Residual pathologic changes and 99mtechnetium pyrophosphate uptake following coxsackievirus B3 perimyocarditis in mice

The myocardial uptake of technetium-99m pyrophosphate (99mTc-PYP) in perimyocarditis induced by coxsackievirus B3 in BALB/c mice was studied on 3rd--90th day after the inoculation. 99mTc-PYP uptake ratio, measured by the ratio of cpm/gm for the heart to cpm/gm for the skull, began to increase five days after virus inoculation and reached a maximum on the seventh day. After the 14th day, 99mTc-PYP ratio began to decrease, however, on the 90th day, a high 99mTc-PYP uptake was shown in mice with severe perimyocardial fibrosis and calcification. The present findings may provide a futher basis upon which 99mTc-PYP imaging may be applied to viral perimyocarditis in humans.     

Relationship between the clinical efficacy of pentoxifylline treatment and elevation of serum T helper type 2 cytokine levels in patients with human T-lymphotropic virus type I-associated myelopathy.

OBJECT: Previously, we reported the efficacy of pentoxifylline (PTX) treatment in human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). Here, we clarify the relationship between the clinical efficacy of PTX treatment and elevation of T helper type 2 (Th2) cytokine levels in HAM patients. PATIENTS AND METHODS: PTX (300 mg) was administered daily by the oral route to 12 HAM patients for 4 weeks. We assessed the relationship between the changes in neurological status (motor disability scores, the degree of spasticity on neurological examination, and the time required to walk 10 m) and the changes in serum and cerebrospinal fluid (CSF) levels of interferon-gamma (IFN-gamma) as a Th1 cytokine and interleukin-4 and -10 (IL-4 and -10) as Th2 cytokines measured by an EASIA (enzyme-amplified sensitivity immunoassay) kit. RESULTS: PTX treatment induced incremental increases in the levels of IL-4 and IL-10 in both sera and CSF of 6 HAM patients. Clinical improvement was associated with this elevation in IL-4 and IL-10. PTX treatment also induced a decrease in IFN-gamma levels in the sera of 6 HAM patients, but this was not correlated with clinical improvement. CONCLUSION: These results suggest that the correction of the immunological imbalance in Th1 to Th2 cytokine responses, with upregulation of IL-4 and IL-10, may account for the clinical improvement in HAM patients treated with PTX.     

U wave inversion during attacks of variant angina.

Sequential 12 lead electrocardiograms were recorded during angina pectoris induced by ergonovine maleate in 38 patients with variant angina. Transient U wave inversion was observed in 17 patients with ST segment elevation in anterior chest leads, but in only three of 21 patients with ST segment elevation in the inferior leads associated with right coronary artery spasm. In the 17, all of whom had spasm of the left anterior descending coronary artery, the sensitivity of ST segment elevation in V5 was only 41%, and that of U wave inversion 71%. U wave inversion without ST segment elevation occurred during attacks in 35% of patients. During the recovery phase, the sensitivity of U wave inversion was 82% in V4 and 65% in V5, though ST segment elevation was absent in both V4 and V5. Thus, inverted U waves without ST segment elevation often appear in marginal ischaemic zones or during the time of recovery from temporary ischaemia. Detection of inverted U waves should aid in the diagnosis of variant angina when only lead V5 is used as a monitor and when electrocardiograms are recorded only during the recovery phase.     

Serum levels of squamous cell carcinoma antigens 1 and 2 reflect disease severity and clinical type of atopic dermatitis in adult patients

Background

Recent studies have indicated that serum levels of squamous cell carcinoma antigen (SCCA) 1 and 2 induced by type 2 cytokines such as IL-4 and IL-13, are increased in patients with atopic dermatitis (AD). However, no clinical studies have analyzed serum levels of SCCA2 in larger series of AD patients or their association with various clinical characteristics. This study was performed to clarify whether serum levels of SCCA2 are associated with disease severity and clinical phenotypes of adult AD patients.

