The importance of vaginal mucosal folds at the urethral external meatus

We report on the vaginal mucosal folds (VMF) at the urethral external meatus. Resection of the VMF reduces the dispersed micturition and other urinary symptoms. EDITORIAL COMMENT: The investigators describe the presence of a vaginal mucosal fold (VMF) just dorsal to the urethral meatus and its relationship to voiding abnormalities. VMF were found on physical examination in 8.9% of the clinic population, all of whom complained of dispersed micturition, and 79% also experienced other voiding abnormalities. The complaint of dispersed micturition was successfully treated with excision of the VMF, and the other associated symptoms were improved. This structure should be routinely looked for on physical examination, especially in patients with voiding symptoms. Only further investigation of this newly described entity at other centers around the world will determine the incidence of the anatomic finding and the prevalence of associated voiding disturbances across different populations.     

The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure

Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst. Desmopressin may be a useful alternative to, or may supplement, other forms of treatment in some patients with autonomic failure.     

Analgesic activity and release of [MET5]enkephalin-Arg6-Gly7-Leu8 from rat spinal cord in vivo

Rat spinal cord contains the opioid peptide including [Met5]enkephalin-Arg6-Gly7-Leu8 (YGGFMRGL) and a higher molecular weight (HMW) immunoreactive peptide which is an N-terminal extended molecular form of YGGFMRGL. Since a high proportion of tissue immunoreactivity resides in the HMW component we have determined whether this form is released during perfusion of the spinal cord subarachnoid space in vivo while (1) electrically stimulating the sciatic nerves bilaterally or (2) superfusing with substance P. We have found that YGGFMRGL and the HMW immunoreactivity are released by both types of stimuli. The HMW material appeared to be the more stable of the two species of immunoreactivity; its presence in the superfusate was more consistently observed than that of YGGFMRGL itself. Injection of YGGFMRGL into the spinal subarachnoid space in chronically catheterized rats produced a suppression of the tail-flick response. This effect of YGGFMRGL was reversed by naloxone suggesting an action mediated by spinal opiate receptors. These data suggest that YGGFMRGL plays an integral role in the neurotransmission process between spinal neurons storing enkephalin and other neurons. The possibility that enkephalin-mediated neurotransmission includes multiple chemical signals can be entertained.     

Enlarged adenomectomy for enclosed prolactinomas: A preliminary study of 26 cases

Summary Preliminary results obtained from 26 cases of prolactinomas less than 20 mm in diameter after treatment by enlarged adenomectomy are described.The operation consisted in removal of the adenoma, a layer of normal pituitary at the outer edge of the tumour and the pituitary capsule in contact with the sellar meninges. 24 women and 2 men were involved whose prolactin levels (PRL) were less than 200 ng/ ml. All presented abnormal PRL responses to Thyrotropin releasing hormone (TRH) and Metoclopramide (MCP) tests and an absence of a nocturnal rise in the sleep cycle study. Postoperatively, three patients developed transitory diabetes insipidus and five transitory adrenal insufficiency. Gonadotropin reserve was always found normal. All 24 women resumed normal menstrual cycles and two became pregnant within one year. From a serological viewpoint, after surgery 100% of patients were found to be normal for levels of prolactin but only 85% turned to normal dynamic tests. The results of this small series of enlarged adenomectomies seem better than those obtained using selective adenomectomy, but must be confirmed with time.     

Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol

 Styrene is stereoselectively oxidized by cytochrome P450 to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione (GSH) to both (R)- and (S)-diastereoisomers of the specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Several investigations have indicated different toxic potential of the (R)- and (S)-configurations of styrene oxide and its GSH- and N-acetyl-conjugates. In this study the mercapturic acid diastereoisomers were measured in the urine of rats exposed to styrene in combination with ethanol, a good inducer of styrene metabolism. Male Sprague-Dawley rats were given an isocaloric liquid diet containing ethanol (5% w/v) for 3 weeks. Starting from the 2nd week, the animals were also exposed to styrene vapours (300 ppm, 6 h/day, 5 days/week) in a dynamic exposure chamber. Both the (R)- and (S)-diastereoisomers of the M1 and M2 as well as the conventional biomarkers, mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in urinary samples. Approximately 30 and 25% reduction of the levels of brain non-protein sulfhydryls (NPS) was observed in the animals given styrene and ethanol, respectively, while the combined ethanol and styrene treatment resulted in a 60% decrease. Ethanol consumption also resulted in higher urinary levels of the M1-R, M1-S and M2 metabolites associated with increased M1-R/S ratio and higher urinary MA excretion compared to animals treated with styrene. These results suggest that the urinary mercapturic acid diastereoisomers may be used as a noninvasive tool to examine stereoselective patterns of styrene metabolism in vivo, as well as their alterations caused by ethanol. These compound-specific mercapturic acids may also be valuable indicators of styrene-induced disorders of GSH homeostasis in nonaccessible organs. Received: 19 December 1995/Accepted: 10 May 1996     

Neutralization Susceptibility of B Subtype Variant B' Primary HIV-1 Isolates

Susceptibility to autologous and heterologous neutralization of primary human immunodeficiency virus (HIV)-1 isolates belonging to subtype B, to the B'-variant of subtype B or to subtype F from infected individuals residing in Rio de Janeiro was assayed. A lower infectivity of the B'- and F isolates when compared to the classical B-subtype HIV-1 isolates was observed. Comparisons of neutralization susceptibilities were carried out for 19 B-subtype, 11 B'-variant and two F-subtype HIV-1 isolates with plasma from autologous and heterologous samples. Frequency of autologous neutralization was slightly lower for B-subtype isolates in comparison to B'-variant isolates. Heterologous intra-subtype neutralization was significantly lower for B-subtype than for the B'-variant or the F-subtype isolates. While B-subtype isolates were neutralized by most anti-F-subtype plasma, F-subtype isolates, although most susceptible to F-subtype antibodies, were highly susceptible to neutralization by anti-B-subtype antibodies. Cross-neutralization for B'-variant and B-subtype isolates was not as extensive as observed for B- and F-subtype isolates. However, the results presented indicate a quite extensive cross-neutralization between Brazilian HIV-1 isolates.     

A brief study of the selectivity of norbinaltorphimine, (-)-cyclofoxy, and (+)-cyclofoxy among opioid receptor subtypes in vitro

Norbinaltorphimine (nor-BNI) is a bifunctional reagent developed as a selective antagonist of the kappa opioid receptor. In this paper we examined the in vitro selectivity of nor-BNI, 6-desoxy-6 beta-fluoronaltrexone (cycloFOXY), and the enantiomer of cycloFOXY, among opioid receptor subtypes. Nor BNI exhibited the highest affinity for kappa binding sites labeled by 3H-U69593 (Ki = 1.8nM), and was 27- to 29-fold less potent at mu and delta binding sites. In contrast, cycloFOXY had the highest affinity for mu binding sites (Ki = 2.62 nM), and bound to kappa and delta binding sites with Ki's of 9.3 nM and 89 nM, respectively. The enantiomer of cycloFOXY, did not inhibit binding even at concentrations greater than 10 microM, validating in part the use of 18F-labeled (+)-cycloFOXY to estimate "non-specific binding" in positron emission tomography. Additionally, we report that (S,S)-U50 488 and (R.R)-U50 488 bind to kappa binding sites labeled by 3H-U69 593 with Ki's of 0.89 nM and 299 nM, respectively.