Respiratory burst in peritoneal exudate cells in response to a modified tuftsin

Intraperitoneal administration of tuftsin-M [Thr–Lys–Pro–Arg–NH–(CH₂)₂–NH–CO–C₁₅H₃₁] to Balb/C mice has been shown to induce a respiratory burst in the peritoneal exudate cells. The macrophages exhibited enhanced levels of O₂ ^–, H₂O₂, NADPH oxidase and myeloperoxidase, but the activities of superoxide dismutase, catalase and glutathione peroxidase remained virtually unchanged. The magnitude of the oxidative burst depended directly on the dose of tuftsin-M; higher activity was observed at higher doses of the peptide. Tuftsin-M enhanced the generation of both O ₂ ^– and H₂O₂ under in vitro conditions, as did phorbol myristate acetate. These results suggest that tuftsin-M could enhance non-specific defence against infections by activating the macrophages.     

Differences in luteinizing hormone release stimulated in rat anterior pituitary cells by leukotriene C4 and by gonadotropin-releasing hormone in vitro

Summary Continuous administration of leukotriene C₄ (LTC₄, 10^–10 M) to superfused rat anterior pituitary cells increased LH release for 40 min only, whereas in a parallel experiment gonadotropin-releasing hormone (GnRH, 10^–9 M) evoked a continuous increase in hormone secretion. In contrast to GnRH, LTC₄ did not desensitize rat anterior pituitary cells. The secretory action resulting from the administration of LTC₄ (10^–10 M) was abolished for 40 min after previous stimulation. The results documented the dual action of LTC₄ on LH exocytosis.     

Participation of ACTH1–10 and ACTH4–10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH_1–10 and ACTH_4–10 on [³H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the B_max (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing K_D (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased B_max, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, K_D values were unchanged. The i.c.v injection of ACTH_1–10 to hypophysectomized animals significantly increased B_max, an effect that was enhanced by simultaneous i.c.v. injection of ACTH_1–10+melatonin, reaching higher values of B_max than the i.c.v. injection of these hormones individually. No significant changes in K_D values were found after ACTH_1–10 and/or melatonin administration. However, the i.c.v. injection of ACTH_4–10 to hypophysectomized rats did not change B_max, although it significantly increased K_D values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH_4–10, returning K_D to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify B_max of BNZ binding in the ACTH_4–10-injected group, the higher dose, 20 ng, significantly increased B_max. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.     

Bicarbonate and chloride transport across rat ileal basolateral membrane

The mechanisms of HCO ₃ ^– and Cl^– transport across basolateral membranes from rat ileum were investigated in isolated vesicles by means of uptake experiments. Neither Cl^–/HCO ₃ ^– exchanger nor Na⁺–(HCO ₃ ^– )_n cotransport seem to be present in ileal basolateral membranes. Moreover Cl^– uptake is unaffected bycis Na⁺ and/or K⁺ gradients, indicating the absence of Na⁺–Cl^–, K⁺–Cl^– and Na⁺–K⁺–2Cl^– symport activity. An electrically conductive pathway seems to be responsible for both HCO ₃ ^– and Cl^– fluxes. Evidence is also given for the presence of a Na⁺/H⁺ exchanger at the basolateral pole of ileal enterocytes.     

Differential sensitivity of the two phases of ear artery contraction to intimal and adventitial norepinephrine

Summary The biphasic contraction of the rabbit ear artery to norepinephrine (NE) was investigated in the normal (adventitial stimulation) and the everted (intimal stimulation) segment of ear artery. The 2nd phase response showed an intimal ED₅₀ of 8.2×10^–8 M which was significantly (p<0.05) lower than the adventitial ED₅₀ of 42.6×10^–8 M. This difference was abolished by inhibition of neuronal and extraneuronal uptake for NE. The 1st phase response also showed an ED₅₀ for the intimal stimulation (6.9×10^–8 M) which was significantly (p<0.05) lower than adventitial (65.5×10^–8 M). This difference was reduced but not abolished by NE uptake inhibition. This suggsets that some feature of the adrenergic neuroeffector apparatus is asymmetrically arranged to favor fast responses to blood borne NE.Supported by American Heart Association-Greater Los Angeles Affiliate Grant No. 602. We wish to thank Dr John Bevan and Dr Alasdair MacLean for helpful advice.     

