Obstructive uropathy and hydronephrosis in male KK-Ay mice: a report of cases.
Uropathy associated with hydronephrosis was observed frequently in our male KK-Ay mouse colony during a long-term study of diabetes. The lesion occurred in 24 of the 31 KK-Ay male mice and accounted for the greatest number of spontaneous deaths among them. It was observed after 4 months of age and involved about hard plugs of altered seminal material resembling the seminal vesicle secretion. The plugs became impacted in the urethral bulb and the bladder. The penile anatomy, with its flexure, pressure on the urethra from the bulbocavernosus muscle, and the characteristic ability of the seminal fluid to easily coagulate to form the vaginal plug may have contributed to the lesion. Correlation between development of the uropathy and diabetes has not been established. (+info)
Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods.
The purpose of the present study was to confirm the presence of beta3-adrenoceptor subtype in the relaxation of human urinary bladder detrusor tissue by reverse transcription-polymerase chain reaction (PCR); direct sequencing of the PCR product, in situ hybridization; and isometric contraction. Using reverse transcription-PCR, the mRNAs of three receptor subtypes (beta1, beta2, and beta3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above beta3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of beta3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective beta-adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective beta3-adrenoceptor agonists); and SR59230A (a putative selective beta3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a beta1-adrenoceptor-selective antagonist) and butoxamine (a beta2-adrenoceptor-selective antagonist) revealed a relaxant effect on the carbachol-induced contraction of the human urinary bladder detrusor. Both BRL37344 and CGP12177A also revealed relaxant effects on the human urinary bladder detrusor, but ZD7114 did not elicit any relaxation. These results suggest that beta3-adrenoceptor may have some role in urine storage in the human urinary bladder. (+info)
Adrenoreceptors of the guinea-pig urinary bladder.
1 Adrenaline, noradrenaline and isoprenaline (5 mug/ml) did not affect the resting tone of the isolated urinary bladder of the guinea-pig. 2 The catecholamines (1-2 mug/ml) inhibited neuronally evoked contractions at various stimulation frequencies; the inhibition was maximum at 2 Hz and minimum at 50 Hz. Isoprenaline produced maximum inhibition. 3 Propranolol (0.5 mug/ml) completely blocked the catecholamine-induced inhibition at all the frequencies employed. The concentration-response curves of isoprenaline at 2, 10 and 50 Hz were characteristically shifted by propranolol (50 ng/ml). Phenoxybenzamine (0.2 mug/ml) was totally ineffective. 4 In some experiments adrenaline significantly raised the tone of the bladder exposed to propranolol; this effect could be blocked by phenoxybenzamine. 5 Acetylcholine-induced bladder contractions were inhibited by adrenaline (2 mug/ml); the inhibition was completely blocked by propranolol (0.5 mug/ml). 6 The results indicate the presence of an inhibitory beta-adrenoceptor and suggest the possibility of an excitatory alpha-adrenoceptor in guinea-pig urinary bladder. (+info)
M2 receptors in genito-urinary smooth muscle pathology.
In vitro bladder contractions in response to cumulative carbachol doses were measured in the presence of selective muscarinic antagonists from rats which had their major pelvic ganglion bilaterally removed (denervation, DEN) or from rats in which the spinal cord was injured (SCI) via compression. DEN induced both hypertrophy (505+/-51 mg bladder weight) and a supersensitivity of the bladders to carbachol (EC50=0.7+/-0.1 uM). Some of the SCI rats regained the ability to void spontaneously (SPV). The bladders of these animals weighed 184+/-17 mg, significantly less than the bladders of non voiding rats (NV, 644+/-92 mg). The potency of carbachol was greater in bladder strips from NV SCI animals (EC50=0.54+/-0.1 uM) than either bladder strips from SPV SCI (EC50=0.93+/-0.3 microM), DEN or control (EC50=1.2+/-0.1 microM) animals. Antagonist affinities in control bladders for antagonism of carbachol induced contractions were consistent with M3 mediated contractions. Antagonist affinities in DEN bladders for 4-diphenlacetoxy-N-methylpiperidine methiodide (4-DAMP, 8.5) and para fluoro hexahydrosilodifenidol (p-F-HHSiD, 6.6); were consistent with M2 mediated contractions, although the methoctramine affinity (6.5) was consistent with M3 mediated contractions. p-F-HHSiD inhibited carbachol induced contraction with an affinity consistent with M2 receptors in bladders from NV SCI (pKb=6.4) animals and M3 receptors in bladders from SPV SCI animals (pKb=7.9). Subtype selective immunoprecipitation of muscarinic receptors revealed an increase in total and an increase in M2 receptor density with no change in M3 receptor density in bladders from DEN and NV SCI animals compared to normal or sham operated controls. M3 receptor density was lower in bladders from SPV SCI animals while the M2 receptor density was not different from control. This increase in M2 receptor density is consistent with the change in affinity of the antagonists for inhibition of carbachol induced contractions and may indicate that M2 receptors or a combination of M2 and M3 receptors directly mediate smooth muscle contraction in bladders from DEN and NV SCI rats. (+info)
Eosinophil peroxidase (EPO), a cationic protein found in eosinophils, has been reported to be cytotoxic independent of its peroxidase activity. This study investigated with electrophysiological methods whether EPO is toxic to mammalian urinary bladder epithelium. Results indicate that EPO, when added to the mucosal solution, increases apical membrane conductance of urinary bladder epithelium only when the apical membrane potential is cell interior negative. The EPO-induced conductance was concentration dependent, with a maximum conductance of 411 microseconds/cm2 and a Michaelis-Menten constant of 113 nM. The EPO-induced conductance was nonselective for K+ and Cl-. The conductance was partially reversed using voltage but not by removal of EPO from the bulk solution. Mucosal Ca2+ reversed the EPO-induced conductance by a mechanism involving reversible block of the conductance. Prolonged exposure (up to 1 h) to EPO was toxic to the urinary bladder epithelium, as indicated by an irreversible increase in transepithelial conductance. These results suggest that EPO is indeed toxic to urinary bladder epithelium via a mechanism that involves an increase in membrane permeability. (+info)
Macrophage inflammatory protein-2 is required for neutrophil passage across the epithelial barrier of the infected urinary tract.
