Cellular and molecular actions of Methylene Blue in the nervous system

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide‐induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 93–117, 2010     

RGD-grafted thermoreversible polymers to facilitate attachment of BMP-2 responsive C2C12 cells

The purpose of this study was to design thermoreversible biomaterials for enhanced adhesion of bone morphogenetic protein-2 (BMP-2)-responsive cells. Peptides containing the arginine-glycine-aspartic acid (RGD) sequence were conjugated to N-isopropylacrylamide (NiPAM) polymers via amine-reactive N-acryloxysuccinimide (NASI) groups. In monolayer cultures, the adhesion of BMP-2-responsive C2C12 cells to RGD-grafted NiPAM/NASI surfaces was significantly higher than adhesion on ungrafted NiPAM/NASI surfaces. Although the morphology of cells adhered to RGD-grafted NiPAM/NASI surfaces was comparable to cells adhered on tissue culture polystyrene (TCPS), long-term cell growth was limited on the NiPAM/NASI surfaces, even for RGD-grafted surfaces. Treatment of C2C12 cells with recombinant BMP-2 induced dose-dependent osteoblastic differentiation as assessed by alkaline phosphatase (ALP) activity. In the absence of BMP-2, cells cultured on NiPAM/NASI polymers (either grafted with RGD peptide or not) expressed significantly higher levels of ALP activity than the cells cultured on TCPS, indicating that the polymer surfaces induced some osteoblastic activity in C2C12 cells without the need for BMP-2. We conclude that NiPAM-based thermoreversible biomaterials, despite their limited ability to support cell growth, allowed an enhanced expression of the chosen osteogenic marker (ALP) by C2C12 cells in vitro.     

Assessment of cell viability,lipid peroxidation and quantification of DNA fragmentation after the treatment of anticancerous drug mitomycin C and curcumin in cultured human blood lymphocytes

Mitomycin C (MMC) is an antineoplastic agent used to fight a number of different cancers including cancer of the stomach, colon, rectum, pancreas, breast, lung, uterus, cervix, bladder, head, neck, eye and oesophagus. It is a potent DNA cross-linker. The prolonged use of the drug may result in permanent bone marrow damage and other various types of secondary tumors in normal cells. The toxic effect of anticancerous drugs may be reduced if supplemented with natural antioxidants/plant products. With this view, the effect of 5, 10 and 15 μM of curcumin was studied against the genotoxic doses of MMC, i.e. 10 and 20 μM, in cultured human lymphocytes using cell viability, lipid peroxidation and DNA damage quantification as parameters. The treatment of curcumin with MMC results in a significant dose-dependent increase in cell viability and decrease in lipid peroxidation and DNA damage suggesting a protective role of curcumin against the anticancerous drug mitomycin C.     

Assessment of atrial conduction time by tissue Doppler echocardiography and P-wave dispersion in patients with mitral annulus calcification

The aim of our study was to investigate atrial conduction time in patients with mitral annulus calcification (MAC) using P-wave dispersion (PWD) and electromechanical coupling measured with the surface electrocardiogram and the tissue Doppler echocardiography. Fifty-nine patients with MAC and 43 control subjects underwent resting the surface electrocardiogram and tissue Doppler echocardiography. The difference between the maximum (Pmax) and minimum P-wave durations was calculated and defined as PWD. Interatrial and intraatrial electromechanical delays were measured with tissue Doppler echocardiography. Both Pmax and PWD were higher in patients with MAC compared with controls (111.4 ± 15.8 vs 97.3 ± 18.8 milliseconds; P < .0001 and 46.4 ± 14.6 vs 31.4 ± 13.1 milliseconds; P < .0001, respectively). Both interatrial and intraatrial conduction time were also delayed in patients with MAC compared with controls (29.8 ± 13.3 vs 17.6 ± 12.5 milliseconds; P < .0001; 9.4 ± 5.1 vs 6.8 ± 4.0 milliseconds; P < .008, respectively). Left atrial (LA) diameter was significantly higher in patients with MAC compared with controls (35.4 ± 5.0 mm vs 32.3 ± 4.2 mm; P < .001). The LA diameter correlated significantly with both interatrial conduction times and PWD (r = 0.56; P < .0001 and r = 0.47; P < .0001, respectively). There is a delay in both intraatrial and interatrial electromechanical coupling intervals in patients with MAC.     

The effect of metoclopramide on QT dynamicity: double-blind,placebo-controlled,cross-over study in healthy male volunteers

BACKGROUND: Metoclopramide, a central and peripheral dopamine type 2 receptor antagonist, has been used as an attractive and safer alternative to cisapride. However, cardiac side-effects have also been reported with this drug. AIM: To evaluate the effects of intravenous metoclopramide administration on cardiac repolarization using QT dynamicity, a reliable indicator of arrhythmic side-effects. METHODS: The effect of metoclopramide on cardiac repolarization was evaluated in 10 healthy male volunteers in the supine position. Metoclopramide (10 mg) or placebo was administered intravenously at random in a double-blind, cross-over manner to the participants during continuous electrocardiographic recording in the supine position. The 30-min stationary segments of the recordings before and after drug administration were used to investigate QT dynamicity. RESULTS: Metoclopramide administration, but not placebo, resulted in steeper QT/RR slopes compared with the pre-drug values (metoclopramide: 0.037 +/- 0.004 vs. 0.064 +/- 0.012; P = 0.041; placebo: 0.045 +/- 0.006 vs. 0.050 +/- 0.004; P = 0.563). In a two-way analysis of variance model, metoclopramide administration also increased the QT variance independently (F = 6.225, P = 0.023). CONCLUSIONS: Metoclopramide administration increases the QT/RR slope and QT variance. These findings may partly explain the underlying mechanism of ventricular arrhythmias associated with metoclopramide.     

Changes in the sexual functions of male patients and their partners after obesity surgery

Sexual functionality significantly contributes to health-related quality of life and can decrease with obesity. In this study, we aimed to prospectively evaluate the changes that occur in the erection function, sexual function and testosterone level of male patients scheduled to undergo bariatric surgery, as well as the changes in the sexual function of their partner. A total of 40 patients and their partners were included. International Index of Erectile Function-5 (IIEF-5) questionnaire and the Arizona Sexual Experience Scale (ASEX) were filled before and 6 months after surgery by the male patients. The ASEX form was also completed by the partners before and 6 months after the procedure. The height and weight measurements and testosterone values were measured before and after surgery. A statistically significant difference was found between the preoperative and post-operative IIEF-5 scores of the patients (p = 0.000 < 0.01). There was also a statistically significant difference between the patients and their partners’ preoperative and post-operative ASEX scores. We can conclude that the partners of men with preoperative erection complaints also experience sexual dysfunction, and with the post-operative decrease in or disappearance of erection complaints, the sexual function of both male patients and their partners improves.     

Persistent mental symptoms and rabies

<正>We read the case report by Wang and colleagues with great interest.The authors linked persistent mental symptoms of the patient with rabies encephalitis.However,we think that the points listed below should be explained more clearly before this diagnosis can be confirmed.1)The incubation period of rabies is only three days.It was not mentioned which body part was bitten by the dog.If the bite was close to the central nervous system,it would be especially important for development of rabies.