Action of D-penicillamine on immunocomplexes containing rheumatoid factor

Summary The affinity between purified rheumatoid factors (RF) and native or heat aggregated human IgG has been studied in vitro by polarization florescence in the presence and in the absence of D-penicillamine. The value of the dissociation constant was the same using native and heat aggregated IgG suggesting that binding to the aggregated protein is not dependent on the exposure of a new determinant lacking in the native molecule. The results obtained in the presence of D-penicillamine suggest that the concentration of the drug necessary to get a pronounced effect on the apparent dissociation constant of the immunocomplex between IgG and RF is not reached in vivo, in clinical situations.     

Effects of D-penicillamine on some oxidative enzymes of rat organs in vivo

Summary In the liver of neonate rats and in tissues of adult rats a study was made of the effect of D-penicillamine treatment in vivo on the enzymes of peroxide metabolism, lipid peroxidation and other components. It was found that D-penicillamine primarily acts by decreasing lipid peroxidation, thus stabilizing the membrane.Properties of enzymes. Serial publication Part XVI.Acknowledgment. We should like to take the opportunity to express our thanks to the Directorate of Knoll AG, Ludwigshafen. FRG, for the kind gift of Metalcaptase^®.     

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.     

Choleretic and cholestatic effects of infused bile salts in the rat

Summary In rats, at low infusion rates taurocholate (TC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TCD) each produced an increase in bile flow of 20–50%. However, at high infusion rates (5–20 moles min^–1 kg^–1) the cholestatic effects of the bile salts were revealed and the relative toxicity of the bile salts was seen to be TDC>TCDC>TC.     

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

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.     

The sterilization of honey with cobalt 60 gamma radiation: a study of honey spiked with spores ofClostridium botulinum andBacillus subtilis

Unprocessed honey is a recognized wound-healing remedy. However, to make clinical use of honey acceptable, it should be sterile. To find the lowest dose of irradiation needed for sterilization, six batches of honey (a?f) were gamma irradiated with 6, 12, 18, 22 and 25 kGy Cobalt-60. After a dose of 25 kGy the antibacterial activity was not altered. Presumably glucose oxidase (EC 1.1.3.4), which produces hydrogen peroxide, is not easily damaged by irradiation. Amylase activity on the other hand was significantly reduced to 19%, 19%, 21%, 22%, 43% in batchesa), b), c), d) andf) respectively, whereas no decrease was observed in batche). All batches spiked with approximately 10⁶ spores fromCl. botulinum orB. subtilis per 50 g honey proved to be sterile after irradiation with a dose of 25 kGy. Honey was also spiked withCl. botulinum at up to 5000 spores per 50 g honey which is the upper limit of natural contamination. The sterilizing dose in this case was 18 kGy.     

The action of D-penicillamine on cytochrome oxidase in vivo and in vitro

Summary The activity of cytochrome oxidase greatly decreases in the organs of rats treated with D-penicillamine for 20 days (30 mg/100 g/day). Although the drug does not affect cytochrome oxidase in vitro, it readily reduces oxidized cyt. c.     

Choleretic and cholestatic effects of infused bile salts in the rat.

In rats, at low infusion rates taurocholate (TC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TCD) each produced an increase in bile flow of 20-50%. However, at high infusion rates (5-20 mumoles min-1kg-1) the cholestatic effects of the bile salts were revealed and the relative toxicity of the bile salts was seen to be TDC greater than TCDC greater than TC.     

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.     

Effects of various media on tissular and cellular structures of the superior cervical ganglion of the rat

Summary The superior cervical ganglia of the rat have been incubated in vitro for 1 h in basal medium Eagle (BME) with Hanks' salts, BME with Earle's salts, Krebs' solution and NCTC 109 medium. Comparison of the cell areas, established by a semi-automatic quantitative method, shows that the three former induce a 30–35% neuronal retraction, whereas NCTC 109 has no effect. Thus this latter medium seems the best one for studies using incubation of these cells.We are indebted to Miss M. Vio, Mrs J. Bottini, Mr C. Cataldo and Mr P. Cau for their helpful assistance.     

