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Biomedical subjects

R Poggioli

Publications and source records attributed to R Poggioli.

At least 19 recordsLinked to original sources

Quality of life after islet transplantation.

This study analyzed quality of life in patients with type 1 diabetes that received islet transplantation. Twenty-three subjects were followed over 3 years. In addition to an interview, patients self-completed two standardized psychometric questionnaires, HSQ 2.0 and DQOL, before and after transplant, and scores were compared. Analysis was also adjusted for potential "confounders" such as graft dysfunction, insulin therapy and adverse events. DQOL: the Impact score significantly improved at all time points of the follow-up; satisfaction and worry scales also significantly improved at selected time points. Longitudinal analysis demonstrated that reintroduction of insulin had a negative effect on all three scales, but significant improvement in Impact scale persisted even after adjusting for this factor. HSQ 2.0: only the Health Perception scale preliminarily showed significant improvement at most time points. Longitudinal analysis showed loss of significance when insulin therapy was considered. Other scores were improved only at selected time points or not affected. Bodily pain scale showed deterioration at selected times. Interview: glucose control stability, not insulin independence, was reported as the main beneficial factor influencing QOL. In conclusion, islet transplantation has a positive influence on patients' QOL, despite chronic immunosuppression side effects. Re-introduction of insulin modifies QOL outcomes.

Female↗

Behavioral and developmental outcomes of prenatal and postnatal vanadium exposure in the rat.

The developmental and behavioral outcomes of uninterrupted exposure to vanadium was studied in the rat. Starting 3 days before birth and up to the 100th day of extrauterine life, rats received as drink either a water solution of vanadyl sulphate (300 mg l(-1)containing 70 mg l(-1)of vanadium element, which is equal to an ingested dose of about 10 mg kg(-1)per day of vanadium element) plus NaCl 5 g l(-1), or a water solution of NaCl 5 g l(-1), or plain water [up to weaning (25th day of extrauterine life) treatment was given to dams and offspring]. At weaning, survivors were fewer and body weight was found to be significantly lower in the offspring of vanadium plus NaCl-treated dams than in the offspring of the other two groups. After weaning, growth retardation continued to be significant in both vanadium plus NaCl- and NaCl-treated rats. Such an effect was more pronounced in males than in females. Locomotor activity--evaluated at 1 month of age--was not significantly different in the three groups of rats. In the open-field, male (but not female) vanadium plus NaCl-treated rats had a reduced outer ambulation, rearing posture and grooming activity, and an increased defecation, in comparison with the males of the NaCl group, and reduced rearing in comparison with control males. As concerns ingestive behaviors, the only significant datum was an increased water intake in NaCl-treated males. Finally, at the 100th day of life, working memory was significantly impaired in both vanadium plus NaCl- and NaCl-treated rats.

Animals↗

L -sulpiride, at antidepressant dosage, prevents conditioned-fear stress-induced gastric lesions in rats.

It has been previously shown that long-term treatment with low doses of l-sulpiride is highly effective in rat models of depression and of anticipatory anxiety/panic behavior. The present study was aimed at investigating whether the same treatment can prevent the ulcerogenic effect of repeated inescapable stresses. In adult rats, the repeated (7 consecutive days) exposure to an uncontrollable stressful condition (inescapable 2.5 mA scrambled shock for 60 s) produced the development of gastric lesions (multiple punctiform telangiectasias in all rats, with superficial erosions or more severe ulcerations in 10 out 13 rats; score 4.67 +/- 0.44). l-sulpiride, intraperitoneally injected once a day at an antidepressant dose level (4 mg kg(-1) per day), starting 21 days before the beginning of the 7-day sequence of inescapable punishments ( = 28 daily treatments), almost completely prevented the stress-induced gastric injury (score 1.67 +/- 0.29; P< 0.001 vs saline-treated rats, Mann-Whitney U test). These results show that, in rats, a long-term treatment with low doses of l-sulpiride prevents the development of gastric lesions induced by chronic exposure to uncontrollable stress.

