Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

412 records · Page 23Linked to original sources

PubMedDate not supplied

The reciprocal protective effects of magnesium and calcium in hyperkalemic cardioplegic solutions on ischemic myocardium.

The cardioprotective effects of magnesium and calcium in hyperkalemic cardioplegic solutions were investigated in isolated rat hearts. Isolated rat hearts were arrested for 30 min at 37 degrees C in cardioplegic solutions containing magnesium and calcium in varying concentrations. In St. Thomas' Hospital cardioplegic solution, the magnesium and calcium concentrations were varied as follows: Mg 0; Ca 0.1, 0.3, 0.6, 1.2 mmol/l (mM)./ Mg 4; Ca 0.1, 0.3, 0.6, 1.2 mM./ Mg 8; Ca 0.1, 0.3, 0.6, 0.9, 1.2 mM./ Mg 12; Ca 0.1, 0.6, 0.9, 1.2 mM./ Mg 16; Ca 0.1, 0.6, 1.2, 1.5 mM. For each magnesium concentration, the percentage recovery of aortic flow generated dose-response curves depending on calcium concentration. The maximum percentage recovery of aortic flow was 76.0% +/- 2.7% (mean +/- SEM) in the Mg0-Ca0.1 mM group, 77.1% +/- 2.0% in the Mg4-Ca0.3 mM group, 78.5% +/- 2.3% in the Mg8-Ca0.6 mM group, 79.8% +/- 2.4% in the Mg12-Ca0.9 mM group and 80.0% +/- 3.4% in the Mg16-Ca1.2 mM (ST solution) group. Significant difference in the recovery of aortic flow has not been observed among these groups, and furthermore, significant differences in the recovery of other parameters of cardiac function and Ck leakage have not been observed among these groups. These results suggest that the cardioprotective effects depend on the relative combination of magnesium and calcium concentrations, and that it is important to maintain an appropriate balance of magnesium and calcium in hyperkalemic cardioplegic solutions.

Animals↗

PubMedDate not supplied

Beneficial actions of acidotic initial reperfusate in stunned myocardium of rat hearts.

The effects of metabolic acidosis and alkalosis in the initial reperfusate on post-ischemic stunned myocardium were investigated in isolated rat hearts. Metabolic acidosis and alkalosis were produced by altering the doses of artificial buffer (Tris) in place of sodium bicarbonate. All hearts were subjected to global ischemia for 15 min at 37 degrees C. The initial reperfusate under study was given during the subsequent 10 min of reperfusion, just prior to release of the aortic clamp. After that, reperfusion using normal Krebs-Henseleit buffer solution was carried out for 40 min. The acidotic initial reperfusate (pH 6.8) resulted in better protection than the alkalotic initial reperfusate (pH 7.8), as demonstrated by 1) a higher recovery of aortic flow (80.6% +/- 3.8% vs 32.7% +/- 4.8%, p less than 0.01), 2) a smaller leakage of creatine kinase during the initial reperfusion phase (6.0 +/- 0.7 vs 14.6 +/- 2.1 IU/10 min/g dry weight, p less than 0.05) and during the post-ischemic Langendorff perfusion phase (8.8 +/- 1.7 vs 37.3 +/- 5.2 IU/10 min/g dry weight, p less than 0.05), and 3) a lower myocardial water content at the end of reperfusion (84.8% +/- 0.2% vs 85.7% +/- 0.3%, p less than 0.05). Not only Tris buffer system, but also HEPES buffer system indicated that acidotic initial reperfusate was effective to protect against myocardial injury. These results suggest that 1) the extracellular pH during initial reperfusion profoundly influences the reversible myocardial dysfunction (stunned myocardium), and 2) the acidotic initial reperfusate improves post-ischemic myocardial performance.

Acidosis↗

PubMedDate not supplied

Characteristics of thyrotropin releasing hormone (TRH) receptors in rat brain.

