Selective ophthalmic arterial injection using a balloon catheter for retinoblastoma: a seven-year clinical evaluation.

PURPOSE: To evaluate the effectiveness and safety of selective ophthalmic arterial injection (SOAI) for retinoblastoma utilizing a microballoon catheter system with an M chamber. STUDY DESIGN: Retrospective analysis. METHODS AND PATIENTS: This study was sanctioned by theNational Cancer Center Hospital' Independent Ethics Committee. The surgeon was a general interventional radiologist. After confirming that the distal internal carotid artery was not delineated by balloon occlusion and the ophthalmic artery was visualized using digital subtraction angiography, melphalan was manually administered. Notably, in cases presenting bilateral retinoblastoma, both eyes received treatment in a singular, low-dose procedure. Between July 2015 and December 2021, 125 patients with retinoblastoma (68 boys and 57 girls) underwent SOAI at our facility. The average age at initial treatment was 19.3 months. The study covered 250 procedures, with patients undergoing an average of 3.7 procedures. RESULTS: The success rate of the procedure was 99.2%, with a mean procedure duration of 18.3 min. Two distinct technical failures were recorded: one attributed to an internal carotid artery having a wide lumen and the other due to the ophthalmic artery remaining undetected on angiography post-balloon occlusion of the internal carotid artery. Adverse events were minimal but included bronchospasm post-procedure and severe orbital inflammation in 0.8% and 0.4% of cases, respectively. CONCLUSION: SOAI using the microballoon catheter with the M chamber is a feasible and safe procedure for the treatment of retinoblastoma. The success rate was 99.2%. This system can be recommended as intra-arterial chemotherapy for retinoblastoma.

Duration of Remote Ischemic Conditioning and Outcome in Acute Ischemic Stroke.

BACKGROUND: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke. METHODS AND RESULTS: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P=0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P=0.05). CONCLUSIONS: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Identifying spatiotemporal trends of SARS-CoV-2 RNA in wastewater: from the perspective of upstream and downstream wastewater-based epidemiology (WBE).

Recently, many efforts have been made to address the rapid spread of newly identified COVID-19 virus variants. Wastewater-based epidemiology (WBE) is considered a potential early warning tool for identifying the rapid spread of this virus. This study investigated the occurrence of SARS-CoV-2 in eight wastewater treatment plants (WWTPs) and their sewerage systems which serve most of the population in Taoyuan City, Taiwan. Across the entire study period, the wastewater viral concentrations were correlated with the number of COVID-19 cases in each WWTP (Spearman's r = 0.23-0.76). In addition, it is confirmed that several treatment technologies could effectively eliminate the virus RNA from WWTP influent (> 90%). On the other hand, further results revealed that an inverse distance weighted (IDW) interpolation and hotspot model combined with the geographic information system (GIS) method could be applied to analyze the spatiotemporal variations of SARS-CoV-2 in wastewater from the sewer system. In addition, socio-economic factors, namely, population density, land use, and income tax were successfully identified as the potential drivers which substantially affected the onset of the COVID-19 outbreak in Taiwan. Finally, the data obtained from this study can provide a powerful tool in public health decision-making not only in response to the current epidemic situation but also to other epidemic issues in the future.

Time from Onset to Remote Ischemic Conditioning and Clinical Outcome After Acute Moderate Ischemic Stroke.

OBJECTIVE: We conducted a post hoc exploratory analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to determine whether early remote ischemic conditioning (RIC) initiation after stroke onset was associated with clinical outcome in patients with acute moderate ischemic stroke. METHODS: In RICAMIS, patients receiving RIC treatment in the intention-to-treat analysis were divided into 2 groups based on onset-to-treatment time (OTT): early RIC group (OTT ≤ 24 hours) and late RIC group (OTT 24-48 hours). Patients receiving usual care without RIC treatment from intention-to-treat analysis were assigned as the control group. The primary outcome was excellent functional outcome at 90 days. RESULTS: Among 1,776 patients from intention-to-treat analysis, 387 were in the early RIC group, 476 in the late RIC group, and 913 in the control group. In the post hoc exploratory analysis, a higher proportion of excellent functional outcome was found in the early RIC versus control group (adjusted absolute difference = 8.1%, 95% confidence interval [CI] = 2.5%-13.8%, p = 0.005), but no difference in outcomes was detected in the late RIC versus control group (adjusted absolute difference = 3.3%, 95% CI = -2.1% to 8.6%, p = 0.23), or in the early RIC versus late RIC group (adjusted absolute difference = 5.0%, 95% CI = -1.3% to 11.2%, p = 0.12). Similar results were found in the per-protocol analysis. INTERPRETATION: Among patients with acute moderate ischemic stroke who are not candidates for intravenous thrombolysis or endovascular therapy, early RIC initiation within 24 hours of onset may be associated with higher likelihood of excellent clinical outcome. ANN NEUROL 2023;94:561-571.