Animals↗

Antitussive effect of K+ channel openers.

The effect of the K(ATP) channel openers, pinacidil and cromakalim, on coughing was studied in guinea pigs exposed to a nebulized aqueous solution of citric acid (0.50 M). Both pinacidil and cromakalim, subcutaneously administered 45 min before the test, inhibited coughing. The D50 (95% CI) were 0.95 +/- 0.90 mg/kg for cromakalim and 3.25 +/- 0.92 mg/kg for pinacidil. Under our experimental conditions, the D50 (95% CI) of codeine was 1.74 +/- 0.75 mg/kg. The combination of cromakalim and pinacidil with codeine produced an additive effect. An additive effect was also produced by the combination of pinacidil with the selective tachykinin NK2 receptor antagonist MEN 10,627 = [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2beta-5beta)]. The antitussive effect of pinacidil and cromakalim was not a consequence of a bronchodilating effect, which was absent at these dose levels under our experimental conditions. These results indicate that K(ATP) channel openers have an opioid-like antitussive effect and may suggest a novel approach to the symptomatic treatment of coughing.

Animals↗

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.

Animals↗

Gamma-hydroxybutyrate increases gastric emptying in rats.

The influence of gamma-hydroxybutyrate (GHB; 10, 50 or 100 mg/kg orally) and of its receptor antagonist, NCS-382 (25, 100 or 200 mg/kg orally, and 100 or 200 mg/kg intraperitoneally), on gastric emptying was studied in rats by measuring the serum level of acetaminophen (20 mg/rat orally, 30 min after GHB or NCS-382) 15, 30, 45 and 60 min after acetaminophen administration, or the amount of acetaminophen still present in the stomach 30 min after its administration. The highest dose of GHB produced a significant increase in 15 and 30 min serum levels of acetaminophen, indicating an acceleration of gastric emptying. A similar result was obtained with the prokinetic drug cisapride, at the oral dose of 2 mg/kg. On the other hand, NCS-382 significantly and dose-dependently reduced the serum levels of acetaminophen at every time of blood sampling, indicating a delay of gastric emptying, an effect confirmed by the amount of acetaminophen still present in the stomach 30 min after administration. Moreover, NCS-382 antagonized the prokinetic effect of GHB. These results may suggest for GHB (and/or possibly for its metabolites) a role in rat stomach motility.

Acetaminophen↗

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.

Animals↗

Effect of potassium channel modulators on male sexual behavior.

In the adult sexually experienced male rat, the intracerebroventricular (i.c.v.) injection of pinacidil, a KATP channel opener, at the dose of 100-150-300 micrograms/rat worsened the copulatory performance in the presence of a receptive female, whereas the administration of glibenclamide, a KATP channel blocker, at the dose of 0.5 and 3 mg/kg intraperitoneally (i.p.) had an improving effect. These data indicate that KATP channels in target neurons may play an important role in the physiology of male sexual behavior.

Animals↗

Use of calcium provocative test in the diagnosis of gastroenteropancreatic endocrine tumors.

Calcium infusion has been advocated as a provocative test for the diagnosis of some endocrine tumors of the pancreas and gastrointestinal tract (gastrinoma, insulinoma, intestinal carcinoids). The release of gastrin from gastrinoma tissue is very sensitive to alterations in the serum calcium level, and the calcium infusion test is recommended in Zollinger-Ellison syndrome when the results of secretin stimulation are equivocal. The calcium provocative test in the detection of insulinoma and carcinoid tumors is less reliable than other safer and simpler procedures. Intravenous injection of calcium followed by pentagastrin stimulates the release of somatostatin in patients with somatostatinoma and offers a reliable means for establishing the diagnosis of this tumor. Calcium administration has not proven to be useful in the diagnosis of other endocrine tumors of the digestive system.

Calcium↗

Nitric oxide is involved in male sexual behavior of rats.

