First Measurement of a Long-Lived π

The adapted DIRAC experiment at the CERN PS accelerator observed for the first time long-lived hydrogenlike π^{+}π^{-} atoms, produced by protons hitting a beryllium target. A part of these atoms crossed the gap of 96 mm between the target and a 2.1 µm thick platinum foil, in which most of them dissociated. Analyzing the observed number of atomic pairs, n_{A}^{L}=436_{-61}^{+157}|_{tot}, the lifetime of the 2p state is found to be τ_{2p}=(0.45_{-0.30}^{+1.08}|_{tot})×10^{-11} s, not contradicting the corresponding QED 2p state lifetime τ_{2p}^{QED}=1.17×10^{-11} s. This lifetime value is three orders of magnitude larger than our previously measured value of the π^{+}π^{-} atom ground state lifetime τ=(3.15_{-0.26}^{+0.28}|_{tot})×10^{-15} s. Further studies of long-lived π^{+}π^{-} atoms will allow us to measure energy differences between p and s atomic states and so to discriminate between the isoscalar and isotensor ππ scattering lengths with the aim to check QCD predictions.

Observation of π

The observation of hydrogenlike πK atoms, consisting of π^{-}K^{+} or π^{+}K^{-} mesons, is presented. The atoms are produced by 24 GeV/c protons from the CERN PS accelerator, interacting with platinum or nickel foil targets. The breakup (ionization) of πK atoms in the same targets yields characteristic πK pairs, called "atomic pairs," with small relative momenta Q in the pair center-of-mass system. The upgraded DIRAC experiment observed 349±62 such atomic πK pairs, corresponding to a signal of 5.6 standard deviations. This is the first statistically significant observation of the strange dimesonic πK atom.

Elective segmental ureterectomy for transitional cell carcinoma of the ureter: long-term follow-up in a series of 73 patients.

UNLABELLED: What's known on the subject? and What does the study add? Upper Urinary Tract (UUT) Transitional Cell Carcinoma (TCC) is an uncommon disease and represents approximately 5% of all urothelial carcinomas. We report our series on 73 patients treated with Kidney Sparing Surgery for UUT TCC. Good results have been achieved in terms of oncological outcome comparing this conservative approach to the radical nephrourectomy. OBJECTIVES: • To report the long-term oncological outcome in patients with transitional cell carcinoma of the ureter electively treated with kidney-sparing surgery. • To compare our data with the few series reported in the literature. PATIENTS AND METHODS: • We considered 73 patients with transitional cell carcinoma of the distal ureter treated in five Italian Departments of Urology. • The following surgeries were carried out: 38 reimplantations on psoas hitch bladder (52%), 21 end-to-end anastomoses (28.8%), 11 direct ureterocystoneostomies (15.1%) and three reimplantations on Boari flap bladder (4.1%). • The median follow-up was 87 months. RESULTS: • Tumours were pTa in 42.5% of patients, pT1 in 31.5%, pT2 in 17.8% and pT3 in 8.2%. • Recurrence of bladder urothelial carcinoma was found in 10 patients (13.7%) after a median time of 28 months. • The bladder recurrence-free survival at 5 years was 82.2%. • The overall survival at 5 years was 85.3% and the cancer-specific survival rate at 5 years was 94.1%. CONCLUSION: • Our data show that segmental ureterectomy procedures do not result in worse cancer control compared with data in the literature regarding nephroureterectomy.

Effects of the cannabinoid antagonist SR 141716 on sexual and motor behaviour in receptive female rats.

1. The aim of the present study was to investigate the effect of the cannabinoid antagonist/inverse agonist SR 141716 (SR) on the receptive behaviour and sexual motivation of female rats. 2. Partner preference, receptivity and proceptivity were evaluated in ovariectomized female rats primed with oestrogen and progesterone and administered SR (1 or 2.5 mg/kg, i.p.) 20 min prior to testing. 3. In the partner preference test, a reduced interest in both stimulus animals (a sexually active male and an ovariectomized hormone-primed female) was detected in rats treated with SR at both doses, but no effect on preference score was observed. In the receptivity test, pronounced reductions in lordosis quotient, lordosis rating and in the percentage of receptive females were found in SR-treated rats compared with control rats. Proceptive behaviours were not significantly affected by either dose of SR. 4. In addition, we explored the behavioural effects induced by SR in female rats using the open field test. Only at the higher dose (i.e. 2.5 mg/kg) did SR markedly increased grooming and scratching behaviour. 5. The results demonstrate the ability of SR to reduce female sexual receptivity, but not sexual motivation. The reduction does not seem strictly related to the motor alterations induced by the cannabinoid antagonist.