Ocular toxicity of investigational anti-cancer drugs in early phase clinical trials.

Ocular toxicities arising from anti-cancer drugs occur sporadically and are sometimes underestimated because they are not life-threatening. Reports focusing on ocular toxicities from cancer therapy are limited. We investigated the detailed progress of ocular toxicities of anti-cancer drugs including first-in-class ones. A retrospective review of medical records was conducted for patients who were involved in early phase clinical trials with scheduled ophthalmologic examinations according to their protocols between January 2014 and August 2021. Patients with ocular toxicity suspected to be related to the investigational drugs in the ophthalmic examination were investigated in detail. In total, 37 ocular toxicities related to investigational drugs occurred in 7.6% of patients (33/434). The median age of the 33 patients was 61 years (range, 33-76 years), and 20 were male. Causal drugs with a high incidence of ocular toxicities were HSP90 inhibitors and FGFR inhibitors. Retinopathy was most frequent, while conjunctivitis, dry eye, keratitis, keratopathy, and uveitis were also observed. Dim vision as a subjective finding was a unique adverse event. Most patients developed ocular toxicities even though their dose was below the drug's maximum tolerated dose. Except for one case, all ocular toxicities occurred bilaterally. About 60% (22/37) of ocular toxicity cases needed a temporary hold of the drug. All except for three cases fully recovered. This study reported the risks and timing of the onset of a variety of ocular toxicities of anti-cancer drugs, which were fundamentally controllable. (Trial registration number. Retrospectively registered).

Antiviral Properties of Pennisetum purpureum Extract against Coronaviruses and Enteroviruses.

Many severe epidemics are caused by enteroviruses (EVs) and coronaviruses (CoVs), including feline coronavirus (FCoV) in cats, epidemic diarrhea disease virus (PEDV) in pigs, infectious bronchitis virus (IBV) in chickens, and EV71 in human. Vaccines and antiviral drugs are used to prevent and treat the infection of EVs and CoVs, but the effectiveness is affected due to rapidly changing RNA viruses. Many plant extracts have been proven to have antiviral properties despite the continuous mutations of viruses. Napier grass (Pennisetum purpureum) has high phenolic content and has been used as healthy food materials, livestock feed, biofuels, and more. This study tested the antiviral properties of P. purpureum extract against FCoV, PEDV, IBV, and EV71 by in vitro cytotoxicity assay, TCID50 virus infection assay, and chicken embryo infection assay. The findings showed that P. purpureum extract has the potential of being disinfectant to limit the spread of CoVs and EVs because the extract can inhibit the infection of EV71, FCoV, and PEDV in cells, and significantly reduce the severity of symptoms caused by IBV in chicken embryos.

Nitrogen-Doped Titanium Dioxide Mixed with Calcium Peroxide and Methylcellulose for Dental Bleaching under Visible Light Activation.

The available tooth whitening products in the market contain high concentrations of hydrogen peroxide (H2O2) as an active ingredient. Therefore, in order to curb the high H2O2 concentration and instability of liquid H2O2, this study evaluated the efficacy and cytotoxicity of the bleaching gel composed of 10% calcium peroxide (CaO2) and visible-light-activating nitrogen-doped titanium dioxide (N-TiO2) with methyl cellulose as a thickener. Extracted bovine teeth were discolored using coffee and black tea stain solution and were divided into two groups (n = 6). Bleaching was performed thrice on each tooth specimen in both the groups, with one minute of visible light irradiation during each bleaching time. The CIELAB L*a*b* values were measured pre- and post-bleaching. The N-TiO2 calcinated at 350 °C demonstrated a shift towards the visible light region by narrowing the band gap energy from 3.23 eV to 2.85 eV. The brightness (ΔL) and color difference (ΔE) increased as bleaching progressed each time in both the groups. ANOVA results showed that the number of bleaching significantly affected ΔE (p < 0.05). The formulated bleaching gel exhibits good biocompatibility and non-toxicity upon exposure to 3T3 cells. Our findings showed that CaO2-based bleaching gel at neutral pH could be a stable, safe, and effective substitute for tooth whitening products currently available in the market.

