Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats

To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (AII) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma AII levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to AII; an increase by 4 orders of magnitude in the threshold dose for AII and a decrease in the maximum AII-stimulated level. The maximum AII-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsiveness to AII. These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells, involving the specific receptors and the aldosterone biosynthesis, to AII.     

Do valsartan and losartan have the same effects in the treatment of coronary artery disease?

BACKGROUND: Many angiotensin II type 1 receptor blockers (ARBs) are available for clinical use, but because they do not all have the same effects, the present study investigated whether all benefits conferred by ARBs are class effects. METHODS AND RESULTS: Study 1 was a case-control study of patients with coronary artery disease, which showed that a non-depressor dose of valsartan significantly decreased the rate of target lesion revascularization at 6 months after stenting compared with the control group without ARB treatment. In Study 2, 44 patients with acute myocardial infarction who randomly received an initial lower dose of either valsartan or losartan after stenting were evaluated. The late loss and decrease in %diameter stenosis in the valsartan group were significantly lower than those in the losartan group as assessed by quantitative coronary angiography after 6 months. In addition, the valsartan group showed a significantly lower expression of intracellular adhesion molecule-1 and L-selectin. CONCLUSION: A non-depressor dose of ARB may have beneficial effects on coronary restenosis that are associated with the regulation of adhesion molecules, and these effects might not be a class effect of ARBs.     

T-helper type 1/T-helper type 2 balance in malignant pleural effusions compared to tuberculous pleural effusions

STUDY OBJECTIVES: Malignant and tuberculous pleurisies are two major causes of lymphocyte-dominant pleurisy. Several studies have already reported that tuberculous pleurisy is a T-helper type 1(Th1)-dominant disease. In this study, we sought to examine the Th1/T-helper type 2 (Th2) balance, especially focusing on the polarizing status of T-cells to Th1/Th2 in malignant pleural effusions by measuring cytokines in pleural effusions and by evaluating the polarizing status of T-cells on the point of stimulation with interleukin (IL)-12 and/or IL-18. Furthermore, we evaluated inhibitors of interferon (IFN)-gamma production in effusions to rule out the possibility of direct inhibition of T-cell polarization. PATIENTS: Effusion samples were collected from 19 patients with malignant pleurisy caused by lung cancer and from 7 patients with tuberculous pleurisy. MEASUREMENTS: Concentrations of pleural fluid IFN-gamma, IL-12, and IL-4 were measured. IFN-gamma production of T-cells enriched from malignant pleural effusions in the presence of IL-12 and/or IL-18 was also examined. We further compared the inhibitory activity of malignant pleural effusions against IFN-gamma production and analyzed the expression of T-cell immunoglobulin mucin, mucin domain (Tim-3), a Th1-specific molecule in pleural fluid T-cells. RESULTS: Although malignant pleural effusions showed low levels of Th1 and Th2 cytokines and ratios of IFN-gamma and IL-12 to IL-4 were low, isolated T-cells produced a significant level of IFN-gamma in the presence of IL-12 and IL-18. Soluble factors were not found to inhibit IFN-gamma production in malignant pleural effusions. In tuberculous pleural effusion, ratios of IFN-gamma and IL-12 to IL-4 were significantly higher, and T-cells showed the expression of Tim-3 messenger RNA. CONCLUSIONS: We confirmed that T-cells in the malignant pleural effusions are mainly na?ve or not definitely polarized to Th1. Moreover, malignant tumor does not actively distort the cytokine condition through production of soluble inhibitors within effusions. The present study indicates that antitumor immunity may be enhanced by restored IFN-gamma activity through combination of IL-12 and IL-18, and that it will lead to new therapies for malignant effusion.     

Pharmacoangiographic diagnosis of venous invasion of carcinoma of the colon with reference to liver metastases

Angiography using prostaglandin E1 was performed on 34 patients with carcinoma of the colon in order to define the degree of venous invasion. Venous findings on angiogram (occlusion and/or encasement) were classified into three groups: AG-V2, above-mentioned venous findings up to marginal vein; AG-V1, these findings up to the vasa recta; AG-V0, no distinct findings on the vein. These venous findings were compared with histologic subserosal venous invasion that was diagnosed with both hematoxylin and eosin and elastica van Gieson's staining. When angiographic findings were compared with histologic subserosal venous invasion, the results of AG-V2, AG-V1, and AG-V0 showed a positive correlation of 92.3 percent, 46.7 percent, and 16.7 percent, respectively. The angiographic findings were also correlated with the degree of fibrosis around the carcinoma of the colon. The incidence rate of liver metastasis in a group of AG-V2 was 46.2 percent. In AG-V1 it was 26.7 percent and in AG-V0 0 percent. In the course of the postoperative follow-up, liver metastases appeared in two cases of AG-V2 and AG-V1, respectively. This finding may suggest the presence of liver micrometastases at the time of surgery.     

Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy

Background/Objectives

A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount.

Characteristics of electrocardiographic repolarization in acute myocardial infarction complicated by ventricular fibrillation

Background and PurposeSome de- and re-polarization patterns can reflect an increased risk of ventricular tachyarrhythmias. We studied whether some electrocardiographic (ECG) patterns are able to predict the development of ventricular fibrillation (VF) during acute myocardial infarction (MI).MethodsWe compared the patterns of ST-T segment of 78 patients who developed VF during acute MI (patient with VF) vs 170 comparable patients with acute MI but with no VF complications.ResultsOf the VF group, 47 developed out-of-hospital VF and 31 developed VF after their admission to the hospital. A steep downsloping ST segment toward a negative T wave with or without a short, flat, or rising portion at the initial portion was observed in 69.2% of the 78 patients: 61.3% in patients with pre-VF and 74.5% in patients with post-VF, vs 9.4% of patients who did not develop VF (P < .0001). In 90.6% of the latter, a typical upward-concave or convex “ischemic” pattern of the ST segment was observed. Thus, the characteristic ST-T patterns were highly associated with VF with a specificity greater than 90%.ConclusionsA steep downsloping ST segment may characterize the ECGs of patients who develop VF during acute MI.