Epiretinal membrane appearance or progression after intravitreal injection in age-related macular degeneration.

BACKGROUND: The purpose of this study is to evaluate the influence of anti-vascular endothelial growth factor (VEGF) in the appearance or progression of epiretinal membranes (ERMs) in age-related macular degeneration (ARMD) and investigate confounding factors causing ERMs. METHODS: Seventy-six eyes that were treated for more than 36 months from the first anti-VEGF injection were assessed. Binary logistic regression analysis was performed between smoking, lens status, subretinal hemorrhage, posterior vitreous detachment (PVD) status, peripheral retinal degeneration, type of AMD, conditions of contralateral eye, and the number of injections as independent variables and appearance or progression of ERMs during 36 months as dependent variables. RESULTS: The presence of vitreomacular adhesion (VMA) or development of PVD during the observation period was significantly associated (Odds ratio [OR]: 5.77; 95% confidence interval [CI], 1.72-19.4; p = 0.005) with the appearance or progression of ERMs. Moreover, peripheral retinal degeneration was significantly associated (OR: 3.87; 95% CI, 1.15-13.0; p = 0.029). Injection number of anti-VEGF was not significantly associated (OR: 1.02; 95% CI, 0.90-1.16; p = 0.72). CONCLUSION: This study suggests possibilities that anti-VEGF injections alone are unable to cause the development of ERMs, that VMA or developing PVD has a prior impact on the developing ERMs in ARMD similar to that of idiopathic ERMs, and that peripheral retinal degenerations and vitreomacular adhesion were both related to ERMs development and pathogenesis of ARMD.

Important factors in left atrial posterior wall isolation using 28-mm cryoballoon ablation for persistent atrial fibrillation-Block line or isolation area?

INTRODUCTION: Left atrial (LA) roof ablation using the cryoballoon technique, combined with pulmonary vein isolation (PVI), has been reported to be beneficial for ablation therapy in patients with persistent atrial fibrillation (AF). Left posterior wall ablation also results in improved patient outcomes. However, the contribution of these techniques to the success of cryoballoon ablation (CBA) treatment of AF is not known. The present study examined the influence of the roofline block and isolation area on outcomes after CBA. METHODS AND RESULTS: We enrolled 78 patients with persistent AF. LA roof ablation was performed using a 28-mm cryoballoon with a single freezing of 3 minutes at each region (median number of freezes: 4) after PVI. After CBA, bipolar voltage amplitude mapping was performed during sinus rhythm using the NavX mapping system. Patients were divided into two subgroups according to the voltage and activation map: the roof-conduction (n = 46) and roofline-block groups (n = 32). Atrial tachyarrhythmia recurred in 20 patients of the conduction group and 4 patients of the roofline-block group. The rate of 12-month freedom from tachyarrhythmia after a single ablation procedure was 78% (95% confidence interval [CI], 60%-89%) in the roofline-block group and 45% (95% CI, 30%-60%) in the conduction group (P = .048). Cox proportional hazard analysis revealed that the isolated area was not a significant predictor of recurrence (hazard ratio, 0.94; 95% CI, 0.86-1.02; P = .15). CONCLUSION: Creating a complete roofline block is the major factor predicting the maintenance of sinus rhythm in patients with persistent AF.

Fluorinated Kavalactone Inhibited RANKL-Induced Osteoclast Differentiation of RAW264 Cells.

Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 µM. A partial structure-activity relationship study revealed the importance of fluorine and its position within the 5,6-dehydrokawain skeleton. The results of a pit formation assay suggested that compound 22 prevents osteoclastic bone resorption by inhibiting osteoclastogenesis. Moreover, compound 22 downregulated mRNA expression levels of RANKL-induced nuclear factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes. These results suggest that (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one scaffold could lead to the identification of new anti-resorptive agents.

A relation between ablation area and outcome of ablation using 28-mm cryoballon ablation: Importance of carina region.

