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Biomedical subjects

G Barbara

Publications and source records attributed to G Barbara.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neurotransmitters modulate cytokine-stimulated interleukin 6 secretion in rat intestinal smooth muscle cells.

BACKGROUND & AIMS: Cytokine production by resident cells of the richly innervated muscularis externa may contribute to neuromuscular changes observed during intestinal inflammation. This study investigated neurotransmitter modulation of cytokine production by intestinal smooth muscle. METHODS: We measured interleukin (IL)-6 messenger RNA expression by reverse-transcription polymerase chain reaction, IL-6 by bioassay, and cyclic adenosine monophosphate by enzyme immunoassay in rat cultured intestinal smooth muscle cells exposed to IL-1beta, in the presence or absence of neurotransmitters. RESULTS: IL-1beta significantly increased IL-6 messenger RNA and protein. This was dose-dependently enhanced by vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and norepinephrine and inhibited by [LYS1,PRO2,5,ARG3,4,TYR6]VIP and propranolol, respectively. Forskolin mimicked the stimulatory effects of these neurotransmitters on IL-6 secretion, and the protein kinase inhibitor6-22 amide abolished the actions of VIP, CGRP, and norepinephrine, but not that of human recombinant IL-1beta, on IL-6 secretion. These agents each increased cyclic adenosine monophosphate activity in muscle substance P, and the neurokinin 1 agonist Ac-[Arg6,Sar9,Met(O2)11] substance P(6-11) inhibited the IL-1beta-induced IL-6 release. CONCLUSIONS: This study shows neuropeptide and sympathetic modulation of IL-1beta-induced IL-6 production by intestinal smooth muscle. These interactions may contribute to altered muscle function during intestinal inflammation.

Adrenergic beta-Antagonists↗
PubMed1999

Putative inflammatory and immunological mechanisms in functional bowel disorders.

The observations that irritable bowel syndrome (IBS) may be precipitated by an acute enteric infection, or occurs commonly in patients in remission from inflammatory bowel disease (IBD) has prompted consideration of inflammation as a putative basis for symptom generation in IBS. In this regard, IBS may follow a pattern of pathogenesis that is similar to asthma--which was once considered a psychosomatic disease. This review examines the basic scientific evidence of a functional interface between the immune and sensory-motor systems of the gut and discusses how this may be relevant to a subgroup of IBS patients. In addition, review will examine the implications of this for the diagnosis and treatment of IBS.

Animals↗
PubMed1999

Predominant symptoms identify different subgroups in functional dyspepsia.

OBJECTIVE: Dyspepsia is a common syndrome that often defies diagnosis. Whether the unexplained (or "functional") dyspepsia represents a homogeneous syndrome or includes different subgroups with specific clinical features has not been clarified. The aim of this study was to investigate the relationship between symptom severity, demographic features, and gastric dysmotility in a large series of patients with functional dyspepsia. METHODS: Severity of individual digestive symptoms, demographic features, and scintigraphic gastric emptying of solids were evaluated in 483 patients with chronic unexplained dyspepsia. RESULTS: Two main subgroups were identified. The first was characterized by predominant epigastric pain, male gender (61%), and normal gastric emptying. The second subgroup was characterized by predominant nonpainful symptoms, female gender (60%), a high frequency of associated irritable bowel syndrome (30%), and delayed gastric emptying (42%). A third group included approximately one-third of patients who did not present with any predominant symptom, and was characterized by a high frequency of delayed gastric emptying (30%), overlapping irritable bowel syndrome (28%), and gastroesophageal reflux disease (41%). CONCLUSIONS: Different subgroups exist among patients with functional dyspepsia seen in a referral center. They can be identified by the predominant symptom and are characterized by different demographic, clinical, and pathophysiological features.

Adult↗
PubMed1999

Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia.

OBJECTIVE: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean +/- SE) of nitrinergic neurons per section was visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 +/- 0.1) and the gastric component (2 +/- 0.6) of the LES as compared to those in controls (15 +/- 5 and 12 +/- 4, respectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 +/- 1) were significantly reduced in comparison to those of controls (10 +/- 2) (p < 0.05). CONCLUSIONS: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Adult↗
PubMed1999

How should Helicobacter pylori negative patients be managed?

Dyspepsia is a digestive syndrome distinct from (although frequently overlapping with) gastro-oesophageal reflux disease (GORD) and irritable bowel syndrome (IBS), which is characterised by various combinations of painful and non-painful symptoms arising from the epigastrium. Dyspepsia can be secondary to a variety of diseases, but in most instances it is idiopathic. Helicobacter pylori infection is responsible for the majority of peptic ulcers and of other diseases potentially associated with dyspepsia. Nevertheless, a causal role for H pylori infection in symptom occurrence has not been established. Experimental data indicate that H pylori eradication does not improve symptoms in the majority of dyspeptic patients. It has been proposed recently that H pylori negative patients should be managed according to their clinical presentation. Some reports suggest that taking into consideration the most relevant or "predominant" symptom may help to identify distinct subgroups among dyspeptic patients with different underlying pathophysiological abnormalities and different responses to treatment. Well designed and conducted prospective studies are needed to verify whether treatment of H pylori negative dyspeptic patients based on the predominant symptom actually is a cost effective approach.

