Evaluation of a minipool reverse transcription-PCR screening method for the detection of hepatitis C virus infection in hemodialysis patients.
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Adult↗
Biomedical subjects
V Theodorou
Publications and source records attributed to V Theodorou.
Antinociceptive effect of pregabalin in septic shock-induced rectal hypersensitivity in rats.
Pregabalin [S-(+)-3-isobutylgaba] is a novel compound under development for its analgesic, anxiolytic, and anticonvulsant properties, and its interaction with the alpha(2)delta-subunit of voltage-dependent Ca(2+) channels. In this study, we investigate the antinociceptive activity of pregabalin in a rat model of delayed visceral hyperalgesia induced by i.p. lipopolysaccharide (LPS) administration. LPS (Escherichia coli, serotype O111:B4) leads to a delayed lowering threshold (9-12 h) of abdominal contractions in response to rectal distension (RD) in awake rats surgically prepared for electromyography of abdominal muscles. This allodynic effect of LPS was blocked by morphine (0.3 mg/kg s.c.), and the action of morphine was antagonized by naloxone (2.5 mg/kg s.c.). A single i.p. (10, 30 mg/kg) and oral (1, 3, 10 and 30 mg/kg) treatment of pregabalin dose dependently suppressed LPS-induced rectal hypersensitivity. When administered 2 h before RD (but preceded 12 h by LPS injection), the oral dose of 10 mg/kg was effective both in the allodynic response induced by LPS and in the intensity of the nociceptive response related to RD. Pretreatment by either naloxone or bicuculline (a GABA(A) antagonist, 0.5 mg/kg i.p.) did not affect the antiallodynic effect of pregabalin. We conclude that pregabalin is a therapeutic candidate in the treatment of gut hypersensitivity not acting through GABA(A) and opiate receptors.
Analgesics, Non-Narcotic↗
Vagally dependent protective action of calcitonin gene-related peptide on colitis.
This work evaluates the mechanism of action of calcitonin gene-related peptide (CGRP) on colitis. Firstly, Wistar rats were intracolonically instilled with trinitrobenzenesulfonic acid (TNBS) and i.v. treated by either alphaCGRP, or hCGRP(8-37), or by vehicle. The inflammatory level was evaluated 8 h and 4 days after TNBS. Secondly, intracerebroventricular alphaCGRP was assessed on the 4-day group with colitis. Finally, i.v. alphaCGRP was administered in vagotomized animals, and tested on the 4-day group with colitis. Colitis was aggravated by hCGRP(8-37), and decreased by peripheral but not central alphaCGRP. AlphaCGRP was inactive on inflammatory parameters in vagotomized colitic rats. This suggests that endogenous peripheral CGRP has an anti-inflammatory role in TNBS-induced colitis, depending upon the integrity of the vagus.
Animals↗
Reduction of the nociceptive response to gastric distension by nitrate ingestion in rats.
BACKGROUND: Dietary nitrates are known to produce nitric oxide in the stomach, which may influence gastric function. AIM: To investigate whether nitrate ingestion modifies gastric sensitivity to distension through a mechanism involving nitric oxide production. METHODS: Nociception, associated with gastric distension ranging from 10 to 40 mmHg, was assessed in anaesthetized rats by the amplitude of cardiovascular depressor responses. Gastric volume corresponding to each distension was recorded. The following intragastric administrations (1 mL) were performed before distension: water (control), KNO3, NaNO3, KCl, NaCl (all at 0.1 mmol/kg), standard food (0.5 g), sodium nitroprusside, a nitric oxide donor (5 mg/kg), and haemoglobin, a nitric oxide scavenger (150 mg/kg) given either with water or KNO3. RESULTS: In controls, the fall in blood pressure increased from 7.8 +/- 2.0 to 31.6 +/- 2. 7 mmHg at distending pressures from 10 to 40 mmHg, respectively. KNO3 significantly reduced the amplitude of blood pressure response for the highest distending pressures (35 and 40 mmHg), while KCl induced a reduction in blood pressure response at all gastric pressures. NaNO3 and NaCl did not induce significant changes in distension-induced depressor responses. Administration of 0.5 g of standard food or sodium nitroprusside reproduced the effect of KNO3, which was reversed by haemoglobin. None of the compounds modified the gastric pressure-volume relationship, except KNO3, which increased gastric volume for the lowest distending pressures, and haemoglobin, which reduced the volume for the highest pressure. CONCLUSIONS: Ingestion of potassium nitrate reduces the sensitivity to gastric distension, through a mechanism involving nitric oxide.