Histamine-induced hypotension modified by H1 and H2 antagonists in the monkey (Macaca mulatta)

Summary Blocking H₂ receptors with burimamide in the dose used (20 mg/kg) approximately doubles the amount) of histamine needed to produced the same effect as seen when H₁ antagonists (chlorpheniramine or mepyramine) are used alone. TheK ₂ ratios for chlorpheniramine-chlorpheniramine plus burimamide are 117–204 and for mepyramine-mepyramine phus burimamide are 200–478. H₁ and H₂ receptors, in the monkey, when stimulated, both cause cardiovascular responses in the same direction.     

Calcium and the contractile response to prostaglandin in the smooth muscle of guinea-pig stomach

Summary In the longitudinal smooth muscle of guinea-pig stomach, verapamil (10^–5 M) which showed marked suppression of high K-induced contractures, did not suppress the contractile response to PGE₁ (1.5×10^–9 to 10^–6 M) markedly. These results suggest that the contractile mechanism of PGE₁ in guinea-pig stomach may mainly depend on a release of bound Ca in the cell and partly depend on a Ca influx from the extracellular origin.     

Aufhebung der Thermothyrin-A-Sekretion der Schilddrüse durch Fütterung mit Methylthiouracil

Summary G. Mansfeld demonstrated that in the serum of overheated animals a substance (thermothyrine A) is present which, injected into normal animals, decreases O₂-consumption. Serum of thyroidectomized animals has no effect.Dogs and rabbits were treated daily with 0.10 g per kg methylthiouracil during 4 weeks, and were than subjected for 5 hours to a temperature of 34–35° C which raised their body temperature by 0.5–1.5° C. 2.5 cm³ of serum obtained at the end of the 5 hours period failed to reduce O₂-consumption of normal rats, while sera of untreated dogs and rabbits produced after similar exposure to high temperature a fall of O₂-consumption by 14–48%. It is therefore evident that methylthiouracil not only inhibits the formation of thyroxine but of thermothyrine A as well.The fact that thermothyrine A contains no iodine proves conclusively that the action of thiouracil compounds cannot be exclusively an inhibition of iodinization.     

Deletion mapping of a new gustatory mutant inDrosophila melanogaster

Summary A gustatory mutant ofDrosophila melanogaster insensitive to the taste of salt has been isolated. Genetic crosses and a deletion mapping analysis show that this mutation, designatedgust-M ₁ is located in the 93C_3–6-93D_6–7 region of the third chromosome.gust-M ₁ is also insensitive to the taste of quinine sulfate. The behavior of this mutant may be explained by assuming thatgust-M ₁ could be a mutation perturbing functions in the central nervous system affecting the responses to both compounds.     

Volume-dependent regulation of the respiratory burst of activated human neutrophils

The effect of incubation medium osmolality on the respiratory burst of human neutrophils was studied using luminol-dependent chemiluminescence (CL) as an indicator of burst activity. Neutrophils were stimulated with N-formyl-Met-Leu-Phe (FMLP), phorbol-12-myristate-13-acetate (PMA), the calcium ionophore A23187, thermoaggregated IgG (IgG_n), and opsonized zymosan (OZ). It was shown that increasing the osmolality of the incubation medium from 320 up to 420 mosM decreased the A231870 and OZ-induced CL responses by 90%. Under the same conditions PMA-, FMLP- and IgG_n-induced CL responses were decreased by 40–60%. A decrease of osmolality to 200 mosM resulted in a 2–3 fold decrease of the A23187-, PMA- and FMLP-induced CL and in a 60–80% increase of OZ- and IgG_n-induced CL. It is suggested that osmolality-mediated alteration of cell volume is an important mechanism for regulating neutrophil activity.     

Zur Wirkungsweise einiger Katalase-Inhibitoren

Summary The mechanism of catalase inhibition by CN^–, N ₃ ^– , and SH^– has been investigated by a polarographic method. CN^– has been found to inhibit reversibly by a coordinating mechanism, whereas N ₃ ^– and SH^– inhibits catalase irreversibly.     

