Rubi Fructus (Rubus coreanus) activates the expression of thermogenic genes in vivo and in vitro.

OBJECTIVE: To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro. METHODS: Male C57BL/6 J mice (n=5 per group) were fed a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF. RESULTS: In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes. CONCLUSIONS: This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.

Involvement of group I metabotropic glutamate receptors and glutamate transporters in the slow excitatory synaptic transmission in the spinal cord dorsal horn.

Our experiments demonstrate a novel role for group I metabotropic glutamate receptor (mGluR) subtypes 1 and 5 in generating a long-lasting synaptic excitation in the substantia gelatinosa (SG) and deep dorsal horn (DH) neurons of the rat spinal cord. In the present study we have investigated a slow excitatory postsynaptic current (EPSC), elicited by a brief high intensity (at Adelta/C fiber strength) and high frequency (20 or 100 Hz) stimulation of primary afferent fibers (PAFs) using whole-cell patch-clamp recordings from neurons located in the DH (laminae II-V) in spinal cord slices of young rats and wild-type and gene-targeted mice lacking mGluR1 subtype. The results shown here suggest that the activation of both mGluR1 and mGluR5 along with NK1 receptors, may be involved in the generation of the slow EPSC in the spinal cord DH. Inhibition of glial and neuronal glutamate transporters by DL-threo-beta-benzyloxyaspartate (TBOA) enhanced the group I mGluR-dependent slow EPSC about eightfold. Therefore, we conclude, that glutamate transporters strongly influence the group I mGluR activation by PAFs possibly at sensory synapses in the DH. Overall these data indicate that stimulus trains can generate a sustained and widespread glutamate signal that can further elicit prolonged EPSCs predominantly mediated by the group I mGluRs. These slow excitatory synaptic currents may have important functional implications for DH cell firing and synaptic plasticity of sensory transmission, including nociception.

Image enhancement based on signal subspace approach.

This paper describes a block-by-block basis image enhancement algorithm which uses the signal subspace method to enhance images corrupted by uncorrelated additive noise. The enhancement is performed by eliminating the noise components in the noise subspace and estimating the clean image from the remaining components in the signal subspace.

An active noise control algorithm for controlling multiple sinusoids.

The filtered-x LMS algorithm and its modified versions have been successfully applied in suppressing acoustic noise such as single and multiple tones and broadband random noise. This paper presents an adaptive algorithm based on the filtered-x LMS algorithm which may be applied in attenuating tonal acoustic noise. In the proposed method, the weights of the adaptive filter and estimation of the phase shift due to the acoustic path from a loudspeaker to a microphone are computed simultaneously for optimal control. The algorithm possesses advantages over other filtered-x LMS approaches in three aspects: (1) each frequency component is processed separately using an adaptive filter with two coefficients, (2) the convergence parameter for each sinusoid can be selected independently, and (3) the computational load can be reduced by eliminating the convolution process required to obtain the filtered reference signal. Simulation results for a single-input/single-output (SISO) environment demonstrate that the proposed method is robust to the changes of the acoustic path between the actuator and the microphone and outperforms the filtered-x LMS algorithm in simplicity and convergence speed.

Short-term change of optic nerve head topography after trabeculectomy in adult glaucoma patients as measured by Heidelberg retina tomograph.

Using Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany) we investigated whether reversal of glaucomatous optic disc cupping occurs in adult glaucoma patients following intraocular pressure (IOP) reduction by trabeculectomy, and whether topographic change in the optic disc differs according to region. Thirteen eyes of 13 glaucoma patients in whom IOP reduction was 25% or more at postoperative follow-up of 2 months were enrolled in the study. Cup/disc area ratio had decreased significantly, while rim area and rim volume showed significant increases (p < 0.05, Wilcoxon signed rank test). Among the optic disc sectors, rim area in the superior and inferior quadrants, especially in the superotemporal and inferotemporal octant, had increased significantly. The decrease in maximum cup death correlated significantly with the recent IOP reduction (r = 0.698, p = 0.016). Reversal of glaucomatous disc cupping after IOP reduction following trabeculectomy in adult patients as confirmed by HRT. Furthermore, the regions of selective reversal in the superior and inferior quadrants coincided with those parts of the optic nerve head in which early functional and structural glaucomatous damage has been known to occur.

