Piroxicam-induced analgesia: evidence for a central component which is not opioid mediated.

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p < 0.05) and 50% (p < 0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.     

Current cases in which epitope mimicry is considered as a component cause of autoimmune disease: immune-mediated (type 1) diabetes

Autoimmune diseases result from a combination of genetic, immunologic, hormonal, and environmental factors. Infectious agents may induce the breakdown of immunological tolerance and the appearance of autoreactivity. However, the specific relationship between infection and autoimmunity is still unclear. One of the mechanisms responsible could be molecular mimicry between the infectious agent and self. The concept of molecular mimicry is a viable hypothesis in the investigation of the etiology, pathogenesis, treatment, and prevention of autoimmune disorders. Immune-mediated (type 1) diabetes in humans and in non-obese diabetic (NOD) mice is polygenic and characterized by autoimmune destruction of insulin-producing pancreatic beta cells in islets of Langerhans. In NOD mice, a T-helper 1 (Th1)-based autoimmune response arises spontaneously against glutamate decarboxylase (GAD) concurrently with the onset of insulitis. Subsequently. this Th1-type autoreactivity spreads intra- and intermolecularly to other beta cell autoantigens, suggesting that a Th1-type response is responsible for the progression of the disease, whereas Th2 responses when experimentally induced are protective. In humans, a homology between GAD and the P2-C protein of Coxsackie B make a cause-and-effect molecular mimicry an attractive hypothesis. Evidence to support the concept of molecular mimicry in diabetes is reviewed.     

Evidence for a direct action of monamines on the chick central nervous system

Zusammenfassung Pharmakologische Untersuchungen im Hinblick auf eine eventuelle Wechselwirkung von psychotropen Pharmaka und biogenen Aminen ergaben: (1) offenbares Eindringen von 5-HT, DA und NE in das Zentralnervensystem junger Hühner. (2) Schlafcharakteristisches Verhalten von EEG und Verhaltensweise nach Verabreichung von 5-HT und NE. (3) Auftreten der ?arousal?-Charakteristika mit anf?nglicher Akinese im EEG und Verhalten nach Dopamin- oder Dopazufuhr.

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Supported by U.S.P.H.S. Grant No. 5 TI MH-6415.     

Lysozyme is a component of human vascular elastic fibers

Lysozyme has been demonstrated in the elastic fibers of normal human arteries and veins by the peroxidase-antiperoxidase technique. Preliminary trypsinization of paraffin sections is necessary to unmask the immunoreactive lysozyme.     

Prothymosin alpha is not a nuclear polypeptide

Summary Using a radioimmunoassay for the NH₂-terminus of prothymosin alpha, the crossreactive material was measured in subcellular fractions of calf thymus and liver. No significant amount of crossreactive material was found in the nucleus. This provides experimental evidence against a recent hypothesis, based on structural evidence, that prothymosin alpha is a nuclear polypeptide.     

Understanding is not simulating: a reply to Gibbs and Perlman

In this response, I do four things. First, I defend the claim that the action compatibility effect does not distinguish between embodied and traditional accounts of language comprehension. Second, I present neuroimaging and neuropsychological results that seem to support the traditional account. Third, I argue that metaphorical language poses no special challenge to the arguments I gave against embodied theories of comprehension. Fourth, I lay out the architecture of language I advocate and suggest the sorts of data that would decide between traditional and embodied accounts.     

Evidence for an olfactory receptor which responds to nicotine--nicotine as an odorant

The tobacco alkaloid (S)(-)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1-100 nM) applied to the olfactory epithelium. Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.     

Prothymosin alpha is not a nuclear polypeptide

Using a radioimmunoassay for the NH2-terminus of prothymosin alpha, the crossreactive material was measured in subcellular fractions of calf thymus and liver. No significant amount of crossreactive material was found in the nucleus. This provides experimental evidence against a recent hypothesis, based on structural evidence, that prothymosin alpha is a nuclear polypeptide.     

Endogenous copper is cytotoxic to a lymphoma in primary culture which requires thiols for growth

With the use of bathocuproine sulfonate, a copper-specific chelator as an indicator, we have demonstrated that copper ions, present as a natural medium constituent are toxic to the growth of a lymphoma in primary culture and are principally responsible for the growth requirement of mercaptoethanol and other thiols. By chelating trace copper normally present in the medium, bathocuproine sulfonate retarded the oxidation of cysteine to poorly utilized cystine, thus permitting its direct utilization by the cells for growth.     

