Effects of physiological and pathological levels of glucocorticoids on skeletal muscle glutamine metabolism in the rat

The effects of physiological and pathological concentrations of glucocorticoids were investigated using the glucocorticoid antagonist RU486 and the synthetic glucocorticoid dexamethasone, respectively. The effects of these treatments on the concentrations of glutamine and other amino acids in skeletal muscle and plasma and on the rates of release of glutamine and alanine from incubated preparations of skeletal muscle of the rat were investigated. Dexamethasone treatment increased the concentration of glutamine and the rate of release of this amino acid from incubated soleus muscle preparations. This treatment decreased the concentration of glutamine in both gastrocnemius and EDL muscles, but was without effect on the rate of glutamine release from EDL muscles. In contrast, administration of the glucocorticoid antagonist RU486 decreased the rate of glutamine release from muscle. It is concluded that glucocorticoids have marked effects on the metabolism of glutamine by skeletal muscle per se and that these hormones may be important in the control of the rate of glutamine release from muscle in both physiological and pathological conditions.     

Synthesis of antimicrobial agents. 3. Syntheses and antibacterial activities of 7-(4-hydroxypiperazin-1-yl)quinolones

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared. The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives. From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives. Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials.     

Free-floating thrombus of the extracranial internal carotid artery

Free-floating clots of the extracranial internal carotid artery are generally considered as surgical emergencies. This retrospective study analyzes six free-floating clots diagnosed by arteriography. Three of these patients had a fixed stroke while the other three had an evolving stroke. Three patients had antecedent ocular or hemispheric transient ischemic attacks. The causes of free-floating clots in the internal carotid artery were atheromatous stenosis in two cases, ulcerated plaque in three cases, and carotid artery dissection in one. All six patients were seen late, approximately 15 hours after their neurologic accident. They were treated with intravenous heparin over a two to five week period. Repeat arteriograms demonstrated complete clot lysis in four instances, while partial lysis was seen in one case. Moderate extension of thrombus occurred in one case only. No further neurologic complications were noted during the treatment by heparin. As indicated by follow-up arteriographic findings, secondary surgery was performed for major carotid lesions and residual clots in five cases. The free-floating thrombus syndrome of the carotid artery should not be considered as a surgical emergency when discovered late in the wake of an acute neurologic accident.     

Factors affecting fusion rate in adult spondylolisthesis

The authors examined factors affecting fusion rate in the surgical treatment of 89 consecutive adult patients with spondylolisthesis. Two factors significantly improved fusion rate: combined anterior and posterior fusion and rigid postoperative immobilization in the cast. In 65 patients with isthmic spondylolisthesis, the fusion rate was raised from 70% when posterior fusion alone was used to 88% when combined anterior and posterior fusion was used. In 20 patients with degenerative spondylolisthesis, frequent use of combined anterior and posterior fusion contributed to a high overall fusion rate of 95%. Among patients with isthmic spondylolisthesis, postoperative cast immobilization resulted in a higher fusion rate of 90% compared with a fusion rate of 63% obtained after brace immobilization.     

Ultrastructural reversible changes in fish neuromuscular junctions after chronic exercise

Neuromuscular junctions (NJs) of fin muscles of teleostean fishes, Lebistes reticulatus, were ultrastructurally analyzed during 60 min of chronic exercise and a subsequent period of 90 min of induced recovery. NJs from 30-min-exercised fishes showed an almost complete depletion of synaptic vesicles (SVs), corresponding to 83% of SV consumption; 76% of axon terminals were branched at the end of this period. During the recovery period, it was possible to observe the reversibility of the changes induced by the exercise and the transitory events that lead to the reacquirement of the normal NJ morphology. After 15 min of rest, SV population increased to a value of 54.6 SVs/micron2 and the percentage of branched axons was 66.5%. At 60 min of recovery the number of SVs reached a value of 84.6 SVs/micron2. The SV population was fully reestablished at 80 min of rest, while the percentage of branched axons was found within normal ranges after 90 min of recovery. These results demonstrate that chronic exercise induced physiological depletion of NJ SVs and other axon terminal morphological changes, as well as that postexercise rest induces the reestablishment of the normal NJ morphology.     

Fetal antigen retained by mature neurons and ependyma studied with a monoclonal antibody (6B9)

A mouse monoclonal antibody (MAb 6B9, isotype IgM) was raised against autopsy tissue samples from the central nervous system (CNS) of multiple sclerosis (MS) patients. By immunofluorescence microscopy, MAb 6B9 intensely stains most or all cells in fetal rats. However, MAb 6B9 differentially stains various cell types in adult rats. Neurons, ependymal cells, and adrenal chromaffin cells are stained intensely, whereas astrocytes and oligodendrocytes are not stained. The 6B9-reactive antigen (6B9 antigen) is sensitive to periodic acid, but insensitive to treatment with protease, RNase, or hyaluronidase. Results from immunofluorescence microscopy on semithin sections and cultured neuroblastoma cells indicate that 6B9 antigen is intracellular. This is supported by immunoelectron microscopy, where labeling for 6B9 antigen appears in the cytoplasm distinct from any identifiable organelle. Further studies on 6B9 antigen should reveal its chemical nature as well as the significance of developmental changes in its distribution.     

Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Corneal endothelial cell loss following trephination

The amount of endothelial cell loss that occurs to the donor cornea during the trephination process was evaluated in 40 porcine eyes. A vital staining technique (alizarin red S and acid violet 19) was used to quantify the extent of endothelial damage and removal. Two types of corneal punches (Weck and H&I0 were used for trephination. The average amount of endothelial loss from the peripheral cornea was 7.9%, accounting for only a 3% loss of endothelial cells over the total surface area of the corneal button. a comparison of the Weck and H&I corneal punches showed no significant difference (P greater than 0.1) by Student's test for both endothelial cell damage and removal.