Gelatin-coated magnetic iron oxide nanoparticles as carrier system: drug loading and in vitro drug release study

Magnetic iron oxide nanoparticles (IOPs) were coated with gelatin A and B and drug-loading efficiency was investigated using doxorubicin (DXR) as a model drug to evaluate their potential as a carrier system for magnetic drug targeting. Drug loading to coated IOPs was done using adsorption as well as desolvation/cross-linking techniques to understand their role. Drug loading by adsorption technique was done by incubating mixture of coated IOPs and drug in various conditions of pH, DXR-to-coated IOPs ratio, gelatin types and IOPs amounts. Drug loading by desolvation/cross-linking technique was done by adding acetone and glutaraldehyde (GTA) to the mixture of coated IOPs and DXR. The results indicated involvement of electrostatic interaction during loading of DXR-to-coated IOPs. Compared to adsorption technique, desolvation/cross-linking technique improved the efficiency of drug loading regardless of type of gelatin used for the coating. The DXR-loaded particles showed pH responsive drug release leading to accelerate release of drug at pH 4 compared to pH 7.4.     

Intraoperative Localization of Insulinoma and Normal Pancreas Using Invisible Near-Infrared Fluorescent Light

Background

Neuroendocrine tumors of the pancreas, such as insulinoma, are difficult to localize, and complete resection is essential for cure. Our hypothesis is that a near-infrared (NIR) fluorophore exhibiting uptake in insulinoma could provide high-sensitivity detection intraoperatively.

Materials and Methods

The optical properties of methylene blue (MB) were measured in vitro in 100% serum at 37°C and in vivo after tissue uptake. MB was injected as a rapid intravenous bolus at doses ranging from 0.25 to 2 mg/kg into wildtype rats and pigs, and into insulinoma-bearing transgenic mice. The FLARE^? imaging system was used to acquire color video and NIR fluorescence images simultaneously and in real-time. The signal-to-background ratios (SBR) of tissues and tumors were quantified using FLARE^? software.

Results

When appropriately diluted, MB exhibits moderate NIR fluorescence emission peaking at 688 nm. At doses ≥1 mg/kg, certain normal tissues, such as pancreas, accumulate MB and remain NIR fluorescent for up to 1 h with an SBR ≥ 1.6. MB spectral properties are maintained after uptake into tissue. Interestingly, insulinoma exhibits even higher MB signal than normal pancreas, resulting in insulinoma-to-pancreas ratios of 3.7 and insulinoma-to-muscle ratios of 16.2. MB permitted high-sensitivity, real-time localization of primary, multicentric, and metastatic insulinoma and permitted differentiation among tumor, normal pancreas, and other abdominal structures.

Conclusion

A single intravenous injection of a clinically available, commonly used NIR fluorophore provides prolonged intraoperative localization of normal pancreas and insulinoma using invisible NIR fluorescent light.     

Reliability of MRI Findings of Peroneal Tendinopathy in Patients with Lateral Chronic Ankle Instability

Background

Patients with chronic lateral ankle instability also have peroneal tendinopathy often. However, preoperative MRIs of these patients are vague in many cases. Our study was performed to see the reliability of MRI findings of peroneal tendinopathy in patients with chronic lateral ankle instability.

Methods

MRI images for 82 patients who had chronic lateral ankle instability, and had received surgical treatment between March 2006 and November 2009 were compared with impressions from operating rooms. The mean age of patients was 36.4 years (range, 15 to 64 years), 82 ankles were studied, and patients with rheumatoid diseases were excluded from the study.

Results

Of the 82 cases, 26 were true positives, 38 true negatives, 13 false positives and 5 false negatives. Of 39 cases of peroneal tendinopathy diagnosed from MRI, 14 had peroneal tendon partial tears, 15 tenosynovitis, 3 dislocations, 17 low-lying muscle bellies, and 6 peroneus quartus muscles. Of 31 cases of peroneal tendinopathy observed in surgery 11 had peroneal tendon partial tears, 4 tenosynovitis, 5 dislocations, 12 low-lying muscle belliess, and 1 peroneus quartus muscle. Sensitivity and specificity of peroneal tendinopathy were 83.9% and 74.5%, respectively. Positive predictive value was 66.7%. Negative predictive value was 88.4%. Accuracy rate was 78.0%.

Conclusions

MRI is a useful diagnostic tool for detecting peroneal tendinopathy in patients with chronic lateral ankle instability. However, MRI is vague in many cases. Therefore, a thorough delicate physical examination and careful observation is needed.     

Usimines A-C, bioactive usnic acid derivatives from the Antarctic lichen Stereocaulon alpinum

Usimines A-C ( 1- 3), three new usnic acid derivatives, have been isolated from a MeOH extract of the Antarctic lichen Stereocaulon alpinum by various chromatographic methods. The structures of 1- 3 were determined by analysis of their spectroscopic data (NMR, UV, MS) and by chemical methods. The known compound usnic acid ( 4) was also obtained. Compounds 1- 4 showed moderate inhibitory activity against therapeutically targeted protein tyrosine phosphatase 1B (PTP1B).     

