The effects of smoking on dry eye parameters in healthy women

Aim: To investigate the effects of chronic smoking on dry eye parameters.

Methods: Ocular surface disease index (OSDI) and tear function tests such as Schirmer’s test, tear break-up-time (TBUT) test and impression cytology of 63 female chronic smokers and 40 age-matched female non-smokers were analyzed statistically.

Results: The mean OSDI scores, Schirmer test results and TBUT levels were 35.85?±?24.01 point, 14.25?±?5.94?mm and 5.17?±?2.85?s in chronic smokers and 15.20?±?12.93 point, 15.48?±?7.01?mm and 10.03?±?3.44?s in non-smokers, respectively. Differences in OSDI scores, TBUT levels and impression cytology grades among the chronic smokers and non-smokers were statistically significant.

Conclusion: Smoking behavior seems to affect the dry eye parameters negatively.     

Reduced central corneal thickness in patients with isotretinoin treatment

Context: It is well known that oral isotretinoin treatment causes numerous ocular side-effects.

Objective: To investigate the effect of systemic isotretinoin treatment on central corneal thickness (CCT) values due to meibomian gland disease (MGD).

Participants: In this prospective study, 47 patients (27 men, 20 women) with nodulocystic acne vulgaris treated with oral isotretinoin (0.8?mg/kg daily) were included.

Methods: All patients were analyzed with the Pentacam Scheimpflug topography at baseline, on the 3rd and 6th month of treatment. Main outcome measures were MGD scores and CCT.

Results: The mean age of patients was 25.1?±?4.4 years. The mean MGD scores were significantly higher at 3rd month (1.3?±?0.9) and 6th month (1.5?±?1.0) of treatment compared with baseline (1.1?±?0.9) (p?p?p?=?0.038, r?=??0.221).

Conclusion: Isotretinoin treatment causes higher MGD scores. A statistically significant decrease in CCT due to MGD was detected at 6th month of treatment.     

The ocular surface side effects of an anti-psychotic drug,clozapine

Purpose: The purpose of this study is to investigate the effects of long-term clozapine usage on tear film stability and corneal topographic parameters.

Material and methods: The study was conducted between March 2014 and November 2014. Thirty patients who were diagnosed of schizophrenia and have been under clozapine treatment for 2.73?±?0.73 years (range 2–4 years) were involved in this study (group 1). Thirty healthy subjects (group 2) who have statistically similar demographic features compared with the group 1, were involved as a control group. Full ophthalmologic examination with biomicroscopy and indirect ophthalmoscopy was applied. Corneal topographic parameters were measured using the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL) program.

Results: K₁ value was measured as 43.39?±?0.17?D (43–43.50?D) and K₂ value was measured as 43.39?±?0.06?D (43.30–43.50?D) in groups 1 and 2, respectively. In groups 1 and 2, K₂ values were noted as 43.86?±?0.27?D (43.50–44.50?D) and 43.72?±?0.18?D (43.50–44.00?D), respectively. Central corneal thickness was found to be 523.93?±?15.66?µm (495–554?µm) and 550.13?±?1.03?µm (520–580?µm) in groups 1 and 2, respectively. Corneal apex thickness was 525.86?±?15.75?µm (497–556?µm) in group 1 and 551.60?±?14.99?µm (521–581?µm) in group 2. The corneal thickness of thinnest location was 520.93?±?15.60?µm (492–551?µm) and 548.06?±?15.17?µm (518–578?µm) in groups 1 and 2, respectively. Corneal volume was determined as 58.13?±?3.46?mm³ (52–64?mm³) in group 1 and 60.73?±?3.76?mm³ (54–66?mm³) in group 2. The Schirmer test showed thichkness of 3.33?±?0.72?mm (2–4?mm) and 13.60?±?1.59?mm (11–16?mm) in groups 1 and 2, respectively. The mean fluorescein break-up time was 5.40?±?1.50?s (3–8?s) and 12.46?±?1.40?s (10–14?s) in groups 1 and 2, respectively. There was a statistically significant difference in the Schirmer test, fluorescein break-up time, central corneal thickness, corneal apex, and the thinnest corneal location thickness between the two groups.

