The effects of anthopleurin-A (AP-A, 1 x 10(-8) M) on the membrane action potential and contraction of isolated rabbit ventricular muscle were compared with those of ouabain (5 x 10(-7) M). Under control conditions, AP-A and ouabain showed submaximal (about 80% of maximal) positive inotropic effects without any toxic manifestations. AP-A caused a marked prolongation of action potential duration (APD) without affecting any other parameters of the action potential, whereas ouabain caused a shortening of APD and a slight decrease in maximum diastolic potential (MDP), overshoot (OS), and upstroke velocity (dV/dtmax) of the action potential. The positive inotropic effect of AP-A was relatively well maintained even under hypoxia or in glucose-free medium. Under these abnormal experimental conditions, AP-A caused a prolongation of APD only at the late stage of repolarization (APD80), whereas APD at the early stage of repolarization (APD30) was further shortened. Other parameters of action potential and resting tension (RT) were not influenced by AP-A. In contrast, under similar experimental conditions, ouabain caused no apparent positive inotropic action, but resulted in a marked increase in RT (contracture). In addition, after exposure to ouabain, a progressive shortening of APD and marked decreases in MDP, OS, and dV/dtmax were observed. These results indicate the AP-A has pharmacological properties quite different from those of ouabain and suggest possible advantages of this newly developed cardiotonic agent over cardiac glycosides when acting on the energy-depleted myocardium.

Animals↗

PubMedDate not supplied

Vascular relaxation in the spontaneously hypertensive rat.

The relaxation of thoracic and abdominal aortae of the spontaneously hypertensive rat (SHR) during prehypertensive (3--5 week old) and hypertensive (12--16 and 22--25 week old) stages was compared to that of matched normotensive Wistar rats (NWRs). In the thoracic aorta, the relaxation response to isoproterenol, acetylcholine, Mg2+, Mn2+, Co2+, and La3+ was less in both prehypertensive and hypertensive SHRs than in the matched NWRs; however, such difference was not evident in the abdominal aorta. Similarly, the relaxing effect of nitroglycerin and papaverine was not different in the aorta preparations of the SHR and NWR. After chronic reserpine treatment of the prehypertensive and hypertensive SHRs, the thoracic aorta still showed less relaxation in response to the aforementioned agents. Isoproterenol, but not other agents tested, produced less relaxation in the thoracic aorta from the renal hypertensive rat than from the control. Our results suggest that the decreased relaxation of the SHR thoracic aorta is not a consequence of hypertension and that the defect in the SHR thoracic aorta cannot be generalized to other vascular beds.

Acetylcholine↗

PubMedDate not supplied

Electromechanical effects of caroverine, a new slow-channel blockade, on the SA node cells of rabbit and atrial muscle fibers of rabbit and guinea pig.

The effects of caroverine on electrical activity of isolated rabbit sinoatrial (SA) node cells and atrial muscle fibers and on contractile force of atrial muscle preparations were examined. In spontaneously firing SA node cells, caroverine (1 X 10(-7) M-1 X 10(-5) M) decreased the action potential amplitude (APA) and the maximal rate of depolarization (MRD) in a concentration-dependent manner. However, the spontaneous firing cycle length of these cells was not prolonged significantly with the drug except at a high concentration. In constantly driven atrial muscle fibers, caroverine at the same concentration range shortened the 30% repolarization time coupled with a depression of the plateau phase of action potentials. The effects of caroverine on the developed tension (DT) of atrial muscle were compared with that of verapamil. The 50% effective dose (ED50) for inhibition on atrial DT was 1 X 10(-5) M for caroverine and 8 X 10(-8) M for verapamil. Caroverine as well as verapamil had a frequency-dependent inhibitory action on atrial DT, which indicates that both of the drugs have an influence on the kinetics of slow channel of cardiac fibers. In conclusion, it is suggested that caroverine has only a small negative inotropic effect while electrophysiological effects are similar to slow-channel blockers.

Action Potentials↗

PubMedDate not supplied

Cardiovascular effects of FR34235, a new dihydropyridine slow channel blocker, in isolated rabbit myocardium and aorta.

