Inhibition of Lipid Peroxidation by Sesquiterpenoid in Heterotheca inuloides

A sesquiterpenoid, 7-hydroxy-3,4-dihydrocadalin, isolated from a Mexican medicinal plant Heterotheca inuloides was evaluated as an antioxidant. This sesquiterpenoid inhibited mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH. Furthermore, 7-hydroxy-3,4-dihydrocadalin protected red cells against oxidative haemolysis. This sesquiterpene was thus shown to be effective in protecting biological systems against oxidative stresses.     

Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture

Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.     

Effect of 7-Bromo-5-(2-pyridyl)-3H-l, 4-benzodiazepine-2(1H)-one, Bromazepam (Ro 5–3350), a New Minor Tranquilizer, on Psychoneurosis with Special Reference to the Obsessive-Compulsive Symptoms

Clinical application of a minor tranquilizer bromazepam, 7-Bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine-2(lH)-one (Ro 5–3350) was made on 18 cases of obsessive-compulsive neurosis, 10 of anxiety neurosis, 6 hypochondriasis, 4 hysteria and 3 of phobia of bodily odor.

• 1) In 18 cases of obsessive-compulsive neurosis, bromazepam was found markedly effective in 6, effective in 3, fairly effective in 5, ineffective in 2, and aggravated in 2 cases. The effective cases were those with obsessive thinking and manifest anxiety. In other kind of neurosis, bromazepam was markedly effective in 5 and effective in 2 of 10 anxiety neurotic cases, whereas it was almost ineffective in the cases of hypochondriasis, hysteria and phobia of bodily odor.
• 3) The maximum daily dose of bromazepam was 10 to 20 mg in many cases, and 20 to 30 mg in some other cases. The durg is quick-acting to such an extent that it took 2 to 5 days for its action to become manifest in markedly effective cases.
• 4) Various laboratory tests revealed no appreciable abnormality in most cases where bromazepam was employed. Physical side effects such as slight hypotension, dizziness, and sleepiness were observed in a few cases, and mental side effects such as loquaciousness and restlessness in about 20 cases.
• 5) The target symptoms of bromazepam were suggested to be anxiety, tension, and irritation like previously reported other benzodiazepines. The fact that its action of relieving anxiety and tension and of elevating mood was found to be more potent than those of other benzodiazepines and that it was effective on some obsessive-compulsive neurosis that showed little response to other benzodiazepines, suggested that bromazepam is a potent and characteristic new minor tranquilizer of clinical value.

     

Adjuvant Immunotherapy for Malignant Brain Tumors

New methods of adjuvant immunotherapy were introduced for thetreatment of malignant brain tumors. Allogeneic bone marrowcell transfusion or local intratumoral infusion of allogeneicor autologous peripheral white blood cells were conducted on18 patients having malignant glioma, after ordinary treatmentof operation, radiation or chemotherapy. The survival rate ofthese patients was significantly prolonged when compared withthe rate normally expected. No side effects were noted. Morphologicalchanges of cells in the cerebrospinal fluid taken from the intratumoralcavity, before and after infusion of peripheral white bloodcells, were studied. Cytolysis and phagocytosis of tumor cellsby macrophages were observed. Suppressive mechanism of immunologicallycompetent cells on glioma cells was partly studied, cytologicallyin vitro.     

STUDIES ON RACEMIZATION DURING COUPLINGS USING A SERIES OF MODEL TRIPEPTIDES INVOLVING ACTIVATED RESIDUES WITH UNFUNCTIONALIZED SIDE CHAINS

Racemization studies have been carried out using as model tests couplings of N-benzyloxycarbonylglycyl-l -χ with benzyl N^e-benzyloxycarbonyl-l -lysinate followed by deprotection and analysis for the diastereomeric tripeptides with an amino acid analyzer, for χ = alanine, leucine, phenylalanine, valine and isoleucine. The order of susceptibility to racemization of residues during these segment couplings depends on whether the solvent is polar or apolar, with isoleucyl and valyl, followed by phenylalanyl, being the most susceptible ones in polar solvents. The racemization depressing effect of some additives on carbodiimide-mediated couplings has been examined. Reconciliation of apparent discrepancies in data in the literature on the relative merits of l-hydroxy-benzotriazole and N-hydroxysuccinimide is made on the basis of the nature of the model tests used in acquiring the data.     