Dyspepsia↗
PubMed1999

Stress, inflammation and the irritable bowel syndrome.

Studies in animals have shown that inflammation of the mucosa of the gastrointestinal tract is accompanied by changes in enteric nerve and smooth muscle function, and in gut motility and sensation. In some instances, these changes persist long after resolution of the mucosal inflammation. Some of these observations have been made in human studies of irritable bowel syndrome (IBS) in patients after an enteric infection or in patients in remission from ulcerative colitis. Stress has also been implicated as a modulator of gastrointestinal inflammation in both animal and human studies. In animals, stress causes a reactivation of previous enteric inflammation and induces the attendant physiological changes. Prior stress also enhances the response to subsequent inflammatory stimuli. In humans, postinfectious IBS tends to occur in patients with psychological profiles similar to those observed in IBS patients and in whom there is a higher incidence of stressful life events just before exposure to the infection. Taken together, these observations link stress and inflammation as a putative pathogenetic mechanism in at least a subset of IBS patients.

Animals↗
PubMed1998

Detection of substance P immunoreactivity in human peripheral leukocytes.

The neuropeptide substance P (SP) has a marked proinflammatory effect and modulates the immune response. In this study, we tested the hypothesis that human peripheral leukocytes contain SP. Resting peripheral leukocytes collected from healthy volunteers (n = 20) were studied by applying a SP rabbit polyclonal antiserum to both flow cytometry and immunohistochemistry. To identify possible changes in Sp expression, we also analyzed both activated T-lymphocytes (cell cultures; n = 5 normal subjects) and neoplastic hematologic samples of different types of leukemias. Flow cytometry showed that normal granulocytes and monocytes contained SP, whereas lymphocytes were generally negative (or weakly positive) with the exception of a few (10-20%) positive subsets. In comparison, activated T-lymphocytes were markedly immunolabeled by SP as well as samples from neoplastic patients demonstrated strong SP immunoreactivity in all cell lineages. This pattern was confirmed by immunohistochemistry on cytospins. Our results support a potential role for SP-mediated immunomodulatory mechanisms both in normal and pathological conditions.

Flow Cytometry↗
PubMed1998

Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea-pig common bile duct.

Application of electrical field stimulation (EFS; trains of 10 Hz, 0.25 ms pulse width, supramaximal voltage for 60 s) to the guinea-pig isolated common bile duct pretreated with atropine (1 microM), produced a slowly-developing contraction ('on' response) followed by a quick phasic 'off' contraction ('off peak' response) and a tonic response ('off late' response), averaging 16+/-2, 73+/-3 and 20+/-4% of the maximal contraction to KCl (80 mM), n=20 each, respectively. Tetrodotoxin (1 microM; 15 min before) abolished the overall response to EFS (n 8). Neither in vitro capsaicin pretreatment (10 microM for 15 min), nor guanethidine (3 microM, 60 min before) affected the excitatory response to EFS (n 5 each), showing that neither primary sensory neurons, nor sympathetic nerves were involved. Nomega-nitro-L-arginine (L-NOARG, 100 microM, 60 min before) or naloxone (10 microM, 30 min before) significantly enhanced the 'on' response (294+/-56 and 205+/-25% increase, respectively; n=6-8, P<0.01) to EFS. The combined administration of L-NOARG and naloxone produced additive enhancing effects (655+/-90% increase of the 'on' component, n = 6, P<0.05). The tachykinin NK2 receptor-selective antagonist MEN 11420 (1 microM) almost abolished both the 'on' and 'off late' responses (P<0.01: n=5 each) to EFS, and reduced the 'off-peak' contraction by 55+/-8% (n=5, P<0.01). The subsequent administration of the tachykinin NK1 receptor-selective antagonist GR 82334 (1 microM) and of the tachykinin NK3 receptor-selective antagonist SR 142801 (30 nM), in the presence of MEN 11420 (1 microM), did not produce any further inhibition of the response to EFS (P>0.05; n=5 each). At 3 microM, GR 82334 significantly reduced (by 68+/-9%, P<0.05, n=6) the 'on' response to EFS. The contractile 'off peak' response to EFS observed in the presence of both MEN 11420 and GR 82334 (3 microM each) was abolished (P<0.01; n=6) by the administration of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 microM). PPADS (30 microM) selectively blocked (75+/-9 and 50+/-7% inhibition, n = 4 each) the contractile responses produced by 100 and 300 microM ATP. Tachykinin-containing nerve fibres were detected by using immunohistochemical techniques in all parts of the bile duct, being distributed to the muscle layer and lamina propria of mucosa. In the terminal part of the duct (ampulla) some labelled ganglion cells were observed. In conclusion, this study shows that in the guinea-pig terminal biliary tract tachykinins, released from intrinsic neuronal elements, are the main NANC excitatory neurotransmitters, which act by stimulating tachykinin NK2 (and possibly NK1) receptors. ATP is also involved as excitatory neurotransmitter. Nitric oxide and opioids act as inhibitory mediators/modulators in this preparation.