Animals↗
Comparison of the enzyme-linked immunosorbant assay III, recombinant immunoblot third generation assay, and polymerase chain reaction method in the detection of hepatitis C virus infection in haemodialysis patients.
Hepatitis C virus (HCV) serotyping assays have evolved from simple antibody screening tests to complex RNA-based qualitative and quantitative methods. The objective of this study was to compare the HCV screening results from 161 patients in long-term maintenance haemodialysis (HD) as assessed by the recently developed Enzyme Linked ImmunosorbantAssay III (ELISA III), confirmed by the Recombinant Immunoblot 3rd generation assay (RIBA 3rd) and determined by the qualitative HCV reverse transcription polymerase chain reaction (RT-PCR) method. One hundred sixty-one HD patients were tested for the presence of anti-HCV antibodies by the ELISA III and confirmed by the RIBA 3rd. HCV RNA was determined by an HCV RT-PCR method. All reported results that were designated as discrepant, anti-HCV (+) and/or HCV RNA (+) were further investigated by means of a quantitative HCV RT-PCR assay. Reported results obtained from ELISA III and qualitative RT-PCR assays were HCV positive for 16/161 patients (9,93%) and these were designated as anti-HCV (+)/HCV RNA (+). Subsequently, these 16 anti-HCV positive/161 HD patients were confirmed by the RIBA 3rd. Three individuals anti-HCV (-)/RIBA (+)/HCV RNA (-)], the viral load that was reported from the quantitative RT-PCR was less than the assay detection level (< 2,000 viral copies/ml). In view of previous observations, our findings suggest that ELISA III remains still a highly reliable and valuable assay. However, despite the cost, the combination of both ELISA III and qualitative RT-PCR allows a definitive classification on HCV diagnosis.
Adult↗
Protective role of vagal afferents in experimentally-induced colitis in rats.
The aim of this study was to evaluate the regulatory role of vagal afferents in the development of colonic inflammation induced by trinitrobenzenesulfonic acid (TNBS) in rats. Groups of Wistar rats were treated with capsaicin or its vehicle applied perivagally (sham treatment). Colonic transit time was evaluated, and, two days later, one half of the animals received an intracolonic instillation of TNBS/ethanol (40 mg/kg), and the other received saline. Inflammation was evaluated functionally (gut permeability), biochemically (myeloperoxydase activity) and histologically. Vagal capsaicin deafferentation did not modify colonic transit time. In TNBS treated groups, inflammation was enhanced by capsaicin pretreatment, as determined by an increased gut permeability, MPO activity, and histological damage score. These results suggest that vagal afferents have a protective role in TNBS-induced colitis in rats, unrelated to changes in colonic transit time.
Animals↗
Synthesis and in vitro cytotoxicity of lipophilic platinum(II) complexes.
A number of lipophilic platinum(II) complexes of the general structures cis-[Pt(LA)2Cl2] and [Pt(LD)Cl2] were synthesised. Long chain amines (LA) and diamines (LD), prepared from lipidic amino acids, were used as ligands. The in vitro cytotoxicity of the complexes was evaluated against four cell lines (P388, NSCLC-N6, E39, M96). cis-Dichloro-bis(2-aminohexadecanol)platinum(II) was the most active against P388, NSCLC-N6 and E39 (IC50: 11 micrograms/ml, 25 micrograms/ml, 31 micrograms/ml), while dichloro(1,3-heptadecanediamine)platinum(II) presented the highest activity against M96 (IC50: 13 micrograms/ml).