Characteristics of TRH-receptors were studied in the rat central nervous system (CNS). Ion species, pH and temperature importantly influenced TRH-receptor binding. Subcellular distribution of TRH-receptor binding revealed that synaptic membranes had the greatest percentage of total sites. Scatchard analysis suggested that the rat CNS had two distinct TRH binding sites with apparent dissociation constants (Kd) of 5 X 10(09) M and 13 X 10(-8) M. Receptor activity is sensitive to trypsin and phospholipase A digestion, suggesting that protein and phospholipid moieties are essential for the binding of [3H]TRH. Thiol reagents reduced the binding activity of the receptor, suggesting that an intrachain disulfide bond may form an important constituent of the binding site for TRH. The TRH-receptor in the rat brain was successfully solubilized with non-ionic detergent Triton X-100. On gel chromatography with Sepharose 6B column, the solubilized TRH-receptor molecule eluted at the fraction corresponding to an apparent molecular weight of 300,000 daltons, with Stokes' radius of 5.8 nm. The regional distribution of TRH-receptor binding was examined to clarify the site of TRH action. The highest level of binding was in the hypothalamus, cerebral cortex and hippocampus, indicating that TRH affects the CNS function mainly through the limbic system, cerebral cortex and hypothalamus. Moreover, tricyclic anti-depressants and Li+ decreased the binding of [3H]TRH. These findings suggest that endogenous TRH and TRH receptor may play the role of a neurotransmission modulator in the brain to control emotional and mental functions.

Animals↗

PubMedDate not supplied

Chronic dihydroergotoxine administration sets on receptors for enkephalin and thyrotropin releasing hormone in the aged-rat brain.

Dihydroergotoxine (DHET) is comprised of equal part of the mesylates of dihydroergocristine, dihydroergocornine and dihydroergocryptine. In the standard radioreceptor assays, DHET components displaced the CNS-receptor binding of [3H]-enkephalin (ENK) and [3H]thyrotropin releasing hormone (TRH). The inhibitory effect of DHET on ENK binding was competitive, and an allosteric effect seems to be involved in the DHET inhibition of TRH binding to its receptor. Intraperitoneal injections of DHET (1 mg/kg/day) to aged rats for 14 days resulted in a significant increase of ENK and TRH binding in the cerebral cortex. Scatchard plots of saturation experiments indicate that the increase of ENK binding is due to the increased affinity of the binding sites, and the increase of TRH binding reflects an increase in numbers of binding sites. The results suggest that the therapeutic efficacy of DHET is derived initially from its effects on the ENK and TRH receptors especially in the cerebral cortex, which in turn influence the function of monoaminergic neurons.

Aging↗

PubMedDate not supplied

Dose- and treatment duration-related effects of p-tert-octylphenol on female rats.

We conducted a study to investigate the relation between estrogenic effects of p-tert-octylphenol (OP) and serum concentration as well as treatment duration. Adult ovariectomized rats were given daily subcutaneous injections of OP for 2 and 14 days. 17beta-Estradiol was also administrated at a dose of 5 microg/kg. OP was detected in serum at doses of 25 mg/kg and above for 2 days and with multiple doses (14 days) of 12.5 mg/kg. Uterine weights and luminal epithelial height were increased although the effects were weak compared to 17beta-estradiol. Estrous conversion of the vaginal smear was detected only in 14-day-treated animals. OP-treatment for 2 days caused a dose-related increase in proliferation of uterine luminal, glandular, and stromal cells and vaginal epithelial cells. From the 14-day experiment, the minimum estrogenic dose level of OP was concluded to be 25 mg/kg/day and the serum level at the dose was determined to be about 80 ng/ml. These findings demonstrated that OP exerts estrogenic activity in the female reproductive tract of ovariectomized rats only at high levels of exposure and that the effects are fundamentally related to serum OP levels.

Animals↗

PubMedDate not supplied

Postoperative pulmonary complications in calves after implantation of an electric total artificial heart.

In long-term studies testing the Penn State Total Artificial Heart involving 30 calves, seven calves died of pulmonary complications within 2 weeks after receiving the implant (Group 1 [G1]) and seven calves survived from 2 weeks to 3 months without infection (Group 2 [G2]). Comparative studies were performed using multiple variables: cardiopulmonary bypass (CPB) time, cardiac index, central venous pressure, leukocyte count, hematocrit, total protein, albumin, serum glutamic oxaloacetic transaminase (GOT), creatinine, water balance, and transfused blood volume. In G1, CPB time was longer than in G2 (182 +/- 19 vs 156 +/- 17 minutes, respectively, p = 0.018). Postoperative minimum total protein and albumin in G1 were lower than those in G2 (56.5% +/- 6.0% and 59.0% +/- 5.5% of preoperative values vs 68.4% +/- 8.5% and 67.8% +/- 6.1%, respectively, p = 0.011 and 0.015). Water balance in G2 was more positive than in G1 (11.7 +/- 6.8 vs 1.4 +/- 8.3 L, respectively, p = 0.020). Other variables showed no significant differences. Microscopic findings of the lung in G1 were congestion, hemorrhage, aggregation of neutrophils, and proteinaceous material within the interstitial tissues and alveoli.

