The pharmacological action of gastrin pentapeptide

Zusammenfassung Bei Stimulation der Magensekretion bei nichtnarkotisierten Hunden mit Heidenhain-Taschen durch Histamin und synthetisches Gastrin-Pentapeptid konnte die Wirkung des letzteren durch Ganglienhemmer vergrössert und durch Atropin vermindert werden. Die Wirkung des Histamins wurde durch Ganglienhemmer herabgesetzt. Die Versuche zeigen, dass Histamin und Gastrin-Pentapeptid verschiedene Wirkungsmechanismen besitzen.     

Comparison of DMSO and glycerol as cryoprotectants for ascites tumor cells

Summary Mouse Ehrlich ascites and rat D23 ascites tumors were stored in liquid nitrogen under identical conditions for up to 3 years. Cell viability (trypan blue exclusion) and transplantability of both tumors in animals remained virtually unaffected if preserved in 10% DMSO containing medium, whereas, cells preserved in 10% glycerol failed to produce lethal tumors in rodents.This work was performed at the Cancer Research Unit, Royal Victoria Infirmary, Newcastle Upon Tyne, England. I thank John Geggie for expert technical assistance; to the North of England Council of the Cancer Research Campaign and the National Science Foundation (ENG-78-25432) for financial support; and to Dr John A. Dickson for advice and encouragement. Also, I am indebted to Professor Rakesh K. Jain for his support.     

Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis

The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G₀/G₁ phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin. Received 14 February 2007; received after revision 26 March 2007; accepted 3 April 2007     

FITC-dextrans as fluorescence and electron microscopic tracers in studies on capillary and cell permeability of the CNS

Summary FITC-dextrans can be detected at the ultrastructural level as round electron dense particles, with no sign of distortion or aggregation. Because this tracer is a stable, non-toxic polymer of biological origin obtainable in a wide range of molecular weights, it may be useful for further studies of tissue permeability.The author is grateful to Ms. H. Büscher and Ms. S. Klemt, Department of Pathology, for their excellent technical assistance.     

FITC-dextrans as fluorescence and electron microscopic tracers in studies on capillary and cell permeability of the CNS

FITC-dextrans can be detected at the ultrastructural level as round electron dense particles, with no sign of distortion or aggregation. Because this tracer is a stable, non-toxic polymer of biological origin obtainable in a wide range of molecular weights, it may be useful for further studies of tissue permeability.     

An effect of DMSO on post-irradiation saccharin avoidance in mice

Zusammenfassung Ein Dimethylsulfoxyd (DMSO)-Effekt wird beschrieben: bei Nachbestrahlung vermeiden Mäuse Sodium-Saccharin. Mit DMSO vorbehandelte Tiere (Eintauchen der Schwänze in diese Substanz kurz vor Bestrahlung) bevorzugen wie unbehandelte Mäuse Saccharin-Sodium.

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This work was supported in part by Grant No. PHS-SOI-FR-5369-04-5 from the University of Illinois, Graduate College of Medicine.     

Anin vitro action of deoxycorticosterone (DOC) on red cell electrolytes

Résumé Dans les suspensions d'érythrocytes humains incubées avec du glucose et du déoxycorticostérone glucoside, K diminue, tandis que Na, H₂O et P augmentent. Ces globules rouges, traîtés avec des hormones, absorbent notablement moins d'oxygène de bleu de méthyle que les érythrocytes de contrôle.     

Glycerol permeability of erythrocytes

Zusammenfassung Untersuchungen über die Unterschiede in der Lipoidzusammensetzung der Erythrocyten von neun Tierarten ergaben eine verschiedene Glyzerinpermeabilität dieser Zellen. Bei der einen Gruppe zeigen die Erythrocyten eine stark temperatur bedingte Glyzerinpermeabilität, bei der anderen eine hohe, kaum temperaturabhängige Permeabilität, die bei Erniedrigung des pH-Wertes im Medium stark abnimmt.     

Physiological and nutritional importance of selenium

Summary The essential trace element selenium has recently attracted attention because of its potentialities in the maintenance of human health. Selenium forms part of the active site of the peroxide-destroying enzyme glutathione peroxidase, and it also has other functions, for example in biotransformation, detoxification and the immune response. Functional and clinical consequences of selenium deficiency states have been described, and the selenium requirement, which is influenced by the usual selenium exposure, has been discussed. Wide variations have been found in selenium status in different parts of the world, and populations or groups of patients exposed to marginal deficiency are more numerous than was previously thought.Current research activities in the field of human medicine and nutrition are devoted to the possibilities of using selenium for the prevention or treatment of degenerative or free radical diseases such as neurological disorders, inflammatory diseases or cancer. Pharmacological selenium doses are also recommended as an adjuvant in some treatments.     

Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of action and therapeutic prospects

There is an ongoing need for effective and targeted cancer treatments that can overcome the detrimental side effects presented by current treatment options. One class of novel anticancer molecules with therapeutic potential currently under investigation are cationic antimicrobial peptides (CAPs). CAPs are small innate immunity peptides found ubiquitously throughout nature that are typically membrane-active against a wide range of pathogenic microbes. A number of CAPs can also target mammalian cells and often display selective activity towards tumor cells, making them attractive candidates as novel anticancer agents warranting further investigation. This current and comprehensive review describes key examples of naturally occurring membrane-targeting CAPs and their modified derivatives that have demonstrated anticancer activity, across multiple species of origin and structural subfamilies. In addition, we address recent advances made in the field and the ongoing challenges faced in translating experimental findings into clinically relevant treatments.     

The age parameter of pharmacological activity

Zusammenfassung Je nach dem Alter wirken Pharmaka sehr verschieden. Hexobarbital ist bei alten Tieren stärker narkotisch; Amphetamin und Ritalin weniger erregend; Amphetamin und Preludin wirken stärker appetithemmend und nach Novokain ist die Hemmung der Wärmeregulation stärker bei alten Tieren. Peripher angreifende Pharmaka zeigen keine Unterschiede.     

Genetic and pharmacological models of cholinergic supersensitivity and affective disorders

Summary Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than normal, or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.     

Genetic and pharmacological models of cholinergic supersensitivity and affective disorders

Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than 'normal', or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.     

The permeability of tumour vessels

Summary Experimental proof that tumour vessels are permeable to humoral agents but impermeable to cellular elements viz. leucocytes. The cause of this impermeability is believed to be the deposition of immunosuppressive alpha globulin on the walls of tumour vessels. This concept is of relevance in organ transplantation and cancer immunotherapy.