Biological activity of fluorinated 3,4-dihydroisoquinolines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 26, No. 1, pp. 44–45, January, 1992.     

Alteration of second-messenger ligand binding following 2-hr hemispheric ischemia in the gerbil brain.

The alterations of second-messenger ligand binding and cerebral blood flow (CBF) were evaluated in the gerbil brain after 2-h unilateral common carotid artery occlusion. [3H]Forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu) were used as specific ligands for adenylate cyclase (AC) and protein kinase C (PKC) activity estimation, respectively. CBF was determined at the end of the experiment by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted simultaneous measurement of the three parameters in the same brain. The levels in the caudate-putamen, globus pallidus, and hippocampus were analyzed. The animals were divided into three groups: Group 1 with severe ischemia (CBF in the lateral nuclei of the thalamus (CBFt) less than 50 ml/100 g/min), Group 2 with mild ischemia (CBFt greater than or equal to 50 ml/100 g/min), and the Sham Group. The PDBu binding revealed a statistically significant increase in the caudate-putamen, lateral nuclei of the thalamus and hippocampus (CA1 and CA3 regions and dentate gyrus) on the ischemic side in Group 1 as compared to that in Group 2 and the Sham Group. In contrast, the FK binding did not show any significant changes in any of the regions. These data and our previous findings for 6-h ischemia suggest that (1) PKC translocation to the cell membrane may occur at the early ischemic phase in particular regions including the caudate-putamen, lateral nuclei of the thalamus and hippocampus, with the translocated PKC gradually diminishing during the subsequent ischemic period; and (2) the suppression of the AC system observed in 6-h ischemia may not appear in the early ischemic phase.     

Tau protein induces bundling of microtubules in vitro: comparison of different tau isoforms and a tau protein fragment.

Expression of tau protein in non-neuronal cells can result in a redistribution of the microtubule cytoskeleton into thick bundles of tau-containing microtubules (Lewis et al.: Nature 342:498-505, 1989; Kanai et al.: J Cell Biol 109:1173-1184, 1989). We reconstituted microtubule bundles using purified tubulin and tau in order to study the assembly of these structures. Taxol-stabilized tubulin polymers were incubated with various concentrations of recombinant human tau and examined by electron microscopy. With increasing concentrations of tau 3 (tau isoform containing three microtubule binding domains) or tau 4 (isoform containing four microtubule binding domains) the microtubules changed orientation from a random distribution to loosely and tightly packed parallel arrays and then to thick cables. In contrast, tau 4L, the tau isoform containing four microtubule binding domains plus a 58-amino acid insert near the N-terminus, showed minimal bundling activity. tau 4-induced bundling could be inhibited by the addition of 0.5 M NaCl or 0.4 mM estramustine phosphate, conditions which are known to inhibit tau binding to microtubules. A tau construct that contained only the microtubule binding domains plus 19 amino acids to the C-terminus was fully capable of bundling microtubules. Phosphorylation of tau 3 with cAMP-dependent protein kinase had no effect on its ability to induce microtubule bundling. These results indicate that tau protein is directly capable of bundling microtubules in vitro, and suggests that different tau isoforms differ in their ability to bundle microtubule filaments.     

Orbital blowout fractures as a cause of sinonasal obstructive disease.

Six cases of orbital blowout fracture with inferomedial herniation of orbital contents into the sinonasal ostiomeatal unit causing obstruction to maxillary sinus outflow are presented. Potential hazards during endoscopic sinus surgery in these cases are outlined.     

Force displacement characteristics of the posterior cruciate ligament.