An electrophoretic investigation of the binding of 3-14C coumarin to rat serum proteins

Summary The binding of coumarin to serum proteins of the rat has been demonstrated. Of the total bound coumarin (37% of injected dose), 36% was bound to the slow and fast ₁ globulins, 11% to the post albumins, 10% to globulin and 9% to albumin.     

Effect of methyl ester of aristolic acid fromAristolochia indica Linn. on fertility of female mice

Summary Methyl ester of aristolic acid, a pure compound isolated from the roots ofAristolochia indica (Linn.), was found to exert 100% abortifacient activity at a single oral dose of 60 mg/kg b. wt when administered on 6th or 7th day of pregnancy; 20 and 25% abortifacient effect were observed at the same dose on day 10 and 12, respectively.The authors wish to thank Dr S.C. Pakrashi and his associate Mr P.P. Ghosh Dastidar for the compound. Thanks are also due to the Director General of Indian Council of Medical Research for granting a fellowship to one of them (C.S.).     

Leishmania donovani in hamsters: Stimulation of non-specific resistance by some novel glycopeptides and impact on therapeutic efficacy

Summary Several glycopeptides structurally related to muramyl dipeptide (MDP) have been synthesized and evaluated for their ability to stimulate the non-specific resistance of hamsters againstL. donovani infection. These compounds have been named CDRI compounds. The synthetic procedure used for compounds 86/448 and 84/212 is described.MDP and its synthetic congeners were administered as immunostimulants at a prophylactic dose of 3 mg/kg at two weeks interval. The challenge infection (1×10⁷ amastigotes i.c./hamster) was given in between two doses of the compounds. One of the glycopeptides, CDRI comp. 86/448, has been found to be significantly more potent than MDP, effecting 92% inhibition of the challenge dose, whereas MDP produced only 26.5% inhibition. The effect of comp. 86/448 lasted until day 7 of challenge. The efficacy of sodium stibogluconate was appreciably improved in hamsters treated with comp. 86/448.     

A propos d'antibiotiques insolubles

Summary The authors show the antibiotic activity of water-insoluble salts of hydrosoluble antibiotics in the case of penicillin G (salts of iron, copper, silver, gold, and uranium) and streptomycin (oleate).     

The antiviral effect of Keishi-ni-eppi-ichi-to,a tranditional Chinese herbal medicine,on influenza A2(H2N2) virus infection in mice

The antiviral effect of Keishi-ni-eppi-ichi-to (TJS-064), a traditional Chinese herbal medicine, was investigation in mice infected with influenza A₂(H₂N₂) virus. When mice exposed to 5 LD₅₀ dose of the virus were treated orally with a 70 mg/kg dose of TJS-064 1 day before and 1 day and 4 days after the infection, 100% survived over a 25-day experimental period. At the end of this period all the control mice, treated with saline alone, had died; their mean survival time in days (MSD) was 11.2 days. When mice infected with a 10 LD₅₀ dose of the virus were treated with TJS-064, the MSD was >17.4 days and there was a 50% survival rate, while the control group had a MSD of 8.7 days and 0% survival rate. No significant antiviral effect TJS-064 was observed when the agent was administered orally to mice infected with a 100 LD₅₀ or large dose of influenza virus. Pulmonary consolidation, virus titers in lung tissues and HAI titers in sera of infected mice treated with TJS-064 were all significantly lower than those of infected mice treated with saline. Interferon activities were detected in sera of mice treated with the agent at a dose of 100 mg/kg orally. Since viricidal and viristatic activities of the agent against influenza virus were not demonstrated, the antiviral effects of TJS-064 may be expressed through the host's antiviral functions including interferon production.     

