Impact of intravitreal triamcinolone acetonide versus intravitreal bevacizumab on retrobulbar hemodynamic in patients with diabetic macular edema

Purpose: To evaluate and compare retrobulbar hemodynamic changes measured with color Doppler imaging (CDI) in diabetic patients receiving intravitreal triamcinolone acetonide (IVTA) versus bevacizumab.

Methods: Patients with diffuse diabetic macular edema were assessed prospectively by CDI following intravitreal injection of triamcinolone acetonide (group I, 12 eyes) versus bevacizumab (group II, 14 eyes). CDI was used to measure the peak systolic velocity (PSV), end diastolic velocity (EDV) and the resistive index (RI) of the central retinal artery (CRA), ophthalmic artery (OA) and posterior ciliary arteries (PCA) one day preoperatively and one week postoperatively.

Results: In group I, EDV of OA and CRA decreased significantly (p?=?0.007 and 0.018, respectively). The PSV and RI of PCA decreased significantly (p?=?0.035 and 0.002, respectively). In group II, both the PSV and EDV of the CRA decreased significantly (p?=?0.000). Comparing the percentage of change in both groups, PSV of the CRA decreased significantly in group II (p?=?0.034), while IVTA has more significant effect on the ophthalmic artery hemodynamic parameters as EDV decreased and RI increased significantly (p?=?0.045 and 0.043, respectively)

Conclusion: Intravitreal injections of triamcinolone acetonide and bevacizumab have a significant effect on the ocular hemodynamic. The effect of bevacizumab is statistically significant on the PSV of CRA compared to IVTA.     

The long-term anatomical and visual effect of intravitreal triamcinolone injection during vitrectomy for the treatment of idiopathic macular epiretinal membrane

Purpose: To compare the long-term anatomical and visual outcomes of patients with idiopathic epiretinal membrane (ERM) removed by vitrectomy and membrane peeling with or without the use of intravitreal injection of triamcinolone acetonide (IVTA).

Methods: A retrospective chart review was performed. Subjects who underwent vitrectomy and who were followed over 12 months were included. The study included two groups of patients. In group 1 (71 eyes), the patients underwent vitrectomy and membrane peeling without the use of IVTA. In group 2 (27 eyes), 2?mg of IVTA was given at the end of the surgery. The main outcome measures were best-corrected visual acuity (BCVA), central foveal thickness (CFT) determined by optical coherence tomography (OCT), the number of cataract surgeries, and the use of anti-glaucomatous drugs during the follow-up period.

Results: This study included 98 eyes with ERM from 98 patients. There was no significant difference between the two groups with respect to age, gender, pre- and postoperative lens status, BCVA, CFT, or length of the follow-up period. The mean age for all of the patients was 62.45?±?10.01 (mean ± SD) years, and the mean follow-up length was 20.58?±?9.64 (mean ± SD) months. In all cases, the mean best-corrected logarithm of minimum angle of resolution (logMAR) acuity improved from a preoperative value of 0.91?±?0.32 [Snellen equivalent (SE), 0.16?±?0.14] to a postoperative value of 0.46?±?0.36 (SE, 0.46?±?0.29) (P?<?0.0001). The CFT was reduced from a preoperative value of 473.46?±?96.91 μm to a postoperative value of 302.44?±?69.80 μm (P?<?0.0001). Six patients (22.2%) in group 2 required anti-glaucomatous drugs to control intraocular pressure (IOP) during the follow-up period, and three patients (4.2%) in group 1 required drugs to control IOP (P?=?0.012).

Conclusions: The postoperative visual outcomes for patients with idiopathic ERM were favorable, but CFT did not return to a normal level, even in eyes in which 2?mg IVTA was used. The IVTA use after ERM removal produced no significant benefits during long-term follow-up, but IVTA did increase the risk of increased IOP.     

Antioxidant effects of piperine in in-vivo chick embryo cataract model induced by steroids

Purpose: The etiopathogenesis of steroid-induced cataracts is unknown. One hypothesis is that the higher reactive oxygen species (ROS) levels play an important role in the pathogenesis of several disorders, including the evolution of cataracts. This study investigated the antioxidant effects of piperine in our steroid-induced chick embryo lens model.

