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Capsular contracture, a common complication of breast implant reconstruction following postmastectomy radiotherapy (PMRT), represents a challenge for plastic surgeons. Regenerative surgery with multiple autologous fat grafts (lipobed) before replacing the implant has been proven to be a satisfactory approach in the radio-damaged breast. Currently, in literature, there are no data available on the histological features of irradiated capsules after regenerative surgery. We enrolled 80 patients after immediate subpectoral alloplastic breast reconstruction, with indication for revision surgery due to grade IV capsular contracture developed after PMRT. Forty patients were undergoing multiple fat grafting (lipobed group, mean age 48) and 40 patients were not undergoing multiple fat grafting (non-regenerative surgery (NRS) group, mean age 49). The removed capsules were addressed to histological and immunohistochemical assessment. The capsules of the lipobed group patients compared with NRS group patients showed: a lower mean thickness (602.17 versus 670.43 µm; P = 0.013), a lower collagen fiber alignment (median value of angle deviation: 30.34 versus 18.38; P = 0.001), a lower immunohistochemical positivity for myofibroblasts (α-smooth muscle actin [α-SMA] expression: 12.5% versus 52.5%; P = 0.00), a higher immunohistochemical positivity for estrogen receptor-β (ER-β; 80% versus 20%; P = 0.00), and a lower immunohistochemical positivity for estrogen receptor-α (ER-α; 53.3% versus 16.7%; P = 0.00). The histological and immunohistochemical differences found are possibly due to alterations in the extracellular microenvironment determined by grafted fat., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background:  After anterolateral thigh (ALT) flap harvesting, skin graft of the donor site is commonly performed. When the defect width exceeds 8 cm or 16% of thigh circumference, it can determine lower limb function impairment and poor aesthetic outcomes. In our comparative study, we assessed the functional and aesthetic outcomes related to ALT donor-site closure with split-thickness skin graft compared with thigh propeller flap., Methods:  We enrolled 60 patients with ALT flap donor sites. We considered two groups of ALT donor-site reconstructions: graft group (30 patients) with split-thickness skin graft and flap group (30 patients) with local perforator-based propeller flap. We assessed for each patient the range of motion (ROM) at the hip and knee, tension, numbness, paresthesia, tactile sensitivity, and gait. Regarding the impact on daily life activities, patients completed the lower extremity functional scale (LEFS) questionnaire. Patient satisfaction for aesthetic outcome was obtained with a 5-point Likert scale (from very poor to excellent)., Results:  In the propeller flap group, the ROMs of hip and knee and the LEFS score were significantly higher. At 12-month follow-up, in the graft group, 23 patients reported tension, 19 numbness, 16 paresthesia, 22 reduction of tactile sensitivity, and 5 alteration of gait versus only 5 patients experienced paresthesia and 7 reduction of tactile sensitivity in the propeller flap group. The satisfaction for aesthetic outcome was significantly higher in the propeller flap group., Conclusion:  In high-tension ALT donor-site closure, the propeller perforator flap should always be considered to avoid split-thickness skin graft with related functional and aesthetic poor results., Competing Interests: None declared., (Thieme. All rights reserved.)

Hafting of stone tools was an important advance in the technology of the Paleolithic. Evidence of hafting in the Middle Paleolithic is growing and is not limited to points hafted on spears for thrusting or throwing. This article describes the identification of adhesive used for hafting on a variety of stone tools from two Middle Paleolithic caves in Latium, Fossellone Cave and Sant'Agostino Cave. Analysis of the organic residue by gas chromatography/mass spectrometry shows that a conifer resin adhesive was used, in one case mixed with beeswax. Contrary to previous suggestions that the small Middle Paleolithic tools of Latium could be used by hand and that hafting was not needed since it did not improve their functionality, our evidence shows that hafting was used by Neandertals in central Italy. Ethnographic evidence indicates that resin, which dries when exposed to air, is generally warmed by exposure to a small fire thus softened to be molded and pushed in position in the haft. The use of resin at both sites suggests regular fire use, as confirmed by moderate frequencies of burnt lithics in both assemblages. Lithic analysis shows that hafting was applied to a variety of artifacts, irrespective of type, size and technology. Prior to our study evidence of hafting in the Middle Paleolithic of Italy was limited to one case only., Competing Interests: The authors have declared that no competing interests exist.

