Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

Thermal Injury Induces Small Heat Shock Protein in the Optic Nerve Head In Vivo.

PURPOSE: To investigate the induction pattern of various heat shock protein (HSP) in the optic nerve head after thermal stress using transpupillary thermotherapy and to determine the dose-response relationship of thermal stress on the induction of various HSP. METHODS: The 810-nm diode laser with 50-µm spot size was aimed to the center of optic nerve head of right eye of Norway brown rats. First, the various exposure powers (100, 120, 140 mW) were used with the same exposure duration, 60 seconds, to investigate power dosing effect. Second, the various exposure durations (1, 2, 3, and 5 minutes) were applied under constant 100 mW laser power to investigate time dosing effect. Left eyes were served as controls. To quantify HSP expression, enucleation was performed at 24 hours after transpupillary thermotherapy. HSP 27 and αB-crystallin inductions in optic nerve head were examined with Western blot. RESULTS: All type of HSP was observed in normal state. After thermal injury, the expression of HSP 27 were increased, and the αB-crystallin were decreased. CONCLUSIONS: Induction pattern of each HSP in the optic nerve head were different after thermal injury. Some HSPs were induced or exhausted. Further research is needed on the characteristic functions and induction conditions of each HSP.

Visual outcomes and associated factors of primary congenital glaucoma in children.

PURPOSE: We evaluated the long-term visual outcomes in children with primary congenital glaucoma and determined the factors associated with the final visual outcomes. METHODS: Medical records of children with primary congenital glaucoma between 2005 and 2016, seen at Seoul National University Children's Hospital in South Korea, were reviewed. The minimum follow-up period after surgery for primary congenital glaucoma was 3 years. Visual acuity (VA) was categorized into good (≧20/70) and poor (< 20/70). Factors including age, VA, refractive errors, intraocular pressure (IOP), laterality, and cup-to-disc (C/D) ratio were compared between the groups. RESULTS: A total of 71 eyes of 44 patients were included. The patients' age at the time of surgery was 14.7 ± 12.2 months. The mean IOP was 28.3 ± 7.0 mmHg. During 6.7 ± 2.7 years of mean follow-up after surgery, 39 eyes (54.9%) needed occlusion treatment. After occlusion, patients with lower IOP values, lesser additional surgeries, reversal of optic disc cupping, and better initially measured VA achieved a better visual outcome. At the final assessment, the mean age was 7.8 ± 2.6 years, and the mean VA gain was 15.0 ± 19.4 letters. There were 44 eyes (62.0%) with VA ≧20/70. CONCLUSIONS: In children with primary congenital glaucoma, IOP control and the optic disc configuration over time are important factors associated with visual outcome. Regular follow-up and correction of refractive errors-along with occlusion for those with difference in VA between the two eyes-might be helpful for achieving better visual outcomes.

Strain-specific anti-biofilm and antibiotic-potentiating activity of 3',4'-difluoroquercetin.

Antibacterial properties of 3',4'-difluoroquercetin (di-F-Q), a fluorine-substituted stable quercetin derivative, were investigated. Even though di-F-Q itself did not show interesting antibacterial activity, treatment of the Staphylococcus aureus strains with di-F-Q resulted in a dose-dependent reduction in biofilm formation with IC50 values of 1.8 ~ 5.3 mg/L. Also, the antibacterial activity of ceftazidime (CAZ) against carbapenem-resistant Pseudomonas aeruginosa (CRPA) showed eightfold decrease upon combination with di-F-Q. Assessment of the antimicrobial activity of CAZ in combination with di-F-Q against 50 clinical isolates of P. aeruginosa confirmed 15.7% increase in the percentages of susceptible P. aeruginosa isolates upon addition of di-F-Q to CAZ. Further mechanistic studies revealed that di-F-Q affected the antibiotics efflux system in CRPA but not the ß-lactamase activity. Thus, di-F-Q was almost equally effective as carbonyl cyanide m-chlorophenyl hydrazine in inhibiting antibiotic efflux by P. aeruginosa. In vivo evaluation of the therapeutic efficacy of CAZ-(di-F-Q) combination against P. aeruginosa showed 20% of the mice treated with CAZ-(di-F-Q) survived after 7 days in IMP carbapenemase-producing multidrug-resistant P. aeruginosa infection group while no mice treated with CAZ alone survived after 2 days. Taken together, di-F-Q demonstrated unique strain-specific antimicrobial properties including anti-biofilm and antibiotic-potentiating activity against S. aureus and P. aeruginosa, respectively.