Animals↗
PubMed1998

Reproducibility of a solid and of a liquid caloric meal for gastric emptying studies.

Simple meals are required for routine scintigraphic gastric emptying studies. We evaluated the reproducibility of a caloric liquid meal (520 kcal) compared to that of a solid meal (638 kcal) in 8 and 11 healthy volunteers, respectively. Gastric emptying rates and half-times were similar in two tests using the same meal, while the methods used to express lag times were not highly reproducible. The emptying rates and half-times of the liquid meal were delayed after the intake of bellafoline. In conclusion, this study demonstrates that: (a) gastric emptying rates and half-times are reproducible parameters for the expression of scintigraphic gastric emptying studies; (b) mathematical methods to express lag times are not highly reproducible; (c) a 500 kcal liquid meal is sensitive to the effects of bellafoline, a drug able to delay gastric emptying. Further clinical evaluation is required to test its applicability in routine studies.

Adult↗
PubMed1998

Constipation: a common problem in patients with neurological abnormalities.

Constipation is a frequent complaint among patients with different neurological diseases. This review provides a brief account of the numerous conditions affecting the central, peripheral and intrinsic (enteric) nervous systems in which constipation can be the only clinical manifestation or a component of a complex syndrome. Recent neuropathophysiological acquisitions show that any structural or functional impairment of the intrinsic innervation of the gut, including both developmental (i.e., Hirschsprung's disease and intestinal neuronal dysplasia) and acquired (i.e., either degenerative or inflammatory neuropathies) disorders, can be associated with constipation. Constipation may also arise from derangements of the peripheral nervous system, including diabetes and primary chronic autonomic failure (pandysautonomias). Finally, in the central nervous system, a wide array of disorders (post-traumatic, degenerative, ischaemic or neoplastic) are recognized to determine bowel dysfunction, ultimately leading to constipation. Further understanding of the fine pathophysiological mechanisms through which the intrinsic and extrinsic nerve supplies to the digestive system are involved in idiopathic constipation or in diseases generating this symptom will hopefully lead to a better treatment of this frequent pathological condition.

Central Nervous System Diseases↗
PubMed1997

Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice.

BACKGROUND & AIMS: Although most acute enteric infections in humans resolve, some herald the onset of chronic symptomatology and persistent gastrointestinal dysfunction--so-called postinfectious irritable bowel syndrome. This entity is poorly understood, and there are no animal models for testing hypotheses. The aim of this study was to investigate changes in intestinal neuromuscular function during and after recovery from acute intestinal inflammation due to primary Trichinella spiralis infections in NIH Swiss mice. METHODS: Morphometric scores and myeloperoxidase activity were used to monitor mucosal inflammation. Neuromuscular function was assessed in vitro by pharmacological or electrical stimulation of longitudinal muscle. RESULTS: Acute inflammation resulted in an approximately 50% reduction of villus height, an approximately 50% increase in crypt depth, and a threefold increase in myeloperoxidase activity. Carbachol- and KCl-induced contractions of longitudinal muscle were also increased threefold, whereas contraction induced by electrical field stimulation of intramural nerves was decreased by 60%. Mucosal morphology and myeloperoxidase activity rapidly returned to control values, but the increased muscle contractility and the decreased excitatory neurotransmission persisted as long as 42 and 28 days after infection, respectively. CONCLUSIONS: These findings show that transient mucosal inflammation alters enteric neuromuscular function; this alteration persists after recovery from the infection and mucosal restitution.

Animals↗
PubMed1996

Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia.

BACKGROUND & AIMS: Although gastric dysmotility and dyspeptic symptoms are often associated, their relationship remains unclear. The aim of this study was to evaluate the relationship between gastric emptying abnormalities and clinical features in functional dyspepsia. METHODS: In 343 patients with functional dyspepsia, the gastric emptying of solids was measured by a radioisotopic technique and four dyspeptic symptoms (epigastric pain and burning, postprandial fullness, nausea, and vomiting) were measured as absent, mild, relevant, and severe, according to their influence on patients' usual activities. RESULTS: Delayed gastric emptying was detected in 33.5% of dyspeptics. Delayed gastric emptying was particularly frequent in patients characterized by female sex, low body weight, presence of relevant and severe postprandial fullness, nausea, vomiting, and absence of relevant and severe epigastric pain. Logistic regression showed that delayed gastric emptying was invariably associated with female sex and postprandial fullness (odds ratio, 2.34; 95% confidence interval, 1.45-3.75) and vomiting (odds ratio, 4.04; 95% confidence interval, 1.30-12.54) when coded as severe and only postprandial fullness (odds ratio, 3.78; 95% confidence interval, 1.78-8.01) when coded as relevant and severe. CONCLUSIONS: Female sex, relevant and severe postprandial fullness, and severe vomiting are independently associated with delayed gastric emptying of solids in patients with functional dyspepsia seen in a referral center.

Adult↗
PubMed1996

[The innervation of the digestive tract: its morphofunctional and neurochemical aspects].

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.

Animals↗