).
Histotropic first stage larvae were only eliminated after three doses of
PF1022A (3 × 100 mg/kg) but not after a single dose. These results indicate
that the cyclooctadepsipeptides are a drug class with promising candidates for
further evaluation for the treatment of trichurosis of humans and livestock
animals in single dose regimens
The influence of the commensal skin bacterium Staphylococcus epidermidis on the epidermal barrier and inflammation: Implications for atopic dermatitis
The skin microbiota is a crucial component in maintaining cutaneous barrier function. Staphylococcus epidermidis is considered as a beneficial commensal member of the cutaneous microbiota promoting skin health. However, S. epidermidis is also frequently detectable in the skin of patients with the inflammatory skin disease atopic dermatitis (AD) and some studies reported a significantly higher presence of S. epidermidis in severe AD as compared to mild AD. Therefore, this study aimed to analyse the impact of S. epidermidis on the expression of cutaneous inflammatory mediators and skin barrier molecules. Various S. epidermidis skin-derived isolates activated the proinflammatory transcription factor NF-kappaB and induced expression of AD-associated proinflammatory cytokines in human primary keratinocytes and 3D skin equivalents. Skin barrier molecules such as filaggrin were downregulated by S. epidermidis. In general, AD-derived S. epidermidis strains elicited a higher response than strains derived from the skin of healthy individuals. Taken together, our results provide further evidence that the abundance of S. epidermidis in AD may trigger the inflammatory scenario associated with this disease
Decreased Susceptibility of Staphylococcus aureus Small-Colony Variants toward Human Antimicrobial Peptides
Staphylococcus aureus is a frequent resident of human nose and skin in many individuals, but it is also able to cause a variety of serious infections including those of the skin and soft tissue. There is increasing evidence that particularly persistent, relapsing, and difficult-to-treat infections caused by S. aureus are associated with the formation of the small-colony variant (SCV) phenotype. The aim of this study was to investigate the hypothesis that (i) skin-derived antimicrobial peptides (AMPs) exhibit a reduced activity against SCVs and (ii) that switching into the SCV phenotype may endow S. aureus with a decreased susceptibility toward the killing activity of human stratum corneum. Here, we show that clinically derived S. aureus SCVs are less susceptible to the bactericidal activity of different human skin-derived AMPs as compared with their isogenic corresponding wild-type strains. Similarly, a S. aureus hemB mutant displaying the SCV phenotype was less susceptible to the antimicrobial activity of AMPs than its hemB-complemented mutant. These findings were accompanied by a higher resistance of SCVs to the killing activity of human stratum corneum. Switching into the SCV phenotype may help S. aureus to subvert cutaneous innate defense, thus contributing to the establishment and persistence of infection
The Antimicrobial and Immunomodulatory Function of RNase 7 in Skin
The human ribonuclease RNase 7 has been originally isolated from human skin and
is a member of the human RNase A superfamily. RNase 7 is constantly released by
keratinocytes and accumulates on the skin surface. The expression of RNase 7 in
keratinocytes can be induced by diverse stimuli such as cytokines, growth factors, and
microbial factors. RNase 7 exhibits a potent broad spectrum of antimicrobial activity
against various microorganisms and contributes to control bacterial growth on the skin
surface. The ribonuclease and antimicrobial activity of RNase 7 can be blocked by the
endogenous ribonuclease inhibitor. There is also increasing evidence that RNase 7 exerts
immunomodulatory activities and may participate in antiviral defense. In this review, we
discuss how these characteristics of RNase 7 contribute to innate cutaneous defense
and highlight its role in skin infection and inflammation. We also speculate how a potential
dysregulation of RNase 7 promotes inflammatory skin diseases and if RNase 7 may have
therapeutic potential
Prenatal human skin expresses the antimicrobial peptide RNase 7
