Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

Demonstration of three distinct immunological disorders on erythropoiesis in a patient with pure red cell aplasia and autoimmune haemolytic anaemia associated with thymoma

A patient with pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA), associated with a thymoma which had already been removed, was studied in order to investigate the pathogenesis of PRCA and AIHA. The autoantibody eluted from the surface of the patient's red blood cells (RBC) reacted with the large E antigen of the Rh complex. Immunoglobulin-G (IgG) purified from the patient's serum suppressed CFU-E and BFU-E but not CFU-GM colony formation in the presence of complement. This antibody was not adsorbed with large E antigen. T-lymphocytes in the bone marrow suppressing autologous CFU-E and BFU-E colonies were demonstrated. Thus, three distinct immunological disorders on erythropoiesis were present in this patient with PRCA and AIHA associated with thymoma in a thymectomized state.     

MLL gene rearrangement in t(9;11) acute myelogenous leukemia with minimal myeloid differentiation (FAB subtype M0)

A 25-year-old man was diagnosed with acute myelogenous leukemia (AML), French-American-British (FAB) subtype M0, based on cytochemical and flow cytometric findings. Cytogenetic analysis revealed the chromosome translocations t(9;11)(p22;q23), and MLL gene rearrangement was identified by Southern blotting. In adult AML, MLL gene rearrangement was initially reported in FAB M4 and M5 cases, and recently in M1 and M2 cases, but was rare in M0 or M3 cases. Because the sensitivity of detecting MLL gene rearrangement by cytogenetic analysis is extremely low compared with Southern blotting analysis, the MLL gene may be involved in substantial numbers of adult AML cases, regardless of FAB subtype.     

Adrenergic regulation of clock gene expression in mouse liver

A main oscillator in the suprachiasmatic nucleus (SCN) conveys circadian information to the peripheral clock systems for the regulation of fundamental physiological functions. Although polysynaptic autonomic neural pathways between the SCN and the liver were observed in rats, whether activation of the sympathetic nervous system entrains clock gene expression in the liver has yet to be understood. To assess sympathetic innervation from the SCN to liver tissue, we investigated whether injection of adrenaline/noradrenaline (epinephrine/norepinephrine) or sympathetic nerve stimulation could induce mPer gene expression in mouse liver. Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro. Electrical stimulation of the sympathetic nerves or adrenaline injection caused an elevation of bioluminescence in the liver area of transgenic mice carrying mPer1 promoter-luciferase. Under a light-dark cycle, destruction of the SCN flattened the daily rhythms of not only mPer1, mPer2, and mBmal1 genes but also noradrenaline content in the liver. Daily injection of adrenaline, administered at a fixed time for 6 days, recovered oscillations of mPer2 and mBmal1 gene expression in the liver of mice with SCN lesion on day 7. Sympathetic nerve denervation by 6-hydroxydopamine flattened the daily rhythm of mPer1 and mPer2 gene expression. Thus, on the basis of the present results, activation of the sympathetic nerves through noradrenaline and/or adrenaline release was a factor controlling the peripheral clock.     

A comparison of differences in the outcome (hospitalization and mortality) between two special nursing homes of the same size managed by the same organization

The purpose of this study was to examine the usefulness of information about outcome in evaluation of the quality of special nursing homes. Two special nursing homes A and B were selected. These two facilities were the same in their service capacity and are also owned as well as managed by the same organization. There were no differences in the structural elements between the two facilities. The hospitalization and mortality rate of the two facilities were compared. There were no significant differences in terms of the distribution of the characteristics of the residents between facility A and B at the time of their admission. However, the average survival time of the persons who died was significantly shorter in facility B than that in facility A. (A facility = 1,165 days, B facility = 831 days; p < 0.05). There were significant differences in cumulative survival and non-hospitalization rate of residents in the two facilities (p < 0.05). The differences were seen even after controlling for the prognostic factors by Cox's proportional hazard model (hazard rate: mortality = 1.562, hospitalization = 2.526, p < 0.01). Furthermore, the proportion of residents hospitalized right after their first visit to the hospital was significantly higher in facility B than that in facility A (A = 9.6%, B = 19.3%; p < 0.05). Also, the mortality risk of hospitalized persons was significantly higher than non-hospitalized persons in facility B (p < 0.05), although there was no significant difference in terms of the mortality risk between the two groups in facility A. Because the differences in the cumulative survival and non-hospitalization rate could occur in the facilities that are similar in institutional structures, it suggests that these outcomes are indicators of the quality of special nursing homes. It would be, therefore, important to collect the information about outcome including cumulative survival and non-hospitalization rate of the residents in order to evaluate the quality of special nursing homes.     

Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese

BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.     

A case of pseudoxanthoma elasticum associated with sick sinus syndrome

Typical angioid streaks were found on routine ophthalmologic examination in a 42-year-old female with yellowish, coalescing papules on her neck without any symptoms. Biopsy of the cutaneous lesion showed degeneration and fragmentation of the elastic fibers and many basophilic-stained calcifications in mid-dermis, which are consistent with pseudoxanthoma elasticum. Twenty-four-hour Holter electrocardiography (ECG) showed sinus arrest for 2.5 seconds, and an electrophysiological study revealed sinus nodal dysfunction (sick sinus syndrome), whereas all of the coronary arteries were intact, despite a treadmill stress ECG test showing significant ST depressions. The association of pseudoxanthoma elasticum and sick sinus syndrome is very rare. One possible explanation for this association here is that the degeneration of elastic fiber in endomysium of the sino-atrial node may have affected heart conduction systems, resulting in sick sinus syndrome.Part of this work was presented at the 76th Japanese Circulation Society Kyushu Meeting, Japan, June 18, 1994     

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.