Biomedical subjects

R Saban

Publications and source records attributed to R Saban.

At least 37 records · Page 2Linked to original sources

PubMed1999

Evaluation of ureteric contraction: a comparison among ring, spiral-cut and longitudinal segments.

OBJECTIVE: To determine the optimal contractile response of isolated ureters to inflammatory mediators and neurotransmitters by evaluating four common methods of ureteric suspension. MATERIALS AND METHODS: Ureters from adult domestic swine were placed immediately in Krebs buffer and cut into 4-5 mm segments. Four methods of suspension were compared: (i) an unopened ring segment suspended horizontally; (ii) a spirally cut segment (lumen cut open at a 45 degrees and suspended end-to-end); (iii) an open longitudinal segment; and (iv) a closed longitudinal segment. All segments were placed in individual water-jacketed tissue baths containing Krebs buffer, the frequency of contraction measured using a force transducer and registered on a polygraph. The sensitivity of all four segments was tested by measuring the tension and frequency in response to increasing frequencies of electric field stimulation, and by a cumulative concentration-response curve to carbachol. RESULTS: Ureteric segments responded with an increased frequency of contraction depending on the intensity of stimulus to both electric field stimulation and carbachol. However, there were no significant differences in spontaneous levels of contraction, sensitivity or maximal response among the methods of suspension in response to electric field stimulation or carbachol. CONCLUSION: These results indicate that all four methods of suspending the ureteric segments produce contractile responses sensitive enough to study the action of various neurotransmitters.

Animals↗

PubMed1999

NK-2 is the predominant tachykinin receptor subtype in the swine ureter.

OBJECTIVE: To determine which of the known tachykinin receptor subtypes is predominant in the swine ureter. MATERIALS AND METHODS: Ureters from adult pigs were harvested, cut into longitudinal strips and placed in 10 mL tissue baths containing Krebs buffer, under 4 g of initial tension. The magnitude and frequency of contractions were recorded. Tissues were incubated with 1 micromol/L solutions of peptidase inhibitors (phosphoramidon and captopril) for 1 h to inhibit degradation of peptides and treated with either CP 96,345 (NK-1 receptor antagonist), SR 48,968 (NK-2 receptor antagonist) or saline (control). Concentration-response curves to the tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were determined. RESULTS: Ureteric segments showed a concentration-dependent response to all tachykinins; NKA stimulated increased contractions at a lower concentration than either SP or NKB (P<0.05). This was reflected by the difference in the effective concentration required to obtain half the maximal response (EC50 ) for each of the peptides. The mean (sd) EC50 values were (micromol/L): NKA, 0.2 (0.02); SP, 3.5 (0.7); and NKB, 4.5 (1.7). In addition, the selective NK-2 antagonist (SR 48,968) significantly reduced contractile responses to all peptides, as indicated by a 10-fold rightward shift of the concentration-response curves (P<0. 05), whereas the NK-1 antagonist (CP 96,345) had no significant effect. CONCLUSION: These results indicate that NK-2 is the predominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical applications for the treatment of ureteric disease.

Animals↗

PubMed1999

Mast cells mediate the severity of experimental cystitis in mice.

PURPOSE: We hypothesized that experimental cystitis induced by substance P (SP) or E. coli lipopolysaccharide (LPS) would be less severe in mice rendered mast cell deficient by genetic manipulation. MATERIALS AND METHODS: Two strains of mast-cell deficient mice (WBB6F1- kitW/kitW-v or kitW/kitW-v and WCB6F1-Sl/Sld or Sl/Sld) and their congenic, normal (+/+) counterparts were used. Cystitis was induced in female mice by intravenous injection of SP (0.1 ml.; 10(-6) M) or E. coli LPS (0.1 ml.; 2 mg./ml.), and inflammation was assessed by Evans blue dye extravasation. In a separate group of kitW/kitW-v and congenic normal mice, cystitis was induced by intravesical infusion of SP (0.05 ml.; 10(-5) M) or E. coli LPS (0.05 ml.; 100 microg./ml.) and compared with intravesical pyrogen-free saline (0.05 ml.; 0.9%). Severity of cystitis was determined by histological evaluation of the bladder wall 24 hours after intravesical infusions. RESULTS: Intravenous SP or LPS stimulated increased plasma extravasation in congenic normal mice but not in mast cell-deficient mice. Intravesical SP or LPS resulted in increased edema, leukocytic infiltration, and hemorrhage within the bladder wall in congenic normal mice, but the only histological evidence of inflammation in the bladders of kitW/kitW-v mice was increased hemorrhage in response to LPS. CONCLUSIONS: This study indicates that mast cells modulate the inflammatory response of the bladder to SP and LPS in mice. Although clinical trials of the use of antihistamines to treat or prevent cystitis have not been successful, these results suggest that therapies directed toward preventing mast cell activation may yet prove effective in treating cystitis.