Experimental data on the energetic flux during glycolytic oscillations in yeast extracts

Calorimetric experiments were performed on yeast extracts in which glycolytic oscillations were occurring. High metabolic fluxes coincided with low amplitudes and with high frequencies in a temperature range from 283 to 303 K, yielding an activation energy ofE _a=76.8 kJ mol^–1 and a mean Q₁₀ value of 2.5±0.4. The calorimetrically determined reaction enthalpy _fH^0, of the glycolytic catabolism of glucose revealed two distinct groups of extract preparations, with no intermediate values. The values were –107.5±28.7 kJ mol^–1 and –30.8±5.7 kJmol^–1, respectively, while –100.0 kJ mol^–1 was predicted from theoretical calculations. Kreuzberg and Betz⁶ predicted rate limiting effects of GAPDH in oscillating extracts. However, when possible effects of GAPDH on frequency, number of oscillations or total heat production were examined, no influence of increasing or reducing the initial GAPDH concentration could be found. The results are discussed with reference to existing models of glycolytic oscillations.     

Effects of selective dopamine D1 and D2 antagonists on male rat sexual behavior

Summary The effects of selective dopamine (DA) D₁ and D₂ antagonists on male rat sexual behavior were investigated. The D₁ antagonist (+)SCH-23390, 25–100 g kg^–1 s.c. –20 min, and the D₂ antagonist raclopride, 0.1–1.6 mg kg^–1 s.c., –20 min, decreased both the number of mounts and intromissions preceding ejaculation. No statistically significant effects in the time up to ejaculation or in the time up to the first intromission were noted, whereas both compounds produced a statistically significant increase in the post-ejaculatory interval. The effect can generally be characterized as psychomotor inhibition, and no evidence was obtained for a specific role of DA D₁ or D₂ receptors in the mediation of male rat sexual behavior.The expert technical assistance of Ms Elisabeth Wallin is gratefully acknowledged. The figures were skilfully prepared by Ms Madelene Kröning at the Department of Psychology. This study received support from the Bank of Sweden tercentenary Foundation, The Swedish MRC and Wilhelm and Martina Lundgren Foundation.     

Fatty acid modulation of antiestrogen action and antiestrogen-binding protein in cultured lymphoid cells

Summary Nonsteroidal antiestrogens reversibly and specifically inhibited the proliferation of two estrogen receptornegative lymphoid cell lines (EL4 and Raji) in a dose-dependent manner. [³H]Thymidine incorporation of concanavalin A-stimulated primary splenocytes was also inhibited by 10^–6 M clomiphene (1-[4-(2-diethylaminoethoxy)phenyl]-1,2-diphenyl-2-chloroethylene). The antiproliferative effect could be prevented by the simultaneous presence in the growth medium of 10^–5 M linoleic acid or 10^–5 M arachidonic acid but not by 10^–6 M estradiol. Both lymphoid cell lines had high affinity antiestrogen-binding sites whose affinity could be altered by conditions of growth. Growth of EL4 cells in RPMI 1640 medium supplemented with charcoal-pretreated 5% fetal calf serum (charcoal-stripped medium) resulted in significantly higher affinity (K_d 0.54 nM±0.11 nM; n=6) than growth in medium supplemented with untreated serum (complete medium) (K_d=1.68 nM±0.48 nM; n=6) (p<0.001). This change in affinity was partly due to removal of fatty acids from the growth medium by charcoal pretreatment, since addition of 10^–5 M linoleic acid or 10^–5 M gamma-linolenic to charcoal-stripped medium decreased the affinity of the antiestrogen-binding protein. In contrast, growth in 10^–5 M stearic acid or 10^–5 M oleic acid did not significantly alter the affinity of the antiestrogen-binding protein, whereas 10^–5 M palmitic acid significantly increased its affinity. The same fatty acids were also tested for their intrinsic effects on EL4 cell proliferation. Oleic, linoleic and gamma-linolenic acids were growth stimulatory while stearic and palmitic acids were not. Thus linoleic and gamma-linolenic acids whose presence in the growth medium was associated with decreased affinity of [³H]tamoxifen (1-[4-(2-dimethylaminoethoxy)phenyl]-1,2-diphenylbut-1(Z)-ene) binding to the intracellular antiestrogen-binding protein were also growth stimulatory. Unsaturated fatty acids have previously been shown to inhibit binding of [³H]tamoxifen to the antiestrogen-binding protein in a cell-free system. The present observations demonstrate that unsaturated fatty acids also modify the affinity of the antiestrogen-binding protein in intact cells.     

