The efficacy of the “no zone” approach for the assessment of traumatic neck injury: a case-control study

Purpose@#Recently, several studies have demonstrated symptom-based, non-zonal algorithms for approaching penetrating neck injuries. The purpose of this study was to confirm the effectiveness of the “no zone” approach in traumatic neck injuries. @*Methods@#Medical charts of patients with traumatic neck injuries who presented at the Regional Trauma Center in South Korea between January 2014 and December 2018 were retrospectively reviewed. Negative final neck findings (FNFs) were compared with positive FNFs (which include major vascular, aerodigestive, nerve, endocrine gland, cartilage, or hyoid bone injuries) using multivariate logistic regression analysis including values of the “zone” and/or no zone approach. @*Results@#Out of 168 trauma patients, 70 patients with a minor injury and 7 patients under the age of 18 years were excluded. Of the remaining 91 patients, 74 (81.3%) had penetrating neck injuries and 17 (18.7%) had blunt neck injuries. Initial diagnosis most frequently revealed external wounds in zone II (84.6%). Twenty (22.0%) and 36 (39.5%) patients had hard and soft signs, respectively, using the no zone approach. Further, there was a significant difference between the negative and positive FNFs in patients with hard signs (11.6% vs. 54.5%; P < 0.01, respectively). According to the multivariate logistic regression analysis, the hard signs were associated with an odds ratio (OR) for FNFs (OR, 18.92; 95% confidence interval, 3.55–157.60). @*Conclusion@#Traumatic neck injuries classified as having hard signs based on the no zone approach may be correlated with internal organ injuries of the neck.

A Case of Endothelial Keratitis Associated with Immunosuppressant in Kaposi's Varicelliform Eruption

PURPOSE: To report a case of endothelial keratitis occurred after reactivation of herpes simplex virus following immunosuppressant therapy for Kaposi's varicelliform eruption. CASE SUMMARY: A 23-year-old female was referred for ocular pain and blurred vision. She had atopic dermatitis and was diagnosed with Kaposi's varicelliform eruption on her face after using an immunosuppressant. Slit lamp examination revealed central corneal edema in the right eye. She was initially diagnosed with contact lens-induced keratitis. Subsequently, the contact lens was removed and topical antiviral agent used for prevention of ocular involvement. Four days after treatment, Wesseley immune ring of deep stromal haze and cells in the anterior chamber were present. She was diagnosed with endothelial keratitis caused by reactivation of herpes simplex virus after using an immunosuppressant. Topical steroid, hypertonic saline eye drops and cycloplegic eye drops were added to the treatment for the progression of endothelial keratitis. Corneal edema was decreased 2 weeks after treatment and anterior chamber cells decreased 1 month after treatment. There was no recurrence during the follow-up period. CONCLUSIONS: Patients diagnosed with Kaposi's varicelliform eruption after using immunosuppressants should have an ophthalmic examination to confirm ocular involvement; use of appropriate eye drops is necessary for the treatment of corneal involvement.

Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal Erosions

PURPOSE: To evaluate the effect of platelet-rich plasma (PRP) eye drops in the treatment of recurrent corneal erosions (RCE). METHODS: A total of 47 eyes were included in this retrospective study. Clinical records of 20 consecutive patients with RCE who had been treated with conventional lubricant eye drops (conventional treatment group) from June 2006 to December 2008 and 27 consecutive patients treated with autologous PRP eye drops in addition to lubricant eye drops (PRP eye drops treated group) from January 2009 to September 2014 were reviewed. Major and minor recurrences were recorded and compared between two groups. RESULTS: This study included 31 men and 16 women. The mean age was 44.5 ± 14.5 years (range, 19 to 86 years), and the mean follow-up duration was 14.9 ± 14.4 months (range, 6 to 64 months). Of the 27 cases in the PRP eye drops treated group, there were seven major recurrences in six eyes (22.2%) and ten minor recurrences in seven eyes (25.9%). In contrast, 16 eyes (80.0%) from the 20 patients in the conventional lubricant eye drops treated group had major recurrences, and all patients in this group reported minor recurrences. The mean frequency of recurrence was 0.06 ± 0.08 per month in the PRP eye drops treated group and 0.39 ± 0.24 per month in the conventional treatment group (p = 0.003). No side effects were noted in any of the patients over the follow-up period. CONCLUSIONS: The use of PRP eye drops for the treatment of RCE was shown to be effective in reducing the recurrence rate without any significant complications.

Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

Gastroprotective Effects of Grape Seed Proanthocyanidin Extracts against Nonsteroid Anti-Inflammatory Drug-Induced Gastric Injury in Rats

BACKGROUND/AIMS: To investigate the gastroprotective effects of grape seed proanthocyanidin extracts (GSPEs) against nonsteroid anti-inflammatory drug (NSAID)-induced gastric mucosal injury in rats. METHODS: Sprague-Dawley rats were randomly allocated to the normal control, indomethacin, low-dose GSPE, high-dose GSPE and misoprostol groups. All groups except the normal control group received pretreatment drugs for 6 consecutive days. On the 5th and 6th day, indomethacin was administered orally to all groups except for normal control group. The microscopic features of injury were analyzed. The levels of gastric mucosal glutathione, gastric mucosal prostaglandin E2 (PGE2), and proinflammatory cytokines were investigated. RESULTS: The total areas of ulceration in the GSPE and misoprostol groups were significantly decreased compared with the indomethacin group (p<0.05). However, a difference in ulcer formation among the drug treatment groups was not observed. Meanwhile, the glutathione levels in the high-dose GSPE group were higher than those of both the indomethacin and misoprostol groups (p<0.05) and were similar to those of the normal control group. Additionally, there was no difference among the groups in the levels of gastric mucosal PGE2 and proinflammatory cytokines. CONCLUSIONS: High-dose GSPE has a strong protective effect against NSAID-induced gastric mucosal injury, which may be associated with the antioxidant effects of GSPE.

Meconium-related Ileus in Extremely Low-birth Weight Newborn Infants Meconium-related Ileus in ELBWI

PURPOSE: Meconium-related ileus (MRI) is one of the major causes of bowel obstruction in extremely low-birth weight newborn infants (ELBWI). Hyperosmolar water-soluble contrast (HWSC) enemas been recognized to be an effective treatment for MRI. The purpose of this study is to observe clinical findings of MRI accompanied by ELBWI and evaluate the therapeutic efficacy and complications of HWSC enemas. METHODS: A total of 15 ELBWI with MRI were treated with HWSC enemas under the guidance of ultrasonography at the bedside in the NICU between 2008 and 2011. Clinical findings of 15 patients were reviewed and compared with those of 48 ELBWI without MRI administered to NICU during the same period. Radiological findings, therapeutic efficacy and complications of HWSC enemas in patients with MRI were also reviewed. RESULTS: Patients with MRI, compared to those without MRI, showed the following significantly lower Apgar score at 1 minute, higher incidence of preeclampsia, bronchopulmonary dysplasia and sepsis, and longer duration of the first meconium passing and non-feeding per oral. Fourteen patients with MRI had resolved bowel obstruction successfully following 1-2 trials of enema. One case was not relieved following 3 trials of enema, showed no clinical improvement, and died of severe intraventricular hemorrhage and multi-organ failure at 45 days old. No complications associated with HWSC enemas were observed in all cases. CONCLUSION: Administration of HWSC enemas under the guidance of abdomen ultrasonography in the NICU is safe and efficacious for the rapid diagnosis and treatment of MRI even accompanied by ELBWI.

