Bang Gee Hsu

Effects of post-treatment with low-dose propofol on inflammatory responses to lipopolysaccharide-induced shock in conscious rats

1.u2002In the present study, we used a low dose of propofol (5 mg/kg per h) to investigate its effects on the pro‐inflammatory cytokines (tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐10) and changes in nitric oxide (NO) following lipopolysaccharide (LPS) for a period of 12 h in conscious rats.

N-Acetylcysteine Ameliorates Lipopolysaccharide-Induced Organ Damage in Conscious Rats

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetylcysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, IL-1 beta, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-1 beta, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-alpha, IL-1 beta, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.

The reduction of tumor necrosis factor-alpha release and tissue damage by pentobarbital in the experimental endotoxemia model.

Sepsis is the leading cause of death for intensive care patients. Lipopolysaccharide (LPS) administration to animals under anesthesia is a strategy for the study of uncontrolled release of proinflammatory cytokines. Anesthetics have been indicated that they can specially affect immune responses, such as the inflammatory response. Pentobarbital is an anesthetic used mainly in animal studies. Thus, the effect of pentobarbital on tumor necrosis factor-&agr; (TNF-&agr;) release was determined. The results revealed that pentobarbital suppressed the expression of TNF-&agr; mRNA and its proteins, which may result from the decrease in the activities of nuclear factor-&kgr;B and activator protein 1 and the reduction of the expression of p38 mitogen-activated protein kinase by pentobarbital. After the inhibitory activity of the pentobarbital for TNF-&agr; release was proven in vivo, the cytotoxic effects of LPS were examined in vivo with or without pentobarbital treatments. In vivo results indicated that plasma levels of alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, creatine kinase, serum urea nitrogen, and amylase decreased dramatically in the anesthetic group with pentobarbital administration. Finally, the effect of pentobarbital on TNF-&agr;-related cell death was monitored in vitro, and the results indicated that pentobarbital could directly enhance the viabilities of cells under the treatment of TNF-&agr; and protected cells from apoptosis induced by deferoxamine mesylate-induced hypoxia. These results suggest that pentobarbital significantly influences the LPS-induced inflammatory responses and protects cells from death directly and indirectly induced by TNF-&agr;. The information provides a perspective to re-evaluate the results of the experiments in which animals were anesthetized with pentobarbital. The anti-inflammatory effects of the drugs may have been caused by the synergistic effect of pentobarbital.

Fasting Serum Total Ghrelin Level Inversely Correlates with Metabolic Syndrome in Hemodialysis Patients

BACKGROUNDnMetabolic syndrome (MS) is a significant risk factor for cardiovascular disease and predicts hospitalization in patients undergoing hemodialysis. An inverse association between circulating ghrelin and MS has been observed in adults. However, no data are available on the relationship between MS and serum total ghrelin levels in hemodialysis patients.nnnMETHODSnFasting blood samples were obtained from 52 hemodialysis patients. MS and its components were defined using diagnostic criteria from the International Diabetes Federation. Total ghrelin levels were measured using a commercial enzyme-linked immunosorbent assay kit.nnnRESULTSnOf the 52 hemodialysis patients, 30 (58%) had MS. Fasting total ghrelin level inversely correlated with MS among these hemodialysis patients (p<0.001). There was a tendency for the fasting total ghrelin level to decrease as the number of diagnostic criteria for MS in patients increased. Univariate linear regression analysis showed that the pre-hemodialysis body weight (r=-0.401; p=0.007), waist circumference (r=-0.554; p<0.001), triglyceride level (r=-0.317; p=0.022), and insulin level (r=-0.353; p=0.015) were negatively correlated with total ghrelin levels, whereas high-density lipoprotein (HDL) (r=0.506; p<0.001) and growth hormone (r=0.305; p<0.040) levels were positively correlated with the total ghrelin level. Multivariate forward stepwise linear regression analysis of the significant variables showed that waist circumference (R(2) change=0.297, p<0.001) was an independent predictor of the total ghrelin among the hemodialysis patients and explained 29.7% of the variance.nnnCONCLUSIONSnWe observed an inverse association between the circulating fasting total ghrelin level and MS among hemodialysis patients. There was a tendency for the total ghrelin level to decrease as the number of diagnostic criteria for MS in patients increased. Waist circumference was an independent predictor of the total ghrelin level among hemodialysis patients.