Animals↗

PubMed1999

Nerve-mediated motility of ileal segments isolated from NK(1) receptor knockout mice.

Tachykinins such as substance P (SP) and neurokinin A (NKA) acting on neurokinin (NK) receptors modulate the nonadrenergic noncholinergic (NANC) neurotransmission in the gastrointestinal tract of several species, but the information about the mouse small intestine is scanty. Both SP and NKA induced concentration-dependent contractions of ileal segments isolated from wild-type mice that were blocked by NK(1) and NK(2) antagonists, respectively. In contrast, segments isolated from NK(1) receptor (NK(1)-R) knockout mice responded only to elevated concentrations of SP. To reveal the inhibitory NANC (iNANC) responses, tissues were pretreated with atropine and guanethidine. Under these conditions, a tetrodotoxin-sensitive relaxation in response to electrical field stimulation (EFS) was observed. NK(1)-R knockout mice presented a trend toward an increase in iNANC responses, whereas the NK(1)-R antagonist significantly potentiated iNANC relaxation in tissues isolated from wild-type mice. N(G)-nitro-L-arginine methyl ester (100 microM) transformed the relaxant response to EFS into a tetrodotoxin-sensitive, frequency-dependent contraction characteristic of an excitatory NANC (eNANC) system. A NK(1)-R antagonist abolished the contractile responses of the mouse ileum to EFS, whereas a NK(2) receptor antagonist had a trend toward reducing EFS-induced contraction. The eNANC component was absent in NK(1)-R knockout mice. Measurement of SP-like immunoreactivity indicated similar amounts of SP per gram of tissue isolated from wild-type and NK(1)-R knockout mice, indicating that the observed differences in response to EFS were not due to a differential peptide content. It is concluded that, in the mouse ileum, both NK(1) and NK(2) receptors modulated the responses to exogenous tachykinins, whereas NK(1) is the primary tachykinin receptor involved in both iNANC and eNANC transmission.

Animals↗

PubMed1999

[The beginnings of physiology of the human brain, from antiquity to the Renaissance].

For more than 3,000 years in Western civilizations, the knowledge of the human body gained very little ground at first, due to taboos. The body was regarded as sacred and Medicine only resorted to plants in order to heal. Hippocrates was not familiar with anatomy as the human body could not be dissected. He developed a theory of humors connected with the primary elements and opposing the dry and the moist. Even though he did not know the nervous system, he nonetheless pointed out that emotions stemmed from the brain and were caused ty particles (pneuma) emitted by the objects around us. Galien was one of the first to mention physiology but could only dissect animals to understand Man. He took up the theory of humors but did not reach any concrete results as he considered the brain as made up of faeces. Only in 1000 AD did Avicenne try to shape the cell theory with its three cells (the ventricles in today's parlance) in direct relation to the nerves, which he described but did not represent. Representation of the nerves was only be given in the mid-13th century by Khalifah in his ophtalmology treaty. Finally, during the Renaissance, when books started conveying both text and pictures, brain physiology emerged; Albert le Grand was its first expounder and his work was then taken up in a 1475 inculabulum in which 5 cells instead of 3 are described and represented. Leonardo da Vinci was the second one; at the end of the 15th century he dissected may corpses to understand human morphology. Unfortunately his work, which was conducted very rigorously from an anatomical point of view only surfaced at the end of the 19th century. He was the first to conduct the anatomical cross-dissection of the brain. Last came Magnus Hundt and Georg Reisch; in the early 16th century they still represented the three cells of Avicenne even though Reisch described more sophisticated connections between the organs of the senses.

