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We describe a case of basal cell carcinoma (BCC) situated on the external upper margin of the right eyelid in a young man aged 28 years. The tumor was diagnosed as an "extended wart in a degenerative phase" and removed during reconstructive plastic surgery. No pathologic examination was performed. Seven years later, the operation was followed by a first recurrence. Pathologic examination was then performed, and the diagnosis was BCC. Therapy was with radiotherapy and chemotherapy. Subsequent recurrences were treated with radiotherapy and surgery (enucleation, exenteration of the orbit), but the evolution of the tumor was not halted. It ended 25 years after its first manifestation with the death of the patient of a hemorrhage of the upper airways during an operation, the aim of which was to reexamine the orbital cavity. The autopsy revealed intracranial extension of the tumor, and all the histological examinations confirmed the diagnosis. No histopathological feature was found that could differentiate a particularly aggressive nature of the tumor. Basal cell carcinoma is a tumor more frequently encountered in elderly patients. Its appearance in a young subject may cause grounds for suspicion, requiring initial radical surgical treatment and careful surveillance of the evolution of the lesion. This case documents the fatal consequences that may arise from the failure to recognize BCC in its first manifestation and highlights the ineffectiveness of repeated radiation and surgical therapy against continual recurrence.

The present study evaluated the sensitivity of several brain sites to the inhibitory effect of the tachykinin (TK) NK-3 receptor agonist aminosenktide (NH2-SENK) on 10% ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring rats. Attention was focused on limbic structures involved in alcohol-seeking behavior and endowed with TK NK-3 receptors. NH2-SENK was bilaterally injected into the shell of the nucleus accumbens (NACC), the medial amygdala (AMY), the dorsal hippocampus (HIPP), the ventral tegmental area (VTA), the bed nucleus of the stria terminalis (BNST), the lateral hypothalamus (LH), and the nucleus basalis magnocellularis (NBM). NH2-SENK (injected up to 25-75 ng/site) into the NACC, AMY, HIPP, and VTA did not significantly modify ethanol intake. Injection of NH2-SENK into the BNST reduced ethanol intake at doses of 25 ng/site or higher, but the same doses also reduced water intake in water-deprived rats and food intake in food-deprived rats. Injection of NH2-SENK into the LH or the NBM at doses of 0.5, 5, or 25 ng/site inhibited 10% ethanol intake even at the lowest dose tested without affecting either food or water consumption in deprived animals. Present results indicate that the LH and the NBM are highly sensitive to the inhibitory effect of the TK NK-3 receptor agonist NH2-SENK on ethanol intake. TK peptides have been shown to evoke conditioned place preference following injection in the LH or the NBM, suggesting that in these brain sites the effect of TK agonists on ethanol intake might be due to interference with reward processes.

The order of potency of tachykinin (TK) receptor agonists suggests that TK NK-1 receptors mediate their inhibitory effect on water intake induced by intracerebroventricular (i.c.v.) injection of angiotensin II (AngII) in rats. The present study was aimed at further evaluating which TK receptor subtype mediates the effect, using selective antagonists for the TK receptor subtypes. Pulse i.c.v. injection of the TK agonist neuropeptide gamma (NP gamma), 31-250 ng/rat, markedly inhibited AngII-induced water intake. The i.c.v. injection of the NK-1 receptor antagonist SR14033, 0.5 microgram/rat, significantly reduced, while 1 microgram/rat completely abolished the inhibitory effect of NP gamma, 125 ng/rat. The selective NK-2 receptor antagonist SR48968 and the selective NK-3 receptor antagonist R820 were devoid of any effect up to the i.c.v. dose of 2 micrograms/rat. On the other hand, i.c.v. injection of SR140333, 1 microgram/rat, did not increase drinking induced by i.c.v. injection of AngII, 0.1-10 ng/rat, and did not increase drinking in water sated or water deprived rats. The results of the present study confirm that central TKergic mechanisms inhibit AngII-induced drinking in rats, and provide further evidence that TK NK-1 receptors mediate the effect. Failure of i.c.v. injected SR 140333 to increase AngII-induced drinking, as well as water intake in sated or deprived rats suggests that brain NK-1 receptor mechanisms apparently do not exert a tonic control on AngII-induced drinking and, in general, on water intake in rats. From a pharmacological point of view, the inhibitory effect of TKs on the dipsogenic action of AngII can represent a functional test for activity at central NK-1 receptors in rats.

Bombesin (BN) elicits in the rat important behavioural modifications, including inhibition of food and of water intake. Recently, it has been observed that the peptide also inhibits the intake of sodium chloride. To state whether BN possesses a selective antinatriorexic effect or it elicits only an aspecific depression of ingestive behaviour, we studied the effects of this peptide on the intake of sodium, water or sucrose of Wistar rats after injections into the fourth brain ventricle or into selected brain areas involved in the control of sodium intake, containing BN-like peptides and/or their precursors or specific receptors. We observed that: a) BN (100-200 ng/rat) injected into the fourth brain ventricle inhibits not only the intake of 2% NaCl of sodium depleted rats but also that of water and of 5% sucrose; b) BN (5-50 ng/rat) administered into the nucleus of the solitary tract and the medial amygdala does not influence the intake of these fluids and c) BN (5-50 ng/rat) injected into the paraventricular nucleus does not influence the intake of water and 5% sucrose but potently inhibits that of 2% NaCl. We concluded that the inhibitory effect elicited on salt intake by intracranial administration of BN is selective for this behaviour and is not the expression of an aspecific depression of ingestive behaviour.