INTRODUCTION: Pulmonary vein isolation (PVI) with wide antral ablation leads to better outcomes in atrial fibrillation ablation therapy, but the ablation area is relatively small during cryoballoon ablation (CBA). The present study tested the hypothesis that wide ablation can lead to better outcomes in CBA. METHODS AND RESULTS: Ninety-six patients with atrial fibrillation were enrolled (paroxysmal 76%, 64.1 ± 11.7 years). All patients underwent preprocedural computed tomography and the PV diameter at left atrial PV junction was measured. PV isolation was performed using a 28-mm CB for 3 minutes with single freezing. Sinus rhythm bipolar voltage amplitude maps with the NavX mapping system were generated after ablation. According to the voltage map, patients were divided into 3 subgroups (68 in the extensive isolation group, 17 in the individual isolation group, and 10 in the incomplete isolation group). Atrial tachyarrhythmias recurred in 9 patients of the extensive isolation group and 6 in the individual isolation group. The rate of 12-month freedom from tachyarrhythmia after a single ablation procedure was 84% (95% confidence interval [C.I.], 72%-91%) in the extensive group and 57% (95% C.I., 28%-78%) in the individual group (P = 0.048). Multiple logistic regression analyses revealed that maximal PV diameter was the only predictor to achieve extensive PVI (odds ratio, 1.57; 95% C.I. 1.08-2.29 P = 0.018). CONCLUSION: Extensive isolation is superior to individual isolation for achieving freedom from atrial arrhythmia in long term follow-up by CBA. Evaluating PV diameter at the left atrial PV junction is essential for applying CBA.

Evaluation of Inhibitory Activities of UK-2A, an Antimycin-Type Antibiotic, and Its Synthetic Analogues against the Production of Anti-inflammatory Cytokine IL-4.

The inhibitory activities of the antimycin-class antibiotics UK-2A, antimycin A, and splenocin B against the production of anti-inflammatory cytokine IL-4, which is related to IgE-mediated allergic responses in rat basophilic leukemia (RBL-2H3) cells, were evaluated. Although antimycin A and splenocin B showed cytotoxicity at concentrations at which IL-4 release from the cells was restricted, UK-2A was found to restrict IL-4 release without cytotoxicity. Three UK-2A analogues (4-6) were then synthesized and assessed. Compound 5 restricted IL-4 release dose-dependently without cytotoxicity, and its effect was more potent than that of UK-2A.

Evaluation of Aculeatin and Toddaculin Isolated from Toddalia asiatica as Anti-inflammatory Agents in LPS-Stimulated RAW264 Macrophages.

Anti-inflammatory activity of aculeatin and toddaculin, which are coumarins with a similar structure isolated from Toddalia asiatica (L.) LAM., was evaluated using lipopolysaccharide (LPS)-stimulated RAW264 mouse macrophage cells. Both aculeatin and toddaculin significantly inhibited mRNA expression of inflammatory mediators and nitric oxide production. Furthermore, Toddaculin suppressed LPS-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 and inhibited LPS-induced activation of nuclear factor-kappaB (NF-κB). However, aculeatin did not exhibit such effects, suggesting that aculeatin and toddaculin suppress LPS-induced inflammation of RAW264 cells via different mechanisms. The cellular uptake of these compounds was also evaluated. Toddaculin was detected in RAW264 cells after 4 and 24 h. However, aculeatin levels were not observed in RAW264 cells at all incubation intervals. These results indicate that de-epoxidation of a prenyl group can increase hydrophobicity of molecule and is thought to accelerate cellular uptake and/or interactions with the phospholipid bilayers of cell membranes.

Comparison of external doses between radio-contaminated areas and areas with high natural terrestrial background using the individual dosimeter 'D-shuttle' 75 months after the Fukushima Daiichi nuclear power plant accident.