Conclusion: Clozapine may induce dry eye syndrome and thus may lead to morphological alterations in corneal parameters through its anticholinergic and antidopaminergic activities. Because of these corneal alterations, one should be aware of evaluating patients having diseases like glaucoma or preoperative selection of corneal refractive surgery candidates.     

The long-term effect of oral isotretinoin therapy on macula ganglion cell complex thickness

Purpose: To evaluate the long-term effect of oral isotretinoin therapy on macula ganglion cell complex (GCC) thickness by spectral domain optical coherence tomography (SD-OCT).

Materials and methods: Newly diagnosed cystic acne patients who received low dose for a long time systemic isotretinoin therapy were included in this study. Thorough ophthalmic evaluation and GCC thickness analysis by using SD-OCT were performed at baseline, and at 1, 3, 6, and 12 months of treatment.

Results: Forty-eight eyes of 24 patients (15 females, 9 males) were included in the study. The mean age of patients was 19.37?±?2.74 years (range 14–25 years). The full ophthalmologic examination was normal in all eyes before treatment. During the treatment there were no change in visual acuity, refractive error, intraocular pressure and tear break-up time. The mean GCC thicknesses were 81.45?±?4.91, 81.45?±?5.12, 81.81?±?4.68, 81.87?±?4.91 and 81.64?±?5.09?μm at pretreatment and at 1, 3, 6, and 12 months of treatment, respectively (p?=?0.803).

Conclusion: One-year systemic use of isotretinoin had no significant effect on the thickness of macula ganglion cell. Macular ganglion cell analysis is useful for determining and following the toxic effects of systemic drugs on the retina. However, it is more rational to consider it as an adjunct to electrophysiological testing rather than used alone.     

Ocular surface changes following oral anticholinergic use for overactive bladder

Objective: To investigate the effect of oral solifenacin succinate on Schirmer I test results, tear break-up time (TBUT) and Ocular Surface Disease Index (OSDI) scores in overactive bladder (OAB) patients and to compare these results with those of healthy control subjects.

Materials and methods: The female OAB patients who were prescribed oral solifenacin succinate 5?mg/day (Group I, N?=?80) and age-matched healthy female subjects (Group II, N?=?40) were recruited for the study and underwent ophthalmological examination prior to oral treatment and after 4 weeks. They completed the OSDI questionnaire and underwent ocular surface tests including Schirmer I test and TBUT.

Results: The statistical analysis of the Schirmer I test and TBUT revealed no significant difference between the baseline and 4th week values in both groups (Group I, p?=?0.506 and p?=?0.070 consecutively) (Group II, p?=?0.810 and p?=?0.823 consecutively). OSDI scores were found to be significantly increased in group I (21.8?±?4.2 vs 23.1?±?4.6, p?=?0.020) and remained unchanged in group II (20.5?±?7.0 vs 20.7?±?7.0, p?=?0.805).

Conclusions: Short-term solifenacin succinate treatment has no effect on the Schirmer I test results and TBUT, but ocular surface symptoms appeared to be exacerbated in respect with increased OSDI scores. However, the clinical significance needs to be further evaluated with larger studies.     

Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biological agent therapy

Purpose: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents.

Methods: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer’s II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed.

Results: Thirty-eight patients with a mean age of 53.00?±?8.19 years were in group 1 and 18 patients with a mean age of 51.00?±?9.54 years were in group 2. The mean duration of RA was 6.89?±?7.96 years in group 1 and 5.70?±?9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer’s II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05).

Conclusions: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower.     

The promising effect of barberry (Zereshk) extract against experimental pulmonary microvascular remodeling and hypertension: A comparison with sildenafil

Context: Despite the beneficial effects of barberry (Berberis integerrima Berberidaceae) on decreasing systemic hypertension, its influence has not been investigated on pulmonary hypertension.

Objective: The objective of this study is to examine the effect of barberry fruit, on monocrotaline-induced pulmonary hypertension.