In 12 patients with superior vena cava syndrome secondary to malignant disease, duplex Doppler ultrasound (US) was performed in the internal mammary veins. In all patients, flow was retrograde. After stent placement, flow direction was again antegrade on one side (17%) or both sides (83%). During follow-up in the internal mammary veins, blood flow remained unchanged in 10 patients and retrograde flow recurred in two patients at 2 and 5 months, respectively. In these two patients, helical computed tomography showed stent failure. Successful treatment in one patient normalized the direction of flow in the internal mammary vein. Doppler US in the internal mammary veins allowed accurate evaluation of function of superior vena cava stents.

It is well-known that central administration of tachykinins (Tks) inhibit salt intake in rats. Recent studies have shown that conditions that arouse salt appetite, such as adrenalectomy and sodium depletion, induce a decrease in preprotachykinin-A (PPT-A) mRNA in discrete regions of the rat brain, suggesting that reduced levels of PPT-A mRNA in the brain may have a permissive role on the expression of salt appetite. It has also been shown that spontaneously hypertensive rats (SHR) show higher avidity for salty solutions than their normotensive control Wistar-Kyoto (WKY) rats. In this regard, the present study tested whether SHR and WKY rats differ in expression of the gene coding for PPT-A, the precursor for Tks peptides. Using semi-quantitative in situ hybridization histochemistry, we examined the level of PPT-A mRNA in discrete rat brain regions of SHR and WKY rats under no treatment, after 1 or 3 days of Na+ depletion. Levels of PPT-A mRNA were analysed in the olfactory tubercle (Tu), in the lateral olfactory tubercle (LOT), in the dorsal and ventral caudate putamen (d/v CPu), in the medial preoptic area (mPOA), in the bed nucleus of the stria terminalis (BNST), in the habenula (Hb) and in the postero-dorsal part of the amygdala (MePD). Semi-quantitative analysis of silver grains revealed a 27.5% lower expression of the PPT-A mRNA levels in SHR opposite to WKY rats under no treatment in v-CPu, mPOA, BNST and Hb. 1 day of Na+ depletion reduced PPT-A mRNA levels when opposite to Na+-repleted animals in Tu and mPOA in both SHR and WKY rats. On the other hand, when comparing SHR and WKY rats after 1 day of Na+ depletion, a 26% lower level of PPT-A mRNA was detected in Tu and d-CPu of SHR opposite to WKY rats whereas a 14% and an 18% lower level was detected in v-CPu and Hb, respectively. A lower expression of PPT-A mRNA in SHR compared to WKY rats was also found in BNST and MePD, although no statistical significance was detected in these two brain areas. In the last experiment, 3 days of Na+ depletion reduced PPT-A mRNA levels in mPOA while negligibly increased mRNA levels in d-CPu and v-CPu, in BNST, Hb and MePD, both in SHR and WKY rats. Conversely, when making comparisons between the two strains, a 35% lower level of PPT-A mRNA in SHR with respect to WKY rats was found after 3 days of Na+ depletion in d-CPu, v-CPu and mPOA. A lower gene expression, even though not statistically significant, was found in Tu, LOT, MePD. These findings show a consistent difference of PPT-A mRNA levels in discrete regions of the SHR brain opposite to WKY rats and confirm that 1 day of Na+ depletion reduces PPT-A mRNA in discrete brain regions. Since SHR are notoriously more salt-avid than WKY rats and Tks are potent inhibitors of sodium intake, the down-regulation of PPT-A mRNA may contribute to the higher natriophilia and, therefore, to the etiology of the hypertensive disease.

Transcatheter chemoembolization with various drugs is employed for palliative treatment of hepatocellular carcinoma. Thirty-seven patients (33 with Child A or B cirrhosis) were treated with 14 mg/m2 of Mitoxantrone and up to 20 ml of Lipiodol, followed by Gelfoam embolization as indicated. Sixty-nine cycles were given, with mean (+/-SD) Lipiodol and emulsified Mitoxantrone doses of 11.3 +/- 3.8 ml and 11.8 +/- 5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123 +/- 60 days. Thirty patients had Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. At the first cycle, 10 patients underwent serial measurements of serum Mitoxantrone up to two hours after a full dose of emulsified drug. Drug levels resulted much lower than those reported after plain arterial infusion, with AUC levels (+/-SE) of 5924 +/- 1015 and 4381 +/- 429 ng/ml x 120 min in 6 and 4 cases treated with and without Gelfoam, respectively. No treatment related deaths occurred. Complications were mild and transient, including nausea vomiting in most cases, fever > 38 degrees C 67%, pain 74%, ascites 8% jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor response) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with Mitoxantrone deserves further evaluation in randomized studies.