After the Fukushima Daiichi nuclear power plant accident, the air dose gradually decreases every year due to the physical decay of radioactive materials and environmental changes, as well as countermeasures. However, there is little information on personal behavioural patterns and individual dose from external exposure among the inhabitants around the nuclear power plant. To evaluate the dose from external exposure in Minamisoma city, and compare the differences with outside Fukushima Prefecture, we started the external dose assessment project in cooperation with city officials in Minamisoma and three other cities in Japan where the natural terrestrial background radiation level is relatively high. In these four cities, external dose was measured every hour for two weeks using an individual electronic dosimeter D-shuttle. The places of activity of participants were recorded every hour to compare and evaluate the dose from external exposure, and to clarify whether there is a difference in the exposure dose by behaviour. The annual effective doses from external exposure for 100 participants from four municipalities ranged from 0.566 to 1.295 with a mean value of 0.784 mSv, which was below the level where it is necessary to initiate further remedial actions. Mean external dose in Minamisoma city (0.820 mSv/year) was comparable to those in municipalities with a relatively high natural radiation background in Japan (0.793, 0.806, and 0.718 mSv/year in Fukuyama, Nanto, and Tajimi, respectively). The time spent at home and in the workplace accounted for most of the time of the participants, and this also contributed to the majority of the total dose from external exposure. The amount of exposure at times other than while at home or in the workplace was very small regardless of the indoor or outdoor location in the city. For future dose reduction and radiation protection, continuous dosimetry and countermeasures at home and in the workplace are important for individuals who present high values.

Synthesis of novel 5,6-dehydrokawain analogs as osteogenic inducers and their action mechanisms.

An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up-regulated Runx2 and Osterix mRNA expression at 10µM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents.

Inhibitory effects of Kaempferia parviflora extract on monocyte adhesion and cellular reactive oxygen species production in human umbilical vein endothelial cells.

PURPOSE: The rhizome of Kaempferia parviflora (KP) is used in traditional Thai medicine. In this study, we investigated the effects of an ethanol KP extract and two of its components [5,7-dimethoxyflavone (DMF) and 5-hydroxy-3,7,3',4'-tetramethoxyflavone (TMF)] on monocyte adhesion and cellular reactive oxygen species (ROS) production in human umbilical vein endothelial cells (HUVECs), which provide an in vitro model of events relevant to the development and progression of atherosclerosis. METHODS: RAW264.7 mouse macrophage-like cells were incubated with various concentrations of KP extract or polymethoxyflavonoids and stimulated with lipopolysaccharide prior to measuring nitrite levels in the culture media. Monocyte adhesion was evaluated by measuring the fluorescently labeled human monocytic leukemia THP-1 cells that is attached to tumor necrosis factor-α (TNF-α)-stimulated HUVECs. Cellular ROS production was assessed by measuring cellular antioxidant activity using pyocyanin-stimulated HUVECs. RESULTS: KP extract and DMF reduced nitrite levels (as indicator of nitric oxide production) in LPS-stimulated RAW264.7 cells and also inhibited THP-1 cell adhesion to HUVECs. These treatments induced mRNA expression of endothelial nitric oxide synthase in TNF-α-stimulated HUVECs and downregulated that of various cell adhesion molecules, inflammatory mediators, and endothelial function-related genes. Angiotensin-converting enzyme activity was inhibited by KP extract in vitro. Furthermore, KP extract, DMF, and TMF inhibited the production of cellular ROS in pyocyanin-stimulated HUVECs. CONCLUSION: KP extract, DMF, and TMF showed potential anti-inflammatory and antioxidant effects in these in vitro models, properties that would inhibit the development and progression of atherosclerosis.

5,6-Dehydrokawain from Alpinia zerumbet promotes osteoblastic MC3T3-E1 cell differentiation.

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). METHODS: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. RESULTS: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with x0394;serum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for x0394;CAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for x0394;mean IMT. CONCLUSION: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

[A case of rapidly progressive glomerulonephritis exhibiting granulomatosis with polyangiitis (GPA) and extremely high level of PR3-ANCA with improvement of renal dysfunction after plasma exchange therapy].

