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Biomedical subjects

J More

Publications and source records attributed to J More.

At least 19 recordsLinked to original sources
PubMed2003

Performance prediction of industrial centrifuges using scale-down models.

Computational fluid dynamics was used to model the high flow forces found in the feed zone of a multichamber-bowl centrifuge and reproduce these in a small, high-speed rotating disc device. Linking the device to scale-down centrifugation, permitted good estimation of the performance of various continuous-flow centrifuges (disc stack, multichamber bowl, CARR Powerfuge) for shear-sensitive protein precipitates. Critically, the ultra scale-down centrifugation process proved to be a much more accurate predictor of production multichamber-bowl performance than was the pilot centrifuge.

Blood Cells↗
PubMed2003

Scale-down of continuous filtration for rapid bioprocess design: Recovery and dewatering of protein precipitate suspensions.

The early specification of bioprocesses often has to be achieved with small (tens of millilitres) quantities of process material. If extensive process discovery is to be avoided at pilot or industrial scale, it is necessary that scale-down methods be created that not only examine the conditions of process stages but also allows production of realistic output streams (i.e., streams truly representative of the large scale). These output streams can then be used in the development of subsequent purification operations. The traditional approach to predicting filtration operations is via a bench-scale pressure filter using constant pressure tests to examine the effect of pressure on the filtrate flux rate and filter cake dewatering. Interpretation of the results into cake resistance at unit applied pressure (alpha) and compressibility (n) is used to predict the pressure profile required to maintain the filtrate flux rate at a constant predetermined value. This article reports on the operation of a continuous mode laboratory filter in such a way as to prepare filter cakes and filtrate similar to what may be achieved at the industrial scale. Analysis of the filtration rate profile indicated the filter cake to have changing properties (compressibility) with time. Using the insight gained from the new scale-down methodology gave predictions of the flux profile in a pilot-scale candle filter superior to those obtained from the traditional batch filter used for laboratory development.

Computer Simulation↗
PubMed2000

Laboratory scaledown of protein purification processes involving fractional precipitation and centrifugal recovery.

The ability to predict the performance of large-scale processes is central to the rapid development of successful operations at the pilot and industrial scale. In this article, we examine the operation, at laboratory scale, of precipitation reactors and centrifuges for protein precipitate recovery and dewatering and how they might best mimic large-scale reactors and centrifuges, in this case, a pilot-scale batch stirred-tank reactor and a multichamber-bowl centrifuge. Novel approaches to bench-top centrifuge operation are provided, in particular with a view to delivery of material for subsequent high-resolution purification, which would be obtained at full pilot scale. Results are presented in terms of properties of the protein precipitates, the fraction of solids recovered, and the extent of dewatering achieved. Good agreement was obtained at bench scale (a 1000-fold scale down factor) for all of these parameters for pilot-scale, batch-feed operation. In addition, the methodology developed allows identification of the extent of break-up that occurs in continuous-feed centrifuges when processing shear-sensitive materials such as the protein precipitates studied here.

Alcohol Dehydrogenase↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Brain Fos expression and intestinal motor alterations during nematode-induced inflammation in the rat.

Brain-gut interactions and intestinal motility were studied during pulmonary and jejunal inflammation induced by Nippostrongylus brasiliensis. Jejunal electromyographic activity was continuously recorded from day 1 before to day 28 after infection. Expression of c-fos was assessed in the brain by immunohistochemistry, and myeloperoxidase (MPO) activity was determined in lung and intestine on days 1,7,14, 21, and 28 postinfection. The cyclic intestinal motor pattern was replaced by an irregular activity from day 4, corresponding to larvae migration to the intestine, to day 14. c-fos was expressed in the caudal nucleus of the solitary tract (NTS) and lateral parabrachial nucleus (LPB) on day 1 (lung stage of N. brasiliensis) and in the medial part of the NTS, the LPB, and locus ceruleus on day 7. Pulmonary and intestinal MPO activity was increased from days 1 to 21 postinfection. During N. brasiliensis infection, c-fos expression indicates that specific and different brain nuclei are activated at the onset of pulmonary and intestinal inflammation, which is associated with motor disorders.

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

Evidence for mast cell, leukotriene and nitric oxide involvement in the regulation of the adrenoceptor number of inflamed small intestine in guinea pigs.

Changes in the populations of neurotransmitter receptors involved in the control of intestinal smooth muscle function have been associated with the altered motility of the inflamed gut. Thus, trinitrobenzenesulphonic acid (TNBS)-induced gut inflammation is accompanied by an increase in alpha- and a decrease in beta-adrenoceptor numbers in guinea pig small intestine. In the present study, we investigated the effects of anti-inflammatory compounds (cyclooxygenase inhibitor indomethacin, lipooxygenase inhibitor MK-886, nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), mast cell stabilizer doxantrazole) on TNBS-induced adrenoceptor changes. Smooth muscle adrenoceptor populations, labelled by subtype-specific radioligands 6 days after TNBS, were significantly different from those of sham-treated controls: alpha 1- and alpha 2-adrenoceptor numbers increased by more than 50%, while beta-adrenoceptor numbers decreased by more than 50%. These changes, associated with severe inflammation as assessed histologically and by myeloperoxidase assay, were prevented by doxantrazole or L-NAME, and only partly by MK-886. In contrast, indomethacin did not prevent these changes. It appears then that: (a) mast cell mediators, nitric oxide and leukotrienes are likely to contribute to TNBS-induced changes in adrenoceptor populations in the guinea pig inflamed intestine; (b) there is no evidence for prostanoid involvement in this process. It was suggested that changes in smooth muscle adrenoceptor populations may be an important mechanism by which gut inflammation alters intestinal motility.

Animals↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

[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↗
PubMed1990

[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↗