The SH test provides an estimate of the full thiol groups in the biological samples, using a limited Ellman method. ( 20, 21 ) When the sample is added to the solution, the SH groups in the sample react with 5,5-dithiobis-2-nitrobenzoic acid, which is followed by development of a stain complex that is spectrophotometrically detectable at 405 new mexico and is proportional to their concentration according to the Beer-Lambert law. ( 16, 19 ) The results were expressed as µmol/L of the SH groups. The BAP quiz provides an estimate of the ball-shaped antioxidant capacity of lineage plasma, measured as its reducing potential against ferric ions. When the sample is added to the color solution obtained by mixing a ferric chloride solution with a thiocyanate derivative solution, decoloration results. The volume of the decoloration is spectrophotometrically detectable at 505 new mexico and is proportional to the ability of plasma to reduce ferric ions. ( 18, 19 ) The results of the BAP test were expressed in µmol/L of the reduced ferric ions. The dROM test reflects the amount of organic hydroperoxides that is related to the loose radicals from which they are formed. When the samples are dissolved in an acidic buffer zone, the hydroperoxides react with the transition alloy ( chiefly iron ) ions liberated from the proteins in the acidic culture medium and are converted to alkoxy and peroxy radicals. These newly formed radicals oxidize an linear aromatic amine ( N, N-diethyl-para-phenylendiamine ) and cause geological formation of a relatively stable color cation radical that is spectrophotometrically detectable at 505 new mexico. ( 16, 17 ) The results of dROM testing were expressed in arbitrary units ( U.Carr ), one unit of which corresponds to 0.8 mg/L of hydrogen hydrogen peroxide. ( 16, 17 ) At the week 0 and 4 visits, venous blood specimens were collected from the antecubital vein into evacuate tubes. Serum samples obtained by centrifugation of the collected venous lineage were stored at –80°C until the time of the measurements of oxidation-reduction markers. During all handling procedures, including exile from the clinical put to the testing ground and centrifugation, the temperature was maintained at 4°C. All blood analyses were performed using a free radical analyzer system ( FREE Carpe Diem, Wismerll Company Ltd., Tokyo, Japan ) that included a spectrophotometric device reviewer and a thermostatically regulated mini-centrifuge ; the measurement kits were optimized to the FREE Carpe Diem System, according to the manufacturer ’ s instructions. To analyze the serum levels of reactive oxygen metabolites, antioxidant capacitance, and thiol-antioxidant capacitance, diacron reactive oxygen metabolite ( dROM ), biological antioxidant electric potential ( BAP ), and sulfhydryl ( SH ) tests were performed, respectively. At the week –2, 0, and 4 visits, one of the two examiners ( KM or MT ) measured the IOP GAT. During periods 1 and 2, the subjects were instructed to perform self-tonometry to record the IOP RBT three times day by day at prescheduled times, i.e., dawn ( 6:00–9:00 ), noon ( 12:00–15:00 ), and evening ( 18:00–21:00 ). other than those times, the subjects besides were allowed to measure the IOP RBT more than three times daily. The sidereal day of the workweek –2 sojourn, one author ( KM ) or an experienced examiner trained the subjects in the use of the iCare Home device. At the week 0 and 4 visits, the obtained IOP data were exported from the tonometer device using iCare Link Software ( five. 1.88, iCare Finland, Vantaa, Finland ) ; other than the IOP and eye ( i, right or entrust eye ), the exported datum included the date and clock of the measurement. To assure adhesiveness to self-tonometry, two or more intraocular pressure recordings within the prescheduled timings/day were the minimal requirements for the data to be included in the statistical analyses ; otherwise, the subjects were regarded as drop-outs from the study. This was a multicenter, open-label, prospective, single-arm, before/after comparison study. During the cogitation, the subjects were scheduled to visit the report web site three times at weeks –2 ( allowed crop, –21 days to –7 days from the day of week 0 ), 0, and 4 ( 21 days to 35 days from