Antioxidant therapy in the management of acute,chronic and post-ERCP pancreatitis:A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis （AP） or chronic pancreatitis （CP） and in the prevention of post-endoscopic retrograde cholangio-pancreatography （post-ERCP） pancreatitis （PEP） up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous.Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PER Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.

Oxidative Stress During Antituberculous Therapy in Young and Elderly Patients

Using allantoin (ATN ) as a marker for reactive oxygen species (ROS), oxidative stress during antituberculous (anti-TB) therapy was compared in 10 young and 9 elderly patients.Before treatment, ATN plasma concentrations in patients were similar to that of volunteers. Administration of a combination of isoniazid (INH ), rifampicin (RIF) and pyrazinamid e (PZA) increased plasma ATN in both groups of patients. ATN concentrations (M± SE) at six hours were higher (P <0.05 ) in elderly than in young patients on day one,8.22 ± 1.50 vs 1.89 ± 0.98 μg/mL); day 30, (5.85 ± 0.82 vs 0.87 ± 0.57 μg/mL; and day 90, (4.84 ± 1.24 vs 0.52 ± 0.50μg/mL). Because total amount of ATN excreted was similar in both groups on the three occasions, more ATN was formed in elderly than young patients. In conclusion, there was more oxidative stress in elderly than young patients. It is thereby suggested that Anti-TB drugs induce formation of ROS and elderly patients are at a greater risk of toxicity probably because of poor antioxidant mechanisms

Mesoporous polydopamine nanoplatforms loaded with calcium ascorbate for amplified oxidation and photothermal combination cancer therapy

Destruction of cellular redox homeostasis to induce cancer cell apoptosis is an emerging tumor therapeutic strategy. To achieve this goal, elevating exogenous oxidative stress or impairing the antioxidant defense system of cancer cells is an effective method. Herein, we firstly report a biocompatible and versatile nanoplatform based on mesoporous polydopamine (MpDA) nanoparticles and a phase-change material (PCM) for delivering calcium ascorbate (Vc-Ca), simultaneously enabling combination therapy of hyperthermia, reactive oxygen species (ROS) generation, and suppression of tumor antioxidant capability. In this design, Vc-Ca encapsulated in MpDA using PCM is controllably released due to the melting of PCM matrix in response to photothermal heating upon near-infrared irradiation. Vc-Ca is proved to be a prooxidant that can promote the production of ROS (H2O2) in the tumor site. Remarkably, MpDA can not only act as a photothermal agent but also can break the redox balance of cancer cells through depleting the primary antioxidant glutathione, thus amplifying Vc-Ca-mediated oxidative therapy. Both in vitro and in vivo results demonstrate the significantly enhanced antitumor activity of boosted ROS combined with local hyperthermia. This study highlights the potential applications of Vc-Ca in cancer treatment, and the prepared multifunctional nanoplatform provides a novel paradigm for highefficiency oxidation-photothermal therapy.

EFFECT OF ACUPUNCTURE ON BLOOD OXYGEN FREE RADICAL AND NO LEVELS IN TREATMENT OF APOPLECTIC SEQUELAE

Objective: To observe the effect of acupuncture on blood oxygen free radical (OFR) and nitric oxide (NO) levels in the treatment of apoplectic sequelae. Methods: A total of 61 cases of apoplectic patients were subjected into this study and randomly divided into "JIN San Zhen" group (n=30) and control group (n=31). Blood lipid peroxidase (LPO), superoxide dismutase (SOD), glutathione peroxidase(GSH Px) and nitric oxide (NO) contents before and after acupuncture treatment were determined with radioimmunoassay. In both groups, acupuncture was given once daily, six times a week, with 4 weeks being a therapeutic course and with the interval between two weeks being a week, 3 courses all together. In "JIN San Zhen" group, acupoints of "JIN San Zhen" were used predominately, while in control group, scalp point Motor Sensory Area (MS 8) was used as the main point. Results: Self comparison showed that after 3 courses of treatment, in both groups, LPO and NO levels decreased significantly (P<0.05-0.01), SOD and GST Px values increased considerably (P<0.05-0.01). Comparison between two groups indicated that the effects of "JIN San Zhen" group are significantly superior to those of control group in raising blood SOD and GST Px levels (P<0.05-0.01) and in lowering blood NO content (P<0.01). Analysis on the correlation between the restoration of neural function and the changes of LPO, SOD and GST Px levels suggested that the effect of acupuncture in improving neural function may be related to changes of the aforementioned indexes. Conclusion: Acupuncture therapy can significantly lower blood LPO and NO levels and evidently raise blood SOD and GST Px levels in stroke patients.

NIR-Ⅱ-absorbing conjugated polymer-based theranostic agent for NIR-Ⅱfluorescence imaging-guided photothermal therapy acting synergistically with tumor microenvironment-responsive nitric oxide therapy

Despite tremendous advances in gas therapy,there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug delivery.Second near-infrared(NIR-Ⅱ)window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive nature.In this study,we engineered an NIR-Ⅱlaser-activated theranostic agent(named CP-bF@PEG)that was composed of amphiphilic polymers(Pluronic F127,with polyethylene glycol,PEG,moieties)coated with an NIR-Ⅱ-absorbing conjugated polymer(PTTBBT,CP)and nitric oxide(NO)donor(benzofuroxan,bF),which served as an NIR-Ⅱphotothermal inducer and NO nanogenerator.Under deep tissue penetration of NIR-Ⅱlaser irradiation,CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal effect.Moreover,CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable manner.This NIR-Ⅱ-absorbing polymer for high-contrast NIR-Ⅱfluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy,as evidenced by pronounced tumor therapeutic efficacy and few side effects.This nanotheranostic agent is a highly promising candidate for high-contrast NIR-Ⅱimaging-guided precision photothermal therapy combined with gas therapy against cancer.

GSH-triggered sequential catalysis for tumor imaging and eradication based on star-like Au/Pt enzyme carrier system

Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.