Injections in the nucleus basalis magnocellularis (NBM) of the tachykinin (TK) NK-3 receptor agonist [Asp5,6,MePhe8]substance P(5-11), also referred to as amino-senktide (NH2-SENK), markedly reduced alcohol intake in genetically selected alcohol-preferring rats, offered 10% ethanol 2 h/day. The threshold dose in the NBM was 0.5 ng/site, while neither 1 nor 10 ng/rat of NH2-SENK inhibited alcohol intake following administration into the lateral ventricle. Injection of NH2-SENK, 25 ng/site, in the NBM did not modify water or food intake in water deprived rats, providing evidence for the behavioral selectivity of the effect on ethanol intake. The selective TK NK-3 receptor antagonist, R-820, injected in the NBM at the dose of 1000 ng/site 5 min before NH2-SENK 5 ng/site, significantly reduced the effect of NH2-SENK. The selective TK NK-1 receptor agonist [Sar9,Met(O2)11]substance P inhibited alcohol intake following injection in the NBM only at 25 ng/site; but the same dose induced marked grooming and inhibited also water intake in water deprived rats. The present results confirm that TK NK-3, but not NK-1, receptor agonists selectively inhibit ethanol intake in alcohol-preferring rats and suggest that the NBM is a site of action for their effect.

Our previous studies have shown that i.c.v. injections of the selective tachykinin NK3 receptor agonist [Asp5,6,MePhe8]substance P(5,11), also referred to as NH2-senktide (NH2-SENK), inhibit salt intake in rats in a two-bottle intake test. The present study evaluated the effect of i.c.v. injections of NH2-SENK on intraoral intake and taste reactivity responses elicited by intraoral infusions of water or NaCl solutions (0.03, 0.15, 0.25 and 0.5 M) in sodium-replete rats. The effect of NH2-SENK on the intake of 0.03, 0.15 and 0.25 M NaCl solutions and of water was also evaluated in a two-bottle intake test. In this test, 31 ng/rat of NH2-SENK significantly reduced the intake of 0.15 and 0.25 M NaCl, but not that of water or of 0.03 M NaCl. The dose of 31 ng/rat of NH2-SENK reduced the intraoral intake of 0.25 and 0.5 M NaCl, while 125 ng/rat reduced the intraoral intake of 0.15, 0.25 and 0.5 M NaCl; neither dose reduced the intraoral intake of water or of 0.03 M NaCl. Taken together, these findings indicate that the effect of NH2-SENK on salt intake is dependent on the concentration of the NaCl solution offered; moreover, the intraoral intake data suggest that the effect of NH2-SENK on salt intake may be exerted to a large extent on the consummatory processes of salt ingestion. NH2-SENK, 31 or 125 ng/rat, altered taste reactivity responses shortly after the beginning of the intraoral infusion. The most peculiar effect was an increase in passive dripping during the first min of intraoral infusion of 0.15, 0.25 and 0.5 M, but not of water or of 0.03 M NaCl. This finding suggests that NH2-SENK elicits a prompt alteration of taste mechanisms for salt, which may account for its antinatriorexic action.

Objectives: To evaluate the reliability of helical computed tomography (CT) as sole preoperative diagnostic technique for abdominal aortic aneurysms (AAA) and to compare these results with the surgical findings., Materials: Thirty-three patients undergoing elective surgical repair., Methods: Helical CT, Doppler exam of lower limbs, digital angiography, in case of peripheral vascular disease, and intraoperative evaluation., Results: Helical CT correctly detected, in all cases, the proximal and distal extent of the AAA. The coeliac axis and its branches, the superior mesenteric artery and renal vessels as well as the inferior vena cava were always clearly depicted, showing anatomical variants or pathological involvement in 14 patients (42.4%)., Conclusions: Helical CT can be used as the sole method for preoperative imaging of AAA. It allows a complete and precise evaluation of size, extent and relationship of the AAA, the surrounding vessels and other abdominal structures.

Neuropeptide gamma (NP gamma) is a 21 aminoacid peptide belonging to the tachykinin (TK) family and including neurokinin A (NKA) in its C-terminal sequence. NP gamma possesses higher affinity than NKA for central NK-2 receptors; it shows lower affinity for NK-1 receptors, however, it potently stimulates salivary secretion, which is mediated by NK-1 receptor activation. Pulse intracerebroventricular (pICV) injection of TKs selectively inhibits water intake in rats. Our studies have suggested that NK-1 receptors may mediate the inhibition of angiotensin II-induced drinking, while NK-2 receptors that of drinking induced by cell dehydration. The present study evaluated the effect of pICV injections of NP gamma on water intake in rats. The injection of NP gamma, 8-250 ng/rat, markedly inhibited angiotensin II-induced drinking, and its effect was blocked by the NK-1 receptor antagonist WIN 62577. NP gamma potently inhibited also drinking induced by SC hypertonic NaCl load or water deprivation. The threshold dose for these effects was 31 ng/rat. Also carbachol-induced drinking was inhibited, but at higher doses. On the other hand, NP gamma did not modify food intake in food deprived rats or 0.1% saccharin intake in water and food sated rats, at the same doses effective on drinking. Present findings support the idea that TKs selectively inhibit water intake in rats and are in keeping with our hypothesis that NK-1 and NK-2 receptors mediate, respectively, inhibition of angiotensin II- and cell dehydration-induced drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study evaluated the effect of SC injections of the selective NK3 tachykinin agonist, Suc-[Asp6,MePhe8]substance P(6-11), also referred to as senktide (SENK), on 8% alcohol intake in genetically selected alcohol-preferring rats. Animals were offered access to 8% ethanol for 2 h/day (between 1800 and 2000 h) and to tap water for 4 h/day (between 1800 and 2200 h); SENK was injected 10 min before access to fluids. The peptide significantly reduced alcohol intake at doses of 125 and 250 micrograms/kg, but not at 62.5 micrograms/kg. The reduction in alcohol intake was accompanied by a sharp increase in water intake, so that total fluid intake was never significantly modified. The same SC doses of SENK did not modify water intake in rats with access to water, as the only fluid, for 4 h/day. In food-deprived rats food intake was not altered by 125 micrograms/kg, whereas 250 micrograms/kg produced a reduction in food intake that was smaller in intensity and shorter lasting than the reduction in alcohol intake. The same doses of SENK did not modify 0.1% saccharin intake, nor did they elicit major competing behaviors. The results of the present study are in keeping with those obtained following central injection of NK3 agonists, and show that a behaviorally selective reduction of alcohol intake can be evoked also by peripheral administration of SENK.