Brain↗

PubMed1999

Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients.

PURPOSE: The 2 prominent features of interstitial cystitis are pain and increased numbers of mast cells in the bladder. In this pilot study we determined the concentration of soluble mediators associated with activation of sensory neurons and/or mast cells that were present in the urine. MATERIALS AND METHODS: The study groups included 4 interstitial cystitis patients, 7 kidney donors with no history of bladder disease as negative controls, 6 bladder cancer patients and 7 patients with urinary tract infection as reference controls. Urine samples were assayed for different soluble mediators using immunoassays for tryptase (a marker for mast cell activation), neurotrophic factors (markers of neuronal plasticity) and chemokines (markers of inflammatory cell activity). Results were normalized based on creatinine concentration. RESULTS: There was a marked increase in the average amounts of tryptase and 3 neurotrophic factors in patient urine. Interestingly, the mediator profile in the urine of bladder cancer patients was indistinguishable from that of interstitial cystitis patients with respect to these same 4 proteins. There was no difference between normal control and urinary tract infection urine samples. CONCLUSIONS: These findings may account for several clinical and pathological features found in interstitial cystitis and bladder cancer. Although preliminary due to the limited numbers of patients, they also suggest that increased levels of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor and tryptase in the urine could serve as a basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.

Adult↗

PubMed1998

Dog model for studying detrusor instability secondary to acutely induced variable bladder outlet obstruction.

BACKGROUND: Involuntary detrusor contractions often cause irritative symptoms such as urgency and incontinence. A dog model for acutely induced variable bladder outlet resistance was developed to investigate the possible role of prostatic afferent nerve fibers in the development and maintenance of detrusor instability. METHODS: Fifty-eight mongrel dogs (weight range 19.5-36.5 kg) were divided into five groups: group I (n = 11) had surgically induced bladder outlet obstruction. Group II (n = 14) had urinary obstruction and bilateral sectioning of the lowest branches of the pelvic plexus supplying the prostate. Group III (n = 10) had prostate denervation only. Groups IV (n = 10) and V (n = 13) were sham-operated and controls, respectively. In the obstructed groups (I and II), an artificial urinary sphincter (length 4.5-6.0 cm) was placed around the bladder neck and connected to a reservoir placed subcutaneously to allow postoperative adjustments of urinary resistance. All dogs were evaluated at baseline and postoperatively at 1, 3, and 6 months with uroflowmetry, postvoid residual urine volume, cystometry as well as serum creatinine, and urinalysis. RESULTS: Occurrences of detrusor instability were not associated with prostatic denervation input. The mean peak flow rates decreased significantly in the obstructed groups at all follow-ups, but did not change significantly in the nonobstructed groups. Postoperatively, the mean maximum bladder capacity was significantly decreased for groups I and II only. However, a significant correlation between maximum bladder capacity and maximum detrusor pressure could not be detected at any time point in any of the groups. Mean postvoid residual urine volume varied considerably in all groups over time. Creation of a urinary model of infravesical obstruction was associated with considerable problems. CONCLUSIONS: In our dog model of bladder outlet obstruction, prostatic sensory nerve fibers appear not to be involved in detrusor instability. Surgical induction of a constant model of bladder outlet obstruction was difficult even in a large animal. The observations from the present study raise questions about the validity of obstructive urinary animal models.

Animals↗

PubMed1998

Anti-immunoglobulin E antibody treatment blocks histamine release and tissue contraction in sensitized mice.

Inhibition of antigen-specific IgE response has been shown to lead to amelioration of allergic disease symptoms. In an effort to design a therapy aimed at decreasing IgE levels, we reported previously that treatment of mice with an anti-IgE antibody coincident with the primary antigen immunization resulted in significant decreases in antigen-specific IgE synthesis, without substantially altering IgG levels. In the present study, we employed this mouse model and a surrogate antibody to investigate the capacity of anti-IgE treatment to block an established IgE response in vivo. Results of these experiments suggest that anti-IgE treatment concomitant with an antigen boost results in removal of detectable circulating IgE for at least 7 weeks (the duration of the study). Moreover, tissues removed from mice following anti-IgE treatment failed to release histamine and contract in response to antigen challenge ex vivo. These findings demonstrate that reduction of circulating IgE correlates to an inhibition of tissue mast cell sensitization and mediator release in response to antigen challenge and further supports the concept of anti-IgE treatment as a promising therapy for the treatment of allergic disease.