In vivo effect of sodium valproate on mouse liver

The in vivo effect of sodium valproate (SV) on the activity of uridine diphosphate glucuronosyltransferase (UDP-GT) and hepatotoxicity in the mouse liver was studied. Mice were injected intraperitoneally (IP) with SV at doses varying from 50 to 800 mg/kg per day, for six consecutive days (dose-response group) or at a standard dose of 300 mg/g per day for 2-10 days (time-response group), whereas the controls were injected with normal saline. Valproic acid levels had a positive correlation to the dose (P < 0.001) and duration of drug administration (P = 0.006). A gradual increase in UDP-GT activity was observed in doses of up to approximately 400 mg/kg per day, whereas in higher doses the enzyme activity gradually decreased. The time course of UDP-GT activity at the standard dose of 300 mg/kg per day increased progressively, with a maximum up to the sixth day and then had a gradual reduction. Hepatic necrosis (which was unrelated to the dose or the duration of drug administration) was found in 13% of the SV-treated animals and in none of the controls. We conclude that at an optimal dose (300-400 mg/kg per day) and at a time course of 6 days, SV causes liver UDP-GT induction, whereas in higher doses and longer duration of administration, UDP-GT activity is gradually reduced. SV also causes hepatotoxicity unrelated to dose and time course.     

Biological activity of enantiomerically pure forms of insect juvenile hormone I and III inBombyx mori

Summary Biological activity of enantiomerically pure juvenile hormones was assayed by topical application on allatectomizedBombyx fourth instar larvae. JHs tested were (10R)-JH I [methyl (2E,6E,10R,11S)-10,11-epoxy-3,11-dimethyl-7-ethyl-2,6-tridecadienoate], (10S)-JH I [methyl (2E, 6E, 10S, 11R)-10,11-epoxy-3,11-dimethyl-7-ethyl-2,6-tridecadienoate], (10R)-JH III [methyl (2E,6E,10R)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate] and (10S)-JH III [methyl (2E,6E,10S)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate]. Among these compounds, natural (10R)-JH I was most active and the dose needed to induce 50% larval molting was 0.04 g/larva; it was approximately 12,000 times more active than unnatural (10S)-JH I. Though natural (10R)-JH III showed slight biological activity, it was only one three-thousandth of that of (10R)-JH I. Unnatural (10S)-JH III exhibited no biological activity at the levels assayed.     

Versuche auf dem Gebiet der Lokalanästhesie mit protrahierter Wirkung. III

Summary The addition of simple quaternary salts (as I and II) to solutions of local anaesthetics, effects a pronounced prolongation of the time of complete infiltration anaesthesia. These salts have no effect on the time of surface anaesthesia. Other pharmacological characteristics of these mixtures were also determined.     

Transaminasenaktivität nach Methyltestosteron-, Testosteronpropionat-, Chlorpromazin- und Methylthiouracilbehandlung

Summary The treatment of 62 patients with chlorpromazine was followed by a rise of SGO-T in the serum in 20% of them. Six other patients were treated with a daily dose of 200 to 400 mg Methylthiouracil for 14 days. No elevation of serum transaminases was observed. The application of a daily dose of 30 mg methyl testosterone to 40 other patients was followed by a rise of SGO-T and SGP-T in 77% of them. The maximal elevation of SGO-T was 275 U. and of SGP-T 260 U., and this was reached during 10 days of therapy on an average. This effect is bound to the methyl group of methyl testosterone, since in 10 patients, treated with the same dose of testosterone propionate, the serum transaminases activity were not influenced.     

Sex pheromone blend of the codling moth,Cydia pomonella: Evidence for a behavioral role of dodecan-1-ol

Summary Pheromone glands and effluvia of the codling moth female containE-8, E-10-dodecadien-1-ol as main component, accompanied by its geometric isomers, the corresponding acetate and aldehyde (both in gland extracts only),E-9-dodecen-1-ol and saturated alcohols of 10 to 18 carbons. Dodecan-1-ol as the most abundant secondary component (about 30% of the female blend) acts in the wind tunnel by widening the dose range over which codling moth males are optimally attracted toE-8, E-10-dodecadien-1-ol.This research was supported by the Swiss National Science Foundation. We thank W. Riggenbach for supplying moths and T. Wildbolz, P. Charmillot and M. Tóth for conducting field trials.