Mechanism of Anti-chronic Alcoholic Liver Injury in Rats of Tibetan Medicine Lagotis brachystachys Extracts by TLR2/MyD88/NF-κB and NALP3 Signaling Pathway / 中国实验方剂学杂志

Objective::To established the model of chronic alcoholic liver injury in rats by long-term(8 weeks) alcoholic gavage, to study the effects of Tibetan medicine Lagotis brachystachys extracts on Toll-like receptor(TLR)2/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B (NF-κB)and NOD like receptor protein 3(NALP3) signaling pathways and study preliminary the mechanism of action of chronic alcoholic liver injury. Method::Sixty male Sprague-Dawley rats were randomly divided into normal group, model group, bifendate positive drug group (0.1 g·kg-1) and L. brachystachys low, medium and high-dose groups (0.5, 1, 2 g·kg-1), the corresponding drugs were given at 10 mL·kg-1 in each morning, and the 56 degree Liquor was administered by the afternoon gradient alcoholic gavage method.After 8 weeks, the levels of serum aspartate transaminase (AST), serum alanineaminotransfease(ALT), serum total cholesterol(TC), triglyceride(TG), interleukin-1β(IL-1β), and the liver levels of L-glutathione(GSH)were measured. The expression of TLR2, MyD88, NF-κB and NALP3 protein in liver were detected by Western blot.Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue. Result::Compared with normal group, the serum levels of AST, ALT, TC, TG and IL-1β in model group were significantly increased (P<0.05, P<0.01). Compared with model group, the serum AST, ALT, TC, TG and IL-1β levels were decreased in the various doses of L. brachystachys, and the high dose group was particularly effective (P<0.05, P<0.01). Compared with normal group, the GSH level in the liver homogenate of model group decreased significantly, and the difference was not statistically significant. The levels of TLR2, MyD88, NF-κB and NALP3 in the liver tissue of model group were significantly increased (P<0.05, P<0.01). The GSH levels in the liver and the protein expression of TLR2, MyD88, NF-κB and NALP3 were decreased in L. brachystachys group (P<0.05, P<0.01). The liver pathological section showed that L. brachystachys can improve the pathological changes of rat liver tissue. Conclusion::L. brachystachys can protect liver from alcohol-induced chronic liver injury in rats. The mechanism was related to TLR2/MyD88/NF-κB and NALP3 signaling pathway.

The microbiological profile and presence of bloodstream infection influence mortality rates in necrotizing fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) is a life threatening infectious disease with a high mortality rate. We carried out a microbiological characterization of the causative pathogens. We investigated the correlation of mortality in NF with bloodstream infection and with the presence of co-morbidities. METHODS: In this retrospective study, we analyzed 323 patients who presented with necrotizing fasciitis at two different institutions. Bloodstream infection (BSI) was defined as a positive blood culture result. The patients were categorized as survivors and non-survivors. Eleven clinically important variables which were statistically significant by univariate analysis were selected for multivariate regression analysis and a stepwise logistic regression model was developed to determine the association between BSI and mortality. RESULTS: Univariate logistic regression analysis showed that patients with hypotension, heart disease, liver disease, presence of Vibrio spp. in wound cultures, presence of fungus in wound cultures, and presence of Streptococcus group A, Aeromonas spp. or Vibrio spp. in blood cultures, had a significantly higher risk of in-hospital mortality. Our multivariate logistic regression analysis showed a higher risk of mortality in patients with pre-existing conditions like hypotension, heart disease, and liver disease. Multivariate logistic regression analysis also showed that presence of Vibrio spp in wound cultures, and presence of Streptococcus Group A in blood cultures were associated with a high risk of mortality while debridement > = 3 was associated with improved survival. CONCLUSIONS: Mortality in patients with necrotizing fasciitis was significantly associated with the presence of Vibrio in wound cultures and Streptococcus group A in blood cultures.

The effect of prolonged ED stay on outcome in patients with necrotizing fasciitis.

OBJECTIVE: Overcrowding in hospitals, especially in EDs, is a serious problem in the United States, Europe, and Taiwan. However, the association between prolonged ED boarding stay and mortality in patients with necrotizing fasciitis remains underinvestigated. METHODS: This was a retrospective study. A total of 195 patients were enrolled and analyzed. The sample was divided into 2 groups: nonmortality and mortality. A stepwise logistic regression model was developed to investigate 3 factors of clinical relevance predicting patient mortality. RESULT: The results of the stepwise logistic regression analysis revealed that hypotension (odds ratio [OR], 32.9; 95% confidence interval [CI], 6.9-156.0) and prolonged ED boarding stay (OR, 3.4; 95% CI 1.3-8.6) were both associated with higher mortality. Early operation (OR: 0.16; 95% CI: 0.06-0.45) was associated with lower mortality. CONCLUSION: Prolonged ED boarding stay was associated with increased mortality in patients with necrotizing fasciitis. Early operation (within 24 hours of ED arrival) was associated with decreased mortality.