A Cohort Study of Subjective Global Assessment and Mortality in Taiwanese Hemodialysis Patients

Many patients with end-stage renal disease are malnourished, and cross-sectional studies have shown that markers of malnutrition may predict death. In this study, we investigated the possible association of Subjective Global Assessment and mortality in a small cohort of Taiwanese hemodialysis patients. Fifty hemodialysis patients at a hemodialysis center in eastern Taiwan were enrolled in June 2002. Height and weight were used to determine the body mass index. Bioelectrical impedance analysis of body fat mass was performed before and after a mid-week dialysis session. Biochemical indexes of the nutritional status included serum albumin, creatinine, transferrin, cholesterol, and the normalized protein catabolic rate. Mortality data during 42 months after enrollment were obtained. Twenty-six hemodialysis patients were classified as well-nourished and twenty-four as malnourished based on Subjective Global Assessment. Decreased body mass index (pu2009=u20090.006), increased body fat mass (pu2009=u20090.019 before hemodialysis; pu2009=u20090.007 after hemodialysis), decreased serum albumin (pu2009=u20090.011), and decreased serum creatinine (pu2009=u20090.006) were significantly higher in the malnourished group. Older age (pu2009=u20090.042), decreased serum albumin (pu2009=u20090.028), decreased serum transferrin (pu2009=u20090.041), and malnourishment (pu2009=u20090.004) were significantly higher in the mortality group. Multivariate forward stepwise linear regression analysis of mortality and nutrition profiles show that Subjective Global Assessment is the independent predictor of mortality (R2u2009=u20090.20). Malnourished hemodialysis patients had a higher mortality rate than well-nourished hemodialysis patients in Taiwan. Subjective Global Assessment of the nutritional status appears to be a simple tool for assessing the nutritional status of hemodialysis patients in long-term care. This assessment tool is also beneficial for hemodialysis patients who are at a greater risk of nutritional-associated mortality.

Use of cardio-ankle vascular index in chronic dialysis patients

Eur J Clin Invest 2010; 41 (1): 45–51

Fasting serum adiponectin level inversely correlates with metabolic syndrome in peritoneal dialysis patients.

Background:Metabolic syndrome is a significant risk factor for cardiovascular disease and predicts hospitalization in peritoneal dialysis (PD) patients. An inverse association between circulating adiponectin and metabolic syndrome has been observed in humans. However, no data are available on the relationship between metabolic syndrome and serum adiponectin levels in PD patients. Method: Fasting blood samples were obtained from 47 PD patients and 47 subjects in an outpatient department were enrolled as a control group. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation. Adiponectin levels were measured using a commercial enzyme immunoassay kit. Results: Twenty-seven of 47 PD patients (57.5%) had metabolic syndrome. PD patients had lower serum albumin (p < 0.001) and higher serum adiponectin levels (p = 0.016), high-sensitivity C-reactive protein (p = 0.008), creatinine (p < 0.001) and metabolic syndrome (p < 0.001) than controls. The fasting adiponectin level inversely correlated with the metabolic syndrome in these PD patients (p = 0.006). Univariate linear regression analysis showed that the waist circumference (r = –0.304; p = 0.038), body mass index (r = –0.347; p = 0.017), body fat mass (r = –0.305; p = 0.037), white blood count (r = –0.631; p < 0.001), triglyceride (TG; r = –0.526; p < 0.001), and fasting glucose (r = –0.394; p = 0.006) were negatively correlated with the fasting serum adiponectin levels, while high-density lipoprotein-cholesterol (r = 0.443; p = 0.002) was positively correlated with the fasting serum adiponectin levels among the PD patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that white blood count (R2 change = 0.398, p < 0.001), and TG (R2 change = 0.118, p = 0.002) were the independent predictors of fasting serum adiponectin levels and explained 51.6% of variance. Conclusions: We observed that PD patients had higher metabolic syndrome than the general population and an inverse association was found between the circulating fasting adiponectin level and metabolic syndrome in PD patients. White blood count and TG were independent predictors of the serum adiponectin level among PD patients.

Fasting Serum Leptin Level Correlates With Mid‐Arm Fat Area in Peritoneal Dialysis Patients

