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J A Terrón

Publications and source records attributed to J A Terrón.

At least 37 records · Page 2Linked to original sources
PubMed1997

A CT-aided PC-based physical treatment planning of TBI: a method for dose calculation.

BACKGROUND AND PURPOSE: As for conventional radiotherapy, one of the basic requirements in Total Body Irradiation (TBI) is to know accurately the dose delivered to the entire body. Both the dosimetry and the treatment planning need to be improved. Physical, technical and dosimetrical aspects of TBI have been widely discussed in the literature. However, to our knowledge, no planning systems specifically designed for TBI are commercially available. This article describes a CT-aided PC-based planning system (TBI-Plansys) and its dose calculation algorithm, which applies scatter and inhomogeneity corrections, developed for the TBI technique currently in use at our centre (AP/PA irradiation with patient positioned on his side). MATERIAL AND METHOD: A description of the material and method followed in the dosimetrical procedure is included as it constitutes the basis of the proposed dose calculation algorithm (more than 2D). A Windows programming environment has been used to develop the software. RESULTS: TBI-Plansys uses patient CT data and indicates absolute and relative dose distributions along midline (at reference points), the transversal axis at the specification point and on transverse sections. The system also calculates the appropriate thicknesses of bolus and shielding to modify undesired dose distributions. TBI-Plansys has been checked against two other well-established systems (beam-zone method and our in vivo semiconductor probe-based system). The checks showed good accuracy with dose differences less than 1% and 3% for homogeneous and inhomogeneous tissues, respectively. CONCLUSIONS: CT calculations by TBI-Plansys allow us to detect undesired distributions which may go unnoticed by calculations at only some specific points. The system has shown clear advantages for routine clinical use as it generates more detailed and accurate information than manual calculations and diminishes the time requirements.

Algorithms↗
PubMed1997

Lateral scatter correction algorithm for percentage depth dose in a large-field photon beam.

Differences between the scatter conditions of dosimetry and treatment situation are more important in the case of large-field photon beams than in standard ones. In the former, the scattering volume is defined by the phantom cross section; in the latter, the radiation field size. Two factors should be considered: the thickness and the cross section of the phantom. Both of them have an effect on the Percentage Depth Dose (PDD) distribution. In a previous study we addressed the influence of backscatter thickness on dose delivered. The aim of this work is to measure the effect of cross section phantom on the PDD curves under our TBI treatment conditions. Results showed a strong dependence of the PDDs on this parameter. A semi-empirical expression has also been derived to calculate (within 0.5% uncertainty) the Lateral scatter Correction Factor (LCF). The model of LCF states a linear dependence on depth whilst slope of these curves depends exponentially on distance to the lateral surface. The algorithm is being applied to our practical Total Body Irradiation (TBI) procedure.

Algorithms↗
PubMed1997

Mediation of 5-HT-induced external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs by the putative 5-HT7 receptor.