Materials and methods: Nine groups were arranged as follows: the control group, the monocrotaline (M) group, the barberry groups with doses of 50, 100, and 200 (mg/kg), the M plus barberry groups, and the M plus sildenafil group. Two weeks after a single injection of monocrotaline (60?mg/kg, s.c.), barberry water extracts or sildenafil (30?mg/kg/d) were gavaged daily for 2 weeks. At the end of the 4th week, hemodynamic, biochemical, and histopathological parameters were assessed.

Results: In comparison with the M group, barberry (200?mg/kg) or sildenafil significantly reduced the right ventricular systolic pressure (RVSP) (22.95?±?1.78?mm Hg and 30.71?±?1.64?mm Hg, versus 41.28?±?1.5?mm Hg), right ventricular hypertrophy (RVH) (0.39?±?0.03 and 0.42?±?0.02, versus 0.57?±?0.02), and the medial wall thickness (MWT) (4.56?±?0.15?µm and 5.97?±?0.19?µm, versus 7.02?±?0.43?µm). Barberry or sildenafil had no significant effect on the plasma level of endothelin-1, glutathione peroxidase, and the malondialdehide of lung.

Conclusion: 200?mg/kg of barberry has an improving effect on the monocrotaline-induced pulmonary hypertension. This effect was stronger than that of the sildenafil's and may have been mediated through mechanisms other than the modulation of the endothelin-1 or redox system.     

Effect of chronic smoking on lens nucleus as assessed by Pentacam HR lens densitometry in young adults

Objective: To evaluate the effects of chronic tobacco smoking on lens nucleus by Pentacam HR lens densitometry (LD) in young adults.

Design: Prospective cross-sectional case series.

Methods: Thirty subjects (23?M, 7 F) who were chronic cigarette smokers (≥10 cigarettes/day for at least 2 years) (group 1) and another 30 subjects (23?M, 7 F) who did not smoke (group 2), were included in this study. The patients were matched for age and sex between the groups. The exclusion criteria were any history of ocular surgery, any systemic disorders and any ocular diseases except for mild refractive disorders. Lens densitometry measurements were done with the Pentacam HR (Oculus, Wetzlar, Germany). The Schirmer test and pachymetry measurements were also performed.

Results: Mean age of the patients for both groups was 28.90?±?8.20 years (range: 18–40 years). Mean lens densitometry (LD) measurements of Group 1 (chronic cigarette smoking group) were higher than those of Group 2 (control group) in all LD techniques; however only mean “peak” LD measurements showed a statistically significant difference between these two groups (Group 1: 8.67?±?0.61, Group 2: 8.44?±?0.70, p?=?0.04). The mean Schirmer test value was 12.43?±?5.60?mm in Group 1 and 13.00?±?4.26?mm in Group 2 (p?=?0.55). The mean central corneal thickness (CCT) value was 564.23?±?34.61?µm in Group 1 and 550.47?±?32.94?µm in Group 2 (p?=?0.03).

Discussion: The Pentacam HR LD seems to be an important option for the evaluation of lens nucleus in young adults, because it gives objective and quantitative data.

Conclusion: Although chronic smoking increases lens nucleus density in young adults, the effect is not statistically significant when compared with the control group.     

Trimetazidine Limits the Effects of Myocardial Ischaemia During Percutaneous Coronary Angioplasty

Summary

This open-label, randomised, controlled study is aimed at assessing the effect of pre-treatment with the metabolic agent trimetazidine on the degree of ischaemia during percutaneous transluminal coronary angioplasty (PTCA).

Overall 44 patients with one-vessel coronary artery stenosis (>70%) in the medial part of the left anterior descending artery were included. One group (n?=?22) was pre-treated with oral trimetazidine. The other group (n?=?22) was the control. All patients (n?=?44) were administered aspirin and conventional treatment.

All patients underwent PTCA; stents were implanted in 11 trimetazidine patients and in seven control patients.