Chemotaxis is not a special case of haptotaxis

Serum peptides containing classical anaphylatoxin (CAT) produce marked chemotatic orientation of human neutrophil granulocytes without modifying cell attachment to the substratum. Furthermore gradients of adhesion produced with gammaglobulins fail to induce morphological orientation of neutrophils. The results suggest that chemotaxis is not a special case of haptotaxis.     

Endogenous copper is cytotoxic to a lymphoma in primary culture which requires thiols for growth

Summary With the use of bathocuproine sulfonate, a copper-specific chelator as an indicator, we have demonstrated that copper ions, present as a natural medium constituent are toxic to the growth of a lymphoma in primary culture and are principally responsible for the growth requirement of mercaptoethanol and other thiols. By chelating trace copper normally present in the medium, bathocuproine sulfonate retarded the oxidation of cysteine to poorly utilized cystine, thus permitting its direct utilization by the cells for growth.     

Chemotaxis is not a special case of haptotaxis

Summary Serum peptides containing classical anaphylatoxin (CAT) produce marked chemotactic orientation of human neutrophil granulocytes without modifying cell attachment to the substratum. Furthermore gradients of adhesion produced with gammaglobulins fail to induce morphological orientation of neutrophils. The results suggest that chemotaxis is not a special case of haptotaxis.The excellent technical assistance of Miss M. Schuster, Mrs A. Damschen and Mr M. Arnold is gratefully acknowledged. This work was supported by the Swiss National Science Foundation and the Sandoz-Stiftung zur Förderung der Medizinisch-Biologischen Forschung.     

The insect antenna is not a molecular sieve

Summary The deposition rate of 2 tritiated odorants onto insect antennae of different sizes and shapes is linearly proportional to the product of odorant concentration times the antennal surface area. This result challenges an assumption in a commonly accepted hypothesis that sensillar shape affects odorant deposition and that a single odorant molecule can initiate an action potential in a receptor cell. Consequently the 1-molecule-1-spike hypothesis bears reinvestigation.     

Synergism of a natural insect growth inhibitor is mediated by bioactivation

Summary Toxic plant allelochemicals are widespread in nature, but their mechanisms of action are largely unexplored. We report an example of bioactivation of a natural product, -asarone, that is mediated via insect mixed-function oxidases (MFO's), enzymes usually involved in detoxication processes. Bioactivity of -asarone is synergised by menthol, a MFO inducer, and antagonized by the MFO inhibitor piperonyl butoxide. Formation of a bioactive epoxide was confirmed by the identification of asarone epoxide and asarone diol in the insect excreta. These experiments represent the first demonstration of synergism between two natural products (-asarone and menthol) where the mechanism involves induction of enzymes usually involved in detoxication.     

Spin: All is not what it seems

Spin is typically thought to be a fundamental property of the electron and other elementary particles. Although it is defined as an internal angular momentum much of our understanding of it is bound up with the mathematics of group theory. This paper traces the development of the concept of spin paying particular attention to the way that quantum mechanics has influenced its interpretation in both theoretical and experimental contexts. The received view is that electron spin was discovered experimentally by Stern and Gerlach in 1921, 5 years prior to its theoretical formulation by Goudsmit and Uhlenbeck. However, neither Goudsmit nor Uhlenbeck, nor any others involved in the debate about spin cited the Stern–Gerlach experiment as corroborating evidence. In fact, Bohr and Pauli were emphatic that the spin of a single electron could not be measured in classical experiments. In recent years experiments designed to refute the Bohr–Pauli thesis and measure electron spin have been carried out. However, a number of ambiguities surround these results—ambiguities that relate not only to the measurements themselves but to the interpretation of the experiments. After discussing these various issues I raise some philosophical questions about the ontological and epistemic status of spin. Because it is a curious hybrid of the mathematical and the physical these questions are relatively complex, and while I do not pretend to have answered them here, the goal of the paper is to uncover and isolate how spin presents problems for traditional realism and to illustrate the power that theories like quantum mechanics have for shaping both philosophical questions and answers.     

Evidence for an olfactory receptor which responds to nicotine — nicotine as an odorant

Summary The tobacco alkaloid (S)(–)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1–100 nM) applied to the olfactory epithelium.Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine.Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.22 September 1986