Temporal Raphe Sign in Elderly Patients With Large Optic Disc Cupping: Its Evaluation as a Predictive Factor for Glaucoma Conversion.

PURPOSE: To determine baseline clinical features associated with conversion to glaucoma in elderly patients with large optic-disc cupping. DESIGN: Retrospective cohort study. METHODS: Seventy-two eyes of 72 untreated elderly (≥65-year-old) patients with large vertical cup-to-disc ratio (CDR ≥0.7) and without any other glaucomatous findings were included. They had undergone a full ophthalmologic examination twice per year for at least 5 years. The optic nerve head (ONH), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell-inner plexiform layer (GCIPL) were imaged with Cirrus high-definition optical coherence tomography (OCT). Presence of temporal raphe sign on the OCT's GCIPL thickness map was assessed as one of the morphologic factors. Conversion to normal-tension glaucoma (NTG) was defined as structural or functional deterioration on either red-free RNFL photography or standard automated perimetry, respectively. The utility of the baseline factors associated with conversion to NTG were identified. RESULTS: During the 5.5-year follow-up, 19 eyes (26.4%) converted to NTG. There were no significant differences in demographics, systemic factors, intraocular pressure factors, or OCT parameters between the nonconverters and converters. Interestingly, the temporal raphe sign was observed in the converters (18/19, 94.7%) much more frequently than in the nonconverters (3/53, 5.7%, P < .001) at baseline. A Cox proportional hazards model indicated the significant influences of temporal raphe sign positivity (hazard ratio 6.823, 95% confidence interval 2.574, 18.088, P < .001) on conversion to NTG. CONCLUSIONS: In elderly subjects with large CDR, temporal raphe sign positivity on the baseline macular GCIPL thickness map was associated with faster conversion to NTG.

Effects of consumption of coffee, tea, or soft drinks on open-angle glaucoma: Korea National Health and Nutrition Examination Survey 2010 to 2011.

We sought to investigate the association between consumption of coffee, tea, or soft drinks and risk of open-angle glaucoma (OAG) among Koreans using nationwide population-based data. This cross-sectional survey was performed through the Korea National Health and Nutrition Examination Survey 2010 to 2011. Participants older than 19 years were included in the sample for analysis after excluding those with any missing data. The diagnosis of OAG was based on the International Society of Geographical and Epidemiological Ophthalmology criteria, and participants without glaucomatous optic neuropathy served as controls. The frequency of beverage consumption during the past 12 months was obtained through a questionnaire. Multivariate logistic regression models were used to determine the relationship between consumption of each type of beverage and prevalence of OAG. A total of 6,681 participants was included in the analysis. The prevalence of OAG was 4.4% (n = 323), including 5.4% (n = 169) among men and 3.5% (n = 154) among women. After adjusting for multiple covariates, coffee consumption was significantly associated with OAG, while no significant association was found between consumption of tea or soft drinks and OAG. Participants who drank coffee had a higher risk of having OAG compared with those who did not drink coffee (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.22-4.72; p = 0.011). In sex-stratified analyses, the robust association of coffee consumption with OAG was observed in men (OR, 3.98; 95% CI, 1.71-9.25; p = 0.001) but not in women. Our results suggest that coffee consumption may affect the risk of OAG, particularly in men.

Selection of an appropriate empiric antibiotic regimen in hematogenous vertebral osteomyelitis.

BACKGROUND: Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO. METHOD: We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. RESULTS: In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). CONCLUSIONS: Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.

