Somatostatin decreases the calcium inward current in guinea-pig atria.

1. The effects of somatostatin on mechanical and electrophysiological responses were studied in guinea-pig atrial muscle preparations and single cells. 2. Somatostatin (greater than or equal to 10(-8) M) decreased the twitch contraction in a concentration-dependent manner in electrically driven left atria and spontaneously beating right atria. However, the beating rate was not affected. 3. The negative inotropic effect of somatostatin was transient. Desensitization to this agent developed slowly during continuous exposure to the peptide. 4. In single atrial cells, somatostatin significantly shortened the action potential duration, but the resting potential and action potential amplitude were not affected. 5. Under whole cell voltage-clamp conditions, somatostatin decreased the calcium inward current without affecting the sodium and potassium currents. 6. These results suggest that somatostatin selectively acts on the calcium channel of guinea-pig atrial cells to reduce the calcium inward current, which in turn gives rise to the negative inotropic effect.     

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.     

Disposition of [3H]flobufen and its active metabolite in rats

The present authors investigated the excretion, distribution and pharmacokinetics of the novel potential antirheumatic agent flobufen and its active metabolite after p.o. and i.v. doses of 2, 10 and 50 mg/kg administered to rats. The drug is resorbed well from the digestive tract and mostly it is metabolized to the principal metabolite M, which is only slowly excreted from the organism mainly by renal clearance. Within the whole dose range the kinetics of the drug is linear. Binding of flobufen and M to proteins is high (95-99%). The highest concentrations of radioactive metabolites (mostly M) were found in the plasma, liver, lungs, kidneys, connective tissue and inflammatory foci. The penetration of metabolites through the placenta and excretion in human milk are relatively important.     

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.     

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.     

Giant hydronephrosis presenting as unilateral iliofemoral vein thrombosis

We report a case of left iliofemoral vein thrombosis with extension to the inferior vena cava associated with giant right hydronephrosis secondary to ureteropelvic junction obstruction. Surgery revealed marked infrarenal vena caval compression and deviation to the left side caused by the dilated right renal pelvis, with resultant kinking of the origin of the left iliac vein. It is postulated that the reduction in blood flow caused by this compression and distortion predisposed this patient to venous thrombosis.