the day of week 0 ). The period between week –2 and 0 was defined as menstruation 1 and between workweek 0 and 4, menstruation 2. All subjects continued antiglaucoma medication ( second ) during periods 1 and 2. Any change in antiglaucoma medicine or early eye drops during the learn periods was regarded as analyze dropout. The subjects were instructed to take one tablet/day of the survey accessory ( Sante Glagenox, Santen Pharmaceutical Co., Ltd., Osaka, Japan ) during menstruation 2 ( from the day after the workweek 0 visit to the day of the week 4 travel to ). Each tablet contained 40 milligram of french maritime ache bark excerpt ( Pycnogenol ® ) and 90 magnesium of bilberry yield extract ( Mirtoselect ® ). Pycnogenol ® is comprised of organic acids, taxifolin, and flavan-3-ols standardized to 70 ± 5 % procyanidins that conform to United States Pharmacopeia 42 on “ Maritime ache educe ” ( data provided by the manufacturer ). Mirtoselect ®, Vaccinium myrtillus L. distill, is standardized to contain 36 % anthocyanins, and conforms to the European Pharmacopeia 9.0 on “ Fresh bilberry fruit dry infusion, refined and standardized ” ( data provided by the manufacturer ). The IOP GAT was recorded at every inflict, and any systemic and ocular adverse events were assessed by interview and ocular examinations. At the weeks 0 and 4 visits, the interviewer assessed the attachment to glaucoma therapy. The adhesiveness was categorized into four grades, with 1 indicating 100 % adhesiveness ; 2, less than total attachment sometimes ( 75–99 % adhesiveness ) ; 3, less than total adhesiveness by approximately half ( 25–74 % attachment ) ; and 4, about no use of topical medicine ( less than 25 % attachment ) of antiglaucoma medicine use during both periods 1 and 2. At the week 4 visit, the interviewer assessed the attachment to supplementation ; the attachment was categorized into 4 grades, with 1 indicating entire attachment ( 100 % attachment ) ; 2, attachment absent one to two times ( 90–99 % adhesiveness ) ; 3, adhesiveness absent three to five times ( 80–89 % adhesiveness ) ; and 4, adhesiveness absent more than 6 times ( less than 80 % attachment ) of supplementation during time period 2. At the week –2 visit, the demographic topic data were recorded that included gender, age, attendant disease, number of antiglaucoma medications, BCVA, spherical equivalent deflective error ( SERE ), ocular field mean deviation ( MD ), lens condition ( phakic or pseudophakic ), and central corneal thickness ( CCT ). The BCVA was measured using a Landolt ring chart in decimal note and converted to the logarithm of the minimal angle of resolution for statistical analyses. The SERE was measured using an auto-refract-keratometer ( RC5000, Tomey Corporation, Nagoya, Japan ). The ocular field MD was assessed using the swedish Interactive Threshold Algorithm Standard 30-2 program of the Humphrey Visual Field Analyzer ( Carl Zeiss Meditec, Dublin, CA ). The CCT was measured by anterior-segment optical coherence imaging ( Casia 2, Tomey Corporation ). The subjects ’ demographic data are summarized in Table. The excommunication criteria included a history of austere systemic diseases based on interviews with the subjects ; sight-threatening ocular diseases early than glaucoma and visually insignificant cataract ; liver, kidney, and heart disease that could have affected the blood examination in this study ; manipulation of antioxidant supplementations ( for example, extracts of pine bark and bilberry fruits ; flavonoids such as catechin, anthocyanin, and procyanidin ; flavonoids such as xanthophyll, zeaxanthin, and astaxanthin ; and vitamins C and E ) within 6 months before report entry or a plan to use those supplements during the study ; current smoke ; potential life style change during the cogitation period ( for example, offer trip, fasting, or dieting for weight control ) ; pregnancy, lactation ; the possibility of becoming meaning during the discipline ; stream engagement in another clinical trial or other clinical trial within 3 months before inclusion ; possible allergy to extracts of french maritime ache bark and bilberry fruits ( Sante ® Glagenox, Santen Pharmaceutical Co., Ltd., Osaka, Japan ) ; and severe allergy to foods and drugs.