IL-8 is a major human neutrophil chemoattractant at mucosal infection sites. This study examined the C-X-C chemokine response to mucosal infection, and, specifically, the role of macrophage inflammatory protein (MIP)-2, one of the mouse IL-8 equivalents, for neutrophil-epithelial interactions. Following intravesical Escherichia coli infection, several C-X-C chemokines were secreted into the urine, but only MIP-2 concentrations correlated to neutrophil numbers. Tissue quantitation demonstrated that kidney MIP-2 production was triggered by infection, and immunohistochemistry identified the kidney epithelium as a main source of MIP-2. Treatment with anti-MIP-2 Ab reduced the urine neutrophil numbers, but the mice had normal tissue neutrophil levels. By immunohistochemistry, the neutrophils were found in aggregates under the pelvic epithelium, but in control mice the neutrophils crossed the urothelium into the urine. The results demonstrate that different chemokines direct neutrophil migration from the bloodstream to the lamina propria and across the epithelium and that MIP-2 serves the latter function. These findings suggest that neutrophils cross epithelial cell barriers in a highly regulated manner in response to chemokines elaborated at this site. This is yet another mechanism that defines the mucosal compartment and differentiates the local from the systemic host response. (+info)
Nosema notabilis (Microsporidia), its ultrastructure and effect on the myxosporean host Ortholinea polymorpha.
Nosema notabilis Kudo, 1939 produces chain-forming meronts with a dense cell coat in direct contact with the host cell cytoplasm. Cytoplasmic microtubules and membranaceous whorls could be observed in meront cytoplasm. Sporonts differ in that they have a thicker cell wall and more conspicuous endoplasmic reticulum (ER) cisternae. Sporoblasts have an externally ridged cell wall. Spores have an apically located anchoring disc, an isofilar polar tube with 6 to 9 turns and polyribosomal strands in the sporoplasm. Diplokarya occur in all stages. Heavily infected plasmodia of Ortholinea polymorpha (Davis, 1917) reveal marked pathological signs. The most prominent are reduction of surface projections and/or pinocytosis, inflated mitochondria with altered inner structures, affected vegetative nuclei, damage to generative cells and occurrence of various anomalous formations in the plasmodium cytoplasm. The damage may result in complete disintegration of the plasmodium. However, the development of the microsporidian is affected by a remarkably high percentage of teratological stages revealing membranaceous and tubular structures. (+info)
Neurogenic plasma leakage in mouse airways.
1. This study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance P on microvascular plasma leakage in the trachea and lungs of male pathogen-free C57BL/6 mice. 2. Single bolus intravenous injections of capsaicin (0.5 and 1 micromol kg(-1), i.v.) or substance P (1, 10 and 37 nmol kg(-10, i.v.) failed to induce significant leakage in the trachea, assessed as extravasation of Evans blue dye, but did induce leakage in the urinary bladder and skin. 3. Pretreatment with captopril (2.5 mg kg(-1), i.v.), a selective inhibitor of angiotensin converting enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg(-1), i.v.), a selective inhibitor of neutral endopeptidase (NEP), increased baseline leakage of Evans blue in the absence of any exogenous inflammatory mediator. The increase was reversed by the bradykinin B2 receptor antagonist Hoe 140 (0.1 mg kg(-1), i.v.). 4. After pretreatment with phosphoramidon and captopril, capsaicin increased the Evans blue leakage above the baseline in the trachea, but not in the lung. This increase was reversed by the tachykinin (NK1) receptor antagonist SR 140333 (0.7 mg kg(-1), i.v.), but not by the NK2 receptor antagonist SR 48968 (1 mg kg(-1), i.v.). 5. Experiments using Monastral blue pigment as a tracer localized the leakage to postcapillary venules in the trachea and intrapulmonary bronchi, although the labelled vessels were less numerous in mice than in comparably treated rats. Blood vessels of the pulmonary circulation were not labelled. 6. We conclude that neurogenic inflammation can occur in airways of pathogen-free mice, but only after the inhibition of enzymes that normally degrade inflammatory peptides. Neurogenic inflammation does not involve the pulmonary microvasculature. (+info)