The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes.

Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino- or carboxyl-termini are eliminated by the N- or C-degron pathways, respectively. We aimed to elucidate the function of C-degron pathways and to unveil how normal proteomes are exempt from C-degron pathway-mediated destruction. Our data reveal that C-degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C-degron and N-degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C-degron pathways, but not of defective proteins, suggesting proteolysis-based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways.

Global stability of a pseudorabies virus model with vertical transmission.

Porcine pseudorabies infection is an acute infectious disease caused by pseudorabies virus. In this paper, we formulate a mathematical susceptible-incubating-infected-treated (SEIT) model with vertical transmission. The existence and stability of the equilibrium points of the model are characteri-zed by the basic reproduction number ℜ0. When ℜ0 < 1, we show that the disease free equilibrium is unique and globally asymptotically stable. When ℜ0 > 1 and p1 ≥ max{ß, b}, using the Lyapunov function method and the theory of competitive system, we obtain the global asymptotical stability of a unique disease endemic equilibrium.

Stem Cell-Based Delivery of Gold/Chlorin e6 Nanocomplexes for Combined Photothermal and Photodynamic Therapy.

Combining photothermal and photodynamic modalities has shown encouraging therapeutic efficacy against various malignant cancers. Developing a delivery method for targeting and penetrating tumors is still a major focus for advancing this therapeutic approach. Herein, we report a novel strategy involving the utilization of stem cells as a live carrier to codeliver photothermal and photodynamic agents for cancer therapy. To this end, a novel gold nanorod (AuNR)-PEG-PEI (APP)/chlorin e6 (Ce6)-loaded adipose-derived stem cell (ADSC) system is proposed in which AuNRs and Ce6 act as the photothermal and photodynamic agents, respectively. To integrate with stem cells, the APP/Ce6 nanocomplexes exhibit advantages of low drug leakage, low cytotoxicity, efficient cellular uptake, and redox-responsive release. After loading of APP/Ce6 nanocomplexes, the ADSCs still maintained good tumor tropism and were capable of penetrating into the tumor spheroids. The photothermal effect induced by exposure to near-infrared light irradiation at 808 nm promoted the release of Ce6 from the stem cells into the surroundings and hence increased its availability to treat cancer cells. APP/Ce6-loaded ADSCs exerted effective dose-dependent in vitro anticancer activities via anticipated photothermal and photodynamic effects. In a murine CT26 colon cancer model, APP/Ce6 delivered by ADSCs resulted in superior tumor suppression compared to other delivery strategies. It was also noted that in vivo applications of APP/Ce6-loaded ADSCs did not induce noticeable detrimental effects on normal tissues/organs.

Prospective evaluation of visual function in patients with ocular diseases after robot-assisted laparoscopic prostatectomy.

OBJECTIVES: To investigate intraocular pressure and visual function in patients with ocular diseases undergoing robot-assisted laparoscopic prostatectomy. METHODS: We carried out a prospective clinical study of patients undergoing robot-assisted laparoscopic prostatectomy for localized prostate cancer at The University of Tokyo Hospital from December 2015 to March 2017. An ophthalmologist measured intraocular pressure, and carried out visual field testing at 0-2 months before and 7 days after robot-assisted laparoscopic prostatectomy. During the surgery, an anesthesiologist measured intraocular pressure at specified time points. RESULTS: A total of 110 patients were enrolled and 98 eligible patients were analyzed; 37 were diagnosed with ocular diseases before robotic-assisted laparoscopic prostatectomy (17 with glaucoma, 20 with other ocular diseases). Intraocular pressure significantly increased during robot-assisted laparoscopic prostatectomy. Transient postoperative visual field defect was detected in 24 eyes of 17 patients, including six patients with ocular diseases at 7 days after surgery. At 3 months after surgery, one of 34 glaucomatous eyes and one of 40 eyes with non-glaucomatous ocular diseases continued to show visual field defect, although visual field defect in the remaining patients recovered to preoperative conditions within 3 months. CONCLUSIONS: Our findings suggest that robot-assisted laparoscopic prostatectomy can be safely carried out in patients with ocular diseases, even those with glaucoma, after precautionary consultation with an ophthalmologist.