Cl−/HCO 3 − exchanger is operative in isolated enterocytes from rat jejunum

Enterocytes isolated from rat jejunum were tested for the existence of a Cl^–/HCO ₃ ^– exchange, previously evidenced in basolateral membrane vesicles but not in brush border. Cells were found to retain functional integrity and transport capabilities long enough to allow Cl^– fluxes to be measured. Both efflux and uptake experiments indicate that a Cl^–/HCO ₃ ^– antiport, inhibited by 4,4-diisothiocyanostilbene-2-2-disulfonic acid (DIDS), is functional under resting conditions.     

Ion-solvent interaction: Viscosity,apparent molar volume and conductivity of univalent electrolytes in dioxanewater mixtures at different temperatures

Summary The viscosity, apparent molar volume and conductivity of NaCl, KCl, NaBr, KBr, NaNO₃ and KNO₃ solutions at mass fraction of dioxane (10, 20 and 30%)-water mixtures at 30–45°C±0.01°C have been measured. The ions appear to interact appreciably, and the ion-solvent interaction is of the order NO₃ ^–>Br^–>Cl^–.     

Ion-solvent interaction from viscosity,apparent molar volume and conductivity data of bromates,iodates and sulphates of potassium and sodium in dioxane-water mixtures at different temperatures

Summary The viscosity, apparent molar volume and conductivity of KBrO₃, NaBrO₃, KIO₃, NaIO₃, K₂SO₄ and Na₂SO₄ at mass fraction of dioxane (10, 20 and 30%) — water mixtures at 30–45°C±0.01°C have been measured. The ions appear to interact and the ion-solvent interaction is of the order BrO ₃ ^– >IO ₃ ^– >SO ₄ ^2– .     

Lack of pressor effect of dopamine in the pentobarbital-anesthetized rat

Summary The blood pressure and heart rate responses to intravenous dopamine infusion at 2.5, 5.0 and 10.0 g·min^–1·100 g^–1 were studied in conscious and pentobarbital-anesthetized Sprague — Dawley rats. In the conscious rats, dopamine caused a significant dose-related increase in the mean arterial blood pressure which was abolished in the anesthetized rats. The heart rate increased significantly only at the highest dose infused. The responses to equipressor doses of noradrenaline (40 ng·min^–1·100 g^–1) and phenylephrine (1.0 g·min^–1·100 g^–1) were also suppressed in the anesthetized rats. The results suggest that pentobarbital anesthesia depresses the blood pressure response to dopamine infusion in the rat through a depression of activation of alpha-adrenoceptors.16 June 1986     

Microbial legradation of bitumen

Summary Bitumen is commonly employed as a matrix for the long-term storage of low and intermediate level radioactive waste. As bitumen can be degraded by microbial activity, it is of great significance to determine the rates at which it may occur in nuclear waste repositories.Experiments have been carried out under optimal culture conditions using bitumen with a highly increased surface area. The potential of different microbial consortia to degrade bitumen has been examined. The investigations showed clearly that bitumen-degrading organisms are ubiquitous. In general the organisms formed biofilms on the accessible substrate surface area. Under oxic culture conditions a bitumen degradation rate of 20–50 g bitumen · m^–2· y^–1 leading to a CO₂ liberation of 15–40 l was observed. Anoxic conditions yielded a 100 times smaller degradation rate of 0.2–0.6 g bitumen · m^–2 · y^–1 and a CO₂ production of 0.15–0.45 l.Based on linear extrapolation the experimentally determined degradation rates would lead to a 25–70% deterioration of the bitumen matrix under oxic and 0.3–0.8% under anoxic conditions within 1000 years.     

Influence of environmental conditions on the amount of N2O released from activated sludge in a domestic waste water treatment plant

Waste water purification is characterized by intensive mineralization and nitrification processes. Because of the high O₂ demand, temporarily anaerobic conditions may be produced, and denitrification by nitrifying organisms as well as heterotropic denitrification may contribute to N₂O release. In situ measurements (1993–1994) suggest that N₂O is released from activated sludge in a domestic waste water treatment plant at an average rate of 1040 g m^–2h^–1 with a range between zero and 6198 g m^–2h^–1. The production of N₂O seems to be related to the concentration of NO ₂ ^– and NO ₃ ^– as well as to the pH. In the waste water about 75–200 g N₂O l^–1 is dissolved. This N₂O is released after discharge into the receiving waters. The N₂O is produced essentially by nitrification rather than by heterotropic denitrification. On a long-term scale the increasing use of mechanical-biological waste water purification plants world-wide may add increasingly to the anthropogenic production of N₂O, although the present amount of N₂O produced is negligible compared to its global terrestrial production.