Antihypertensive activity of some novel pyridinylidene arylurea derivatives in spontaneously hypertensive rats.

3 novel pyridinylidene arylurea derivatives were found to lower arterial pressure in spontaneously hypertensive rats. Their relative oral potency ranged from 6 to 32 times that of guanethidine. The onset of antihypertensive action following their oral administration was less than 1 h and the duration of action ranged from 8 to over 24 h. The antihypertensive activity of the pyridinylidene arylureas was found to be assoicated with depletion of tissue catecholamines. Compound C depleted cardiac norepinephrine with little or no effect on total brain norepinephrine levels. It is suggested that compound C may have useful antihypertensive properties without CNS depressant activity.     

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.     

Activity of the principal alkaloids of Polyalthia oliveri Engler (Annonaceac) on the central nervous system and the cardiovascular system]

Polyalthia oliveri leaf alkaloid, oliveroline, shows in Mice antiparkinsonian properties which decrease or disappear with the alkalo?ds extracted from the bark of the trunk, oliveridine and oliverine. The latter alkaloid has an antihypertensive effect which is not found in oliveridine, only hypotensive by a relaxant close to papaverine action on vascular smooth muscles.     

Heat shock enhances thermotolerance of infective juvenile insect-parasitic nematodesHeterorhabditis bacteriophora (Rhabditida: Heterorhabditidae)

Insect-parasitic nematodes possess many of the attributes of ideal biological control agents, but intolerance to extreme temperatures can restrict their use. We examined whether heat-shock treatments could improve nematode survival and infectivity at temperatures that normally inhibit their activity (35 and 40°C). Nematodes exposed to a sub-lethal temperature (35°C) for 3 h with a latency period of 1–2 h at 25°C killed insects at 35 and 40°C. Correlative evidence was obtained between increased thermotolerance and the synthesis of 70-kDa heat-shock proteins (hsps). These results provide the first evidence of hsp synthesis in the development of thermotolerance and biological activity in the non-feeding, developmentally arrested, infective juvenile nematodes.     

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.     

Über den zeitlichen Ablauf der Aktivierung von Cyclophosphamid im Menschen und die Testung der zytostatisch aktiven Form an Ehrlich-Mäuse-Aszites-Tumorzellen

Summary The cytostatic action of human blood serum, following intravenous injection of cyclophosphamid, on cell proliferation and lactic production of Ehrlich mouse ascites tumour cells in vitro was tested. The maximum cytostatic activity was found 2 h after injection.     

3-Amino-1-(3,4-dichloro-α-methyl-benzyl)-2-pyrazolin-5-one (Bay g 2821), a potent diuretic from a new substance class

Summary Chemistry, salidiuretic activity and mechanism of action of 3-amino-1-(3,4-dichloro--methyl-benzyl)-2-pyrazolin-5-one (Bay g 2821), a new diuretic, are described. Owing to the initial rapid onset of activity, the reserve in capacity and the additional long duration of activity, this substance represents a potent diuretic and antihypertensive agent.     

Cellular internalization of proinsulin C-peptide

Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide, we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at 4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action. Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006     

Can blockade of presynaptic adrenergic beta receptors explain the antihypertensive effects of propranolol?]

Pretreatment with 6-hydroxydopamine abolished the antihypertensive effects of intravenously and intracisternally administered dl-propranolol in dogs with acute neurogenic hypertension. These results show that the anti-hypertensive action of this drug is dependant on the integrity of central catecholaminergic neurones and suggest an action on presynaptic bêta-adrenoceptors.     

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.).     

Species difference in sensitivity to the diabetogenic action of triphenyltin hydroxide

The sensitivity to the diabetogenic action of triphenyltin hydroxide (TPTOH) was investigated in 5 species of experimental animals. A single oral administration of TPTOH produced marked hyperglycemia and triglyceridemia in rabbits and hamsters, but no evidence of diabetes was found in mice, rats and guinea-pigs. No morphological abnormality was observed in islet tissue from TPTOH-treated hamsters.     

Species difference in sensitivity to the diabetogenic action of triphenyltin hydroxide

Summary The sensitivity to the diabetogenic action of triphenyltin hydroxide (TPTOH) was investigated in 5 species of experimental animals. A single oral administration of TPTOH produced marked hyperglycemia and triglyccridemia in rabbits and hamsters, but no evidence of diabetes was found in mice, rats and guinea-pigs. No morphological abnormality was observed in islet tissue from TPTOH-treated hamsters.     

