High Power Electromagnetic Waves Exposure of Healthy and Tumor Bearing Mice: Assessment of Effects on Mice Growth, Behavior, Tumor Growth, and Vessel Permeabilization.

High power radiofrequencies may transiently or permanently disrupt the functioning of electronic devices, but their effect on living systems remains unknown. With the aim to evaluate the safety and biological effects of narrow-band and wide-band high-power electromagnetic (HPEM) waves, we studied their effects upon exposure of healthy and tumor-bearing mice. In field experiments, the exposure to 1.

High power electromagnetic pulse applicators for evaluation of biological effects induced by electromagnetic radiation waves.

The effects of electromagnetic radiation waves on health is one of the major public concerns. These waves are mainly produced at a large scale but it is important to evaluate these effects on biological samples at the laboratory scale. Here we developed a set of micro applicators, which allow evaluating the effect of electromagnetic fields on biological samples with volumes in the microliter range.

NLX-112, a highly selective 5-HT receptor agonist: Effects on body temperature and plasma corticosterone levels in rats.

NLX-112 (a.k.a.

The novel analgesic and high-efficacy 5-HT1A receptor agonist, F 13640 induces c-Fos protein expression in spinal cord dorsal horn neurons.

The very-high-efficacy, selective 5-HT(1A) receptor agonist, F 13640 produces uniquely powerful analgesia in rat models of chronic pain by novel neuroadaptive mechanisms (inverse tolerance and co-operation with nociception) [Neuropharmacology 43 (2002) 945-958]. A signal transduction theory and evidence suggest that F 13640 initiates these mechanisms, paradoxically, by mimicking the central effects of nociceptive stimulation. We report that the i.

Tolerance and inverse tolerance to the hyperalgesic and analgesic actions, respectively, of the novel analgesic, F 13640.

5-HT(1A) receptor activation by the very-high-efficacy, selective 5-HT(1A) receptor agonist F 13640 [(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-([(5-methyl-pyridin-2-ylmethyl)-amino]-methyl)piperidin-1-yl]-methanone] was recently discovered to constitute a novel central mechanism of broad-spectrum analgesia that, remarkably, grows rather than decays with chronicity. However, in rodents not exposed to nociception, F 13640 induces its analgesic effect only after having initially induced hyperalgesia. Numerical simulations implementing a signal transduction theory here show that the progressive increase in the intensity of nociceptive stimulation which F 13640 presumably mimics should eventually produce a large analgesic effect without initially causing marked pain.

Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain.

Previously, we have reported that in rat models of chronic pain, in particular, the very-high-efficacy 5-HT(1A) agonist F 13640 induces unprecedented pain relief by novel neuroadaptative mechanisms that involve inverse tolerance and cooperation with nociceptive stimulation in producing analgesia. The present studies detailed the actions of F 13640 and other compounds in the formalin model of tonic nociceptive pain. Intraperitoneal injection of F 13640 (0.

Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia.

We report the discovery of F 13640 and evidence suggesting this agent to produce powerful, broad-spectrum analgesia by novel molecular and neuroadaptative mechanisms. F 13640 stimulates G(alphaomicron) protein coupling to 5-HT(1A) receptors to an extent unprecedented by selective, non-native 5-HT(1A) ligands. Fifteen minutes after its injection in normal rats, F 13640 (0.

Experimental conditions for the continuous subcutaneous infusion of four central analgesics in rats.

For the analysis of pharmacotherapeutic regimens for chronic pain in animals, it is important to establish delivery methods in which analgesics can be administered continuously and at a constant rate for a prolonged period of time. This allows for the assessment of how drug effects may vary over time in the presence of ongoing pain. The present study determined, for four analgesic compounds, the maximal doses that met all of the following criteria: (i) water-soluble, (ii) stable over 14 days at 38 degrees C, and (iii) devoid of undesirable side-effects in normal rats, as assessed by evolution of body weight and temperature after the subcutaneous implantation of an osmotic mini-pump that continuously infused the compounds over a 14-day period.