A Biodegradable Poly-l-lactic Acid Coronary Stent in the Porcine Coronary Artery

Although biocompatibility of biodegradable stents is controversial, stents made of high molecular weight poly- l -lactic acid (PLLA) are thought to be the most promising. We investigated the biocompatibility of PLLA stents histologically and angiographically in porcine coronary arteries. The Igaki-Tamai stent is made of PLLA monofilaments (molecular mass 183 kD) with a zigzag helical coil design. Fourteen PLLA stents in 6 pigs and 9 Palmaz-Schatz half stents in 9 pigs were implanted in 15 normocholesterolemic pigs. Stents were mounted on a delivery catheter, and were implanted percutaneously into coronary arteries. Coronary angiography was performed before and immediately after stenting, at 2 and 6 weeks in five PLLA pigs and nine Palmaz-Schatz pigs. Histological studies were performed in PLLA pigs: 2 pigs at 2 weeks, 3 pigs at 6 weeks, and 1 pig at 16 weeks with hematoxylin-eosin and elastica van Giesons stains. All PLLA stents were successfully delivered. No stent thrombosis was detected in either group. There were no significant differences in minimal lumen diameter (MLD) or percent diameter stenosis between the PLLA and Palmaz-Schatz stent groups immediately after implantation, or at 2 or 6 weeks after implantation. Histological studies at 2, 6, and 16 weeks revealed no inflammation and minimal neointimal coverage on the PLLA stent struts. The PLLA stent maintained its structure for up to 16 weeks. These results suggest sufficient biocompatibility and strength of PLLA biodegradable stents in porcine coronary arteries. Clinical trial is now underway to validate the safety and usefulness of PLLA stents in humans.     

Experimental and Clinical Studies of Biodegradable Polymeric Stents

The metallic stent has become the most common device to reduce acute occlusion and late restenosis after balloon angioplasty, but the long-term effects of metallic stents in human coronary arteries are still unknown. To overcome several problems of conventional stenting, there have been many attempts to manufacture stents made of biodegradable materials. Although some studies have noted various degrees of inflammatory responses after biodegradable stent implantation, stents made of poly-1-lactic acid (PLLA) showed high biocompatibility with minimal inflammatory response and neointimal formation in porcine coronary arteries. A clinical study of PLLA self-expanding stent implantation is underway in Japan. The initial and 6-month results are favorable and suggest the feasibility, safety, and efficacy of the PLLA biodegradable stent in humans. However, long-term follow-up with larger numbers of patients will be required to validate the long-term efficacy of PLLA stents.     

A Case of Pacemaker Lead Fracture Associated with Thoracic Outlet Syndrome

A pacemaker lead fracture in the left subclavian vein was caused by compression of the clavicle and the first rib; subsequent coil elongation at the same site on the right side was observed in the replacement lead in a patient with thoracic outlet syndrome. Venography showed narrowing of the subclavian vein at the site where the lead abnormalities were observed. This case illustrates that a lead in the subclavian vein can be easily damaged when a patient has thoracic outlet syndrome.     

VDD Pacing with a Previously Implanted Single Lead System

Three patients who had undergone implantation of a rate modulated, afrial sensitive RS4 pacemaker, with a single orthogonal lead underwent replacement of a depleted unit with a DDD pulse generator, reusing the original lead with an adapter that allowed conversion of the bipolar atrial electrode into unipolar configuration. The mean atrial electrogram amplitude was 1,8 mV and no significant atrial sensing defects were found during Holler monitoring. As the RS4 pulse generator is no longer available, continued VDD pacing is possible by replacing it with a DDD pulse generator using the previously implanted single lead system.