The effects of FR34235 (FR) on isolated rabbit cardiac muscle, sinus node, and aortic strips were evaluated and compared with those of nifedipine. FR decreased the developed tension and shortened the action potential duration of ventricular and atrial muscle without affecting the upstroke velocity (Vmax). Nifedipine induced similar but more pronounced electromechanical changes. The ED50 values for FR and nifedipine for producing their negative inotropic effects on ventricular muscle were 1.0 +/- 0.4 X 10(-6) and 2.0 +/- 0.6 X 10(-7), respectively. The slow response and its associated contraction of ventricular muscle were inhibited by FR (5 X 10(-6) M). Both effects of FR were antagonized by increasing [Ca]0. FR, at concentrations higher than 10(-7) M, reduced the amplitude and Vmax of the sinus node action potential. However, these effects were less than those of nifedipine. Spontaneous firing rate was not affected by either drug. The high K+-induced contractile response in rabbit aortic strips was inhibited by both FR and nifedipine at lower concentrations than in cardiac tissue, whereas the potency of FR was greater than nifedipine. The ED50 values for FR and nifedipine were 1.0 +/- 0.3 X 10(-9) and 4.0 +/- 0.4 X 10(-9) M, respectively. The inhibitory action of FR on the contractile response to excess Ca2+ was also greater than that of nifedipine. The inhibitory actions of both FR and nifedipine on the norepinephrine response were less than those on the K+ response. These results indicate that FR has characteristics of slow channel blockade similar to those of nifedipine. However, inhibitory action of FR was more potent in vascular smooth muscle of rabbit aorta and less potent in cardiac tissue than that of nifedipine.

Animals↗

PubMedDate not supplied

Electrical and mechanical effects of amrinone on isolated guinea pig ventricular muscle.

The electromechanical effects of amrinone on isolated guinea pig papillary muscle were studied at various driving frequencies and under the influence of several antagonists and a low calcium medium. Amrinone (3 X 10(-5)-2 X 10(-3)M) caused a positive inotropic effect on preparations driven at 1.0 Hz in a concentration-dependent manner. When the preparations were driven at a frequency lower than 0.5 Hz, the positive inotropic effect of the drug was markedly attenuated. Amrinone caused a significant prolongation in action potential duration at an early repolarization phase--but not at a late repolarization phase--without affecting any other parameters of action potential. These effects of amrinone were not blocked by a beta-adrenoceptor antagonist or tetrodotoxin, but were inhibited by treatment with verapamil (5 X 10(-6)M) or a low calcium medium (0.1 or 0.3 mM). In papillary muscles depolarized by 30 mM [K+]o, amrinone enhanced the slow action potentials. In voltage clamp experiments using a single sucrose-gap method, amrinone (6 X 10(-4)M) caused a marked increase in the peak amplitude of the slow inward current, while it did not affect the net outward current. The results suggest that the slow calcium inward current may play a predominant role in the positive inotropic effect of amrinone.

Action Potentials↗

PubMedDate not supplied

Epithelial-myoepithelial carcinoma: An unusual tumor of the paranasal sinus.

A 65-year old woman presented with nasal obstruction and on examination was found to have a huge mass in the maxillary sinus. This was removed, and histological examination revealed a mixture of trabecular structures consisting of inner dark cells, outer clear cells and solid structures consisting of only clear cells. Immunohistochemical examination showed the clear cells to be positive for alpha-smooth muscle actin. Ultrastructural examination confirmed the myoepithelial cell origin. The characteristic morphological, immunohistochemical and ultrastructural features aided in the diagnosis of epithelial-myoepithelial carcinoma.

Aged↗

PubMedDate not supplied

Two modes of auditory hair cell loss following acoustic overstimulation in the avian inner ear.

To determine the type of cell death occurring and how the removal of damaged cells proceeds following overstimulation, we examined chick basilar papillae using an in situ DNA nick end labeling method and transmission electron microscopy. Two distinct modes of hair cell loss were identified. First, hair cells which had not progressed into typical cell death processes, apoptosis or necrosis, were deleted by extrusion from the epithelium just after sound exposure. Second, hair cells manifested degeneration through the process of apoptosis, then further deterioration within the epithelium after the beginning of the process of hair cell regeneration. The latter mode may contribute to the following repair processes.

Acoustic Stimulation↗

PubMedDate not supplied

Purification and some properties of alpha-L-fucosidase isolated from Streptococcus sanguis.

alpha-L-Fucosidase acting on naturally occurring substrates was highly purified from the growth culture of Streptococcus sanguis ATCC 10557. The molecular weight of the enzyme was approximately 120,000 and the optimal pH was at 5.5. The purified enzyme showed specificity toward the linkage of alpha-(1 leads to 2) fucosides in oligosaccharides and glycoproteins. The enzyme released L-fucose from glycoprotein in human parotid saliva.