The mean ST-segment elevation during all balloon inflations was significantly lower in the trimetazidine group than in the control group (?1.66?±?1.50?mm vs. 3.29?±?1.59?mm, p?=?0.001). Maximal ST-segment elevations and

mean ST elevation values during sequential balloon inflations were also significantly lower with trimetazidine (p?=?0.018). The mean amplitude of the T-wave alterations during all balloon inflations was significantly lower with trimetazidine (3.09?±?2.39?mm vs. 6.83?±?4.31?mm; p?=?0.001). Similarly, the maximal amplitude of the T-wave alterations was 4.50?±?2.90?mm with trimetazidine vs. 9.25?±?4.97?mm in control patients (p?=?0.0005). Angina and rhythm disturbances were more frequent in the control group. Time from balloon inflation to onset of angina was 50?±?26.2s with trimetazidine vs. 32?±?15.0s, for control group (p?=?0.03). The time to pain relief after deflation was 19.3?±?11.4s with trimetazidine vs. 28.2?±?16.8s (p?=?0.001).

Trimetazidine administered a few days before PTCA appears to be a cardioprotective agent for the prevention of myocardial ischaemia.     

Effect of intravitreal injection of dexamethasone implant on corneal endothelium in macular edema due to retinal vein occlusion

Objective: To evaluate the effects of dexamethasone (DEX) implant (Ozurdex®) on corneal endothelium in patients with retinal vein occlusion complicated with macular edema.

Materials and methods: Patients (n?=?31) received 1–3 intravitreal DEX implants in one eye. Measurements were intraocular pressure (IOP) at baseline and 1, 3, and 6 months after the first intravitreal injection and corneal specular microscopy and central corneal thickness (CCT) at baseline and 1 and 6 months. We analyzed endothelial cell density (ECD), coefficient of variation of cell size (CV), and percentage of hexagonality.

Results: Mean follow-up period was 9.7?±?3.3 months. Mean number of injections was 1.5?±?0.8. Mean IOP values were 15.6?±?2.6?mm Hg at baseline, 17.7?±?3.6?mm Hg at one month, 16.4?±?4.1?mm Hg at three months, and 16.0?±?2.7?mm Hg at six months. There was a significant difference in mean IOPs at one month and six months (p?=?0.008). There were no significant differences in mean ECD (p?=?0.375), CV (p?=?0.661), percentage of hexagonality (p?=?0.287), and CCT (p?=?0.331).

Conclusion: Although intravitreal injection of 0.7?mg DEX causes moderate elevation of IOP, it does not seem to have detrimental effects on corneal endothelium at six months.     

Effect of isotretinoin treatment on the inflammatory markers in patients with acne vulgaris: can monocyte/HDL be a new indicator for inflammatory activity of isotretinoin treatment?

Abstract

Background: Oral isotretinoin (ISO) can effect markers of inflammation in patients with acne vulgaris. To our knowledge, there are no data on the relationship between ISO and monocyte to HDL cholesterol ratio (MHR). In this study, it is aimed to examine the effect of the ISO treatment on the MHR and other inflammatory markers in patients with acne vulgaris.

Materials and methods: In this study, 89 out of 120 patients with severe/very severe acne vulgaris according to the Global Acne Grading Scale who received at least 3 months of ISO treatment were evaluated. The complete blood counts including mean levels of mean platelet volume, plateletcrit (PTC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), MHR, and serum biochemistry panel were evaluated before and after ISO treatment.

Results: The mean platelet value, NLR, and PLR levels underwent a statistically significant decrease after ISO treatment (p?<?0.05) while MHR increased significantly 3 months after ISO treatment (p?=?0.017). The mean platelet value, NLR, and PLR levels were 9.56?±?1.05, 2.15?±?0.81, and 142.45?±?48.33 before treatment while were 9.32?±?1.45, 1.90?±?0.99, and 127.94?±?41.38 after treatment, respectively. On the other hand, MHR was 9.76?±?4.27 and 10.86?±?4.12 before and after treatment, respectively.

Conclusions: In this study, we found that ISO may have both inflammatory and anti-inflammatory effects by using MPV, PTC, NLR, PLR, and MHR. The inflammatory effects of ISO may be associated with possible inflammatory diseases. MHR can be used as a novel marker to investigate the inflammatory effect of the ISO.     

The short-term and long-term adverse ocular effects of fesoterodine fumarate

Aim: To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA).

Method: Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4?mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically.