Laboratory risk indicator for necrotizing fasciitis score and the outcomes.

BACKGROUND: Laboratory risk indicator for necrotizing fasciitis (LRINEC score) is a simple laboratory tool used to distinguish between necrotizing soft-tissue infections (NSTI) and other soft-tissue infections. A LRINEC score of > or =6 is considered as denoting a high risk of necrotizing fasciitis. A certain LRINEC score might also be associated with mortality and other outcomes of patients with NSTI. METHODS: A review of the medical charts of patients was carried out. The study sites were one tertiary academic centre and one community, university-affiliated hospital. All adult patients with necrotizing soft-tissue infections from 2002 to 2005 were selected then LRINEC scores were calculated for each patient. We enrolled patients where there was sufficient information to determine that the LRINEC score was either <6 or > or =6. RESULTS: A total of two hundred and nine patients were enrolled and analysed. The overall mortality rate was 33 of 209 (15.8%) and amputation rate was 55 of 209 (26.3%). The amputation rates were defined as numbers of patients who received amputation divided by numbers of total patients. Enrolled patients were divided into two groups. Group I was those whose LRINEC score was <6 and group II was those whose LRINEC score was > or =6. Significant differences in mortality rate (P = 0.04) and amputation rate (P = 0.002) were noted between two groups. CONCLUSION: The LRINEC score is associated with the outcomes of patients with NSTI. Patients with a LRINEC score of > or =6 have a higher rate of both mortality and amputation.

Metformin-associated lactic acidosis in a pregnant patient.

Metformin-associated lactic acidosis is a rare but serious condition and potentially even more hazardous during pregnancy. We reported a case of lactic acidosis in a 28-year-old pregnant woman (gravida 3, para 0, abortion 2, ante-partum 22 weeks) after ingestion of 39.50 g (approximately 80 tablets) metformin in a suicide attempt. She had no pre-existing systemic illness. Analysis of arterial blood gases revealed a high anion gap (28.1 mEq/l) and a normal osmol gap (8 mEq/l) metabolic acidosis. Other etiologies of high anion gap and normal osmol gap metabolic acidosis were excluded by laboratory investigation. The patient was treated on an emergency basis and received aggressive fluid management, intravenous sodium bicarbonate (1 mEq/kg) and activated charcoal, orally. The fetal condition was monitored intensively. The fetus was delivered smoothly via vaginal delivery in a healthy state at the 38th gestational week. Clinical follow-up over the next 2 years confirmed no congenital abnormality. We present a case of successful management of metformin-associated lactic acidosis during pregnancy, treated simply, with intravenous sodium bicarbonate and intensive fetal monitoring. This relatively noninvasive method is an effective treatment option. However, hemodialysis still has a valuable role in the management of acidosis which proves refractory to conservative treatment, such as that described.

Cardiac tamponade secondary to haemopericardium in a patient on warfarin.

Acute cardiac tamponade requires urgent diagnosis and treatment. We report a case involving a 70-year-old man who was receiving warfarin treatment for 12 years following mitral valve replacement. The international normalised ratio (INR) was checked and echocardiography performed regularly in the clinic. The last INR was 2.1, checked 2 weeks before admission to the emergency department. The last echocardiography performed 3 months previously revealed no pericardial effusion. The patient suffered from progressive dyspnoea and orthopnoea for several days. Cardiac tamponade was diagnosed, and the INR at that time was 7.52. Urgent pericardiocentesis and pericardiotomy were undertaken and 1300 ml of pericardial blood was drained. Following surgery the patient's recovery was uneventful. An intravenous vitamin K injection and fresh frozen plasma transfusion were administered to reverse the patient's over-anticoagulated state. The final pathology revealed chronic inflammation and there was no malignancy, and no bacteria or mycobacterium were seen. Emergency physicians should remember that over-anticoagulation with warfarin may contribute to certain complications, including haemopericardium, and that strict control of target INR should be the goal for patients who require continuous warfarin treatment.