Entry of Scotophilus Bat Coronavirus-512 and Severe Acute Respiratory Syndrome Coronavirus in Human and Multiple Animal Cells.

Bats are natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Scotophilus bat CoV-512 demonstrates potential for cross-species transmission because its viral RNA and specific antibodies have been detected in three bat species of Taiwan. Understanding the cell tropism of Scotophilus bat CoV-512 is the first step for studying the mechanism of cross-species transmission. In this study, a lentivirus-based pseudovirus was produced using the spike (S) protein of Scotophilus bat CoV-512 or SARS-CoV as a surface protein to test the interaction between coronaviral S protein and its cell receptor on 11 different cells. Susceptible cells expressed red fluorescence protein (RFP) after the entry of RFP-bound green fluorescence protein (GFP)-fused S protein of Scotophilus bat CoV-512 (RFP-Sco-S-eGFP) or RFP-SARS-S pseudovirus, and firefly luciferase (FLuc) activity expressed by cells infected with FLuc-Sco-S-eGFP or FLuc-SARS-S pseudovirus was quantified. Scotophilus bat CoV-512 pseudovirus had significantly higher entry efficiencies in Madin Darby dog kidney epithelial cells (MDCK), black flying fox brain cells (Pabr), and rat small intestine epithelial cells (IEC-6). SARS-CoV pseudovirus had significantly higher entry efficiencies in human embryonic kidney epithelial cells (HEK-293T), pig kidney epithelial cells (PK15), and MDCK cells. These findings demonstrated that Scotophilus bat CoV-512 had a broad host range for cross-species transmission like SARS-CoV.

Gold nanorod-encapsulated biodegradable polymeric matrix for combined photothermal and chemo-cancer therapy.

PURPOSE: A biocompatible nanocomplex system co-encapsulated with gold nanorods (AuNRs) and doxorubicin (DOX) was investigated for its potentials on the combined photothermal- and chemotherapy. MATERIALS AND METHODS: Hydrophobic AuNRs were synthesized by the hexadecyltrimethyl-ammonium bromide (CTAB)-mediated seed growth method, and then, they received two-step surface modifications of polyethylene glycol (PEG) and dodecane. The AuNR/DOX/poly(lactic-co-glycolic acid) (PLGA) nanocomplexes were prepared by emulsifying DOX, AuNR, and PLGA into aqueous polyvinyl alcohol solution by sonication. Human serum albumin (HSA) was used to coat the nanocomplexes to afford HSA/AuNR/DOX-PLGA (HADP). Size and surface potential of the HADP nanocomplexes were determined by using a Zetasizer. Cytotoxicity and cellular uptake of the HADP were analyzed by using MTT assay and flow cytometry, respectively. In vitro anticancer effects of the HADP were studied on various cancer cell lines. To assess the therapeutic efficacy, CT26 tumor-bearing mice were intravenously administered with HADP nanocomplexes and laser treatments, followed by monitoring of the tumor growth and body weight. RESULTS: Size and surface potential of the HADP nanocomplexes were 245.8 nm and -8.6 mV, respectively. Strong photothermal effects were verified on the AuNR-loaded PLGA nanoparticles (NPs) in vitro. Rapid and repeated drug release from the HADP nanocomplexes was successfully achieved by near-infrared (NIR) irradiations. HSA significantly promoted cellular uptake of the HADP nanocomplexes to murine colon cancer cells as demonstrated by cell imaging and flow cytometric studies. By combining photothermal and chemotherapy, the HADP nanocomplexes exhibited strong synergistic anticancer effects in vitro and in vivo. CONCLUSION: An NIR-triggered drug release system by encapsulating hydrophobic AuNR and DOX inside the PLGA NPs has been successfully prepared in this study. The HADP NPs show promising combined photothermal- and chemotherapeutic effects without inducing undesired side effects on a murine colon cancer animal model.

Antibacterial Effects of Magnetically-Controlled Ag/Fe3O4 Nanoparticles.