Animals↗

PubMed1998

Lipopolysaccharide upregulates bradykinin 1 receptors in the isolated mouse bladder.

PURPOSE: Bradykinin 1 (B1) receptors have been shown to be upregulated at sites of inflammation. The purpose of this study was to determine the effect of lipopolysaccharide (LPS) on B1 receptor modulation in the isolated mouse bladder. MATERIALS AND METHODS: The contractile responses of isolated mouse bladder to B1 and B2 agonists were determined in vitro following prolonged incubation with LPS or saline. RESULTS: Bradykinin (BK), a B2 agonist, but not des-Arg9-bradykinin (DABK), a B1 agonist, was found to be a potent contractile agonist of the mouse urinary bladder under basal conditions. However, both sensitivity and maximal response to DABK increased during a second exposure to the agonist in a time-dependent manner. In vivo or in vitro treatment with LPS increased both sensitivity and maximal response of isolated bladders to DABK, whereas bladder contraction to BK and other peptides remained the same. Treatment of tissues with a B1 receptor antagonist 45 minutes prior to second exposure to DABK, or the prostaglandin synthesis inhibitor, indomethacin, 30 minutes prior to LPS or saline incubation, significantly inhibited the increase of both maximal response and sensitivity. CONCLUSIONS: These results indicate that bladder B1 receptors can be upregulated by LPS, and that prostaglandins seem to mediate the effects of the B1 receptor activation in the isolated mouse bladder.

Animals↗

PubMed1998

In vitro passive sensitization of the ureter as a basis for the study of noninfectious ureteral inflammation.

PURPOSE: To develop an in vitro model of passive sensitization for the ureter for the study of noninfectious ureteral inflammation. MATERIALS AND METHODS: Human ureteral tissues were obtained from excess segments of ureters from patients undergoing donor nephrectomy. Following excision, ureters were placed in physiologic salt solution (PSS) and passively sensitized by incubating with ragweed serum from allergic donor (1 ml. serum: 4 ml. PSS) for 20 hours at room temperature. Ureteral segments were incubated with PSS only and served as non-sensitized controls (n = 4). After sensitization, excess serum was removed by serial washing with PSS without serum. Ureteral strips were then suspended in vitro for determination of tissue contraction. Contractile responses and histamine release were measured. Tissues were then exposed to antigen. To investigate the role of inflammatory mediators in tissue contraction, 4 groups of 8 sensitized ureteral segments were incubated for 1 hour with the following substances: a H1 histamine receptor antagonist (pyrilamine), an inhibitor of prostaglandin synthesis (indomethacin), an inhibitor of leukotriene synthesis (A-64077), and a control substance (DMSO). Following incubation, the tissues were exposed to antigen, and contraction and histamine release were determined. RESULTS: Sensitized ureteral segments (n = 8) responded to antigen with contraction (30% BaCl maximum; p <0.01) and histamine release (205/ng./gm. tissue) within the first 5 minutes of superfusion. Non-sensitized control segments (n = 4) did not respond. Both indomethacin and pyrilamine reduced (7-10% of BaCl maximum; p <0.05) the contractile response of sensitized ureter to antigen, whereas A-64077 did not. Analysis of the superfusate for histamine indicates that indomethacin reduced histamine release (150 ng./gm.) whereas A-64077 and pyrilamine did not (p <0.05). CONCLUSION: We have demonstrated that ureteral segments can be passively sensitized and that subsequent antigen challenge stimulates contraction and histamine release. Our findings suggest that contraction of ureteral tissue and histamine release may be utilized as an inherent bioassay indicating the activity of inflammatory mediators. In addition, these results suggest that both prostaglandins and histamine, but apparently not leukotrienes, participate in the early inflammatory response to antigen challenge of the sensitized ureter.