1. The vasodilator effects of 5-hydroxytryptamine (5-HT) in the external carotid bed of anaesthetized dogs with intact sympathetic tone are mediated by prejunctional sympatho-inhibitory 5-HT1B/1D receptors and postjunctional 5-HT receptors. The prejunctional vasodilator mechanism is abolished after vagosympathectomy which results in the reversal of the vasodilator effect to vasoconstriction. The blockade of this vasoconstrictor effect of 5-HT with the 5-HT1B/1D receptor antagonist, GR 127935, unmasks a dose-dependent vasodilator effect of 5-HT, but not of sumatriptan. Therefore, the present study set out to analyse the pharmacological profile of this postjunctional vasodilator 5-HT receptor in the external carotid bed of vagosympathectomized dogs pretreated with GR 127935 (20 micrograms kg-1, i.v.). 2. One-minute intracarotid (i.c.) infusions of 5-HT (0.3-30 micrograms min-1), 5-carboxamidotryptamine (5-CT; 0.01-0.3 microgram min-1), 5-methoxytryptamine (1-100 micrograms min-1) and lisuride (3-1000 micrograms min-1) resulted in dose-dependent increases in external carotid blood flow (without changes in blood pressure or heart rate) with a rank order of agonist potency of 5-CT > > 5-HT > or = 5-methoxytryptamine > lisuride, whereas cisapride (100-1000 micrograms min-1, i.c.) was practically inactive. Interestingly, lisuride (mean dose of 85 +/- 7 micrograms kg-1, i.c.), but not cisapride (mean dose of 67 +/- 7 micrograms kg-1, i.c.), specifically abolished the responses induced by 5-HT, 5-CT and 5-methoxytryptamine, suggesting that a common site of action may be involved. In contrast, 1 min i.c. infusions of 8-OH-DPAT (3-3000 micrograms min-1) produced dose-dependent decreases, not increases, in external carotid blood flow and failed to antagonize (mean dose of 200 +/- 33 micrograms kg-1, i.c.) the agonist-induced vasodilator responses. 3. The external carotid vasodilator responses to 5-HT, 5-CT and 5-methoxytryptamine were not modified by intravenous (i.v.) pretreatment with either saline, (+/-)-pindolol (4 mg kg-1) or ritanserin (100 micrograms kg-1) plus granisetron (300 micrograms kg-1), but were dose-dependently blocked by i.v. administration of methiothepin (10 and 30 micrograms kg-1, given after ritanserin plus granisetron), mesulergine (10 and 30 micrograms kg-1), metergoline (1 and 3 mg kg-1), methysergide (1 and 3 mg kg-1) or clozapine (0.3 and 1 mg kg-1). Nevertheless, the blockade of the above responses, not significant after treatment with the lower of the two doses of metergoline and mesulergine, was nonspecific after administration of the higher of the two doses of methysergide and clozapine. 4. Based upon the above rank order of agonist potencies and the antagonism produced by a series of drugs showing high affinity for the cloned 5-ht7 receptor, our results indicate that the 5-HT receptor mediating external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs is operationally similar to the putative 5-HT7 receptor mediating relaxation of vascular and non-vascular smooth muscles (e.g. rabbit femoral vein, canine coronary artery, rat systemic vasculature and guinea-pig ileum) as well as tachycardia in the cat.

5-Methoxytryptamine↗
PubMed1997

Role of 5-ht7 receptors in the long-lasting hypotensive response induced by 5-hydroxytryptamine in the rat.

1. The receptor mediating the long-lasting hypotensive effect of intravenous (i.v.) 5-hydroxytryptamine (5-HT) in the rat was originally classified as 5-HT1-like. Since some pharmacological properties of this receptor are closely similar to those for the cloned 5-ht7 receptor, the present study investigated the effects of several 5-HT receptor agonists and antagonists showing high affinity for the cloned 5-ht7 receptor in pithed rats with artificially raised blood pressure. 2. I.v. bolus administration of 5-HT, 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine, lisuride and sumatriptan to bilaterally vagotomized pithed rats pretreated with ketanserin (0.18 mumol kg-1, i.v.), the diastolic blood pressure of which had been raised by a continuous i.v. infusion of methoxamine (60-80 nmol kg-1 min-1), produced dose-dependent hypotensive responses; only 5-HT and 5-CT displayed similar maximum effects. In addition to mimicking the hypotensive action of 5-HT with a lower maximum effect, lisuride strongly antagonized the 5-CT-induced hypotensive responses thus suggesting a partial agonist effect. The rank order of hypotensive agonist potency was 5-CT > > 5-HT > or = 5-methoxytryptamine > or = lisuride > > sumatriptan. 3. In experiments with antagonists, i.v. treatment with metergoline (2.48 mumol kg-1), mesulergine (2.76 mumol kg-1), methysergide (2.13 mumol kg-1), lisuride (0.22 mumol kg-1), methiothepin (0.68 mumol kg-1), mianserin (10.6 mumol kg-1), or the atypical antipsychotic drugs, clozapine (11.0 mumol kg-1) or risperidone (78.0 nmol kg-1), produced significant rightward displacements of the dose-response curve for 5-CT in methoxamine-infused pithed animals pretreated with ketanserin (0.18 mumol kg-1, i.v.); lisuride, methiothepin and risperidone behaved as non-competitive antagonists as they elicited a significant reduction of the maximum effect to 5-CT. In contrast, blockade of 5-HT1, 5-HT3 and 5-HT4 receptors with i.v. propranolol (3.38 mumol kg-1), MDL-72222 (1.59 mumol kg-1) and GR125487 (1.91 mumol kg-1), respectively, did not alter 5-CT-induced hypotensive responses; ketanserin (0.18 mumol kg-1, i.v.) failed to modify the dose-response curve for 5-CT in saline-pretreated animals. Lastly, inhibition of the prostaglandin-forming cyclo-oxygenase and nitric oxide synthase with indomethacin (14 mumol kg-1, i.v.) and NG-nitro-L-arginine methyl ester (L-NAME, 120 mumol kg-1, i.v.), respectively, had no significant effects on 5-CT-induced hypotensive effects. 4. Taken together, the present pharmacological data suggest that the long-lasting vasodepressor action of 5-HT in the rat involves activation of receptors closely similar to the cloned 5-ht7 subtype. Since no evidence for an indirect mechanism could be obtained, these receptors may be primarily located in the vascular smooth muscle of the systemic resistance vessels. These findings represent further evidence favouring the functional role of the 5-ht7 receptor.

