Expressions of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death

BACKGROUND：As the regulators of cytokines, suppressors of cytokine signaling （SOCS） play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death （SCD）.METHODS： Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis （non-myocardial infarction） leading to SCD （non-MI group）, 7 died of acute myocardial infaction （MI group）, and 8 died from traffic accidents and trauma （control group）. The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 sottware and the data were analyzed by ANOVA.RESULTS： The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[（0.788±0.101）, （0.741±0.111） vs. （0.436±0.044）, （P〈0.01）; （0.841±0.092）, （0.776±0.070） vs. （0.454±0.076）, （P〈0.01）] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[（320.00±48.48）, （347.14±70.88） vs. （42.50±10.35）, （P〈0.01）] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[（381.11 ±59.25） vs. （40.00±10.69）, （P〈0.01）] and[（332.86±111.91） vs. （40.00±10.69）, （P=0.001）].CONCLUSION： The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.

Functional and morphological changes of the gut barrier during the restitution process after hemorrhagic shock

AIM： To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response to ischemia/ reperfusion injury. METHODS： Forty-seven Sprague-Dawley rats with body weight of 250-300 g were divided into two groups： control group （sham shock n = 5） and experimental group （n = 42）. Experimental group was further divided into six groups （n = 7 each） according to different time points after the hemorrhagic shock, including 0^th group, 1^st group, 3^rd group, 6th h group, 12^th group and 24^th group. All the rats were gavaged with 2 mL of suspension of lactulose （L） （100 mg/2 mL） and mannitol （M） （50 mg/each） at the beginning and then an experimental rat model of hemorrhagic shock was set up. The specimens from jejunum, ileum and colon tissues and the blood samples from the portal vein were taken at 0, 1, 3, 6, 12 and 24 h after shock resuscitation, respectively. The morphological changes of the intestinal mucosa, including the histology of intestinal mucosa, the thickness of mucosa, the height of villi, the index of mucosal damage and the numbers of goblet cells, were determined by light microscope and/or electron microscope. The concentrations of the bacterial endotoxin lipopolysaccharides （LPS） from the portal vein blood, which reflected the gut barrier function, were examined by using Limulus test. At the same time point, to evaluate intestinal permeability, all urine was collected and the concentrations of the metabolically inactive markers such as L and M in urine were measured by using GC-9A gas chromatographic instrument.RESULTS： After the hemorrhagic shock, the mucosal epithelial injury was obvious in small intestine even at the 0th h, and it became more serious at the 1^stand the 3^rd h. The tissue restitution was also found after 3 h, though the injury was still serious. Most of the injured mucosal restitution was established after 6 h and completed in 24 h. Two distinct models of cell deathapoptosis and necrosis-were involved in the destruction of rat intestinal epithelial cells. The number of goblet cells on intestinal mucosa was reduced significantly from 0 to 24 h （the number from 243±13 to 157±9 for ileum, 310±19 to 248±18 for colon; r= -0.910 and -0.437 respectively, all P〈0.001）, which was the same with the large intestine, but the grade of injury was lighter with the values of mucosal damage index in 3 h for jejunum, ileum, and colon being 2.8, 2.6, 1.2, respectively. The mucosal thickness and the height of villi in jejunum and ileum diminished in 1 h （the average height decreased from 309±24 to 204±23 pm and 271±31 to 231±28 pm, r = -0.758 and -0.659, all P〈0.001, the thickness from 547±23 to 418±28μm and 483±45 to 364±35μm, r= -0.898 and -0.829, all P〈0.001）, but there was no statistical difference in the colon （F= 0.296, P = 0.934）. Compared with control group, the urine L/M ratio and the blood LPS concentration in the experimental groups raised significantly, reaching the peak in 3-6 h （L/M： control vs 3 h vs6 h was 0.029±0.09 vs 0.063±0.012 vs 0.078±0.021, r = -0.786, P〈0.001; LPS： control vs3 h vs6 h was 0.09±0.021 vs 0.063±0.012 vs0.25±0.023, r=- -0.623, P〈0.001）, and it kept increasing in 24 h. CONCLUSION： The gut barrier of the rats was seriously damaged at the early phase of ischemic reperfusion injury after hemorrhagic shock, which included the injury and atrophy in intestinal mucosa and the increasing of intestinal permeability. Simultaneously, the intestinal mucosa also showed its great repairing potentiality, such as the improvement of the intestinal permeability and the recovery of the morphology at different phases after ischemic reperfusion injury. The restitution of gut barrier function was obviously slower than that of the morphology and there was no direct correlation between them. Compared with the small intestine, the large intestine had stronger potentiality against injury. The reduction of the amount of intestinal goblet cells by injury did not influence the ability of intestinal mucosal restitution at a certain extent and it appeared to be intimately involved in the restitution of the epithelium.

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.

Changes of end-tidal carbon dioxide during cardiopulmonary resuscitation from ventricular f ibrillation versus asphyxial cardiac arrest

BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation(CPR). This study was to investigate changes of PETCO2 during CPR in rats with ventricular fi brillation(VF) versus asphyxial cardiac arrest.METHODS: Sixty-two male Sprague-Dawley(SD) rats were randomly divided into an asphyxial group(n=32) and a VF group(n=30). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.RESULTS: The initial values of PETCO2 immediately after PC in the VF group were signifi cantly lower than those in the asphyxial group(12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of PETCO2 after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation(ROSC), compared with those in rats without ROSC(16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of PETCO2 after 2 minutes of PC in rats with ROSC were signifi cantly higher than those in rats without ROSC(20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic(ROC) curves of PETCO2 showed signifi cant sensitivity and specifi city for predicting ROSC in VF versus asphyxial cardiac arrest.CONCLUSIONS: The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.