Vasodilator action of guinea pig vasoactive intestinal polypeptide (VIP): comparison with common mammalian VIP.

The vascular activity of guinea pig (gp) and common mammalian (p) VIP were compared in anesthetized guinea pigs and dogs. In the guinea pig, intravenous injections of gpVIP and pVIP increased pancreatic blood flow and reduced the systemic arterial pressure and pancreatic vascular resistance in a dose-related manner. There were no significant differences in the vasodilator actions of these two VIPs, indicating that the overall cardiovascular actions of gpVIP and pVIP are similar in guinea pigs. In the dog, gpVIP, when given intra-arterially, was less potent (about 1/4) than pVIP in its action on femoral blood flow, suggesting that the blood vessels of the dog hind leg are more sensitive to its own VIP than to gpVIP. Oxidation of pVIP and gpVIP with H2O2 greatly reduced their vasodilator effects on the femoral arterial blood flow. The vascular effects were restored to control levels by reduction of the oxidized peptides with mercaptoethanol, which suggests that methionine residues of gpVIP and pVIP are important in the vasodilator effect on the femoral arterial bed in dogs.     

Adrenocortical carcinoma responded to treatment with o,p'-DDD--a case report

A case of a huge inoperable adrenocortical carcinoma which secreted testosterone without characteristic symptoms was treated with o,p'-DDD (2,2-bis(2-chlorophenyl-4 cholorophenyl) 1,1-dichloroethane). With this therapy, the tumor decreased in size which was confirmed by the computed tomography (CT). Eighteen months later, however, lethargy and logopathy appeared and the tumor grew again rapidly with the withdrawal of o,p'-DDD performed for the evaluation of these mental disturbances. The tumor then diminished gradually in size soon after the treatment was resumed and the above unfavorable symptoms were not developed again with the combined administration of a central nervous stimulant. During o,p'-DDD treatment, plasma testosterone and estrogen decreased, and plasma aldosterone also decreased but within the normal range. Plasma cortisol also tended to decrease despite hydrocortisone was administered. Plasma adrenocorticotropic hormone (ACTH) was maintained within the normal range for the first six months but then increased gradually. It decreased and became normal with the additional administration of hydrocortisone. The patient's normal menstruation at the preadministrative stage changed to oligomenorrhea, then amenorrhea after the treatment, but no endocrinological sign except for the menses was observed during the treatment.     

High-performance liquid chromatographic determination of α-keto acids in plasma with fluorometric detection

This paper describes a sensitive high performance liquid chromatographic method for the quantitative determination of α-keto acids in plasma using a fluorescence detector. This method is about ten times more sensitive than that reported in a previous paper. Only 50 μl of plasma are needed for the determination of α-keto acids. However, p-hydroxyphenylpyruvic acid could not be analysed because the quinoxalinol derived from it does not exhibit fluorescence.     

Repeated freeze–thaw cycles reduce the survival rate of osteocytes in bone-tendon constructs without affecting the mechanical properties of tendons

Frozen bone-patellar tendon bone allografts are useful in anterior cruciate ligament reconstruction as the freezing procedure kills tissue cells, thereby reducing immunogenicity of the grafts. However, a small portion of cells in human femoral heads treated by standard bone-bank freezing procedures survive, thus limiting the effectiveness of allografts. Here, we characterized the survival rates and mechanisms of cells isolated from rat bones and tendons that were subjected to freeze–thaw treatments, and evaluated the influence of these treatments on the mechanical properties of tendons. After a single freeze–thaw cycle, most cells isolated from frozen bone appeared morphologically as osteocytes and expressed both osteoblast- and osteocyte-related genes. Transmission electron microscopic observation of frozen cells using freeze-substitution revealed that a small number of osteocytes maintained large nuclei with intact double membranes, indicating that these osteocytes in bone matrix were resistant to ice crystal formation. We found that tendon cells were completely killed by a single freeze–thaw cycle, whereas bone cells exhibited a relatively high survival rate, although survival was significantly reduced after three freeze–thaw cycles. In patella tendons, the ultimate stress, Young’s modulus, and strain at failure showed no significant differences between untreated tendons and those subjected to five freeze–thaw cycles. In conclusion, we identified that cells surviving after freeze–thaw treatment of rat bones were predominantly osteocytes. We propose that repeated freeze–thaw cycles could be applied for processing bone-tendon constructs prior to grafting as the treatment did not affect the mechanical property of tendons and drastically reduced surviving osteocytes, thereby potentially decreasing allograft immunogenecity.     

Electrophysiological analysis of structural aspects of voltage-dependent SR K+ channel.

This article presents a brief review on the electrophysiological analysis of the structural aspects of the voltage-dependent SR (sarcoplasmic reticulum) K+ channel. In the first half, early attempts to determine the physical dimensions of the ion conducting mechanism such as the mouth, narrow tunnel, or ion selective filter of the channel, are reviewed. The depicted cartoon of the SR K+ channel, as an extremely short, busy district with a big mouth on each side, is quite similar to the recently-obtained reconstructed structural image of the acetylcholine receptor channel. In the latter half, we introduce our recent attempts to draw a physical image of the gating mechanism of the SR K+ channel. We examined, for example, the location of the gate and the voltage sensor, and the relationship between them. It is suggested that the gate and the sensor are connected tightly and that the sensor would be exposed to the surface of the lumen side of SR when the gate opens. Finally, the issue of substates in SR K+ channel is discussed. It is implied that the substrate-conductances reflect a partial occlusion of the pore by an intermediate-open gate.