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.     

No-scalpel vasectomy (NSV) procedure and nursing care

The no-scalpel vasectomy technique, introduced by a Chinese surgeon in 1974, is increasingly becoming the method of choice for permanent male sterilization. Conventional vasectomy is being challenged by the new procedure, which results in less pain, fewer infections, and a smaller wound. The use of 2 specially designed instruments lessens tissue damage from the procedure and reduces time required for the operation. In the United States, Dr. Mark Goldstein of Cornell Medical Center, New York City, has instructed surgeons in the no-scalpel technique. The Association for Voluntary Surgical Contraception has also promoted no-scalpel vasectomy, which is gaining popularity among urologists worldwide. The procedure was developed in China by Dr. Li Shunquiang of the Chongquing Family Planning Scientific Research Institute and has been performed on over 8 million men. Statistics reveal that this method produces a smaller singular incision and also reduces postoperative infection and hematoma. In China, the rate of hematoma in 179,741 men was 0.09% and the rate for infections was 0.91%. In a New York study, 238 men had no evidence of infection or hematoma following no-scalpel vasectomy. Since the technique was introduced in 1974, urologic surgeons have responded to the need to offer alternatives for male contraception. Under the direction of Dr. Shunquiang, surgeons received the necessary training to bring the no-scalpel vasectomy to their respective countries. Dr. Marc Goldstein was the first United States urologic surgeon to be trained in this method. By December 1990, data reported by the Association for Voluntary Surgical Contraception revealed that more than 125 United States physicians were trained in no-scalpel vasectomy. This new option is becoming an increasingly popular method for both patients and urologic surgeons.     

Characteristics of the demand for cranial computerized tomography: reasons and costs of the exam]

It was reviewed a series of 2860 cerebral computed tomography (CCT) in order to compare the main reasons at referral to investigation with the CCT results and the costs with normal and abnormal CCT. It was also studied the age and sex of the patients. Data were collected from one out of three diagnostic centers in Salvador, Brasil, for a three years period. The 2860 CCT exclude all investigation carried out for the follow-up of a previously diagnosed abnormality. CCT abnormalities were detected in 1152 (40.3%). The following reasons showed the highest proportion of abnormal CCT, for males and females respectively: demential syndrome (91.7 and 83.3%); cerebrovascular accidents (85.1 and 73.6%); infectious and parasitary diseases (76.5 and 78.6%); tumors (65.8 and 55.4%); and head injuries, 63.6% for males. In the female group, 65.0% of the CCT were normal, in a range of 65.0 to 80.0% for the age groups under 54 years old. In the male group, the highest proportion of normal CCT was found in the age groups: 25-34 (68.4%), < 15 (62.9%) and 35-44 (62.7%). The most common reasons for normal CCT for males and females were: headache (81.3 and 87.5%); dizziness/vertigo (79.3 and 78.6%); seizures (67.3 and 70.0%); psychomotor deficiency (72.0 and 67.7%) and "endocrine disorders", 75.0% for each sex. The highest proportion of normal CCT (65.3%) was requested by medical "convenios". The cost with normal CCT reached US$565,225 and with the abnormal ones, US$381,247. Costs with normal CCT were 2.2 higher for medical "convenios" as compared to those of the National Institute of Security requests and 2.8 more than those of private medicine.     

Bidirectional cavopulmonary shunts: clinical applications as staged or definitive palliation

A standard Glenn anastomosis between the superior vena cava and the right pulmonary artery has been the accepted mode of treatment for patients with complex cyanotic congenital heart disease. We report our experience in 18 patients with such disease who underwent a bidirectional cavopulmonary shunt because of increasing cyanosis and growth cessation. All patients were considered less than "ideal" candidates for a Fontan procedure. We divided the patients into two groups: group 1 had azygos continuation and group 2 did not. Fourteen patients required hypothermic cardiopulmonary bypass. Bidirectional pulmonary blood flow was achieved in all patients. Only 1 death occurred (group 2). The improvement in oxygen saturation and overall clinical condition of these patients, together with the low mortality and morbidity, is encouraging. However, long-term follow-up is mandatory for a comprehensive evaluation of this surgical approach as definitive palliation or as a first stage for a Fontan operation.