A 68-year-old Japanese man was diagnosed with left otitis media with effusion and left uveitis more than 5 months before admission. He was urgently admitted to our hospital for progressive deterioration of his renal function [serum creatinine(Cr) 7.59 mg/dL] with proteinuria and urinary red blood cell casts, inflammation, and anemia. Additionally, his serum proteinase 3 antinuclear antibody (PR3-ANCA) level, determined by using the chemiluminescence enzyme immunoassay method, had increased to more than 3,500 U/mL. Hemodialysis (HD) was initiated on the third day after admission and renal biopsy was performed on the eighth day. The histological findings showed necrotic cellar crescents, hence, he was diagnosed as granulomatosis with polyangiitis on the basis of the clinical criteria. Methylprednisolone pulse therapy was administered from the 11th day. Thereafter, the administration of oral prednisolone (PSL) was started, and plasma exchange was initiated for the purpose of RP3-ANCA removal. In his clinical course, PSL was tapered as soon as possible because of the development of steroid psychosis, and we started intravenous cyclophosphamide on the 25th day instead of tapering the PSL. Subsequently, his renal function improved even without HD, and he was discharged on the 49th day. Although his PR3-ANCA level was still high after discharge, the administration of azathioprine led to a decrease in the PR-3 ANCA levels. About 2 years after discharge, the PR3-ANCA level decreased to 10.0 U/mL, and there has been no sign of GPA recurrence.

Factors affecting the progression of renal dysfunction and the importance of salt restriction in patients with type 2 diabetic kidney disease.

BACKGROUND: Type 2 diabetic kidney disease (DKD) is the most common cause of end-stage renal failure, and the prevention of its progression has been a topic of discussion. METHODS: Sixty type 2 DKD patients were retrospectively evaluated for 1 year. Factors independently affecting the annual Ccr decline were examined by multivariable linear regression analysis. Patients were further divided into 2 groups based on their degree of renal function, and between-group differences at study initiation were evaluated. RESULTS: Ccr values were 21.0 ± 11.8 mL/min/1.73 m(2) at study initiation, and 15.7 ± 10.9 mL/min/1.73 m(2) after 1 year of observation. The multivariable linear regression analysis indicated salt intake (standardized coefficient: -0.34, P = 0.010) and urinary protein excretion (standardized coefficient: -0.33, P = 0.011) to be factors independently affecting the annual Ccr decline. Although decliners (-9.8 ± 4.7 mL/min/1.73 m(2)/year) had a significantly higher salt intake than non-decliners (-1.1 ± 3.8 mL/min/1.73 m(2)/year) at study initiation, this difference disappeared at the end of the study as a result of intensive dietary education. In 21 decliners with an additional year of follow-up, the annual Ccr decline significantly improved from -10.1 ± 5.3 to -5.3 ± 7.4 mL/min/1.73 m(2)/year (P = 0.02). CONCLUSION: Salt intake and urinary protein excretion were associated with annual Ccr decline in type 2 DKD patients. Furthermore, dietary education covering salt intake may have positively affected the change in Ccr.

Renoprotective effects of thiazides combined with loop diuretics in patients with type 2 diabetic kidney disease.

BACKGROUND/AIMS: Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. METHODS: This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m(2) who were suffering from severe edema even with loop diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. RESULTS: Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month, D-BP: at 12 months, p < 0.05 vs. 0 month, proteinuria: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month). The annual decline in eGFR was not significantly different before and after HCTZ therapy (-7.7 ± 8.5 and -8.4 ± 4.8 mL/min/1.73 m(2)/year, respectively). CONCLUSION: Our findings suggest that the combination of HCTZ and loop diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.

Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism.

