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Biomedical subjects

P Bass

Publications and source records attributed to P Bass.

At least 19 recordsLinked to original sources
PubMed2002

Intravesical meglumine gamma-linolenic acid in superficial bladder cancer: an efficacy study.

OBJECTIVES: Gamma-linolenic acid (GLA) is known to be cytotoxic to malignant cells. We assessed the efficacy of the novel intravesical formulation, meglumine gamma-linolenic acid (MeGLA), in a phase II trial, in patients with recurrent, superficial bladder cancer. PATIENTS AND METHODS: Thirty patients with recurrent, superficial transitional cell carcinoma (TCC) were recruited. The tumour pattern was recorded at flexible cystoscopy. Patients received a single intravesical instillation of 50ml of either 50mg (1mg/ml) (15 patients), or 125mg (2.5mg/ml) (15 patients) of MeGLA in water, retained for one hour. At subsequent cystoscopy, the tumour patterns were recorded, prior to undertaking routine cystodiathermy. Biopsies were obtained for histological assessment. Responses were divided into complete, partial or none. RESULTS: All 30 patients retained the drug for 1 hour without significant local or systemic side effects. There were 4 (13%) complete responses, 9 (30%) partial responses, and 17 (57%) non-responders. Histology showed no evidence of damage to surrounding urothelium. CONCLUSIONS: Our data confirms the safety and tolerability of MeGLA, which is consistent with findings from a previous phase I trial. A response rate of 43% also indicates that MeGLA has a significant cytotoxic effect against TCC and the results are similar to those obtained using standard, single-dose, intravesical regimens.

Administration, Intravesical↗
PubMed2002

Small intestinal transections decrease the occurrence of tapeworm-induced myoelectric patterns in the rat.

Abstract Luminal infection by the noninvasive tapeworm, H. diminuta, alters rat small intestinal myoelectric activity. The significance of continuity between small intestinal enteric nervous system (ENS) and that of both the stomach/pylorus and colon/caecum regarding the induction of tapeworm-altered myoelectric patterns was evaluated. A total of 32 rats were implanted with four serosal electrodes placed at sites in the duodenum through the mid-jejunum. Sixteen of the 32 rats underwent intestinal transections and anastomoses at both the duodenum and ileum. After recording myoelectrical activity of both normal and transected intestines, eight rats from each group (normal and transected) were infected with H.diminuta. Phase III frequency, duration of the migrating myoelectric complex (MMC), slow wave frequency, percentage of slow waves associated with spike potentials and the occurrence of the the two tapeworm-initiated myoelectric patterns, repetitive bursts of action potentials (RBAP) and sustained spike potentials (SSP), were measured. In infected rats, the frequency of the RBAP and SSP electric patterns were significantly reduced by the double transection. Intestinal transection did not affect the other changes caused by infection, such as decreased MMC phase III frequency and percentage of slow waves associated with spike potentials. In conclusion, a small intestinal ENS in continuity with other segments of the GI tract is required to generate maximal numbers of tapeworm-induced SSP and RBAP myoelectric activity in the small intestine of the rat.

Anastomosis, Surgical↗
PubMed2001

Intestinal regrowth is amplified after jejunal but not ileal resection during tapeworm infection in the rat.

The ileum possesses functions required by a healthy individual that are not fully supplanted by the duodenum or jejunum. Evidence suggests that the ileum may also be necessary to maintain an enteric parasite-host interaction. We hypothesized that the ileum is essential to the survival of the lumen-dwelling, rat tapeworm, H. diminuta. Male rats were divided into three groups: those with ileal or jejunal resections and nonresected controls. Half of each rat group was infected with the tapeworm. After jejunal resection, the weight but not length of intestinal remnant (duodenum + ileum) in infected rats returned to that of control, nonresected intestine 29 days after surgery and tapeworm numbers were fully maintained. In contrast, after ileal removal intestinal length and weight of the remaining duodenum and jejunum in infected rats were significantly decreased and tapeworm survival diminished. Data indicates that intestinal growth following resection is amplified by tapeworm infection when the ileum remains but diminished when the ileum is removed. Furthermore, loss of the ileum results in decreased infection intensity and dry weight of the tapeworm.

Animals↗
PubMed2001

Effect of surgical alteration of the rat gastrointestinal tract on the growth and development of Hymenolepis diminuta.

