Washington y Ginebra llegan a Buenos Aires: notas sobre la historia del hábito de fumar y su medicalización / Washington and Geneva arrive in Buenos Aires: notes on the history of the habit of smoking and its medicalization

Durante gran parte del siglo XX tanto los gobiernos civiles como los militares no encontraron en el tabaquismo un tema prioritario. Recién en la última década del siglo el movimiento internacional contra el cigarrillo, liderado por la Organización Mundial de la Salud, organizaciones norteamericanas y académicos, empezó a tener algún impacto en la escena política argentina. Fue en ese contexto que un nuevo grupo profesional logró impulsar la constitución de un amplio bloque político antitabaco. En ese proceso, el voluntarismo centrado en programas individuales para dejar de fumar que había marcado gran parte de las iniciativas del siglo XX, terminó desplazado por políticas públicas destinadas a producir ambientes libres de humo y a combatir la exposición pasiva al humo de tabaco ajeno.

For much of the twentieth century both the civilian and military governments did not consider smoking a priority concern. It was only in the last decade of the twentieth century that the international movement against cigarettes, led by the World Health Organization, US organizations and academics, began to have some impact on Argentina's political scene. It was in this context that a new professional group managed to foment the creation of a broad anti-smoking political bloc. In this process, voluntarism focused on individual programs to quit smoking that had marked much of the initiatives of the twentieth century, ended up being replaced by public policies designed to ensure smoke free environments and combat passive smoking.

Curso temporal dos efeitos da exposição combinada de nicotina e etanol no sistema colinérgico cerebral durante adolescência / Time course of the effects of combined exposure to nicotine and ethanol in the brain cholinergic system during adolescence

O etanol e a nicotina são as drogas mais comumente usadas no mundo. Como claramente indicado por estudos epidemiológicos, existe uma forte associação entre o tabagismo e o consumo de etanol principalmente durante o período da adolescência. Entretanto, existem poucos estudos em neurobiologia básica que avaliem o efeito da exposição combinada de nicotina e etanol durante o período da adolescência. Considerando que a nicotina é um agonista do receptor colinérgico nicotínico (nAChR) e que tem sido demonstrado que o etanol interage com os nAChRs, o presente trabalho tem como foco o estudo dos efeitos da exposição à nicotina e/ou ao etanol no sistema colinérgico durante a adolescência. Do 30º ao 45º dia pós-natal (PN) camundongos da cepa C57BL/6 foram expostos à nicotina (NIC) e/ou etanol (ETOH). Quatro grupos foram analisados: 1) exposição concomitante (NIC+ETOH) à solução de nicotina (50ug/ml) e etanol (25%, 2g/kg i.p. em dias alternados), 2) exposição a NIC, 3) exposição ao ETOH, 4) exposição ao veículo. Foram quantificadas a expressão/afinidade do [3H] hemicolinium-3 (HC-3) ao transportador de alta afinidade présinaptico de colina, ao final da exposição (PN45), após curto (PN50) e longo período de retirada (PN75). Ao final da exposição, o grupo NIC+ETOH apresentou upregulation de nAChRs, refletindo simples somação dos efeitos da NIC e ETOH no córtex cerebral e sinergismo no mesencéfalo. A upregulation devido à exposição combinada foi mantida mesmo após alguns dias de retirada das drogas. Um mês após o término da exposição, os valores foram semelhantes aos obtidos para os animais veículo. Em PN45, machos NIC apresentaram aumento da ChAT no córtex cerebral, mas o ETOH foi capaz de reverter este efeito. Ao contrário, fêmeas NIC apresentaram diminuição da ChAT. No mesencéfalo, somente ETOH promoveu aumento da ChAT. Já em PN50, o grupo NIC apresentou aumento na ChAT que foi revertido na retirada combinada de NIC+ETOH. Em PN75, o grupo NIC+ETOH...

