Characterization of P1-purinoceptors on rat duodenum and urinary bladder.

1. The P1-purinoceptors mediating relaxation of the rat duodenum and inhibition of contraction of the rat urinary bladder were characterized by use of adenosine and its analogues 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclopentyladenosine (CPA) and 2-p-((carboxyethyl)phenethylamino)-5'- carboxamidoadenosine (CGS 21680), as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable analogue of adenosine 5'-triphosphate (ATP), adenylyl 5'-(beta,gamma-methylene)diphosphonate (AMPPCP), was also used as previous work had indicated that it has a direct action on some P1 receptors in addition to its P2-purinoceptor activity. 2. In the rat duodenum, the order of potency of the adenosine agonists was NECA greater than or equal to CPA greater than AMPPCP = adenosine greater than CGS 21680, and DPCPX antagonized CPA and AMPPCP at a concentration of 1 nM whereas equivalent antagonism of NECA and adenosine required a concentration of 1 microM. This suggests the presence of a mixture of A1 and A2 receptors in this tissue, with CPA and AMPPCP acting on the A1 and NECA and adenosine acting on the A2 receptors. 3. In the rat bladder, the order of potency of the adenosine agonists for inhibition of carbachol-induced contractions was NECA much greater than adenosine greater than CPA = CGS 21680, and a concentration of DPCPX of 1 microM was required to antagonize responses to NECA and adenosine. This suggests the presence of A2 receptors in this tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Congential dislocation of the hip and adult low back pain: a report of three cases

Congenital dislocation of the hip (CDH) in an adult can accompany or cause mechanical low-back pain. This in turn, can create confusion in making the proper diagnosis. The mechanical alterations caused by CDH create an added strain to the lumbosacral spine. Manipulative treatment for back pain in these patients must not subject the dislocated hips to undue torque.     

Is endometrial infection with Candida albicans a cause of recurrent vaginal thrush?

OBJECTIVE--It was hypothesised that the endometrium might act as a reservoir for candida, thus infecting the vagina as the endometrium is shed during menstruation. DESIGN--A prospective study of women with recurrent vulvo-vaginal candidiasis. The endometrium was sampled and cultured for candida species. SETTING--Central London STD clinic. SUBJECTS--26 women were enrolled, of whom 20 completed the study. RESULTS--One patient had a positive endometrial culture for candida species, the isolate being Candida krusei. CONCLUSIONS--The endometrium is not a common resevoir for candida species and therefore, infection at this site is an unlikely cause of recurrent vaginal candidiasis.     

Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

Behavioural effects of selective μ-, κ-, and δ-opioid agonists in neonatal rats

The behavioural effects of selective -, - and -opioid agonists in 5-, 10- and 20-day-old rats were investigated by observational analysis. The predominant response to -agonists was behavioural depression. High doses (10 mg/kg IP) of morphine and DAGO (d-Ala², NMe-Phe⁴, Glyol⁵-enkephalin) produced overt sedation in all the age groups and also induced catalepsy which was particularly apparent in the 5- and 10-day-old animals. These compounds did not produce any signs of behavioural activation in the neonatal rats. In contrast, rat pups treated with the -agonists U50,488H and PD 117,302 (1,10 mg/kg IP) exhibited marked hyperactivity with increases in wall-climbing and locomotion. Sedative effects of the highest dose of the -agonists began to emerge, however, as the animals grew older, resulting in significant decreases in behaviours such as gnawing and grooming at 20 days of age. The -agonist (+)-tifluadom (0.1–10 mg/kg), but not its corresponding (-)-isomer, produced an increase in activity in 5-day-old rats, thus extending the observations made with U50,488H and PD 117,302 and establishing the stereoselective nature of the response. The involvement of -receptors in opioid-induced hyperactivity was further substantiated by using a variety of opioid antagonists. In this context, the increase in activity induced by U50,488H (10 mg/kg) in 5-day-old neonates was attenuated by naltrexone (1 mg/kg IP) but not by larger doses (10 mg/kg) of either M8008 (which has low affinity for -receptors) or the selective -receptor antagonist ICI 174,864. Finally, DPDPE (d-Pen², d-Pen⁵-enkephalin) which acts selectively at -opioid receptors, did not exert any behavioural effects in either the 5-, 10- or 20-day-old rat pups at doses of up to 10 mg/kg. These results demonstrate behavioural effects of - and -but not -agonists in neonatal rats. There is a clear differentiation between - and -receptor effects and both - and -mediated behaviours show dissimilarities from the adult profile.     

Somatostatin analogue (octreotide) inhibits bile duct epithelial cell proliferation and fibrosis after extrahepatic biliary obstruction.

Extrahepatic biliary obstruction leads to bile duct epithelial cell proliferation. Somatostatin and its analogue, octreotide, have been shown to inhibit DNA synthesis and proliferation in hepatocytes. We investigated the effect of octreotide on the biliary epithelial cell proliferative responses to biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial cells, and periportal connective tissue was performed by computerized point counting. Hepatocyte volume was preserved with octreotide treatment, which also significantly decreased bile duct proliferation and periportal extracellular matrix deposition in response to biliary obstruction compared with saline treated, duct-ligated animals. These results indicate that octreotide prevents the morphological changes that accompany extrahepatic biliary obstruction.