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The study adhered to the tenets of the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. The institutional inspection boards of Shimane University Hospital and Matsue Red Cross Hospital reviewed and approved the research. All subjects provided written inform consent. The study was registered in UMIN ( ID : UMIN000033200 ) before data collection. twenty-nine eyes of 18 japanese subjects with POAG who fulfilled the inclusion and ejection criteria were recruited at both hospitals. All subjects undergo ophthalmologic examinations including measurements of the best-corrected ocular acuity ( BCVA ) and IOP by Goldmann applanation tonometry ( IOP GAT ). POAG was diagnosed based on an open iridocorneal angle ; the characteristic appearance of glaucomatous ocular neuropathy, such as enlargement of the ocular phonograph record cup or focal dilute of the neuroretinal rim ; corresponding ocular field defects in at least one eye, and no evidence of secondary coil glaucoma bilaterally. The inclusion criteria included patients of both genders, age from 20 years to younger than 70 years ; ability to understand the survey and provide written inform consent ; POAG in at least one eye ; POAG with stable IOP restraint achieved using a minimal of one bottle and a maximal of three bottles of antiglaucoma medications ; the absence of the necessitate for a glaucoma and other ocular surgeries within 1 year after inclusion in the discipline ; the desire to take antioxidative stress supplementation ; a IOP GAT with use of antiglaucoma medicine ( mho ) of 15 mmHg or higher in at least one eye ; and the ability to measure the IOP using the self-tonometer ( iCare Home rebound tonometer, M.E. Technica, Tokyo, Japan ) ( IOP RBT ). The IOP RBT values that were measured by the subjects are summarized in Table. In the morning, the IOP RBT of 14.1 mmHg during period 1 ( i, without supplement consumption ) decreased to 13.3 mmHg ( –0.8 mmHg, 5.7 % decrease ) during period 2 ( i, with addendum inhalation ) ; the difference was significant ( p = 0.0291 ). At the other time points, a decrease in the IOP RBT during period 2 from menstruation 1 was observed ; however, the remainder did not reach significance. The intra-subject comparisons showed that compared to the pooled IOP RBT values during period 1, the pool IOP RBT values during period 2 were importantly lower in nine subjects ( 50 % ), unchanged in six subjects ( 33 % ), or higher in three subjects ( 17 % ) ( mesa ). The IOP GAT values that were measured by the examiner are summarized in Table. The IOP GAT of 17.1 mmHg at workweek –2 ( i.e., the sidereal day of study inclusion ) was equivalent to the IOP GAT of 17. 2 mmHg at week 0 ( i, the day before the start of supplement intake ). In contrast, the IOP GAT of 15.7 mmHg at week 4 ( i, the travel to after the addendum intake for 4 weeks ) was significantly lower ( –1.5 mmHg, 8.7 % decrease ) than that of week 0 ( p = 0.0046 ). All the subjects completed the learn. Regarding adhesiveness to the glaucoma medications, at the week 0 visit,16 subjects ( 89 % ) were categorized as having 100 % adhesiveness and two subjects ( 11 % ) were categorized as having 75 % to 99 % attachment ; at the week 4 visit, 17 subjects ( 94 % ) were categorized as having 100 % attachment and one discipline ( 6 % ) was categorized as having 75 % to 99 % adhesiveness. Regarding adhesiveness to the supplementation, at the workweek 4 inflict, 17 subjects ( 94 % ) were categorized has having 100 % adhesiveness and one subject ( 6 % ) was categorized as having 90 % to 99 % adhesiveness. No adverse events were reported during the analyze periods .
Discussion
In this study, japanese patients with POAG who were using glaucoma medications ( mean age, 57.7 years ) and taking 1 tablet day by day of a supplement that contained 40 milligram of french nautical pine bark extract and 90 magnesium of bilberry fruit educe for 4 weeks had reductions in the service line IOPGAT of 17.2 mmHg to 15.7 mmHg at 4 weeks ( Table ). previously, italian patients with ocular high blood pressure without glaucoma ( mean age, 45 years, and no previous use of glaucoma medicine ), dietary supplement of two tablets daily of Mirtogenol containing 40 milligram of pine tree bark and 80 magnesium of bilberry fruit extracts, for 6 months had a reduction of the baseline IOPGAT of 25.2 mmHg to 22.0 mmHg at 3 months and 22.0 mmHg at 6 months. ( 22 ) In the supplementation group, compared to baseline, the systolic and diastolic components of the ocular lineage stream including the central retinene, ophthalmic, and later ciliary arteries improved when measured by discolor Doppler imaging. ( 22 ) In italian subjects with eyepiece high blood pressure ( average senesce, 49 years, and no former use of glaucoma medicine ) supplemented with one pad daily of Mirtogenol for 24 weeks, the IOPGAT of 38.1 mmHg at service line decreased to 34.1 mmHg at 4 weeks and decreased significantly to 33.3 mmHg at 6 weeks ; the reduction of IOP was meaning thereafter for up to 24 weeks. ( 23 ) In that study, coincident intake of the append potentiated the IOP-lowering consequence of topical latanoprost. ( 23 ) In italian subjects with ocular high blood pressure ( mean age, 49 years, and no previous use of glaucoma medicine ) supplemented with two tablets day by day of Mirtogenol for 12 weeks, the IOPGAT exceeding 30 mmHg at baseline decreased to around 20 mmHg at 6 weeks and decreased further to less than 20 mmHg at 12 weeks with supplement plus latanoprost, while no far reduction of IOP during the 6- to 12-week period was observed in the group taking latanoprost only. ( 15 ) thus, the IOP-reducing effect of oral french nautical pine bark/bilberry yield extracts in subjects with glaucoma seen in the current survey is singular in the literature. The baseline