Role of ATP and related purines in inhibitory neurotransmission to the pig urinary bladder neck

Background and purpose:

As adenosine 5′-triphosphate (ATP) is one of the inhibitory mediators of the bladder outflow region, this study investigates the possible release of ATP or related purines in response to electrical field stimulation (EFS) and the purinoceptor(s) involved in nerve-mediated relaxations of the pig urinary bladder neck.

Experimental approach:

Urothelium-denuded and intact phenylephrine-precontracted strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O₂ and 5% CO₂ for isometric force recordings.

Key results:

EFS, in the presence of atropine, guanethidine and N^G-nitro-L-arginine, and exogenous purines, produced frequency- and concentration-dependent relaxations respectively. Adenosine 5′-diphosphate (ADP) and adenosine were more potent than ATP in producing relaxation, while uridine 5′-triphosphate, uridine 5′-diphosphate and α,β-methylene ATP were less effective. The non-selective P2 antagonist suramin, and the P2Y₁ and P1 receptor blockers 2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate tetrasodium and 8-(p-sulphophenyl)theophylline, respectively, inhibited the responses to EFS and ATP. The P1 agonist''s potency was: 5′-N-ethylcarboxamidoadenosine (NECA)>4-2[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzene propanoic acid hydrochloride>2-chloro-N⁶-cyclopentyladenosine>-2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide = adenosine. 4-(-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol, an A_2A antagonist, reduced the relaxations to EFS, adenosine and NECA. In urothelium-intact samples, relaxations to EFS and purines were smaller than in urothelium-denuded preparations. Neuronal voltage-gated Na⁺ channels blockade failed to modify ATP relaxations. At basal tension, EFS- and ATP-induced contractions were resistant to desensitization or blockade of P2X₁ and P2X₃ receptors.

Conclusions and implications:

ATP is involved in the non-adrenergic, non-cholinergic, non-nitrergic inhibitory neurotransmission in the pig bladder neck, producing relaxation largely through muscle A_2A receptors after breakdown to adenosine, and P2Y₁ receptors after breakdown to ADP. Antagonists of these receptors may be useful for urinary incontinence treatment produced by intrinsic sphincteric deficiency.     

Direct identification of Yersinia enterocolitica in blood by polymerase chain reaction amplification

Primers based on the nucleotide sequence of the virF gene in the pYV plasmid and the chromosomal ail gene were used in polymerase chain reaction (PCR) amplifications to directly identify Yersinia enterocolitica in blood. Approximately 500 bacteria seeded into 100 microL of blood can be extracted and amplified by PCR to yield positive results. PCR analyses of seven Y. enterocolitica isolates previously implicated in blood contaminations showed that only one isolate harbored the plasmid-borne virF gene; however, all seven isolates were identified effectively by the PCR product amplified from the chromosomal gene. The PCR assay has the potential for use in the identification of Y. enterocolitica contamination in stored units of blood or in the rapid diagnosis of transfusion-related bacteremia caused by Y.     

Differential effects of neuropeptide Y and opioids on neurogenic responses of the perfused rat mesentery

In perfused rat mesentery transmural nerve stimulation activates both adrenergic and capsaicin-sensitive sensory nerves. When adrenergic nerves were blocked with guanethidine and smooth muscle tone was increased, transmural nerve stimulation caused a dilator response which was attenuated by tetrodotoxin and abolished by capsaicin. Indomethacin increased the vasodilator response to transmural nerve stimulation, but did not affect the dilation to calcitonin gene-related peptide. Neuropeptide Y (NPY) potentiated vasoconstrictor responses to transmural nerve stimulation, but suppressed capsaicin-sensitive vasodilation, an effect which was unaltered by indomethacin. Opioid agonists selective for mu, delta or kappa receptors, DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin), DPDPE ([D-Pen2,D-Pen5]enkephalin) and ethylketocyclazocine, had no effect on the vasoconstrictor response to transmural nerve stimulation. DAMGO and DPDPE significantly inhibited vasodilator responses to transmural nerve stimulation, but ethylketocyclazocine was without effect. After treatment with indomethacin, DAMGO still inhibited the vasodilator response, but DPDPE was no longer effective. Prejunctional control of transmitter release by NPY or opioids is dependent on the specific nerve type as well as, in some cases, the participation of endogenous prostaglandins.     

Multiple sites of action of ( +)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (( +)-3PPP) in blood vessels

Functional effects of the σ ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), were explored in perfused rat tail and rabbit ear arteries in vitro. In the rat tail artery (+)-3PPP inhibited contractile responses to adrenergic nerve stimulation, an effect which was reversed to potentiation by the dopamine D₂ receptor antagonist sulpiride. In the rabbit ear artery, however, (+)-3PPP potentiated contractile responses to nerve stimulation, an effect which was unchanged by sulpiride. In the rat tail artery, blockade of norepinephrine uptake by cocaine and deoxycorticosterone in the presence of sulpiride revealed two additional actions of (+)-3PPP. First, an inhibitory action on the monoamine uptake site was confirmed by direct measurement of [³H]norepmephrine accumulation. Second, at higher concentrations, an action to inhibit contractile responses to adrenergic nerve stimulation was manifested at a still unidentified site. These studies demonstrate that the observed functional effect of (+)-3PPP results from its combined actions on three individual sites with the net effect dependent on the relative densities of these different receptor sites in each type of vessel.     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.     

Fetal intracranial teratoma: US diagnosis of three cases and a review of the literature

We describe three cases of fetal intracranial teratoma diagnosed by ultrasound and review the literature. Sonographic features include cranial enlargement, gross distortion of normal cerebral architecture by a hyperechoic, multicystic mass, and polyhydramnios. Despite early diagnosis, the cesarean section rate is high and the overall prognosis is dismal.     

Retroperitoneal sarcomas: A review of disease spectrum,radiological features,characterisation and management

Retroperitoneal sarcomas are a rare disease. The overall 5‐year survival rate for these lesions remains low, and surgical management offers the only option for effective treatment and potential for cure. Radiotherapy is increasingly being employed in addition to standard surgical treatment. Improvements in cross‐sectional imaging have also facilitated better characterisation of lesions, preoperative planning and long‐term follow‐up. This article reviews the current literature and documents the various types of retroperitoneal sarcomas with a particular approach to their imaging features. We also highlight the pathology, diagnostic methods and most current management of these tumours.