Control of Lobesia botrana (Lepidoptera: Tortricidae) by biodegradable ecodian sex pheromone dispensers.

Mating disruption with a high density of sex pheromone dispensers is a new strategy recently developed for the control of the moth Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae). Ecodian LB dispensers, made of low-cost biodegradable material, were formulated with 10 mg of (E,Z) -7,9-dodecadienyl acetate and placed at a rate of 1,600 dispensers per ha. Seasonal dispenser performances were studied using different methods. The female attractiveness disruption and the efficacy of the method were evaluated in the field. The release rates of field-aged Ecodian LB dispensers, measured directly by solid phase microextraction, was comparable with that of the standard monitoring lure after 50-60 d of field exposure and significantly lower beyond 60 d; however, at the end of the season, it was approximately 46 times higher than that of a calling L. botrana female. Electroantennographic recordings showed that dispensers of different field age strongly stimulated male antennae. In a wind tunnel test, dispensers elicited close-range approaches and direct source contacts irrespective of their age. In fields treated with Ecodian dispensers the attractiveness of traps lured with calling females and monitoring baits was significantly reduced. Our data suggest that Ecodian dispensers are active sources of pheromone throughout the season. The efficacy of Ecodian strategy for L. botrana control was comparable with standard mating disruption and curative insecticides.

Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors.

We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/- 4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL-2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl-D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1-induced cardiovascular and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N-methyl-D-aspartate receptors, a significant influence on endothelin-1-induced cardiovascular and behavioral effects after its injection into the periaqueductal area.

Cobalt blocks L-glutamate-induced apnea and arterial hypotension in the nucleus tractus solitarii of anaesthetized rats.

The local application of cobalt reversibly blocks calcium-channel conductance and therefore synaptic transmission. In this study pretreatment with a solution of cobalt (100 mM) in the nucleus tractus solitarii (NTS) of anaesthetized rats significantly blocked the apnea (P < 0.01) and arterial hypotension induced by L-glutamate (25 mM) and N-methyl-D-aspartate (0.4 mM) microinjected in the NTS. We conclude that cobalt causes these effects by acting at the postsynaptic level.

Participation of arginine vasopressin-mediated and adrenergic system-mediated mechanisms in the hypertension induced by intracerebroventricular administration of NMDA in freely moving rats.

Effects of intracerebroventricular (third ventricle) injection of N-methyl-D-aspartate (NMDA) on arterial blood pressure, on heart rate, on arginine vasopressin (AVP) and levels of catecholamines in plasma and on the behaviour of normotensive freely-moving rats have been evaluated. N-Methyl-D-aspartate significantly (P less than 0.01) increased arterial blood pressure and levels of catecholamines and AVP in plasma. With 0.1-1.0 micrograms/rat all animals presented psychomotor agitation, stereotyped movements, hyperexcitability, exophthalmus, dyspnoea, jumping, rearing and teething. The selective antagonist for NMDA receptors, 2-APV injected in the third ventricle, significantly (P less than 0.01) antagonized the hypertension, the increase in levels of catecholamines and AVP in plasma and behavioural effects. An antagonist of alpha 1 adrenergic receptors, prazosin (i.v.), an agonist of alpha 2 adrenergic receptors, clonidine (i.c.v.) and a relatively selective antagonist of V1 subtype of receptor of AVP, CGP 25838 (i.c.v. and i.v.), 15 min before NMDA, significantly (P less than 0.01) decreased the effects induced by the injections of NMDA. On the contrary, an antagonist of opiate receptors, naloxone (i.v.), 15 min before NMDA, significantly (P less than 0.01) increased the NMDA-induced modifications. Pretreatment with the antagonists at these doses, did not significantly modify the basal values of arterial blood pressure and behaviour. Only 2-APV sometimes induced ataxia, lasting about 5 min. This study points out an increase in the central sympathetic efferent activity and in release of AVP involved in the NMDA-induced cardiovascular and behavioural effects.

Metabotropic glutamate receptors are involved in the control of breathing at the medulla oblongata level of anaesthetized rats.

