Biomedical subjects

V Theodorou

Publications and source records attributed to V Theodorou.

30 records · Page 2Linked to original sources

PubMed1996

Integrative neuroimmunology of the digestive tract.

The epithelium of the gastrointestinal tract is continuously exposed to the external environment containing food antigens, microbes and other pathogens. Immunologic and nonimmunologic mechanisms contribute to the neutralization and elimination of these foreign antigens. The immune system of the intestine is the most extensive in the organism and involves diffuse populations of immune cells, lymphoid aggregates and intraepithelial lymphocytes. On the other hand, the functions of the digestive tract contribute to the overall host defense (mucus secretion, gastric acid secretion, water and electrolyte secretion and peristaltism). These functions are regulated by intrinsic and extrinsic nervous systems. It is currently recognized that the physiological and pathological responses of the intestine require an integrate neuroimmune network. Such neuroimmune regulation is based on anatomical and biochemical supports. Indeed, there are membrane-to-membrane contacts between axonal varicosities and the immune cells. Specific receptors for neurotransmitters such as substance P, vasoactive intestinal polypeptide and somatostatin have been identified in many immune cells. Nerve profile change has been described under pathological conditions such as parasitic infections and acute phase of inflammation. In addition to supporting the growth and survival of several populations of nerves the classical nerve growth factor (NGF) has been shown to affect an immune cell population by inducing mast cell hyperplasia. Furthermore the NGF can induce mast cell degranulation, acting directly on mast cell membrane NGF receptors or indirectly by NGF-mediated release of substance P by peripheral extrinsic or intrinsic nerves. Moreover, non-immune cells such as epithelial and smooth muscle cells can produce immunologic messengers under pathological conditions such as infectious diseases or inflammation. Besides the local regulation of gut functions, neuroimmune control can be exerted at extra-intestinal sites. During physiological and pathological conditions, gastrointestinal secretions and motor events are strongly regulated by the central nervous system. Moreover, infectious agents can induce cytokine and particularly interleukin-1 release by the brain astrocytes and microglial cells which have been shown to play a pivotal role in fever induction and modifications of the gastrointestinal functions. Visceral afferent fibers play a pivotal role in 'cross-communication' between central sites and immune response. Recent studies evoke, more specifically, the role of vagus as a key modulatory participant in the close relationship between the extraintestinal nerves and the immune system. Future work in this field will clarify the role of the different participants in the intimate communication between the gastrointestinal tract, immune system and central nervous system.

Animals↗

PubMed1995

Boosted systemic immune and local responsiveness after intestinal inflammation in orally sensitized guinea pigs.

BACKGROUND & AIMS: Intestinal inflammation resulting in disruption of the mucosal barrier function has been proposed as a cause of increased incidence of allergic diseases. This study was designed to evaluate whether intestinal inflammation is able to change the immune responsiveness to sensitization and antigen challenge responses. METHODS: Guinea pigs orally sensitized to cow's milk proteins were either treated or not treated with trinitrobenzenesulfonic acid (TNBS) to induce intestinal inflammation and compared with control animals (not sensitized). Systemic immune and local responsiveness to antigen challenge were assessed by measuring antibody serum titers, colonic fluid secretion, mucosal histamine level, and mucus depletion. Intestinal permeability was evaluated from 51Cr-ethylenediaminetetraacetic acid (EDTA) recovery and beta-lactoglobulin serum level. RESULTS: Immunoglobulin E titers were higher in TNBS-treated animals than in non-TNBS-treated sensitized animals. Antigen challenge in TNBS-treated animals induced a fourfold increase of colonic secretion and greater histamine and mucus depletion than in non-TNBS-treated animals. Permeability to 51Cr-EDTA increased 5 days after TNBS treatment but was unchanged after antigen challenge. In contrast to controls, beta-lactoglobulin was not detected in the sera of challenged sensitized and TNBS-treated animals. CONCLUSIONS: Intestinal inflammation increasing gut permeability enhances the sensitization process. Therefore, local anaphylactic reactions are exacerbated after antigen challenge.