The present study investigated the effect of 24-h continuous ICV infusion of four different tachykinins on the enhanced need-free sodium intake induced by previous repeated sodium depletions in female rats. Female rats were employed because, in response to sodium depletions, they develop a higher need-free sodium intake than male rats. The following tachykinins were used: eledoisin, substance P (SP), [Sar9,Met(O2)11]SP and [Asp5,6,MePhe8]SP(5-11), also referred to as NH2-senktide, all at the same doses of 300 or 600 ng/h x 24 h. Food pellets, water, and 3% NaCl sodium solution were freely available. Eledoisin and NH2-senktide were more potent than SP in reducing the need-free sodium intake. On the other hand, [Sar9,Met(O2)11]SP had no effect. None of the tachykinins employed completely blocked the intake. Water intake was reduced, but this reduction was apparently a consequence of reduced intake of hypertonic sodium chloride solution, because at the same doses TKs did not inhibit water intake in a single-bottle test. Food intake remained unchanged at either dose used. These findings confirm previous studies in which pulse injection of the same drugs potently inhibited sodium intake. They also demonstrate that tachykinins endowed with high affinity for the NK3 receptor are the most potent in inhibiting sodium intake. Furthermore, these findings indicate that the tachykinins reduce the need-free sodium intake only during the infusion period, indicating that in these conditions they do not evoke either aversion for salt, or toxic consequences in the follow-up period.

Aims and Background: In patients undergoing potentially curative surgery for colorectal adenocarcinoma, the presence of occult disease is thought to be responsible for distant metastases, particularly of the liver. During the 1980's preoperative intra-arterial chemotherapy was used in patients with adenocarcinoma of the sigmoid colon since it was thought that the biological effects induced by radiation in rectal lesions could be induced by cytotoxic agents in sigmoid cancer which was found to be less sensitive to radiation. The aim of the present paper is to report long-term results of an early pilot study on 20 patients with sigmoid colon adenocarcinoma treated with a 6 preoperative intra-arterial infusion of mitomycin-C followed by curative surgery., Methods: From January 1980 to December 1986, 20 patients with adenocarcinoma of the sigmoid colon were treated with a 6 hours preoperative intra-arterial infusion of mitomycin-C followed by potentially curative surgery (Group A). Eighteen hours prior to surgery the patients underwent selective arteriography of the inferior mesenteric artery through puncture of the femoral artery at the inguinal fold. The Seldinger technique was applied and Cook BP6 catheter was used. At the end of the examination, the catheter was positioned in the inferior mesenteric artery and mitomycin-C, 10 mg/m2, was infused in 500 ml of normal saline over a 6 hours period after which the catheter was definitively removed. Within 18 hours following intra-arterial mitomycin-C infusion all 20 patients underwent potentially curative surgery of their sigmoid adenocarcinoma. During the same period, 48 comparable sigmoid colon cancer patients underwent potentially curative resection alone (Group B)., Results: At 5 years overall recurrence rate was 30% and 39.6% in Group A and B patients, respectively (P = n.s.). In patients with Stage C disease, recurrence was less frequently observed in Group A (44.4%) than in Group B (77.7%) (P = n.s.). Overall survival at 5 years was comparable in the two groups of patients (70% and 64% for Group A and B, respectively) and median survival was > 60 months in both groups. In patients with Stage C lesions, there was a trend for improved survival at 5 years in Group A patients (55%; median > 60 months) compared to Group B (22%; median 27 months) patients (P = n.s.)., Conclusions: Although the difference indicating decreased recurrences and improved survival for Stage C patients treated with preoperative intra-arterial mitomycin-C were not statistically significant, the long term results of this small pilot study are encouraging.

The present study investigated the effect of the central injection of selective tachykinin (TK) agonists on the need-free intake of 0.9% NaCl in rats. Isotonic NaCl was offered for 60 min (between 1800 and 1900 h); water was offered for 4 h (between 1800 and 2200 h). The TK agonists were injected into the third ventricle just before access to fluids. The NK3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and Succ[Asp6,MePhe8]substance P(6-11), as well as the NK1-selective agonist [Sar9, Met(O2)11]substance P, markedly reduced salt intake, the threshold dose for their effects being 5 ng/rat. The NK2-selective agonist GR64349 reduced salt intake only at 500 ng/rat. At the dose of 31.2 ng/rat, neither the NK1 nor the NK3 agonists inhibited water intake, when water was the only fluid offered (between 1800 and 2200 h), or modified food intake in food-deprived rats. The present study shows that a) TKs inhibit not only the need-induced salt intake, but also the need-free intake of isotonic saline, b) this effect is behaviorally selective, and c) the effect is apparently mediated by NK1 and NK3 receptors. The finding that TKs suppress salt intake in a large variety of experimental conditions supports the idea that the antinatriorexic effect of TKs is independent of the physiological and hormonal status of the animal. It is hypothesized that TKs might modify taste sensitivity or the hedonic evaluation of the salty taste.