The goal of the present study was to identify sites in the medulla oblongata where metabotropic glutamate receptors are involved in regulating respiration. Unilateral microinjections (50 nl) of L-glutamate (L-glu) (10-25-50 mM) into the nucleus tractus solitarii (NTS) of anaesthetized rats elicited apnea (8.6 +/- 0.3 sec; 21.3 +/- 3.6 sec; 66.3 +/- 16.5 sec respectively; N = 6) and arterial hypotension (7.3 +/- 2.4 mmHg; 10.1 +/- 2.3 mmHg; 35.3 +/- 7.5 mmHg respectively; N = 6). Similarly, in other rats 1-aminocyclopentane-1, 3-dicarboxylic acid (ACPD) (1-5-10 mM), a selective agonist of metabotrophic glutamate receptors, also induced apnea (22.4 +/- 2.5 sec; 32.5 +/- sec; 92.5 +/- 1.4 sec respectively; N = 6) and arterial hypotension (12.7 +/- 2.2 mmHg; 19.6 +/- 4.3 mmHg; 26.5 +/- 1.5 mmHg respectively; N = 6). Paired experiments showed that unilateral microinjections of L-glu (50 mM) and ACPD (1 mM) into the nucleus retroambigualis (NRA) of anaesthetized rats elicited apnea (20.2 +/- 2.6 sec and 33.8 +/- 3.2 sec respectively; N = 6) and arterial hypotension (15.7 +/- 3.7 mmHg and 22.5 +/- 4.5 mmHg respectively; N = 6). The ACPD effects on apnea and hypotension in NTS and NRA were not prevented by a 3 min pretreatment with L-AP3 (30 mM), a putative antagonist of metabotropic glutamate receptors (19.5 +/- 1.4 sec; 12.3 +/- 3.2 mmHg and 30.6 +/- 2.9 sec; 23.4 +/- 3.8 mmHg respectively; N = 6). These data suggest that metabotropic glutamate receptors are involved in NTS and NRA regulation of cardiorespiratory functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of nitric oxide in cardiorespiratory regulation in the nucleus tractus solitarii.

The aim of this study was to investigate whether nitric oxide (NO) is involved in cardiorespiratory regulation in the nucleus tractus solitarii (NTS). Unilateral microinjections (50 nl) of the NO-donor, sodium nitroprusside (SNP, 40-100-200 mM), into the NTS of anaesthetized rats elicited dose-dependent apnea (7.3 +/- 2.3 sec; 28.6 +/- 5.7 sec; 35.6 +/- 6.4 sec, respectively; n = 6) and a decrease in arterial blood pressure (8.4 +/- 3.1 mmHg; 18.2 +/- 5.8 mmHg; 25.8 +/- 6.7 mmHg, respectively; n = 6). Similarly, unilateral micro-injections (50 nl) of another NO-donor, 3-morpholinosydnonimine (SIN-1, 20-40-100 mM), also induced apnea (5.1 +/- 2.4 sec; 8.7 +/- 4.3 sec; 26.3 +/- 6.4 sec, respectively; n = 6) and a decrease in arterial blood pressure (6.2 +/- 2.3 mmHg; 11.1 +/- 3.3 mmHg; 18.3 +/- 6.1 mmHg, respectively; n = 6). The SNP- and SIN-1-induced apnea and arterial blood pressure decrease were significantly (p < 0.01) blocked by a 3 min pretreatment with two calcium-channel blockers, diltiazem (0.1 mM) and cobalt (10 mM), while lower doses (diltiazem 0.01 and cobalt 1) were ineffective. Microinjections of diltiazem (0.01 mM) and cobalt (1 mM) alone did not induce any change in basal cardiorespiratory values like diltiazem (0.1 mM) and cobalt (10 mM). These data suggest that NO may be involved in NTS cardiorespiratory regulation via calcium-channel activation.

Effects of the polyamine spermidine on NMDA-induced arterial hypertension in freely moving rats.