The incidence of cholesterol crystal embolism (CCE) has increased along with increases in the prevalence of atheromatous diseases and intravascular procedures. CCE frequently results in the deterioration of renal function, which sometimes leads to end-stage renal failure. Although there has been no established therapy for CCE, the possibility that low-density lipoprotein apheresis (LDL-A) is an effective therapy for renal CCE was previously reported. However, whether LDL-A improves renal CCE remains uncertain. This study aimed to evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE patients (9 men and 3 women, mean age 70.6 ± 1.7 years) were included in this retrospective study. All patients had received LDL-A therapy, and estimated glomerular filtration rate (eGFR) values were examined before and after LDL-A. In addition, monthly changes in eGFR before and after LDL-A were calculated for each patient. At initial diagnosis of renal CCE, the eGFR was 35.2 ± 4.8 mL/min/1.73 m(2). At the initiation of LDL-A, the eGFR significantly decreased to 11.0 ± 1.2 mL/min/1.73 m(2), and monthly changes in eGFR reached -7.2 ± 2.5 mL/min/1.73 m(2)/month. After the initiation of LDL-A, the progression of renal dysfunction stabilized in nearly two-thirds of patients, and monthly changes in eGFR after LDL-A significantly diminished to -0.3 ± 0.7 mL/min/1.73 m(2)/month (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes.

Toddalia asiatica (L.) Lam. (T. asiatica) has been utilized traditionally for medicinal purposes such as the treatment of diabetes. Currently, the extract is considered to be a good source of anti-diabetic agents, but the active compounds have yet to be identified. In this study, we investigated the effects of fractionated T. asiatica extracts on the differentiation of 3T3-L1 preadipocytes and identified aculeatin as a potential active agent. When 3T3-L1 preadipocytes were treated with aculeatin isolated from T. asiatica in the presence of insulin, aculeatin increased cellular triglyceride levels and glycerol-3-phosphate dehydrogenase activity. This indicated that aculeatin could enhance the differentiation of preadipocytes into adipocytes. Further analyses using a DNA microarray and real-time quantitative reverse-transcription PCR showed an increase in the expression of peroxisome proliferator-activated receptor-γ target genes (Pparg, Ap2, Cd36, Glut4 and Adipoq) by aculeatin, suggesting that aculeatin enhances the differentiation of 3T3-L1 cells by modulating the expression of genes critical for adipogenesis. Interestingly, after treatment of differentiated adipocytes with aculeatin, glucose uptake and lipolysis were enhanced. Overall, our results suggested that aculeatin is an active compound in T. asiatica for enhancing both differentiation and lipolysis of adipocytes, which are useful for the treatment of lipid abnormalities as well as diabetes.

Evaluation of cerebral oxygenation in patients undergoing long-term hemodialysis.

BACKGROUND/AIMS: Patients undergoing hemodialysis (HD) have higher occurrence rates of cerebral diseases, including uremic encephalopathy, cognitive impairment, dementia, and cerebrovascular disease, than the general population. During HD, ultrafiltration is performed to maintain an adequate fluid condition and is associated with subsequent blood volume (BV) reduction. We aimed to (1) monitor changes in cerebral oxygenation and BV reduction during HD, and (2) clarify the mechanism that influences cerebral oxygenation in HD patients. METHODS: Eighteen HD patients and 12 healthy controls were recruited. Regional saturation of oxygen (rSO2) was continuously monitored in the frontal cortex using INVOS 5100C before, during, and after HD, and in healthy controls. Relative change in BV (%ΔBV) was simultaneously monitored during HD using a BV monitor. RESULTS: Before HD, patients had significantly lower rSO2 values than controls (56.1 ± 1.4 vs. 70.4 ± 2.5%, p < 0.001). Although %ΔBV significantly decreased from 20 min to the end of HD (20 min: -3.3 ± 0.3%, p < 0.05; end of HD: -12.0 ± 1.0%, p < 0.01), changes in rSO2 values during HD were not significant. No relationship existed between rSO2 values and blood pressure levels, hemoglobin levels, oxygen pressure, HCO3(- ), oxygen saturation, and arterial O2 content before and after HD. Furthermore, changes in rSO2 were not correlated with changes in these parameters. CONCLUSION: rSO2 values before HD were significantly lower in HD patients than in healthy controls. rSO2 values were maintained during HD and were not influenced by BV reduction.

