Biomedical subjects

R Ciccocioppo

Publications and source records attributed to R Ciccocioppo.

At least 73 records · Page 4Linked to original sources

PubMed1995

The selective angiotensin AT1 receptor antagonist LR-B/081 potently inhibits drinking induced by central injection of angiotensin II in rats.

LR-B/081, methyl-2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl] methyl]-1(6H)-pyrimidinyl] methyl]-3-thiophenecarboxylate, is a recently developed nonpeptide antagonist selective for angiotensin AT1 receptors. The drug has been reported to be an insurmountable angiotensin AT1 receptor antagonist endowed with long-lasting antihypertensive activity. A large body of evidence indicates that angiotensin AT1 receptors mediate the dipsogenic action of angiotensin II in the central nervous system. The present study evaluated the ability of LR-B/081, in comparison with losartan and with its active metabolite EXP3174, to inhibit drinking induced by central injection of angiotensin II in water-sated rats. LR-B/081, in the dose range of 10-1000 pmol/rat, dose dependently inhibited the drinking response to angiotensin II, 10 pmol/rat. The ID50 of LR-B/081 was 25.9 pmol/rat, while that of losartan and EXP3174 was 357 and 3.9 pmol/rat, respectively. Therefore LR-B/081 was about 7 times less potent than EXP3174, but about 14 times more potent than the parent molecule losartan. LR-B/081 altered neither carbachol-induced water intake, nor 15% fat milk intake in rats, suggesting that its effect on angiotensin II-induced drinking is a behaviourally selective effect. These findings show that LR-B/081 potently inhibits central angiotensin AT1 receptors involved in behaviourally selective effect. These findings show that LR-B/081 potently inhibits central angiotensin AT1 receptors involved in the control of body fluid homeostasis and suggest that this drug might be an interesting pharmacological tool to further investigate the role of the central renin-angiotensin system in physiological or pathological conditions.

Analysis of Variance↗

PubMed1995

Effects of the dopamine D1 receptor antagonist SCH 39166 on the ingestive behaviour of alcohol-preferring rats.

The present study evaluated the effect of the selective and long-acting dopamine D1 receptor antagonist SCH 39166 on several aspects of the ingestive behaviour of genetically selected alcohol-preferring rats, bred from Sardinian alcohol-preferring rats. The effect of subchronic (8 days) subcutaneous drug administration was evaluated on the simultaneous daily intake of 10% ethanol, food and water. SCH 39166, 0.1 mg/kg, did not significantly modify the intake of the three ingesta. The dose of 1 mg/kg differentially modified rat ingestive behaviour, inhibiting intake of 10% ethanol, without modifying total fluid and food intake. The higher dose of 5 mg/kg produced a non-selective suppression of ingestive behaviour, which was accompanied by behavioural impairment. Acute drug injection was tested on 2-h intake of 10% sucrose, 0.1% saccharin, water or food. The doses of 0.1 and 1 mg/kg markedly inhibited the 2-h intake of 10% sucrose and 0.1% saccharin, but they did not modify either the 2-h water intake in water deprived and water sated rats or the 2-h food intake in food deprived rats. These findings suggest an important role of mechanisms mediated by D1 receptors in the control of alcohol and sweet solution intake, but not in water and food intake. Moreover, they indicate that SCH 39166, in relation to its selectivity and long-lasting activity, is an interesting pharmacological tool to investigate further the role of D1 receptor mechanisms in the control of ingestive behaviour.

Alcohol Drinking↗

PubMed1995

Low responsiveness to agents evoking 5-HT2 receptor-mediated behaviors in Sardinian alcohol-preferring rats.

