Degeneration of retinal neuroblasts by chinoform-ferric chelate

The possible mechanism of neuropathic effect of chinoform was investigated using cultured retinal neuroblasts from chick embryos. Retinal neuroblasts completely degenerated by chinoform-ferric chelate within a day. This change, however,, was not observed with free chinoform or ferric ion alpha-Tocopherol had a potent protective effect on the toxicity of the chelate. From these results, it was concluded that the lipid peroxidation due to ferric ion chelated with chinoform incorporated into the membrane of nerve tissues is the most important step in induction of the neuropathy.     

Formation of lipoperoxide in isolated sciatic nerve by chinoform-ferric chelate.

Effects of chinoform and chinoform-ferric chelate on formation of lipoperoxide in isolated sciatic nerve were investigated. Free chinoform did not increase the lipoperoxide level, while chinoform-ferric chelate significantly increased it. Assuming that the lipoperoxide formed denatures the associated protein in the nerve, the effect of chinoform-ferric chelate could explain, at least partly, the demyelination of nerve tissues caused by massive doses of chinoform.     

Formation of lipoperoxide in isolated sciatic nerve by chinoform-ferric chelate

Summary Effects of chinoform and chinoform-ferric chelate on formation of lipoperoxide in isolated sciatic nerve were investigated. Free chinoform did not increase the lipoperoxide level, while chinoform-ferric chelate significantly increased it. Assuming that the lipoperoxide formed denatures the associated protein in the nerve, the effect of chinoform-ferric chelate could explain, at least partly, the demyelination of nerve tissues caused by massive doses of chinoform.     

Lipid peroxidation caused by chinoform-ferric chelate in cultured neural retinal cells

Summary Incorporation of chinoform-ferric chelate was demonstrable in cultured neural retinal cells of chick embryos after 1 h of incubation, and the lipid peroxide level in the cells was increased strikingly 1 h thereafter. On the other hand, free ferric ions were scarcely incorporated into the cells, and a significant increase in the lipid peroxide level in the cells was not observed. These data indicate that chinoform is carrier of iron for its passage through cell membranes and that the incorporated iron induces lipid peroxidation which in turn leads to neural cell degeneration.This work was supported in part by a grant from the Ministry of Health and Welfare of Japan     

Lipid peroxidation caused by chinoform-ferric chelate in cultured neural retinal cells

Incorporation of chinoform-ferric chelate was demonstrable in cultured neural retinal cells of chick embryos after 1 h of incubation, and the lipid peroxide level in the cells was increased strikingly 1 h thereafter. On the other hand, free ferric ions were scarcely incorporated into the cells, and a significant increase in the lipid peroxide level in the cells was not observed. These data indicate that chinoform is carrier of iron for its passage through cell membranes and that the incorporated iron induces lipid peroxidation which in turn leads to neural cell degeneration.     

Effect of albumin on uncoupling of oxidative phosphorylation by chinoform in rat liver mitochondria.

Addition of serum albumin diminished the uncoupling effect of chinoform on oxidative phosphorylation in rat liver mitochondria. Upon increasing the concentration of magnesium ions in the medium, the action of serum albumin was diminished. These results indicate that serum albumin combines with chinoform in competition with magnesium ions.     

Cadmium-induced changes in avian renal morphology

Summary The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd²⁺/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated FeEDTA plus cadmium.In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups.These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered.     

Inhibition of neurotensin (NT)-induced glucagon release by [D-Trp11]-NT1

Summary A synthetic analog of neurotensin (NT), [D-Trp¹¹]-NT, antagonized NT-induced hyperglucagonemia and hyperglycemia, and also NT-induced glucagon release from pancreatic islets in rats.This work was supported in part by a grant from the Imanaga Medical Research Foundation, Nagoya, Japan. Address for reprint requests: M.U., Department of Surgery, National Nagoya Railway Hospital, Taiko 1-chome, Nakamura-ku, Nagoya 453, Japan.     

Inhibition of paraquat phytotoxicity by a novel copper chelate with superoxide dismutating activity

Summary A chelate with superoxide dismutase activity, D-penicillamine copper complex, was shown to inhibit paraquat toxicity in flax cotyledons (Linum usitatissimum var. Reina). Paraquat-stimulated chlorophyll loss and ethane production were markedly reduced by this complex. The role of superoxide in the action of paraquat is briefly discussed.This work was supported by grants from the German Academic Exchange Service to R.J. Youngman and by I.C.I. Ltd, Plant Protection Division.     

A method for the incorporation of radioactive isotopes in the sea urchin egg

Riassunto Con la iniezione di 10–20µc di Metionina-S³⁵ nella cavità celomatica di femmine adulte diParacentrotus lividus si ottiene una rapida ed efficiente incorporazione dell'isotopo nelle uova. Si discutono i vantaggi del metodo rispetto a quello attualmente in uso.

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Aided by a Grant from the Rockefeller Foundation, on leave from the Nagoya University, Japan.     

Plasma triiodothyronine,thyroxine and thyrotrophin levels in germfree rats

Summary Plasma T₃, T₄ and TSH levels in developing germfree rats were high, low and normal as compared with those in conventional counterparts. The high T₃/T₄ ratio in germfree rat plasma was lowered by cholestyramine feeding.This work was supported in part by a grant from the Imanaga Foundation, Nagoya, Japan.     

