Enantiomeric cannabinoids: stereospecificity of psychotropic activity

The 1,1-dimethylheptyl homolog of (-)-(3R,4R)-7-hydroxy-delta-6- tetrahydrocannabinol (compound II) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED50 of (II).     

Influence of hydrochlorothiazide on the pain threshold and on the antinociceptive activity of morphine,in rats

Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.This work was supported in part by grants from Consiglio Nazionale delle Ricerche, and by Ministero della Pubblica Istruzione, Roma.     

Long-term motor activity recording of dogs and the effect of sleep deprivation

Summary Motor activity of laboratory dogs was recorded for several weeks with an ambulatory monitoring device. The effect of 24 h sleep deprivation (SD) on motor activity during recovery was investigated. A clear rest-activity rhythm was established. The dogs exhibited a similar mean daily rest-activity pattern: 1) rest occurred mainly in the dark; 2) the amimals were most active after light onset; activity increased during the last two dark hours; 3) a rest period was found at noon and reduced activity during afternoon hours. There was a marked difference in total activity between individual dogs. Activity patterns varied as a function of the day of the week; this may have been a reflection of variations in the level of human activities in the laboratory. There was a significant reduction of motor activity during the 24-h period following SD. This was particularly evident in the first 6 h of the light period immediately following the deprivation.In addition, there was a significant increase in the number of episodes with activity 5 counts during recovery. The study confirms the possibility of measuring motor activity to assess compensatory mechanisms during recovery after SD. Sleep regulation, therefore, does not necessarily need to be exclusively examined by the invasive technique of EEG registration.     

The ovicidal activity ofcis-dehydromatricaria ester: time-dependance of its enhancement by UV light

Summary Freshly laid eggs ofDrosophila melanogaster were treated with the polyacetylenic compoundcis-dehydromatricaria ester. The toxicity of the chemical was enhanced by treatments with long-wavelength ultraviolet light, and the maximum effect was observed when the UV irradiation was performed 4–5 h after the initial contact of the eggs with the chemical.We are grateful to Professor E. Spiess for advice and assistance, and to the National Institutes of Health (GM 24144) for financial support.     

Sperm enzyme activity analysis in individual sperm for detection of heritable mutations in mammals

Summary Male mice were injected i.p. with 2.5 mg/kg mitomycin C, 100 mg/kg ethyl nitrosourea or saline and mated with untreated virgin females five weeks later. Sperm from 64 of the F₁ male progeny were analyzed histochemically for acrosin, succinic dehydrogenase and alpha-glycerophosphate dehydrogenase activity. The frequency of F₁ males with sub-normal sperm enzyme activity was significantly higher among progeny from treated males than in controls. These results show that analysis of sperm enzyme activity in F₁ males is a practical method for detection of transmitted mutations induced in a treated parent.We gratefully acknowledge USPHS, NIEHS grant 1 RO1 ES02607-02 and technical assistance by G. M. Oldford.     

Lysozyme activity in female genital tissues of normal and genetically lysozyme-deficient rabbits

Summary The internal genitalia of female normal rabbits and mutant lysozyme-deficient rabbits, which lack genetically the leukocytic isozyme of lysozyme, were assayed for lysozyme activity. The ovaries, uteri, and vaginas of the lysozyme-deficient rabbits had less than 20% of the lysozyme activity of normals. The oviducts, and in particular the caudal portions of the oviducts, had lysozyme activities up to 71% of the levels in normal. These observations suggest that the lysozymes of oviduct and leukocytes of rabbits are under the control of different genes.Supported in part by grants RR00515, RR05465, K04-RR00003, and T32-GM07160 from the National Institutes of Health. We acknowledge the excellent technical assistance of LeeAndra Froseth.     

Flow microcalorimetry as a tool for an improved analysis of antibiotic activity: The different stages of chloramphenicol action

Summary Flow microcalorimetry in combination with photometric mass determination of staphylococci in suspension was used to reveal alterations in the intensity, extent and efficiency of bacterial metabolism during inhibition of protein synthesis by chloramphenicol. It could be demonstrated that these three parameters of metabolic activity were distinctly affected by this drug, and that the method described promises to be a more reliable tool for assaying the degree and the mode of bacteriostatic inhibition than the conventional determination of the minimum inhibitory concentration.     

