Differential lethality in developmental stages ofDrosophila following X-irradiation

Summary ADrosophila melanogaster line has been treated with ionizing radiations. The dose-response relationship has been studied upon separate treatment of male and female gametes. The results show that while the total survival is similar, at different developmental stages differences can be observed between progenies from treated male and female gametes. It is suggested that developmental patterns may affect the expression of induced mutations.     

Dexamethasone protection against the acute lethality of ethanol in mice

Summary The administration of dexamethasone (DXM, 2.00 mg/kg) 1 h prior to the injection of lethal doses of ethanol was found to offer complete protection against ethanol toxicity at doses up to 5.25 g/kg and partial protection using higher doses. It is suggested that DXM central action might be involved in the protection against ethanol toxicity.Supported by a grant from U.S. National Aeronautics and Space Administration.     

Influence of oral glucose feeding on endotoxin lethality in mice

Summary Prolonged feeding of physiological solutions of glucose (5%) by gavage did not protect against either endotoxin death or liver glycogen depletion in mice.Supported by grants from the INSERM (CL 76.5.001.4), the CNRS (03 7860) and the DGRST. Thanks are due to M. Philippe for technical assistance.Maitre de Recherche au CNRS, to whom all correspondance should be addressed.     

Preadult lethality in four populations ofDrosophila melanogaster treated with formaldehyde

Summary Samples from 4 populations ofD. melanogaster were treated with formaldehyde by the larval feeding method, and induced lethality was scored. The results showed relevant differences among the populations analyzed.     

Preadult lethality in four populations of Drosophila melanogaster treated with formaldehyde

Samples from 4 populations of D. melanogaster were treated with formaldehyde by the larval feeding method, and induced lethality was scored. The results showed relevant differences among the populations analyzed.     

Targeting NOX enzymes in pulmonary fibrosis

Oxidative stress has been associated with a number of human fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Oxidative stress is most often defined as an imbalance between the generation of reactive oxygen species (ROS) in excess of the capacity of cells/tissues to detoxify or scavenge them. Additionally, the regulated production of ROS participates in cellular signaling. Therapeutic strategies to treat IPF have, thus far, focused on augmenting anti-oxidant capacity. Recent studies have demonstrated a critical role for ROS-generating enzymatic systems, specifically, NADPH oxidase (NOX) family oxidoreductases in fibrotic processes. In this review, we examine the evidence for NOX isoforms in the generation and perpetuation of fibrosis, and the potential to target this gene family for the treatment of IPF and related fibrotic disorders.     

Protection by chlorpromazine against lethality and renal toxicity of cisplatin in mice

The effect of chlorpromazine on acute lethal toxicity and nephrotoxicity induced by cisplatin was studied in mice. Chlorpromazine given (i.p.) 1 h before cisplatin greatly reduced lethal and renal toxicities of cisplatin. Chlorpromazine did not reduce the antitumor activity of cisplatin against Sarcoma 180 in ddY mice or EL-4 Leukemia in C57BL/6J mice.     

Differential lethality following treatment with ionizing radiations of various energies in Drosophila

Male and female gametes of Drosophila were treated with various doses of ionizing radiations: X-rays at different energy, and gamma-rays from 2 sources given singly and in 2 temporal sequences. The induced lethality was assessed in successive developmental stages by scoring the number of eggs, larvae and adults. The results clearly show that the effects of various radiations appear in terms of difference among developmental stages and/or between treated sexes/genotypes. It is suggested that the various energies affect different gene functions which are not completely independent, as supported by the non-additive effects of the two temporal sequences.     

Protection by chlorpromazine against lethality and renal toxicity of cisplatin in mice.

The effect of chlorpromazine on acute lethal toxicity and nephrotoxicity induced by cisplatin was studied in mice. Chlorpromazine given (i.p.) 1 h before cisplatin greatly reduced lethal and renal toxicities of cisplatin. Chlorpromazine did not reduce the antitumor activity of cisplatin against Sarcoma 180 in ddY mice or EL-4 Leukemia in C57BL/6J mice.     