The selective NK3 tachykinin agonist senktide evokes in rodents 5-HT mediated behaviors, including 5-HT2 receptor-mediated wet dog shakes (WDS) and head shakes (HS). It was observed previously that genetically selected Sardinian alcohol-preferring (sP) rats show a small number of WDS and HS following intracerebroventricular (ICV) injection of senktide. The present study was aimed at confirming these observations and at providing information on the reasons accounting for the anomalous response of sP rats. Senktide (500-2000 ng/rat, ICV) produced a much lower number of WDS and HS in sP rats than in nonselected Wistar (nsW) rats. Both behaviors were suppressed by the 5-HT2 antagonist ritanserin (1 mg/kg, subcutaneously), confirming that 5-HT2 receptors mediate the response. HS induced by the ICV injection of 5-HT agonists endowed with marked activity at 5-HT2 receptors, such as quipazine (1500-6000 ng/rat) or DOI (500-3500 ng/rat), were much less pronounced in sP rats than in nsW rats. Moreover, WDS following peripheral injection of 5-hydroxytryptophan, 25-100 mg/kg, and carbidopa, 12.5 mg/kg, were less intense in sP and in ethanol-naive sP rats than in nsW and in Sardinian alcohol-nonpreferring rats. These findings suggest that sP rats have an inherent different regulation of central 5-HT2 mechanisms.

5-Hydroxytryptophan↗

PubMed1995

The 5-HT4 receptor antagonist, GR113808, reduces ethanol intake in alcohol-preferring rats.

The present study evaluated the effect of the selective 5-HT4 receptor antagonist, GR113808, on ethanol intake in alcohol-preferring rats. Rats were offered 10% ethanol 2 h/day. In the first experiment, rats had food and water ad lib and 10% ethanol was offered from 1800 to 2000 h. In the second experiment, food was freely available, 10% ethanol was offered 2 h/day, from 1800 to 2000 h, and water was offered for 4 h, from 1800 to 2200 h. In both experiments GR113808 was subcutaneously injected at doses of 1, 3, or 10 mg/kg for 4 consecutive days, 5 min before access to ethanol. From the first day of administration, GR113808 significantly reduced the volitional ethanol intake in water sated rats at the three doses tested. In water-deprived rats, it reduced ethanol intake at 3 and 10 mg/kg, without modifying total fluid and food intake. In both experiments the effect of GR113808 remained rather stable during the 4 days of administration. The present findings, showing that the 5-HT4 receptor antagonist, GR113808, selectively reduces ethanol intake in alcohol-preferring rats, suggest that 5-HT4 receptors may play a role in alcohol intake control.

Alcohol Deterrents↗

PubMed1995

Subcutaneous injections of the tachykinin senktide reduce alcohol intake in alcohol-preferring rats.

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.

Alcohol Drinking↗

PubMed1994

Effect of tachykinins on the need-free sodium intake of female rats: a continuous intracerebroventricular infusion study.

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.

Animals↗

PubMed1994

Inhibition of isotonic sodium chloride intake in the rat by selective tachykinin agonists.

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.

Animals↗

PubMed1994

Selective agonists at NK3 tachykinin receptors inhibit alcohol intake in Sardinian alcohol-preferring rats.

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.

Alcohol Drinking↗

PubMed1994

Role of nitric oxide-dependent and -independent mechanisms in peristalsis and accommodation in the rabbit distal colon.

Previous findings, which have been confirmed in this study, indicate that nitric oxide (NO)-dependent and -independent (apamin-sensitive) mechanisms underlie the electrically induced non-adrenergic, noncholinergic (NANC) relaxation in the circular muscle of rabbit distal colon. Based on this evidence, we further investigated whether, and to what extent, these separate NANC components participate in the maintenance of circular muscle tone, reflex relaxations evoked by localized balloon distension or during peristalsis (descending inhibition) and in the accommodation of colonic wall in response to graded intraluminal fluid delivery. NG-nitro-L-arginine (L-NNA) (10-300 microM), apamin (100 nM) and tetrodotoxin (60 nM), enhanced the spontaneous low tone and phasic activity in circular muscle strips. In experiments on peristalsis, L-NNA (30 and 300 microM) shortened the latency of peristaltic wave initiation and increased the velocity of propulsion of an intraluminally distended balloon (range, 0.1-1 ml). The latter effect was mimicked by the NO scavenger oxyhemoglobin (30 microM). Velocity of propulsion was enhanced by apamin (100 nM) at low balloon distension (0.1 and 0.2 ml), whereas it was reduced at high distension volumes (1 ml), due to disruption of descending inhibition. A combination of L-NNA (300 microM) and apamin (100 nM) blocked peristalsis, due to persisting spasms of the circular muscle. L-NNA (300 microM) did not affect the amplitude of distension-evoked ascending reflex contraction and slightly inhibited the descending reflex relaxation. By contrast, the latter reflex was virtually abolished by apamin (100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

5-HT2 receptor antagonists do not reduce ethanol preference in Sardinian alcohol-preferring (sP) rats.