Eight groups of rats were used to study the involvement of the enteric (ENS) and central (CNS) nervous systems in the development of Hymenolepis diminuta using surgical intestinal transection, or CNS denervation, or both procedures. The transection procedure was used to isolate the ENS of the small intestine from either orad and/or caudal portions of the alimentary system, while the CNS denervation was used to eliminate direct visceral efferent inputs from the CNS. Nine days after the surgical procedures, all rats were infected with 35 cysticercoids of H. diminuta. On 20 days postinfection, the infection intensity, tapeworm dry weight, tapeworm morphology, intestine length, and intestinal wet weight were recorded. Only the combination of the duodenal and ileal transections with a CNS denervation reduced infection intensity and prevented the increased intestinal length normally observed in infected rats. In contrast, none of the various intestinal transection procedures alone or CNS denervation alone had any effect on the survival, ability to produce oncospheres or morphology of the tapeworms. In conclusion, tapeworm survival is decreased when both CNS and ENS inputs into the small intestine are altered or absent.

Animals↗
PubMed2001

Myoelectric response of the small intestine to the orad presence of the tapeworm Hymenolepis diminuta.

During its 24-hr migratory cycle in the small intestine, Hymenolepis diminuta is located in the orad part of the small intestine during the early morning hours and then in the caudad part of the small intestine during the late afternoon and early evening. During the later period, tapeworm-induced alterations of interdigestive myoelectric activity, a correlate of smooth muscle contraction or intestinal motility, are most intense in the ileal region. The hypothesis tested was that the tapeworm-induced changes in intestinal motility are local responses of the intestine responding to the close proximity of the lumenally positioned tapeworm and to the nutritional state of the host. The small intestine was monitored before and for 20 days after infection using electrodes implanted on the serosa of the small intestine. Myoelectric recordings were analyzed for the frequency of the normal patterns of interdigestive myoelectric spiking patterns and the altered myoelectric spiking related to tapeworm infection. During the morning hours, when the tapeworms are situated in the orad small intestine, no changes were observed during the normal myoelectric pattern of the digestive phase in any region of the intestine. When examined after the conversion of the digestive to interdigestive phase of motility, only on day 10 postinfection was the interdigestive phase significantly altered. It was concluded that the presence of the tapeworm in the orad small intestine during the satiety stage of the rat causes no changes in the electric events of the small intestine, with the exception of day 10 postinfection. Because tapeworms in the orad small intestine do not induce the tapeworm-altered myoelectric activity observed in the afternoon and evening with caudally positioned tapeworms, tapeworm-altered motility is not simply a response of the small intestine to the local presence of the tapeworm.

Animals↗
PubMed2001

Modulation of caudal intestinal permeability in the rat during infection by the tapeworm Hymenolepis diminuta.

Bidirectional movement of solutes between the intestinal lumen and systemic circulation is restricted by tissue barriers that may be altered under conditions such as intestinal infection. In a study using an in vitro everted sac preparation to assess small intestinal permeability in a lumen-to-serosa direction, 51Cr-EDTA movement was compared regionally in the jejunum and ileum of rats infected and uninfected by tapeworms. Whereas jejunal segments showed no significant differences in permeability to 51Cr-EDTA at 6, 15, or 32 days postinfection (dpi), ileal segments displayed an increased permeability on 15 and 32 dpi, but not 6 dpi. The alterations in permeability were not reversed 1 wk after removal of the tapeworm from the intestine. In conclusion, the strictly lumen-dwelling tapeworm infection allows increased movement of molecules from the lumen into ileal, but not jejunal, tissues by 15 dpi.

Animals↗
PubMed2000

Late summer and fall (March-May) pollen allergy and respiratory disease in Northern New South Wales, Australia.

BACKGROUND: Many people in the subtropical Northern Rivers area of New South Wales, Australia, blame the pollen of Tibouchina tree, which flowers at the same time as ragweed, Bahia grass and Bermuda grass, for hayfever and asthma exacerbations during fall between March and May. OBJECTIVES: To determine whether Tibouchina pollen is allergenic. To determine whether airborne ragweed pollen is present in this region for sufficient length of time and concentration to cause fall respiratory symptoms, and to determine if Bahia grass and Bermuda grass are associated with fall respiratory symptoms. METHODS: Pollen and Alternaria spores were monitored using a Burkard 7-day spore trap. Two hundred and six volunteers in the Northern Rivers area filled in questionnaires before skin prick tests (SPT) were performed with a panel of skin testing extracts. RESULTS: One hundred fifty-three (74.3%) subjects were atopic and reacted to one or more aeroallergens. Seventy were SPT positive to ragweed, OR 3.36 (CI 1.03 to 12.15) and 11 to Tibouchina (OR incalculable). Fifty of the 70 ragweed-positive subjects had fall hayfever or exacerbations of hayfever and/or asthma, OR 23.4 (CI 8.90 to 64.00). Eleven subjects were SPT positive to Tibouchina extract. There was a statistical association between Bermuda grass and hayfever, but not asthma OR 13.44 (CI 1.85 to 27.04). CONCLUSIONS: Ragweed pollen was present for a sufficient length of time and concentration to sensitize and provoke fall hayfever and asthma exacerbations. Tibouchina pollen is an aeroallergen causing mild-to-moderate allergic symptoms in a few people. There is an association between Bahia grass and asthma in children, and between Bermuda grass and allergic rhinitis in adults.

