Effect of a sesquiterpene fromAristolochia indica Linn. on fertility in female mice

Summary A sesquiterpene isolated from the roots ofAristolochia indica (Linn.) was found to exert 100% interceptive activity and 91.7% anti-implantation activity in mice at a single oral dose of 100mg/kg b. wt. No toxic effect was found at the dose levels used.The authors wish to thank Dr S. C. Pakrashi and his associate Mr P. P. Ghosh Dastidar of Medicinal Chemistry Department for isolating the compound for this study. Thanks are also due to Director-General of Indian Council of Medical Research for granting a Junior Research Fellowship to C.S.     

Effect of p-coumaric acid on immature estrogen treated and cyclic female mice

Summary Oral administration of p-coumaric acid to estrogen-primed immature female mice exerts neither estrogenic nor anti-estrogenic activity, but when it is administered to cyclic female mice in single dose at proestrus or in repeated doses, induces alteration in estrus cycle, ovarian and uterine weight and structure.The authors wish to thank Dr S. C. Pakrashi and his associates of Medicinal Chemistry Department for isolating the compound. Thanks are also due for granting Senior Research Fellowship to P.P. and Junior Research Fellowship to S.N.K. respectively.     

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.     

Low ambient oxygen tolerance in some freshwater teleosts

Summary Measurements of the asphyxial oxygen level forRhinomugil corsula, Tilapia mossambica, Puntius sarana andCarassius auratus at 30 and 35°C revealed that at 35°C the lethal oxygen level was higher forT. mossambica andP. sarana and lower forR. corsula, but it remained the same forC. auratus at 30 and 35°C. From a thesis (M.P.M.) approved for the degree of Doctor of Philosophy, Madurai Kamaraj University, madurai, India. We wish to express our thanks to Prof. S. Krishnaswamy for providing facilities and to Dr S.V. Job for suggestions.     

Effect of the extracts fromAristolochia indica Linn. on interception in female mice

Summary The crude petroleum ether, chloroform and alcoholic extracts of the roots ofAristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.The authors are thankful to Mr.P. P. Ghosh Dastidar, Medicinal Chemistry Division for the plant extracts. Thanks are also due to Indian Council of Medical Research and Council of Scientific and Industrial Research for granting scholarships to two of them (B.C. and A.D.) and to Prof.R. N. Chakravarti, Director of the Institute for encouragement.     

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.     

The role of glycine in the biosynthesis of steroids

Zusammenfassung Während der Biosynthese von Cholesterol mit homogenisierter Rattenleber wird [2-¹⁴C] des Glycins viel besser eingebaut als [1-¹⁴C].Saccharomyces cerevisiae produziert radioaktives Squelen (ausser Ergosterol mit Radioaktivität des Ringsystems) mit [2-¹⁴C] Glycin und mit [3-¹⁴C] Serin, aber nicht mit [1-¹⁴C] Glycin.

---

---

Studies on Biosynthesis. Part VI. For Part V, seeA. K. Bose, K. S. Khanchandani andB. L. Hungund, Experientia,27, 1403 (1971). b) Presented at the 164th National Meeting of the American Chemical Society, New York, August, 1972.

---

The support of this research by Stevens Institute of Technology and Sandoz Foundation is gratefully acknowledged. We wish to thank Drs.P. T. Funke, M. S. Manhas, P. K. Bhattacharyya, M. Anchel andH. Levey for valuable discussions and help with some of the experiments.     

Action duCorynebacterium parvum sur les taux de lysozyme (muramidase) sérique

Summary An i.v. injection of 548 g of killedCorynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day.     