Antineoplastic Agents↗
Involvement of interleukin-1, prostaglandins and mast cells in rectal distension-induced colonic water secretion in rats.
1. In vivo rectal distension (RD) induces a neurally mediated colonic net water hypersecretion in rats. Interleukin-1 beta (IL-1 beta) also induces neural colonic water hypersecretion involving the release of prostaglandins (PGs) and a mast cell degranulation in rats. This study investigated in vivo the role of IL-1, PGs and mast cells in RD-induced colonic hypersecretion. 2. Proximal colonic net water flux was determined using [14C]polyethylene glycol (PEG) 4000 (mol. wt. 4000) in anaesthetized rats. On strips taken from the distal colon: (i) a histological analysis was performed to determine the number of mucosal mast cells (MMC); and (ii) histamine levels were measured by radioimmunoassay after stimulation with compound 48/80. 3. RD induced a net colonic water secretion that was blocked by i.c.v. administration of IL-1ra (an IL-1 receptor antagonist) and indomethacin, and by systemic treatment with doxantrazole and indomethacin. RD decreased the number of resident mast cells and the release of histamine from the distal colonic strips. Moreover, using SDS-PAGE immunoblotting the expression of IL-1 beta was detected in the brain. 4. These results suggest that, in rats, RD induces colonic net water hypersecretion by the activation of a neuro-immunological reflex pathway, involving IL-1 beta, PG release and peripheral mast cell degranulation.
Animals↗
Low-level exposure to diquat induces a neurally mediated intestinal hypersecretion in rats: involvement of nitric oxide and mast cells.
Diquat, a nonselective desiccant herbicide, induces a significant secretion of fluid into the lumen of the gastrointestinal tract of rats at sublethal doses (from 0.5 to 50 mg/kg). This study investigated the effect of an acute low-level exposure to diquat (0. 1, 0.5, and 1 mg/kg) on intestinal net water flux and the mechanisms involved. In anesthetized rats, an intestinal loop (7 cm) was infused with Ringer's buffer containing [14C]-polyethylene glycol 4000. After equilibration, diquat (0.1, 0.5, and 1 mg/kg) was added to Ringer's buffer during 60 min. Net water flux was calculated according to [14C] activity determined in the effluent collected at 15-min intervals. Infused in the intestinal loop for 60 min at doses of 0.5 and 1 mg/kg but not at 0.1 mg/kg, diquat induced an intestinal net water secretion during 180 min with a maximal effect at the highest dose used and during the first hour following the end of diquat infusion. Diquat-induced (1 mg/kg) intestinal net water secretion was blocked by a neurotoxin, tetrodotoxin (5 micrograms/kg iv), doxantrazole (5 mg/kg ip), a mast cell stabilizer, and two inhibitors of NO synthases: l-NAME (25 mg/kg ip) and aminoguanidine (2 mg/kg ip). It is concluded that a single low-level (0.5 and 1 mg/kg) intrajejunal administration of diquat induces a net water intestinal secretion and that this secretory effect is nerve-mediated, implying mast cell degranulation and NO release.
Animals↗
Comparative effects of nonpeptide tachykinin receptor antagonists on experimental gut inflammation in rats and guinea-pigs.
