Cellular and functional evidence for a protective action of neurosteroids against vincristine chemotherapy-induced painful neuropathy

Painful neuropathy is a major side-effect limiting cancer chemotherapy. Therefore, novel strategies are required to suppress the neuropathic effects of anticancer drugs without altering their chemotherapeutic effectiveness. By combining biochemical, neuroanatomical/neurochemical, electrophysiological and behavioral methods, we demonstrated that progesterone-derived neurosteroids including 5α-dihydroprogesterone and 3α,5α-tetrahydroprogesterone suppressed neuropathic symptoms evoked in naive rats by vincristine. Neurosteroids counteracted vincristine-induced alterations in peripheral nerves including 2′,3′-cyclic nucleotide 3′-phosphodiesterase, neurofilament-200 kDa and intraepidermal nerve fiber repression, nerve conduction velocity, and pain transmission abnormalities (allodynia/hyperalgesia). In skin-tumor rats generated with carcinosarcoma-cells, vincristine, which suppressed the skin tumor and restored normal blood concentration of vascular endothelial growth factor (VEGF), reproduced neuropathic side-effects. Administered alone, neurosteroids did not affect the tumor and VEGF level. Combined with vincristine, neurosteroids preserved vincristine anti-tumor action but counteracted vincristine-induced neural side-effects. Together, these results provide valuable insight into the cellular and functional mechanisms underlying anticancer drug-induced neuropathy and suggest a neurosteroid-based strategy to eradicate painful neuropathy.     

Le degré de polymérisation de l'amylose,de l'amylopectine et du glycogène

Summary A colorimetric method based on the reducing power of the aldehydic end group has been developed in order to determine the M. W. of polysaccharides. It has been found that corn amylose contains chain molecules of much higher degree of polymerization than potato amylose.     

Increased liver calcium after calcium or milk gavage in rats

Summary For 1 or 2 h following a gavage of milk or 300 mM CaCl₂ (2 ml/100 g b.wt), rats had an increased liver calcium content when compared to rats receiving a deionized water gavage.Supported in part by a grant from the National Science Foundation (PCM 75-23603). We are grateful to Mr John O'Brien for his technical assistance.     

Simplifications to substrate preparation for the cultivation of dissociated nerve cells

Résumé Nous avons simplifié la méthode de préparation du substrat «collagène» pour la culture de cellules nerveuses dissociées. On obtient une fixation et une différenciation rapide des cellules sur ce substrat. Les cultures conviennent pour des études morphologiques, biochimiques et électrophysiologiques.

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Chargée de Recherche au CNRS.

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Acknowledgments. The technical assistance of Mrs.Dorea van Weele andMrs. Marie-France Knoetgen is gratefully acknowledged.     

Biotic and abiotic factors related to redband trout occurrence and abundance in desert and montane streams

Redband trout Oncorhynchus mykiss gairdneri in the Columbia River Basin of western North America occupy desert and montane streams with variable habitat conditions. In general, desert streams are lower in gradient and elevation, contain less large substrate and more silt substrate, are less shaded by overhead vegetation, and have higher summer water temperature than montane streams. Consequently, we assessed whether the relationships between biotic and abiotic factors and the occurrence and abundance of redband trout in southwestern Idaho differed between desert and montane streams (<25 m mean width). Increased occurrence of redband trout in desert streams was most strongly related to increased stream shading and decreased amounts of silt substrate, followed by increased amounts of cobble/boulder substrate and absence of piscivorous fish (i.e., smallmouth bass Micropterus dolomieui and northern pikeminnow Ptychocheilus oregonensis ). In montane streams, increased occurrence of redband trout was most strongly related to decreased site elevation and increases in cobble/boulder substrate, followed by decreases in stream gradient and width. Furthermore, occurrence of redband trout decreased in desert streams at mean summer (June–August) water temperature (Temp smr ) >16 °C, whereas for montane streams, occurrence increased at Temp smr >9 °C. Redband trout density in desert streams was most strongly related to higher stream order (i.e., headwater streams), increased stream shading, and increased amounts of cobble/boulder substrate. In montane streams, redband trout density was not well explained by any stream conditions, but stream shading had the strongest positive relationship with density. Redband trout density was negatively related to Temp smr in desert streams, but the relationship was weak for montane streams. That environmental conditions related to the occurrence and abundance of redband trout differ between desert and montane streams is important for fisheries managers who manage these disparate populations occurring in such close proximity to each other.     

Die Zucht vonLytta vesicatoria im Laboratorium und Nachweis der Cantharidinsynthese in Larven

Summary Adult males ofLytta vesicatoria (Coleopt., Meloidae) synthesize cantharidin, but females do not, although the substance is present in the females too. We developed a method for rearing larvae of this parasitic beetle in the laboratory. It is shown that there exist 7 larval stages and 4 hypermetamorphic forms (triungulinus, second larva,pseudochrysalis and fourth larva). Larvae from the second to the fifth stage (second larva) synthesize cantharidin. Therefore, we conclude that the substance present in the adult female is at least in part synthesized in the larval period. Nothing is known about the biological significance of this biochemical sexual dimorphism.

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Coleoptera, Meloidae.     

Regulation ofL-valine absorption by opioids interacting withμ-receptors in rabbit ileum

In intact tissue, [d-Ala²,MePhe⁴, Gly-ol⁵] enkephalin (10^–5 M;-ligand), diminsihed short-circuit current (I_sc) and increased water, Na⁺ and Cl^– net fluxes in vitro under open circuit conditions; it also inhibitedL-valine absorption andL-valine-dependent variations of short-circuit current (I_{sc, val}). Naloxone (10^–6 M) antagonized these effects. In the absence of the muscularis and myenteric plexus this enkephalin or morphine (-ligand) reduced I_sc and I_{sc, val}. These enkephalin effects occurred at different times. Different concentrations of enkephalin were tested for their effects on I_{sc, val}. [d-Ala²,d-Leu⁵] enkephalin (mainly a -ligand) significantly decreased I_sc but not I_{sc, val}. The reduction ofL-valine absorption does not depend on the effects on basal ion transport. Interaction of opioids with-receptors located in the submucosal plexus and/or in the epithelial cell accounts for this reduction. This enkephalin effect seems to be at least partially under the control of the myenteric plexus.