The present study evaluated the effect of tachykinin agonists, selective for different neurokinin (NK) receptors, on alcohol intake in genetically selected, Sardinian alcohol-preferring rats. Tachykinins were given by intracerebroventricular injection just before access to fluids. In rats offered both water and 8% ethanol 2 h/day, the NK3 selective agonists [Asp5.6,MePhe8]substance P(5-11), Suc[Asp6,MePhe8]substance P(6-11), and [MePhe7]neurokinin B markedly suppressed alcohol intake. The NK1 selective agonist [Sar9,Met(O2)11]substance P and the NK2 selective agonist GR 64349 did not At doses that inhibited alcohol intake, the NK3 agonists did not modify water intake; total fluid intake was significantly reduced only following 500 ng/rat of [Asp5.6,MePhe8]substance P(5-11). When rats were given a longer access to fluids (8% alcohol for 2 h, but water for 4 h), again, NK3 agonists suppressed alcohol intake, but not total fluid intake. Moreover, NK3 agonists did not modify solid food intake in food-deprived rats, nor water intake in water-deprived rats, when alcohol was not available. These findings indicate that NK3 agonists inhibit alcohol intake in Sardinian alcohol-preferring rats and that their effect is behaviorally selective. They also suggest that central NK3 receptors may be involved in alcohol intake control in rats.

Cytomegalovirus retinitis is the most frequent ocular opportunistic infection in AIDS patients. In selected cases intravitreal injections of foscarnet may be the sole therapeutic possibility. The retinal toxicity of the drug, however, has not yet been thoroughly investigated. Our present study in the rabbit eye concerns the retinal toxicity of 2, 4, and 6 intravitreal injections of 3.6 mg of foscarnet, using ophthalmoscopy, histology and electrophysiology to evaluate retinal damage. The results show that foscarnet may be employed intravitreally without substantial damage to the retina, but only in short courses of injections when no other therapeutic possibility may be utilized.

Brain oxytocin (OT) has been suggested to be involved in the inhibition of sodium appetite in the rat. Sodium depleted male rats showed no decrease in sodium intake after they were given a pulse intracerebroventricular (pICV) injection of either OT (1 microgram/microliter) or the selective OT agonist Tyr4-Gly7OT (1 microgram/microliter). Administration of the OT selective antagonists, d(CH2)5Tyr(Me)-[Orn8]vasotocin and Compound VI [d(CH2)5,Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (1 microgram/microliter), did not further increase their sodium intake. On the other hand, sodium appetite of sodium depleted female rats were inhibited by the same dose of pICV OT but not by the selective agonist Tyr4-Gly7 OT (1 microgram/microliter). The reduction od sodium appetite in female rats may have been in part due to the competitive behavior of grooming that followed the OT injection. Nevertheless, the OT inhibition in females of the need-free sodium intake and of the sodium appetite that occurs after furosemide but not in adrenalectomized or DOCA treated rats, argue for a mechanism independent from angiotensin or aldosterone alone related sodium appetite and the mechanism involved in the suppression of these salt intakes remain to be clarified.

The data relative to 13 years' experience with percutaneous transluminal renal angioplasty (PTRA) in the 13 major interventional radiology centers in Italy were collected and analyzed to evaluate technical and clinical results. Our aim was to collect homogeneous results in a large series of patients, evaluating both the technical and the clinical success with a long-term follow-up (1 month-13 years). One thousand three hundred forty seven PTRA procedures (including 42 restenoses) in 1,073 patients were retrospectively reviewed. In 807 cases the cause of stenosis was atherosclerosis, in 442 cases fibromuscular dysplasia and in 24 cases arteritis in 12 cases, stenoses were present in patients that had undergone a surgical by-pass. Sixty-two stenoses in patients with solitary kidney and 102 in patients with renal failure were studied separately. The technical success (based on the morphology of the dilated tract) obtained in 91% of cases was considered, together with the clinical success (in 81% of cases), based on the decrease in blood pressure evaluated according to Martin's classification. The blood pressure values collected after the maneuver were also evaluated separately for the different types of stenosis etiology: atherosclerosis, fibromuscular dysplasia or arteritis; moreover, blood pressure was studied in solitary kidney patients and in those with renal failure. Complications were classified as major (4.2%) and minor (4.9%). The high success rate and the low incidence of complications we observed in our series suggest PTRA as the procedure of choice for high blood pressure patients with renal artery stenosis > 50% of the normal caliber.