The present study investigated the effect of the 5-HT2/1C receptor antagonist ritanserin, and of the 5-HT2/D2 receptor antagonist risperidone on ethanol preference in Sardinian alcohol-preferring (sP) rats. Rats were offered free access to both tap water and 8% (in one experiment 3%) ethanol solution. Subchronic (10 or 1 mg/kg/day, for 10 days) or chronic (1 mg/kg/day, for 30 days) subcutaneous (SC) ritanserin treatment failed to reduce 8% ethanol preference. Risperidone doses that produce marked 5-HT2, but low dopamine D2, receptor blockade (1 and 0.1 mg/kg/day, SC, for 9 and 10 days, respectively) did not modify 8% ethanol preference. On the other hand, a high risperidone dose (10 mg/kg/day, SC, for 14 days), which produces pronounced dopamine D2 receptor blockade, reduced 8% ethanol preference, like the dopamine receptor antagonist haloperidol. Previous studies have shown that both ritanserin and risperidone evoke long-lasting and pronounced suppression of 3% ethanol preference in genetically nonselected rats. However, in the present study, SC ritanserin treatment (1 mg/kg/day for 10 days) did not modify 3% ethanol preference in sP rats. The failure of 5-HT2 antagonists to reduce ethanol preference in sP rats raises the question whether genetic selection might have resulted in altered regulation of 5-HTergic mechanisms in sP rats.

Alcohol Drinking↗

PubMed1993

The nucleus accumbens is a site of action for the inhibitory effect of ritanserin on ethanol intake in rats.

The present study evaluated the effect of central injections of the 5-HT2/1C receptor antagonist, ritanserin, on ethanol intake in rats with developed preference for 3% ethanol. Intracerebroventricular (ICV) injections of ritanserin (10 micrograms/rat/day for 10 days) decreased ethanol preference, while subcutaneous (SC) treatment with the same dose was ineffective. Ritanserin ICV, 1 microgram/rat/day, did not reduce alcohol preference. Bilateral injections of ritanserin into the nucleus accumbens (NAC; 0.5 microgram/site/day for 10 days) produced a prompt and very pronounced suppression of ethanol preference, without affecting total fluid intake. Bilateral injections of ritanserin (0.5 microgram/site/day for 10 days) into the ventral tegmental area (VTA) or into the medial prefrontal cortex (MPC) evoked only slight and variable reduction of ethanol preference. Injections of ritanserin, 5 micrograms/site/day, into the VTA gave a nonselective suppression of the ingestive behavior. The present results provide evidence for a central site of action for the effect of ritanserin on ethanol intake and suggest that the NAC might be a highly sensitive site for its action. Since the NAC is a major target of the mesolimbic dopaminergic system, they also suggest that the effect of ritanserin might be due to interference with this system.

Alcohol Drinking↗

PubMed1993

Effects of selective 5-HT1 receptor agonists in water-deprived rats on salt intake in two-choice tests.

Twenty-two-hour water-deprived rats were divided into two groups: The first was given access to 1.8% saline and water in a 30-min two-choice test; the second was given access to 0.9% saline and water in the same type of intake preference test. Animals were tested following administration of several selective 5-hydroxytryptamine1 (5-HT1) receptor agonists. The results indicated a clear-cut distinction between the effects of selective 5-HT1A receptor agonists, on the one hand, and putative 5-HT1B/1C agonists on the other. Ipsapirone, gepirone, and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all showed evidence of increasing the consumption of 1.8% saline (less preferred to water) but had no effect on intake of the more preferred 0.9% saline. In contrast, 1-3-(chlorophenyl)piperazine (mCPP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) (5-HT1B/1C agonists) reduced intake of 1.8 and 0.9% saline in the two tests. One interpretation of these results is to assume that the 5-HT1A agonists act at inhibitory autoreceptors to diminish central serotonergic activity, while mCPP and TFMPP act postsynaptically to enhance serotonergic activity. The possibility is discussed that mCPP and TFMPP may act to increase the perceived salt concentration during drinking, whereas the 5-HT1A agonists may have the opposite effect.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1991

Effect of capsaicin neonatal treatment on the salt intake of the adult rat.

