Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus.

Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid E max model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 μg/mL, respectively. The BBCs (32-64 μg/mL) and MBECs (64-256 μg/mL) of these study strains were much higher than their corresponding BPC values (1-2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R (2) = 96.2%) and the MBIC (fT > MBIC, R (2) = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R (2) = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating S. aureus biofilm-related infections

Ba-enhanced dwarf and subgiant stars in the LAMOST Galactic surveys

Ba-enhanced stars are interesting probes of stellar astrophysics and Galactic formation history. In this work, we investigate the chemistry and kinematics for a large sample of Ba-enhanced ([Ba/Fe]$>$1.0) dwarf and subgiant stars with $5000 < T_{\rm eff }< 6700$\,K from LAMOST. We find that both stellar internal evolution process and external mass exchange due to binary evolution are responsible for the origins of the Ba-enhancement of our sample stars. About one third of them exhibit C and N enhancement and ultraviolet brightness excess, indicating they are products of binary evolution. The remaining Ba-enhanced stars with normal C and N abundances are mostly warm stars with $T_{\rm eff} > 6000$\,K. They are likely consequences of stellar internal elemental transport processes, but they show very different elemental patterns to the hotter Am/Fm stars. Our results reveal a substantially lack of high-[$\alpha$/Fe] Ba-enhanced stars in the [Fe/H]--[$\alpha$/Fe] plane, which we dub as a {\em high-$\alpha$ desert}. We suggest it is due to a lower efficiency for producing Ba-enhanced stars by low-mass AGB progenitors in binary systems. Our results call for detailed modellings for these Ba-enhanced stellar peculiars, in the context of both stellar internal elemental transport and external mass accretion.Comment: 20 pages, 17 figures. Accepted for publication in Ap

Src-family protein tyrosine kinases: a promising target for treating chronic pain

Abstract Despite growing knowledge of the mechanisms of chronic pain, it remains a major challenge facing clinical practice. Src-family protein tyrosine kinases (SFKs), a group of non-receptor protein tyrosine kinases, have been implicated in neuronal development and synaptic plasticity. SFKs are critically central to various transmembrane receptors e.g. G-protein coupled receptor (GPCR), EphB receptor (EphBR), increased intracellular calcium, epidermal growth factor (EGF) and other growth factors that regulate the phosphorylation of N-methyl-D-aspartic acid receptor (NMDAR) 2B subunit, thus contributing to the development of chronic pain. SFKs have also been regarded as an important point of convergence of intracellular signaling components that regulate microglia functions and the immune response. Additionally, intrathecal administration of SFKs inhibitors significantly alleviates mechanical allodynia in different chronic pain models. Thus, here we reviewed the current evidence of the role of SFKs in the development of chronic pain caused by complete Freund's adjuvant (CFA) injection, peripheral nerve injury (PNI), streptozotocin (STZ) injection and bone metastasis. Moreover, the role of SFKs on the development of morphine tolerance has also been discussed. Management of SFKs therefore emerged as a potential therapeutic target for the treatment of chronic pain in terms of safety and efficacy. Key words Chronic pain; Src-family protein tyrosine kinases; N-methyl-D-aspartic acid receptor; Microglia

Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice

Aims. To determine whether multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (≤1 year after disease onset; 1A) or late (1–3 years after onset; 2A) MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B) received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2): 7.37% versus 8.21%; 12 months (T3): 7.61% versus 8.41%; 24/36 months (T4/T5): 7.61% versus 8.72%; all P<0.05), but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; P=0.04). Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; P<0.05). Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management

The relationship between hepatic resistin overexpression and inflammation in patients with nonalcoholic steatohepatitis

BACKGROUND: The relationship between resistin and non-alcoholic steatohepatitis (NASH) is not clear, some studies claimed that serum resistin levels were associated with neither the presence of NASH nor its severity, others declared that serum resistin was related with inflammation and fibrosis in NASH. Our animal study verified that the distribution of resistin in the liver is correlated with inflammation in NASH. However, there is no pertinent study in humans. METHODS: Thirty patients with NASH, 28 simple steatosis, and 43 controls were recruited. Blood was collected for resistin, liver chemistries, fasting insulin and some metabolic parameters. Liver histology was scored according to NAFLD activity scoring system. Hepatic resistin expression was examined by real-time polymerase chain reaction, immunohistochemistry. Resistin protein expression was confirmed by western blotting in 13 patients with concomitant NAFLD and gallstone. RESULTS: Serum resistin was significantly elevated in both NASH and simple steatotic subjects compared with controls (all P < 0.05). Hepatic resistin was significantly increased in NASH patients in both mRNA and protein levels than those in simple steatosis and control subjects (all P < 0.05). Both serum and hepatic resistin had a correlation with obesity, but not with insulin resistance. The distribution of resistin positive cells was predominantly in perisinusoidal cells (such as Kupffer cells and hepatic stellate cells) in human NASH. Multivariate analysis revealed that waist-hip ratio, higher serum triglyceride, and hyperresistinemia were independent factors related to higher grade of steatosis; whereas hepatic resistin and serum cytokeratin predict NASH and severity of liver fibrosis. CONCLUSIONS: Hepatic resistin overexpression in NASH patients is associated with the severity of liver inflammation and fibrosis. Liver-derived resistin may be involved in the pathogenesis of human NASH

Separation and economic recovery of strontium from Nanyishan oil-field water, China

The mass ratio of Ca to Sr is greater than 10 in Nanyishan oil-field water, which causes significant problems during the economic extraction and recovery of selected trace elements in the oil-field water. The oilfield water was isothermally evaporated and various salts such as Li, K, Mg, Ca, Na, Sr, Rb, Cs, Br, and I were obtained from the solution. The Sr content of each phase was determined by ICP-AES, the Sr distribution rule in this process was obtained, and the best separation stage for Sr was identified, to optimize the separation of Sr from Nanyishan oil-field water

Epidemiology and outcomes of anal abscess in patients on chronic dialysis: a 14-year retrospective study

OBJECTIVES: We conducted this retrospective study to elucidate the clinical presentation and outcomes of anal abscess in chronic dialysis patients. METHODS: We performed a chart review of patients who were hospitalized for anal abscess from Jan. 2002 to Dec. 2015. A total of 3,074 episodes of anal abscess were identified. Of these, 43 chronic dialysis patients with first-time anal abscess were enrolled. Patients were divided into a surgical group and a nonsurgical group according to the treatment received during hospitalization. The baseline characteristics, clinical findings, treatments and outcomes were obtained and analyzed. The endpoints of this study were in-hospital mortality, one-year mortality and one-year recurrence. RESULTS: Of the 43 patients, 27 (62.7%) received surgical treatment, and 16 (37.2%) received antibiotic treatment alone. There was no significant difference in age, sex, body mass index, smoking habits, comorbidities, or dialysis characteristics between the two groups. Perianal abscess was the most common type of anal abscess, and 39.5% of patients experienced fistula formation. Most patients had mixed aerobic and anaerobic flora. Our data demonstrate that there was no significant difference in hospital stay, one-year survival or recurrence rate between the surgical group and nonsurgical group. However, there was a trend toward better in-hospital survival in patients who received surgical treatment (p=0.082). CONCLUSION: In chronic dialysis patients with anal abscess, there was no statistically significant difference in clinical presentation and outcomes between the surgical and nonsurgical groups, although the surgical group had a trend of better in-hospital survival

The Other Press, February 19, 1987

<p>Energy profile (in kcal.mol^-1) of face-on path for Erlotinib bioactivation by the Cpd I model of CYP3A4 and 1A2 in the gas and solvent phases.</p