Analysis of Variance↗

PubMed1995

Implication of NK1 and NK2 receptors in rat colonic hypersecretion induced by interleukin 1 beta: role of nitric oxide.

BACKGROUND & AIMS: Interleukin (IL) 1 beta is known to induce a neurally mediated colonic water secretion in vivo. The aim of this study was to investigate the mechanism of action of IL-1 beta on colonic net water flux and the role of tachykinins and nitric oxide. METHODS: In anesthetized rats, isolated colonic loops were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent that was collected at 15-minute intervals. RESULTS: Recombinant human IL-1 beta induced a 30-minute colonic hypersecretion. This effect was blocked by NK1 and NK2 antagonists, tetrodotoxin, and NG-methyl-L-arginine (L-NMA). L-arginine reversed the antisecretory effect of L-NMA on IL-1 beta-induced hypersecretion but did not modify the IL-1 beta-induced hypersecretion. Both NK1 and NK2 agonists induced a colonic hypersecretion, and their effects were blocked by L-NMA and tetrodotoxin. The NK3 agonist had no effect on water movements. The NK2 antagonist abolished the secretory effect of NK1 agonist; in contrast, the NK1 antagonist had no effect on the NK2 agonist-induced secretion. CONCLUSIONS: IL-1 beta-induced colonic hypersecretion in vivo involves NK1- and NK2-receptor activation in cascade, suggesting a release of substance P and neurokinin A acting through NO release.

Animals↗

PubMed1995

Adamantinoma of the olecranon. A report of a case with serial metastasizing lesions.

Adamantinomas are slow-growing, invasive malignant tumors. Although the majority of cases have arisen in the tibia, these aggressive tumors have been reported in most of the long bones. This is the first known report of a patient with adamantinoma of the olecranon, an unusual site for this lesion. However, the patient not only had a novel site of appearance of the tumor and local recurrence of the disease, but also had a series of distant, isolated, bony tissue metastases before a fatal metastasis to the lung within a 9-year period. Although metastasis to other bony sites has been reported, a series of metastases to bony and soft tissues is unusual.

Ameloblastoma↗

PubMed1994

Interleukin 1 induces a neurally mediated colonic secretion in rats: involvement of mast cells and prostaglandins.

BACKGROUND/AIMS: Interleukin 1 beta (IL-1 beta) is known to regulate intestinal ion and water transport in vitro through prostaglandin release. This study investigated the effect of IL-1 beta on colonic net water flux in vivo to determine its nature (nerve mediation versus action on the epithelium), the mediators involved, and its relationship with mast cell degranulation. METHODS: Isolated colonic loops of anesthetized animals were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent collected at 15-minute intervals. Histological analysis was used to identify intact mast cells in colonic sections and radioimmunoassay to determine histamine levels. RESULTS: Both IL-1 beta and the calcium ionophore A23187 induced colonic hypersecretion during 30 minutes. This effect was blocked by tetrodotoxin, doxantrazole, and indomethacin but not chlorpheniramine. Recombinant human interleukin 1 beta decreased the number of intact mast cells. This effect was eliminated by doxantrazole but not tetrodotoxin or indomethacin. A23187 or IL-1 beta increased histamine levels in the effluent during 75 and 45 minutes, respectively. CONCLUSIONS: In vivo, rhL-1 beta induces colonic hypersecretion in rats. This effect is nerve mediated but not H1 receptor mediated and involves mast cell degranulation and prostaglandin release.

Animals↗

PubMed1994

Protective action of diosmectite treatment on digestive disturbances induced by intestinal anaphylaxis in the guinea-pig.