We investigated the effect of the polyamine spermidine (SPD) (0.01-1 microgram/rat) on hypertension induced by N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) microinjected into the latero-caudal periaqueductal gray (PAG) area of freely moving rats. Pretreatment with a low dose of SPD (0.01 microgram/rat) significantly increased NMDA-induced hypertension. On the contrary, higher doses of SPD (0.1 and 1 microgram/rat) significantly decreased NMDA-induced cardiovascular changes. SPD alone did not modify arterial blood pressure. Arcaine (1 microgram/rat), a putative antagonist at the polyamine recognition site on NMDA receptors, when microinjected into the PAG area, prevented the negative but not the positive modulatory effects of SPD on the NMDA-induced cardiovascular changes. Pretreatment with SPD did not affect cardiovascular effects induced by quisqualic acid (QUIS), a non-NMDA receptor agonist. These data, in agreement with the in vitro results, suggest that at the level of the PAG area, the polyamines also show multiple actions at NMDA receptors in vivo.

Interactive role of L-glutamate and vasopressin, at the level of the PAG area, for cardiovascular tone and stereotyped behaviour.

The periaqueductal gray (PAG) area may modulate cardiovascular functions and trigger several stereotyped behavioural responses through a mechanism mediated by the interaction of L-glutamate with arginine vasopressin (AVP). Moreover, only the NMDA- but not the non-NMDA-glutamergic subtype receptors might participate in the control of these neurovegetative functions also modifying the homeostasis of the hypothalamic-neurohypophysis system. This latter effect may be due to the tight connections between the PAG area neurons to the more cephalic nuclei within the brainstem.

Pregnenolone sulfate increases the convulsant potency of N-methyl-D-aspartate in mice.

The neurosteroid pregnenolone sulfate is known to specifically enhance NMDA-gated currents in spinal cord neurons. The response does not appear to be mediated by the glycine/NMDA modulatory site. Here we found that pregnenolone sulfate significantly increased the convulsant potency of N-methyl-D-aspartate (NMDA), but not of pentylenetetrazol (PTZ). In agreement with previous in vitro reports showing that the glutamergic NMDA receptor is also specifically modulated by steroids, our findings suggest that pregnenolone sulfate selectively activates the NMDA receptors involved in convulsions in the intact animal.

NMDA receptors are involved at the ventrolateral nucleus tractus solitarii for termination of inspiration.

The purpose of the present study was to determine whether blockade of excitatory amino acid receptors at the ventrolateral nucleus of the tractus solitarius would influence respiratory activity. This was done by microinjecting excitatory amino acid receptor antagonists into the ventrolateral nucleus of the tractus solitarius of alpha-chloralose-anesthetized animals while monitoring respiratory activity using a Fleisch pneumotachograph and arterial blood pressure and heart rate. Bilateral microinjection of the NMDA receptor antagonist, 3-[(R)-carboxypiperazin-4-yl]-propyl-1- phosphomic acid (CPP), 5.62 nmol per side, produced an increase in inspiratory duration (+4 +/- 1.6 s, n = 8) which progressed to an apneustic pattern of breathing. Similar results were obtained with CPP microinjected into the ventrolateral nucleus of the tractus solitarius of three vagotomized animals. Bilateral microinjection of a second NMDA receptor antagonist, 2-amino-7-phosphono-heptanoic acid (AP7), 562 nmol per side, produced qualitatively similar effects on respiration as seen with CPP. In contrast, blockade of non-NMDA receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNXQ), 0.125 nmol per side, had very little effect on respiration. Activation of NMDA receptors at the ventrolateral nucleus of the tractus solitarius with bilateral microinjection of NMDA, 39 pmol, produced a large increase in expiratory duration (+11 +/- 3 s, n = 8), and apnea during the expiratory phase of the respiratory cycle in half of the animals studied. Similar results were obtained with D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazol-proprionate (AMPA). These results indicate that an endogenous excitatory amino acid released at the ventrolateral nucleus of the tractus solitarius and acting at the NMDA receptor, plays a significant role in respiratory timing.

Hypothalamic paraventricular nucleus involvement in the pressor response to N-methyl-d-aspartic acid in the periaqueductal grey matter.

