Metformin -associated lactic acidosis.

Lactic acidosis is a feared complication of metformin therapy. In our article we describe 2 case reports of patients treated with metformin, who developed this complication. In the first case, which was fatal, cummulation of lactate was a result of acute kidney failure caused by diarrhea. In the second patient, lactic acidosis developed in the terrain of preexisting chronic kidney disease, when dyspepsia and decreased fluid intake caused progression into acute kidney failure. In this case, treatment of lactic acidosis was successful. Death of the first patient was probably caused by the presence of serious comorbidities and other complications which developed early after her addmission to intensive care unit. Lactic acidosis can be prevented by strict avoidance of metformin use in case of contraindications and interruption of its use during intercurrent disease.

High soluble endoglin levels regulate cholesterol homeostasis and bile acids turnover in the liver of transgenic mice.

AIMS: Increased plasma soluble endoglin concentrations (sEng) are frequently detected in metabolic disorders accompanied with hypercholesterolemia in serum, but effect of sEng on the cholesterol biochemistry is unknown. Cholesterol and bile acids (BA) are important products of liver metabolism with numerous functions within the organism. Turnover of these substances requires precise regulation due to potential toxicities during their cumulation. In this study, we hypothesized that high sEng levels affect cholesterol homeostasis and BA turnover in mice liver. MAIN METHODS: Nine-month-old transgenic male mice overexpressing human sEng and wild-type mice underwent plasma, bile, stool, and organ samples analysis by analytical, qRT-PCT and Western blot methods. KEY FINDINGS: sEng mice demonstrated decreased plasma total and LDL cholesterol concentrations due to upregulation of hepatic Sr-b1 and Ldlr receptors, increased liver cholesterol content, and increased Abcg8-mediated cholesterol efflux into bile. sEng also increased conversion of cholesterol into bile acids (BA) via upregulation of Cyp7a1 and increased Mdr1 expression. Plasma concentrations of BA were increased in sEng mice due to their enhanced reabsorption via ileum. Increased hepatic disposition of BA led to their increased biliary excretion coupled with choleretic activity. SIGNIFICANCE: For the first time, we have shown that high sEng plasma levels affect cholesterol and BA homeostasis on the basis of complex liver and intestinal effects. The significance of these findings for pathophysiology of diseases associated with increased sEng concentrations remains to be elucidated in prospective studies.

In vitro comparison of efficacy of catheter locks in the treatment of catheter related blood stream infection.

BACKGROUND & AIMS: Venous access used for parenteral nutrition (PN) application is extremely important for patients with intestinal failure. Potential loss of venous access might be a catastrophy for the patient. Catheter infections are a serious complication of PN application. Systemic administration of antibiotics as well as local antibiotic locks into the catheter to sterilize the catheter are used to treat catheter infections. However, there is no clear recommendation applying use of antibiotic locks, that would specify the type and concentration of antimicrobial medication. Our objective were to compare the efficacy of different types of antimicrobial lock therapy (especially taurolidine) and their concentrations to eradicate infectious agents. METHODS: Bacterial strains of microorganisms (Staphylococcus epidermidis, Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Pseudomonas aeruginosa, multidrug-resistant P. aeruginosa, Candida albicans) were used. Subsequently, the catheter was exposed to the microbes and then was incubated with a specific lock for 2 or 24 h at 37 °C. We used these locks: ethanol 70%, taurolidine, gentamicine in concentrations 0,5, 1 and 10 mg/ml and vancomycine in concentrations 1, 5, and 10 mg/ml. The number of remaining CFU (colony forming units) was compared after incubation. RESULTS: 70% ethanol and taurolidine were most effective for all studied microorganisms. Gentamicine was more effective than vancomycine. CONCLUSIONS: The most effective antimicrobial lock solutions to eradicate selected pathogenic agents were ethanol and taurolidine. Use of antibiotics is often effective after many hours of treatment and there is a risk of inadequate therapy.