Block of potassium channels and facilitation of acetylcholine release at the neuromuscular junction by the venom of the scorpion, Pandinus imperator

Venom from the scorpion Pandinus imperator potently and selectively blocks voltage-gated K+ channels in bullfrog neurones (Pappone, P. A. and Cahalan, M. D. 1987, J. Neurosci. 7, 3300-3305). Its effects on neuromuscular transmission have now been assessed. Twitch tension studies on chick biventer cervicis preparations showed that the venom (1 microgram/ml and above) significantly augmented responses to nerve but not muscle stimulation; there was little change in postjunctional sensitivity to cholinoceptor agonists or K+-induced depolarization. Electrophysiological studies on mouse triangularis sterni preparations revealed that the venom had no effect on spontaneous transmitter release, but increased evoked transmitter release. Extracellular recordings of nerve terminal action potentials showed that the venom selectively reduced the component of the waveform associated with K+ currents. These results confirm that this venom can selectively block neuronal K+ currents, and they show that this can facilitate the release of acetylcholine at the neuromuscular junction.     

Pharmacokinetics of ketoprofen in man after repeated percutaneous administration

A topical formulation of ketoprofen, a widely used nonsteroidal antiinflammatory drug, has recently been developed. Ten healthy young subjects (mean age 23.5 +/- 2.5 years) received daily 15 g of 2.5% ketoprofen gel, corresponding to 375 mg on the skin of the back over an area of 750 cm2. Plasma samples were collected after the first dose and after 10 days of chronic treatment. Urine was also collected. Ketoprofen was assayed by HPLC. The peak plasma concentration was 144 +/- 91 ng/ml after the first administration with apparent absorption and elimination half-lives of 3.2 +/- 2.4 h and 27.7 +/- 18.0 h, respectively. The total quantities of ketoprofen eliminated in the urine represented about 2.6% of the first dose applied. At the end of the study, the apparent half-life of unchanged ketoprofen was 17.1 +/- 9.1 h, and there was no accumulation. In this study, no sign of local intolerance was seen.     

3H]Ro 19-6327: a reversible ligand and affinity labelling probe for monoamine oxidase-B

This study demonstrated the existence of specific binding sites for [3H]Ro 19-6327 in human platelet membranes. This compound is a novel, time-dependent inhibitor of monoamine oxidase type B (MAO-B) and is structurally closely related to [3H]Ro 16-6491. The density of the sites labelled with high affinity by [3H]Ro 19-6327 was similar to that observed in previous studies with [3H]Ro 16-6491 as ligand. Binding was reversible at 20 degrees C and showed a relatively slow dissociation (t1/2 = 220 min). The dissociation rate was markedly decreased (t1/2 = greater than 24h) at 0 degrees C. MAO-B, but not MAO-A inhibitors, effectively prevented the binding of [3H]Ro 19-6327. Like [3H]Ro 16-6491, [3H]Ro 19-6327 is recognized as a substrate by MAO-B, being eventually deaminated by the enzyme. Since the deaminated aldehyde derivative of Ro 19-6327 did not inhibit MAO-B, a still unidentified reversible adduct, formed at the MAO-B active site, might explain the high potency and selectivity of [3H]Ro 19-6327. Incubation of the radioligand-enzyme complex from platelet and brain membranes with NaBH3CN and acetic acid (to pH 4.5) caused the irreversible incorporation of the radioactivity into a single polypeptide as shown by SDS-PAGE analysis. This polypeptide had a molecular weight identical to that of the MAO-B subunit, i.e. 58,000. The presence of unlabelled MAO-B inhibitors in the incubation mixture prevented the covalent incorporation of [3H]Ro 19-6327. The irreversible MAO-B inhibitor, [3H] pargyline, labelled a protein with a molecular weight identical to the protein labelled by [3H]Ro 19-6327.(ABSTRACT TRUNCATED AT 250 WORDS)     

Scanning Electron Microscopic Observations on the Epithelium of the Human Prostatic Urethra

The human prostatic urethra has been investigated by means of scanning electron microscopy. On the posterior wall of the urethra, the seminal colliculus with the orifices of the ejaculatory ducts is clearly detectable. The upper portion of the prostatic urethra shows a typical transitional epithelium with large superficial cells of a ruffled appearance. In the lower portion of the organ (underneath the openings of the ejaculatory ducts), the apical pattern of the cells varies considerably. Four main aspects are recognizable: apices provided with microvilli, dome-shaped apices with an almost smooth surface, large apices with labyrinthic microplicae and ciliated apices. Also, apices showing intermediate characteristics can be noted. The functional significance of the morphological patterns as well as the possibility of a transition among the various types of surface structures are discussed.     