Antimicrobial peptides and proteins (AMPs) play important roles in skin immune defense due to their capacity to inhibit growth of microbes. During intrauterine life, the skin immune system has to acquire the prerequisites to protect the newborn from infection in the hostile environment after birth, which includes the production of skin AMPs. The aim of this study was to analyze the expression of RNase 7, HBD-2/3 and psoriasin during human skin development, thus, providing a deeper insight about the maturity of a fundamental component of the innate immune system. We found low RNase 7 expression levels in the periderm but no expression of HBD-2/3 and psoriasin in first trimester human skin using immunohistochemistry. At the end of the second trimester, RNase 7 is expressed weakly in all epidermal layers with a marked signal in the stratum corneum. HBD-3 and psoriasin are focally expressed while HBD-2 is not detectable. Analysis of supernatants from cultured prenatal skin cells showed that in contrast to adult control, RNase 7 and psoriasin are not found in prenatal skin, suggesting that AMPs are detectable but are not secreted. This study shows the differential expression of AMPs in developing, non-perturbed human prenatal skin. It is conceivable that the combined expression of RNase 7, HBD-3 and psoriasin in fetal skin constitutes a developmental program to exert a broad spectrum of antimicrobial activity to maintain sterility in the amniotic cavity
Characterization of the Ca2+-gated and voltage-dependent k+-channel slo-1 of nematodes and its interaction with emodepside
The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and related Strongylida. Molecular and bioinformatic analyses identified full-length Slo-1 cDNAs of Ascaris suum, Parascaris equorum, Toxocara canis, Dirofilaria immitis, Brugia malayi, Onchocerca gutturosa and Strongyloides ratti. Two paralogs were identified in the trichocephalids Trichuris muris, Trichuris suis and Trichinella spiralis. Several splice variants encoding truncated channels were identified in Trichuris spp. Slo-1 channels of trichocephalids form a monophyletic group, showing that duplication occurred after the divergence of Enoplea and Chromadorea. To explore the function of a representative protein, C. elegans Slo-1a was expressed in Xenopus laevis oocytes and studied in electrophysiological (voltage-clamp) experiments. Incubation of oocytes with 1-10 µM emodepside caused significantly increased currents over a wide range of step potentials in the absence of experimentally increased intracellular Ca2+, suggesting that emodepside directly opens C. elegans Slo-1a. Emodepside wash-out did not reverse the effect and the Slo-1 inhibitor verruculogen was only effective when applied before, but not after, emodepside. The identification of several splice variants and paralogs in some parasitic nematodes suggests that there are substantial differences in channel properties among species. Most importantly, this study showed for the first time that emodepside directly opens a Slo-1 channel, significantly improving the understanding of the mode of action of this drug class
Clinical response to Auron Misheil Therapy in a man with advanced multifocal hepatocellular carcinoma: A case report
<p>Abstract</p> <p>Introduction</p> <p>Auron Misheil Therapy was developed based on similarities between carcinogenesis and inflammation. Auron Misheil Therapy is a combination of natural and synthetic compounds, including anti-inflammatory drugs and insulin, expected to exhibit synergistic effects.</p> <p>Case presentation</p> <p>Here, we report the case of a 78-year-old Caucasian male patient who presented with multifocal hepatocellular carcinoma and chronic hepatitis C virus infection. Over a four-year period our patient was treated with radiofrequency ablation and transarterial chemoembolization. After these treatments there was tumor progression, with new hyperperfused lesions without evidence of extrahepatic tumor involvement. Our patient refused sorafenib therapy. Therefore, he received twice daily intramuscular injections of Auron Misheil Therapy on an outpatient basis for two months. Partial remission of the hepatic lesions was observed eight weeks after the start of treatment, and confirmed four weeks later. Unfortunately, at that time our patient refused therapy due to dizziness. During follow-up two target lesions remained stable, but one lesion increased in size. At the latest follow-up, one year later, there was still tumor control.</p> <p>Conclusion</p> <p>While the mechanisms underlying the antitumor effects of Auron Misheil Therapy are not fully understood, stable disease and remissions have been observed in different types of tumors, including hepatocellular carcinoma.</p
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