Leptin correlates with body fat content and plays a pivotal role in inflammatory response. This study aimed to investigate the relationships of fasting serum leptin levels and the anthropometric fat components among peritoneal dialysis (PD) patients. Fasting blood samples were obtained from 40 PD patients. Leptin levels were measured using a commercial enzyme‐linked immunosorbent assay kit. Body weight (ru2003=u20030.424; Pu2003=u20030.006), waist circumference (ru2003=u20030.352; Pu2003=u20030.026), body mass index (BMI; ru2003=u20030.483; Pu2003=u20030.002), body fat mass (ru2003=u20030.352; Pu2003=u20030.026), high sensitivity C‐reactive protein (hs‐CRP; ru2003=u20030.494; Pu2003=u20030.001), triceps skinfold thickness (TSF; ru2003=u20030.505; Pu2003=u20030.001), mid‐arm circumference (MAC; ru2003=u20030.471; Pu2003=u20030.002), and mid‐arm fat area (MAFA; ru2003=u20030.564; Pu2003<u20030.001) were positively correlated, while high density lipoprotein (HDL)‐cholesterol (ru2003=u2003−0.345; Pu2003=u20030.028) was negatively correlated with fasting serum leptin levels among the PD patients. Multivariate forward stepwise linear regression analysis showed that MAFA (R2u2003=u20030.318, Pu2003=u20030.011) was the independent predictor of fasting serum leptin levels among the PD patients. In conclusion, fasting leptin level was positively associated with body fat composition (body weight, waist circumference, BMI, body fat mass, TSF, MAC, and MAFA) and hs‐CRP among PD patients, and MAFA was the independent predictor of fasting serum leptin levels among the PD patients.

A Clinical Study of Prognosis and Glucocorticoid Pulse Treatment in Patients with Acute Paraquat Intoxication

Objective: Paraquat is a highly toxic herbicide that binds strongly to tissue and causes high mortality rates due to pesticide intoxication in Taiwan. In this study, we evaluated the usefulness of methylprednisolone pulse therapy and calculation of the severity index of paraquat poisoning (SIPP) to predict the prognosis in patients with oral paraquat intoxication. Materials and Methods: Thirty-two patients with paraquat poisoning from January 2003 to April 2005 were enrolled into this study at a medical center in eastern Taiwan. All 32 patients had history of oral intake of paraquat and urine paraquat was positive at the emergency department. Time of oral intake of paraquat and serum paraquat levels were assayed at the emergency department for calculating SIPP (hour×mg/L) level. Sixteen patients with oral paraquat poisoning were treated with intravenous methylprednisolone 1 g/day and charcoal hemoperfusion for 3 days (MP group), and 16 patients with oral paraquat poisoning were treated with charcoal hemoperfusion only for 3 days (control group). Results: The mortality rate of the patients with oral paraquat poisoning was high (87.5%). There were no statistically significant differences in death (p=1.000), age (p=0.706), sex (p=0.069), serum blood urea nitrogen (p=0.104), creatinine (p=0.174), aspartate aminotransferase (p=0.083), alanine aminotransferase (p=0.365), plasma level of paraquat (p=0.880) and SIPP level (p=0.734) between the MP group and control group. Young age (p=0.030), lower initial plasma paraquat level (p=0.002), lower serum creatinine (p=0.009), female sex (p=0.033), lower elapsed time from ingestion of paraquat to arrival at hospital (p=0.035) and SIPP level less than 10 (p＜0.001) were associated with survival in patients with oral paraquat poisoning. Multivariate forward stepwise linear regression analysis of deaths showed that SIPP＞10 (hour×mg/L) (p＜0.001) was an independent predictor of death in patients with oral paraquat poisoning and explained 77.1% of the variance (R^2=0.771). Conclusion: Treatment with methylprednisolone pulse therapy did not show better results in patients with acute oral paraquat poisoning. SIPP was an independent predictor of death in patients with oral paraquat poisoning.

Effects of different fluid resuscitation speeds on blood glucose and interleukin-1 beta in hemorrhagic shock.

BACKGROUNDnFluid resuscitation is an important treatment for hemorrhagic shock. However, evidence of guidelines for fluid resuscitation is limited. The expressions of blood glucose and proinflammatory cytokines under different resuscitation rates are still unknown. In this study, the status of blood glucose and interleukin-1beta (IL-1beta) between rapid and slow fluid resuscitation for hemorrhagic shock were compared.nnnMETHODSnTwenty-four male Wistar-Kyoto rats were used in the study. The volume of blood withdrawal was 40% of the total blood volume of a rat and fluid resuscitation was given immediately after blood withdrawal. Rats were randomly divided into control group, 10 minutes rapid group, and 12 hours slow group.nnnRESULTSnOur findings show that a 10 minutes rapid infusion may provide the blood pressure and heart rate stability at early phase of hemorrhage. Moreover, rapid infusion decreases blood glucose and IL-1beta at 1, 3, 6, 9, 12, 18, and 48 hours after fluid resuscitation. However, the levels of glucose and IL-1beta were not different between control and the slow group.nnnCONCLUSIONnRapid fluid resuscitation ameliorates hyperglycemia and inflammatory response after hemorrhagic shock. Knowledge of advanced treatment will facilitate optimal care delivery for patients with hemorrhagic shock.