Rhythms of enzymatic activity in maternal and umbilical cord blood

The 24-h activity patterns of variouns enzymes were determined in human serum, red blood cells and white blood cells of maternal and umbilical cord blood. Blood was drawn from the brachial vein of mothers and from the umbilical cord within ten minutes after delivery. Corresponding blood specimens were obtained from 83 spontaneous labors, occurring at different hours over a period of 60 days. For each variable (variable=activity of a specific enzyme in one of the blood components) the results were grouped according to delivery hour, forming a 24-h pattern which was analyzed to elucidate time dependency. Five out of six corresponding maternal and fetal variables were similar with regard to pattern and peak time. The activity rhythms of glyceraldehyde-3-phosphate dehydrogenase and glucose phosphate isomerase in red blood cells of mothers and fetuses possessed a significant bimodal pattern. The activity rhythms of the latter enzyme in white blood cells and sera exhibited a significant 24-h period. Hexosaminidase activity exhibited a distinct 24-h rhythm in maternal white blood cells, but no significant rhythm could be detected in the fetal white blood cells. The activity of hexosaminidase showed, identical 24-h patterns in maternal and cord serum when analyzed by best fit cosine, and no significant time-dependency when analyzed by ANOVA.     

Antiviral activity of coralloid root ofCycas revoluta extract against some viruses of tomato plant

Summary Crude coralloid root extract ofCycas revoluta showed significant antiviral activity against viruses of the tomato plant (PVX, PVY, TMV, TAV and TRSV) when applied 24 h before virus inoculation, or when mixed with different virus inocula before virus inocultion, in hypersensitive and systemic hosts. No such inhibition was observed when extract was applied 24 h after virus inoculation. TAV did not show any inhibitory response in a systemic host.Authors are thankful to Dr S. N. Gupta and Dr (Smt.) K. Shukla for their valuable guidance and providing laboratory facilities and U.G.C. for financial assistance.     

Binding of matrilysin-1 to human epithelial cells promotes its activity

Matrix metalloproteinase-7 (MMP-7, matrilysin- 1) modulates crucial biological events by processing many epithelial cell surface-associated effectors. We addressed MMP-7 interaction with human epithelial cells and its resulting activity. In human endometrium, a model of controlled tissue remodeling, proMMP-7 was diffusely immunolocalized inside epithelial cells, whereas MMP-7 delineated their entire plasma membrane. Endometrial explants preferentially retained active MMP-7, but not proMMP-7. Endometrial epithelial cells and carcinoma cells from various tissues bound active MMP-7. Endometrial carcinoma-derived Ishikawa cells showed high affinity (K_D of ~2.5 nM) and capacity (~260 000 sites per cell) for MMP-7. MMP-7 binding decreased by extracting membrane sterols or interfering with heparan sulfate proteoglycans, and was abrogated by tissue inhibitors of metalloproteinase-2 (TIMP-2) or synthetic MMP inhibitors. Bound MMP-7 not only remained fully active towards a macromolecular substrate but also became resistant to TIMP-2. We conclude that MMP-7-selective targeting to the plasma membrane of epithelial cells promotes its activity by conferring resistance to TIMP-2. A. Berton, C. Selvais: These authors contributed equally to this work. P. J. Courtoy, E. Marbaix, H. Emonard: These authors contributed equally to the supervision of this work. Received 20 September 2006; received after revision 30 November 2006; accepted 18 January 2007     

Interdependence between locomotor activity and duration of wakefulness in humans during isolation

Summary Locomotor activity was recorded in 14 subjects who lived singly in an isolation unit for 16 to 88 days. Their free-running circadian rhythms had a mean period of 25.9 h, with individual means in the duration of wakefulness () ranging from 12.1 to 22.9 h. Intraindividually, the hourly means of activity were negatively correlated with to such a degree that the total amount of activity per day remained constant irrespective of large variations in .     

Antibacterial activity in the egg mass of a sea hare

Summary The eggs of a sea hare,Aplysia kurodai, contained antibacterial factors which probably play a role in the defense of eggs against bacterial infection. The active factors were composed of several heat-labile proteins, unrelated to lysozyme, and were produced in the albumen gland.     

The effect of head heating on the flight activity of the cockroach

Summary Internal head heating restricted the flight activity in the cockroachPeriplaneta americana. Heating the metathoracic ganglion did not have any pronounced effect on the flight. It is concluded that in the cockroach the head nervous centers are very heat-susceptible and might be the coordinating center for temperature responses.     

