Characteristics of an ovariectomized osteopenic rat model

Although osteoporosis induced by ovariectomy (Ovx) in the rat has been widely used as a model for postmenopausal osteoporosis in humans, the findings of different investigators are not always consistent. This might be mainly due to differences in the age of the animals at Ovx, time after Ovx, and the variables measured. Therefore, in the present study, Ovx was performed at 4, 10, or 52 weeks and bone changes were observed in rats for 6 months. The effects of Ovx on body weight, femoral length, and femoral volume were marked in rats operated on at the age of 4 weeks, slight in rats operated on at the age of 52 weeks, and intermediate in rats operated on at the age of 10 weeks. A reduction in the ratio of cortical thickness to bone width at the midshaft of the femur was observed only in rats ovariectomized at 52 weeks of age. The specific gravity of the femur and the density of the metaphysis of the femur decreased after Ovx in all rats. The ratio of ash weight to dry weight of the femur, a measure of the normal calcification of bone, was unchanged shortly after Ovx but gradually decreased in all rats.     

The evaluation of left ventricular eccentric hypertrophy by 201Tl-myocardial scintigraphy

In order to elucidate the mechanism of left ventricular eccentric hypertrophy in conditions of volume overload, Tl-201 myocardial scintigraphy was performed patients with aortic valve regurgitation and mitral valve regurgitation. There was a good relationship between the severity of Tl-defects, as determined by Tl-201 myocardial scintigraphy, and the changes in the T wave on the ECG on the one hand and the NYHA functional classification of heart diseases. In 17 of 18 patients where LVDd increased with increasing severity of Tl-defects and the defects were moderate to severe, LVDd was 65 mm or larger. There was a significant negative correlation between the washout rate for the whole circumference of the left ventricle, as determined by exercise Tl-201 SPECT, and LVDd (r = -0.603, p less than 0.01). The phenomenon of redistribution as determined by exercise Tl-201 myocardial scintigraphy was observed relatively early. Our results suggest that mechanical volume overload and ischemic changes are involved in left ventricular wall damage in left ventricular eccentric hypertrophy. For patients with moderate to severe Tl-defects valve replacement is indicated, no matter whether they may have heart failure or arrhythmia.     

General pharmacological action of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride). Influence on respiratory and cardiovascular systems, renal function, autonomic nervous system, isolated smooth muscle and digestive organs

MCI-2016 at 3 mg/kg, i.v., caused slight changes in systemic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and ECG but at 10 mg/kg, i.v., it caused a significant increase in RR, decrease in SBP, increase or decrease in HR and a moderate change in ECG. Biphasic changes in SBP, HR and blood flow were sometimes observed after high doses. MCI-2016 also decreased SBP at 30 mg/kg, i.p., in SHR. MCI-2016 (50 mg/kg, p.o./day) showed little influence on SBP, HR and ECG in conscious beagle dogs. In isolated hearts, MCI-2016 decreased HR and contractility at the concentrations above 10(-5) g/ml, and 30 micrograms, i.a. MCI-2016 prolonged the AVCT at 10 mg/kg, i.v. MCI-2016 (i.v. or i.a.) moderately increased cerebral and femoral artery blood flows. MCI-2016 did not change CMRO2, but decreased MVO2. Coronary and renal artery flows were moderately increased by 10 mg/kg, i.v., of MCI-2016. Renal function was suppressed after 10 mg/kg, i.v., or 300 mg/kg, p.o., of MCI-2016. MCI-2016 potentiated the action of NE (increase in SBP, contractions of nictitating membrane and vas deferens), but showed little anti-cholinergic action. In contrast, MCI-2016 moderately increased gastrointestinal motility and salivatory response. As for the influence on isolated smooth muscles, MCI-2016 antagonized the contraction of blood vessels by high K+ at 10(-6) g/ml, or more, and it depressed the contractions by ACh, 5-HT, histamine and BaCl2 and also depressed spontaneous movements of uterus and ileum at 10(-5) M or more, in a nonspecific manner. MCI-2016 had no influence on liver damage and bile secretion, but inhibited stress ulcer and gastric acid secretion on the one hand, and caused gastric damage (125 mg/kg p.o., or more) on the other hand.     

