Neuroprotective effect of mexiletine in the central nervous system of diabetic rats

Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord.30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05).This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.     

Voltammetric discrimination of mandelic acid enantiomers

We report a novel electrochemical biosensor for direct discrimination of d- and l-mandelic acid (d- and l-MA) in aqueous medium. The glassy carbon electrode (GCE) surface was modified with reduced graphene oxide (rGO) and γ-globulin (GLOB). Electrochemical characterization of the modified electrodes was investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The modified electrode surfaces were also characterized by scanning electron microscopy. Electrochemical response of the prepared electrode (GCE/rGO/GLOB) for discrimination of d- and l-MA enantiomers was investigated by cyclic voltammetry and was compared with bare GCE in the concentration range of 2 to 10 mM. Whereas the bare GCE showed no electrochemical response for the MA enantiomers, the GCE/rGO/GLOB electrode exhibited direct and selective discrimination with different oxidation potential values of 1.47 and 1.71 V and weak reduction peaks at potential values of −1.37 and −1.48 V, respectively. In addition, electrochemical performance of the modified electrode was investigated in mixed solution of d- and l-MA. The results show that the produced electrode can be used as electrochemical chiral biosensor for MA.     

Improving of Catalase Stability Properties by Encapsulation in Alginate/Fe3O4 Magnetic Composite Beads for Enzymatic Removal of H2O2

The aim of this study was enhancing of stability properties of catalase enzyme by encapsulation in alginate/nanomagnetic beads. Amounts of carrier (10–100 mg) and enzyme concentrations (0.25–1.5 mg/mL) were analyzed to optimize immobilization conditions. Also, the optimum temperature (25–50°C), optimum pH (3.0–8.0), kinetic parameters, thermal stability (20–70°C), pH stability (4.0–9.0) operational stability (0–390 min), and reusability were investigated for characterization of the immobilized catalase system. The optimum pH levels of both free and immobilized catalase were 7.0. At the thermal stability studies, the magnetic catalase beads protected 90% activity, while free catalase maintained only 10% activity at 70°C. The thermal profile of magnetic catalase beads was spread over a large area. Similarly, this system indicated the improving of the pH stability. The reusability, which is especially important for industrial applications, was also determined. Thus, the activity analysis was done 50 times in succession. Catalase encapsulated magnetic alginate beads protected 83% activity after 50 cycles.     

Dynamic thiol/disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer

Abstract

Thiol groups are important anti-oxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species (ROS). The aim of our study is to evaluate thiol–disulphide homeostasis with a novel recent automated method in patients with localized prostate cancer (PC) before and six months after radical prostatectomy (RP). 18 patients with PC and 17 healthy control subjects were enrolled into the study. Blood samples were collected from the controls subjects and patients before and six months after RP. Thiol–disulphide homeostasis was determined using a recently developed novel method. Prostate-specific antigen (PSA), albumin, total protein, total thiol, native thiol, disulphide and total antioxidant status (TAS) were measured and compared between the groups. Native thiol, total thiol and TAS levels were significantly higher in the control group than the patients before RP (p?<?.001). There was a non-significant increase in the native thiol, total thiol and TAS levels in the patients six months after RP in comparison to the levels before RP (p values .3, .3 and .09, respectively). We found a significant negative correlation between PSA and thiol levels. Our study demonstrated that the decreased thiol and TAS levels weakened anti-oxidant defence mechanism in the patients with PC as indicated. Increased oxidative stress in prostate cancer patients may cause metabolic disturbance and have a role in the aetiopathogenesis of prostate cancer.     

The effects of tracking responses and the day of mailing on physician survey response rate: three randomized trials

Background

The response rates to physician postal surveys remain modest. The primary objective of this study was to assess the effect of tracking responses on physician survey response rate (i.e., determining whether each potential participant has responded or not). A secondary objective was to assess the effects of day of mailing (Monday vs. Friday) on physician survey response rate.

Methods

We conducted 3 randomized controlled trials. The first 2 trials had a 2×2 factorial design and tested the effect of day of mailing (Monday vs. Friday) and of tracking vs. no tracking responses. The third trial tested the effect of day of mailing (Monday vs. Friday). We meta-analyzed these 3 trials using a random effects model.

Results

The total number of participants in the 3 trials was 1339. The response rate with tracked mailing was not statistically different from that with non-tracked mailing by the time of the first reminder (RR = 1.01 95% CI 0.84, 1.22; I² = 0%). There was a trend towards lower response rate with tracked mailing by the time of the second reminder (RR = 0.91; 95% CI 0.78, 1.06; I² = 0%). The response rate with mailing on Mondays was not statistically different from that with Friday mailing by the time of first reminder (RR = 1.01; 95% CI 0.87, 1.17; I² = 0%), and by the time of the 2^nd reminder (RR = 1.08; 95% CI 0.84, 1.39; I² = 77%).

Conclusions

Tracking response may negatively affect physicians'' response rate. The day of mailing does not appear to affect physicians'' response rate.     

Enzymatic characterization of a serralysin-like metalloprotease from the entomopathogen bacterium, Xenorhabdus

We investigated the enzymatic properties of a serralysin-type metalloenzyme, provisionally named as protease B, which is secreted by Xenorhabdus bacterium, and probably is the ortholog of PrA peptidase of Photorhabdus bacterium. Testing the activity on twenty-two oligopeptide substrates we found that protease B requires at least three amino acids N-terminal to the scissile bond for detectable hydrolysis. On such substrate protease B was clearly specific for positively charged residues (Arg and Lys) at the P1 substrate position and was rather permissive in the others. Interestingly however, it preferred Ser at P1 in the oligopeptide substrate which contained amino acids also C-terminal to the scissile bond, and was cleaved with the highest k(cat)/K(M) value. The pH profile of activity, similarly to other serralysins, has a wide peak with high values between pH 6.5 and 8.0. The activity was slightly increased by Cu(2+) and Co(2+) ions, it was not sensitive for serine protease inhibitors, but it was inhibited by 1,10-phenanthroline, features shared by many Zn-metalloproteases. At the same time, EDTA inhibited the activity only partially even either after long incubation or in excess amount, and Zn(2+) was inhibitory (both are unusual among serralysins). The 1,10-phenanthroline inhibited activity could be restored with the addition of Mn(2+), Cu(2+) and Co(2+) up to 90-200% of its original value, while Zn(2+) was inefficient. We propose that both the Zn inhibition of protease B activity and its resistance to EDTA inhibition might be caused by an Asp in position 191 where most of the serralysins contain Asn.