Antigens↗

PubMed1997

Involvement of leukotrienes, TNF-alpha, and the LFA-1/ICAM-1 interaction in substance P-induced granulocyte infiltration.

Substance P (SP) has been shown to mediate granulocyte infiltration into the mouse skin by inducing mast cell degranulation. In this study, using a variety of specific inhibitors, we investigated the cascade of events involved in the response of neutrophils and eosinophils to SP. The prostaglandin inhibitor, indomethacin, had little effect on SP-induced leukocyte migration. In contrast, pretreatment with the leukotriene (LT) synthesis inhibitor, A-64077, completely blocked neutrophil but not eosinophil migration in response to SP. Participation of tumor necrosis factor alpha (TNF-alpha) and LFA-1/ICAM-1 interaction was confirmed by inhibition of SP-induced leukocyte migration by pretreatment of mice with monoclonal antibodies to TNF-alpha, LFA-1, and ICAM-1. Moreover, alteration in leukocyte migration by indomethacin was found to depend on the concentration of TNF-alpha used. Indomethacin did not alter the number of leukocytes induced by low concentrations of TNF-alpha (0.1 ng), but reduced the number of cells stimulated with high TNF-alpha concentrations (1.0 ng). These results support the concept that SP modulates in vivo neuroinflammatory responses, as measured by granulocyte migration, initiating a cascade of events that includes LT production, TNF-alpha secretion, and engagement of LFA-1 and ICAM-1.

Animals↗

PubMed1997

Neurogenic vasoreactive response of human internal thoracic artery smooth muscle.

The interaction between primary afferent neurons containing neuropeptides and the vascular smooth muscle is incompletely understood. To explore the function of perivascular afferent neurons and to determine whether they produce local effects on vascular smooth muscle cells, we investigated the effects of acute capsaicin and substance P administration in vitro on human internal thoracic arteries (ITA). Vessels were obtained from patients undergoing coronary bypass or from multiorgan transplant donors. Fourteen ITA segments (5 mm wide) were suspended as rings between two stainless-steel stirrups in water-jacketed (37 degrees C) tissue baths under 2.5 to 3 g of basal tension. The tissue baths contained 10 mL physiological salt solution (PSS) of the following composition (mM): NaCl, 119; KCl, 4.7; NaH2PO4, 1.0; MgCl2, 0.5; CaCl2, 2.5; NaHCO3, 25; and glucose, 11; aerated continuously with 95% O2 and 5% CO2. Peptidase inhibitors (phosphoramidon and captopril) were added to PSS to decrease peptide degradation. Mechanical responses were measured isometrically and recorded on a polygraph via isotonic force transducers. Vessels were preconstricted with submaximal concentrations of norepinephrine. After the tension had stabilized, substance P or capsaicin was added cumulatively to the tissue bath. At the end of the experiments, the viability of ITA was verified by its responses to endothelial-dependent (acetylcholine) and endothelial-independent (sodium nitroprusside) vasodilators. In the endothelium-intact ITA segments, substance P produced relaxation of ITA smooth muscle while it induced slight contraction when the ITA was devoid of its endothelium (P = 0.0585). The addition of capsaicin to human ITA primarily produced contractile effects on the developed smooth muscle force. The capsaicin-induced contraction of the ITA smooth muscle was independent of endothelial cell integrity, although contraction was greater in the endothelium-intact ITA segments (P = 0.0165). The acute capsaicin exposure of human ITA revealed that primary afferent neurons containing neuropeptides innervate human ITAs. There is a real potential for perivascular afferent neurons and sensory peptides to influence the ITA smooth muscle function.

Acetylcholine↗

PubMed1997

Use of gold-labeled ovalbumin to correlate antigen deposition and localization with tissue response.