Background: Phthorimaea operculella is a key pest of potato. The authors characterised the P. operculella olfactory system, selected the most bioactive host plant volatiles and evaluated their potential application in pest management. The electrophysiological responses of olfactory receptor neurons (ORNs) housed in long sensilla trichodea of P. operculella to plant volatiles and the two main sex pheromone components were evaluated by the single-cell recording (SCR) technique. The four most SCR-active volatiles were tested in a laboratory oviposition bioassay and under storage warehouse conditions., Results: The sensitivity of sensilla trichodea to short-chained aldehydes and alcohols and the existence of ORNs tuned to pheromones in females were characterised. Male recordings revealed at least two types of ORN, each of which typically responded to one of the two pheromone components. Hexanal, octanal, nonanal and 1-octen-3-ol significantly disrupted the egg-laying behaviour in a dose-dependent manner. Octanal reduced the P. operculella infestation rate when used under storage conditions., Conclusions: This work provides new information on the perception of plant volatiles and sex pheromones by P. operculella. Laboratory and warehouse experiments show that the use of hexanal, octanal, nonanal and 1-octen-3-ol as host recognition disruptants and/or oviposition deterrents for P. operculella control appears to be a promising strategy., (© 2013 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

We report the effects of some bisorbicillinoids isolated from biomass of the fungus Trichoderma citrinoviride on settling and feeding preference of the aphid Schizaphis graminum. Purification of the fungal metabolites was carried out by a combination of column chromatography and thin-layer chromatography using direct and reverse phases. Chemical identification was performed by spectroscopic methods including nuclear magnetic resonance and mass spectrometry. The identified bisorbicillinoids appeared to be bislongiquinolide, its 16,17-dihydro derivative, trichodimerol, and dihydrotrichodimerol. A feeding preference test with alate morphs of S. graminum was used to identify the active fractions. Among the four bisorbicillinoids, dihydrotrichodimerol and bislongiquinolide influenced aphid feeding preference, restraining specimens from settling on leaves treated with metabolites. Taste neurons sensitive to these compounds, particularly to bislongiquinolide, were located on tarsi of the S. graminum alate morphs.

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.

Background: Six Sigma methodology is a data management process that can be used to achieve a goal of near perfection in process performance. An audit of 615 surgeries over 2 mo revealed only 38% of noncardiac patients admitted on the day of surgery at our institution received perioperative antimicrobial prophylaxis within the target interval of < or =60 min before incision., Methods: Six Sigma methodology was used to improve our process of timing of antimicrobial prophylaxis administration. A multidisciplinary team was assembled which identified seven process inputs by which patients receive antimicrobial prophylaxis. Interventions for improvement included reinforcement of use of preoperative antibiotic order forms, eliminating administration of antibiotics in the preoperative admission area, and sending appropriate antibiotics and IV tubing with the patient to the operating room. We concurrently developed a control plan to sustain this improvement using a recently deployed electronic anesthesia record keeping system using real-time measurement and reporting capabilities of antimicrobial prophylaxis administration. After defining the new process and undertaking a system-wide educational effort, implementation was begun with data collection and analysis occurring over the next 7 mo., Results: For the 8-mo postintervention interval, there was a significant improvement with 86% of 1716 surgical patients receiving their antibiotic prophylaxis within the specified time frame (P < 0.01). The time interval for antibiotic administration before surgical incision also decreased from a preintervention mean of 88 (CI 56-119 min) to 38 min (CI 25-51 min) (P < 0.01)., Conclusion: We conclude that Six Sigma methods were used to successfully improve our process for timing of perioperative antibiotic prophylaxis before surgical incision. An electronic anesthesia record keeping system is a useful tool to monitor this process improvement.

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.