Combined Use of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Event-based Progression Analysis.

PURPOSE: To evaluate patterns of glaucomatous structural progression using the combined retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) event-based progression analysis feature provided by spectral-domain optical coherence tomography (SD-OCT)'s - (GPA) software. DESIGN: Retrospective observational case series. METHODS: Seventy-nine (79) patients were identified with open-angle glaucoma (OAG) showing clinically confirmed structural progression within a minimum 3-year follow-up period. For each eye, RNFL and GCIPL GPA data were obtained from serial SD-OCT data from 2012 to 2017. An integrated GPA map thereafter was merged by vascular landmark-guided superimposition of RNFL and GCIPL GPA event-based progression maps onto the RNFL imagery (resulting in what we call the GPA PanoMap). The GPA PanoMap progression patterns were classified as (1) RNFL-only, (2) GCIPL-only, (3) concurrent (both RNFL and GCIPL), (4) GCIPL after RNFL, and (5) RNFL after GCIPL. The locations of structural progression were classified, based on an earlier schematic model, as (1) superior vulnerability zone (SVZ), (2) papillomacular bundle (PM), (3) macular vulnerability zone (MVZ), and (4) inferoinferior portion. Structural progression patterns on the GPA PanoMap were evaluated according to the location of progression. Among the eyes with progression in the inferior hemiretina, structural progression patterns on the GPA PanoMap were evaluated according to the baseline structural damage. RESULTS: On the GPA PanoMap, when structural progression was located in the SVZ or inferoinferior portion, it was detected only in the RNFL area; when progression was located in the PM or MVZ, various patterns were observed, among which the concurrent pattern was the majority in both areas (43.8% and 45.6% in the PM and MVZ, respectively). Among the eyes with progression in the inferior hemiretina (n = 66), the location of progression varied but did not differ significantly according to the baseline deviation map (P = .440). The progression patterns of MVZ were significantly different among the baseline deviation map patterns (P = .023); however, all of the progression patterns of the inferoinferior portion were RNFL-only. CONCLUSION: The various progression patterns were confirmed according to the locations and baseline patterns of glaucomatous structural change on the integrated GPA map (GPA PanoMap). Combined use of RNFL and GCIPL GPA or the GPA PanoMap could be useful for determination of structural progression and understanding of its patterns in patients with glaucoma.

Hospital-acquired fever in oriental medical hospitals.

BACKGROUND: Traditional Oriental medicine is used in many Asian countries and involves herbal medicines, acupuncture, moxibustion, and cupping. We investigated the incidence and causes of hospital-acquired fever (HAF) and the characteristics of febrile inpatients in Oriental medical hospitals (OMHs). METHODS: Patients hospitalized in two OMHs of a university medical institute in Seoul, Korea, were retrospectively reviewed from 2006 to 2013. Adult patients with HAF were enrolled. RESULTS: There were 560 cases of HAF (5.0%). Infection, non-infection, and unknown cause were noted in 331 cases (59.1%), 109 cases (19.5%), and 120 cases (21.4%) of HAF, respectively. Respiratory tract infection was the most common cause (51.2%) of infectious fever, followed by urinary tract infection. Drug fever due to herbal medicine was the most common cause of non-infectious fever (53.1%), followed by procedure-related fever caused by oriental medical procedures. The infection group had higher white blood cell count (WBC) (10,400/mm3 vs. 7000/mm3, p < 0.001) and more frequent history of antibiotic therapy (29.6% vs. 15.1%, p < 0.001). Multivariate analysis showed that older age (odds ratio (OR) 1.67, 95% confidence interval (C.I.) 1.08-2.56, p = 0.020), history of antibiotic therapy (OR 3.17, C.I. 1.85-5.41, p < 0.001), and WBC > 10,000/mm3 (OR 2.22, C.I. 1.85-3.32, p < 0.001) were associated with infection. CONCLUSIONS: Compared to previous studies on HAF in Western medicine, the incidence of HAF in OMHs was not high. However, Oriental medical treatment does play some role in HAF. Fever in patients with history of antibiotic therapy, or high WBC was more likely of infectious origin.