Animals↗
PubMed1997

Effects of thiopental on endothelium-dependent responses in rat aorta.

Effects of pretreatment with thiopental on endothelium-dependent vasodilator responses elicited by drugs in rat aortic rings were investigated. The vasodilators employed were acetylcholine and histamine (endothelium- and receptor-dependent), A23187 (endothelium-dependent but receptor-independent) and sodium nitroprusside (endothelium-independent); they were tested 15 or 60 min after aortic preparations were exposed during 15 min to thiopental. Pretreatment with the barbiturate reversibly inhibited relaxation elicited by either acetylcholine and histamine, but a high concentration of the anesthetic was needed (3.1 mg/ml). On the contrary, thiopental did not modify the relaxation elicited by sodium nitroprusside or A23187. In addition, the barbiturate inhibited basal and acetylcholine-stimulated production of nitrites (an indicator of nitric oxide output) in aortic rings. In conclusion, thiopental inhibited the endothelium-dependent relaxation elicited by either acetylcholine or histamine. Although the barbiturate also inhibited nitric oxide production, the reduction in the relaxant response provoked by it does not seem to be the result of direct guanylate cyclase or nitric oxide synthase alterations, since thiopental did not modify the effect of sodium nitroprusside or A23187. Disturbances elicited by thiopental on endothelial receptors or on signal transduction elements may indirectly provoke nitric oxide synthase inhibition.

Animals↗
PubMed1996

GR127935 is a potent antagonist of the 5-HT1-like receptor mediating contraction in the canine coronary artery.

The effects of the recently developed 5-HT1D receptor antagonist, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1,-biphenyl]-4-carboxamide), and those of the preferential human 5-HT1D alpha receptor antagonist, ketanserin, on the isometric contraction induced by 5-hydroxytryptamine (5-HT) and sumatriptan in endothelium-denuded ring segments of canine coronary artery were analyzed. Sumatriptan mimicked 5-HT with lower potency but similar efficacy. GR127935 (1,3 and 10 nM) concentration dependently antagonized the contractions elicited by both agonists; only the 5-HT maximum was reduced. Ketanserin and mianserin (both at 1 microM) were inactive. These data strongly suggest that a 5-HT1D receptor mediates contraction in the dog coronary artery. The possibility that this 5-HT1D receptor resembles the cloned human 5-HT1D beta subtype is discussed.

Animals↗
PubMed1996

Role of alpha1-adrenoceptors in the reduction of external carotid blood flow induced by buspirone and ipsapirone in the dog.