Assessment of pulmonary function in patients before and after laparoscopic and open esophagogastric surgery.

BACKGROUND: Laparoscopy is a technique used in various surgical procedures. Few studies in the literature compare stress between laparoscopic and open surgery used for esophagogastric surgical procedures. Pulmonary function is known to be significantly affected in open surgeries, increasing postoperative morbidity and mortality. The current study aimed to assess pulmonary function in patients before and after open and laparoscopic esophagogastric surgery. METHODS: For this study, 75 patients were divided into two groups: 50 patients undergoing laparoscopy and 25 patients undergoing open surgery. The following parameters were determined by spirometry before and after surgery: forced expiratory volume in the first second (FEV(1)), forced vital capacity (FVC), and forced expiratory flow in the midexpiratory phase (FEF(25-75%)). RESULTS: A decrease in FEV(1,) FVC, and FEF((25-75%)) was observed in the two groups on postoperative days 2, 3, and 4, as compared with the preoperative period. Likewise, FEV(1) and FVC showed a significant reduction on postoperative days 2, 3, and 4 in the patients who underwent to open surgery, but only on the day 2 in those who underwent to laparoscopic surgery. A significant decrease in FEF((25-75%)) was observed only on postoperative day 2 in the group that underwent open surgery. Significant differences in FEV(1) between the groups were observed on postoperative days 2, 3, and 4. No significant difference in FVC was noted between the groups, and a difference in FEF((25-75%)) was observed only on postoperative day 4. CONCLUSIONS: Postoperative pulmonary dysfunction was more important for the patients undergoing open surgery than for those undergoing laparoscopic surgery.

Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats.

1. S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons in involved in the therapeutic mechanisms of antidepressants. 2. The effect of SAMe in an animal model of 'depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats. 3. Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg-1 daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg-1 daily i.p.) produced a similar effect after a 3 week treatment. 4. Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg-1 daily i.m.)--and in imipramine (10 mg kg-1 daily i.p.)--treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats. 5. Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test. 6. While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment. 7. These results show that SAMe reverses an experimental condition of 'depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects.

Effects of a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)phenoxy]2-methyl propionic acid (alpha-1081) on biliary lipid secretion in rats.

1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)-phenoxy]2-methyl propionic acid (alpha-1081, 1.150 g/kg body wt., daily), cholestyramine (1.125 g/kg body wt. daily), procetofenic acid (25 mg/kg body wt. daily) and saline respectively (six rats for each group). 3 Cholesterol saturation index significantly (P less than 0.005) increased (from 0.21 +/- 0.01 to 0.39 +/- 0.09, mean +/- s.d.), in rats fed with procetofenic acid but it did not in alpha-1081- and cholestyramine-treated animals. 4 Procetofenic acid and, to a lesser extent, cholestyramine increased the bile flow. Procetofenic acid increased cholesterol secretion from 0.45 +/- 0.17 to 0.94 +/- 0.19 mumol kg-1 body wt. h-1 (mean +/- s.d.). 5 Cholestyramine increased both serum cholesterol and bile acid secretion from 0.45 +/- 0.17 to 0.68 +/- 0.10 and 25.8 +/- 9.48 to 39.96 +/- 6.68 mumol kg-1 body wt. h-1 respectively; alpha-1081, on the contrary, had no effect on bile lipid secretion. 6 These data suggest that alpha-1081 may be used as a new hypolipidaemic drug without any risk of increasing cholesterol in bile.

Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats.

The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.

Stimulating property of Turnera diffusa and Pfaffia paniculata extracts on the sexual-behavior of male rats.

Sexually potent and sexually sluggish/impotent male rats were treated orally with different amounts of Turnera diffusa and Pfaffia paniculata fluid extracts (0.25, 0.50, 1.0 ml/kg). While having no effect on the copulatory behavior of sexually potent rats, both plant extracts--singly or in combination--improved the copulatory performance of sexually sluggish/impotent rats. The highest dose of either extract (1 ml/kg) (as well as the combination of 0.5 ml/kg of each extract) increased the percentage of rats achieving ejaculation and significantly reduced mount, intromission and ejaculation latencies, post-ejaculatory interval and intercopulatory interval. Neither extract affected locomotor activity. These results seem to support the folk reputation of Turnera diffusa and Pfaffia paniculata as sexual stimulants.

l-Sulpiride, at a low, non-neuroleptic dose, prevents conditioned fear stress-induced freezing behavior in rats.