Early administration of appropriate antimicrobial agents to improve the outcome of carbapenem-resistant Acinetobacter baumannii complex bacteraemic pneumonia.

Carbapenem-resistant Acinetobacter baumannii complex (CRABC) is an emerging pathogen that causes bloodstream infections and nosocomial pneumonia. This study aimed to describe severe infection associated with CRABC bacteraemic pneumonia and to investigate risk factors for 28-day mortality. All patients aged ≥18 years with CRABC bacteraemic pneumonia were enrolled retrospectively at five teaching hospitals in South Korea. Empirical antimicrobial therapy was defined as appropriate if administration of at least one antimicrobial agent, to which the causative pathogen was susceptible, for >48 h, within 5 days of the onset of bacteraemia. During the study period, 146 patients with CRABC bacteraemic pneumonia were enrolled. Among them, 128 (87.7%) patients were treated in the intensive care unit; of these, 110 (75.3%) had ventilator-associated pneumonia. A total of 42 patients (28.8%) received appropriate empirical therapy. There was no difference in baseline characteristics between the appropriate and inappropriate empirical treatment groups. However, 28-day mortality was higher in the inappropriate therapy group (54.8% vs. 76.9%; P = 0.008). Multivariate Cox regression analysis revealed that Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥20 [hazard ratio (HR) = 1.28, 95% confidence interval (CI) 1.04-1.58; P = 0.02], septic shock (HR = 3.49, 95% CI 2.15-5.67; P <0.001) and inappropriate empirical therapy (HR = 3.24, 95% CI 1.94-5.42; P <0.001) were independently associated with an adverse outcome. In conclusion, the mortality rate of CRABC bacteraemic pneumonia was extremely high. Appropriate empirical therapy might improve the outcome of patients with CRABC bacteraemic pneumonia.

Giant Magnetic Heat Induction of Magnesium-Doped γ-Fe2 O3 Superparamagnetic Nanoparticles for Completely Killing Tumors.

Magnetic fluid hyperthermia has been recently considered as a Renaissance of cancer treatment modality due to its remarkably low side effects and high treatment efficacy compared to conventional chemotheraphy or radiotheraphy. However, insufficient AC induction heating power at a biological safe range of AC magnetic field (Happl ·fappl < 3.0-5.0 × 109 A m-1 s-1 ), and highly required biocompatibility of superparamagnetic nanoparticle (SPNP) hyperthermia agents are still remained as critical challenges for successful clinical hyperthermia applications. Here, newly developed highly biocompatible magnesium shallow doped γ-Fe2 O3 (Mg0.13 -γFe2 O3 ) SPNPs with exceptionally high intrinsic loss power (ILP) in a range of 14 nH m2 kg-1 , which is an ≈100 times higher than that of commercial Fe3 O4 (Feridex, ILP = 0.15 nH m2 kg-1 ) at Happl ·fappl = 1.23 × 109 A m-1 s-1 are reported. The significantly enhanced heat induction characteristics of Mg0.13 -γFe2 O3 are primarily due to the dramatically enhanced out-of-phase magnetic susceptibility and magnetically tailored AC/DC magnetic softness resulted from the systematically controlled Mg2+ cations distribution and concentrations in octahedral site Fe vacancies of γ-Fe2 O3 instead of well-known Fe3 O4 SPNPs. In vitro and in vivo magnetic hyperthermia studies using Mg0.13 -γFe2 O3 nanofluids are conducted to estimate bioavailability and biofeasibility. Mg0.13 -γFe2 O3 nanofluids show promising hyperthermia effects to completely kill the tumors.

Double Anterior Segmental Osteotomy Under Local Anesthesia for Correcting Adult Protrusion With Thin Alveolus and Ankylosed Tooth.