Chromatography, Gas↗

PubMedDate not supplied

Acute effects of griseofulvin on the pharmacokinetics and pharmacodynamics of warfarin in rats.

It has been reported that prothrombin time (PT), which is prolonged by warfarin, is reduced when patients on warfarin also take griseofulvin repeatedly. We investigated the cause of the drug interaction and the initial effects of griseofulvin on warfarin pharmacokinetics. Total cytochrome P-450, and the activities of aminopyrine N-demethylase, aniline p-hydroxylase and 7-ethoxycoumarin O-deethylase, after repeated administration of griseofulvin (100 mg/kg orally daily for 5 days) were examined. Acute effects of single doses of griseofulvin (100 mg/kg) on coagulation activity (prothrombin time) and warfarin pharmacokinetics after administration of warfarin were also studied. Repeated administration of griseofulvin induced warfarin-metabolizing enzymes. In contrast, a single administration of griseofulvin increased prothrombin time and serum warfarin concentrations. The activity of a warfarin-metabolizing enzyme (7-ethoxycoumarin O-deethylase) was reduced when griseofulvin was added to rat liver microsomes. The results suggest that reduced warfarin action after repeated administration of griseofulvin may be due to induction of warfarin-metabolizing enzymes, but that there is also an initial increase in warfarin action.

Animals↗

PubMedDate not supplied

Altered erythropoiesis and increased hemolysis in hemoglobin M Akita (M Hyde Park beta92 His replaced by Tyr) disease.

Hb M Akita disease is a cyanotic hemoglobinopathy found in Akita Prefecture, Japan. The abnormal hemoglobin was found to be the same as Hb M Hyde Park (beta92 His replaced by Tyr) by chemical analysis in 1967. In this disease signs of accelerated hemolysis (serum bilirubin, 2.4 mg/dl; splenomegaly, 2 finger breadths; Hb, 10.7 g/dl; reticulocyte index, 2.7) were noted, but the causes of its slight anemia were revealed to be fairly complex by ferrokinetic study, RBC life-span measurement, and 99mTc myeloscintigram. The anemia in this disease is caused not only by shortened erythrocyte survival (T 1/2 = 11.5 days by 51Cr-tagging method) and sequestration of red cells in the spleen (Spleen: liver ratio = 2.5 approximately 3.0 by 51Cr-surface counting), but also by slow supply of erythrocytes to the peripheral blood from the bone marrow, presumably, related to the existence of unstable Hb M Akita and its derivative (Hb Akita) in the erythroid cells. Both Carrell's isopropanol test and Heinz body formation test were positive. In spite of maximally increased total erythropoiesis (8 times as high as the normal level; M:E ratio = 0.22:1.0), supply of red cells from the bone marrow to the peripheral blood was significantly decreased. The distribution of hematopoietic sites throughout the body was reasonably uniform.

Adult↗

PubMedDate not supplied

Transient rapid growth of uterine leiomyoma in a postmenopausal woman.

We report a case of transient rapid growth of uterine leiomyoma in a postmenopausal woman. A 58-year old woman presented with a rapidly enlarging pelvic tumor, from a 14-week to a 20-week gestational size in the one month. Transcervical needle biopsy revealed a smooth muscle tumor with 5 mitotic figures per 10 high power fields. However, surgical specimen obtained 1 month later revealed less than 1 mitotic figure per 100 high power fields. This variation may influence the final histopathological diagnosis because mitotic index is believed to be one of the most reliable histopathological parameters for differentiating between uterine leiomyoma and leiomyosarcoma.

Cell Division↗

PubMedDate not supplied

Diagnostic accuracy of needle biopsy of uterine leiomyosarcoma.

We previously reported on the efficacy of transcervical needle biopsy of a uterine muscle tumor. In this study, to examine diagnostic accuracy of our needle biopsy with small specimen size, previous slide preparations were used from 8 cases diagnosed with leiomyosarcoma and from 24 post-operative leiomyoma cases. Each tissue specimen was examined through needle biopsy-sized slit that had been randomly positioned over the slide. Three predictors: mitotic index, cytologic atypism, and tumor cell necrosis were evaluated on a 3-point scale (0, 1, or 2 points). When the diagnostic cut-off value was set to two, the sensitivity was 92.5% and the specificity was 100%.

Biopsy, Needle↗