Methods: The study included 36 specific pathogen-free (SPF) fertilized eggs divided into six groups: phosphate buffer saline (PBS, pH 7.4 Saline Solution (0.9%) isotonic) group (G1), hydrocortisone succinate sodium (HC)-treated group (G2), 100?mg/kg piperine and HC treated group (G3), 50?mg/kg piperine and HC treated group (G4), 25?mg/kg piperine and HC treated group (G5), and 10?mg/kg piperine and HC treated group (G6). On the 15th day of incubation, the SPF eggs in the six groups were removed from the incubator; all were injected using insulin injectors into the chorioallantoic membrane. On day 17, all of the chick embryos were removed from the eggs and all lenses were dissected from the embryos. Cataract formation was evaluated in all lenses, and total antioxidant status (TAS), total oxidant status (TOS), reduced glutathione (GSH), and lipid peroxidation (MDA, malondialdehyde) levels were measured in all lens.

Results: The lenses in the G1 group had higher levels of GSH and TAS (p?p?p?p?p?p?p?Conclusion: Steroid therapy causes a decrease in GSH and TAS levels and an increase in TOS and MDA levels in lens tissues, indicating increased oxidative stress. Piperine exerts its effects as an antioxidant substance, in increasing doses.     

Changes in pharmacokinetic profiles of acetaminophen and its glucuronide after pretreatment with combinations of N-acetylcysteine and either glycyrrhizin,silibinin or spironolactone in rat

Abstract

1. The present study was to investigate the effects of giving N-acetylcysteine (NAC) alone and in combination with either glycyrrhizin (GL), silibinin (SIB) or spironolactone (SL) on the plasma pharmacokinetic (PK) profiles, hepatic exposure, biliary excretion and urinary excretion of acetaminophen (APAP) and its major metabolite, acetaminophen glucuronide (AG).

2. Groups of rats (n?=?5) were pretreated with oral doses of either NAC, NAC?+?GL, NAC?+?SIB or NAC?+?SL on five occasions every 12?h. At 1?h, after the last dose, they received APAP (200?mg/kg) by intraperitoneal injection. Blood, bile, liver and urine samples were collected at various times after APAP injection and analyzed for APAP and AG by HPLC. NAC alone and NAC?+?SIB did not significantly change the PK profiles of APAP and AG. In contrast, NAC?+?GL decreased the biliary excretion of APAP and AG leading to accumulation of APAP in the liver and systemic circulation whereas NAC?+?SL [multidrug resistance associated 2 (Mrp2) inducer] increased the biliary excretion of AG and decreased the hepatic exposure to APAP and AG.

3. Our results suggest that Mrp2 inhibitor GL should be discouraged with NAC to treat APAP hepatotoxicity. Such PK drug–drug interactions should be considered in the treatment of APAP-induced liver injury.     

The effects of Melissa officinalis (lemon balm) pretreatment on the resistance of the heart to myocardial injury

Context: The antihyperlipidemic, antiarrhythmic, neuroprotective and hepatoprotective effects of Melissa officinalis L. (Lamiaceae) have been reported. However, no study has examined its effects on the resistance of the heart to stressful conditions.

Objective: The objective of this study is to evaluate the effects of aqueous extract of M. officinalis aerial parts on Wistar rat heart with/without cardiac injury.

Materials and methods: Animals were grouped as control, isoproterenol (ISO), M. officinalis without (M50, M100, and M200) and with isoproterenol (M50?+?ISO, M100?+?ISO, and M200?+?ISO). The aqueous extract of M. officinalis was orally administered at dosages of 50, 100, and 200?mg/kg/d, respectively, for 7 consecutive days. On the 6th and 7th day, ISO, M50?+?ISO, M100?+?ISO, and M200?+?ISO groups received 85?mg/kg of isoproterenol for myocardial injury induction. On day 8, hemodynamic parameters were recorded and samplings were done.