Antidepressant drugs are effective in anxiety states, including panic disorder. Both clinical and animal studies indicate that l-sulpiride, at low, non-neuroleptic doses, has antidepressant activity. The present study examined the effect of an antidepressant dose of l-sulpiride (4 mg/kg per day SC), compared with a well-established antidepressant drug (fluoxetine, 3 mg/kg per day SC), in a rat model of anticipatory anxiety/panic behavior: conditioned fear stress-induced freezing behavior. Long-term (26 days) administration of l-sulpiride almost completely abolished freezing, a similar effect being produced by fluoxetine (freezing duration, in seconds: controls, 148.1 +/- 29.6; l-sulpiride, 27.5 +/- 8.3; fluoxetine, 72.0 +/- 15.2). The same doses of l-sulpiride (4 mg/kg SC) and fluoxetine (3 mg/kg SC) had no effect when administered for shorter periods (1, 5, or 12 days). No effect was produced by the long-term (26 days) administration of a neuroleptic dose of l-sulpiride (20 mg/kg per day SC). These results demonstrate that long-term administration of low, non-neuroleptic doses of l-sulpiride, is highly effective in an animal model of anticipatory anxiety/panic behavior.

Pharmacological manipulation of brain galaninergic system and sexual behavior in male mice.

RATIONALE: Available data suggest a complex role for the brain galaninergic system in male sexual behavior; however, the results so far obtained in animals with either galanin or galanin antagonists are conflicting. OBJECTIVE: To define the better influence of galanin on male sexual behavior by studying, in mice, (i) the effect of galanin and of the chimeric galanin peptide M40 on the copulatory performance, and (ii) galanin mRNA levels in hypothalamic arcuate and dorso-medial nuclei. METHODS: For the behavioral testing, only sexually sluggish male mice were used. Galanin mRNA levels were studied in both sexually potent and impotent mice by means of in situ hybridization. Standard behavioral parameters for sexual behavior were recorded or calculated. Synthetic galanin (0.05, 0.1 or 1 microg/mouse) and M40 (5 or 20 microg/mouse) were intracerebroventricularly (ICV) injected, 15 min before the copulatory test. Galanin mRNA levels were evaluated. RESULTS: In sexually sluggish male mice, both galanin (0.1 and 1 microg/mouse ICV) and M40 (20 microg/mouse ICV), significantly increased intromission frequency and ejaculation latency; M40 also improved copulatory efficacy. On the other hand, in the hypothalamic arcuate and dorso-medial nuclei, the levels of galanin mRNA were not significantly different in sexually potent and impotent male mice. CONCLUSIONS: These results show that in sexually sluggish male mice the ICV injection of either galanin or the chimeric analogue M40 greatly prolongs the duration of the copulation; without a reduction of the sexual drive or of the copulatory performance. On the other hand, the hybridization experiments seem to rule out an important physiological role of the brain galaninergic system in the regulation of male sexual behavior, at least in mice.

Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.

The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi.

Influence of oxytocin on feeding behavior in the rat.

Oxytocin, whether administered intraperitoneally (IP) (375-6,000 micrograms/kg) or intracerebroventricularly (ICV) (1-10 micrograms/rat), dose-dependently reduced food consumption and time spent eating and increased the latency to the first meal in rats fasted for 21 hr. Pretreatment with the oxytocin antagonist d(CH2)5Tyr(Me)-[Orn8]vasotocin (ICV 10 micrograms/rat) completely prevented the feeding inhibitory effect of an equal dose of ICV oxytocin, and per se increased food intake. Our data further support the hypothesis that oxytocin plays the role of neurotransmitter or neuromodulator in the CNS, and suggest that its involvement in a number of homeostatic systems may include appetite control.

Nitric oxide is involved in the ACTH-induced behavioral syndrome.

In many animal species, the ICV injection of ACTH and of several shorter sequences of the ACTH molecule (melanocortin peptides) induces a peculiar behavioral syndrome mainly characterized by excessive grooming and by repeated acts of stretching and yawning. In adult males, spontaneous penile erections with ejaculation are also induced. We have studied the effect of NO synthase inhibition on this behavioral syndrome. The IP injection of the NO synthase inhibitor L-NG-nitroarginine methyl ester (NAME) significantly prevented--at the doses of 50 and 100 mg/kg--all the behavioral symptoms induced by the ICV administration of ACTH(1-24) (4 micrograms/rat). On the other hand, the ICV injection of NAME (up to 300 micrograms/rat) had no influence on the ACTH-induced excessive grooming and stretching, while significantly inhibited the display of yawnings and penile erections. These data indicate that brain NO synthase is involved in the mechanism of ACTH-induced yawning and penile erections, whereas peripheral NO synthase is involved in the induction of stretching and grooming.