Antifungal properties of leaf extract ofRanunculus sceleratus L

Summary Studies on various antifungal properties of the leaf extract ofRanunculus sceleratus L. showed that it was thermostable up to 100°C, retained activity on autoclaving, and remained active up to 15 days at room temperature. It possessed quick fungicidal action, tolerance against heavy fungal inoculum, activity on broad pH range, broad fungicidal spectrum, non-phytotoxicity and non-systemic activity. The extract was lethal at 140 dilution and its volatile vapours were also fungitoxic.Acknowledgment: The authors are thankful to Prof. K.S. Bhargava, Head, Department of Botany, Gorakhpur University, Gorakhpur for providing laboratory facilities.     

The in vitro characterization of the inhibition of mouse brain protein kinase-C by retinoids and their receptors

The mechanism of the in vitro inhibition of Ca2+-, phosphatidylserine-dependent protein kinase C (PK-C)2 by the purified holo (ligand-saturated) forms of cellular retinol-binding protein (cRBP) and cellular retinoic acid-binding protein (cRABP) was studied. We report here that the PK-C-inhibitory action of holo-cRBP and holo-cRABP is due to their respective ligands, all-trans-retinol and all-trans-retinoic acid; the reduced phosphorylation of the holo-retinoid-binding proteins and brain cytosolic proteins is not the result of a retinoid-induced soluble phosphatase or protease activity; retinoids reduce PK-C affinity for calcium and phosphatidylserine in vitro; and the structure-function activity of the retinoids and the specific interaction of these compounds with their binding proteins are important in blocking the activity of PK-C. These observations suggest that the inhibitory effect of retinoids on plasma membrane-associated PK-C activity pays a significant role in defining the early epigenetic aspects of PK-C-dependent tumor promotion and may be a physiological mechanism by which retinoids induce terminal differentiation in cell types that do not express soluble retinoid-binding proteins.     

Antihypertensive and cardiac effects of two novel beta-adrenoceptor blocking drugs.

Two new beta-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert.butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert.butylamine-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are like to be at least partially due to stimulation of beta-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.     

Studies onHolothuria polii (Echinodermata) antibacterial proteins. I. Evidence for and activity of a coelomocyte lysozyme

Summary Lysozyme activity has been detected in coelomocyte lysate of the echinodermHolothuria polii. The bacteriolytic reaction was stable when the lysate was heated in acidic buffer but heat-labile in alkaline medium. An incubation temperature of 35°C, acidic pH values (5.2 and 6.2) and an ionic strength of 0.175 were found to be the best conditions for the coelomocyte enzymatic activity. A low level of lysozyme was also evidenced in cell-free coelomic fluid where it could represent a basal defense level of bacteriolytic molecules released by the coelomocytes.Acknowledgments. This work was supported in part by a grant from MRES (C. C.). The authors thank M. Lasségues and F. Lassalles for their help and criticism.     

Ectopic human chorionic gonadotropin in breast carcinoma

Summary Immunoreactive human chorionic gonadotropin (hCG) was found in 9 of 65 surgically removed malignant breast tumors. Concentrations ranged from 5 to greater than 500 mIU hCG/g tumor. hCG was measured by a -chain specific radioimmunoassay. In further study of these specimens, an immunoperoxidase staining technique was used to stain for hCG in formalin-fixed sections. The hCG was shown to be localized within the cytoplasm and on the surface of the malignant cells.     

The generation of toxic activity from trypanosoma congolense.

Trypanosoma congolense organism, on incubation at 20 degrees C for 91/2h, were found to generate phospholipase like activity which was capable of mediating lysis of both nucleated cells and erythrocytes as well as acute inflammatory response on intradermal inoculation.     

Nachweis einer physiologischen Spontanaktivität in Einzelfasern des N. opticus der Katze

Summary Spike potentials were recorded with metal micro-electrodes from single fibers in the intracranial part of the cat's optic nerve with the retina left completely intact. All units studied as yet showed a marked spontaneous activity irrespective of differences in their response to light stimuli. The spontaneous activity in the intracranial part of the optic nerve could be suppressed reversibly by increasing the intraocular pressure up to 200 mm Hg. Thus spontaneous activity has been verified as a normal feature of the retina. A spontaneous firing rate of 22±11/s after 1 h dark adaptation was found in altogether 12 well-isolated fiber units.