The effects of the 5-HT1A receptor agonist with anxiolytic properties, buspirone and ipsapirone, in the external carotid bed of anaesthetized dogs were analyzed. Since these agonists produce several vascular effects via activation of both 5-HT receptors and alpha1-adrenoceptors, their effects were compared with those elicited by the 5-HT agonist, quipazine, and the alpha1-adrenoceptor agonist, methoxamine. 1-Min intracarotid (i.c.) infusions of buspirone (300 microgram/min), ipsapirone (40 microgram/min), quipazine (300 microgram/min) and methoxamine (15 microgram/min) produced consistent decreases in external carotid blood flow (ECBF); since these changes in blood flow were not accompanied by modifications in systemic blood pressure, the agonists produced parallel increases in external carotid resistance. After interruption of the sympathetic tone by bilateral cervical vagosympathectomy, the vasoconstrictor responses to all the agonists remained unaffected. The intravenous (i.v.) administration of the nonselective 5-HT1-like receptor antagonist, methiothepin (1-100 microgram/kg), potently and dose-dependently antagonized buspirone-, ipsapirone- and quipazine-induced vasoconstriction; methiothepin similarly antagonized the vasoconstrictor responses to methoxamine. Interestingly, the alpha1-adrenoceptor antagonist, prazosin (1-100 microgram/kg, i.v.), also antagonized the vasoconstrictor responses to buspirone, ipsapirone and methoxamine in a dose-dependent manner. Finally, buspirone (300 microgram/min, i.c.) and ipsapirone (40 microgram/min, i.c.) did not modify the responses to noradrenaline (10 microgram/min, i.c.) or tyramine (100 microgram/min, i.c.). It is concluded that canine external carotid vasoconstriction induced by buspirone and ipsapirone is mainly mediated by activation of alpha1-adrenoceptors located in vascular smooth muscle. These data further highlight the ability of the above anxiolytics to produce significant vascular effects under in vivo conditions.

Adrenergic alpha-Agonists↗
PubMed1996

The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-ht7 receptor subtype.

1. The relaxant effect of 5-hydroxytryptamine (5-HT) in the dog isolated coronary artery deprived of endothelium is mediated by a receptor unrelated to the 5-HT1, 5-HT2, 5-HT3 or 5-HT4 types. Based upon the pharmacological characteristics of this relaxant 5-HT receptor and those reported for the new members of the 5-HT receptor family, the present study explored the possibility that the relaxant 5-HT receptor referred to above, corresponds to the cloned 5-ht7 subtype. Thus, the relaxing and/or blocking effects of several 5-HT receptor drugs as well as some typical and atypical antipsychotic drugs with high affinity for the cloned 5-ht7 receptor in precontracted ring segments were analyzed. 2. 5-HT, 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine, but not 8-OH-DPAT or sumatriptan, produced concentration-dependent relaxations in endothelium-denuded canine coronary artery rings precontracted with prostaglandin F2a (2 microM). Clozapine (1 microM) produced in some cases a small relaxing effect and antagonized 5-HT- and 5-CT-induced relaxation suggesting a partial agonist effect. In the presence of the 5-HT1D receptor antagonist, GR127935 (100 nM), the rank order of agonist potency was 5-CT > 5-HT > clozapine > or = 5-methoxytryptamine. 8-OH-DPAT and sumatriptan remained inactive as agonists. 3. In GR127935-treated preparations, methiothepin (3 nM) and mianserin (1 microM), as well as the antipsychotics, clozapine (1 microM), pimozide (300 nM), risperidone (3 nM) and spiperone (1 microM), failed to induce a significant relaxation in prostaglandin F2x-precontracted vessels, but produced significant rightward displacements of the concentration-response curves to 5-HT and 5-CT without significantly reducing the Emax. In a final set of experiments with 5-CT, metergoline (100 nM) and mesulergine (300 nM) behaved as competitive antagonists. In contrast, lisuride (3 nM) noncompetitively antagonized 5-CT-induced relaxation. The estimated affinity (apparent pKa values) of the above antagonist drugs for the relaxant 5-HT receptor significantly correlated with their reported affinity at the cloned 5-ht7 receptor. 4. Taken together, the above pharmacological data may suggest that the relaxant 5-HT receptor in the smooth muscle of the canine coronary artery is similar to the cloned 5-ht7 receptor subtype.

Animals↗
PubMed1996

Influence of 5-hydroxytryptamine on the pressor responses induced by norepinephrine and electrical sympathetic stimulation in the pithed rat.

Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The present study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 micrograms/kg) or electrical stimulation at increasing frequencies (0.1-3 Hz) were evaluated before and during continuous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1-10 micrograms/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure - but not those in heart rate - produced by stimulation of the appropriate spinal segments. These effects of 5-HT were more pronounced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents.

Animals↗
PubMed1995

5-hydroxytryptamine inhibits pressor responses to preganglionic sympathetic nerve stimulation in pithed rats.