The percent force changes in the posterior cruciate ligament were calculated using a previously validated computerized knee model after the femoral insertion sites were varied 2.5 and 5.0 mm in an anterior, posterior distal, anterior distal, and posterior distal direction. The tibial insertion sites were also varied 2.5 and 5.0 mm in the medial, lateral, proximal, and distal directions. Percent force changes were measured over a range of 0 degree to 90 degrees. These insertion sites simulated potential surgical placement errors. Results of this study demonstrated that the greatest percent force changes in the posterior cruciate ligament were at full extension. The greatest absolute percent force change between 0 degree and 90 degrees of flexion was with a femoral insertion of the posterior cruciate ligament placed 5 mm anterior to its normal attachment site, which resulted in a 39% change in the posterior cruciate ligament force. Distal femoral site attachment had the least effect (10% at 5.0 mm). Alterations at the tibial attachment site were less sensitive than on the femur; the greatest absolute percent force changes occurred with medial and lateral attachment sites (14% and 15%, respectively, at 5.0 mm). A minimal amount of percent force changes were seen between 45 degrees and 75 degrees of knee flexion in all positions tested for both tibial and femoral attachment sites. This model suggests that, like the anterior cruciate ligament, the force in the posterior cruciate ligament is also sensitive to attachment site position. As in anterior cruciate ligament studies, the femoral attachment site was found to be more sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway obstruction due to inoperable intrathoracic goitre treated by tracheal endoprosthesis.

Thyroidectomy is the treatment of choice in patients with thyroid enlargement complicated by compression or displacement of the trachea because of the risk of complete airway obstruction due to sudden enlargement of the goitre by, for example, haemorrhage. In patients who are medically inoperable an endoscopically inserted tracheal endoprosthesis may provide longstanding airway patency, as reported here.     

Treatment of post-traumatic limb shortening]

The physiological phenomenon of changes in callus formation during distraction was first described by Codivilla at the beginning of this century. Having investigated and proved the influence of tension stress on callus formation, Ilizarov used this as a method to treat limb shortening and deformities. Because of his remarkable results we introduced this method in our hospital in 1990, using the original Ilizarov ring fixator. From November 1990 to December 1991, we used this technique in 10 cases of combined post-traumatic bone shortening with deformity (the tibia was affected in six patients, the femur in three and the forearm in one). The mean shortening was 3.1 cm, the mean varus or valgus deformity 9.5 degrees, the mean anteflexion or recurvation 8.3 degrees, and the mean rotation deformity 8.5 degrees. Distraction/correction lasted between 8 and 55 days (mean: 37 days). Fixation was necessary for between 60 and 339 days. If corticotomy was performed in the diaphyseal bone, fixation lasted almost twice as long (11.33 days/mm lengthening) as in the metaphyseal area (6.55 days/mm lengthening). There were 14 complications, most of which were considered minor. The latter included pin infections (4), wire breaking (1) and restricted range of motion of the knee or ankle (5). Among the major complications were two nerve irritations, which recovered spontaneously, and two pin-induced local bone infections, which required surgical intervention. Achievement of the goals of treatment-complete correction of shortening and deformity-was not affected by these complications.     

Influence of spinal immobilization on consolidation of posterolateral lumbosacral fusion. A roentgen stereophotogrammetric and radiographic analysis.

To determine the influence of the duration of postoperative lumbar immobilization with the aid of a rigid lumbar orthosis on the consolidation of posterolateral lumbosacral fusions, 22 patients with no previous osseous spinal surgery and with fusion without osteosynthesis due to spondylolysis-olisthesis Grade 1 to 2 or intervertebral disc or facet joint disorder were examined by roentgen stereophotogrammetric analysis in supine and erect positions and by conventional radiography for 1 year after surgery. In Series 1, patients (n = 11) were instructed to keep the trunk straight with the aid of a molded, rigid lumbar orthosis for 5 months after surgery; and in Series 2 (n = 11), the same instructions were given, but for 3 months. In Series 1, osseous fusion was seen on radiographs in eight patients. In these patients, the intervertebral translations between the fused vertebrae began to decrease 3-6 months after surgery, and within 1 year, the fusions became rigid, as defined by roentgen stereophotogrammetric analysis, or intervertebral translations of mostly less than 1 mm persisted. In three patients with poor fusion still seen on radiographs 1 year after surgery, no rigid fusion was obtained and intervertebral translations of up to 10 mm persisted. In Series 2, a similar roentgen stereophotogrammetric analysis pattern was noted in two patients with osseous fusion and in seven with poor fusion seen on radiographs. The fusion was radiographically doubtful in two patients. In these patients, the intervertebral translations decreased, but translations of 1.5 mm persisted 1 year after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)