Adolescent↗
PubMed2000

Relation between colonic inflammation severity and total low-molecular-weight antioxidant profiles in experimental colitis.

Tissue antioxidant status is altered as a response to oxidative stress. This oxidative stress, caused by reactive oxygen species, is associated with inflammatory bowel disease (IBD). Our aim was to examine the relationship between total tissue low-molecular-weight antioxidant (LMWA) profile and inflammation severity in dinitrobenzene sulfonic acid (DNBS) experimental colitis in the rat. Rats were treated with three doses of DNBS: 1, 10, and 20 mg. Inflammation severity was assessed by tissue colonic wet weight, macroscopic evaluation, and tissue myeloperoxidase (MPO) activity. The capacity of water-soluble LMWA was assessed by measuring the reducing power of the tissues with cyclic voltammetry (CV) and by measuring tissue levels of reduced glutathione. While typical markers of inflammation (MPO, macroscopic examination, and colonic wet weight) indicated DNBS dose dependency, such dependency could not be demonstrated for the tissue LMWA as measured by reduced glutathione levels and by the tissues' reducing power. Mild colonic inflammation (induced by ethanol or by 1 mg of DNBS) caused an increase in the overall capacity of water-soluble LMWA. However, severe inflammation (induced by 20 mg of DNBS) caused a reduction in the tissue LMWA capacity. An intermediate dose of DNBS (10 mg) caused moderate inflammation, but did not cause a significant change in the tissue LMWA compared with a saline control treatment. In conclusion, LMWA changed in a biphasic pattern reflective of the severity of mucosal colonic inflammation. It is suggested that: low dose of DNBS (1 mg) and topical alcohol (25% v/v) caused an adaptation effect to the mild oxidative stress associated with mild inflammation. This resulted in an increase in the LMWA. A higher dose of DNBS (20 mg) caused more severe inflammation with an overall reduction in LMWA. The increased efflux of reactive oxygen species, associated with severe inflammation, led to an overall consumption of the tissue LMWA, which masked the increase in LMWA caused by the mild oxidative stress.

Animals↗
PubMed2000

The effect of local attachment of cationized antioxidant enzymes on experimental colitis in the rat.

PURPOSE: To investigate the possibility of local treatment of colitis with the adhesive antioxidant enzymes catalase and superoxide dismutase (SOD). METHODS: The net electric charge of the enzymes' surfaces was modified from negative to positive, to cause their adherence to the colon epithelium. The effects of this local administration were assessed in inflamed rat colon. Inflammation severity (colitis) was assessed by measuring colonic tissue myeloperoxidase (MPO) activity, amounts of tumour necrosis factor alpha (TNFalpha) and concentrations of reduced glutathione (GSH). The measurements were carried out in two types of protocols: preventive (pre-colitis induction) and treatment (post-colitis induction). In addition, the efficacy of treatment with the cationized enzymes was compared to 5-aminosalicylic acid (5-ASA) and betamethasone with similar administration routes. RESULTS: The two cationized antioxidant enzymes were found to be efficient in both prevention and treatment of experimental colitis. The two cationized enzymes caused a significant reduction in MPO activity. A reduction in TNFalpha concentration was noted only after the treatment protocol. No correlation was found between inflammation severity and tissue levels of GSH. In most cases the cationized enzymes were more effective than 5-ASA and betamethasone. CONCLUSION: Cationized catalase and cationized SOD have the potential to be efficient therapeutic tools in the local treatment of colitis.

Animals↗
PubMed1999

Culture of human renal tubular cells: positive selection of kallikrein-containing cells.