Higher Plasma Thrombospondin-1 Levels in Patients With Coronary Artery Disease and Diabetes Mellitus

BACKGROUND AND OBJECTIVES: Thrombospondin-1 (TSP-1) is associated with atherosclerosis in animals with diabetes mellitus (DM). But, no study has investigated the role of TSP-1 in human atherosclerosis. This study investigated the relationship among plasma TSP-1 concentration, DM, and coronary artery disease (CAD). SUBJECTS AND METHODS: The study involved 374 consecutive subjects with suspected CAD, who had undergone coronary angiography to evaluate effort angina. Patients were divided into four groups as follows: DM(-) and CAD(-), DM(-) and CAD(+), DM(+) and CAD(-), and DM (+) and CAD(+). RESULTS: We found that plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) (n=103) than those in other patients (n=271) (p<0.01). A multivariate analysis showed that male gender {odds ratio (OR), 2.728; 95% confidence interval (CI), 1.035-7.187}, high density lipoprotein-cholesterol (OR, 0.925; 95% CI, 0.874-0.980), glycated hemoglobin (OR, 1.373; 95% CI, 1.037-1.817), and plasma TSP-1 (OR, 1.004; 95% CI, 1.000-1.008) levels were independently associated with the presence of CAD in patients with DM. CONCLUSION: Plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) than those in other patients, and plasma TSP-1 levels were independently associated with the presence of CAD in patients with DM. These findings show a possible link between human plasma TSP-1 concentration and CAD in patients with DM.

Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long-term Potentiation in the Rat Visual Cortex

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-week-old rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-HT2 receptors, but not by the activation of either 5-HT1A or 5-HT3 receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

A Randomized, Prospective Clinical Comparison of the Efficacy and Safety of Topical Fluoroquinolone Antibiotics in Ophthalmologic Microsurgery

PURPOSE: To report the results of a clinical comparison study of a prophylactic new generation fluoroquinolone (FQs; levofloxacin 0.5%, gatifloxacin 0.3% and moxifloxacin 0.5%) topical antibiotic regimen administered prior to intraocular microsurgery. METHODS: From May 2007 to April 2010, Trial 1, 214 eyes of 211 patients scheduled for intravitreal injection were randomized into one of three FQ-treated groups or the control (non-treated) group. Patients who were randomized into FQ-treated groups were treated with eye drops containing one of three FQ antibiotics (levofloxacin 0.5%, gatifloxacin 0.3% and moxifloxacin 0.5%) preoperatively four times a day for three days before surgery. The rate of positive bacterial cultures from conjunctival scrapings were assessed and compared. Trial 2, 159 eyes of 159 patients scheduled for cataract surgery were randomized into one of three FQ-treated groups, and treated with eye drops as same method in trial 1. The concentration of antibiotics in the anterior chamber of the eye were measured and compared. RESULTS: The positive bacterial culture rates of trial 1 were 48.9%, 38.3%, 23.4% in the levofloxacin-treated group, the gatifloxacin- group, and the moxifloxacin-treated group, respectively. These rates were all significantly lower than the 70.2% positivity rate observed in the control group. Average antibiotic residue concentrations in the aqueous humor measured in trial 2 were 0.37 +/- 0.49 microg/ml in the levofloxacin-treated group, 0.31 +/- 0.37 microg/ml in the gatifloxacin-treated group and 0.59 +/- 0.72 microg/ml in the moxifloxacin-treated group. These concentrations were not significantly different. There were no reported side effects during the study period. CONCLUSIONS: Eye drops containing new generation FQ antibiotics instilled three days before microscopic ophthalmic surgery can be used safely and effectively for the prevention of postoperative endophthalmitis.

Inhibition of NF-kappaB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells

Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-kappaB (NF-kappaB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-kappaB activation. Also, we determined whether selective inhibition of NF-kappaB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-kappaB or expression of a recombinant adenovirus vector encoding an IkappaB-alpha mutant (Ad-IkappaBalphaM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-kappaB activation was determined by immunohistochemical staining, NF-kappaB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-kappaB activity. Treatment with inhibitors of NF-kappaB such as MG132, PDTC or expression of Ad-IkappaB-alphaM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-kappaB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.