The effect of dopaminergic antagonists on plasma aldosterone in normal subjects and patients with hypopituitarism

Although angiotensin II, ACTH and potassium are generally acknowledged as major factors in regulating the influences on aldosterone secretion, it has recently been reported that dopamine is a potent inhibitor of aldosterone secretion in man and animals. In the present study, we investigated the effect of two kinds of dopaminergic receptor antagonists, metoclopramide and sulpiride, on plasma aldosterone concentration (PAC) and serum prolactin (PRL) in man. Normotensive volunteers and patients with hypopituitarism were injected with metoclopramide (10 mg i.v.) or sulpiride (10 mg i.m.). In normal volunteers, metoclopramide increased both PAC and PRL levels, and showed a maximum level at 30 minutes after injection. In patients with hypopituitarism, PAC tended to increase without change of PRL, which suggested that the increase in PAC by metoclopramide might have a direct inhibitory effect on the dopaminergic receptor in the adrenal gland. Moreover another antagonist, sulpiride also increased PRL but contrary tended to decrease PAC. These results suggested that PRL responses to both inhibitors were mediated by dopaminergic antagonist activity at the level of pituitary receptors. However dopamine-induced modulation of aldosterone secretion may be different from that of PRL at dopaminergic receptors. These results suggested that modulatory inhibition of aldosterone secretion by dopamine may be affected by difference of affinity of dopamine to receptor as organ specificity, or different affinity of metoclopramide and sulpiride to adrenal dopamine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interventricular septal motion in acute myocardial infarction with proximal and distal left anterior descending coronary lesions

To evaluate the ability of echocardiography to detect and localize lesions of the proximal and distal left anterior descending (LAD) coronary arteries, the systolic excursion of the left side of the septum and the ratio of septal to posterior wall excursion (IVS/PW) were measured in 26 patients with acute myocardial infarction (AMI) and nine normal control subjects. The patients with proximal LAD lesions had septal wall excursions of less than 3 mm, whereas in those with distal LAD lesions septal wall excursions were more than 3 mm. All patients with proximal LAD lesions showed an IVS/PW ratio of less than 0.4, but in those with distal LAD lesions the ratio was 0.4 or greater. We conclude that reduced or absent interventricular septal motion in anterior AMI suggests an LAD lesion, and a septal excursion of less than 3 mm suggests involvement of the proximal LAD artery, whereas septal excursion of 3 mm or more indicates involvement of the distal LAD artery.     

Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity

Smoking is a major risk factor for atherosclerotic vascular diseases, but the mechanism for its genesis is unknown. We have recently shown that the gas phase of cigarette smoke (nicotine- and tar-free cigarette smoke extract; CSE) likely to reach the systemic circulation contains stable substances which cause cytotoxicity like plasma membrane damage and cell death in cultured cells, and also that the plasma membrane damage is caused through sequential activation of protein kinase C (PKC) and NADPH oxidase (NOX) and the resulting generation of reactive oxygen species (PKC/NOX-dependent mechanism), whereas cell death is caused through PKC/NOX-dependent and -independent mechanisms. To identify these stable substances, the CSE was prepared by passing the main-stream smoke of 10 cigarettes through a Cambridge glass fiber filter, trapping of the smoke in a vessel cooled at ?80 °C, and subsequent dissolution in 10 ml of water. The CSE was fractionated into nine fractions using reversed-phase HPLC, and each fraction was screened for cytotoxicity in cultured cells, using propidium iodide uptake assay for cell membrane damage and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] reduction assay for cell viability. The cytotoxicity was positive in two of the nine fractions (Fr2 and Fr5). After extraction of the active fractions into dichloromethane, GC/MS analysis identified 2-cyclopenten-1-one (CPO) in Fr5 but none in Fr2. After derivatization of the active fractions with O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride, GC/MS analysis identified acrolein, acetone and propionaldehyde in Fr2, and methyl vinyl ketone (MVK) in Fr5. After 4-h incubation, authentic acrolein and MVK induced concentration-dependent cytotoxicity with EC₅₀ values of 75.9 ± 8.2 and 47.0 ± 8.0 μM (mean ± SEM; n = 3), respectively, whereas acetone, propionaldehyde and CPO were without effect. However, after 24-h incubation, CPO induced concentration-dependent cytotoxicity with an EC₅₀ value of 264.0 ± 16.9 μM (n = 3). The concentrations of acrolein, MVK and CPO in the CSE were 3368 ± 334, 2429 ± 123 and 392.9 ± 31.8 μM (n = 4), respectively, which were higher than the cytotoxic concentrations. The cytotoxicity of acrolein and MVK consisted of plasma membrane damage and decreased cell viability: the plasma membrane damage was totally prevented by treatment with an inhibitor of PKC or NOX, whereas the decreased cell viability was only partially prevented by these inhibitors. The cytotoxicity of CPO consisted only of decreased cell viability, which was totally resistant to these inhibitors. These results show that acrolein and MVK are responsible for the acute cytotoxicity of the CSE through PKC/NOX-dependent and -independent mechanisms, whereas CPO is responsible for the delayed cytotoxicity of the CSE through a PKC/NOX-independent mechanism.