This paper presents the use of a magnetic manipulation device to remotely control the movement of Ag/Fe3O4 nanoparticles (NPs) for enhancing the antibacterial effect of Ag particles in aqueous suspensions containing Escherichia coli (E.coli). The Ag/Fe3O4 magnetic NPs were prepared by co-precipitation method where the Ag particles are simultaneously synthesized with the Fe3O4 particles to form Ag and Fe3O4 nanocomposite materials. The manipulation system utilized a homogeneous rotating magnetic field to carry out magnetic stirring of NPs in the petri dishes containing bacterial suspensions. The optimum magnetron parameters and best antibacterial effects were implemented with six different concentrations from 0.6 wt % to 6.6 wt % of the NPs at driving frequencies from 50 rpm to 200 rpm for 3 min. The highest antibacterial effect of 99.4% was achieved at 5.4 wt % of NPs and the driving frequency of 100 rpm. A time-dependent antibacterial effect in 0.1 wt % of Ag/Fe3O4 was also observed. The results indicate that the use of specific rotating magnetic fields to manipulate Ag/Fe3O4 magnetic NPs can significantly improve the antibacterial efficacy. Due to the good biocompatibility of the Ag NPs, the presented technique can be applied to clean water resources in the future.

Hedgehog signaling establishes precursors for germline stem cell niches by regulating cell adhesion.

Stem cells require different types of supporting cells, or niches, to control stem cell maintenance and differentiation. However, little is known about how those niches are formed. We report that in the development of the Drosophila melanogaster ovary, the Hedgehog (Hh) gradient sets differential cell affinity for somatic gonadal precursors to specify stromal intermingled cells, which contributes to both germline stem cell maintenance and differentiation niches in the adult. We also report that Traffic Jam (an orthologue of a large Maf transcription factor in mammals) is a novel transcriptional target of Hh signaling to control cell-cell adhesion by negative regulation of E-cadherin expression. Our results demonstrate the role of Hh signaling in niche establishment by segregating somatic cell lineages for differentiation.

Antiviral Activity of Graphene-Silver Nanocomposites against Non-Enveloped and Enveloped Viruses.

The discovery of novel antiviral materials is important because many infectious diseases are caused by viruses. Silver nanoparticles have demonstrated strong antiviral activity, and graphene is a potential antimicrobial material due to its large surface area, high carrier mobility, and biocompatibility. No studies on the antiviral activity of nanomaterials on non-enveloped viruses have been reported. To investigate the antiviral activity of graphene oxide (GO) sheets and GO sheets with silver particles (GO-Ag) against enveloped and non-enveloped viruses, feline coronavirus (FCoV) with an envelope and infectious bursal disease virus (IBDV) without an envelope were chosen. The morphology and sizes of GO and GO-Ag were characterized by transmission, scanning electron microscopy, and X-ray diffraction. A virus inhibition assay was used to identify the antiviral activity of GO and GO-Ag. Go-Ag inhibited 25% of infection by FCoV and 23% by IBDV, whereas GO only inhibited 16% of infection by FCoV but showed no antiviral activity against the infection by IBDV. Further application of GO and GO-Ag can be considered for personal protection equipment to decrease the transmission of viruses.

Synthesis of High Valence Silver-Loaded Mesoporous Silica with Strong Antibacterial Properties.

A simple chemical method was developed for preparing high valence silver (Ag)-loaded mesoporous silica (Ag-ethylenediaminetetraacetic acid (EDTA)-SBA-15), which showed strong antibacterial activity. Ag-EDTA-SBA-15 exhibited stronger and more effective antibacterial activity than commercial Ag nanoparticles did, and it offered high stability of high valence silver in the porous matrix and long-lasting antibacterial activity. The synthesized materials were characterized using Fourier transform infrared spectroscopy, powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) analysis, and transmission electron microscopy (TEM). Ag existed in both surface complexation and Ag particles. EDTA anchored within a porous structure chelated Ag ions in higher oxidation states and prevented their agglomeration and oxidation reduction. The XRD results showed that most Ag in the Ag-EDTA-SBA-15 existed in higher oxidation states such as Ag(II) and Ag(III). However, the XPS and TEM results showed that Ag easily reduced in lower oxidation states and agglomerated as Ag particles on the exterior layer of the SBA-15.

Genotyping of turkey coronavirus field isolates from various geographic locations in the Unites States based on the spike gene.