The aim of this study was to demonstrate paraventricular hypothalamic nucleus (PVN) involvement in the cardiovascular changes induced by N-methyl-d-aspartic acid (NMDA) microinjections at the level of periaqueductal grey (PAG) matter. The study was carried out in anaesthetized rats and the arterial blood pressure monitored by a polygraph. NMDA injections (0.68-6.8 nmol/rat) into the PAG area induced a significant increase in blood pressure. After pretreatment by injection of the NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (2-APV, 0.05-5 nmol/rat) into the PVN, administration of NMDA (0.68 nmol/rat) into the PAG area elicited a decrease, rather than an increase, of blood pressure. We observed a significant reduction of the pressor effect induced by 6.8 nmol/rat NMDA after 2-APV injection into the PVN. 2-APV injection into the dorsomedial hypothalamic nucleus, an area near the PVN, did not modify the increase in blood pressure induced by NMDA in the PAG area. We suggest the existence of a glutamatergic connection between the PAG area and the PVN in the cardiovascular effects of NMDA.

[Local administration of somatostatin in joint diseases in athletes]. / Somatostatina per via locale nelle patologie articolari degli sportivi.

Somatostatin is a hormone produced by the hypothalamus, and is widely diffused outside the CNS. It inhibits the secretion of many glands. Recently it has been shown that somatostatin has been proposed in the treatment of phlogistic diseases of the joints by intra-articular administration. The authors show the results of a study conducted in 16 patients (athletes) with arthrosynovitis or tendinitis of the knee or of the ankle, in which somatostatin was administered (250 mg/treatment, 1 treatment/week). Somatostatin significantly reduced pain, improved movement function and decreased the effects of pain on daily activities. The treatment was very well tolerated locally and generally. In conclusion, somatostatin may be considered useful in the treatment of articular and tendineous phlogistic diseases, almost in athletes.

Amides of 1,3,3-trimethyl-n-[(2-pyridyl)methyl]-2-oxabicyclo [2.2.2]octan-6-amine with depressant and antiarrhythmic activities.

The synthesis of 1,3,3-trimethyl-N-[(2-pyridyl)methyl]-2- oxabicyclo [2.2.2]octan-6-amine (II) (exo, endo mixture) starting from 1,3,3-trimethyl-N-nitro-2-oxabicyclo [2.2.2]octan-6-imine (I), as well as of a series of amides (III) derived from the above amine, is described. Some compounds (III) showed remarkable depressant and antiarrhythmic activities in rats and mice, respectively, whereas the clofibric acid amide (III e) showed an appreciable hypolipidemic activity in rats. Moreover, the above compounds usually exhibited a moderate infiltration anesthesia in mice, as well as a weak hypotensive and bradycardic activity in rats.

2H-[1]benzothiepino [5,4-b]pyran derivatives with local anesthetic and antiarrhythmic activities.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-[1]benzothiepino [5,4-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzothiepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The 4-methylphenylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine and the 4-morpholino derivative showed an antiarrhythmic activity in rats comparable to that of quinidine.

5-[4-(omega-dialkylaminoalkoxy)phenylmethylene] -1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ones with platelet antiaggregating and other activities.

The synthesis of 5-[4-(omega-dialkylaminoalkoxy)phenylmethylene]- 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ones 3 by reaction of some 4-(omega-dialkylaminoalkoxy)benzaldehydes with (+)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-one in the presence of sodium methoxide is described. Some aminoethers 3 showed platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak antiarrhythmic activity in rats and moderate infiltration anesthesia in mice.

Modulation by glycine on vascular effect of NMDA: in vivo experimental researches.

The present study has been carried out to determine if glycine, an allosteric modulator of NMDA receptor, is involved in the vascular effect induced by the activation of the CNS NMDA receptors.Icv NMDA (from 0.01 to 1µg/rat in the 3rd ventricle) determined a significant increase in arterial blood pressure in conscious freely moving rats. Moreover, the hypertension was associated with behavioural modifications (jumping, rearing, teething and running). Glycine pretreatment (1 and 10µg/raticv), significantly increased the NMDA hypertension. Alone glycine did not cause any arterial blood pressure modification while it induced a slight sedation. HA-966 (an antagonist of the glycine site on NMDA receptor) administration (1-10µg/raticv 5 min before glycine) significantly antagonized the glycine effects on NMDA hypertension.Alone HA-966 neither modified arterial blood pressure nor antagonized NMDA hypertension. In conclusion, our investigations confirm NMDA receptor involvement in cardiovascular function and they demonstrate that in vivo glycine positively modulates NMDA receptor.

Modulation by glycine on vascular effects of NMDA:in vivo experimental research.