Results: The mean age of 120 women was 52.06?±?9.39 years (30–70 years). The mean PD, IOP and AA values were 4.12?±?0.61?mm (3.00–5.70?mm), 15.58?±?1.74?mmHg (11–20?mmHg) 2.28?±?1.26?Diopter (D) (0.50–5.50?D) at baseline; 4.68?±?0.65?mm (3.20–5.80?mm), 16.11?± 1.72?mmHg (11–20?mmHg), 1.68?±?1.04?D (0.25–4.50?D) at 30th day; and 4.28?±?0.58?mm (3.10–5.70?mm), 16.09?±?1.96?mmHg (11–19?mmHg), 2.18?±?1.19?D (0.50–5.00?D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p?<?0.001 for each), the changes in IOP values were not as such (p?=?0.642). Visual complaint was not observed in any patient.

Discussion: The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient.     

Ocular findings in breast cancer patients using tamoxifen

Aim: To examine ocular findings of breast cancer patients using tamoxifen.

Methods: The records of 79 consecutive breast cancer patients were examined, retrospectively. Female patients who had previously been diagnosed to have breast cancer with either stage I, II, or III disease, and were older than 25 years of age were included in the study. Results of the ophthalmic examination, color discrimination, and contrast sensitivity tests were recorded. Short wavelength automated perimetry (SWAP) sensitivity values were obtained, and average sensitivity values of test points at 5°, 9°, 15°, and 21° from the fixation were calculated.

Results: Forty-nine of the patients had received 20?mg daily dose of tamoxifen therapy (tamoxifen group), while remaining 30 patients had not used tamoxifen (control group). Anterior and posterior segment examination revealed no pathologic findings in both groups. Two patients (5%) in the tamoxifen group had diffuse color loss, while none did in the control group (p?=?0.523). Statistically significant differences were not detected between two groups when square roots of total error in color vision, red-green, and blue-yellow partial error scores were compared. Contrast sensitivity values were similar in both groups. Average mean deviation (MD) and average sensitivity values of test points at each 4° were statistically significantly lower in the tamoxifen group than the control group (p?=?0.002, p?=?0.001, p?p?p?=?0.002, p?=?0.001, p?p?r?=??0.832 and r?=??0.842 for right and left eyes, respectively) and cumulative dose of tamoxifen use (r?=??0.864 and r?=??0.854 for right and left eyes, respectively).

Conclusion: Clinically significant ocular toxicity is not frequently encountered in breast cancer patients, however, SWAP changes may occur early after tamoxifen utilization.     

Effect of topiramate on choroidal thickness and anterior chamber parameters in the treatment of patients with migraine

Objective: To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.

Methods: A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.

Results: Mean age of the patients was 40.2?±?6.5?years. Mean CT at central fovea was 324?±?47?μm initially, 341?±?45?μm in the first month and 344?±?46?μm in the second month, thus first and second month measures were significantly higher than base values (p?p?=?0.001). Baseline ACD (3.66?±?0.22?mm) measures significantly decreased at the first month (3.63?±?0.22?mm) and second month (3.62?±?0.22?mm, p?=?0.009). Also, a significant reduction was detected in the first (36.2?±?4.9°) and second month (35.9?±?5.1°) ACA measures comparing with baseline (39.1?±?5.1°, p?=?0.05). A significant myopic shift was determined in the first and second month SphEq values (?0.08?±?0.6, ?0.10?±?0.6, respectively, p?=?0.05).

Conclusions: The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.     

Effects of selective serotonin reuptake inhibitors on intraocular pressure and anterior segment parameters in open angle eyes

Purpose: To evaluate the short- and long-term effects of selective serotonin reuptake inhibitors (SSRIs) on intraocular pressure (IOP) and anterior segment parameters in open angle eyes.

Materials and methods: This cross-sectional study included 325 eyes of 166 subjects. Subjects were divided into three groups: Group 1 included 116 eyes of 58 patients receiving SSRIs for 1?week–6?months, Group 2 included 102 eyes of 53 patients receiving SSRIs for longer than 6?months and Group 3 included 107 eyes of 55 healthy subjects not receiving any drugs. All of the patients receiving SSRIs were diagnosed as major depressive disorder. All groups were chosen to be similar in terms of age and gender. All patients underwent a detailed ophthalmologic examination including IOP measurement by Goldmann applanation tonometer and gonioscopy. Anterior segment parameters including pupil diameter (PD), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were assessed by a Scheimpflug system.

