Measurement of α-dicarbonyl compounds in human saliva by pre-column derivatization HPLC.

Background α-Dicarbonyl compounds (α-DCs) have been detected in body fluids including plasma and urine and elevation of this sort of compounds in vivo has been associated with the development of many kinds of chronic diseases. However whether α-DCs are present in human saliva, and if their presence/absence can be related with various chronic diseases is yet to be determined. Methods In this study, a pre-column derivatization HPLC-UV method was developed to measure 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane-2,3-dione (PD) in human saliva employing 4-(2,3-dimethyl-6-quinoxalinyl)-1,2-benzenediamine (DQB) as a derivatizing reagent. The derivatization of the α-DCs is fast and the conditions are facile. The method was evaluated and the results show that it is suitable for the quantification of α-DCs in human saliva. Results In the measurements of these α-DCs in the saliva of 15 healthy subjects and 23 type 2 diabetes mellitus (T2DM) patients, we found that the concentrations of GO and MGO in the saliva of the diabetic patients were significantly higher than those in healthy subjects. As far as we know, this is the first time that salivary α-DC concentrations have been determined and associated with T2DM. Conclusions The developed method would be useful for the measurement of the salivary α-DC levels and the data acquired could be informative in the early screening for diabetes.

Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats.

AIM: To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats. METHODS: The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres. RESULTS: rhEPO was almost completely released from the PLGA microspheres in vitro, following zero-order release kinetics over approximately 30 d. After intramuscular injection (10,000 or 30,000 IU rhEPO/kg) in the rats, the serum rhEPO concentration reached maximum levels on d 1, then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism. A good linear correlation (R(2)=0.98) was obtained between the in vitro and in vivo release data. A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10,000 or 30,000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO. CONCLUSION: The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month.

Singlet Oxygen-Responsive Polymeric Nanomedicine for Light-Controlled Drug Release and Image-Guided Photodynamic-Chemo Combination Therapy.

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.

Liposomal bupivacaine versus interscalene nerve block for pain control after total shoulder arthroplasty: A systematic review and meta-analysis.

OBJECTIVE: To illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain management after total shoulder arthroplasty. METHODS: A systematic search was performed in Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Data on patients prepared for total shoulder arthroplasty in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) and opioid consumption. Fixed/random effect model was used according to the heterogeneity tested by I2 statistic. Software of Stata 11.0 was used for pooling the final outcomes. RESULTS: Four randomized controlled trials (RCTs) including 510 patients met the inclusion criteria. The present meta-analysis indicated that there were no significant differences between groups in terms of VAS score at 12 h, 24 h, and 48 h (p > 0.05). No significant differences were found regarding to opioid consumption at postoperative 12 h, 24 h and 48 h (p > 0.05). CONCLUSION: Compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and opioid consumption. Higher quality RCTs are required for further research.