Animals↗

PubMedDate not supplied

Steady state hemodynamic and energetic characterization of the Penn State/3M Health Care Total Artificial Heart.

Total Artificial Heart (TAH) development at Penn State University and 3M Health Care has progressed from design improvements and manufacturing documentation to in vitro and in vivo testing to characterize the system's hemodynamic response and energetic performance. The TAH system is completely implantable and intended for use as an alternative to transplantation. It includes a dual pusher plate pump and rollerscrew actuator, welded electronics and battery assembly, transcutaneous energy transmission system, telemetry, and a compliance chamber. In vitro testing was conducted on a Penn State mock circulatory loop with glycerol/water solution at body temperature. Tests were performed to characterize the preload and afterload response, left atrial pressure control, and power consumption. A sensitive preload response was demonstrated with left atrial pressure safely maintained at less than 15 mm Hg for flow rates up to 7.5 L/min. Variations in aortic pressure and pulmonary vascular resistance were found to have minimal effects on the preload sensitivity and left atrial pressure control. In vivo testing of the completely implanted system in its final configuration was carried out in two acute studies using implanted temperature sensors mounted on the electronics, motor, and energy transmission coil in contact with adjacent tissue. The mean temperature at the device-tissue interface was less than 4 degrees C above core temperature.

Animals↗

PubMedDate not supplied

MRI of adenomyotic cyst of the uterus.

The radiologic and pathologic features of three cases of adenomyotic cysts are presented. Two cases were subserosal and one was intramyometrial. All three cases had cystic spaces filled with hyperintense fluid on T1-weighted images, which were surrounded by hypointense tissue on T2-weighted images.

Adult↗

PubMedDate not supplied

Powerful solvent systems useful for synthesis of sparingly-soluble peptides in solution.

Our maximum protection strategy for the synthesis of human parathyroid hormone(1-84) indicates that fully protected peptide segments in the form of Boc-peptide phenacyl (Pac) ester are relatively soluble in ordinary organic solvents such as DMF, NMP or DMSO, which are suitable for coupling segments. However, about 1% of such segments synthesized were found to be insoluble even in the most polar solvent, DMSO. Thus, a more powerful solvent which can be used for their peptide synthesis was pursued. Among the solvent systems tested, a mixture of trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) and trichloromethane (TCM) or dichloromethane (DCM) was found to be most powerful for dissolving such sparingly-soluble protected peptides. These solvent systems were confirmed to be useful for the removal reaction of the carboxy-terminal Pac esters from the sparingly-soluble segments. They were then tested for the coupling reactions of fully protected Boc-peptides with other sparingly-soluble peptide esters. The TFE/TCM or TFE/DCM system was extremely useful for coupling segments without danger of racemization and of trifluoroester formation, if WSCI was used as the coupling reagent in the presence of 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (HOOBt).

Amino Acid Sequence↗

PubMedDate not supplied

Development of inductive heating equipment using an inductive aperture-type applicator.

We designed an inductive aperture-type applicator, IATA, consisting of a one-turn, square, column-like coil made of a metal strip. In experiments using a phantom, this applicator was seen to have the following characteristics: (1) it does not excessively heat the fat layer; (2) deep portions can be heated effectively; (3) heat can be applied to the subject, without contact with the applicator; (4) excessive generation of heat does not occur in parts of tissue near the edge of the aperture; (5) size of the aperture can be changed for adaptation to size of the site to be heated; (6) the aperture can be modified to fit the shape of the subject and the depth of penetration is influenced by size of the subject being heated; (7) the applicator can be driven at an arbitrary frequency; (8) efficiency of heat generation to the input power is low. The inductive heating equipment, 'Inductron', which we have developed possesses the necessary requirements for adequate clinical application.

Adipose Tissue↗

PubMedDate not supplied

Magnetic resonance imaging (MRI) and technetium-99m-methoxyisonitrile (MIBI) scintigraphy to evaluate the abnormal parathyroid gland and PEIT efficacy for secondary hyperparathyroidism.