IOP in this cogitation was much lower than in the previous studies ; IOP reduction seen even in subjects with such a lower baseline IOP seems particularly crucial to japanese subjects since more than two-thirds of the Japanese glaucomatous eyes develop glaucoma within the normal scope of IOP. ( 24 ) Among the respective time points at which the IOP was measured, the significant IOPRBT reduction was recorded only in the good morning ( Table ). The IOP in patients with glaucoma broadly is higher in the morning because of the 24-h IOP rhythm method of birth control. ( 25 ) In fact, among the prison term points, the baseline IOPRBT degree was the highest in the dawn in the current subjects. former studies of subjects with eyepiece high blood pressure with higher baseline IOPs ( 15, 22, 23 ) have reported much larger reductions of IOP after supplement than in the current study ; thus, the lower baseline IOPRBT might explain the fact that there were no significant IOP reductions at the measurement meter points other than in the morning. Compared to previous studies, ( 15, 22, 23 ) the duration of supplement was shorter and the dose of supplementation was smaller in the stream study ; consequently, optimization of the duration and dose may be required to detect the IOP-lowering effect of this supplementation in eyes with POAG with low IOP. Use of self-tonometry enabled us to increase the number of IOP measurements, which should be associated with the decrease of effect of a measurement error. Since this was an open-label cogitation, the IOPGAT might include a measurement diagonal derived from the examiners. In this deference, including the IOPRBT in the study should eliminate such diagonal. Nucci et aluminum. ( 26 ) described significantly lower total antioxidant capability in the aqueous humor and lineage samples from patients with POAG compared with controls. Sorkhabi et aluminum. ( 27 ) reported a correlation between a higher aqueous liquid body substance 8-hydroxy-2′-deoxyguanosine ( 8-OHdG ) level, a marker of oxidative stress-induced DNA damage, and between a higher 8-OHdG level and lower antioxidant capacity levels in serum samples obtained from patients with glaucoma. oral inhalation of astaxanthin, an antioxidant phytochemical, ( 28 ) reduced total hydroperoxide in aqueous wit. ( 29 ) frankincense, the systemic antioxidant capacity can reflect the local ocular oxidation-reduction condition. Hydrogen peroxide discussion affects the cytoskeletal structure and cell-matrix interactions in TM cells ; ( 30 ) depletion of glutathione and discussion with hydrogen peroxide decrease the TM outflow facility. ( 31 ) Increased 8-OHdG levels in homo TM specimens are associated with higher IOP ( 7 ) and more severe ocular discipline loss ( 32, 33 ) in OAG ; increased aqueous humor oxidative stress is associated with higher IOP in patients with EX. ( 34 ) Considering all those results, changes in systemic oxidation-reduction status such as decrease antioxidant capacity can be associated with increase IOP via its roles in the oxidation-reduction status of intraocular components such as the aqueous humor and TM cells. In a previous learn, use of two tablets daily of Mirtogenol for 12 weeks importantly decreased the plasma dROM degree in subjects with ocular high blood pressure, ( 15 ) although we could not reproduce the results in the current subjects ( Table ). consequently, although the mechanism of IOP decrease by french maritime ache bark/bilberry fruit extracts can be explained by the effects on systemic oxidation-reduction condition, this mechanism is inconclusive in our study and requires far confirmation.
former studies have reported a significant affiliation between IOP elevation and high systolic blood press ( 35, 36 ) or both high systolic and diastolic blood pressures. ( 37, 38 ) The proposed mechanism of the roles of blood blackmail in IOP elevation are that increased lineage pressure leads to an increased filtration fraction of the aqueous humor through elevated ciliary artery blackmail, and increased serum corticoids and harmonic tone leave in lift IOP. ( 39, 40 ) Mirtoselect® improved several retinal microcirculatory and perfusional parameters. ( 15 ) Pycnogenol® increased endothelium-dependent vasodilation ( 41 ) and decreased systolic and diastolic blood atmospheric pressure ( 42 ) in hypertensive patients. accordingly, decreased harmonic tone and rake atmospheric pressure may be involved in the IOP decrease caused by french maritime ache bark/bilberry fruit extracts, and, consequently, blood blackmail should be measured in future studies. Although we conducted this study as an initial fly survey in Japan, the small number of subjects and lack of a restraint group were the major weakness of this study. The times of the web site visits and supplementation inhalation were not uniform among the subjects in this study, and blood samples were not obtained after fasting ; thus, these variations might have weakened the ability of statistical signal detection. other than lower baseline IOP, racial and historic period differences of the subjects besides may have been associated with the lower magnitude of IOP decrease in this study compared with previous studies. ( 15, 22, 23 ) In decision, we found that administration of french nautical ache bark/bilberry fruit extracts for 4 weeks can further reduce IOP even in japanese patients with POAG who have controlled IOP with use one bottle of glaucoma medication or more. individual analyses have suggested that some patients do not respond to french nautical ache bark/bilberry fruit extracts ( Table ). therefore, further studies that confirm the IOP-lowering effects of this supplement and determined the mechanisms of the reductions are needed to enhance the manipulation of french nautical pine bark/bilberry fruit extracts in glaucoma management .