A Case Report of Acute Zonal Occult Outer Retinopathy Showing Acute Idiopathic Blind Spot Enlargement

PURPOSE: To present a case of acute zonal occult outer retinopathy (AZOOR) with acute idiopathic blind spot enlargement (AIBSE) investigated using indocyanine green angiography (ICGA), multifocal electroretinography (multifocal ERG) and spectral domain-OCT (SD-OCT). CASE SUMMARY: A healthy 31-year-old female with photopsia and a five-day visual field defect in her left eye showed no abnormal findings in ocular examinations such as slit lamp and fundus examination, fluorescein angiography (FAG), or full field ERG as well as in the systemic neurologic examination. In the late phase of ICGA, there were multiple hypofluorescent spots around the optic disc and scattered through the posterior pole. The patient showed an amplitude decrease of multifocal ERG and the destruction of the boundary between the inner and outer segments of the photoreceptors in the SD-OCT examined in the retinal area corresponding to the visual field defect. The patient was diagnosed with AZOOR and was followed-up without treatment. After three months, no abnormal SD-OCT or visual field test findings were observed and no symptoms remained; however, a slightly depressed response on multifocal ERG was present. CONCLUSIONS: ICGA, multifocal ERG and SD-OCT could be useful methods to detect AZOOR with EBS.

Association of Hypercapnia in the First Week of Life with Severe Intraventricular Hemorrhage in the Ventilated Preterm Infants

PURPOSE: The aim of this study was to examine whether hypercapnia during the first seven days of life was associated with severe intraventricular hemorrhage (IVH) in preterm infants requiring mechanical ventilation. METHODS: A matched pair analysis was performed for 19 preterm infants with severe IVH (grade> or =3) and 38 infants with no severe IVH (normal or grade 1), who required mechanical ventilation for more than seven days. The univariate and multivariate analysis of severe IVH with maximal and minimal PaCO2, averag PaCO2, SD of PaCO2, and difference in the PaCO2 were assessed. The major perinatal factors and maximal ventilator index (VI) were also compared. RESULTS: Infants with severe IVH had a higher maximal PaCO2 (86.1+/-18.4 mmHg vs. 60.1+/-11.6 mmHg, P<0.001) and mean PaCO2 (47.5+/-5.6 mmHg vs. 41.2+/-6.3 mmHg, P=0.004) and a larger SD or difference in PaCO2 (14.0+/-4.4 mmHg vs. 9.0+/-2.4 mmHg; 60.3+/-20.9 mmHg vs. 35.5+/-11.8 mmHg, P<0.001). However the minimal PaCO2 values did not differ between the groups. Disseminated intravascular coagulation, pulmonary hemorrhage, and the air leak syndrome were more frequent in the IVH group than in the controls. The maximal VI on each day was higher in the IVH group. The multivariate logistic regression analysis after controlling for bleeding tendency showed that the air leak syndrome, maximal VI, and maximal PaCO2 were independently associated with severe IVH [OR, 1.324 (95% CI, 1.011-1.733; P=0.041)]. CONCLUSION: Extreme hypercapnia was significantly associated with severe IVH in preterm infants, after adjustment for major perinatal risk factors. Frequent monitoring of the PaCO2 may be important for early detection of inadvertent hypercapnia and prompt correction of high PaCOS levels.

Octyl Gallate Inhibits ATP-induced Intracellular Calcium Increase in PC12 Cells by Inhibiting Multiple Pathways

