Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.

Summary Edwardsiella tarda, a member of the family Enterobacteriaceae, is a rare human pathogen. Gastroenteritis is the most frequently reported manifestation of E. tarda infection. In contrast, extraintestinal infection with E. tarda has rarely been reported. This study made a retrospective case and microbiological data review of patients with extraintestinal E. tarda infections to further understand this disease. This study retrospectively reviewed the charts of all isolates of E. tarda cultures from clinical specimens other than faeces at Chang Gung Memorial Hospital, Taoyuan, Taiwan from October 1998 through December 2001. Edwardsiella tarda was isolated from 22 clinical specimens from 22 hospitalised patients (13 females and nine males). The extraintestinal manifestations of E. tarda infection included biliary tract infection, bacteraemia, skin and soft tissue infection, liver abscess, peritonitis, intra-abdominal abscess, and tubo-ovarian abscess. The major underlying diseases predisposing to E. tarda extraintestinal infection were hepatobiliary diseases, malignancy and diabetes mellitus. The overall mortality rate of E. tarda extraintestinal infection in the present series was 22.7% (5/22), and four (40%) of 10 patients with bacteraemia expired. Although rare, human E. tarda extraintestinal infections can have diverse clinical manifestations and moreover may cause severe and life-threatening infections. Consequently, E. tarda should be considered a potentially important pathogen.

The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.

Introduction: There is a paucity of literature analyzing outcome of chlorpyrifos intoxication. Methods: A total of 40 patients with chlorpyrifos intoxication were seen at Chang Gung Memorial Hospital between 2008 and 2017. Patients were stratified into two subgroups according to their prognosis, as good ( n = 12) or poor ( n = 28). Good prognosis group were defined as patients who survived without serious complications, and poor prognosis group included patients who died and survived after development of severe complications. Demographic, clinical, laboratory, and mortality data were obtained for analysis. Results: Patients aged 53.8 ± 16.3 years and most were male (80.0%). All patients (100.0%) developed acute cholinergic crisis such as emesis (45.0%), respiratory failure (42.5%), tachycardia (30.0%), kidney injury (22.5%), and seizure (7.5%). Intermediate syndrome developed in 12.5% of patients, but none had delayed neuropathy (0%). The poor prognosis group suffered higher incidences of respiratory failure ( p = 0.011), kidney injury ( p = 0.026), and prolonged corrected QT interval ( p = 0.000), and they had higher blood urea nitrogen level ( p = 0.041), lower Glasgow coma scale score ( p = 0.011), and lower monocyte count ( p = 0.023) than good prognosis group. All patients were treated with atropine and pralidoxime therapy, but six patients (15.0%) still died of intoxication. In a multivariate logistic regression model, blood urea nitrogen was a significant risk factor for poor prognosis (odds ratio: 1.375, 95% confidence interval: 1.001–1.889, p = 0.049). Nevertheless, no mortality risk factor could be identified. Conclusion: The mortality rate of patients with chlorpyrifos intoxication was 15.0%. Furthermore, acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 12.5%, and 0% of patients, respectively.