5-Hydroxytryptamine (5-HT) inhibits contractile responses to adrenergic nerve stimulation in several blood vessels and organs. We have now investigated the potential ability of 5-HT to inhibit the pressor responses caused by preganglionic sympathetic stimulation (T7-T9) in pithed rats. Sympathetic stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) resulted in frequency-dependent increases in diastolic blood pressure; these effects were augmented after i.v. treatment with desipramine (50 micrograms/kg). During continuous infusions of 5-HT (1.8, 3.1, 5.6 and 10 micrograms/kg.min, i.v.), but not of saline, the pressor responses were dose-dependently inhibited in both control and desipramine-pretreated rats; this inhibitory effect of 5-HT was significantly more pronounced at lower frequencies of stimulation. In contrast, the above infusions of 5-HT did not inhibit the pressor responses induced by i.v. bolus injections of exogenous norepinephrine (up to 3 micrograms/kg). Taken together, the above findings suggest an operative 5-HT-induced prejunctional inhibition of sympathetic nerve activity on the systemic vasculature in vivo.

Animals↗
PubMed1995

Constancy of wedge factors in a Siemens Mevatron 74 linear accelerator.

The variation of the wedge factor (WF) with field size is an important piece of data which determines the radiation output in treatments using wedge filters. WF is closely related with the accelerator head layout, and the choice of the wedge tray mounted above or below the jaws plays a predominant role. In this work we have studied the WF variations in our linac and found that, in apparent contradiction with the literature, the WF remains constant with field size. Nevertheless, these results cannot be used directly in other linacs, and individual dosimetry must be carried out.

Particle Accelerators↗
PubMed1995

Characterization of prejunctional 5-HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat.

1. It has recently been shown that continuous infusions of 5-hydroxytryptamine (5-HT) are able to inhibit, in a dose-dependent manner, the pressor responses induced by preganglionic (T7-T9) sympathetic stimulation in pithed rats pretreated with desipramine (50 micrograms kg-1, i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03-I Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5-HT (up to 5.6 micrograms kg-1 min-1). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-HT. 2. The inhibition induced by 5.6 micrograms kg-1 min-1 of 5-HT on sympathetically-induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg-1), ritanserin (0.1 mg kg-1), MDL 72222 (0.15 mg kg-1) or tropisetron (3 mg kg-1), which did not modify the sympathetically-induced pressor responses per se, but was significantly antagonized by the 5-HT1-like and 5-HT2 receptor antagonist, methysergide (0.3 mg kg-1), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se. 3. Unexpectedly and contrasting with methysergide, the 5-HT1-like and 5-HT2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg-1) and metergoline (1 and 3 mg kg-1), apparently failed to block the above 5-HT-induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically-induced pressor responses per se, presumably by blockade of vascular alpha 1-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HT1-like receptors. 4. Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HT1-like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5-HT with the following rank order of agonist potency: 5CT > > 5-HT > metergoline > or = methysergide. 5. Taken together, the above results suggest that the inhibitory action of 5-HT on the electrically-induced pressor responses is primarily mediated by an action on inhibitory prejunctional 5-HT1-like receptors leading to a decrease in the sympathetic nerve discharge. Interestingly, 5-HT-induced excitatory mechanisms could be made manifest once the inhibitory action of 5-HT had been antagonized.

Animals↗
PubMed1995

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5-HT in vagosympathectomized dogs.

