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Biomedical subjects

J More

Publications and source records attributed to J More.

At least 19 recordsLinked to original sources

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

Role of 5-HT3 receptors and afferent fibers in the effects of mast cell degranulation on colonic motility in rats.

BACKGROUND/AIMS: Mediators released by mast cell degranulation contribute to digestive motility disturbances. According to the role of serotonin and the close proximity of mast cells to nerves, the aim of this study was to assess the role of 5-hydroxytryptamine 3 (5-HT3) receptors, capsaicin-sensitive afferent fibers, and some of their neuropeptides (substance P and calcitonin gene-related peptide) in colonic motor alterations induced by degranulation of mast cells by the compound BrX-537A. METHODS: The effects of BrX-537A (2 mg/kg intraperitoneally) were determined by electromyography in conscious rats implanted with electrodes in the cecocolonic wall. RESULTS: BrX-537A inhibited cecocolonic myoelectric activity for 7-8 hours. A primary and dramatic reduction of spike burst frequency, lasting 30 minutes, was affected by none of the pretreatments tested. The following inhibition was fully antagonized by ketotifen (mast cell stabilizer), granisetron and ondansetron (5-HT3 antagonists), RP-67,580 (NK1 antagonist), and perivagal capsaicin pretreatment. A temporary blockade was observed after administration of CP-96,345 (NK1 antagonist) and in rats systemically treated by capsaicin. The calcitonin gene-related peptide antagonist hCGRP(8-37) did not modify the BrX-537A-induced inhibition. CONCLUSIONS: 5-HT3 receptors, sensory afferent fibers reaching the vagus nerves, and substance P are major components of the colonic motor inhibition induced by mast cell degranulation.

Afferent Pathways

Neurosurgical management of the rheumatoid cervical spine.

Rheumatoid arthritis affects the cervical spine in up to 88% of patients with seropositive disease. Neurologic sequelae result either from direct compression by a rheumatoid pannus or from spinal subluxations. Indications for and techniques of neurosurgical intervention are discussed.

Arthritis, Rheumatoid

Platelet-activating factor and interleukin 1 are involved in colonic dysmotility in experimental colitis in rats.

BACKGROUND: Intracolonic administration of trinitrobenzene sulfonic acid (TNBS) to rats produces chronic colitis associated with an increased release of eicosanoids, platelet-activating factor (PAF), and interleukins. METHODS: Motor effects of TNBS on proximal colon were evaluated electromyographically in rats. Mediator involvement was investigated using eicosanoids and PAF antagonists. RESULTS: The colonic myoelectrical activity was 59 +/- 17 spike bursts per hour lasting 6.9 +/- 1.3 seconds. Two to eight days after TNBS treatment, spike-burst duration was significantly (P < 0.05) higher, with a maximal 1.5-4-fold enhancement at day 3. These alterations were significantly (P < 0.05) reduced by daily treatment with MK-886, a 5-lipoxygenase inhibitor (10 mg/kg, orally), whereas indomethacin (1 mg/kg per day, intramuscularly) was ineffective. At day 3, RP55778, a PAF antagonist (45, 60 mg/kg, intraperitoneally), and rIRAP, an interleukin 1 antagonist (0.3 mg/kg, intraperitoneally) but not KT1-32, a thromboxane A2 antagonist (30, 60 mg/kg orally), nor SKF104,353, a leukotriene D4 antagonist (2, 4 mg/kg, orally), significantly (P < 0.05) reduced the TNB-induced motor effects. CONCLUSION: TNBS-induced colitis in rats involves a delayed long-lasting dysmotility involving PAF, interleukin 1, and some leukotrienes but not leukotriene D4, thromboxane A2, or other cyclo-oxygenase products.

Animals

Preparation of a gelatin-binding conjugate containing gold thiomalate.