Results: Pupil diameter was significantly larger in patients receiving SSRIs for <6?months and ≥6?months than the control subjects (3.53?±?0.71?mm, 3.48?±?0.60?mm versus 3.11?±?0.72?mm, p?p?Conclusions: Selective serotonin reuptake inhibitors cause mydriasis which is persistent during the treatment. In depression patients with open angle eyes, short- and long-term use of SSRIs leads to decrease in IOP.     

Evaluation of proton beam radiation sensitivity of proliferating choroidal endothelial and retinal ganglion cells with clonogenic assay

Context: Proton beam therapy offers the advantage of precise delivery with limited damage to the healthy tissue and is being tested in the management of exudative age-related macular degeneration (AMD). However, the dosages tested are empirical and not based on preclinical studies.

Objective: In this study we evaluated the effects of varying doses of proton beam radiation on choroidal endothelial cells (CECs) and retinal ganglion cells (RGCs) using clonogenic assay to determine differential sensitivity.

Materials and methods: Each cell type has different efficiency to replicate (plating efficiency (PE)). PE of CEC (RF/6A) and RGC (RGC-5) grown in culture flasks was determined by plating 250 cells each (without any treatment) and counting the number of colonies after 13 days. Radiation induced sensitivity was determined by exposing the semi-confluent RF/6A and RGC-5 cells to proton beam at the doses of 0 (control), 2, 4, 8 and 12 cobalt gray equivalent (CGE). The ability of the cells to repair and replicate to form colonies were analyzed 13 days after radiation with crystal violet stain and the survival ratio was calculated. The significance of survival was analyzed using ANOVA (Graphpad Instat.3).

Results: The PE of CEC and RGC was 12.96?±?0.29% and 40.7?±?1.48%, respectively. A survival ratio of CEC at 2, 4, 8 and 12 CGE proton radiation was 66.0?±?8.6%, 44.3?±?6.5%, 7.6?±?0.3% and 1.14?±?0.06% on exposure to 2, 4, 8 and 12 CGE proton radiation, respectively, p?<?0.01). Survival ratio of RGC was 71.1?±?22.4% (p?=?0.05), 40.2?±?7.9%, 8.89?±?2.6% and 0.78?±?0.31% at 2, 4, 8 and 12 CGE dosages (p?<?0.001).

Discussion: CEC showed dose-dependent decrease in survival rate with values attaining significance at all radiation dosages. In contrast, RGC was comparatively radio resistant and were able to replicate at lower doses and sensitive at higher doses after proton beam radiation.

Conclusion: Since CECs proliferate during neovascularization, this clonogenic assay is a useful assay to assess the sensitivity of CEC to radiation. This study identified that CEC were more sensitive to proton beam radiation than RGC at all doses. This may provide a therapeutic window for administration of proton beam radiation in the management of AMD.     

Hydroxysafflor yellow A attenuates left ventricular remodeling after pressure overload-induced cardiac hypertrophy in rats

Context: Hydroxysafflor yellow A (HSYA), the main chemical component of the safflower yellow pigments, is used extensively in traditional Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.

Objective: The present study determined the effects of HSYA on left ventricular hypertrophy after pressure overload and investigated the underlying mechanisms.

Materials and methods: Cardiac hypertrophy was induced by the ligation of abdominal aorta in male Wistar rats. The rats were then divided into five groups and treated with captopril (100?mg/kg) or HSYA at different doses (0, 10, 20 and 40?mg/kg). Six weeks after treatment, the weight of left ventricle, LVMI (left ventricular mass index) and pathological changes were measured. MMP-2 (metalloproteinase 2) and MMP-9 (metalloproteinase 9) levels were determined by ELISA. Protein expressions of Bcl-2 and Bax were evaluated by immunohistochemistry.

