Characterization of the role of metallothionein-3 in an animal model of Alzheimer’s disease

Among the dementias, Alzheimer’s disease (AD) is the most commonly diagnosed, but there are still no effective drugs available for its treatment. It has been suggested that metallothionein-3 (MT-3) could be somehow involved in the etiology of AD, and in fact very promising results have been found in in vitro studies, but the role of MT-3 in vivo needs further analysis. In this study, we analyzed the role of MT-3 in a mouse model of AD, Tg2576 mice, which overexpress human Amyloid Precursor Protein (hAPP) with the Swedish mutation. MT-3 deficiency partially rescued the APP-induced mortality of females, and mildly affected APP-induced changes in behavior assessed in the hole-board and plus-maze tests in a gender-dependent manner. Amyloid plaque burden and/or hAPP expression were decreased in the cortex and hippocampus of MT-3-deficient females. Interestingly, exogenously administered Zn₇MT-3 increased soluble Aβ40 and Aβ42 and amyloid plaques and gliosis, particularly in the cortex, and changed several behavioral traits (increased deambulation and exploration and decreased anxiety). These results highlight that the control of the endogenous production and/or action of MT-3 could represent a powerful therapeutic target in AD.     

Diffusion of d-glucose measured in the cytosol of a single astrocyte

Astrocytes interact with neurons and endothelial cells and may mediate exchange of metabolites between capillaries and nerve terminals. In the present study, we investigated intracellular glucose diffusion in purified astrocytes after local glucose uptake. We used a fluorescence resonance energy transfer (FRET)-based nano sensor to monitor the time dependence of the intracellular glucose concentration at specific positions within the cell. We observed a delay in onset and kinetics in regions away from the glucose uptake compared with the region where we locally super-fused astrocytes with the d-glucose-rich solution. We propose a mathematical model of glucose diffusion in astrocytes. The analysis showed that after gradual uptake of glucose, the locally increased intracellular glucose concentration is rapidly spread throughout the cytosol with an apparent diffusion coefficient (D _app) of (2.38 ± 0.41) × 10^?10 m² s^?1 (at 22–24 °C). Considering that the diffusion coefficient of d-glucose in water is D = 6.7 × 10^?10 m² s^?1 (at 24 °C), D _app determined in astrocytes indicates that the cytosolic tortuosity, which hinders glucose molecules, is approximately three times higher than in aqueous solution. We conclude that the value of D _app for glucose measured in purified rat astrocytes is consistent with the view that cytosolic diffusion may allow glucose and glucose metabolites to traverse from the endothelial cells at the blood–brain barrier to neurons and neighboring astrocytes.     

Reinigung mikrobiologischer Objekte zur Vorbereitung elektronenmikroskopischer Präparate durch Ultrafiltration

Summary A method for preparation of electron microscopic specimens by ultrafiltration can be used for bacteriophages, mycoplasma, and fragile biological particles, especially from solutions containing low concentrations of these particles and when it is necessary to remove also macromolecules up to a certain size.     

35S-Sulphate incorporation into myelin sulphated mucopolysaccharides during rat brain development

Summary Rat brain myelin acid mucopolysaccharides (AMPS) incorporate 15%, 8%, 5.5% and 4% of tojtal associated³⁵S-sulphate, 14, 21, 30 and 75 days after birth, respectively. The course of³⁵S-sulphate incorporation into total rat brain mucopolysaccharides, as well in those from myelin, had a similar feature with peak on the 2nd week and a significant decrease on the 3rd and 4th week postnatally.     

Die biosynthetische Inkorporation von externem S35O2 in Glucobrassicin

Summary In plants of theBrassica oleracea species contaminated with S³⁶O₂, incorporation of radioactive sulphur into glucosinolate glucobrassicin has been found. The label is present also in the isothiocyanate group of glucobrassicin, which by decomposition under the action of myrosinase liberates labelled thiocyanate.     

Effect of human serum oxytocinase on the antidiuretic action of lysine vasopressin and oxytocin in the rat

Zusammenfassung Nach i.v. Dauerinfusion von Lysin-Vasopressin oder Oxytocin wird bei der experimentellen Analyse der Wirkung menschlicher Oxytocinase eine Erniedrigung des antidiuretischen Effekts gefunden; diese rührt vom Absinken der Peptidkonzentration sowohl im Blutplasma als auch am Wirkort her.     

Radiation-induced changes in gentamicin pharmacokinetics

Summary Decreased clearance of i.v. or intratracheally administered gentamicin was observed in rats following single whole-body irradiation, 6 Gy⁶⁰Co, reaching its lowest rate on the 7th post-irradiation day. Simultaneously the absorption rate of gentamicin from the lungs was found to be increased.     

The in vivo activity of combinations of 5-azacytidine and cytidine on leukemia L-1210

Zusammenfassung Cytidin- oder Uridinzufuhr, bei an Leukämie L-1210 erkrankten Mäusen entweder 1 h vor oder gleichzeitig mit 5-Azacytidin verabreicht, bewirkt eine Herabsetzung der Toxizität von 5-Azacytidin, die sich in der Gewichtsveränderung und Verlängerung der Lebenszeit zeigt. Aufgrund der gefundenen zeitlichen Verhältnisse wird die Hypothese aufgestellt, dass Cytidin oder Uridin nur dann wirksam werden, wenn der Ort der metabolischen Vorgänge gleichzeitig mit 5-Azacytidin erreicht wird.     

Glucan-induced enhancement of hemopoietic recovery in gamma-irradiated mice

Summary A single pre- or postirradiation application of -(13)-D-glucan, a potent reticuloendothelial stimulant, enhances hemopoietic recovery in sublethally gamma-irradiated mice. Pretreatment of mice with glucan significantly reduces lethal radiation effects.     

Tuftsin and D-Arg3-tuftsin possess analgesic action

Summary Tuftsin has marked analgesic activity but is less potent than D-Arg³-tuftsin. The absence of an antagonistic effect of naloxone on tuftsin and its analogue suggests that these substances do not act on opiate receptors. Tuftsin and its analogues may represent a new class of substances of interest in the search for new analgesics.