This study was performed to evaluate a technique for correlating the location of antigen within sensitized tissues with physiological response. Guinea pigs actively sensitized by intraperitoneal injection of ovalbumin (OVA) were euthanized, and urinary bladders were removed. Gold beads (18 nM diameter) were conjugated to OVA (OVA-Au) and bovine serum albumin (BSA-Au). Bladder tissue was suspended in tissue baths, exposed to OVA, OVA-Au, BSA, and BSA-AU, and tissue contraction and histamine release were determined. Bladder tissues were examined by electron microscopy to determine distribution of gold-labeled antigen at 1 and 5 min after exposure. Exposure of bladder tissue from sensitized guinea pigs to OVA stimulated concomitant contraction and histamine release which reached maximal levels within 3 min; bladder tissue from control, nonsensitized guinea pigs did not respond to OVA. BSA failed to stimulate response from OVA-sensitized or control bladder tissue. Labeled antigen was adhered to mucosa of sensitized bladder tissue 1 min after exposure to OVA-Au. OVA-Au was present within the mucosa and submucosa of sensitized tissues within 5 min. OVA-Au did not adhere to, or become internalized by, control tissues, and BSA-Au did not adhere to, or become internalized by, any tissues. Labeling of antigen with gold allowed the location of antigen within tissues to be determined and did not affect the response of sensitized tissues to antigen exposure.

Animals↗

PubMed1997

Spontaneously released substance P and bradykinin from isolated guinea-pig bladder.

OBJECTIVES: To investigate whether the isolated urinary bladder spontaneously releases substance P (SP) or bradykinin (BK), which can act as potent mediators of pain and inflammation of the urinary bladder, and whether peptidase inhibitors enhance peptide release. MATERIALS AND METHODS: Urinary bladder segments (2 x 10 x 0.8-1 mm) were isolated from guinea pigs and studied in vitro; tissue contraction was assessed using force-displacement transducers and the release of peptides by specific enzyme immunoassays. RESULTS: In the absence of any exogenous agonists, the inhibition of neutral endopeptidase and angiotensin-converting enzyme by phosphoramidon and captopril, respectively, increased the frequency and magnitude of spontaneous motility of isolated bladder strips. Phosphoramidon increased the net release of SP-like immunoreactivity (SP-LI) and captopril increased the net release of SP-LI and BK-LI, concomitant with contraction. Peptide-LI was recovered primarily from bladder mucosa and to a lesser degree from detrusor smooth muscle. Similarly, peptidase inhibitors primarily affected the bladder mucosa; phosphoramidon induced a fourfold increase in SP-LI and captopril induced a significant increase of SP-LI and BK-LI from the mucosa. Tissues contracted in response to peptidase inhibitors in the presence of atropine and indomethacin, but contraction was reduced significantly by in vitro capsaicin desensitization or removal of bladder mucosa. BK stimulated SP-LI release from mucosa but not detrusor. SP stimulated increased BK-LI release from mucosa and detrusor. CONCLUSIONS: These findings indicate the basal release of peptide-like immunoreactivity by isolated bladder and further support the concept that peptidases located in the bladder mucosa are important in terminating the effects of endogenous peptides.

Animals↗

PubMed1997

Kinetics of peptide-induced release of inflammatory mediators by the urinary bladder.

OBJECTIVE: To investigate the release of inflammatory mediators by the urinary bladder in response to exposure to pro-inflammatory peptides. MATERIALS AND METHODS: Isolated guinea pig urinary bladder was incubated with 10 mumol/L each of substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), octreotide acetate (a long-acting analogue of somatostatin, SOM), or bradykinin (BK), and the release of histamine, prostaglandin (PG) E2, PGF2 alpha and leukotriene B4 (LTB4) was determined during 0-5, 5-30 and 30-120 min after addition. RESULTS: Substance P, NKA, VIP and BK stimulated the release of histamine, while CGRP and SOM suppressed the release to below the spontaneous rates. All peptides, except CGRP and SOM, stimulated the release of PGE2 between 0 and 30 min, and only VIP failed to stimulate the release of PGF2 alpha within 5 min of exposure. Substance P, NKA, VIP and BK stimulated the release of LTB4 and this required > 5 min of exposure. CONCLUSION: These results indicate that the peptides evaluated induce an immediate and transient release of histamine and activation of cyclooxygenase and delayed activation of 5-lipoxygenase. These actions may directly regulate the participation of these peptides in the pathogenesis of cystitis.

Animals↗

PubMed1997

Effect of octreotide, a somatostatin analogue, on release of inflammatory mediators from isolated guinea pig bladder.