Hypotensive activity of histidine-containing analogues of C-terminal hexapeptide of Substance P

Summary Four new hexapeptide analogues of C-terminal Substance P fragment with increased solubility in aqueous solutions are described. The peptides contain histidine in positions 6, 8, 9 and 10, respectively. The effect of the structural changes on the hypotensive activity and antigenic properties of analogues was compared. It was found that substitution of amino acid residues in various positions in the C-terminal hexapeptide of Substance P resulted in different effects on the hypotensive and antigenic properties, respectively. Only the [His⁶] SP_6-11 analogue had an unchanged antigenic structure when compared with the C-terminal region of Substance P, but it showed an almost total loss of hypotensive activity. The [His⁹] SP_6-11 analogue retained 50% of the hypotensive activity of the C-terminal hexapeptide but showed a markedly reduced expression of the antigenic epitope localized in this region of Substance P.     

Cofactor-induced and mutational activity enhancement of coagulation factor VIIa

Coagulation factor VIIa (FVIIa) is an atypical member of the trypsin family of serine proteases. It fails to attain spontaneously its catalytically competent conformation and requires its protein cofactor tissue factor (TF) to accomplish this. Over a number of years, this unique behaviour of FVIIa has prompted investigations of the TF-induced activation mechanism and the zymogenicity determinants in factor VIIa. Factor VIIa has gained additional interest in the past decade because of its development into a clinically useful haemostatic agent. Here, we present an overview of the current knowledge about the TF-induced allosteric activation of FVIIa and the various molecular approaches to enhance the intrinsic activity and efficacy of FVIIa. Received 18 October 2007; received after revision 12 November 2007; accepted 14 November 2007     

Calcium activity and post-ischemic suppression of protein synthesis

Increase in intracellular calcium concentration is a prominent feature of ischemia and has been considered a major factor in the initiation of ischemic pathology, which involves inhibition of protein synthesis. A reduction of calcium ion activity during and immediately after in vitro ischemia did not prevent inhibition of protein synthesis in hippocampae slices. When slices were overloaded with calcium by NMDA receptor activation or by the calcium ionophore A23187, no significant inhibition of protein synthesis was observed. We conclude that calcium overload plays only a limited role in ischemic inhibition of protein synthesis.     

The potential significance of microbial activity in radioactive waste disposal

Summary Active microorganisms can exist in any proposed environment if the basic requirements for life are satisfied, i.e. a suitable temperature and pH, the presence of the necessary nutrients and water. If conditions are not favourable microbes may survive in a dormant state until a change will allow activity. In local pockets microenvironments may become established where microbial activity may increase leading to altered environmental conditions and to changes in the near-field, e.g. degradation and breakdown of barriers, gas generation and/or uptake and transport of nuclides.     

Cytotoxic activity of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide is underlain by DNA interchain cross-linking

Currently, chemical bifunctional cross-linkers are regarded as promising therapeutic agents capable of affecting cell metabolism. Depending on the nature of the active groups and on the length of their mediating spacer, these cross-linkers have been shown to influence mitochondrial functions, the cell cycle and cell death. The current study was aimed to assay cellular effects of a cross-linker with ‘zero’-length spacer, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). When added to cultures of transformed cells, EDC induced a G2/M blockade followed by cell death. Analysis of the molecular targets revealed that alteration of the cell cycle was caused by EDC-induced interchain cross-linking within double-stranded DNA. Administration of EDC to animals with experimental tumors increased their life span. The analysis of tumor cells from EDC-treated mice showed up-regulation of p21/WAF1, disturbance of tumor cell cytokinesis and, hence, cell death. Thus, both in vitro and in vivo, EDC exhibits cytotoxic activity, which may be of potential therapeutic use. Received 15 August 2005; received after revision 23 September 2005; accepted 15 November 2005     

Interaction between the effects of centrally administered arecoline and leucocyte pyrogen on the activity of posterior hypothalamic neurons in the rabbit

Summary In experiments with urethane-anesthetized rabbits, the alteration in the activity of posterior hypothalamic neurons resulting from intracerebroventricular injection of leucocyte pyrogen was attentuated by subsequent administration of arecoline. Atropine failed to alter the neuronal response to leucocyte pyrogen but abolished the effect of arecoline. The neuronal response to arecoline was reversed in the absence of leucocyte pyrogen.     

The significance of temperature and barometric pressure changes for the snow surface activity ofIsotoma hiemalis (Collembola)

Summary Temperature is limiting for the snow surface activity ofIsotoma hiemalis: values below a threshold of –2.5° to –3°C are avoided. Changing barometric pressure leads to increased surface activity, thus being responsible for mass appearances. These experiments provide the first evidence for sensitivity to and reaction to barometric pressure changes in insects.The financial support by the Swiss National Science Foundation is highly acknowledged. I thank W. Matthey for the unpublished data onGerris remigis.