BACKGROUNDS: This paper describes an additional benefit in double anterior segmental osteotomy to correct severe anterior protrusion in adult patients with extremely thin mandibular alveolus and ankylosed tooth. For the optimal anterior segmental retraction, an ankylosed posterior tooth needed surgical inclination reposition. During anterior segmental osteotomy surgery under local anesthesia, additional single tooth osteotomy was performed without challenge. METHODS: For anterior segment retraction, osteotomy cuts were made by the surgeon to define a block of bone embedding 6 mandibular anterior teeth. First premolars were extracted during initial orthodontic treatment period. But the ankylosed lower left lateral incisor and lower right second premolar root which remains mesially with uprighted crown hindered further anterior segment retraction. The authors removed cortical bone around second premolar root and repositioned to be upright. Anterior segment was retracted to proper position utilizing the space gained. RESULT: Thin alveolar mandibular anterior segment retraction and the second premolar uprighting were managed effectively with additional single tooth segmental osteotomy during anterior segmental osteotomy. CONCLUSION: Double anterior segmental osteotomy can be an effective alternative to conventional orthognathic surgery in selected adult patients.

Temporal Relation between Macular Ganglion Cell-Inner Plexiform Layer Loss and Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma.

PURPOSE: To investigate the temporal relationship between inferior macular ganglion cell-inner plexiform layer (mGCIPL) loss and corresponding peripapillary retinal nerve fiber layer (pRNFL) defect on the optical coherence tomography (OCT) deviation map in glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 151 patients with early-stage glaucoma (visual field [VF] mean deviation between -1.5 and -5.5 decibels [dB]). METHODS: Spectral-domain OCT mGCIPL and pRNFL deviation maps were obtained for the baseline (from January 2012 to August 2012) and again for the follow-up (from January 2015 to August 2015). An integrated deviation map thereafter was merged by vascular landmark-guided superimposition of mGCIPL and pRNFL deviation maps onto RNFL imagery. On the basis of an earlier schematic model, the inferotemporal peripapillary area was divided into (1) the macular vulnerability zone (MVZ) and (2) the inferoinferior portion. MAIN OUTCOME MEASURES: Temporal sequence of inferior mGCIPL loss and corresponding pRNFL (i.e., pRNFL in MVZ) defect on integrated deviation map. RESULTS: At baseline, 99 (65.6%) of the 151 eyes showed inferior mGCIPL loss. In addition, 112 eyes (74.2%) and 5 eyes (3.3%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. At the 3-year follow-up, 112 (74.2%) of the eyes showed inferior mGCIPL loss, whereas 123 eyes (81.5%) and 25 eyes (16.6%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. Ninety-four eyes initially showed inferior mGCIPL loss without pRNFL defect in the MVZ; among them, 19 (20.2%) subsequently showed defect during the 3-year follow-up interval. Meanwhile, among the 52 eyes without preexisting inferior mGCIPL loss, only 1 (1.9%; P < 0.001) developed a pRNFL defect in the MVZ during the 3-year follow-up interval. CONCLUSIONS: In eyes with early glaucoma, mGCIPL change is frequently detected before corresponding pRNFL change. This could be the result of a superior sensitivity of mGCIPL deviation map that allows detection of an abnormality in the mGCIPL thickness earlier. In this light, OCT pRNFL analysis alone likely would overlook macular damage. Macular OCT imaging should be included in the imaging algorithm for the serial observation of patients with glaucoma.

Understanding the reasons for loss to follow-up in patients with glaucoma at a tertiary referral teaching hospital in Korea.

