A rat mutant unable to synthesize vitamin C

A colony of Wistar rats with a hereditary defect in L-ascorbic acid-synthesizing ability was established. This rat, like primates and guinea pigs, lacks L-gulonolactone oxidase (EC 1.1.3.8) which catalyzes the last step of L-ascorbic acid biosynthesis. When L-ascorbic acid was added to their drinking water, the rats grew almost normally and were fertile. These mutant rats should be useful not only for nutritional and pharmacological studies on vitamin C, but also for genetic studies on the lack of this enzyme.     

Effects of L-lysine administration on certain aspects of ascorbic acid metabolism in weanling rats

Summary L-lysine administration to male weanling rats at a dose of 110.4 mg (25% LD₅₀) per 100 g body weight per day for 15 days reduced the liver total ascorbic acid level. The biosynthesis as well as the degradation of L-ascorbic acid was diminished under these conditions. The fall in liver total ascorbic acid level after L-lysine administration was ascribed to its reduced synthesis.Acknowledgment. The authors are thankful to the Council of Scientific and Industrial Research, India, for providing Junior Research Fellowships to Miss J. Basu and Miss K. Sen Gupta.     

Ascorbic acid biosynthesis in the mammalian kidney

Summary The egg-laying mammals (Prototheria) synthesize L-ascorbic acid only inkidney, as is characteristic of reptiles. Bandicoots (Marsupialia) synthesize it in both kidney and liver. 2 other species of marsupials (kangaroos) synthesize it primairly in liver, but some individuals also synthesize in kidney.This study was supported by NSF grant INT77-15934; the Carnegie Museum of Natural History provided one field assistant. We thank M. Birney, D. Dellow, K. Jenness, and L. Robbins for field assistance, A. G. Lyne for providing the live bandicoots, and the New South Wales National Parks and Wildlife Service for issuance of collecting permits (SLF52 and SLF84).     

L-gulonolactone oxidase is present in the invertebrate,Limulus polyphemus

Summary L-Gulonolactone oxidase (EC 1.1.3.8) which catalyzes oxidation of L-gulonolactone to L-ascorbic acid was detected in tissues ofLimulus polyphemus.     

Ascorbic acid biosynthesis in the mammalian kidney

The egg-laying mammals (Prototheria) synthesize L-ascorbic acid only in kidney, as is characteristic of reptiles. Bandicoots (Marsupialia) synthesize it in both kidney and liver. 2 other species of marsupials (kangaroos) synthesize it primarily in liver, but some individuals also synthesize in kidney.     

Luteolytic potency of 16-phenoxy-derivatives of prostaglandin F2 alpha

The binding of 16-phenoxy derivatives of prostaglandin (PG) F2 alpha to rat luteal membranes, and also their abortifacient potency in pregnant rats, have been studied. Competitive binding studies with various PG-analogues were performed in ovaries of juvenile rats pretreated with PMSG and HCG, and in parallel studies the abortifacient potency of these substances was tested in pregnant rats. It was observed that this class of derivatives bound to the PGF2 alpha receptor as well as, or even better than the parent compound PGF2 alpha. Modifications in the carboxyl group at C-1 yielded derivatives with a higher affinity for the receptor, in decreasing order of effectiveness as follows: -COOR greater than COOH greater than OH. The data obtained from the binding studies also compared well with data on the abortifacient potency in pregnant rats. It is concluded that the addition of a phenoxy group to either the lower or upper side chain of PGF2 alpha may augment the binding to the receptor as well as the biological responses induced by the post receptor effect.     

Chronic quercetin exposure affects fatty acid catabolism in rat lung

Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin diet using whole genome microarrays. We show here that fatty acid catabolism pathways, like beta-oxidation and ketogenesis, are up-regulated by the long-term quercetin intervention. Up-regulation of genes (Hmgcs2, Ech1, Acox1, Pcca, Lpl and Acaa2) was verified and confirmed by quantitative real time PCR. In addition, free fatty acid levels were decreased in rats fed the quercetin diet, confirming that quercetin affects fatty acid catabolism. This in vivo study demonstrates for the first time that fatty acid catabolism is a relevant process that is affected in rats by chronic dietary quercetin. Received 6 July 2006; received after revision 29 August 2006; accepted 28 September 2006     

Les glycoprotéines sériques dans le granulome expérimental provoqué par la carrageenine

Summary We studied serum glycoproteins in rats and guinea pigs during the development of granulomas, provoked by carrageenin injection. In rats total serum sialic acid was raised as well as sialic acid soluble in sulfosalicylic acid and haptoglobin. The rise of these 2 fractions, seromucoid and haptoglobine accounts quantitatively for the rise of the total sialic acid. In guinea pigs total serum sialic acid was unchanged, but sulfosalicylosoluble sialic acid as well as haptoglobin were much higher than basal values. Quantitatively the serum glycoprotein reaction was much higher in rats than in guinea pigs.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin

Summary I.v. botulinum toxin after 60–90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.Acknowledgment. We are grateful to the generosity of Dr Edward J. Schantz, Food Research Institute, University of Wisconsin, for the botulinum toxin used. — This research was supported by NIH grant 1 RO1 AM 17125, The Secretion of Pepsin.     