Human renal tubular cells derived from nephrectomy specimens were maintained in culture and grown to confluence. Immunocytochemistry, using a panel of antibodies selected for their ability to bind to different cell types within the nephron, showed the cells to be predominantly of epithelial origin with no significant contamination by fibroblasts or cells of endothelial origin. Ten to thirty percent of the cells expressed the putative distal marker, epithelial membrane antigen (EMA), a finding confirmed by flow cytometry. Cells expressing EMA were positively selected from mixed cultures by magnetic activated cell sorting (MACS). Kallikrein activity, expressed as mU/10(6) cells, in the EMA +ve cells, was increased fourfold to sixfold when compared with that in the EMA -ve cells. Cultures of characterized human renal tubular cells and sub-populations enriched with distal cells should prove useful in studies of synthesis and release of parameters of the kallikrein kinin system (KKS) to physiological stimuli. Furthermore, a better understanding of the toxic effect on the KKS of clinically useful drugs, particularly those used for immunosuppression, may lead to therapeutic interventions to lessen unwanted effects.

Cell Culture Techniques↗
PubMed1999

Differences in the reducing power along the rat GI tract: lower antioxidant capacity of the colon.

The ability of the gastrointestinal (GI) tract, as well as other tissues, to cope with reactive oxygen species (ROS) efflux in pathological events is determined partly by epithelial antioxidant levels. These levels are comprised of tissue antioxidant enzymes and low molecular weight antioxidants (LMWA). While glutathione levels and the activity of enzymatic antioxidants along the GI tract have been studied, the contribution of the overall LMWA to the total antioxidant capacity has not yet been determined. In this study the overall antioxidant activity in the mucosa/submucosa and muscularis/serosa of various sections along the small intestine and colon of the rat was evaluated by determining the reducing power, which reflects the total antioxidant activity derived from LMWA, using cyclic voltammetry. The activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase was also measured. The reducing power (total antioxidant activity) was higher in the mucosa/submucosa of the small intestine as compared to the mucosa/submucosa of the colon. Similarly, catalase and SOD activity in the mucosa/submucosa of the small intestine was significantly higher than in the mucosa/submucosa of the colon. Differences were also observed in the reducing power and SOD activity in the muscularis/serosa of the rat small intestine as compared to the colon. The low antioxidant capacity in the colon may facilitate reactive oxygen species (ROS)-mediated injury and lead to inflammatory diseases such as ulcerative colitis, specifically in the colon.

Animals↗
PubMed1999

Peripheral and central actions of orphanin FQ (nociceptin) on murine colon.

Orphanin FQ (OFQ), also known as nociceptin, is a recently isolated endogenous peptide with a structure similar to the endogenous opioid peptides. The present study examines the actions of centrally administered OFQ on in vivo murine gastrointestinal and colonic transit as well as the actions of OFQ on the isolated colon. Intracerebroventricular injections of OFQ dose dependently inhibited colonic propulsive activity. OFQ inhibition of colonic propulsion was unaffected by coadministration of the competitive opioid receptor antagonist naltrexone. A subadditive response was observed when approximately equipotent doses of either morphine sulfate or the delta-agonist DPDPE were coadministered with OFQ. No subadditivity was observed with coadministration of the micro-agonist DAMGO, suggesting a functional interaction between OFQ and delta-opioid central pathways regulating colonic transit. High, but not low, doses of OFQ also inhibited the transit of a nonabsorbable charcoal marker through the stomach and/or small intestine. OFQ potently contracted isolated colon preparations; contractile activity was abolished by TTX or chlorpromazine. Our results suggest that OFQ may be an important peptide ligand acting on a novel inhibitory neural pathway that modulates gastrointestinal transit.

Animals↗
PubMed1998

Hymenolepsis diminuta: mucosal mastocytosis and intestinal smooth muscle hypertrophy occur in tapeworm-infected rats.

The mechanisms mediating motility changes during noninvasive tapeworm infection have not been characterized. In contrast, host intestinal motility changes during invasive nematode infection are mediated by mucosal mast cells (MMC). The purpose of this study was to examine and the correlate onset of myoelectric alterations 8 days after initial tapeworm infection with changes in intestinal morphology, MMC numbers, and MMC secretory activity. Segments of the small intestine, the tapeworms normal habitat, along with stomach, colon, and bladder were taken from tapeworm-infected and control rats. Tissues were fixed and stained to identify MMC and for morphologic measurement. Tapeworm-infected and uninfected rats with chronically implanted intestinal electrodes were treated with ketotifen, a mast cell stabilizer, and in vivo myoelectric activity monitored. In tapeworm-infected rats, the muscularis externa, on day 20 postinfection, and crypts of Lieberkuhn, on day 26 postinfection, from the entire small intestine appeared thickened or deeper, respectively. Increased muscularis thickness was due to smooth muscle hypertrophy in both the circular and the longitudinal muscle layers. Mucosal mastocytosis was first observed on day 26 postinfection and occurred only in the ileum of tapeworm-infected rats. Pharmacologic stabilization of mast cells with ketotifen did not prevent onset of enteric myoelectric alterations during tapeworm infection. Stomach, colon, and bladder MMC numbers and tissue dimensions were not different between Hymenolepis diminuta-infected rats and uninfected controls. Initiation of myoelectric alterations 8 days after infection precedes and may be a contributing factor to the onset of both smooth muscle hypertrophy and mucosal mastocytosis. Taken together, our data indicate that mast cells are not an initiating factor nor chronic stimulus maintaining intestinal myoelectric alterations during H. diminuta infection.