Plasma fibronectin has a range of binding sites, for ligands, including denaturated collagen (gelatin). It has been proposed that this activity may be used for nonimmune drug targeting to sites in the extra-cellular matrix such as the targeting of gold thiomalate to rheumatoid joints. In the present study, a novel conjugate has been developed, consisting of the gold thiomalate bound at high density to the gelatin-binding domain of fibronectin, through a polylysine carrier. Isolation and cross-linking of suitable fragments of fibronectin (relative molecular weights 65 and 52 kDa) to polylysine is followed by conjugation to gold thiomalate on a solid phase, gelatin-agarose affinity absorbent. Although gold thiomalate has the ability to inactivate, the protein-gold conjugate produced by this technique retained its gelatin-binding activity.

Drug Carriers

[Changes in gastrointestinal mucins caused by attapulgite. Experimental study in rats].

A histochemical study was carried out to evaluate the changes occurring in mucins secreted by the rat stomach and intestine following a 7 day-treatment with a cytoprotective clay: attapulgite. Staining of gastrointestinal sections was performed with periodic acid-Schiff reagent, alcian blue pH 2.5 and pH 1.0, and with lectin conjugated with horseradish peroxidase for detecting complex carbohydrates. When compared with controls, attapulgite induced an increase in carboxylic mucin content in the cells of the crypts associated with a decrease in sulphated mucins and in binding with soy bean agglutinin in surface epithelial cells in the fundic zone. In the antrum, staining with wheat germ agglutinin was decreased in the crypt cells while Ulex europaeus agglutinin affinity was increased in the glandular cells. The duodenum was characterized by increased binding with Ulex europaeus agglutinin in Brunner's glands. These results show that the polysaccharidic components of the gastrointestinal glycoproteins are modified by attapulgite, and this mechanism may be involved in its cytoprotective effects.

Acetylglucosamine

[Multicenter study of fluconazole in the treatment of oropharyngeal candidiasis in immunodepressed patients].

We have evaluated the efficacy of fluconazole, 50 mg/day for 2 weeks, to treat oropharyngeal candidiasis in immunologically compromised patients. There were overall 27 patients, 25 of which were HIV+ and 2 had neutropenia. The rate of clinical response at the end of therapy, and one week and one month afterwards were 96%, 76% and 64%, respectively. The microbiological eradication was achieved in 36% of patients. The tolerance of the drug was satisfactory, although in 3 cases features of hepatic toxicity were detected. The convenience, good tolerance and clinical efficacy of fluconazole make it the therapy of choice for oropharyngeal candidiasis in immunologically compromised patients.

Adult

A monoclonal antibody to human insulin-like growth factor-I: characterization, use in radioimmunoassay and effect on the biological activities of the growth factor.

A monoclonal antibody (BPL-M23) to insulin-like growth factor-I (IGF-I) was obtained following immunization of BALB/c mice with human IGF-I conjugated to ovalbumin. The affinity constant of BPL-M23 for IGF-I was 10.5 litres/nmol and the cross-reactivities of IGF-II, multiplication-stimulating activity III-2 and insulin were 0.8, 0.03 and less than 0.0001% respectively. Porcine, bovine, ovine and rabbit sera, but not rat or mouse sera, showed substantial reactivity with the antibody. Comparison of radioimmunoassay analyses of 54 human serum samples from normal subjects and acromegalic and GH-deficient patients using BPL-M23 and a polyclonal rabbit antiserum (R557A) to human IGF-I showed a high correlation, indicating the usefulness of the monoclonal antibody in radioimmunoassay. Monoclonal antibody BPL-M23 was capable of abolishing the sulphation, mitogenic and insulin-like activities of IGF-I in in-vitro bioassays, suggesting that these activities may rely upon the same receptor-binding site which is near to the antibody-binding site.

Animals

The urethral muscle (musculus urethralis) of the female calf. Anatomical, histological, histochemical and morphometrical data.

