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Systemic toxicity and tumor cell resistance still limit the efficacy of chemotherapy in colorectal cancer. Therefore, alternative treatments are desperately needed. The thiazolide Nitazoxanide (NTZ) is an FDA-approved drug for the treatment of parasite-mediated infectious diarrhea with a favorable safety profile. Interestingly, NTZ and the thiazolide RM4819—its bromo-derivative lacking antibiotic activity—are also promising candidates for cancer treatment. Yet the exact anticancer mechanism(s) of these compounds still remains unclear. In this study, we systematically investigated RM4819 and NTZ in 2D and 3D colorectal cancer culture systems. Both compounds strongly inhibited proliferation of colon carcinoma cell lines by promoting G1 phase cell cycle arrest. Thiazolide-induced cell cycle arrest was independent of the p53/p21 axis, but was mediated by inhibition of protein translation via the mTOR/c-Myc/p27 pathway, likely caused by inhibition of mitochondrial respiration. While both thiazolides demonstrated mitochondrial uncoupling activity, only RM4819 inhibited the mitochondrial respiratory chain complex III. Interestingly, thiazolides also potently inhibited the growth of murine colonic tumoroids in a comparable manner with cisplatin, while in contrast to cisplatin thiazolides did not affect the growth of primary intestinal organoids. Thus, thiazolides appear to have a tumor-selective antiproliferative activity, which offers new perspectives in the treatment of colorectal cancer.

Dieser Artikel liefert einen Überblick über die Kriterien für die Zulassung von Tierarzneimitteln gegen Zeckenbefall bei Hunden und Katzen. In diesem Rahmen erfolgt eine kurze Beschreibung der in Europa relevanten Zeckenarten bei Hunden und Katzen. Anschließend wird ein Überblick über die Inhalte der aktuell gültigen CVMP-Leitlinie gegeben. Im Einzelnen wird näher auf den Nachweis und die Berechnung der Wirksamkeit, die Wirkungskomponenten und Indikationen, die indirekte Infektionsprophylaxe sowie kurz auf die durchzuführenden Feldstudien eingegangen. This article provides an overview of the criteria for the authorisation of veterinary medicinal products for the treatment and prevention of tick infestation in dogs and cats. In this context, the most relevant tick species in dogs and cats in Europe are characterised. Regarding the current relevant CVMP-guideline, specific points such as testing, evaluation and criteria of efficacy, indications and field studies are addressed.

Häufige Reinigungsintervalle machen das Milch-Fouling zu einem Problem der milchverarbeitenden Industrie. Der Einsatz einer pulsierenden Strömung hat ein Potenzial zur Verbesserung des Reinigungsprozesses. Die Reinigungszeit kann auch bei niedrigen Temperaturen um mehr als die Hälfte verkürzt werden. Welligkeit der Pulsation und maximale Strömungsgeschwindigkeit sind die entscheidenden Parameter für die Effektivität des Reinigungsprozesses.

Customer values associated with medium-voltage switchgear have undergone a significant shift during the last decade. The privatisation of the electrical distribution industry in the UK has resulted in increased demands on MV switchgear in performance terms, including procurement and operating costs, ease of installation and reduced maintenance. Safety has remained of paramount importance and the environmental impact has become an essential element of designs.

Calculations of ultraviolet absorption and circular dichroic (CD) spectra in the π−π* band for fully extended chains of poly(β-amino acids) yield simple spectra dominated by a single normal mode, using our classical dipole interaction theory with parameters developed previously for peptides and proteins. These molecules represent the unusual case of a purely translational helix, in which the array of amide chromophores is achiral. The CD spectra are thus unusual in deriving all of their rotational strength by “borrowing” from the nonchromophoric atoms in the molecule. Calculations are presented also for parallel and antiparallel sheet structures, whose existence is known, and for both single chains and sheets in the presence of solvent, using a lattice-filled cavity model for the surrounding medium. The molecules treated are poly(β-alanine), poly(β-aminobutyric acid), poly(β-aminoisobutyric acid), poly(3-amino-2-methylbutanoic acid), and poly(2-aminocyclohexanecarboxylic acid).