Previous studies have shown tachykinins implicated in gut inflammation. The aim of this work was to evaluate the effect of treatments with tachykinin NK1, NK2, and NK3 selective receptor antagonists on the development of gut inflammation induced by trinitrobenzenesulfonic acid (TNBS) in rats and guinea-pigs. On day 0, rats and guinea-pigs received an intraluminal instillation of TNBS/ethanol (40 mg/kg). Each group was daily treated with intraperitoneally injected NK1 (SR 140333; 0.3 mg/kg/day), NK2 (SR 48968; 5 mg/kg/day), or NK3 (SR 142801; 1, 5, or 10 mg/kg/day) receptor antagonists or their vehicle. On day 4, inflammatory levels were evaluated by measuring gut permeability, myeloperoxidase activity, macro- and microscopic damage scores. In TNBS treated rats, daily administration of SR 140333 (0.3 mg/kg/day) and SR 48968 (5 mg/kg/day) reduced colonic inflammation. In TNBS treated guinea-pigs, daily administration of SR 48968 (5 mg/kg/day) and SR 142801 (at 5 and 10 mg/kg/day) attenuated significantly ileal injury. These results suggest that non-peptide tachykinin receptor antagonists are potent anti-inflammatory agents on gut inflammation in rats and guinea-pigs. However, their activity depends upon the animal species and type of receptor considered.
Animals↗
Rectal distention-induced colonic net water secretion in rats involves tachykinins, capsaicin sensory, and vagus nerves.
BACKGROUND & AIMS: Distention of the intestine induces neural anion secretion in vitro. Both substance P and neurokinin A modify water and ion transport in vivo. This study investigated in vivo (1) the effect of rectal distention (RD) on proximal colonic net water flux, (2) the role of tachykinins, and muscarinic and nicotinic connections, and (3) the influence of capsaicin-sensitive nerves and vagotomy in this effect. METHODS: In anesthetized rats, colonic loops were infused with [14C]polyethylene glycol 4000 Ringer's buffer. Net water flux was calculated according to 14C activity in the effluent collected. RD was performed by inflation of a balloon (2 mL) in the rectum. RESULTS: RD induced a colonic net water hypersecretion. This effect was blocked by previous systemic capsaicin, vagotomy, atropine, and hexamethonium treatment. Both neurokinin 1 (NK1) (SR-140,333; 1 mg/kg) and NK2 (MEN-10,627; 150 microg/kg) antagonists administered intraperitoneally suppressed the RD-hypersecretory effect, whereas NK2 (MEN-10,627; 1.5 microg/kg) and NK3 (SR-142,801; 0.01 mg/kg) antagonists are active when injected intracerebroventricularly. CONCLUSIONS: In vivo, RD induces colonic net water secretion in rats, involving capsaicin-sensitive innervation and vagal nerves. This effect involves tachykininergic pathways at both peripheral and central levels.
Animals↗
Decrease in sensitisation rate and intestinal anaphylactic response after nitric oxide synthase inhibition in a food hypersensitivity model.
BACKGROUND: Although nitric oxide (NO) has been found to have a role in gut inflammation and to modulate immunoglobulin production, little is known about its part in food hypersensitivities. AIM: This study aimed to evaluate the role of NO through the inhibition of constitutive and inducible NO synthase (cNOS and iNOS respectively) on the sensitisation process (antibody titres) and on intestinal anaphylactic responses (colonic hypersecretion upon antigen challenge). ANIMALS AND METHODS: Guinea pigs sensitised to cow's milk proteins were treated either during the sensitisation period or before antigen challenge by N-nitro-L-arginine methyl ester (L-NAME) (inhibiting both cNOS and iNOS) or amino-guanidine (selective iNOS inhibitor). RESULTS: Chronic treatment by L-NAME or aminoguanidine reduced antibody titres and the secretory response to antigen challenge. In contrast, only L-NAME administered before challenge was able to antagonise the hypersecretion induced by the challenge. CONCLUSIONS: NO generated by iNOS has a role in the sensitisation process: iNOS inhibition results in lower rates of antibodies leading to a reduced secretory response upon challenge. In contrast, blockade of colonic hypersecretion by L-NAME but not by aminoguanidine suggests that NO via cNOS is a key mediator in intestinal anaphylactic reactions.
Animals↗
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↗
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↗
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↗
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↗
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↗
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↗