Novel Sources of Mammalian C-S Lyase Activity

The C-S lysis of L-cysteine conjugates is one biotransformation pathway which is responsible for the generation of mutagenic and cytotoxic metabolic species. Thirteen cysteine S-conjugates were synthesized in our laboratories and incubated with aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) enzymes from porcine heart tissue. The C-S lyase (CSL) activity for each enzyme-substrate combination was determined. ASAT and ALAT were shown to exhibit CSL activity and it was also demonstrated that this activity was inhibited in the presence of the pyridoxal phosphate-dependent enzyme inhibitor amino(oxyacetic acid) confirming the pyridoxal phosphate-dependent mechanism by which C-S lysis is known to take place. This finding has potentially important implications for the risk assessment of compounds which produce L-cysteine conjugates during their biotransformation.     

INTRADERMAL STUDY OF A NEW LOCAL ANAESTHETIC AGENT: APTOCAINE

In a double-blind trial in 28 human volunteers, a new localanaesthetic agent, aptocaine, was compared intradermally at1, 2 and 3% concentrations with lignocaine 2% and bupivacaine0.5%. In a second trial in 27 subjects, 1% aptocaine was comparedwith mepivacaine and prilocaine, both 1, 2 and 3 %. In termsof activity as determined by area of anaesthesia, and of durationof action, aptocaine was similar to mepivacaine and more activeand long-lasting than lignocaine and prilocaine. By this routeaptocaine also appeared longer-lasting than bupivacaine. Durationof action was unaffected by concentration. Aptocaine had markedvasoconstrictor activity, which was maximal at 1%. These localanaesthetic properties suggest that aptocaine merits clinicaltrials, especially in dentistry.     

The use of rectus abdominis myocutaneous flaps following excision of vulvar cancer

Summary. Rectus abdominis myocutaneous flaps have been used in 16 women following radical excision of extensive vulvar cancer. In two women the procedure was part of the primary surgery, in 11 for recurrence of vulvar cancer and in three for symptomatic palliation. Fifteen (94%) of the grafts took with primary healing. Thirteen of the 16 patients are alive 6–60 months (median 29 months) after surgery and the three who died benefited from symptomatic palliation. Simultaneous vulvar reconstruction allows good cosmetic rehabilitation and is an important part of the armametarium for the management of patients with advanced primary or recurrent vulvar carcinoma. This technique offers excellent surgical clearance of massive offensive and painful vulvar tumours.     

Immunosuppressive properties of pregnancy serum on the mixed lymphocyte reaction

Summary. The human fetus may escape immunological attack because of serum factors which have immunomodulatory influence on maternal cellular effector responses. Paired peripheral and retroplacental sera were shown to inhibit the allogenic mixed lymphocyte reaction (MLR) used as an in-vitro model of cell-mediated immunity. There was no correlation between the suppressive effect of the peripheral and retroplacental sera and the serum concentrations of four pregnancy-related proteins (α-fetoprotein, pregnancy-associated α₂ glycoprotein, pregnancy-associated plasma protein A and Schwangerschaftsprotein 1) to which immunosuppressive properties have been ascribed, but there was a negative correlation between peripheral AFP and MLR inhibition (r =−0·62, P < 0·001). Hence, the factor or factors responsible for suppressing the MLR are not those investigated in the present study.     

Estimating the probability of spontaneous delivery conditional on time spent in the second stage

Summary. The duration of second stage labour was studied, retrospectively, among 410 primigravidas who received epidural analgesia in the first stage of spontaneous labour at term (>37 weeks). Survival analysis was used to investigate how the likelihood of a spontaneous delivery was related to time spent in the second stage, and how some maternal and fetal factors influenced this relationship. The proportion of spontaneous deliveries that had occurred by any given time was greatly influenced by maternal age and infant birthweight. However, the women who were least likely to have been delivered by any given time after full dilatation, were also the ones who were least likely to be delivered within any given subsequent time interval. If delivery had not occurred by 3h, the probability that it would take place in the next 3 h was well under 30% in most cases. We conclude that second stage labour in excess of 3 h is likely to be beneficial only if certain criteria, which are defined in the paper, are met.     

Preferential neural processing of attended stimuli in attention-deficit hyperactivity disorder and normal boys

Event-related auditory and visual potentials were recorded from 36 attention-deficit hyperactivity disorder (ADHD) and 35 normal 6-year-old subjects engaged in a two-choice discrimination task. When normal subjects attended to stimuli in a given modality, enhanced negative (N2) and positive (P3b) responses (as compared with responses to nonattended stimuli) were found for auditory and visual target stimuli. In contrast, when ADHD subjects attended, little or no enhanced negative responses were found in either modality, and enhanced positive P3b responses were found only in response to visual target stimuli. Auditory N1, N2, and P3b and visual N2 amplitudes to attended target stimuli were significantly reduced in ADHD subjects as compared with normal subjects. No between-group differences were found for responses to nonattended stimuli. Both amplitude and latency abnormalities indicate that ADHD boys suffer from deficient preferential processing of attended stimuli. P3b and N2 abnormalities found here suggest deficiencies in two independent cognitive processes thought to be crucial to what we perceive, learn, and remember.     

Pathophysiology of Gap Junctions in Heart Disease

Cardiac Gap Junctions. Electrical coupling between cardiac muscle cells is mediated by specialized sites of plasma membrane interaction termed gap junctions. These junctions consist of clusters of membrane channels that directly link the cytoplasmic compartments of neighboring cells. Each gap-junctional channel consists of two connexons, one from each of the interacting plasma membranes, extending across the narrow extracellular gap. Connexons are constructed from connexins. a multigene family of conserved proteins. Different connexins confer specific electrophysiologic characteristics on the assembled channel protein. The major connexin of the mammalian heart is connexin43, although other types of connexins are also expressed, notably connexin40 in myocytes of the atrioventricular conduction system. Confocal laser scanning microscopy of anti–connexin43 immunolabeled samples reveals two major abnormalities in myocardial gap junctions in ischemic heart disease: loss of the usual ordered distribution of gap junctions at border zones adjacent to infarct scars, and reduction in the quantity of connexin43 gap junctions in myocardium distant from the infarct. These and other changes reported in myocardial gap-junctional communication pathways following infarction may result in heterogeneous anisotropic conduction and reduced conduction velocity, (hereby forming a proarrhythmic substrate. Current evidence suggests that reduction in conuexin43 content is a general pathogenetic feature of cardiac disease, and that changes in the expression levels of other connexin types may contribute to altered electrophysiologic function in the diseased heart.