Results: HSYA (20, 40?mg/kg) significantly attenuated the increase of LVMI (ventricular weight/body weight) by 13.04 and 30.43% respectively, when compared with the model group. This was associated with the amelioration of pathological lesion, such as cardiac muscle fibers were smaller and the nuclei of cardiomyocytes were lightly stained in animals treated with HSYA (20, 40?mg/kg). In addition, the administration of HSYA at doses of 20 and 40?mg/kg increased the Bcl-2/Bax ratio (1.17?±?0.08 and 1.39?±?0.07 versus 0.71?±?0.06). In addition, the serum MMP-2 and MMP-9 levels were blocked by the treatment at doses of 20 and 40?mg/kg HSYA (MMP-2, 76.1?±?9.2 and 65.6?±?6.8 versus 82.9?±?6.2, ng/ml; MMP-9, 66.6?±?4.8 and 57.5?±?5.0 versus 83.5?±?6.0, ng/ml).

Conclusion: These findings indicated that HSYA has beneficial effects on hypertensive ventricular remodeling, which may involve mechanisms of inhibiting cell apoptosis and suppressing metalloproteinases expression.     

Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats

Context: Diabetic neuropathic (DN) pain is one of the diabetes complications. Rosmarinic acid (RA), a natural phenol antioxidant, shows some biological activities, including anti-inflammatory, analgesic, and anti-diabetic effects.

Objectives: We investigated the efficacy of RA administration (10 and 30?mg/kg) on streptozotocin (STZ)-induced neuropathy in rats.

Material and methods: The animals received saline or RA (10 and 30?mg/kg, p.o.; once daily) for 8 weeks. DN was evaluated by the tail flick (TF) method, formalin test, and tactile allodynia. At the end, all rats were weighed and underwent plasma glucose measurement.

Results: There was an increase in licking time during both formalin test phases in diabetic animals (138.5?±?10.7 and 448.7?±?2.6?s) that was decreased by RA10?mg/kg (103.5?±?7.5 and 284.4?±?19?s) and RA 30?mg/kg (81.8?±?11 and 192.7?±?14?s). RA 30?mg/kg caused anti-nociception during the early phase in treated controls (52.1?±?6?s) than untreated controls (99.4?±?5.9?s). The TF latency in diabetics (2.9?±?0.1?s) was increased in RA10 and 30?mg/kg treated diabetics (5.3?±?0.4 and 6?±?0.86?s). The paw withdrawal threshold (PWT) of the diabetics (3.6?±?0.7?g) was increased after RA 10 and 30?mg/kg (13.8?±?0.3 and 14?±?0.4?g) treatment. RA did not induce a significant change in body weight and plasma glucose of rats.

Conclusion: RA showed efficacy in amelioration of some aspects of DN. Therefore, RA makes a good candidate for DN treatment in clinical studies.     

Attaining United States and European Guideline LDL-C Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

SUMMARY

Objectives: The primary objective was to assess the effects of rilmenidine monotherapy and in combination with perindopril on blood pressure (BP) in patients assessed with grade 1 or 2 essential hypertension. The study also examined the effects of 2-year rilmenidine monotherapy on left ventricular hypertrophy (LVH) and on diastolic function of the left ventricle, along with the effects of rilmenidine on left ventricular mass index in hypertensive patients with no LVH, and the relationship between BP reduction and any change in LVH.

Research design and methods: Mild-to-moderate hypertensive patients (n?=?500) were enrolled in a multicentre 2-year open study and treated with rilmenidine (1-2?mg per day) monotherapy or rilmenidine plus perindopril (2, 4 or 8?mg per day) if control of hypertension was not achieved with rilmenidine monotherapy within 12 weeks. Blood pressure was recorded at regular intervals by the investigators and LVH measured by centralised single-blind echocardiographic reading.

Results: Rilmenidine monotherapy (average dose 1.42?mg) produced a significant decrease in BPfrom the baseline of 163?±?10/100?±?5?mmHg to 134?±?10/86?±?7?mmHg at 1 year and to 136?±?10/84?±?7?mmHg at 2 years (p?2 at 2 years (p?Conclusions: Long-term rilmenidine monotherapy was shown to be efficient in controlling BP and in reducing LVH. The addition of perindopril to rilmenidine monotherapy proved to be effective and well tolerated in those patients who did not respond to rilmenidine alone.