BACKGROUND/AIMS: To assess the reasons and factors for discontinuation of follow-up among patients with glaucoma at a tertiary referral teaching hospital in Seoul, Korea. METHODS: We identified all adult patients with glaucoma (≥18 years), who had visited the glaucoma clinic of Seoul National University Hospital between April 2012 and March 2014 and had missed an appointment by at least 12 months. These patients were traced via cellular phone, and their true status and reasons for discontinuation of follow-up were documented. RESULTS: A total of 6848 patients with glaucoma (3512 men and 3336 women) were considered. Among them, 247 (3.61%) had missed a scheduled appointment by 12 months or more. Among 230 (93.1%) who were successfully traced, 4 (1.7%) had died and 96 (41.7%) had self-transferred to another glaucoma clinic. Of the 130 patients left, 123 (94.6%) had treatment and follow-up interruptions, and 7 (5.4%) had been treated with alternative medicine. The two main reasons cited for treatment and follow-up interruptions were lack of understanding regarding the necessity of follow-up (46.3%) and unawareness of appointment schedule (30.9%). In stepwise linear regression analysis, older age (p=0.001. ß=0.13), male gender (p=0.013, ß=0.08) and lower baseline intraocular pressure (p=0.005, ß=0.11) were independently associated with follow-up loss involving treatment interruptions. CONCLUSIONS: This study's results emphasise the need for ongoing educational support and improved appointment notification, especially for the elderly, men and patients with low baseline intraocular pressure.

Magnetically softened iron oxide (MSIO) nanofluid and its application to thermally-induced heat shock proteins for ocular neuroprotection.

Magnetically softened iron oxide (MSIO) nanofluid, PEGylated (Mn0.5Zn0.5)Fe2O4, was successfully developed for local induction of heat shock proteins (HSPs) 72 in retinal ganglion cells (RGCs) for ocular neuroprotection. The MSIO nanofluid showed significantly enhanced alternating current (AC) magnetic heat induction characteristics including exceptionally high SLP (Specific Loss Power, > 2000 W/g). This phenomenon was resulted from the dramatically improved AC magnetic softness of MSIO caused by the magnetically tailored Mn(2+) and Zn(2+) distributions in Fe3O4. In addition, the MSIO nanofluid with ultra-thin surface coating layer thickness and high monodispersity allowed for a higher cellular uptake up to a 52.5% with RGCs and enhancing "relaxation power" for higher AC heating capability. The RGCs cultured with MSIO nanofluid successfully induced HSPs 72 by magnetic nanofluid hyperthermia (MNFH). Moreover, it was interestingly observed that systematic control of "AC magnetically-induced heating up rate" reaching to a constant heating temperature of HSPs 72 induction allowed to achieve maximized induction efficiency at the slowest AC heating up rate during MNFH. In addition to in-vitro experimental verification, the studies of MSIO infusion behavior using animal models and a newly designed magnetic coil system demonstrated that the MSIO has promising biotechnical feasibility for thermally-induced HSPs agents in future glaucoma clinics.

Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis.

BACKGROUND: In this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules. METHODS: Male Sprague-Dawley rats were induced focal cerebral ischemia by a transient middle cerebral artery occlusion (tMCAO) for 90 min, and then orally administrated with the water extract of A. gigas hairy roots (AG). After 24 h reperfusion, infarction volume and the changes of BBB permeability were measured by TTC and Evans Blue (EB) staining. The neuronal cell damage and the activation of glial cells were assessed by immunohistochemistry in the ischemic brain. The expression of angiogenesis-induced proteins such as angiopoietin-1 (Ang-1), and vascular endothelial growth factor (VEGF), inflammatory protein such as intercellular adhesion molecule-1 (CAM-1), tight junction proteins such as ZO-1, and Occludin and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT were determined in the ischemic brains by Western blot, respectively. RESULTS: The treatment of AG extract significantly decreased the volumes of brain infarction, and edema in MACO-induced ischemic rats. AG extract decreased the increase of BBB permeability, and neuronal death and inhibited the activation of astrocytes and microglia in ischemic brains. AG extract also significantly increased the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin through activation of the PI3K/Akt pathway. AG extract significantly increased the expression of ICAM-1 in ischemic brains. CONCLUSIONS: Our results indicate that the hairy root of AG has a neuroprotective effect in ischemic stroke.

Trimeric intracellular cation channels and sarcoplasmic/endoplasmic reticulum calcium homeostasis.