Nicotine and ethanol are the most commonly consumed drugs. As clearly indicated by epidemiological studies, there is a close interrelationship between smoking and alcohol consumption manly during adolescence period. However, there are few studies on the basic neurobiology of the effects of the combined nicotine and ethanol exposure in the adolescent brain. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChR), the current proposal will focus on the cholinergic effects of nicotine and/or ethanol treatment during adolescence. From the 30th to the 45th postnatal day (PN), C57BL/6 mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: 1) concomitant (NIC+ETOH) exposure of nicotine (50 ug/ml) and ethanol (25%, 2 g/kg i.p. every other day); 2) NIC exposure; 3) ETOH exposure; 4) vehicle. We assessed nAChR (alfa4beta2) binding, choline acetyltransferase (ChAT) activity and [3H] hemicholinium-3 (HC-3) binding to the high affinity presynaptic choline transporter at the end of exposure period (PN45), at short (PN50) and long term (PN75) withdrawal. At the end of exposure period, NIC+ETOH elicited a pronounced upregulation which reflect simple additivity of the effects of nicotine and ethanol in the cerebral cortex and synergism in the midbrain. On PN45, male NIC mice presented an increase in ChAT in the cerebral cortex. However, ETOH reversed this effect. In contrast, female NIC mice presented decreased ChAT activity. In the midbrain, ETOH increased ChAT. On PN50, NIC mice presented an increase in ChAT activity that was reversed by ETOH withdrawal. In addition, NIC+ETOH long term withdrawal elicited a decrease in ChAT activity. Regarding HC-3, binding was not affected on PN45. ETOH and NIC+ETOH withdrawal promoted a decrease at short and long-term withdrawal. These results provide experimental evidences that nicotine and ethanol during adolescence...

Nicotine-evoked cytosolic Ca2+ increase and cell depolarization in capillary endothelial cells of the bovine adrenal medulla

Endothelial cells are directly involved in many functions of the cardiovascular system by regulating blood flow and blood pressure through Ca2+ dependent exocitosis of vasoactive compounds. Using the Ca2+ indicator Fluo-3 and the patch-clamp technique, we show that bovine adrenal medulla capillary endothelial cells (B AMCECs) respond to acetylcholine (ACh) with a cytosolic Ca2+ increase and depolarization of the membrane potential (20.3±0.9 mV; n=23). The increase in cytosolic Ca2+ induced by 10µM ACh was mimicked by the same concentration of nicotine but not by muscarine and was blocked by 100 µM of hexamethonium. On the other hand, the increase in cytosolic Ca2+ could be depressed by nifedipine (0.01 -100 µM) or withdrawal of extracellular Ca2+. Taken together, these results give evidence for functional nicotinic receptors (nAChRs) in capillary endothelial cells of the adrenal medulla. It suggests that nAChRs in B AMCECs may be involved in the regulation of the adrenal gland's microcirculation by depolarizing the membrane potential, leading to the opening of voltage-activated Ca2+ channels, influx of external Ca2+ and liberation of vasoactive compounds.

Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar beta amyloid peptide (1-42)-stimulated microglia

Recent studies have reported that the "cholinergic anti-inflammatory pathway" regulates peripheral inflammatory responses via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and that acetylcholine and nicotine regulate the expression of proinflammatory mediators such as TNF-alpha and prostaglandin E2 in microglial cultures. In a previous study we showed that ATP released by beta-amyloid-stimulated microglia induced reactive oxygen species (ROS) production, in a process involving the P2X7 receptor (P2X7R), in an autocrine fashion. These observations led us to investigate whether stimulation by nicotine could regulate fibrillar beta amyloid peptide (1-42) (fA beta(1-42))-induced ROS production by modulating ATP efflux-mediated Ca2+ influx through P2X7R. Nicotine inhibited ROS generation in fA beta(1-42)-stimulated microglial cells, and this inhibition was blocked by mecamylamine, a non-selective nAChR antagonist, and a-bungarotoxin, a selective alpha7 nAChR antagonist. Nicotine inhibited NADPH oxidase activation and completely blocked Ca2+ influx in fA beta(1-42)-stimulated microglia. Moreover, ATP release from fA beta(1-42)-stimulated microglia was significantly suppressed by nicotine treatment. In contrast, nicotine did not inhibit 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP)-induced Ca2+ influx, but inhibited ROS generation in BzATP-stimulated microglia, indicating an inhibitory effect of nicotine on a signaling process downstream of P2X7R. Taken together, these results suggest that the inhibitory effect of nicotine on ROS production in fA beta(1-42)-stimulated microglia is mediated by indirect blockage of ATP release and by directly altering the signaling process downstream from P2X7R.

