Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg⁻¹·min⁻¹ increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg⁻¹·min⁻¹ showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg⁻¹·min⁻¹, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice.     

Ascorbic acid prevents ischemia-reperfusion injury in the rat small intestine

Ischemia-reperfusion injury by free radicals and lipid peroxides is observed in various organs. Ascorbic acid (AsA) or glutathione (GSH) in various doses (AsA:2, 0.5, 0.1 mmol/kg, GSH:2 mmol/kg) was intraperitoneally administered to male Wistar rats. The entire small intestines were resected just before ischemia, after ischemia, and after 20 min of reperfusion (n = 7–10 at each time point). At each time point, the specimens were subjected to assays of lipid peroxides, GSH, and glutaminase activity of the tissues; they were also examined histologically. In the AsA group, the production of lipid peroxides after reperfusion was significantly suppressed in a dose-dependent manner, and the ratio of oxidized GSH to total GSH was also significantly low. Tissue glutaminase activity decreased to a lesser extent, and the degree of injury was apparently less marked in the AsA group. This study indicates that AsA acts as an antioxidant against peroxidative tissue injury, possibly by scavenging radicals, preserving reduced GSH, and reducing the peroxidative reaction. Received: 21 June 1996 Received after revision: 8 October 1996 Accepted: 12 November 1996     

Plasma atrial natriuretic peptide during hemodialysis with or without fluid removal

Plasma immunoreactive human atrial natriuretic peptide (hANP) levels were measured in 9 patients with chronic renal failure treated with maintenance hemodialysis in order to evaluate the effects of fluid removal and osmotic pressure. Under hemodialysis without fluid removal plasma hANP levels remained unchanged, but the levels were significantly decreased during extra-corporeal ultrafiltration (p less than 0.01). The present study provided strong evidence that the fall in plasma hANP levels in hemodialysis patients is mainly due to the reduction in circulating plasma volume.     

Effects of activin A on anterior pituitary cells fractionated by centrifugal elutriation.

We have shown previously that activin A increases the number of immunoreactive follicle-stimulating hormone (FSH) cells. To further investigate the action of activin A, we examined its effects on anterior pituitary cells fractionated by centrifugal elutriation. Before activin A treatment, FSH cells were widely distributed among various fractions; a higher proportion of FSH cells was found in larger cell fractions (fractions 5-9), and a lower proportion in smaller cell fractions (fractions 2-4). After culture of the cells in each fraction with activin A (10 ng/ml) for 72 h, the number of FSH cells in fraction 4 only was significantly (P less than 0.05) higher by 225% than that in cells cultured without activin A. The amount of FSH secreted into the medium was minimal or undetectable in fractions 1-4. However, FSH secretion tended to be, or was significantly (P less than 0.01 in fraction 9), stimulated by activin A in fractions 5-9, in which the numbers of FSH cells were not significantly affected. These results suggest a dual mode of action of activin A on FSH: activin A increases the number of FSH cells in a specific type(s) of middle-sized cell fraction, and stimulates FSH secretion at least from larger cells without affecting the number of FSH cells.     

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through, an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrorcyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern. blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

An Autopsied Case of Interferon Encephalopathy

Abstract: A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organlc brain syndrome such 88 : dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed difise white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptably severe IFN neurotoxicity.     

Temperature-responsive cross-linked poly(epsilon-caprolactone) membrane that functions near body temperature.

The objective of this study is to develop a sensitive temperature-responsive material that would function near body temperature. To achieve this purpose, we compounded 2-branched and 4-branched poly(epsilon-caprolactone) macromonomers to modulate the transition temperatures of the resulting cross-linked materials. The temperature-responsive properties were studied using differential scanning calorimetry and X-ray diffraction measurements. As a result, the mixing ratios of each macromonomer or the total macromonomer concentrations were very dominant in modulating the transition temperatures. The materials could successfully control the permeation of the model drug, prednisolone, near body temperature.     

Imaging of a large collection of human embryo using a super-parallel MR microscope.

Using 4 and 8-channel super-parallel magnetic resonance (MR) microscopes with a horizontal bore 2.34T superconducting magnet developed for 3-dimensional MR microscopy of the large Kyoto Collection of Human Embryos, we acquired T(1)-weighted 3D images of 1204 embryos at a spatial resolution of (40 microm)(3) to (150 microm)(3) in about 2 years. Similarity of image contrast between the T(1)-weighted images and stained anatomical sections indicated that T(1)-weighted 3D images could be used for an anatomical 3D image database for human embryology.