Topical cyclosporine and glaucoma drainage implant surgery in rabbits.

BACKGROUND AND OBJECTIVE: To assess the effect of topical cyclosporine on the function of filtering blebs and fibroblast proliferation after glaucoma drainage implant surgery in rabbits. MATERIALS AND METHODS: Intraocular pressure, flow resistance through the implant capsule, and fibroblast density in the capsule were compared between 12 eyes that received implant surgery only (group A) and 11 eyes treated with topical 2% cyclosporine twice a day for 2 weeks after implant surgery (group B). RESULTS: There were significantly larger decreases in intraocular pressure at 1,2,4, and 8 weeks postoperatively in group B than in group A (n = 12, P < .05). Flow resistance was significantly lower in group B than in group A (n = 5, P < .05) at 8 weeks postoperatively. Fibroblast density was not significantly different between the two groups (n = 3, P > .05). CONCLUSION: These results suggest that topical 2% cyclosporine may enhance the effectiveness of glaucoma drainage implant surgery.

Relationship between optic nerve head parameters of Heidelberg Retina Tomograph and visual field defects in primary open-angle glaucoma.

To investigate the correlation between optic nerve head configuration and visual field defects, optic nerve head analysis using confocal scanning laser tomography (Heidelberg Retina Tomograph, HRT) and automated static threshold perimetry using a Humphrey Field Analyzer (program C30-2) were performed on 81 eyes of 44 primary open-angle glaucoma (POAG) patients. The optic nerve head parameters-rim area, rim volume, mean retinal nerve fiber layer thickness, height variation contour, and third moment in contour were measured by HRT and were analyzed for correlation with visual field indices-mean deviation, and corrected pattern standard deviation. All optic nerve head parameters except HVC correlated significantly with the visual field indices; the highest correlation was between rim area and mean deviation (r = 0.6172, p < 0.00001). The rim area of the superior and inferior quadrants correlated significantly with the visual field defects in corresponding sectors. Structural optic disc measurements by HRT correlated significantly with functional optic nerve head damage in POAG.

The effect of low-and high-dose adjunctive mitomycin C in trabeculectomy.

To compare the effects of three different concentrations of mitomycin C (MMC) as an adjunct therapy to trabeculectomy, we reviewed 26 patients (36 eyes) who underwent trabeculectomy in which MMC was applied intraoperatively. The time of application was 5 minutes, and the concentration of MMC was 0.1 mg/ml (n = 10), 0.2 mg/ml (n = 17) and 0.4 mg/ml (n = 9), respectively. Complete success was defined by intraocular pressure (IOP) of 21 mmHg or less without medication at postoperative 3 months. There was no statistical difference among the three groups in mean age of patients, preoperative IOPs, and the numbers of premedication. The mean IOP at postoperative 3 months was significantly lower in the 0.4 mg/ml group (10.4 +/- 5.5 mmHg) than in the 0.2 mg/ml group (16.1 +/- 4.7 mmHg) (p < 0.05). The complete success rate in the 0.4 mg/ml group was 100%, which was significantly higher than the rate of 40% obtained with the 0.1 mg/ml group (p < 0.05), but was not significantly different to the rate of 70.6% in the 0.2 mg/ml group (p > 0.05). There was no statistical difference among the three groups in the success rate regardless of medication, and the size and longevity of the filtering bleb. Postoperative hypotony was noted in two eyes of the 0.4 mg/ml group.

Evaluation of pupillary block component in angle-closure glaucoma.

To evaluate the amount of the pupillary block component in primary angle-closure glaucoma, the dark-room prone-position test was carried out in 30 eyes of 20 primary angle-closure glaucoma patients, before and one month after argon laser iridotomy. The pupillary block component in the prone position (5.8 +/- 5.6 mmHg), which is the amount of reduction in IOP rise in the post-laser dark-room prone-position test, composed 67.8% of the IOP rise in the pre-laser dark-room prone-position test (8.6 +/- 5.6 mmHg). The amount of the pupillary block component correlated significantly with the IOP rise in the pre-laser dark-room prone-position test (r = 0.880, P < 0.001). The amount of the non-pupillary block component was relatively constant and correlated poorly with the IOP rise in the pre-laser dark-room prone-position test (r = 0.163, P = 0.386). The pupillary block component was significantly larger than the non-pupillary block component in the eyes with an IOP rise of > or = 7 mmHg in the pre-laser dark-room prone-position test (P < 0.01). The dark-room prone-position test could be useful in evaluating the pupillary block component in angle-closure glaucoma eyes and helpful in making a decision for laser iridotomy.