Development of fetal nicotine and muscarinic receptors in utero

The role of acetylcholine in the central and peripheral nervous systems is well established in adults. Cholinergic modulation of vascular functions and body fluid balance has been extensively studied. In the embryo-fetus, cholinergic receptors are widespread in the peripheral and central systems, including smooth muscle and the epithelial lining of the cardiovascular, digestive, and urinary systems, as well as in the brain. Fetal nicotine and muscarinic receptors develop in a pattern (e.g., amount and distribution) related to gestational periods. Cholinergic mechanisms have been found to be relatively intact and functional in the control of vascular homeostasis during fetal life in utero at least during the last third of gestation. This review focuses on the development of fetal nicotine and muscarinic receptors, and provides information indicating that central cholinergic systems are well developed in the control of fetal blood pressure and body fluid balance before birth. Therefore, the development of cholinergic systems in utero plays an important role in fetal vascular regulation, gastrointestinal motility, and urinary control.

Natural probes for cholinergic sites: L-bebeerine actions on the neuromuscular transmission, the nicotinic receptor/ionic channel complex, and contraction of skeletal muscles

The mechanisms underlying the muscle relaxant of 1-bebeerine (BB), a tertiary alkaloid isolated from the roots of Chondrodendron platyphyllum, were examined in mammalian and amphibian skeletal muscles. Injections of BB (0.05 - 1 g/kg,i.p.) in rats caused a dose-related flaccid paralysis and respiratory arrest at high doses. In isolated rat diaphragmand toad sartorius muscles, BB depressed the indirectly elicited muscles twitches (IC50:228 muM and 5.4 muM, respectively, at 22 degree) and blocked the nerve-elicited muscle action potential. The neuromuscular blockade was not reserved by neostigmine (10 muM). High concentrations of BB (170 and 340 muM) caused muscle contracture unrelated to the junctional blockade, and intensified by increasing the bath temperature. Analysis of the contraction properties showed that BB (40 and 80 muM)increaded the twitch/tetanus ratio (46 percent and 125 percent) and prolonged the relaxation time; the falling phase of the directly elicited action potential in toad sartorius muscle fibers was slower probably by a decreased potasium conductance. BB (0.1 - 340 muM) reduced the binding of [1251]alpha- -bungarotoxin to the junctional AACh receptor of the rat diaphragm (IC50:47.7 muM, at 37 degree. At low concentrations BB (1.5 - 15 muM) induced either opening or blockade of the Ach receptor-ionic channel. The results showed that BB blocked noncompetitively the neuromuscular transmission through a mechanism that affects the Ach recognition site and the ionic channel properties. The alkaloid also produced muscle contracture and changed the contractile properties through its extra-junctional action at the calcium handling by the sarcoplasmic reticulum or the contractile machinery.

Ultrastructure of Psammobatis extenta (Rajidae) electrolytes and cytochemical localization of acetylcholinesterase, acetylcholine receptor and F-actin