PURPOSE: Percutaneous ethanol injection therapy (PEIT) of the abnormal parathyroid gland is an effective treatment in patients with chronic renal failure with dialysis that tends to be unresponsive to medication. To evaluate the efficacy of PEIT, we investigated the correlation between serum intact PTH (iPTH), and the findings of MR imaging and 99mTc-MIBI scintigraphy. MATERIALS AND METHODS: PEIT was performed 32 times in 24 patients with secondary hyperparathyroidism. Both MR imaging and MIBI scintigraphy were performed before and after PEIT. The detectability of parathyroid lesions was evaluated by MRI and MIBI scintigraphy with reference to ultrasound (B-mode) findings (as a standard) and the comparison of each treatment was done between imaging changes and serum iPTH levels. RESULTS: In the small parathyroid glands (< 0.5 ml with US), MR images detected abnormal glands in 74.0% (20/27), and MIBI accumulation was observed in 40.7% of the cases. Whereas, MR images and MIBI showed similar detectability (95.0% vs. 90.0%) to large parathyroid glands (> or = 0.5 ml with US). After PEIT, glands in which ethanol was successfully injected showed decreased signal intensity on T2-weighted images and decreased accumulation of MIBI. MR imaging and MIBI scintigraphy showed almost equivalent high sensitivity in evaluating therapeutic changes (73.3% vs. 76.4%) according to our evaluation category of more than 30% reduction of iPTH as effective. However, the specificity of MR imaging was much higher (100%) than that of MIBI scintigraphy in evaluating therapeutic effects. CONCLUSION: In conclusion, MRI provided better detectability of abnormal parathyroid glands than 99mTc-MIBI scintigraphy. The reduction of high signal intensity area after PEIT on T2-weighted MR images is considered an useful therapeutic evaluation guideline than the reduction of MIBI accumulation on scintigraphy.

Adult↗

PubMedDate not supplied

Ultrastructural study of the remnant liver after extensive hepatectomy in dogs; especially morphological alterations of sinusoidal endothelial cells.

BACKGROUND/AIMS: To investigate the role of sinusoidal endothelial cells in the mechanism of the remnant liver dysfunction after extensive hepatectomy, morphological alteration of sinusoidal endothelial cells and cytoprotective effects of prostaglandin I2 analog were studied by ultrastructural analysis. METHODOLOGY: Mongrel dogs (n = 24) were divided into 3 groups according to the extent of hepatectomy and the use of prostaglandin I2 analog preoperatively. Group 1: 70% hepatectomy (n = 8), Group 2: 84% hepatectomy (n = 8), and Group 3: 84% hepatectomy with administration of prostaglandin I2 analog, preoperatively (n = 8). Morphology of hepatic sinusoidal endothelial cells was examined after hepatectomy in all cases. RESULTS: Group 2: Enlargement of the sinusoidal endothelial fenestrations was transitorily occurred immediately after hepatectomy, but were dramatically decreased in size 24 h after the operation. Most sinusoidal endothelial cells were destroyed and separated from the sinusoidal wall. Fibrin deposits and sludge were found in the Disse's space and sinusoidal lumens, resembling liver failure at 24 h after the operation. Group 1 and 3: sinusoidal endothelial fenestrations remained slightly enlarged at 24 h after the operation, but fibrin deposits or sludge were not observed in sinusoidal lumens. CONCLUSIONS: Our data suggest that extensive hepatectomy changed the morphology of sinusoidal endothelial cells. Administration of prostaglandin I2 analog helped maintain structural integrity of sinusoidal endothelial cells, improved hepatic microcirculation and thus served to reduce remnant liver dysfunction.

Animals↗

PubMedDate not supplied

Hemodynamic changes during dynamic exercise in patients after mitral valve replacement for chronic mitral regurgitation.

