Characterization of degradation behavior for PLGA in various pH condition by simple liquid chromatography method

The aim of this study was to detect the amount of lactic acid (LA) and glycolic acid (GA) in poly(D,L-lactide-co-glycolide) (PLGA) by development a simple HPLC method and to determine the pH of media, which can influence on degradation of PLGA and drug release. Analysis of in vitro degradation behavior of PLGA with two different molecular weights as 8000 and 33,000 g/mol were performed in various media conditions (pH 3.0, 5.0, 7.0, and 9.0 of PBS and distilled water (approx. pH 5.8)). Also, effect of some additives on PLGA degradation was also investigated in pH 7.0 of PBS. GA and LA were easily detected by a simple HPLC method (retention time: 6.5 min and 10.2 min, respectively). The result showed that GA was released larger amount than that of LA considering the initial sample weight of polymers, due to the higher hydrophilic property. In the lower pH of media conditions, the PLGA was faster degraded generally. The presence of various additives, moreover, affected decrease of pH and slight acceleration of LA and GA detection.     

ESP‐102, a combined extract of Angelica gigas,Saururus chinensis and Schizandra chinensis,protects against glutamate‐induced toxicity in primary cultures of rat cortical cells

It was reported previously that ESP‐102, a combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, significantly improved scopolamine‐induced memory impairment in mice and protected primary cultured rat cortical cells against glutamate‐induced toxicity. To corroborate this effect, the action patterns of ESP‐102 were elucidated using the same in vitro system. ESP‐102 decreased the cellular calcium concentration increased by glutamate, and inhibited the subsequent overproduction of cellular nitric oxide and reactive oxygen species to the level of control cells. It also preserved cellular activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and glutathione reductase reduced in the glutamate‐injured neuronal cells. While a loss of mitochondrial membrane potential was observed in glutamate treated cells, the mitochondrial membrane potential was maintained by ESP‐102. These results support that the actual mechanism of neuroprotective activity of ESP‐102 against glutamate‐induced oxidative stress might be its antioxidative activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Sexual function and psychological characteristics of penile paraffinoma

Aim:To identify the sexual, emotional and psychological status of men who augmented their penis with mineral oil injection for their small penis. Methods: Men who had penile paraffin were asked to answer the semi-structured questionnaire. The questionnaire was designed to assess the motivation, method of penile injection, changes in erectile function and satisfaction after penile injection. SCL (Symptom checklist)-90-R, STAI (State and Trait Anxiety Inventory) and Zung SDS (Self-rating depression scale) were also included in the questionnaire for psycho-logical evaluation. Results: A total of 357 men completed the questionnaire. The first-ranked motivation of the injection was recommendation by their acquaintances (48.9 %). The majority of the respondents had the procedure by non-medical person (78.0 %). Before injection, 17.2 % had a sense of inferiority in their penis and 32 % worried about their weak erectile function. After injection, 33.0 % have found relief from their sense of inferiority and 17.8 % wish to feel improvement in their cr~tile function. Most of the respondents (91%) were not satisfied with their penis and 74 % of them replied that they want to remove the injected material. Only 15.6 % did not experience side effects.Most of the subjects have suffered from various side effects such as inflammation, skin necrosis, pain, etc. No evidence of psychiatric pathology was found in psychological evaluation. Conclusion: The motivations of mineral oil injection were recommendation by their acquaintances or desire to be more mannish. Most of them had suffered from various side effects and only a small number of them felt improvement in their sense of inferiority, in their penis and erectile function. Increased public awareness is needed for the prevention of this physically and psychologically debilitating problem. (Asian J Andro12003 Sep; 5:191-194 )     

Clinical Outcomes after Spinal Cord Stimulation According to Pain Characteristics

ObjectiveSpinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. However, its clinical efficacy in regard to specific types of pain has not been well studied. The primary objective of this study was to retrospectively analyze the clinical outcomes of paddle-type SCS according to the type of neuropathic pain. MethodsSeventeen patients who underwent paddle-lead SCS at our hospital were examined. Clinical outcomes were evaluated pre- and postoperatively (3 months, 1 year, and last follow-up) using the Neuropathic Pain Symptom Inventory (NPSI). The NPSI categorizes pain as superficial, deep, paroxysmal, evoked, or dysesthesia and assess the duration of the pain (pain time score). Changes in NPSI scores were compared with change in Visual analogue scale (VAS) scores. ResultsAfter SCS, the pain time score improved by 45% (independent t-test, p=0.0002) and the deep pain score improved by 58% (independent t-test, p=0.001). Improvements in the pain time score significantly correlated with improvements in the VAS score (r=0.667, p=0.003, Spearman correlation). Additionally, the morphine milligram equivalent value was markedly lower after vs. before surgery (~49 mg, pared t-test, p=0.002). No preoperative value was associated with clinical outcome. ConclusionThe NPSI is a useful tool for evaluating the therapeutic effects of SCS. Chronic use of a paddle-type spinal cord stimulation improved the deep pain and the pain time scores.     

Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells

Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET.     

Effects of Transglutaminase 2 Inhibition on Ventilator-Induced Lung Injury

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

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