The present study has been carried out to determine if glycine, an allosteric modulator of NMDA receptor, is involved in the vascular effect induced by the activation of the CNS NMDA receptors.Icv NMDA (from 0.01 to 1µg/rat in the 3rd ventricle) caused a significant increase in arterial blood pressure in conscious freely moving rats. Moreover, the hypertension was associated with behavioural modifications (jumping, rearing, teething and running). Glycine pretreatment (1 and 10µg/raticv), significantly increased the NMDA hypertension. Glycine alone did not cause any arterial blood pressure modification while it induced a slight sedation. HA-966 (an antagonist of the glycine site on NMDA receptor) administration (1-10µg/raticv 5 min before glycine) significantly antagonized the glycine effects on NMDA hypertension.Alone HA-966 neither modified arterial blood pressure nor antagonized NMDA hypertension. In conclusion, our investigations confirm NMDA receptor involvement in cardiovascular function and they demonstrate thatin vivo glycine positively modulates NMDA receptors.

Research on heterocyclic compounds. XXVI. Antiinflammatory and related activities of some 2-phenylimidazo[1,2-b]pyridazines.

Five acidic phenyl derivatives of the imidazo[1,2-b]pyridazine system were subjected to some tests in vivo in order to evaluate their biological activity. Antiinflammatory activity was studied by means of the carrageenin rat paw edema, whereas writhing induced in mice by acetic acid was used to assess analgesic activity. The irritative and ulcerogenic action on the rat gastric mucosa was examined after oral administration of larger doses. The inhibitory activity on platelet malondialdehyde production was studied in vitro. The experimental results are discussed from the point of view of structure-activity relationships and mode of action.

Effects of dietary vitamin D deficiency on the cardiovascular system.

Experiments were performed on normotensive rats exposed to vitamin D deficient and control diets from the 22nd to the 180th day of age. In 60-120- and 180-day-old rats. The following parameters were evaluated: a) The vasomotor responses elicited by receptor agonists in the absence and in the presence of the respective antagonists [L-norepinephrine (NE) before and 5 min after prazosin; L-isoprenaline (I) before and 5 min after DL-propranolol; L-dopamine (DA) before and 5 min after L-sulpiride or SCH 23390 or chlorpromazine; acetylcholine (Ach) before and 5 min after atropine; histamine (H) before and after chlorpheniramine; 5-hydroxytryptamine (5-HT) before and 5 min after methysergide or ketanserin]; by carotid-sinus baroreceptor stimulation (CO) before and 5 min after hexamethonium, and by electrical stimulation of the vagus peripheral head (V) before and after atropine; b) Reflex tachycardia elicited by bilateral carotid occlusion (CO) (for 40 sec) and by sodium nitroprusside; c) Catecholamine (norepinephrine, epinephrine) and arginine-vasopressin plasma levels; d) Cholesterol, triglyceride and electrolyte (Na+, K+, Cl-, Ca2+) serum levels. Our results showed that vitamin D deficient diets induced a decrease in pressor responses to NE and CO, and an increase in hypotensive responses to I, DA, Ach, H, 5-HT and V. Changes of arterial blood pressure, heart rate, catecholamine and arginine-vasopressin plasma levels were not observed. Cholesterol, triglyceride and electrolyte (Na+, K+, Cl-) serum levels were not modified, while Ca2+ serum levels decreased. In conclusion, our data suggest that vitamin D depletion can induce changes of pressor and depressor vasomotor responses and suppose a direct role for vitamin D in regulating vasomotor reactivity.

Prenatal and postnatal vanadium exposure in rats: effect on vasomotor reactivity development of pups.

The study has been carried out on albino rats pre and/or postnatally exposed to vanadate (1 and 10 mg/dl). In pups pre- and postnatal or postnatal vanadate exposure significantly decreased on the 30th and 60th day of age the pressor response to 1-noradrenaline, and increased the pressor response to sinus-carotid baroreceptor stimulation and the hypotensive responses to 1-isoprenaline and acetylcholine. The effects were observed at vanadate doses that did not interfere with gestation, maternal and pup body weight, maternal systolic arterial blood pressure during pregnancy, and pup systolic arterial blood pressure. These doses have not determined any macroscopic teratogenic effects.