In male rats, whether sexually experienced or sexually naive, the intraperitoneal administration of L-arginine (the natural substrate for nitric oxide synthase) (10, 25, 50 mg/kg) both increased the percentage of copulating in sexually naive rats and improved the indexes of sexual performance in sexually experienced rats, whereas the intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME) (a potent inhibitor of nitric oxide synthase) (10, 25, 50 mg/kg) had opposite effects. In contrast, after intracerebroventricular administration, L-arginine (25, 50, 100 microg/rat) had no effect - whether in naive or in experienced rats - whereas L-NAME completely prevented ejaculation in naive rats, at the dose of 100 microg/rat, but had no effect at all in experienced rats, up to the dose of 300 microg/rat. Finally, a direct relationship seems to exist between male copulatory performance and nitric oxide synthase activity in a discrete and defined brain area, the paraventricular nucleus of the hypothalamus: indeed, nitric oxide synthase mRNA expression in this nucleus in sexually potent rats is about twice that in sexually impotent rats. It is concluded that nitric oxide synthase is involved in the expression of male sexual activity, in spite of some inconsistencies that are hard to interpret.

Animals↗

K+ channel openers delay intestinal transit and have antidiarrheal activity.

The effect of pinacidil and cromakalim, two KATP channel openers, on intestinal transit and castor oil-induced diarrhea was studied in mice. Both drugs, administered orally, dose dependently inhibited the intestinal propulsion of charcoal, and castor oil-induced diarrhea, comparing favorably with morphine. These results may suggest a new approach for the symptomatic treatment of diarrhea.

Animals↗

Aged rats are still responsive to the antidepressant and memory-improving effects of oxytocin.

Oxytocin, intraperitoneally injected to 26-month-old male rats 60 min before testing, significantly improved social memory (at doses of 3 and 6 ng/kg) and reduced the duration of immobility in the behavioral despair test (at doses of 50 and 500 micrograms/kg). These results are in agreement with previous data obtained in adult rats and indicate that aging does not compromise the social memory improving and antidepressant-like activities of oxytocin.

Aging↗

Polymodal dose-response curve for oxytocin in the social recognition test.

Available data concerning the effect of oxytocin on memory are often inconsistent. In the present study it was found that oxytocin, intracerebroventricularly injected to adult male rats in a dose range of 1 fg-10 ng/rat immediately after a 5-minute encounter with a juvenile, significantly reduces the social investigation time of the adult rat towards the same juvenile during a second encounter (120 min later) with two peaks of activity, at 10 fg and 1 ng/rat. Larger doses of oxytocin were ineffective. The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin, injected 5 min before oxytocin by the same route and at the same doses, while being ineffective per se, completely abolished the memory-improving effect of a low dose of oxytocin (1 ng/rat) and, on the other hand, turned into memory-improving the effect of a high dose of oxytocin (500 ng/rat).

Animals↗

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.

Animals↗

Old rats are unresponsive to the behavioral effects of adrenocorticotropin.

In 28 month-old male rats, the i.c.v. injection of adrenocorticotropin [ACTH-(1-24)] (4 micrograms/rat) did not induce the typical behavioral syndrome (excessive grooming, stretching, yawning, penile erections). This indicates that the behavioral effects of melanocortins are age-dependent, suggesting either an aging-linked impairment of the nervous circuitries involved or a reduction of the number (or affinity, or both) of the brain melanocortin receptors in the elderly.

Aging↗

Galantide stimulates sexual behaviour in male rats.

While intracerebroventricular injection of galanin (5 micrograms/rat) inhibited sexual behavior in experienced male rats--without producing any other locomotor or behavioral deficit-, injection of the galanin antagonist, galantide, by the same route (1 or 2 micrograms/rat) stimulated sexual behavior (improving arousal, motivation and performance indexes) and antagonized the effect of galanin. These data further suggest that galanin plays a physiological role in male sexual behavior.

Animals↗

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.

Animals↗

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.

Animals↗