Phenolic compounds affect intracellular free Ca2+ concentration ([Ca2+]i) signaling. The study examined whether the simple phenolic compound octyl gallate affects ATP-induced Ca2+ signaling in PC12 cells using fura-2-based digital Ca2+ imaging and whole-cell patch clamping. Treatment with ATP (100 micrometer) for 90 s induced increases in [Ca2+]i in PC12 cells. Pretreatment with octyl gallate (100 nM to 20 micrometer) for 10 min inhibited the ATP-induced [Ca2+]i response in a concentration-dependent manner (IC50=2.84 micrometer). Treatment with octyl gallate (3 micrometer) for 10 min significantly inhibited the ATP-induced response following the removal of extracellular Ca2+ with nominally Ca2+-free HEPES HBSS or depletion of intracellular Ca2+ stores with thapsigargin (1 micrometer). Treatment for 10 min with the L-type Ca2+ channel antagonist nimodipine (1 micrometer) significantly inhibited the ATP-induced [Ca2+]i increase, and treatment with octyl gallate further inhibited the ATP-induced response. Treatment with octyl gallate significantly inhibited the [Ca2+]i increase induced by 50 mM KCl. Pretreatment with protein kinase C inhibitors staurosporin (100 nM) and GF109203X (300 nM), or the tyrosine kinase inhibitor genistein (50 micrometer) did not significantly affect the inhibitory effects of octyl gallate on the ATP-induced response. Treatment with octyl gallate markedly inhibited the ATP-induced currents. Therefore, we conclude that octyl gallate inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both non-selective P2X receptor-mediated influx of Ca2+ from extracellular space and P2Y receptor-induced release of Ca2+ from intracellular stores in protein kinase-independent manner. In addition, octyl gallate inhibits the ATP-induced Ca2+ responses by inhibiting the secondary activation of voltage-gated Ca2+ channels.

Effects of Serotonin on the Induction of Long-term Depression in the Rat Visual Cortex

Long-term potentiation (LTP) and long-term depression (LTD) have both been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. In a previous study, we suggested that a developmental increase in serotonin [5-hydroxytryptamine (5-HT)] might be involved in the decline of LTP, since 5-HT inhibited its induction. In the present study, to further understand the role of 5-HT in a developmental decrease in plasticity, we investigated the effect of 5-HT on the induction of LTD in the pathway from layer 4 to layer 2/3. LTD was inhibited by 5-HT (10 micrometer) in 5-week-old rats. The inhibitory effect was mediated by activation of 5-HT2 receptors. Since 5-HT also regulates the development of visual cortical circuits, we also investigated the role of 5-HT on the development of inhibition. The development of inhibition was retarded by chronic (2 weeks) depletion of endogenous 5-HT in 5-week-old rats, in which LTD was reinstated. These results suggest that 5-HT regulates the induction of LTD directly via activation of 5-HT2 receptors and indirectly by regulating cortical development. Thus, the present study provides significant insight into the roles of 5-HT on the development of visual cortical circuits and on the age-dependent decline of long-term synaptic plasticity.

The Development of Phasic and Tonic Inhibition in the Rat Visual Cortex

Gamma-aminobutyric acid (GABA)-ergic inhibition is important in the function of the visual cortex. In a previous study, we reported a developmental increase in GABAA receptor-mediated inhibition in the rat visual cortex from 3 to 5 weeks of age. Because this developmental increase is crucial to the regulation of the induction of long-term synaptic plasticity, in the present study we investigated in detail the postnatal development of phasic and tonic inhibition. The amplitude of phasic inhibition evoked by electrical stimulation increased during development from 3 to 8 weeks of age, and the peak time and decay kinetics of inhibitory postsynaptic potential (IPSP) and current (IPSC) slowed progressively. Since the membrane time constant decreased during this period, passive membrane properties might not be involved in the kinetic changes of IPSP and IPSC. Tonic inhibition, another mode of GABAA receptor-mediated inhibition, also increased developmentally and reached a plateau at 5 weeks of age. These results indicate that the time course of the postnatal development of GABAergic inhibition matched well that of the functional maturation of the visual cortex. Thus, the present study provides significant insight into the roles of inhibitory development in the functional maturation of the visual cortical circuits.

Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Vascular endothelial growth factor (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF treatment has any effects on the pancreatic islets in an animal model of type 2 diabetes mellitus. METHODS: Anti-VEGF peptide (synthetic ATWLPPR, VEGF receptor type 2 antagonist) was injected into db/db mice for 12 weeks. We analyzed pancreatic islet morphology and quantified beta-cell mass. Endothelial cell proliferation and the severity of islet fibrosis were also measured. VEGF expression in isolated islets was determined using Western blot analysis. RESULTS: When anti-VEGF was administered, db/db mice exhibited more severe hyperglycemia and associated delayed weight gain than non-treated db/db mice. Pancreas weight and pancreatic beta-cell mass were also significantly decreased in the anti-VEGF-treated group. VEGF and VEGF receptor proteins (types 1 and 2) were expressed in the pancreatic islets, and their expression was significantly increased in the db/db group compared with the db/dm group. However, the elevated VEGF expression was significantly reduced by anti-VEGF treatment compared with the db/db group. The anti-VEGF-treated group had more prominent islet fibrosis and islet destruction than db/db mice. Intra-islet endothelial cell proliferation was also remarkably reduced by the anti-VEGF peptide. CONCLUSION: Inhibition of VEGF action by the VEGF receptor 2 antagonist not only suppressed the proliferation of intra-islet endothelial cells but also accelerated pancreatic islet destruction and aggravated hyperglycemia in a type 2 diabetes mouse model. Therefore, the potential effects of anti-VEGF treatment on pancreatic beta cell damage should be considered.

Effects of Apigenin on Glutamate-induced Ca2+i Increases in Cultured Rat Hippocampal Neurons

Flavonoids have been shown to affect calcium signaling in neurons. However, there are no reports on the effect of apigenin on glutamate-induced calcium signaling in neurons. We investigated whether apigenin affects glutamate-induced increase of free intracellular Ca2+concentration ([Ca2+]i) in cultured rat hippocampal neurons, using fura-2-based digital calcium imaging and microfluorimetry. The hippocampal neurons were used between 10 and 13 days in culture from embryonic day 18 rats. Pretreatment of the cells with apigenin (1micrometerto 100micrometer for 5 min inhibited glutamate (100 micrometer 1 min) induced [Ca2+]i increase, concentration-dependently. Pretreatment with apigenin (30micrometer for 5 min significantly decreased the [Ca2+]i responses induced by two ionotropic glutamate receptor agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA, 10 micrometer 1 min) and N-methyl-D-aspartate (NMDA, 100 micrometer 1 min), and significantly inhibited the AMPA-induced peak currents. Treatment with apigenin also significantly inhibited the [Ca2+]i response induced by 50 mM KCl solution, decreased the [Ca2+]i responses induced by the metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine (DHPG, 100micrometer 90 s), and inhibited the caffeine (10 mM, 2 min)-induced [Ca2+]i responses. Furthermore, treatment with apigenin (30micrometer significantly inhibited the amplitude and frequency of 0.1 mM [Mg2+o-induced [Ca2+]i spikes. These data together suggest that apigenin inhibits glutamate-induced calcium signaling in cultured rat hippocampal neurons.

Effects of Antenatal Steroid on Postnatal Fluid Balance in Very Low Birth Weight (VLBW) Infants during the First Week of Life

PURPOSE: Antenatal steroid (AS) may result in lower insensible water loss (IWL), and higher urine output (UO) in early life. We examined if the postnatal fluid balance differed between infants exposed to AS or not (control) in VLBW infants. METHODS: Fifty-four VLBW infants were grouped into AS (n=24) or control (n=30). Fluid intake, UO, IWL and maximal % of weight loss on day 1, day 2, day 3 and day 7 after birth were analyzed. Daily maintenance fluid was determined in each infants by calculation of insensible water loss (IWL=[intake-output]-Delta wt) and UO. RESULTS: Fluid intake (AS vs control; 117.2+/-33.9 vs 126.0+/-29.6 mL/kg/d, P=0.315), IWL (28.1+/-23.7 vs 21.1+/-20.5 P=0.248), UO and maximal % of weight loss on day 7 were not different between groups: similar findings were observed on day 1, day 2, and day 3 after birth. Neonatal morbidities and clinical relevant factors were not different between groups. The duration of assisted ventilation was shorter in the AS than in the control (10.8+/-9.2 vs 27.6+/-26.2, P=0.002). However, the difference disappeared after adjustment for RDS severity and oxygenation index. CONCLUSION: VLBW infants exposed to AS did not have an alteration in postnatal fluid balance during the first week of life, when given fluid based on needs reflected by IWL and UO. The decreased need for assisted ventilation in the AS group may be related to the effects of steroid on fetal lung fluid absorption or maturity, but not on postnatal fluid balance.