Oxytocin-induced inhibition of feeding and drinking: no sexual dimorphism in rats.

The effect of oxytocin on feeding and drinking behaviours was compared in male and female rats. Dose-dependent feeding and drinking inhibition was observed in either sex to about the same degree, both following intracerebroventricular or intraperitoneal administration. The results were obtained whether in animals with free access to food and water or in schedule-fed animals fasting for 21h and in two different models of thirst (water deprivation for 16h, s.c. administration of hypertonic saline). These data show that there is no sexual dimorphism in oxytocin-induced inhibition of feeding and drinking.

Influence of oxytocin on nociception and morphine antinociception.

In the hot plate test the intracerebroventricular (i.c.v.) injection of oxytocin produced a significant decrease in nociception, starting from the dose of 1 microgram/rat. A comparable effect was obtained with 10-200 times higher intraperitoneal (i.p.) doses. The i.c.v. injection of the oxytocin antagonist d(CH2)5-Tyr(Me)-[Orn8]-vasotocin, while having no influence per se, completely prevented the antinociceptive effect of an equal i.c.v. dose of oxytocin. The antinociceptive effect of oxytocin was also prevented by naltrexone, and oxytocin caused a small but significant increase of the antinociceptive effect of morphine and of its duration. These data indicate that pharmacological amounts of oxytocin produce antinociception, that occurs through the activation of oxytocin receptors; endogenous opioid systems seem to be involved altogether.

Improved recovery of nigro-striatally hemitransected rats induced by (Nle4, D-Phe7)alpha-MSH: a central effect.

Rats were subjected to nigro-striatal hemitransection and then intracerebroventricularly infused with the potent and long-acting alpha-MSH analogue, (Nle4, D-Phe7)alpha-MSH, at two different doses (15 or 30 ng/h/rat), or with saline (0.6 microliter/h/rat), continuously for 14 days starting on day 2 after lesion. (Nle4, D-Phe7)alpha-MSH dose-dependently improved the sensorimotor deficit (postural asymmetry, impaired limb reflexes and coordinated limb use, signs of cortical and pyramidal lesion), reduced turning behaviour induced by apomorphine, and increased spontaneous motility in the open field. 3H-Spiperone binding showed that (Nle4, D-Phe7)alpha-MSH treatment caused a down regulation of the striatal DA receptors in the lesioned side, contrary to the supersensitivity developed by the corresponding receptors of saline treated rats. These results indicate that melanopeptides improve the functional recovery of nigro-striatally hemitransected rats, by an action at CNS level.

Benextramine, an NPY antagonist, improves sexual behavior in male rats.

In adult, sexually-experienced male rats, the NPY-antagonist benextramine--at the doses of 5 and 10 mg/kg i.p. and of 50 micrograms/rat i.c.v.--significantly and specifically improved several parameters of copulatory activity. These data may further support the idea that NPY plays a role in the complex regulation of male sexual function, seemingly at the brain level.

Diabetic rats are unresponsive to the penile erection-inducing effect of intracerebroventriculary injected adrenocorticotropin.

The penile erection-inducing effect of intracerebroventricularly (i.c.v.) injected adrenocorticotropin-(1-24) [ACTH-(1-24)] (4 or 10 microg/animal) was almost completely absent in diabetic rats, either 8 days or 2 months after streptozotocin administration. The other behavioral symptoms (stretching, yawning, excessive grooming) were unevenly affected: stretching was significantly reduced either in early or in long-standing diabetes; yawning was practically absent in early diabetes and significantly reduced at the highest dose of ACTH-(1-24) in long-standing diabetes; grooming was reduced only at the highest dose of ACTH-(1-24), both in early and in long-standing diabetes. The fact that ACTH-induced penile erections (a centrally mediated effect) are practically absent even a few days after streptozotocin injection suggests that diabetes mellitus-induced penile dysfunction occurs, at least in part, through central mechanisms, and is not solely the consequence of peripheral nerve and vascular lesions.

Oxytocin enhances, and oxytocin antagonism decreases, sexual receptivity in intact female rats.

In intact, non-ovariectomized female rats in spontaneous behavioral estrus, the i.c.v. injection of oxytocin significantly increased lordosis quotient and lordosis duration, starting from a dose of 1 ng/rat. On the other hand, the oxytocin antagonist, d(CH2)5Tyr(Me)-[Orn]8-vasotocin, injected at the same doses and by the same route, decreased lordosis quotient and lordosis duration, and prevented the effect of oxytocin. These data further support the notion that oxytocin plays a physiological role in female sexual receptivity.