OBJECTIVE: Somatostatin has been demonstrated to inhibit inflammation under certain circumstances. We hypothesized that in vivo treatment with octreotide, a long-acting analogue of somatostatin analogue, would diminish the capacity of inflammatory peptides to stimulate in vitro release of inflammatory mediators by the bladder. METHODS: Female guinea pigs were injected with octreotide (20 mg./kg. i.m.) prior to euthanasia. Control guinea pigs received no treatment prior to euthanasia. Urinary bladders were removed and incubated with substance P (SP, 10 microM), neurokinin A (NKA, 10 microM), or bradykinin (BK, 10 microM) in the presence or absence of indomethacin (50 microM), and release of histamine, prostaglandins (PGE2 and PGF2 alpha), and leukotriene (LTB4) was determined. RESULTS: Sensory peptides and BK induced time-dependent release of histamine and eicosanoids from isolated urinary bladder. Blockade of cyclooxygenase with indomethacin (50 microM) abolished peptide-induced prostaglandin release but enhanced LTB4 release. In vivo octreotide pretreatment decreased peptide-induced histamine release, had no effect on PGE2 or PGF2 alpha release, and LTB4 release. However, octreotide prevented the increase in LTB4 release in tissues incubated with indomethacin. CONCLUSIONS: These results indicate that somatostatin has the capacity to suppress the release of histamine and prevents potentiation of LTB4 release by indomethacin by the guinea pig bladder in response to pro-inflammatory peptides, indicating that somatostatin may be useful in preventing or treating some forms of cystitis.

Animals↗

PubMed1997

Human anti-IgE monoclonal antibody blocks passive sensitization of human and rhesus monkey bladder.

IgE antibodies may play an important role in noninfectious urinary inflammation, including interstitial cystitis (IC). In this study, urinary bladder strips were passively sensitized for 20 hours with serum from a ragweed-sensitive patient in the absence or presence of an anti-human IgE monoclonal antibody (MaE11) at 0, 1-, or 5-fold IgE concentration. The urinary bladder strips then were suspended in a superfusion apparatus for measurement of contraction and histamine release in response to antigen E (AgE) challenge. Non-sensitized tissues did not react to AgE challenge, whereas AgE challenge of passively-sensitized tissues resulted in time-dependent bladder contraction and histamine release. MaE11 abolished AgE-induced contraction and histamine release in a concentration-dependent manner. The safety of MaE11 was confirmed by its failure to contract or release histamine from passively-sensitized bladder tissues. The results of this study suggest that MaE11 may have immunotherapeutic benefit for amelioration of IgE-mediated diseases of the urinary system.

Adult↗

PubMed1997

Effects of Pasteurella haemolytica leukotoxin and lipopolysaccharide on histamine, prostanoid, and leukotriene release by bovine lung parenchyma in vitro.

OBJECTIVE: To identify the effect of Pasteurella haemolytica lipopolysaccharide (LPS) and leukotoxin (LKT) on spontaneous and calcium ionophore-induced histamine and inflammatory mediator release from isolated bovine lung parenchyma. SAMPLE POPULATION: Lungs from 8 healthy cattle. PROCEDURE: Isolated bovine lung parenchyma was incubated in vitro for 2 hours with LKT or LPS, and spontaneous and induced release of inflammatory mediators was determined. RESULTS: LKT and LPS increased spontaneous release of histamine and leukotriene B4. In addition, incubation with LPS increased spontaneous release of prostaglandin E2. Moreover, a differential effect of the 2 toxins on calcium ionophore-induced inflammatory mediator release was observed. LKT specifically primed isolated lung parenchyma to release leukotriene B4 and thromboxane B2 in response to calcium ionophore, whereas LPS did not alter the profile of prostanoids released by bovine lung tissue exposed to calcium ionophore. CONCLUSIONS: Pasteurella haemolytica toxins have a direct effect on bovine lung parenchyma, causing release of inflammatory mediators, which contribute to response to infection. Furthermore, bacterial toxins (LKT in this study) may sensitize tissues to the effects of other irritant stimuli, amplifying the inflammatory response.

Animals↗