1. 5-Hydroxytryptamine (5-HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone. Hence, external carotid vasodilatation to 5-HT in dogs with intact sympathetic tone is primarily mediated by prejunctional 5-HT1-like receptors similar to the 5-HT1D subtype, which inhibit the carotid sympathetic outflow. The present investigation is devoted to the pharmacological analysis of the receptors mediating external carotid vasoconstriction by 5-HT in vagosympathectomized dogs. 2. Intracarotid (i.c.) infusions for 1 min of 5-HT (0.3, 1, 3, 10, 30 and 100 micrograms) resulted in dose-dependent decreases in both external carotid blood flow and the corresponding conductance; both mean arterial blood pressure and heart rate remained unchanged during the infusions of 5-HT. These responses to 5-HT were resistant to blockade by antagonists at 5-HT2 (ritanserin) and 5-HT3/5-HT4 (tropisetron) receptors, but were partly blocked by the 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (0.3 mg kg-1); higher doses of methiothepin (1 and 3 mg kg-1) caused little, if any, further blockade. These methiothepin (3 mg kg-1)-resistant responses to 5-HT were not significantly antagonized by MDL 72222 (0.3 mg kg-1) or tropisetron (3 mg kg-1). 3. The external carotid vasoconstrictor effects of 5-HT were mimicked by the selective 5-HT1-like receptor agonist, sumatriptan (3, 10, 30 and 100 micrograms during 1 min, i.c.), which produced dose-dependent decreases in external carotid blood flow and the corresponding conductance; these effects of sumatriptan were dose-dependently antagonized by methiothepin (0.3, 1 and 3 mg kg-1), but not by 5-HT1D-like receptor blocking doses of metergoline (0.1 mg kg-1). 4. The above vasoconstrictor effects of 5-HT remained unaltered after administration of phentolamine, propranolol, atropine, hexamethonium, brompheniramine, cimetidine and haloperidol, thus excluding the involvement of alpha- and beta-adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors. Likewise, inhibition of either 5-HT-uptake (with fluoxetine) or cyclo-oxygenase (with indomethacin), depletion of biogenic amines (with reserpine) or blockade of calcium channels (with verapamil) did not modify the effects of 5-HT. 5. Taken together, the above results support our contention that the external carotid vasoconstrictor responses to 5-HT in vagosympathectomized dogs are mainly mediated by activation of sumatriptan-sensitive 5-HT1-like receptors. It must be emphasized, notwithstanding, that other mechanisms of 5-HT, including an interaction with a novel 5-HT receptor (sub)type and/or an indirect action that may lead to the release of a known (or even unknown) neurotransmitter substance cannot be categorically excluded.

Animals↗
PubMed1995

5-hydroxytryptamine: considerations about discovery, receptor classification and relevance to medical research.

Serotonin (5-hydroxytryptamine; 5-HT), an endogenous and ubiquitous monoamine, has become a subject of "explosive" research. Though its vasoconstrictor properties were first noticed in defibrinated or clotted blood, 5-HT was discovered 75 years later going through several denominations such as "enteramine, serotonin or 5-HT". Once confirmed that serotonin, enteramine and 5-HT were the same substance, the compound was synthesized and efforts with a view to analyze 5-HT receptors were performed. On the basis of the actions of 5-HT and other drugs on several smooth muscle experimental preparations, it was originally suggested that 5-HT could act via different receptors. Thus, Gaddum and Picarelli proposed the "D" and "M" classification based on the differential sensitivity of guinea pig ileum 5-HT-induced contraction to some drugs. Later on, this classification was confronted with the new Peroutka's 5-HT, and 5-HT2 classification derived from radioligand binding studies. Since these 5-HT receptors were being referred to by many names, an international committee formulated some criteria for the characterization and a framework for the nomenclature of 5-HT receptors into 5-HT1, 5-HT2 and 5-HT3 categories. More recently, functional evidence unrelated to activation of the above 5-HT receptor types was given and a new 5-HT (5-HT4) receptor was proposed to exist. From this stage, molecular biologists have been cloning several 5-HT receptors which are different from the various receptors (sub)types characterized thus far. This review is focused on the discovery of 5-HT and the evolution of the classification of 5-HT receptors, from historical remarks to the modern concepts about receptor characterization; furthermore, the relevance of this development to medical research is considered.

Animals↗
PubMed1994

Midline dose algorithm for in vivo dosimetry.

The high level of accuracy required in radiotherapy treatment dosimetry makes necessary good treatment quality control. The common way is the use of in vivo dosimetry equipment that allows the direct measurement of dose delivered to the patient. Control of homogeneity and constancy of the incident beam on the patient can be achieved directly by means of entrance dose measurement; however, control of dose delivered to tumours and internal organs is difficult because of the impossibility of a direct measurement. In this case calculations are made using external measurements (entrance and exit sides of the patient) to obtain the dose delivered. In this work, an algorithm that allows the real-time knowledge of midline dose as a function of thickness and entrance and exit doses coming from semiconductor detectors is presented. By having the electrometer connected to the computer, these three values (entrance, midline, and exit dose) are displayed instantaneously when the algorithm is included in the acquisition program. The model has been developed both for standard (source to surface distance = 100 cm) and special treatment techniques such as total body irradiation (SSD = 314 cm). There is a good agreement of experimental and calculated values with differences below 0.04%.

Algorithms↗