In the formalin model of tonic nociceptive pain, 8-OH-DPAT produces 5-HT1A receptor-mediated, behaviorally specific analgesia.

The experiments examined antinociceptive and intrinsic behavioral effects induced by the prototypical 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino] tetralin) in rats. 8-OH-DPAT (0.01-2.

Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats.

The study examined the validity of oral fentanyl self-administration (FSA) as a measure of the chronic nociceptive pain that develops in rats with adjuvant arthritis independently of acute noxious challenges. Arthritic rats self-administered more of a 0.008 mg/ml fentanyl solution (up to 3.

Lack of toxic effects of F 12511, a novel potent inhibitor of acyl-coenzyme A: cholesterol O-acyltransferase, on human adrenocortical cells in culture.

Inhibition of acyl-coenzyme A: cholesterol O-acyltransferase (EC 2.3.1.

Pharmacological profile of F 12511, (S)-2',3', 5'-trimethyl-4'-hydroxy-alpha-dodecylthioacetanilide a powerful and systemic acylcoenzyme A: cholesterol acyltransferase inhibitor.

The pharmacological profile of F 12511 (S)-2',3', 5'-trimethyl-4'-hydroxy-alpha-dodecylthio-phenylacetanilide, a new inhibitor of acyl-CoA: cholesterol acyltransferase (EC 2.3.1.

F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine.

F 11356 (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl] ben zonitrile) was designed to take advantage of the superior potency and efficacy characteristics of 5-hydroxytryptamine (5-HT) compared with tryptamine at 5-HT1B/1D receptors. F 11356 has subnanomolar affinity for cloned human and nonhuman 5-HT1B and 5-HT1D receptors, and its affinity for 5-HT1A and other 5-HT receptors, including the 5-ht1F subtype, is 50-fold lower and micromolar, respectively. In C6 cells expressing human 5-HT1B or human 5-HT1D receptors, F 11356 was the most potent compound in inhibiting forskolin-induced cyclic AMP formation (pD2 = 8.

F 11440, a potent, selective, high efficacy 5-HT1A receptor agonist with marked anxiolytic and antidepressant potential.

F 11440 (4-methyl-2-[4-(4-(pyrimidin-2-yl)-piperazino)-butyl]-2H, 4H-1,2,4-triazin-3,5-dione) was the outcome of a research effort guided by the hypothesis that the magnitude of the intrinsic activity of agonists at 5-HT1A receptors determines the magnitude of their antidepressant and anxiolytic-like effects. The affinity of F 11440 for 5-HT1A binding sites (pKi, 8.33) was higher than that of buspirone (pKi, 7.

Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid.

Vinflunine, or 20',20'-difluoro-3',4'-dihydrovinorelbine, is a novel Vinca alkaloid obtained by hemisynthesis using superacidic chemistry. The most impressive structural modification of this vinorelbine derivative was the selective introduction of two fluorine atoms at the 20' position, a part of the molecule previously inaccessible by classic chemistry. The antitumor activity of vinflunine was evaluated against a range of transplantable murine and human tumors.

Model of bronchial allergic inflammation in the brown Norway rat. Pharmacological modulation.

Exposure of non-sensitized Brown Norway (BN) rats to a 10%-ovalbumin aerosol induced an increase in the number of neutrophils in the broncho-alveolar lavage (BAL) fluid 3 and 6 h later but with no change in number of cells at 24 h. When the BN rats were actively sensitized (i.m.

Theophylline reduces pulmonary eosinophilia after various types of active anaphylactic shock in guinea-pigs.

The action of theophylline was studied on the inflammatory reaction obtained in bronchoalveolar lavage fluid 24 h after an active anaphylactic shock had been induced by ovalbumin inhalation in conscious sensitized guinea-pigs. The compound was administered twice by intraperitoneal administration after the anaphylactic reaction at a dose of 50 mg kg-1. When the guinea-pigs were sensitized by intramuscular injection of 30 mg kg-1 ovalbumin or by ovalbumin aerosol, theophylline reduced the number of eosinophils and mononuclear cells in the fluid.