Plasminogen activator inhibitor activity as a possible indicator of disease activity in rest angina with angiographically insignificant coronary artery stenosis.

To assess the role of fibrinolytic system, 19 patients with rest angina and insignificant coronary artery stenosis and 23 controls performed symptom-limited multistage exercise. Vasospasm was angiographically demonstrated in 12 patients. Pre- and peak exercise blood samples from each patient were assayed to determine the fibrinolytic components. The patients displayed significantly increased PAI activity both under the basal conditions (p less than 0.01) and at peak exercise (p less than 0.01) as compared with the controls. However, the values of other fibrinolytic components, such as t-PA antigen, t-PA/PAI-1 complex and free PAI-1 antigen, in the controls and patients were similar. Nineteen patients were divided into two groups according to PAI activity levels under basal conditions. Nine patients displayed high PAI activity (more than the mean + 1 SD of the control value) under the basal conditions. When compared to the remaining 10 patients, the high PAI activity group had both a significantly short time interval from the last attack to the time of getting the blood sample (p less than 0.05), and a worse short-term prognosis (p less than 0.05). Thus, the level of PAI activity under basal conditions reflected the extent of disease activity, suggesting that PAI activity may be a useful clinical indicator of the severity of rest angina in patients without significant coronary stenosis.     

ABC transporters of pathogenic fungi: recent advances in functional analyses]

ABC (ATP binding cassette) transporters consist of transmembrane domains which confer specificity, and structurally conserved nucleotide binding domains that contain highly conserved amino acid motifs. They act not only as transporters but also as receptors or channels that use energy generated by ATP hydrolysis. ABC transporters are widely dispersed in nature. They are found in cells ranging from prokaryotes (bacteria) to eukaryotes (including humans) and several are considered to play crucial roles in cellular homeostasis. Defects in ABC transporters in humans are associated with severe diseases such as type 2 diabetes and cystic fibrosis. Some ABC transporters extrude xenobiotics and confer resistance to chemotherapeutics on microbial pathogens and cancer cells. Thus ABC transporters are of considerable medical importance. Structure-function analysis of ABC transporters has begun to elucidate their mechanisms of substrate recognition, the functional regulation of ATP-binding and hydrolysis and to identify intrinsic physiological functions. In pathogenic fungi, ABC transporters contribute to the clinical problem of drug resistance. The application of new technologies to the examination of fungal ABC transporter function is providing new insights into the use of antifungal drugs in medical mycology and contributing to a better understanding of these important membrane proteins.     

Changes in fatty acid composition in rat blood and organs after infusion of docosahexaenoic acid ethyl ester

An infusible emulsion of docosahexaenoic acid ethyl ester (DHA-EE) was prepared. One hundred milliliters of the emulsion contained 10 g DHA-EE (90% pure). Three milliliters of the emulsion was infused into tail veins of 22 Wistar rats weighing approximately 300 g. They were killed 1, 6, and 24 h and 3 and 7 d after the infusion, and fatty acid composition of various organs and plasma was analyzed along with that of control rats. DHA concentrations reached their peaks within 24 h after DHA infusion in plasma lipid fractions and in the phospholipid fraction of liver and lung. DHA did not increase at all in cardiac phospholipid fraction. However, DHA concentrations increased markedly (from 0.7% to 11%) in the free fatty acid fraction of heart 1 h after the infusion. DHA emulsion might be useful for patients in whom a rapid increment in DHA in tissues is beneficial.     

Adaptation, stimulus color, and the human electroretinogram

(1) The human electroretinogram was recorded using two procedures that were designed to change the ratio of photopic to scotopic activity. (2) With the first procedure, responses were recorded with patterns that alternated with an asymmetrical time period to produce two average responses, one of which was more adapted than the other. (3) The second employed symmetrical alternation, but red and blue stimulation were used. (4) The electroretinogram was larger in responses to patterns of low spatial frequency for all conditions. The evoked potential, which was recorded simultaneously, was larger at intermediate frequencies. (5) The electroretinogram must be mediated before the antagonistic receptive field organization. (6) Sensitivity of electroretinogram with blue stimuli was higher than those with red at low spatial frequency. The possible scotopic contribution was discussed.