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.

Animals↗

PubMedDate not supplied

The role of serotonin in craving: from basic research to human studies.

Increasing evidence suggests that craving may play a central role in the mechanisms of addiction. The experience of craving is largely characterized by obsessional thoughts about drugs, triggering compulsive drug-seeking and drug-taking behaviour. In the present article the possible involvement of brain 5-hydroxytryptamine (5-HT) in the mechanisms of craving and relapse is discussed by integrating the results of basic research with those obtained in human studies. Based on studies suggesting that the brain serotonergic system plays a central role in the regulation of impulse-control mechanisms, it is proposed that 5-HT deficiency may contribute to the loss of control over drug-taking, which is a crucial factor for the maintenance of addictive behaviour.

Animals↗

PubMedDate not supplied

Effects of Hypericum perforatum extraction on alcohol intake in Marchigian Sardinian alcohol-preferring rats.

The present study investigated the effect of acute intragastric (i.g.) administration of dry Hypericum perforatum extract (HPE), containing 0.3% hypericin, on ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. The i.g. administration of HPE, 125 or 250 mg/kg, induced a 30-40% reduction in ethanol intake in rats offered 10% (v/v) ethanol for 2 h/day. The effect of these doses was selective, since they modified neither food intake nor food-associated drinking; neither did the same doses modify the rat's gross behaviour in the open-field test. A dose of 500 mg/kg frequently induced immobility and a general suppression of ingestive behaviour. In rats offered 10% ethanol for 12 h/day, ethanol intake following treatment with 250 mg/kg HPE was significantly lower than that of controls for up to 10 h. The effect on ethanol intake was not related to the antidepressant-like effect of HPE revealed in the forced swimming test. In this regard, the effect on ethanol intake was observed after a single administration of 125 mg/kg, whereas the antidepressant effect was observed only after repeated treatment with doses higher than 125 mg/kg HPE. The i.g. administration of HPE, 250 mg/kg, did not affect blood-alcohol levels following i.g. treatment with 0.7 g/kg ethanol, the amount usually ingested in a single drinking episode; thus, the effect is not related to changes in the pharmacokinetics of ethanol. The present study shows that HPE markedly reduces ethanol intake in msP rats, without significantly modifying food intake.

Alcohol Deterrents↗

PubMedDate not supplied

Effects of a methanolic extract and a hyperforin-enriched CO2 extract of Hypericum perforatum on alcohol intake in rats.

Hypericum perforatum extracts (HPE) inhibit ethanol intake in rats. Hypericin and hyperforin have been proposed as major active principles of HPE. The present study compared the effect on ethanol intake in alcohol-preferring rats of two Hypericum perforatum extracts: a methanolic extract containing 0.3% hypericin and 3.8% hyperforin (HPE1) and a CO2 extract (HPE2) with 24.33% hyperforin and very low hypericin content. Freely feeding and drinking rats were offered 10% ethanol 2 h/day and HPE were given intragastrically 1 h before access to ethanol. Both extracts dose-dependently reduced ethanol intake, HPE2 being about eight times more potent than HPE1. Food and water intakes were not affected by doses that reduced ethanol intake. HPE2, unlike HPE1, reduced blood-alcohol levels (BAL) at doses of > or = 31.2 mg/kg, whereas the dose of 15.6 mg/kg, which reduced ethanol intake, did not significantly modify BAL; blood-acetaldehyde levels were never increased. As previously observed for HPE1, intracerebroventricular pretreatment with 5,7-dihydroxytryptamine (150 microg/rat) did not affect attenuation of ethanol intake induced by HPE2, but reduced its effect in the forced swimming test (FST). Intraperitoneal pretreatment with the sigma-1 receptor antagonist NE-100 (0.25 mg/kg) did not affect inhibition of ethanol intake induced by HPE1 (250 mg/kg) or HPE2 (125 mg/kg), but abolished the effect of both extracts in the FST. In conclusion, the present results indicate that HPE2 inhibits ethanol intake more potently than HPE1; the higher potency of HPE2 parallels the hyperforin content, suggesting that hyperforin may have an important role in reducing ethanol intake. Moreover, different neurochemical mechanisms are apparently responsible for the reduction of ethanol intake and for the antidepressant-like effect of HPE.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Coeliac Disease in the Elderly. A multicentre Italian study.