METHODS: Colonic transit time, faecal moisture and intestinal permeability were assessed in guinea-pigs sensitized intraperitoneally with cow's milk and challenged with an oral administration of beta-lactoglobulin. One group of animals was treated for 1 week with diosmectite (500 mg.kg/day) and another with placebo. A control group was not sensitized but treated with diosmectite. RESULTS: In sensitized animals receiving placebo, challenge with beta-lactoglobulin induced a significant (P < 0.05) decrease in colonic transit time, and increases in faecal moisture and intestinal permeability. These changes were not observed in animals treated with diosmectite. CONCLUSION: Diosmectite pre-treatment protects against allergic digestive disturbances induced by antigen administration in guinea-pigs sensitized to cow's milk.

Anaphylaxis↗

PubMed1994

Anaphylactic colonic hypersecretion in cow's milk sensitized guinea-pigs depends upon release of interleukin-1, prostaglandins and mast cell degranulation.

METHODS: The effect of beta-lactoglobulin (beta-LGI) challenge on net water movements into the proximal colon and the role of Interleukin-1 (IL-1), prostaglandins and mast cell degranulation on the challenge-induced net water changes were assessed in vivo using isolated colonic loops in anaesthetized guinea-pigs immunized to bovine milk. RESULTS: beta-lactoglobulin challenge infused into the colonic loop during 30 min reversed the net water flux into a net secretion during the period of antigen infusion. Doxantrazole, a mast cell stabilizing agent, administered 120 min before challenge infusion, suppressed challenge-induced hypersecretion. Similarly recombinant IL-1 receptor antagonist protein abolished the antigen-induced colonic secretory effect. Indomethacin, a prostaglandin synthesis inhibitor, administered 20 min prior to antigen infusion, significantly (P < 0.05) reduced, but did not abolish, the challenge-induced colonic secretory effect. CONCLUSIONS: These results suggest that IL-1 plays an important role in antigen challenge-induced colonic hypersecretion which involves mast cell degranulation and prostaglandin release.

Anaphylaxis↗

PubMed1993

Recombinant interleukin-1 receptor antagonist protein prevents sensitization and intestinal anaphylaxis in guinea pigs.

Recombinant interleukin-1 receptor antagonist protein (rlRAP, 0.5 mg/kg) administered intraperitoneally in guinea pigs one hour before primary and booster parenteral sensitization (1 ml) by cow milk, led to a reduced immunoglobulin E (IgE) production, as displayed by a passive cutaneous anaphylaxis test. rlRAP administered intraperitoneally in sensitized guinea pigs at 0.5 mg/kg 10 min before challenge administration (beta-lactoglobulin, 100 mg per os), also prevents the colonic motor and secretory changes induced by intestinal anaphylaxis. These results suggest the involvement of interleukin-1 in food allergy and evidence a double protective role for rlRAP in food hypersensitivity.

Anaphylaxis↗

PubMed1992

Absence epilepsy: early prognostic signs.

We have studied 124 children with typical absence epilepsy. The onset of symptoms was in 12% under 4 years, in 51% between 4-8 years and in 37% above 8 years. The F:M ratio was 2:1 in children under 4 years versus 1:1 above 8 years. Absences alone occurred in 82% and absences followed or preceded by generalized tonic-clonic seizures (GTCS) in 6.5% and 11%, respectively. Simple absences were not seen in children under 4 years and were more frequent (14%) in the 4-8 years age group. Family history was positive for epilepsy in 20% and febrile convulsion in 7%. Sixteen percent had a positive past history of febrile convulsions. All patients showed bilateral, synchronous spike-wave discharges from 2.5 to 4 c/s. Lateralized spikes, spike-slow wave complexes were found in 27%. Photosensitivity was present in 18% and was marked in 12%. Monotherapy with sodium valproate or ethosuximide (91% SV) was successful in 85% of patients with absences alone and 68% of the absences with GTCS. Only 2% were not fully controlled either on monotherapy or polytherapy. Treatment was withdrawn in 41 patients and 13 relapsed. We have identified four factors associated with relapses: (a) poor initial response to treatment, (b) lateralized focal EEG abnormality and/or marked photosensitivity, (c) the evolution to myoclonic epilepsy, and (d) early withdrawal of AED (< 3 years).