The present study evaluated the sensitivity of spontaneously hypertensive (SHR) and of Wistar Kyoto (WKY) rats to the hypotensive effect of tachykinins (TKs). Eledoisin, substance P, and the NK-1-selective agonist [Sar9,Met(O2)11]substance P evoked a smaller hypotensive response in SHR than in WKY rats. The hypotensive effect of NKA was slightly smaller in SHR, but no significant strain difference was observed. The NK-2-selective agonist [beta Ala8]NKA(4-10) was a very weak hypotensive agent in WKY rats, while being completely inactive in SHR. The NK-3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and [MePhe7]NKB did not modify blood pressure in both strains. Heart rate was essentially unmodified following the NK-3 agonists, while it was increased after injection of substance P, [Sar9,Met(O2)11]substance P, and neurokinin A, the increase being greater in WKY than in SHR. Surprisingly, eledoisin increased heart rate in SHR, but not in WKY rats, despite the greater hypotensive effect elicited in the latter strain. The present results confirm that the hypotensive effect of peripheral TKs is mediated by NK-1 receptors and show that SHR are less sensitive than WKY rats to this effect.

A[Sar1, Ile7] AngIII, an angiotensin III analogue apparently devoid of any affinity for vascular angiotensin II (AngII) receptors, inhibits AngII-induced drinking but neither affects cellular dehydration-induced drinking nor produces any intake of water in water replete rats, suggesting that the dipsogenic effect of AngII is not of vascular origin. Thus, [Sar1, Ile7] AngIII is an interesting tool to study the central effects of AngII.

Repeated sodium depletions produce a persistent, enhanced need-free salt intake in the rat, particularly in the female. The neurochemical mechanisms underlying the phenomenon are still unknown. The present studies evaluated the effect on the enhanced need-free salt intake of the female rat (1) of pharmacological interference with the natriorexigenic hormones angiotensin II and aldosterone and (2) of the central injection of the tachykinin peptides, which are endowed with antinatriorexic activity. The need-free salt intake of the female rat is not modified by treatment with the angiotensin-converting enzyme inhibitor captopril or by the aldosterone receptor antagonist RU-28318. On the other hand, the behavior is highly sensitive to the inhibitory effect of central tachykinins, suggesting the possibility that need-free salt intake might be linked to modification (down-regulation) of the inhibitory tachykininergic system.

Central injection of the tachykinins (TKs) neurokinin A (NKA), eledoisin (ELE), and kassinin (KASS) produced long-lasting inhibition (up to 6 h) of drinking induced by subcutaneous hypertonic NaCl, while substance P (SP) and physalaemin (PHYS) evoked short-lasting effects. The hypothesis that water retention or increased Na+ excretion by the kidney (induced by TKs) may reduce the need for water ingestion was tested. The results obtained both in urine collection experiments and in nephrectomized rats showed that the duration of the effect of NKA, ELE, and KASS is not due to water retention or increased Na+ excretion by the kidney. The effect of NKA, but not that of ELE and KASS, was shortened by nephrectomy, even though NKA did not modify urine volume or Na+ excretion. Indomethacin pretreatment, like nephrectomy, reduced the duration of the NKA effect, suggesting that renal prostaglandins are involved in it. On the other hand, the long-lasting effect of the three TKs cannot be easily explained in terms of slow metabolic degradation, particularly for NKA. Alternatively, it might be hypothesized that these TKs produce a modification of osmoreceptor function lasting well beyond the life of the peptide, and/or that they produce Na+ loss through emunctories different from the kidney.

The present study investigated the effect on water and food intake in the rat of the intracerebroventricular (ICV) injection of neuropeptide K (NPK), the N-terminally extended form of neurokinin A. NPK inhibited water deprivation-induced water intake even at 31.2 ng/rat. At higher doses, it inhibited also water intake induced by ICV angiotensin II or by subcutaneous hypertonic NaCl, and food-associated drinking, the threshold dose being 125 ng/rat. In response to 125 ng/rat, food intake following 16 h food deprivation was not reduced. NPK inhibited food intake only at 500 ng/rat, a dose that evoked excessive grooming in treated animals. Thus NPK is a potent inhibitor of water deprivation-induced drinking and at higher doses it exerts a general antidipsogenic effect towards several dipsogenic determinants, without affecting food intake. On the other hand, it inhibits food intake only at high doses, 500 ng/rat or more, but this inhibition might be just related to the intense grooming evoked. The effects of NPK on ingestive behavior are markedly different from those of neurokinin A, which selectively inhibits osmotic drinking and food-associated drinking. These differences suggest that NPK itself may exert its effects on the central nervous system, not necessarily through the conversion to neurokinin A.

The present study investigated the sensitivity of the posterior part of the medial division of the bed nucleus of the stria terminalis (BNST) to the antinatriorexic action of the tachykinin eledoisin in the rat. Salt appetite was evoked by sodium depletion following furosemide-induced natriuresis. The results obtained show that bilateral injection of eledoisin into the BNST evokes a very potent antinatriorexic effect, a statistically significant inhibition being observed even at the dose of 3.1 ng/BNST. On the other hand, when eledoisin was injected into the lateral ventricle, just above the BNST, much larger doses were required to elicit comparable inhibition of salt appetite. The antinatriorexic effect of eledoisin into the BNST is apparently behaviorally selective, since the same doses, which inhibited salt appetite, did not significantly affect the intake of 10% sucrose solution in the sodium-depleted animal. Present results suggest that the BNST is a site of action for the effect of tachykinins on salt appetite.