Turkey flocks have experienced turkey coronaviral enteritis sporadically in the United States since the 1990s. Twenty-four field isolates of turkey coronavirus (TCoV) from multiple states in the United States were recovered from 1994 to 2010 to determine the genetic relationships among them. The entire spike (S) gene of each TCoV isolate was amplified and sequenced. Pairwise comparisons were performed using the Clustal W program, revealing 90.0% to 98.4% sequence identity in the full-length S protein, 77.6% to 96.6% in the amino terminus of the S1 subunit (containing one hypervariable region in S1a), and 92.1% to 99.3% in the S2 subunit at the deduced amino acid sequence level. The conserved motifs, including two cleavage recognition sequences of the S protein, two heptad repeats, the transmembrane domain, and the Golgi retention signal were identified in all TCoV isolates. Phylogenetic analysis based on the full-length S gene was used to distinguish North American TCoV isolates from French TCoV isolates. Among the North American TCoV isolates, three distinct genetic groups with 100% bootstrap support were observed. North Carolina isolates formed group I, Texas isolates formed group II, and Minnesota isolates formed Group III. The S genes of 24 TCoV isolates from the United States remained conserved because they contained predominantly synonymous substitutions. The findings of the present study suggest endemic circulation of distinct TCoV genotypes in different geographic locations.

WSSV-induced crayfish Dscam shows durable immune behavior.

One of the major gaps in our understanding of arthropod specific immune priming concerns the mechanism[s] by which the observed long-term (>2 weeks) protective effects might be mediated. Hypervariable Dscam (Down syndrome cell adhesion molecule) might support arthropod innate immunity with specificity for more extended periods. We show here that, in the relatively long-lived arthropod Cherax quadricarinatus, CqDscam does not behave like a typical, immediately-acting, short-lived innate immune factor: CqDscam was not induced within hours after challenge with a lethal virus, but instead was only up-regulated after 2-5 days. This initial response faded within ∼ 2 weeks, but another maximum was reached ∼ 1 month later. At around 2 months after the initial challenge, the virus-induced CqDscam bound to the virus virion and acted to neutralize the virus However, although CqDscam helped crayfish to survive during persistent infection, it nevertheless failed to provide any enhanced protection against a subsequent WSSV challenge. Thus, CqDscam is capable of supporting extended anti-virus immune memory in arthropods. Also, during a persistent virus infection, the balance of "immune firepower" in crayfish appears to be altered such that the general immune factors become depleted while CqDscam becomes relatively predominant.

Hyperbaric pressure and increased susceptibility to glutamate toxicity in retinal ganglion cells in vitro.

PURPOSE: To investigate the effect of hyperbaric pressure on purified retinal ganglion cells (RGCs) and the additive effect of hyperbaric pressure on glutamate-induced RGC death. METHODS: An RGC primary culture from 8-day-old Wistar rats was prepared and cultured in a hyperbaric chamber. The RGC survival rate under various pressure conditions and with 5 or 25 µM of glutamate stimulation was determined and compared with that of RGCs under isobaric conditions. First, RGCs were cultured at atmospheric pressure (0 mmHg) and under hyperbaric pressure (+30 and +90 mmHg, with pressure fluctuations varying from 0 to +30 or +60 mmHg). Next, RGCs were cultured at +15, +30, and +90 mmHg with the addition of 5 or 25 µM of glutamate. The effects of N-Methyl-D-aspartic acid (NMDA) and 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA)/kainate receptor antagonists, MK-801, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), on cell survival were assessed. Additionally, types of cell death and the induction of Bcl-2-associated X protein (BAX) leading to apoptosis were studied under hyperbaric pressure conditions and/or with 5 µM of glutamate. RESULTS: RGC death was not induced under increasing or fluctuating pressure conditions. RGC death was induced by 25 µM of glutamate and increased as pressure increased. RGC death was not induced by 5 µM of glutamate but was induced by and increased with increasing pressure. MK-801 and DNQX significantly reduced glutamate-induced RGC death, and DNQX was more effective than MK-801. Under hyperbaric pressure conditions, the addition of 5 µM of glutamate resulted in the induction of apoptosis and BAX, which did not occur under hyperbaric pressure conditions or with the addition of glutamate alone. CONCLUSION: In a rat RGC culture, hyperbaric pressure alone did not induce RGC death but increased RGC susceptibility to glutamate toxicity, which may be of relevance to ocular diseases with pressure-induced RGC death.