Adolescent↗

PubMed1991

Involvement of 5-hydroxytryptamine in the intestinal motor disturbances induced by mast cell degranulation in rats.

Fasted rats with chronically implanted electrodes were used for investigation of the effects of mast cell degranulation induced by compound 48/80 and BrX-537A and their antagonism by previous administration of 5-hydroxytryptamine (5-HT) antagonists on duodenal and jejunal myoelectric activity. Administered i.p., both 48/80 (1 mg/kg i.p.) and BrX-537A (2 mg/kg i.p.) abolished the intestinal spiking activity of duodeno-jejunum with a progressive recovery, BrX-537A being less active. These effects were dose-related. Injected prior to 48/80, methysergide (1 mg/kg) reduced by about 80% both duodenal and jejunal inhibition of spiking activity with early recovery of a normal pattern. In contrast, ketanserin (1 mg/kg) had selective reducing effects on the duration of the spiking inhibition induced by 48/80 and BrX-537A on the duodenum only. Zacopride (1 mg/kg) and ICS 205-930 (50 micrograms/kg) shortened and suppressed, respectively, the inhibition of intestinal spiking activity with early restoration of intestinal motility in both duodenum and jejunum. We conclude that, in fasted rats (i) the degranulation of peritoneal mast cells induces alterations in intestinal myoelectric activity through the release of 5-HT (ii) these effects are mainly mediated through both 5-HT1 and 5-HT3 receptors.

Animals↗

PubMed1989

Water absorption from the pig proximal colon: relations with feeding and flow of digesta.

Net water absorption from the proximal colon was determined at 2 h intervals for 10 h after a meal in four pigs chronically fitted with two cannulas in the proximal colon (1st and 2nd coil) and a catheter in the ileum. Water flux was measured by infusing a marker (51Cr-EDTA) at a constant rate into the ileum and by sampling colonic content through the cannulas. Two hours after the meal water was absorbed by the colonic segment situated between the two cannulas at a rate of 0.7 +/- 0.1 ml/min. Then the net water absorption increased progressively and reached a maximum (1.7 +/- 0.3 ml/min) 8 h after eating. These postprandial changes in water absorption were positively correlated (r = 0.63, n = 40) with changes in the flow of digesta at the level of the proximal cannula. The concentration of volatile fatty acids and the osmolality of the digesta, as well as the transit time of a marker (phenolsulphonphthalein) between the two cannulas, did not significantly fluctuate after the meal and were not correlated with water absorption. Antibiotic treatment for 3 days (neomycin, 15 g/day, continuously infused into the ileum) induced a 90% decrease in volatile fatty acid concentration but did not modify colonic water absorption nor its postprandial changes. These results show a postprandial pattern of colonic water absorption which is mainly controlled by the flow of digesta into the colon.

Animals↗

PubMedDate not supplied

Design, synthesis, and conformational study of biologically active photolabeled analogues of the main immunogenic region of the acetylcholine receptor.

Photoaffinity labeling is a powerful tool for the characterization of the molecular basis of ligand binding to acceptor molecules, which provides important insights for mapping the bimolecular interfaces. The autoimmune disease myasthenia gravis is caused by autoantibodies against the acetylcholine receptor (AChR). The majority of the anti-AChR antibodies bind to the "main immunogenic region" (MIR) of the AChR. To identify the contact points between the complementarity determining regions of the anti-MIR antibodies that recognize the MIR contact sites of the AChR, we present here three photoreactive dodecapeptide MIR analogues containing the photolabel p-benzoyl-L-phenylalanine (Bpa) moiety, either in position 1 or 11. The structure of the produced 12-mers was analyzed using two-dimensional (1)H-NMR spectroscopy, whereas their binding to anti-MIR monoclonal antibodies (mAbs) was determined by immunochemical assays. In all cases the modifications resulted in conservation of the beta-turn conformation of the N-terminus, which has been proved essential for antibody recognition and increased anti-MIR binding relative to the MIR decapeptide.

Affinity Labels↗