The present study investigated the involvement of capsaicin-sensitive sensory neurons on salt intake control in the rat, following capsaicin neonatal treatment. Capsaicin did not affect salt appetite induced by intramuscular injection of deoxycorticosterone enantate, or by intracranial injection of renin. Moreover, it did not alter salt preference of rats given access to a variety of NaCl concentrations, or the need-free salt intake of multidepleted male rats. On the other hand, in response to furosemide-induced sodium depletion, the salt intake of capsaicin-treated rats was lower than that of controls. However, furosemide-induced Na+ excretion of capsaicin-treated rats proved to be lower than that of controls, thus suggesting that difference in salt intake might be secondary to lower sensitivity of capsaicin-treated rats to the natriuretic action of furosemide. Salt intake is known to be influenced by sensory information from the oral cavity, from the liver and from the intravascular compartment. The absence of effect of capsaicin neonatal treatment suggests that sensory fibers relevant to salt intake control may not be capsaicin sensitive. On the other hand, our findings indicate that capsaicin treatment alters the renal response to furosemide and stimulate further studies on the effects of capsaicin on renal function.

The present study evaluated the effect of the intracerebroventricular injection of the tachykinins, substance P, neurokinin A and [Asp5.6,MePhe8]substance P(5-11) (also referred to as NH2-senktide), on the alcohol intake of genetically selected, alcohol-preferring rats. Animals were offered both water and 8% ethanol 2 h/day; tachykinins were administered just before access to fluids. Neurokinin A and substance P did not modify alcohol intake at doses up to 1000 and 2000 ng/rat, respectively. On the other hand, NH2-senktide potently suppressed alcohol intake at doses of 31.2-500 ng/rat. At the same doses, however, it did not significantly affect water intake. This finding suggests that its effect on alcohol intake might be rather selective and not due to general impairment of the behavior. Activation of tachykinin NK-3 receptors, for which NH2-senktide is a highly selective agonist, produces angiotensin II release in the brain; however, the effect of NH2-senktide on alcohol intake is probably not mediated by angiotensin II, as suggested by the fact that it is not modified by captopril pretreatment.

The intracerebroventricular injection of eledoisin (ELE), or of other tachykinins with potent agonist activity at neurokinin B (NK-3) receptors, increases plasma vasopressin in the rat. The effect is antagonized by saralasin pretreatment, thus suggesting that it is mediated by angiotensin receptor activation. Since the magnocellular part of the hypothalamic paraventricular nucleus (PVN) is very rich in NK-3 receptors, the present study was aimed at investigating the role of this nucleus in the effect of ELE on plasma vasopressin. Direct injection of ELE into the PVN increased plasma vasopressin levels more potently than the injection of the same doses into the lateral ventricle. Lesioning of the magnocellular part of the PVN completely abolished the increase in plasma vasopressin induced by the injection of ELE 100 ng/rat into the lateral ventricle. Pretreatment into the PVN either with saralasin or with captopril resulted in a marked suppression of the effect of ELE on plasma vasopressin. These findings indicate the PVN as a site of action for the central effect of tachykinins on plasma vasopressin and suggest that the angiotensin mediation of the effect might take place in the same nucleus.

The present study was aimed at investigating which tachykinin receptor subtypes mediate the inhibitory effects of tachykinins a) on salt intake induced by sodium depletion, b) on water intake induced by subcutaneous hypertonic NaCl administration and c) on water intake induced by central angiotensin II injection. The study was carried out by evaluating the potency of action, following intracerebroventricular injection, of several peptides, including both naturally occurring tachykinins and synthetic peptides selective for a given receptor subtype. The results obtained show different rank orders of potency of the agonists in the different behavioral tests, thus suggesting that different receptor subtypes are involved in the effects of tachykinins on water and salt intake. NK-3 receptors appear to be involved in the inhibitory effect of tachykinins on depletion-induced salt appetite. NK-2 receptors apparently mediate the inhibitory effect of tachykinins on drinking induced by hyperosmotic NaCl administration, while NK-1 receptors are probably involved in the inhibition of angiotensin II-induced drinking.

The present study investigated the sensitivity of the medial region of the amygdala to the antinatriorexic action in the rat of the tachykinins eledoisin, substance P, neurokinin A and [Asp5,6, MePhe8] substance P(5-11) (also referred to as amino-senktide; NH2-SENK), which is a highly selective agonist for NK-3 receptors. The results obtained show that only the potent NK-3 agonists eledoisin and NH2-SENK inhibit salt appetite when injected into the medial region of the amygdala. Eledoisin and NH2-SENK inhibited salt appetite induced by sodium depletion, that has been proven to be governed by the synergism of angiotensin and aldosterone. They inhibited also salt appetite evoked by central renin injection, that is due to production of angiotensin II. On the other hand, eledoisin and NH2-SENK did not inhibit salt appetite evoked by subcutaneous deoxycorticosterone treatment. These findings suggest that the medial region of the amygdala is a site of action for the antinatriorexic effect of tachykinins and that their action at this site is mediated by NK-3 receptors. Moreover, our results show that in the medial amygdala, the antinatriorexic action of tachykinins appears to be directed toward the angiotensinergic component of the neural mechanism for salt appetite.