Parts of the female urethra were examined topographically and microscopically in the female calf. The thickness and the straight course of the fibres of the musculus urethralis could best be analyzed in the ventromedian region of the urethra. Examination of the surface area and the distribution of the two primary metabolic fibre types showed that the urethral muscle is capable of contracting quickly with predominantly anaerobic metabolism. The different relationships between type I and type II fibres could be determined also in relation to the position of the lamina propria mucosae.

Adenosine Triphosphatases

[Effects of 2 anabolizing substances with estrogenic action on the urethral muscle of the calf. Histochemical and morphometric study].

The testing of anabolizer utilization in cattle farming needs quick, sure and cheap detection techniques. The administration of oestrogen to cattle produces hypertrophy of the prostate, bulbourethral glands and urethral muscle. The aim of this study was to quantify the effect of the association of zeranol (an hormonomimetic drug acting as an oestrogen) and trembolone (a steroidic structure originating from testosterone) on the urethral muscle of bull calves which is easy to sample in the slaughter-house. An histoenzymological and morphometric study of the urethral muscle of 90 bull calves that had been treated showed considerable hypertrophy in transversal sections of the muscle fibers that was increased by more than 90% in the two main types of striated muscle fiber. The morphological method used is proposed for monitoring the meat of untreated bull calves, requested by a class of consumers.

Animals

Nifedipine in the treatment of renal colic.

A double-blind randomized, clinical trial was conducted in 43 patients to evaluate the efficacy of sublingual nifedipine in the treatment of pain in renal colic. Comparison was made with a combination of dipyrone, pitofenone and fenpipramide, which is usually administered intravenously in Spain. With nifedipine, pain completely disappeared in 44% of the cases, and with the combination of drugs, in 89% (p less than 0.005). More adverse effects were noted with the combination than with nifedipine. Both treatments brought about a slight drop in arterial pressure without leading to hypotension in any case. There was no change in heart rate. The possible causes of the relatively low level of success with nifedipine were analyzed. The possibility of using nifedipine under certain circumstances in which other drugs are contraindicated or when their administration is unfeasible is suggested.

Adult

An in vivo model for pharmacokinetic studies in the kidney.

In order to assess drug renal kinetics in vivo, the two kidneys of seven ewes were surgically placed under the skin. Through the use of renal function tests and a series of biopsies, we found that the kidneys remained normal in their subcutaneous location. Gentamicin renal kinetics were evaluated in conscious animals by a series of biopsies. Histological controls showed only slight lesions due to biopsy; based upon plasma hydrocortisone concentration, there was no indication of chronic stress affecting the renal pharmacokinetics. We suggest that this model has great potential as a method for studying in vivo the kinetics of drug disposition in the renal tissue and assessing the residue level of a drug.

Animals

Impairment of drug metabolism by the liver in experimental fascioliasis in the rat.

Fascioliasis has been produced in the rat by an oral administration of 20 metacercariae of Fasciola hepatica. Hepatic microsomal cytochrome P450 and b5 contents and both aminopyrine demethylase and aniline hydroxylase activities have been measured during the course of the experimental distomiasis. The cytochrome P450 concentration and microsomal drug metabolizing enzymes generally fell by weeks 3 to 8 post-infestation and recovered to normal values thereafter. For the same period, both the histoenzymatically assayed liver cytochrome oxidase and arylsulphatase activities were reduced whereas there were correlated increases in glutamic pyruvic and glutamic oxaloacetic plasma transaminases. Tissue inflammation and destruction provoked by young histophagous migrating flukes could be responsible for these changes that have already been observed in several hepatic diseases. The possible influence of naturally-induced fasciolasis on liver drug metabolism is discussed.

Aminopyrine N-Demethylase

Evaluation of the trace metal supplements for a synthetic low lactose diet.

A trace element supplement used with a synthetic low lactose milk (Galactomins 17 and 18) has been evaluated by means of metabolic balance studies in 4 infants with dissacharide intolerances. The supplement was considered satisfactory for iron and manganese but increases in its zinc and copper content are probably necessary to ensure adequate retentions of these metals.

Body Weight