1. The electrocytes from the electric organ of the Patagonian ray P. extenta are very unusual cells: semicircular in shape, multinucleated and highly polarized. They have an anterior, concave, innervated face, which exhibits positive histochemical reactions for acetylcholinesterase and for the nicotinic acetylcholine receptor. Multiple nerve-endings are covered with Schwann cell projections, similar to those present in skeletal muscle. Their posterior face is convex, non-innervated and is in contact with collagen fibres. 2. The cytoplasm of these electrocytes possesses abundant filamentous actin (F-actin), orderly distributed in the cell and exhibiting intense fluorescence with NBD-phallacidin. The F-actin is in contact with Z-lines as in muscle, and in contrast with Torpedo (Kordeli et al., 1986, 1987) and Discopyge (Vidal et al., 1986, 1989a) electrocytes, where it is confined to the non-innervated face. 3. Electrocytes of this Rajidae are an ideal model for the study of F-actin because of the similar embryological origin with skeletal muscle tissue and also because of the peculiar characteristics of their cytoplasm, packed full with F-actin. In addition, electric organs could constitute an alternative biological source for the study of the cholinergic synapse.

Transport of a nicotinic acetylcholine receptor subunit in axonal systems

The effect of neural lesions upon the distribution of a neuronal nicotinic acetylcholine receptor subunit was investigated in the chick nervous system. Following unilateral retinal lesions, the neuropil staining with an antibody against the Beta2 receptor subunit was dramatically reduced or completely eliminated in all retinorecipient structures. Lesions of the lateral spiriform nucleus, a major Beta2 subunit-containing mesencephalic nucleus, produced a marked reduction of neuropil staining in the deeper layers of the tectum, which represent the main target of that nucleus. The present results indicate that the Beta2 subunit is transported in axonal systems, and might therefore constitute presynaptic receptors in some brain areas.

Lipid effects on nicotinic acetylcholine receptor gating and kinetics: a structural-functional correlation

The nicotinic acetylcholine receptor (AChR) is still the paradigm of rapid ligand-gated ion channels. Since the early finding of a motionally restricted shell of lipids ( annulus ) in the immediate perimeter of the membrane-bound AChR, experimental evidence has supported the notion that the interface between the protein moiety and the adjacent lipid molecules is the site of action of a variety of pharmacologically relevant substances, including non-competitive inhibitors of the cholinergic system like some local anesthetics, short-chain alcohols, and steroids. Patch-clamp data on cells expressing the AChR protein add another dimension to this knowledge, enabling correlations to be established between the chemical composition of lipid-modified cells and the functional properties (ligand binding, channel gating) of the receptor protein in situ

Polarization of different actin isoforms in Discopyge tschudii electrocytes

Se realizó uno estudio histoquímico en cortes criostáticos de electrocitos de Discopyge tschudii con el objeto de investigar la distribución de isoformas de actina y la posible relación entre estas y el AChR. La membrana ventral del electrocito fue diferenciada de la no inervada mediante beta-cobrotoxina, marcador específico del AChR, conjugada con isotiocinato de tetrametil rodamina y la histoquímica de la AChE. La falacidina, una toxina que tiene la propiedad de unirse con alta afindad a la forma filamentosa (F) de la actina, detectó a la misma exclusivamente en la cara dorsal del electrocito. Utilizando dos líneas de anticuerpos monoclonales (mAbs) anti-actina (QAB1 y QAB2 obtenidas empleando com inmunógeno actina de músculo pectoral de codorniz) evidenciamos distintas isofromas de actina en el electrocito. El mAb QAB1 mostró una fluorescencia puntual a nivel de las terminales nerviosas; el mAb QAB2, en cambio, se distribuyó en todo el citoplasma del electrocito. De los presentes resultados podemos concluir que cada una de las isoformas de actina coexistentes en el electrocito de D. tschudii posee una polaridad estructural distinta: 1) la actina filamentosa (F) localizada exclusivamente en la cara dorsal o no-inervada; 2) la isoforma de actina reconocible por el mAb QAB1, probablemente análoga a la descrita por Walter y cols. (1981) en el electrocito de Torpedo y 3) la reconocible poer el mAb QAB2, la cual puede corresponder a la actina monomérica (G) evidenciada por Kordely y cols. (1986, 1987). La actina detectada por métodos bioquímicos en las membranas ricas en AChR parece no corresponder a ninguna de las isoformas descritas aquí por métodos inmunocitoquímicos, o se halla en cantidades, no detectadas por estos métodos