3,5-Dibromo-2′-chloro-4′-isothiocyanatosalicylanilide,a potent anthelminitic

Summary The compound, 3,5-dibromo-2-chloro-4-isothiocyanatosalicylanilide, has been tested against various nematode and cestode parasites in experimental and domestric animals. It shoved 100% activity againstAncylostoma ceylanicum, A. tubaeformis, Syphacia obvelata, Ascaridia galli, Toxocara spp.,Toxascaris sp.,Gnathostoma spinigerum, Hymenolepis nana, Raillietina spp. andTaenia spp. in doses 25–70 mg/kg given in single or multiple administrations.Acknowledgments. We express sincere thanks to Dr Nitya Nand, F.N.A., CDRI, Lucknow, for his keen interest in the work, to Dr B. N. Dhawan, F.N.A. for providing informations about general pharmacology of the compound, and to Dr R. K. Chatterjee and Dr P. K. Murthy for carrying out antifilarial sreening. Technical assistance of Mr S. C. Bhar and Mr S. Ram is acknowledged.     

Ontogenetic changes in isozyme patterns during seed germination of self-pollinatedSecale species

Summary Six isozymatic systems have been studied comparatively during the first week of germination of seeds of self-pollinatedSecale species (S. silvestre Host. andS. vavilovii Gross.). Isozymatic systems do not change at all, or reach their definitive adult plant pattern early during germination.Acknowledgements. This work was carried out at the Dpto. de Genética, Univ. Complutense, Madrid and supported by grants from the C.A.I.C.Y.T. (1789-82) and the P.F.P.I.     

Leishmania donovani in hamsters: Stimulation of non-specific resistance by novel lipopeptides and their effect in antileishmanial therapy

Several novel type of lipopeptides were synthesized and evaluated for their ability to stimulate non-specific resistance againstLeishmania donovani infection. Peritoneal macrophages isolated from young male hamsters treated with muramyl dipeptide (MDP) and various synthetic lipopeptides (6 mg/kg i.p.) 7 days earlier, were cultured in vitro and challenged 24 h later withL. donovani promastigotes. One lipopeptide, Central Drug Research Institute (CDRI) compound 86/450, exhibited significantly higher immunostimulatory activity than MDP. Its prophylactic activity was further confirmed in hamsters by giving 2 split doses of 3 mg/kg of the compound spaced at 2 weeks, i.e. on day –7 and +7 of challenge withL. donovani amastigotes. The prophylactic effect lasted for 7 days following the last treatment with compound 86/450. The antileishmanial action of sodium stibogluconate (SAG) was also found to be enhanced by 16% in hamsters primed with compound 86/450.CDRI Communication No. 5034.     

Laccase production byPolyporus sanguineus under different nutritional and environmental conditions

Summary Laccase production was higher in malt extract medium than in lignin, andPolyporus sanguineus appears to be better thanPolyporus versicolor andTrametes hirsuta (syn.Polyporus hirsutus) for enzyme production. Phenolic compounds, of which resorcinol was the most active, induced enzyme production; while sugars repressed it. A temperature of 37°C, pH 3 and indulin AT at a concentration of 0.2% gave the best enzyme yield.A part of Ph. D. thesis of D.S. Arora.Acknowledgments. We thank Westvaco Chemical Division, USA, and Dr P.S. Rehill, Forest Research Institute, Dehradun, India for providing lignin samples and the fungal strain, respectively. D.S. Arora further thanks University Grants Commission, New Delhi for financial assistance.     

Ansamitocin P-3, a maytansinoid,fromClaopodium crispifolium andAnomodon attenuatus or associated actinomycetes

Summary Guided by cytotoxicity, ansamitocin P-3, a maytansinoid, was isolated in very low yield from two members of the moss family Thuidiaceae,Claopodium crispifolium (Hook.) Ren & Card. andAnomodon attenuatus (Hedw.) Hueb. Ansamitocin P-3 showed potent cytotoxicity against the human solid tumor cell lines A-549, HT-29. A possible basis for the occurrence of this compound in mosses is discussed.Presented at the XV International Symposium on Natural Product Chemistry, Monterrey (Mexico) April 28–30, 1988 and at the International Research Congress on Natural Products, Park City (Utah, USA) in July 1988.Acknowledgments. This work was supported by grant No. CA 33326 from the NCI, NIH, USA. K.S. is the recipient of support from the Anandha-Mahidol Foundation, Thailand. The 470 MHz NMR instrument was available through the Purdue University Biochemical Magnetic Resonance Laboratory supported by NIH grant No. RR1077 from the Biotechnology Resources Program of the Division of Research Resources. Special thanks are due to the Purdue Cell Culture Laboratory for in vitro testing data and to Dr M. Antoun forC. crispifolium extraction. The animal testing data are the results of screening performed under the auspices of the Developmental Therapeutics Program, Division of Cancer Treatment, the NCI.     