Experimentally designed glaucoma implant surgery with mitomycin C in rabbit.

An attempt was made to observe the possibility of controlling intraocular pressure (IOP) without hypotony and ocular motility disorder by installing an experimentally designed glaucoma implant through a small conjunctival incision with the aid of a stylet and maintaining the aqueous reservoir using mitomycin C (MMC). The implant was made of silicone tube, of which one end was occluded by glue and on the same end 4 check-valve-like slits were made. Thirty-five healthy white rabbits were used and subdivided into 4 groups. In groups I to III, implants having 2.0, 2.5, 3.0 mm slit lengths, respectively, were installed with MMC application in one eye of each of the 10 rabbits. In group IV, a 2 mm slit-length implant was installed without MMC in one eye of each of the 5 rabbits. Pneumatonometry and ultrasonography were performed to check the IOP and the formation of aqueous reservoir in the implanted eyes for 8 weeks. In group I through III, there was a statistically significant 4-5 mmHg pressure-lowering effect in the implanted eyes compared to the contralateral control eyes for 8 weeks. The aqueous reservoirs were observed throughout the follow-up period. In group IV, we could observe neither a pressure-lowering effect nor aqueous reservoir formation in the implanted eyes after 2 weeks postoperatively. Hypotony did not occur in implanted eyes in any of the groups. This study shows the possibility of IOP control by installing a specially designed glaucoma implant with application of MMC.

Quantitative analysis of changes of automated perimetric thresholds after pupillary dilation and induced myopia in normal subjects.

We quantitatively analyzed the changes of the (retinal) threshold sensitivities between normal status and dilated emmetropic status, and between dilated emmetropic status and -1.0D induced myopic status. Three consecutive visual field examinations by Humphrey Field Analyzer C-30-2 threshold test and STATPAC program were performed in 36 eyes of 21 normal subjects who ranged in age from 23 to 40 years. The results were as follows: 1) There was a statistically significant decrease (0.87 +/- 0.91dB)in the mean threshold sensitivity within the central 30 degrees at the dilated emmetropic status (27.90dB) as compared with the normal status (28.77dB)(p = 0.0001). 2) There was a statistically significant decrease(0.99 +/- 0.61dB) at -1.0D induced myopic status(26.91dB) as compared with the dilated emmetropic status(27.90dB)(p = 0.0001). 3) After dilation, the mean threshold sensitivity between 20 and 30 degrees of field showed statistically significant decrease as compared with those within the central 20 degrees of visual field(p < 0.05). In case of -1.0D induced myopia, there were uniform decreases in the mean threshold sensitivities within the central 30 degrees of visual field (p > 0.05). Therefore, we emphasize the importance of consistent pupillary size and correct refractive state in performing the serial automated visual field tests.

Effects of intracameral carbachol and acetylcholine on early postoperative intraocular pressure after cataract extraction.

We performed a randomized, prospective study to evaluate the effect of intraoperative, intracameral carbachol or acetylcholine on early postoperative intraocular pressure(IOP) after extracapsular cataract extraction(ECCE) and posterior chamber lens(PCL) implantation. Fifty-six eyes of 56 patients scheduled for routine ECCE and PCL implantation were randomly assigned into three groups: (1)carbachol infusion (19 eyes) (2) acetylcholine infusion (15 eyes) (3)balanced salt solution (BSS) infusion (control, 22 eyes). We compared the preoperative IOP, early postoperative IOP, postoperative 24 hours IOP and postoperative 1 week IOP. In the measurement of early postoperative IOP, IOP was measured at least twice at 3, 6 or 9 hours postoperatively. There was no significant difference in IOP between the three groups preoperatively, at postoperative 3 hours, and 1 week. At postoperative 6 hours, both the carbachol infusion group and acetylcholine infusion group were significantly different from the BSS infusion group. At postoperative 9 and 24 hours, only carbachol infusion group had a significant difference from BSS infusion group in suppression of postoperative IOP increase. Our results suggest that intraoperative, intracameral administration of carbachol or acetylcholine prevents early postoperative IOP increase, and that carbachol has a more lasting effect.