Identification and evaluation of anti-inflammatory compounds from Kaempferia parviflora.

The rhizome of Kaempferia parviflora has been used in traditional Thai medicine. In this study, we identified and compared specific compounds from the hexane extract of K. parviflora with those from other Zingiberaceous plants by using gas chromatography-mass spectrometry. We identified 5,7-dimethoxyflavone (DMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (TMF), estimated 3,5,7-trimethoxyflavone, 5-hydroxy-7,4'-dimethoxyflavone, 3,5,7,4'-tetramethoxyflavone, and investigated their anti-inflammatory effects in rat basophilic leukemia (RBL-2H3) cells stimulated with an IgE antigen or a calcium ionophore. We found that DMF and TMF more potently inhibited antigen-induced degranulation than did nobiletin, a well-known anti-inflammatory agent. In addition, compared to RBL-2H3 cells stimulated with a calcium ionophore, those treated with DMF and TMF showed more marked inhibition of the degranulation and the production and mRNA expression of inflammatory mediators. These results suggest that DMF and TMF inhibit an early step in the high-affinity IgE receptor signaling cascade rather than intracellular calcium release and protein kinase C activation.

Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration.

BACKGROUND: To evaluate the plasma vascular endothelial growth factor (VEGF) levels after one intravitreal injection of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD). METHODS: Twenty-four Japanese with exudative AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation were included. Fourteen patients received an intravitreal injection of aflibercept, and ten patients received an intravitreal injection of ranibizumab. Plasma VEGF levels were evaluated within 7 days before the intravitreal injections and 1 day, 1 week, and 1 month after the intravitreal injection. RESULTS: In the ranibizumab group, the mean plasma VEGF levels were 245.7 ± 233.4 pg/ml before the injection, 246.6 ± 304.8 pg/ml after 1 day, 217.8 ± 212.9 pg/ml after 1 week, and 260.0 ± 290.1 pg/ml after 1 month. The plasma VEGF levels did not decrease significantly in patients in the ranibizumab group at any time point. In the aflibercept group, the mean plasma VEGF levels were 280.0 ± 170.3 pg/ml before the intravitreal injection and 8.2 ± 12.9 pg/ml after 1 day, 9.1 ± 9.1 pg/ml after 1 week, and 41.9 ± 41.4 pg/ml after 1 month (p < 0.0001, vs before injection). CONCLUSION: Intravitreally injected aflibercept reduced plasma VEGF over at least 1 month. In contrast, intravitreal injection of ranibizumab did not cause a significant reduction in the plasma VEGF levels.

[Nocturnal dipping of heart rate in patients with proliferative diabetic retinopathy and iris and/or angle neovascularization].

PURPOSE: To evaluate the relationship between nocturnal dipping in heart rates and iris and/or angle neovascularization (NV) in patients with proliferative diabetic retinopathy(PDR). SUBJECTS AND METHOD: One hundred fifty-one patients with PDR who underwent surgery were divided into groups based on either the presence or absence of iris and/or angle NV (NV group, 37; non-NV group, 114 patients). Pulse oximetry was conducted overnight and the heart rates were measured both before and during sleep; the resting and nocturnal heart rates and the resting-nocturnal heart rate dip ratio were calculated. RESULTS: The resting and nocturnal heart rates did not differ significantly between the two groups. The resting-nocturnal heart rate dip ratio was significantly lower in the NV group than in the non-NV group (p = 0.006). In the NV group, the frequency of insulin therapy (p = 0.003) and a history of coronary artery disease were significantly (p = 0.033) higher than in the non-NV group. Pearson's correlation analysis showed that only the NV group was significantly negatively correlated with the resting-nocturnal heart rate dip ratio (r = -0.18, t value = -2.2, p = 0.028). CONCLUSION: In patients with PDR, the non-occurrent of nocturnal dip in heart rate may be a related factor for iris and/or angle neovascularization.