Two different hemodynamic patterns underlying hypotension during desynchronized sleep

Riassunto L'ipotensione presente durante il sonno desincronizzato del gatto, con riflessi seno-aortici intatti o aboliti, è dovuta soprattutto a diminuzione delle resistenze periferiche e in ben piccola parte a riduzione della gettata cardiaca. Solo negli episodi di sonno desincronizzato, osservati talora nel gatto con deafferentazione senoaortica, in cui l'ipotensione è cosi profonda da produrre ischemia cerebrale, la gettata cardiaca diminuisce marcatamente e l'indice di resistenza paradossalmente aumenta.

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This research has been sponsored by the Air Force Office of Scientific Research, through the European Office of Aerospace Research (OAR), United States Air Force, under Grant No. AF EOAR 66-47, and by Consiglio Nazionale delle Ricerche (Gruppo Nazionale di Medicina Sperimentale). Dr.Kumazawa was a visiting investigator from Nagoya University, Nagoya, Japan, under a IBRO-Unesco fellowship.     

The effect of bile salts on thyroxine 5′-monodeiodination in rat liver homogenate

Summary Unconjugated and conjugated bile salts inhibited the conversion of thyroxine to 3,3,5 triiodothyronine in rat liver homogenate.This work was supported in part by a grant from the Imanaga Foundation, Nagoya, Japan.     

La glycolyse anaérobie au niveau des lobes optiques isolés de l'embryon de poulet

Summary A series ofin vitro experiments have been made on lactic acid production in anaerobiosis in the developing optic lobes (mesencephalon) of the chick embryo. The rate of anaerobic glycolysis is relatively important during multiplication of the neuroblasts; but, during the differentiation of the neuroblasts into mature neurons, the anaerobic processes are lower than the phosphorylation and oxidation mechanisms essential for the growth of nerve expansions and onset of functional activity.     

Cadmium-induced changes in avian renal morphology

The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd2+/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated with FeEDTA plus cadmium. In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups. These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered.     

Antidiuretic activities of substance P and its analogs

Summary Substance P (SP) and analogs, including 5 nucleoside (ARA or HRA)-peptides, were examined for antidiuretic activity in ethanolized rats. The activity was potent in the analogs embodying the C-terminal hexapeptide, weak in the nucleoside-pentapeptide, and negligible in the nucleoside-tetrapeptide. In addition, the activity was increased by acylation of the hexapeptide. The antidiuretic potencies were also compared with the hypotensive potencies.This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, and by a grant from the Imanaga Foundation, Nagoya, Japan.     

A comparative study on the effects of brain extracts and mesodermal membrane extracts on nerve cell differentiation.

Extracts prepared from the mesodermal tissue surrounding the brain stimulate the differentiation of morphologically undifferentiated neuroblasts, while the differentiation of more mature neuroblasts is influenced by brain extracts.     

Anticomplementary fraction from the poisonous secretion of the paratoid gland of the toad (Bufo marinus paracnemis Lutz)

Summary Fractionation of the poisonous secretion of the toadBufo marinus paracnemis Lutz, by dialysis and chromatography on QAE-Sephadex, led to the isolation of a fraction which was adsorbed to the ion exchanger. This fraction, when incubated with human serum, yielded an anticomplementary effect that was evaluated by measuring the kinetics of lytic activity on sensitized sheep red cells (classical pathway) and unsensitized rabbit cells (alternative pathway).We are very much indebted to Dr Lewis J. Greene for valuable discussions. Thanks are due to Dr Antonio C. Nero and Miss Ester G. Silva for their cooperation. This work was supported in part by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).     

Betel nut residues in archaeological samples of human teeth from the Mariana Islands

Two tetrahydropyridine alkaloids, arecaidine and guvacine that are characteristic of betel nut (Areca catechu L.) have been detected in the deliberately stained labial surface of female teeth excavation on Rota, Mariana Islands. This was accomplished using selected ion monitoring techniques in conjunction with gas chromatography/electron impact-mass spectrometry. These alkaloids were not present on the buccal surface of the teeth and indicate the use of betel nut to effect the staining.     

Nature of the FeO2 bonding in myoglobin: An overview from physical to clinical biochemistry

Summary The iron(II)-dioxygen bond in myoglobin and hemoglobin is a subject of wide interest. Studieas range from examinations of physical-chemical properties dependent on electronic structure, to investigations of stability as a function of oxygen supply. Stability properties are of particular importance in vivo, since the oxygenated form is known to be oxidized easily to the ferric form, which cannot be oxygenated and is therefore physiologically inactive.Kinetic and thermodynamic studies of the stability of native oxymyoglobin have revealed a new feature in FeO₂ bonding. In vivo. the iron center is always subject to a nucleophilic attack of the water molecule or hydroxyl ion, which can enter the heme pocket from the surrounding solvent, and thereby irreversibly displace the bound dioxygen from MbO₂ in the form of O ₂ ^– so that the iron is converted to the ferric form. A free energy diagram for the potential reactions of FeO₂ visualizes myoglobin as a molecular structure that can provide in solution the delicate balance of kinetic and thermodynamic factors necessary to stabilize reversible oxygenation, as opposed to irreversible autoxidation to metmyoglobin.