Animals↗
PubMed1998

Jejuno-ileal bypass, enteric hyperoxaluria, and oxalate nephrosis: a role for polarised light in the renal biopsy.

Enteric hyperoxaluria, a complication of jejuno-ileal bypass, is associated with renal failure owing to oxalate nephrosis or tubulo-interstitial nephritis. A 54 year old woman developed renal failure 17 months after jejuno-ileal bypass for morbid obesity. Renal biopsy showed widespread acute on chronic damage to the tubulo-interstitial compartment with extensive deposition of oxalate crystals. The extent of oxalate deposition was only evident on polarisation of the biopsy.

Acute Kidney Injury↗
PubMed1998

Hymenolepis diminuta fractions but not previous tapeworm infection stimulate intestinal myoelectric alterations in vivo in the rat.

Infection of rats with the enteric, lumen-dwelling tapeworm Hymenolepis diminuta causes electric changes in host intestinal smooth muscle and decreased luminal transit. The mechanisms that stimulate host intestinal alterations during this nontissue invasive infection may include the tapeworm's biomass, its diurnal migratory behavior, a host immune-mediated response, or direct parasite stimulation of host motor activity. In vivo intestinal myoelectric activity was monitored to evaluate the following: (1) that reinfection with H. diminuta is influenced by host immune regulation and (2) that administration of tapeworm fractions to never-before-infected rats initiates an alteration of enteric smooth muscle activity. To address the first hypothesis, we determined that altered intestinal myoelectric activity patterns were no different and did not occur earlier in a second infection with H. diminuta than in a primary infection. The lack of either a change in myoelectric pattern or an earlier onset of intestinal myoelectric changes indicates that tapeworm-induced myoelectric activity is not anamnestically stimulated by host immunomodulatory mechanisms. Consistent with the second hypothesis, administration of either H. diminuta carcass homogenate or tegument-enriched fractions directly into the intestinal lumen of tapeworm-naive rats initiated myoelectric patterns previously characteristic of chronic H. diminuta infection. Additionally, the appearance of characteristic nonmigrating myoelectric patterns in uninfected rats administered tapeworm fractions indicates that a substance from H. diminuta acts as the triggering signal molecule for intestinal myoelectric alterations. These findings also indicate that neither the tapeworm's biomass nor its diurnal movement is required for initiation of H. diminuta-altered myoelectric patterns. We have shown that H. diminuta possess a signal molecule(s) that alters host enteric electric activity, and we suggest that these alterations may play an important role in the symbiotic rat-tapeworm interrelationship.

Action Potentials↗
PubMed1997

Tapeworm infection decreases intestinal transit and enteric aerobic bacterial populations.

Intestinal myoelectric patterns in rats are altered after chronic luminal infection with the tapeworm Hymenolepis diminuta. This study evaluates whether these altered patterns were associated with changes in intestinal fluid transit and endogenous enteric microbe levels. Luminal transit, measured throughout the small intestine during the interdigestive state, was significantly decreased during tapeworm infection. Reduced transit was regional, occurring in the same location as that of the tapeworm and maximal myoelectric alterations. In other experimental systems, aerobic and anaerobic bacterial overgrowth is associated with decreased transit; however, reduced transit during tapeworm infection was unexpectedly associated with decreased numbers of aerobic bacteria, whereas anaerobic bacterial populations remained unchanged. The lack of overgrowing endogenous microflora suggests that overgrowth is not responsible for tapeworm-stimulated alterations in host myoelectric patterns. We speculate that a tapeworm secretion could be responsible for both transit and motility changes while delayed intestinal transit could prevent tapeworm expulsion, aid the tapeworms' migration, and contribute to the digestion and absorption of nutrients by hosts and/or parasites.

Animals↗