Effects of postoperative mitomycin C on glaucoma filtration surgery in rabbits treated preoperatively with antiglaucoma medications.

In a rabbit model, we evaluated the effects of topically applied postoperative mitomycin C (MMC) on the success rate of glaucoma filtration surgery in animals treated preoperatively with pilocarpine hydrochloride 4% and levobunolol hydrochloride (Betagan) for 16 weeks. Full-thickness filtration surgery was performed with a single 5-minute intraoperative exposure to a sponge soaked with 0.4 mg/mL MMC of one eye in nine rabbits in one group (group A) and to both eyes in 13 rabbits in a second group (group B). In addition, one eye of each rabbit in group B received a daily drop of 0.4 mg/mL MMC for 13 days after the operation. All of the eyes were then followed for 80 days. The intraoperatively applied MMC enhanced the success rate of the filtration surgery in the group A eyes. However, the eyes that also received postoperative drops of MMC (group B) had longer periods of reduced intraocular pressure (IOP) (P [chi-squared = 5.94] < .025), fewer bleb failures (P [chi-squared = 8.09] < .005), and more complications than the eyes that received only intraoperative MMC.

The effects of intraoperative mitomycin-C or 5-fluorouracil on glaucoma filtering surgery.

We compared the success rate of filtering surgery of a single 5-minute intraoperative application of mitomycin-C (MMC) or 5-fluorouracil (5-FU). Animal experiment and clinical study were done. In animal study, thirty pigmented rabbits (60 eyes) weighing 2.0 to 2.5 Kg were enrolled. We divided into 4 groups, such as BSS, 5-FU 50 mg/ml, MMC 0.2 mg/ml and MMC 0.4 mg/ml subconjunctival soaked group. Each group consisted of 15 eyes. In each group, 10 eyes was for examination of bleb survival and complications, 3 eyes for light microscopic examination and 2 eyes for electron microscopic examination. Bleb was survived 6.1 days (3 to 13 days) for BSS treated group, 16.3 days (9 to 23 days) for 5-FU 50mg/ml treated group, 32.7 days (17 to 55 days) in MMC 0.2 mg/ml treated group, and 64.4 days (49 to 84 days) in MMC 0.4 mg/ml treated group. Duration of bleb survival was significantly prolonged in 5-FU, MMC 0.2 mg/ml and MMC 0.4 mg/ml group respectively. In clinical study, fifty-five eyes of 40 patients were enrolled. 29 eyes of 21 patients were treated with MMC 0.2 mg/ml and 26 eyes of 19 patients were treated with 5-FU 50 mg/ml. The success rate was 89.7% in MMC 0.2 mg/ml treated group and 84.6% in 5-FU 50 mg/ml treated group at postoperative 3 months, and postoperative 6 months 89.7% in MMC 0.2 mg/ml treated group and 76.9% in 5-FU 50 mg/ml treated group. There was no statistical significance at postoperative 3 months (P > 0.05), but statistical significance at postoperative 6 months (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of topical mitomycin C on glaucoma filtration surgery.

We studied the efficacy and safety of using topical mitomycin C (MMC) as an adjunct to glaucoma filtration surgery. Trabeculectomy was performed in 23 eyes of 19 patients with poor surgical prognosis. After the preparation of a scleral flap, 0.2 mg or 0.4 mg/ml MMC was applied to the exposed tissue for 5 minutes. The wound was then irrigated with 250ml of normal saline. The mean follow-up period was 7.8 months. Preoperative mean intraocular pressure (IOP) was 33.8mmHg, and the mean IOPs on 1, 3, 6, and 12 months after operation were 10.3, 12.5, 12.4 and 12.3mmHg, respectively. At postoperative 12 months, 74.7% achieved an IOP of less than or equal to 20mmHg without any antiglaucoma medication. There were early postoperative complications of aqueous leaking from conjunctival wounds in 3 eyes (13.0%), shallow anterior chamber in 2 eyes, and hyphema in one eye and one eye had long-term hypotony lasting more than 3 months. Although MMC is simple to use, it is a potent adjunct to glaucoma filtration surgery, more work should follow to determine the mechanism of action, indications, dosage and optimal exposure time of MMC.