Trimeric intracellular cation channels (TRIC) represents a novel class of trimeric intracellular cation channels. Two TRIC isoforms have been identified in both the human and the mouse genomes: TRIC-A, a subtype predominantly expressed in the sarcoplasmic reticulum (SR) of muscle cells, and TRIC-B, a ubiquitous subtype expressed in the endoplasmic reticulum (ER) of all tissues. Genetic ablation of either TRIC-A or TRIC-B leads to compromised K(+) permeation and Ca(2+) release across the SR/ER membrane, supporting the hypothesis that TRIC channels provide a counter balancing K(+) flux that reduces SR/ER membrane depolarization for maintenance of the electrochemical gradient that drives SR/ER Ca(2+) release. TRIC-A and TRIC-B seem to have differential functions in Ca(2+) signaling in excitable and nonexcitable cells. Tric-a(-/-) mice display defective Ca(2+) sparks and spontaneous transient outward currents in arterial smooth muscle and develop hypertension, in addition to skeletal muscle dysfunction. Knockout of TRIC-B results in abnormal IP3 receptor-mediated Ca(2+) release in airway epithelial cells, respiratory defects, and neonatal lethality. Double knockout mice lacking both TRIC-A and TRIC-B show embryonic lethality as a result of cardiac arrest. Such an aggravated lethality indicates that TRIC-A and TRIC-B share complementary physiological functions in Ca(2+) signaling in embryonic cardiomyocytes. Tric-a(-/-) and Tric-b(+/-) mice are viable and susceptible to stress-induced heart failure. Recent evidence suggests that TRIC-A directly modulates the function of the cardiac ryanodine receptor 2 Ca(2+) release channel, which in turn controls store-overload-induced Ca(2+) release from the SR. Thus, the TRIC channels, in addition to providing a countercurrent for SR/ER Ca(2+) release, may also function as accessory proteins that directly modulate the ryanodine receptor/IP3 receptor channel functions.

Physical contribution of Néel and Brown relaxation to interpreting intracellular hyperthermia characteristics using superparamagnetic nanofluids.

In this work, the AC magnetically-induced heating characteristics of various viscous nanofluids with either soft ferrite (Fe3O4) or hard ferrite (CoFe2O4) superparamagnetic nanoparticles (SPNPs) were investigated to empirically and physically interpret the contribution of "Néel relaxation loss power, P(Néel relaxation loss)," or "Brown relaxation loss power, P(Brown relaxation loss)," to the total AC heat generation of intracellular hyperthermia or in-vivo hyperthermia. It was found that the contribution of P(Brown relaxation loss) to the total AC heating power, P(totaI), and the specific loss power (SLP) was severely affected by the surrounding environment (or in-vivo environment) while the contribution of P(Néel relaxation loss) to the P(total) was independent of the variation of surrounding environment. Furthermore, all the theoretical and experimental results strongly suggested that highly efficacious intracellular hyperthermia (or in-vivo hyperthermia) modality can be achieved by enhancing the P(Néel relaxation loss) rather than the P(Brown relaxation loss) of SPNP agents in nanofluids.

Effect of the semen extract of Thuja orientalis on inflammatory responses in transient focal cerebral ischemia rat model and LPS-stimulated BV-2 microglia.

In the central nervous system inflammation is dependent upon the synthesis of various inflammatory mediators by local neurons, astrocytes and especially microglia. In this study, we investigated the anti-inflammatory activities of the semen extract of Thuja orientalis (Thujae Orientalis Semen; TOS) on transient middle cerebral artery occlusion (tMCAO)-induced ischemia in rats and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokine, interleukin (IL)-1ß in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. TOS extract significantly decreased the infarction volumes of ischemic brains and also inhibited microglia activation and neuronal death. In addition, TOS extract significantly decreased the production of NO, PGE(2) and IL-1ß in LPS-stimulated BV-2 microglia. TOS extract also attenuated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-1ß mRNAs and proteins in activated microglia. Furthermore, TOS extract significantly suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. Our results indicate that TOS extract is capable of inhibiting microglia activation in an ischemic brain through the down-regulation of inflammatory responses, suggesting that the TOS extract may have therapeutic potential as an anti-inflammatory drug for ischemic stroke.