The present study reports the effects of ICV administered eledoisin, the most potent anti/dipsogenic member of the tachykinin family, in three species. Sheep with chronic parotid fistula lost daily 200-400 mmol sodium in 3-4 l of saliva. During ICV infusion of eledoisin, 2 to 50 ng/min, a decrease in sodium intake was observed. If water was withheld for 22 hours, sheep normally drank 5.4 l water on presentation. During ICV infusion of eledoisin, 50 ng/min, water intake increased significantly. Wild rabbits lost 5 mmol sodium in 50 ml of urine after injection of furosemide. During ICV infusion of eledoisin, 30 ng/min, a decrease in sodium intake and an increase in water drinking was observed. Cows prepared with parotid fistula had access to sodium solution every other day to replace salivary sodium loss. During ICV infusion of eledoisin, 50 and 150 ng/min, a decrease in sodium intake occurred, and water intake was unaffected. These results confirm that central administration of eledoisin specifically influences ingestive behaviour in mammals and draws attention to some species differences in the observed effects.

Neurokinin A (NKA), which selectively inhibits only cellular dehydration (CD)-induced drinking in adult rats, exerts a more general antidipsogenic effect in pups in which it also inhibits drinking induced by angiotensin II (AII) or suckling deprivation (SD). The inhibition of drinking is precocious (1st-3rd day) and never involves the intake of milk. The inhibition of CD-induced drinking increases with age, while that of AII- or SD-induced drinking progressively decreases and disappears on day 12-15. In the rat, NKA is therefore a precocious and selective inhibitor of drinking behavior and its selectivity is achieved ontogenetically.

Intravenous (i.v. 320 and 640 micrograms/kg) and intracerebroventricular (i.c.v.; 1 microgram/rat) injection of Escherichia coli lipopolysaccharide (LPS) powerfully inhibited drinking induced by 24 h water deprivation. Pretreatment with acetylsalicylic acid (ASA) into the preoptic area (POA) completely abolished the effect induced by i.v. LPS, but did not modify that elicited by i.c.v. LPS. Intraperitoneal ASA injections significantly reduced the antidipsogenic effect of i.c.v. LPS. Electrolytic ablation of the subfornical organ (SFO) did not modify the effect induced by either i.v. or i.c.v. LPS. Present findings indicate that: (1) the antidipsogenic effect of i.v. LPS is mediated by prostaglandin synthesis into the POA, (2) the SFO is not involved in this effect, and (3) prostaglandins in other brain areas, besides POA, modulate the effect of i.c.v. LPS. It is suggested that at least two different brain sites, inside the blood-brain barrier, might be involved in the antidipsogenic effect of LPS.

Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.

The effects on ingestive behavior of the naturally occurring bombesin-like peptides ranatensin and litorin were studied in comparison to those of bombesin by intracerebroventricular pulse injection or by continuous infusion in the rat. Ranatensin and litorin, like bombesin, proved to inhibit drinking and feeding behavior. Marked differences, however, were observed in their effects. In particular our results indicate that these peptides possess different selectivity of action on drinking elicited by different dipsogenic stimuli and different potency and effectiveness in inhibiting food intake induced by food deprivation. Moreover, the effects of the three peptides were markedly affected also by the modality of administration (pulse injection or continuous infusion). On the basis of these results it seems possible to hypothesize that the endogenous bombesin-like peptides may differently affect rat ingestive behavior according to their structure and to the rate and modality of their release in the brain.

The effect on water intake, urine flow and vasopressin release of intracranial injections of substance P, physalaemin and eledoisin was studied in Wistar and Brattleboro, homozygous and heterozygous, rats. The tachykinins strongly inhibited water intake both in Wistar and in Brattleboro, homozygous and heterozygous, rats. Physalaemin and eledoisin reduced urine flow in Wistar and heterozygous, but not in homozygous, Brattleboro rats. Substance P never affected urine elimination. Physalaemin and eledoisin produced a dose-dependent, long lasting release of vasopressin in Wistar rats. Substance P did not affect the release of vasopressin. The results suggest that both substance P and physalaemin could influence brain mechanisms which control water intake, acting as thirst inhibitors, and that physalaemin could also participate in body fluid control by conserving water through vasopressin release.

The syntheses and a preliminary pharmacological evaluation of some aminopropylindolizines and aminopropyltetrahydroindolizines are reported. All compounds showed anti-5-hydroxytryptamine, anti-histamine, and antiacetylcholine activities. Some also exhibited weak CNS activity.

The effect on renin release and water intake of subcutaneous injections of the beta-adrenergic agonist carbuterol has been studied in the rat. Carbuterol, as well as isoprenaline, elicited a clear dipsogenic effect, dose-dependent, apparently mediated by stimulation of the renin-angiotensin system. The dipsogenic potency of carbuterol, in comparison to that of isoprenaline, was weaker; the ratio of dipsogenic potency between the two substances proved to be very similar to that of their relative vasodepressor activities. These findings appear to be consistent with the hypothesis that beta 2-adrenergic receptors of vascular type are involved in renin release and water intake stimulation.

Nonmammalian peptides of the tachykinin, bombesin and opioid families, injected into the brain ventricles, potently and specifically affect drinking behaviour of rats and pigeons. These peptides, or at least their counterparts, have been found in the brain of mammals and birds. It has been hypothesized that these endogenous brain peptides belong to a "brain peptidergic system" which participates in the control of water intake and body fluid homeostasis.