Bronchial inflammation and hyperreactivity after anaphylactic shock in guinea pigs actively sensitized by systemic or aerosol route.

Hyperreactivity and bronchial inflammation resulting from active anaphylactic shock induced by aerosol have been studied in guinea pigs after sensitization by intramuscular injection of large-dose ovalbumin or aerosol ovalbumin. When animals were sensitized by i.m.

Action of tioxamast on various models of anaphylactic shock, hyperreactivity and bronchial inflammation in guinea-pigs.

Tioxamast, an anti-allergic compound inhibiting the release and synthesis of certain mediators of allergy and having no major antagonist effect towards such mediators, was experimented on various models of anaphylactic shock, hyperreactivity and bronchial inflammation in guinea-pigs. Tioxamast does not reduce passive pulmonary anaphylactic shocks induced in anaesthetized or conscious guinea-pigs by i.v.

Pharmacological modulation of a model of bronchial inflammation after aerosol-induced active anaphylactic shock in conscious guinea pigs.

Twenty-four hours after an active anaphylactic shock induced by inhalation of antigen in conscious guinea pigs sensitized by a large dose of ovalbumin in complete Freund's adjuvant, a noteworthy bronchial inflammation, characterized by increased numbers of neutrophils, mononuclear cells and eosinophils in the bronchoalveolar lavage fluid, was observed. Some drugs administered after the anaphylactic shock were investigated using this model. Disodium cromoglycate primarily reduced the number of mononuclear cells and eosinophils.

Comparative actions of immunosuppressants, glucocorticoids and non-steroidal anti-inflammatory drugs on various models of delayed hypersensitivity and on a non-immune inflammation in mice.

Various models of delayed hypersensitivity (DH) were used in mice: contact hypersensitivity reactions to picryl chloride and oxazolone and reactions to methylated bovine serum albumin (MBSA) and sheep red blood cells (SRBC). Drugs of different classes were tested in these models by systemic treatment around the challenge period: non-steroidal anti-inflammatory drugs (cyclooxygenase inhibitors, and inhibitors of both cyclooxygenase and lipoxygenase); glucocorticoids and immunosuppressants (cyclosporin A. CsA; cyclophosphamide, Cy; methotrexate, Mtx; azathioprine, Aza).

Model of bronchial hyperreactivity after active anaphylactic shock in conscious guinea pigs.

A model of bronchial hyperreactivity at various times after an active anaphylactic shock in conscious guinea pigs is described. The bronchial inflammation was quantified in parallel by determination of the number of mononuclear cells, neutrophils, and eosinophils in bronchoalveolar lavage (BAL) fluids. The guinea pigs were sensitized by an intramuscular (i.

Antiallergic and anti-inflammatory action of tioxamast in rats. II. Anti-inflammatory action in vivo.

Tioxamast is an antiallergic drug that inhibits anaphylaxis in various models in rats, and it inhibits the release and synthesis of certain mediators of inflammation [see Tarayre et al., this issue]. Here we report that the drug also has an anti-inflammatory effect in vivo in various nonimmunological models in rats.

Antiallergic and anti-inflammatory action of tioxamast in rats. I. Antiallergic activity in vivo and in vitro.

Tioxamast (F 1865) is an antiallergic drug that, administered systemically, reduces anaphylaxis in various models in rats. This action is due mainly to the inhibition of the synthesis and release of certain mediators. Orally or intraduodenally administered tioxamast inhibits IgE-dependent passive cutaneous anaphylaxis (ED50 = 0.

Pharmacological studies on zymosan inflammation in rats and mice. 2: Zymosan-induced pleurisy in rats.

Injection of zymosan in rat pleural cavity provokes an exudate which is already detectable at 15 min and which is maximum at 24 h. The leucocyte count (mostly neutrophils) increases at 2-4 h and is maximum at 48 h. In this paper the reaction has been studied up to 6 h.