Effects of sodium hyaluronate on filtration bleb in rabbits.

Sodium hyaluronate can be used during a trabeculectomy to prevent early postoperative hypotony and shallow anterior chamber. To determine its long-term effect on the outcome of filtration surgery, fifteen rabbits underwent a posterior-lip sclerectomy in both eyes. Into their right eyes 0.2ml sodium hyaluronate, and into left eyes 0.2ml balanced salt solution were injected intracamerally. Gross and histopathological differences of bleb were observed. There was no statistically significant difference in longevity of the filtration bleb.

Chemosensitization to adriamycin by cyclosporin A and verapamil in human retinoblastoma cell lines.

The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were investigated using MTT assay against two human retinoblastoma cell lines, Y79 and WERI-Rb-1. Y79 and WERI-Rb-1 were totally resistant to doses up to 5.0 micrograms/ml of verapamil. Cyclosporin A inhibited the survival of Y79 and WERI-Rb-1 dose-dependently, however, the maximum inhibition at the highest concentration tested (5.0 micrograms/ml) was less than 50% (% survival at 5.0 micrograms/ml of cyclosporin A: 65.6% and 66.9% in Y79 and WERI-Rb-1, respectively). Combination of cyclosporin A and verapamil did not further inhibit the survival of Y79 and WERI-Rb-1 compared with cyclosporin A alone. Adramycin inhibited the survival of Y79 and WERI-Rb-1 dose-dependently. The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were evaluated in terms of sensitizing index (SI: the ratio of IC50 to adriamycin alone to IC50 to adriamycin in the presence of cyclosporin A and/or verapamil). Cyclosporin A significantly enhanced SI and the addition of verapamil enhanced SI further: SI values at 5.0 micrograms/ml of cyclosporin A, 5.0 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of verapamil, 5.0 micrograms/ml of cyclosporin A plus 3.0 micrograms/ml of verapamil were 2.0, 2.6 and 2.8 in Y79 and 2.6, 5.8 and 9.7 in WERI-Rb-1, respectively. These results suggest that cyclosporin A and verapamil are promising chemosensitizers to adriamycin in the treatment of retinoblastoma.

The use of cytosine arabinoside in glaucoma filtering surgery.

Posterior lip sclerectomies were performed in rabbits and cytosine arabinoside (Ara-C) was applied by topical instillation or subconjunctival injection. In both groups, the mean intraocular pressure (IOP) of the treated eyes was significantly lowered at postoperative week 1 and 2, but there was no significant difference between the mean IOP of the control eyes and that of the treated eyes at postoperative week 3 and 4. In both groups, at postoperative week 2, the sclerectomy sites of the control eyes were totally occluded by granulation tissue, but those of the treated eyes were partially replaced by granulation tissue. At postoperative week 4, the sclerectomy sites of the treated eyes were totally occluded by the granulation tissue ultimately in both groups. There were no differences in the mean IOP and the histologic finding of the treated eyes between the topical instillation group and the subconjunctival injection group. We concluded that either topical instillation or subconjunctival injection of Ara-C can delay wound healing at the surgical site after glaucoma filtering surgery in rabbits.

On detecting the presence of fetal R-wave using the moving averaged magnitude difference algorithm.

An efficient algorithm detecting the presence of a fetal QRS complex is presented. The proposed fetal QRS detection method computes the averaged magnitude of the difference between the fetal ECG signal and the reference signal to detect the fetal QRS event. The detected fetal QRS complexes are exponentially averaged to generate the template signal which can track the slowly varying shape of the fetal ECG signal. As an effort to obtain improved detection performances, two approaches of normalizing the fetal ECG signal and the template are considered.