BACKGROUND: In the last few decades, we have observed either an increased incidence of coeliac disease (CD) or an increased frequency of its diagnosis. However, only scant information is available about the prevalence and clinical features of CD in the elderly. AIM OF THE STUDY: To determine the proportion of elderly patients (age > or =65 years) in a large group of consecutive newly-diagnosed cases of adult CD and to analyze the clinical pattern and causes of death. PATIENTS AND METHODS: 1,353 adult patients with active CD were diagnosed by 10 Italian Gastroenterology Units over a period of 10 years. For each patient, a questionnaire comprising demographic data, signs and symptoms with their duration at the moment of the diagnosis, and associated diseases or complications and the causes of death, was drawn up. RESULTS: A total of 60 patients (4.4%) were over 65 years at diagnosis with a M/F ratio of 1/2.75 which was similar to 1/2.42 in the under-65-year age group. The mean time of delayed diagnosis was 17 +/- 19 years in the elderly and 14 +/- 13.8 years in the adults. Classical features of malabsorption were the main presenting symptoms and gastrointestinal disorders were very often also present in the geriatric patients. Twelve aged subjects (20%) died during the follow-up period (mean 4.6 years) often due to cachexia (5%) and heart failure (5%), even though complications such as intestinal lymphoma were present in 8.3% of cases and caused death in 3.3% of the elderly. CONCLUSIONS: In spite of classical manifestations of CD in the elderly, the diagnosis was made in only 4.4% of subjects aged over 65 years and the delay was 17 years. These observations, together with the shortening of life expectancy of elderly CD patients, emphasize the importance for clinicians to consider CD as a possible diagnosis and the need for further investigations to be carried out in the elderly general population.

Adult↗

PubMedDate not supplied

Small bowel enterocyte apoptosis and proliferation are increased in the elderly.

BACKGROUND: It is known that in the elderly the small bowel does not reveal structural and functional deteriorations in normal conditions, whereas the absorptive function is impaired in stress conditions. OBJECTIVE: The balance between enterocyte apoptosis and proliferation being responsible for the maintenance of tissue size, mucosal morphology and function in the gastrointestinal tract, the aim of our study was to evaluate the rates of enterocyte apoptosis and proliferation in the duodenal mucosa of aged human beings in comparison to adults. METHODS: For this purpose, the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end labelling (TUNEL) technique and immunohistochemistry for MIB-1 detection were applied on histological sections of endoscopic duodenal biopsy specimens obtained from 12 healthy elderly subjects (mean age 77.6 years; M/F 7/5) and 12 healthy adult subjects (mean age 37.7 years; M/F 8/4). Counts were performed, at a constant magnification (x200), by computer-aided analysis and the results expressed as median percentages of positive enterocytes. RESULTS: The results showed a significant increase in enterocyte apoptosis in the elderly (15.3 vs. 2.1% in the adults, p < 0.001) which was positively correlated (r(s) = 0.65, p < 0.05) with a significant increase in enterocyte proliferation (37.7 vs. 15.8% in the adults, p < 0.0001). CONCLUSIONS: These data suggest that the maintenance of mucosal architecture throughout the process of aging is due to either a hyperproliferative state or an exaggerated apoptosis with a consequent cellular immaturity, which may impair the absorptive function observed in stress conditions.

Adolescent↗