Solvent effects on the electronic absorption and circular dichroic spectra of helical polypeptides and globular proteins are modeled by placing the molecule in a spherical cavity in a continuous dielectric medium and filling voids in the cavity with a simple cubic lattice of solvent molecules. Effects on the amide π−π* spectra near 200 nm are treated. The interactions among the solute atoms, solute chromophores, and discrete solvent molecules are treated by the partially dispersive dipole interaction treatment applied previously to the isolated molecules, while the dielectric continuum is treated by a rigorous reaction field formalism. Calculations are given for helical polypeptides αR-(Ala)10, (Pro)10 II, βP-(Abu)6×3, βA-(Abu)6×3 and globular proteins erabutoxin, cytochrome c, and myoglobin. Predicted solvent effects are generally small, but include potentially measurable increases in intensities of CD bands in αR-(Ala)10, (Pro)10 II, and the three proteins, and hypochromic shifts in the absorption bands of β-sheets.

Absorption and circular dichroic (CD) spectra of the π−π* transition near 190 nm are predicted for helical structures proposed for poly(β-amino acids) in accordance with the hydrogen-bonding schemes of Fernández-Santín et al. We consider four helical structures which are sterically unhindered when alkyl substituents on C^α and C^β are in R configurations, including two right-handed forms and two left-handed forms. Calculations are made for polymers of β-alanine, (R)-3-amino-2-methylpropanoic acid, (R)-3-aminobutanoic acid, (2R,3R)-3-amino-2-methylbutanoic acid, and (1R,2R)-2-aminocyclohexanecarboxylic acid. The predicted absorption and CD spectra are qualitatively similar for the four helices, showing some sensitivity to backbone structure and relatively little sensitivity to side-chain substitutions. The most notable features of the spectra are (i) CD band couplets centered near 200 nm with a +/− pattern, (ii) large hyperchromicities of 48−115% in the absorption spectra, and (iii) linear dichroic spectra dominated by a strong parallel dichroism in one of the right-handed helices and strong perpendicular dichroism in the left-handed helices. It is suggested that poly[(1R,2R)-2-aminocyclohexanecarboxylic acid] would be a good candidate for experimental study because one of the helices should be particularly stable for this case. Available experimental absorption and CD spectra are qualitatively consistent with the predictions for any of the four helices, though the observed CD spectra are less intense.

Summary Iron tolerance of rice (Oryza sativa L.) was investigated using an oxygen depleted hydroculture system. Treatment with high concentrations of Fe2+ induced yellowing and bronzing symptoms as well as iron coatings at the root surface. Root and shoot growth were inhibited by increasing iron concentration in the medium. All symptoms were more pronounced in an iron sensitive cultivar (IR 64) compared to an iron tolerant one (IR 9764-45-2). Superoxide dismutase and peroxidase activity of root extracts of IR 97 were about twice that of IR 64 in untreated control plants. No significant increase of peroxidase activity was detected with increasing iron concentration in the medium. Catalase activity of IR 64 was slightly higher than that of IR 97, independent of iron concentration.

Anschließhere an frühere Unterrsuchungen wurde eine neue Versuchseinrichtung zur Messung der Wärmeleitfähigkeit von Metallen im Temperaturbereich oberhalb 100 ° bis 500 ° aufgebaut und kritisch geprüft. Das Versuchsverfahren beruht auf der stationären axialen Wärmeleitung in einem Zylinder von 50 mm Durchmesser und 90 mm Länge mit drei Bohrungen im Abstand von je 30 mm zur Aufnahme von Thermopaaren für die Temperaturmessung in der Achse des Zylinders. Die Zuverlässigkeit des Meßverfahrens wird in zahlreichen Vorversuchen (Wärmeverlust, verschiedene Wärmeströmung, Verstimmung des Temperaturfeldes) erprobt. Die Wärmeleitfähigkeit folgender Metalle wird zwischen 20 und 500 °C gemessen: Armco-Eisen, sehr reines Kupfer, sehr reines Aluminium, reines Molybdän, Remanit, Baustahl St 37.

Tells how political news reporting on network television has changed in recent years, and gives examples of the problems in covering political stories.

Recounts why the author traded a fast-track career in network television for a slower, better life in a small Indiana town.

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