The effect of acupuncture at PC-6 on the electroencephalogram and electrocardiogram

The present study aims to examine the effect of acupuncture stimulation of an acupuncture point (PC-6) and nonacupuncture point on electroencephalograms (EEGs) and electrocardiograms (ECGs). We used EEG in 10 healthy subjects to investigate cortical activation during stimulation of acupuncture points (neiguan: PC-6) and nonacupuncture points. Our most interesting finding was the marked differences of amplitude of EEG power between acupuncture points and nonacupuncture points stimulation. Wavelet transform was used as the EEG signal processing method, because it has advantages in a time domain and frequency domain characteristics analysis. EEGs were collected from 16 channels, and the alpha-wave (8-13 Hz), beta-wave (13-30 Hz), theta-wave (4-8 Hz) and delta-wave (0.5-4 Hz) were used as standards for frequency bands. According to the experiment results, EEG signals increased considerably after acupuncture stimulation; in each frequency band, the average amplitude was higher after acupuncture stimulation; ECG heart rates were faster by at least 10% after acupuncture stimulation. Consequently, it will be possible to verify the function of acupuncture stimulation on neiguan (acupuncture points; PC-6) more effectively.     

Encapsulation of Fe3O4 in gelatin nanoparticles: effect of different parameters on size and stability of the colloidal dispersion

Encapsulation of magnetite (IOPs) in gelatin nanoparticles has been carried out by in situ precipitation of the particles in presence of gelatin, followed by desolvation and cross-linking of the composite nanoparticles. The aim of the study was to investigate the effect of various formulation parameters (viz; desolvating agent, cross-linking agent and percentage of IOPs) on the hydrodynamic size of the gelatin-coated magnetic iron oxide composite nanoparticles (GIOPs) and stability of the colloidal dispersion. Extensive characterization by dynamic light scattering, thermogravimetric analysis, X-ray diffraction, infrared spectroscopy, transmission electron microscopy and atomic force microscopy shows complete encapsulation of IOPs of size below 8 nm into gelatin nanoparticles of varying size. Size as well as stability of the colloidal dispersion of the GIOPs was found to be dependent on the investigated parameters. Furthermore, the nanoparticle dispersion was found to be stable in pH ranges from 2-12. Thus, obtained composite nanoparticles could hold promise as a carrier system in biomedical applications.     

Effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells

The effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalpalactone at 5–30 μM decreased intracellular dopamine content with the IC₅₀ value of 22.1 μM. Catalpalactone at 5–20 μM, but not 30 μM, did not alter cell viability. Catalpalactone at 20 μM inhibited tyrosine hydroxylase (TH) and aromatic-l-amino acid decarboxylase (AADC) activities. Catalpalactone also decreased cyclic AMP levels and inhibited TH phosphorylation. In addition, catalpalactone at 20 μM reduced the increases in dopamine levels induced by L-DOPA (20–50 μM). Catalpalactone (5–30 μM) associated with L-DOPA (50–100 μM) enhanced L-DOPA-induced cytotoxicity at 48 h, which was prevented by N-acetyl-l-cysteine. These results suggest that catalpalactone inhibited dopamine biosynthesis by reducing TH and AADC activities and enhanced L-DOPA-induced cytotoxiciy in PC12 cells.     

A study of South Korean casino employees and gambling problems

Background Casino employees are exposed to disproportionatelyhigh levels of gambling, drinking and smoking compared to otheroccupations. Because of their occupation, they have the opportunityto detect and prevent pathological gambling (PG). Aims To identify differences in the mental health status andsocial attitudes towards PG among casino workers in South Koreadepending upon whether they report any gambling problems. Methods Data were collected from 388 full-time casino employees.This data provided information about the prevalence of gamblingproblems, alcohol and tobacco use and depression. Employeeswere grouped according to their scores on the Korean versionof South Oaks Gambling Screen (SOGS), and those employees whogambled without experiencing any gambling problems (Group NP:SOGS = 0) and those who reported any gambling problems (GroupP: SOGS > 0) were compared. An exploratory factor analysesidentified the domains of casino employee social attitudes towardsgambling. Results Employees who reported gambling problems (Group P) reporteda higher prevalence of smoking, alcohol problems and depression(P < 0.01) compared to employees who did not report gamblingproblems (Group NP). The primary employee social attitude towardsgambling was identified by the factor of ‘Disease concept/socialawareness’. Group NP reported more positive attitudesin this domain than Group P (P < 0.01). Conclusions Employees who reported any gambling problems reporteda less positive attitude towards developing the public healthsystem to be responsive to gambling problems. These findingsindicate a need to develop health education programmes thatfocus more specifically on casino employees with gambling problems.