Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy.

INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I). MATERIALS AND METHODS: After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7). RESULTS: In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed. CONCLUSION: These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage.     

Influence of Chewing and Clenching on Salivary Cortisol Levels as an Indicator of Stress

PURPOSE: The purpose of this study was to investigate the effects of chewing and clenching on salivary cortisol levels as an indicator of stress. MATERIALS AND METHODS: Seventeen healthy dentulous subjects were given arithmetic exercises to perform within a 20-minute time limit in order to elicit stress (stress loading). In the first experiment (chewing), after stress loading, the subjects were asked to chew a paraffin wax while reading printed material (books, magazines, etc.) in silence for 10 minutes. The same procedure was then carried out again for control purposes, but this time the subjects were not required to chew wax. In the second experiment (light clenching), after stress loading, the subjects were required to carry out 5 seconds of light clenching followed by 5 seconds of rest repeatedly over a 3-minute period. The whole 3-minute process was repeated a total of three times. The control data for this second experiment consisted of measurements taken during the rest periods. Saliva specimens were collected in both experiments both before stress loading and after each procedure during 1-minute intervals to measure cortisol levels. RESULTS: In the chewing experiment, salivary cortisol levels were significantly reduced by chewing, compared with those in the controls (p < 0.05). This reduction in salivary cortisol was observed during chewing over a 10-minute period following stress loading. In the clenching experiment, salivary cortisol levels also showed a significant reduction during clenching, compared with those in the controls (p < 0.05). CONCLUSIONS: These results suggest that chewing and clenching promote relaxation in subjects under stress.     

Localization of mRNA for inflammatory cytokines in radicular cyst tissue by in situ hybridization, and induction of inflammatory cytokines by human gingival fibroblasts in response to radicular cyst contents

The expression of mRNA encoding the inflammatory cytokines interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) have been examined in radicular cysts by in situ hybridization. Furthermore, the biological activity of the contents of radicular cysts (RCC) has been assayed by adding extracts of RCC to cultured human gingival fibroblasts (HGFs) and analyzing the culture medium for the release of inflammatory cytokines. In the epithelial layer, keratinocytes expressed all cytokine mRNAs examined at various levels. Basal layer cells expressed mRNA for each cytokine. In the subepithelial granulation tissue of the cysts, fibroblasts and macrophages expressed mRNA for IL-6, IL-8, IL-1β and TNF-α mRNA at varying levels; especially clear expression of TNF-α and IL-1β mRNA was detected on macrophages. The infiltrating lymphoid cells, largely composed of T cells and plasma cells, expressed these cytokine mRNAs, especially those encoding IL-6 and IL-8, at various levels. In vitro analysis indicated dose-dependent release of both IL-6 and IL-8 by HGFs in response to RCC. After heating to 100°C for 10 min, RCC almost completely failed to stimulate IL-6 release from HGFs. Furthermore, anti-IL-1β antibody (neutralization test) did not prevent the stimulation of IL-6 release by RCC. Significant amounts of IL-6 and IL-8 were detected in RCC in two cases, and a trace amount of IL-1β was detected in one case. This study demonstrated the wide expression of mRNA encoding inflammatory cytokines in radicular cyst tissues, and RCC itself was capable of stimulating 1L-6 and 1L-8 production from HGFs.     

Reduced Expression of nm23 Is Associated with Metastasis of Human Gastric Carcinomas

Reduced expression of nm23 gene is implicated in high metastatic potential In a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty-two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non-neoplastic mucosa. No obvious correlation was observed between clinico-pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.     

Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.