The Effect of Epicatechin on the High Glucose-induced TSP-1 Expression and MMP-2 Activity in Rat Vascular Smooth Muscle Cells / 대한내분비학회지

BACKGROUND: The incidence of atherosclerosis is well correlated with the progression of type 2 diabetes mellitus. High plasma glucose in uncontrolled diabetic patients evokes many vascular complications such as atherosclerosis. Specifically, high glucose was reported to induce thrombospondin-1 (TSP-1), which activates matrix metalloproteinase-2 (MMP-2) and leads to the invasion of vascular smooth muscle cells (VSMCs) into the intima. Catechins with antioxidant effects are known to inhibit MMP-2 activity. Therefore, this study was aimed at revealing the effect of epicatechin, one of catechins, on high glucose-induced TSP-1 and the invasiveness of VSMCs. METHODS: VSMCs were primarily isolated from Sprague-Dawley rat aorta. The VSMCs were incubated with different doses (30, 100 and 300 micrometer) of epicatechin under high glucose concentration (30 mM). The TSP-1 protein and mRNA expressions were analyzed by performing Western blotting and Northern blot analyses, respectively. RT-PCR was performed to observe the MMP-2 mRNA expression. Gelatin zymography was performed for the measurement of MMP-2 activity. Invasion assays were performed to evaluate the invasiveness of VSMCs. RESULTS: Epicatechin inhibited the high glucose-induced TSP-1 expression and the MMP-2 activity in a dose-dependent manner. Also, epicatechin inhibited the high glucose-induced invasiveness of VSMCs across the matrix barrier in a dose-dependent fashion. CONCLUSION: Collectively, epicatechin may prevent the high glucose-induced proliferation and invasion of VSMCs by inhibiting the TSP-1 expression and the MMP-2 activity. Therefore, epicatechin appears to play a protective role in the development of atherosclerosis.

The Effect of Epicatechin on the High Glucose-induced TSP-1 Expression and MMP-2 Activity in Rat Vascular Smooth Muscle Cells / 대한내분비학회지

BACKGROUND: The incidence of atherosclerosis is well correlated with the progression of type 2 diabetes mellitus. High plasma glucose in uncontrolled diabetic patients evokes many vascular complications such as atherosclerosis. Specifically, high glucose was reported to induce thrombospondin-1 (TSP-1), which activates matrix metalloproteinase-2 (MMP-2) and leads to the invasion of vascular smooth muscle cells (VSMCs) into the intima. Catechins with antioxidant effects are known to inhibit MMP-2 activity. Therefore, this study was aimed at revealing the effect of epicatechin, one of catechins, on high glucose-induced TSP-1 and the invasiveness of VSMCs. METHODS: VSMCs were primarily isolated from Sprague-Dawley rat aorta. The VSMCs were incubated with different doses (30, 100 and 300 micrometer) of epicatechin under high glucose concentration (30 mM). The TSP-1 protein and mRNA expressions were analyzed by performing Western blotting and Northern blot analyses, respectively. RT-PCR was performed to observe the MMP-2 mRNA expression. Gelatin zymography was performed for the measurement of MMP-2 activity. Invasion assays were performed to evaluate the invasiveness of VSMCs. RESULTS: Epicatechin inhibited the high glucose-induced TSP-1 expression and the MMP-2 activity in a dose-dependent manner. Also, epicatechin inhibited the high glucose-induced invasiveness of VSMCs across the matrix barrier in a dose-dependent fashion. CONCLUSION: Collectively, epicatechin may prevent the high glucose-induced proliferation and invasion of VSMCs by inhibiting the TSP-1 expression and the MMP-2 activity. Therefore, epicatechin appears to play a protective role in the development of atherosclerosis.