Cardiovascular-compensatory and decompensatory responses in rats anesthetized with pentobarbital compared to chloralose-urethane

The data presented in these studies suggests that rats anesthetized with pentobarbital are better able to compensate for acute blood loss, but are less able to sustain the compensatory effort during hemorrhagic hypotension than rats anesthetized with chloralose-urethane. However, following reinfusion of shed blood the pentobarbital rats are better able to maintain their blood pressure.     

Influence of pinealectomy on serum estrogen and progesterone levels in blind-anosmic female rats

Summary Previous studies show that the suppression of gonadal function in blind-anosmic rats is dependent on the pineal gland. The present results demonstrate that in young female rats both the pineal gland and dual sensory deprivation have additional independent antigonaldal effects.This work was partially supported by state institutional funds and by NSF grant No. PCM 74-06276-276-A02. The radioimmunoassays of the steroids were carried out with the aid of the Radioimmunoassay Core which is supported by USPHS grant No. 1T30 HD-10202. We also thank Constance Stahl for typing assistance.     

Lysosomal enzyme release associated with the invasion of rat liver by Novikoff hepatoma

Summary The lysosomes of both Novikoff hepatoma and liver from Novikoff hepatoma-bearing rats were found to be relatively intact structurally, lower in acid phosphatase activity, greatly depleted in number but with nearly normal membrane integrity when compared with normal liver.Acknowledgments. We thank Dr Ellen Rasch for her valued advice and interest in the project. We are grateful to M. P. Shaw for help with the acid phosphatase assay.     

Acid sphingomyelinase in macrophage biology

Macrophages play a central role in innate immune responses, in disposal of cholesterol, and in tissue homeostasis and remodeling. To perform these vital functions macrophages display high endosomal/lysosomal activities. Recent studies have highlighted that acid sphingomyelinase (ASMase), which generates ceramide from sphingomyelin, is involved in modulation of membrane structures and signal transduction in addition to its metabolic role in the lysosome. In this review, we bring together studies on ASMase, its different forms and locations that are necessary for the macrophage to accomplish its diverse functions. We also address the importance of ASMase to several disease processes that are mediated by activated macrophages.     

Toxin bioportides: exploring toxin biological activity and multifunctionality

Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides—a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity.     

Irradiation of the head by 60Co opens the blood-brain barrier for drugs in rats

The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a 60Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of 3H2O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

Effect of cortisone or triiodothyronine administration to pregnant rats on lysosomal hydrolases in fetal forebrain and cerebellum

Triiodothyronine injected daily to pregnant rats for the last week of gestation (50 microgram/100 g b.wt) increased the specific activities of 5 acid glycosidases in the fetal forebrain and cerebellum. Cortisone (50 mg/100 g b.wt) administered in the same period had no effect on cerebellum acid hydrolases, but decreased their activity in the forebrain.     

Clara cell surface of the rat: scanning and transmission electron microscopic study

Summary In normal young rats, groups of Clara cells in the bronchioles showed the formation of many cytoplasmic blebs on their cytoplasmic domes. Detached blebs rested on the bronchiolar epithelial cells. The scanning (SEM) and transmision electron microscope (TEM) studies suggest localized changes of Clare cell surface activities by increased formation of cytoplasmic blebs which may represent the apocrine type of secretion.This project was supported by research grants from NIH HD-10139 and the American Heart Association, Kansas Affiliate. We used the Electron Microscope Research Service Laboratory of the University of Kansas Medical Center.     

Luteolytic potency of 16-phenoxy-derivatives of prostaglandin F2α

Summary The binding of 16-phenoxy derivatives of prostaglandin (PG) F₂ to rat luteal membranes, and also their abortifacient potency in pregnant rats, have been studied. Competitive binding studies with various PG-analogues were performed in ovaries of juvenile rats pretreated with PMSG and HCG, and in parallel studies the abortifacient potency of these substances was tested, in pregnant rats. It was observed that this class of derivatives bound to the PGF₂ receptor as well as, or even better than the parent compound PGF₂. Modifications in the carboxyl group at C-1 yielded derivatives with a higher affinity for the receptor, in decreasing order of effectiveness as follows:-COOR>COOH>OH. The data obtained from the binding studies also compared well with data on the abortifacient potency in pregnant rats. It is concluded that the addition of a phenoxy group to either the lower or upper side chain of PGF₂ may augment the binding to the receptor as well as the biological responses induced by the post receptor effect.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to its specific antagonizing action on the Na+ -K+ -ATPase in the gastric mucosa.