Lead potentiation of endotoxin lethality in rats: Lack of effect of kininase inhibition

Summary Although lead and SQ₂₀₈₈₁ are potent in vitro inhibitors of kininase II activity, SQ₂₀₈₈₁ does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbility and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.This investigation was supported by the Naval Medical Research and Development Command, NNMC, Department of the Navy, Research Task No. MR041.20.01.0435. The opinions and assertions contained herein are the private ones of the author, and are not to be construed as official or reflecting the views of the Navy Department or the naval service at large.The experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, DHEW Pub. No. (NIH) 74-23.     

Lead potentiation of endotoxin lethality in rats: lack of effect of kininase inhibition.

Although lead and SQ20881 are potent in vitro inhibitors of kininase II activity, SQ20881 does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbidity and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.     

Targeting abnormal DNA double strand break repair in cancer

A major challenge in cancer treatment is the development of therapies that target cancer cells with little or no toxicity to normal tissues and cells. Alterations in DNA double strand break (DSB) repair in cancer cells include both elevated and reduced levels of key repair proteins and changes in the relative contributions of the various DSB repair pathways. These differences can result in increased sensitivity to DSB-inducing agents and increased genomic instability. The development of agents that selectively inhibit the DSB repair pathways that cancer cells are more dependent upon will facilitate the design of therapeutic strategies that exploit the differences in DSB repair between normal and cancer cells. Here, we discuss the pathways of DSB repair, alterations in DSB repair in cancer, inhibitors of DSB repair and future directions for cancer therapies that target DSB repair.     

RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency

The receptor for activated C-kinase 1 (RACK1) is a conserved structural protein of 40S ribosomes. Strikingly, deletion of RACK1 in yeast homolog Asc1 is not lethal. Mammalian RACK1 also interacts with many nonribosomal proteins, hinting at several extraribosomal functions. A knockout mouse for RACK1 has not previously been described. We produced the first RACK1 mutant mouse, in which both alleles of RACK1 gene are defective in RACK1 expression (ΔF/ΔF), in a pure C57 Black/6 background. In a sample of 287 pups, we observed no ΔF/ΔF mice (72 expected). Dissection and genotyping of embryos at various stages showed that lethality occurs at gastrulation. Heterozygotes (ΔF/+) have skin pigmentation defects with a white belly spot and hypopigmented tail and paws. ΔF/+ have a transient growth deficit (shown by measuring pup size at P11). The pigmentation deficit is partly reverted by p53 deletion, whereas the lethality is not. ΔF/+ livers have mild accumulation of inactive 80S ribosomal subunits by polysomal profile analysis. In ΔF/+ fibroblasts, protein synthesis response to extracellular and pharmacological stimuli is reduced. These results highlight the role of RACK1 as a ribosomal protein converging signaling to the translational apparatus.     

Antiarrhythmic action of synthetic oxytocin in anesthetized man

Zusammenfassung Synthetisches Oxytocin wurde für die Behandlung von ventrikulären Arrhythmien, welche bei Patienten im Lauf einer Allgemeinnarkose aufgetreten sind, verwendet. In 8 von 10 Fällen erfolgte eine prompte Wiederherstellung des normalen Sinusrhythmus. Es konnten keine unerwünschten kardiovaskulären Wirkungen beobachtet werden.     

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.     

DNA synthetic rates among cells of populations in vitro

Zusammenfassung In vitro gezüchtete Hühnerembryozellen werden mit³H-Thymidin oder¹⁴C-Thymidin «pulse-labeled», wobei «grain counts» und DNS-Gehalt in individuellen Zellen gemessen werden. Für keine der beiden Isotopen wurde eine Beziehung zwischen DNS-Gehalt und «grain count» gefunden, woraus folgt, dass die Geschwindigkeit der DNS-Synthese von Zelle zu Zelle variiert.