Alkylation mutagenesis in Saccharomyces cerevisiae: lack of evidence for an adaptive response

Summary We have found no evidence for an adaptive response for either lethality or mutagenesis following treatment of Saccharomyces cerevisiae with N-methyl-N-nitro-N-nitrosoguanidine (MNNG). The rad6 and rad52 mutants of S. cerevisiae are highly defective in MNNG and ethyl methanesulfonate induced mutagenesis of both stationary and exponential phase cells. These and other observations indicate that the mechanisms of repair of alkylation damage and mutagenesis differ markedly between S. cerevisiae and Escherichia coli.     

Postembryonic growth of the optic lobe of Octopus vulgaris, Lam

The pattern of growth of the optic lobe of Octopus vulgaris has been investigated from 0.1 to 6.0 gms body weight by measuring the weight of the lobe and the number of nuclei present in the tissue homogenate. In the normal habitat, the rate of increase in nulcear number relative to increase in body weight is 1.32 up to 1.5–1.8 gms, but undergoes a three-fold decrease above this size. On the other hand, the rate of increase in tissue weight remains essetially constant throughout the same period of development, with the exception of the interval between 1.0 g and 1.5 gms during which it rises markedly. Nuclear density increases steadily up to approximately 1.2 gms and approaches a constant value above this size. In octopuses reared in transparent containers or under an opaque cover the rates of increment in number of nuclei and in tissue weight are generally lower than normal between 0.2 g and 1.5 gms. In both experimental conditions the wave of acceleration in the rate of increase of tissue weight occurring between 1.0 g and 1.5 gms in normal animals appears earlier particularly in octopuses reared under an opaque cover. At body weights larger than 1.5–2.0 gms the rates of increment in number of nuclei and tissue weight become higher than normal in octopuses reared in transparent boxes, but change in the opposite direction when rearing takes place in opaque containers. In the former condition, the nuclear density of newly added tissue starts decreasing earlier than normal but reaches a higher level at body weights above 2 gms, while in octopuses reared under an opaque cover the decrease occurs at approximately normal timing but attains lower values at higher body weights.     

Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats

The experimentally induced neurotoxic effects of paclitaxel and docetaxel have never been compared, since no animal models of docetaxel peripheral neurotoxicity have yet been reported. In this experiment, we examined the effect of the chronic administration of these two taxanes in the Wistar rat using neurophysiological, neuropathological and morphometrical methods. Our results showed that both paclitaxel and docetaxel induced a significant, equally severe and dose-dependent reduction in nerve conduction velocity. On the contrary, the morphometric examination demonstrated that the effect on the nerve fibres was more severe after paclitaxel administration when the same schedule was used. However, the overall severity of the pathological changes was milder than expected on the basis of the neurophysiological results. Our results support the hypothesis that taxanes (and particularly docetaxel) may exert their neurotoxic effect not only on the microtubular system of the peripheral nerves, but also on other less obvious targets.     

Multiple juvenile xanthogranulomas in a 13-year-old

A 13-year-old Caucasian girl presented with a 1(1/2) month history of multiple, asymptomatic, discrete, orange-yellow to skin-colored, dome-shaped, smooth, 3 to 6 mm papules on the arms, legs, trunk, and buttock. Pathology showed a dermal infiltrate of Touton-type giant cells, scattered lymphocytes, and macrophages. The patient was diagnosed with juvenile xanthogranuloma. We present this patient because of the uncommon presentation of multiple juvenile xanthogranulomas in a 13-year-old. Although juvenile xanthogranuloma generally occurs in infancy, it must be included in the differential diagnosis for an older child. This entity can less frequently occur in adults and typically a solitary lesion is found. Multiple juvenile xanthogranuloma is rare in older children and adults. Work-up should include a thorough review of systems, physical examination, and ophthalmology examination. Pediatricians and dermatologists should be aware that juvenile xanthogranulomas might occur in older children.     

Development of nociceptin receptor (NOP) agonists and antagonists

The nociceptin opioid (NOP) receptor is the most recently discovered member of the family of the opioid receptors; its endogenous agonist is the peptide nociceptin. Due to the subsequent elucidation of its physiological role in both central and peripheral nervous system and in some non‐neural tissues, there is a rapidly growing interest in the pharmacological application of substances active on this receptor. Despite the current clinical use of a morphinane‐based NOP/MOP mixed ligand (buprenorphine) as an analgesic and in the treatment of drug addictions, so far just a few clinical trials have been made with selective NOP ligands. However, the perspective of their utilization is rapidly growing. Agonists can find applications in the treatment of neuropathic pain, anxiety, cough, drug addition, urinary incontinence, anorexia, congestive heart failure, hypertension; and antagonists for pain, depression, Parkinson's disease, obesity, and as memory enhancers. Besides peptide ligands, which are still subjected to many pharmacological investigations, many different chemical classes of NOP ligands have been discovered: piperidines, nortropanes, spiropiperidines, 4‐amino‐quinolines and quinazolines, and others. The new advances in establishing structure–activity relationships, also with the help of modeling studies, can permit the development of more active and selective molecules. © 2010 Wiley Periodicals, Inc. Med Res Rev 31:605‐648,2011     

Lupinus albus γ-Conglutin: New Findings about Its Action at the Intestinal Barrier and a Critical Analysis of the State of the Art on Its Postprandial Glycaemic Regulating Activity

γ-Conglutin (γ-C) is the glycoprotein from the edible seed L. albus, studied for long time for its postprandial glycaemic regulating action. It still lacks clear information on what could happen at the meeting point between the protein and the organism: the intestinal barrier. We compared an in vitro system involving Caco-2 and IPEC-J2 cells with an ex vivo system using pig ileum and jejunum segments to study γ-C transport from the apical to the basolateral compartment, and its effects on the D-glucose uptake and glucose transporters protein expression. Finally, we studied its potential in modulating glucose metabolism by assessing the possible inhibition of α-amylase and α-glucosidase. RP-HPLC analyses showed that γ-C may be transported to the basolateral side in the in vitro system but not in the pig intestines. γ-C was also able to promote a decrease in glucose uptake in both cells and jejunum independently from the expression of the SGLT1 and GLUT2 transporters.