To evaluate hemodynamic changes during dynamic exercise, we investigated 13 patients after mitral valve replacement (MVR) for chronic mitral regurgitation (MR) and 5 control subjects by right heart catheterisation during supine bicycle exercise. According to the sizes of the St. Jude Medical (SJM) prosthesis during MVR, patients were divided into group A (n = 8) with SJM 31mm and group B (n = 5) with SJM 29mm. Significant rise in cardiac index (CI) was noted during exercise in both groups A and B (from 3.3 +/- 0.8 to 5.5 +/- 0.9 l/min/m2, p < 0.01 and from 3.0 +/- 0.6 to 5.6 +/- 0.6 l/min/m2, p < 0.01 respectively) and also in control subjects (from 3.4 +/- 0.7 to 6.2 +/- 0.6 l/min/m2, p < 0.01). Mean pulmonary artery and pulmonary capillary wedge pressure were significantly higher during exercise in patients of both groups A and B than control subjects (p < 0.05 and p < 0.01 respectively). Total pulmonary vascular resistance was significantly higher during exercise in both groups A and B than control subjects (p < 0.05 and p < 0.01 respectively). No difference in hemodynamics were noted between the patients of group A and B during exercise. It is concluded that response of CI to exercise in patients after MVR for chronic MR was adequate in comparison to control subjects irrespective of two different valve sizes.

Adult↗

PubMedDate not supplied

Solution synthesis of Na+,K(+)-ATPase inhibitor-1 (SPAI-1).

SPAI-1, a 49-amino acid peptide including eight Cys residues with Na+,K(+)-ATPase inhibitory activity, was synthesized by the solution procedure. Protecting groups, including the formyl group on the Trp residue, were cleaved simultaneously by HF treatment in the presence of a sufficient amount of thiol compound. After removal of the Acm group on the Cys residue, the resulting octa SH peptide was subjected to an oxidative folding reaction in the presence or absence of redox reagents and/or denaturant. Addition of redox reagents accelerated the reaction but was not crucial to the formation of the correct disulfide bonds in the molecule. The product was purified to homogeneity and found to have the same physicochemical properties and inhibitory potency as those reported for the natural product. Four intramolecularly linked disulfide bridges were assigned as connecting Cys8 to Cys37, Cys15 to Cys41, Cys24 to Cys36, and Cys30 to Cys45 based on results from a combination of enzymatic and synthetic approaches.

Amino Acid Sequence↗

PubMedDate not supplied

Solution synthesis of calciseptine, an L-type specific calcium channel blocker.

Calciseptine, an L-type specific calcium channel blocker consisting of 60 amino acid residues with four intramolecular disulfide bonds, was synthesized by the solution procedure applying our maximum protection strategy. The recently developed solvent systems used were a mixture of chloroform or dichloromethane and trifluoroethanol; they were useful for the synthesis of slightly soluble protected peptides. After removal of all the protecting groups by our two-step HF procedure followed by treatment with mercuric acetate, the peptide was folded into its native form by air oxidation, in which redox reagents were necessary to accelerate the correct disulfide bond formation. The product was purified to homogeneity and found to block contractions of the rat thoracic aorta induced by 40 mM K+ with the same potency as that of the natural product. In addition, this peptide was found to block contractions of various rat smooth muscle preparations as well as increase in cytosolic free calcium concentration induced by a high concentration of extracellular K+.

Amino Acid Sequence↗

PubMedDate not supplied

Cardiac function of an acute ischemic heart failure model produced by microsphere injection into the left coronary artery. Pressure-volume relationship as determined by a conductance catheter.

The authors produced an acute canine heart failure model by injecting microspheres (phi 15.5 +/- 0.1 mm, 5 x 10(5)) into the left coronary artery, and characterized the model in terms of the pressure-volume relationship obtained by the conductance catheter method. Cardiodynamics of the microsphere injection group (M group: n = 10) and control group (C group: n = 12) were studied with 1) heart rate, 2) aortic pressure, 3) cardiac output (CO), 4) maximal ventricular elastance, 5) effective arterial elastance/maximal ventricular elastance, and 6) external work/pressure-volume area efficiency. With microsphere injection, CO and external work/pressure-volume area efficiency significantly decreased. With administration of dobutamine (5 mg/kg/min), CO and maximal ventricular elastance recovered to normal and aortic pressure became higher than normal. These changes in heart rate, aortic pressure, CO, maximal ventricular elastance, and external work/pressure-volume area efficiency in the M group were comparable in percentage to those in the C groups. Cardiodynamics of this heart failure model generally were stable for 3 hrs after microsphere injection. The authors concluded that this model would be an excellent acute heart failure model for investigating hemodynamic effects of circulatory assist devices.

Animals↗