Changes in the free amino acid pattern of haemolymph of the common indian scorpionPalamnaeus bengalensis during moulting

Summary Haemolymph ofPalamnaeus bengalensis contains normally 12 and during moulting up to 15 free amino acids, being in maximal number at the end of ecdysis. Aminoacidaemia is most pronounced during the pharate stage. Tyrosine appeared for tanning of the cuticle. Taurine and methionine were not present.Acknowledgment. The author is thankful to Dr.S. C. Shrivastava for valuable guidance and State C.S.I.R. (U.P.) for funds.     

RH-5849, a nonsteroidal ecdysone agonist,does not mimic makisterone-A inDysdercus koenigii

The response of final instar nymphs ofDysdercus koenigii to topical application of the non-steroidal ecdysone agonist, RH-5849, was dose dependent. The candidate compound produced mortality even at moderate doses, but precocious adult development was not observed. Similar results were obtained after oral administration or injection. Conversely, injections of makisterone-A (the principal moulting hormone ofDysdercus) into 5th instar nymphs resulted in precocious adult development within 4 days. We conclude that RH-5849 does not mimic makisterone-A, as is the case with ecdysone, and that toxicity is mediated instead through non-endocrine targets in this insect species.     

Antiarrhythmic properties of 3-(2-hydroxy-3 isopropylamino-propoxy)-3 phenyl-2 isoindolinone-1, (RS, SR) in the dog]

In the Dog, 3-(2-hydroxy-3 isopropylamino-proxy)-2-phenyl-1-isoindolinone (RS, SR) possesses an anti-arrhythmic activity similar to that of quinidine but at dose levels 2 to 6 times lower than in the case of the latter compound. Furthermore, in contrast to quinidine, at the dose levels where the antiarrhythmic activity is well observed, the compound is devoid of hypotensive activity and of depressive action on cardiac contractility. The first clinical studies of this compound have shown its usefulness in the treatment of ventricular and supraventricular arrhythmias.     

Development of visual sensitivity in the fly,Sarcophaga bullata

Summary Ontogeny of light response in the compound eyes of the fly,Sarcophaga bullata was investigated. Even though the eyes are structurally differentiated before eclosion they become electrophysiologically functional only after eclosion.Supported by grants from University of New Brunswick and NSERC to P.S. and NIH grant DHHS-1-RO1-EY 03408-03 to W.S.S. We would like to thank Mark Biagi and Roger Smith for technical assistance.     

Cortinarius speciosissimus toxins — a preliminary report

Summary Methanolic extracts ofCortinarius speciosissimus yielded a fluorescent compound which was crystallized and shown to be a cyclic polypeptide. The compound, or an analogue, has been found in most members of the genusCortinarius.The authors acknowledge the help of Dr M. Stewart, Department of Biochemistry, Royal Infirmary, Glasgow, for the amino acid analysis. This work was supported by the Scottish Home and Health Department, grant No. H/MRS/S)/C350.     

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.     

Electric organ discharges of the weakly electric fishGymnarchus niloticus (mormyriformes) in its natural habitat

Summary Electric organ discharges (EODs) ofGymnarchus niloticus in its natural habitat (Chari River, Chad Basin) and accompanying ecological data (pH, conductivity, temperature, turbidity, O₂ dissolved) were recorded. The EOD frequencies ranged from 204 to 313 Hz (day) and 196–326 Hz (night). In social swimming the range of interfish EOD frequency differences was from 4 to 82 Hz. The EOD frequency seems to decrease with the age of the fish.Supported by CUNY/RF No. 10748; Hunter College; American Philosophical Society, Penrose Fund No. 7135.Supported by C. N. R. S./R. C. P.