Three-dimensional spinal curvature in idiopathic scoliosis

Scoliosis is usually considered as a deformity of the spine in the frontal plane, without reference to curvatures in other planes. In this study, the three-dimensional shape of the spine of 104 patients with untreated idiopathic scoliosis (5-55 degrees Cobb) was studied by means of stereo radiographs to determine relationships between curvature of the spine in the frontal plane view, in the lateral view, and in the intermediate views. There was a weak but statistically significant correlation (r = 0.2) relating greater scoliosis with lesser kyphosis or greater lordosis. In the thoracic region, the sagittal plane spinal curvature was less than that measured in a population without scoliosis (mean difference, 7.72 +/- 9.9 degrees). Seventy-four of 76 scolioses in the upper region of the spine with lateral curvature greater than 5 degrees Cobb were kyphotic. Sixty-four of 84 curves greater than 5 degrees Cobb in the lower region were lordotic. Measuring curvatures in the plane of symmetry of the rotated apical vertebra altered these ratios to 69 of 76 kyphotic in the upper region and 68 of 84 lordotic in the lower region. The plane of maximum curvature of sections of the spine with scoliosis was not related to the plane of symmetry of the rotated apical vertebra, for in kyphotic regions of the spine the rotations of these two planes were in opposite directions. In all cases, the magnitudes of the rotations were quite different, i.e., by a factor of -0.22 for curves in thoracic region and by a factor of 0.24 for curves in the lumbar region. This implies that mechanical measures to correct this spinal deformity or to prevent progression should apply different rotations to the apex from those applied to the curve as a whole and, in opposite senses, in curves in kyphotic regions. There was no evidence of an abnormality of sagittal curvature of a magnitude to implicate it in the etiology or in the treatment.     

Extensor mechanism complications following total knee arthroplasty

Extensor mechanism complications following 281 knee arthroplasties that included patellar resurfacing, performed by two surgeons in one hospital over a 6-year period, were reviewed. The mean follow-up period was 42 months. There were 28 (10%) extensor mechanism complications: 3 quadriceps tendon ruptures, 5 patellar fractures, 4 patellar tendon ruptures, 11 recurring patellar subluxations, 4 cases of patellar pain, and 1 malrotated patella. Nine (3%) required further surgery. Surgical technique may have contributed to the tendon ruptures; patellar fractures occurred mainly in patients who had rheumatoid arthritis. Patients with patellar subluxation had abnormal preoperative valgus deformities of their knees and presented with this subluxation problem an average of 4 months after surgery, but it appeared to cause them less discomfort with time. Patellar resurfacing as part of a knee arthroplasty procedure is recommended but should be performed with care to the integrity and vasculature of the extensor mechanism.     

Predicting failure in polytetrafluoroethylene vascular access grafts for hemodialysis: a pilot study

In order to determine if serial, noninvasive evaluation of polytetrafluoroethylene (PTFE) vascular access grafts could identify a subgroup of patients at risk for thrombosis, the authors studied flow characteristics, using duplex ultrasonic scanning, in 18 hemodialysis patients with forearm loop grafts. On average, five examinations were performed per patient over the 10-month study period. Seven episodes of thrombosis occurred in six patients. The mean Doppler flow in grafts that subsequently thrombosed was significantly lower than in those that did not (544 +/- 218 ml/min versus 843 +/- 391 ml/min, p less than 0.001). The interval from last examination to thrombosis ranged from 13 to 58 days. At a defined cut-off flow of 450 ml/min, this test yielded a sensitivity of 83% and a specificity of 75% for episodes of thrombosis occurring within 2 to 6 weeks. The authors conclude that episodes of thrombosis in PTFE arm loop grafts are usually preceded by significantly lower Doppler-measured flow than grafts that do not thrombose and that it may be possible, by this means, to identify grafts at risk.     

Comparison between a swim-up and a Percoll gradient technique for the separation of human spermatozoa

Two methods of separating human sperm were compared using twenty-two semen samples. The sperm were separated by a swim-up technique or by self-migration on a Percoll gradient followed by medium change. After separation, the sperm obtained were assessed for progressive motility, ATP content, energy charge index ([ATP + 0.5 ADP]/[ATP + ADP + AMP]) and morphology. In general, and especially for semen samples containing less than 20 X 10(6) sperm/ml, separation by Percoll gradient selected sperm that were superior to those separated by the swim-up technique. The relatively high energy charge index (greater than 0.8) showed that the sperm tolerated the separation conditions well. It is suggested that self-migration on a Percoll gradient should prove useful for obtaining sperm of high quality.     

Histological assessment of follicular development and its applicability to risk assessment

The objective of this article is to describe histological methods currently used to study ovarian physiology that may have applicability to reproductive toxicology. Histologic techniques are, for the most part, inexpensive and easy to perform. Many of these techniques require little equipment and can be readily implemented in small laboratories. The resulting histological preparations are permanent, can be used over again for several different types of analyses, and provide objective, quantifiable endpoints. These techniques have been extremely useful for studying the ovary.