Results: The extract (50, 100, and 200?mg/kg) significantly reduced the heart rate (264?±?5, 259?±?5 and 281?±?3 versus 377?±?13 in control group, p?<?0.01). Blood pressure was significantly decreased in M50?+?ISO (75?±?5) versus M50 (110?±?6) and M100?+?ISO (72?±?6) versus M100 (105?±?5?mmHg, p?<?0.01). The malondialdehyde levels of the injured hearts were lower in M50?+?ISO and M100?+?ISO groups than in the ISO group (p?<?0.05). Serum cardiac troponin I was higher in the M200?+?ISO group (5.1?±?1.7) than in the ISO group (2.7?±?0.7?ng/ml, p?<?0.05).

Conclusion: The lower dose of extract, by improving the balance of the redox system and by reducing the heart rate, may increase the heart resistance to injury. However, the higher doses of extract may intensify the injury of ischemic heart.     

Antidiabetic mechanism of Coptis chinensis polysaccharide through its antioxidant property involving the JNK pathway

Abstract

Context: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae) polysaccharide (CCPW) has been reported. However, its molecular mechanism remains unclear.

Objective: An attempt was made to further verify the antidiabetic activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism of antidiabetic activity.

Materials and methods: Male Wistar rats were fed with high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4) were investigated.

Results: FBG level of diabetic rats could be significantly inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of 200, 100, and 50?mg/kg b.w., respectively (p?<?0.01). CCPW also could significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%, respectively (p?<?0.05 or p?<?0.01). CCPW showed an obvious antioxidant effect through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA contents (p?<?0.05 or p?<?0.01). Furthermore, CCPW could inhibit JNK and phospho-IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared with those in the DM group (p?<?0.05 or p?<?0.01).

Discussion and conclusion: CCPW can produce antidiabetic activity in rats with T2DM through its antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.     

Rosmarinic acid exerts a neuroprotective effect in the kainate rat model of temporal lobe epilepsy: Underlying mechanisms

Abstract

Context: Temporal lobe epilepsy (TLE) is an intractable neurological disorder. Rosmarinic acid (RA) is a natural polyphenol with antioxidant, anti-apoptotic, and anti-inflammatory properties.

Objective: This study evaluates beneficial effect of RA in intrahippocampal kainate-induced model of TLE.

Materials and methods: Rats were divided into sham, RA-pretreated sham, kainate, and sodium valproate (VA) or RA-pretreated kainate groups. Rats received RA or VA p.o. at doses of 10 or 300?mg/kg/d, respectively, starting 1?week before the surgery. After 6?weeks, seizure intensity, apoptosis, and oxidative stress markers were evaluated in addition to determination of Timm index as an indicator of mossy fiber sprouting (MFS) and the number of Nissl-stained neurons.

Results: All rats in the kainate group had seizure and 24.3% of rats in the kainate?+?VA group and 36.7% of rats in the kainate?+?RA group showed seizure. The kainate group had a significant elevation of malondialdehyde (MDA) (p?<?0.05) and nitrite (p?<?0.01) and reduction of glutathione (GSH) and catalase activity (p?<?0.05) and pretreatment of kainate-lesioned rats with RA or VA significantly lowered MDA and nitrite content (p?<?0.05) and raised activity of catalase (p?<?0.05). The kainate group also had a significant reduction of neurons in CA1 and CA3 regions and an elevation of Timm index (p?<?0.05–0.001) and RA or VA significantly (p?<?0.05–0.01) prevented these changes.

Discussion and conclusion: RA could attenuate seizure, mitigates oxidative stress, augments the activity of defensive systems, and prevent hippocampal neuronal loss and MFS in the kainate model of TLE.     

Treatment of diabetic macular edema with sustained-release glucocorticoids: intravitreal triamcinolone acetonide,dexamethasone implant,and fluocinolone acetonide implant

Introduction: Diabetic macular edema (DME) can be treated with intravitreal glucocorticoids, particularly triamcinolone acetonide, dexamethasone (DEX), and fluocinolone acetonide (FA).

Areas covered: The pathophysiology of DME includes multiple growth factors such as VEGF and also inflammatory mediators. Glucocorticoids act on DME through multiple pathways, and current research into their efficacy, safety, and therapeutic potential when administered intravitreally is discussed.

Conclusion: The intravitreal route of administration minimizes systemic side effects of glucocorticoids. Furthermore, sustained-release low-dose delivery via the DEX implant or the FA implant will limit frequent intravitreal injection and possibly some cost associated with intravitreal anti-VEGF therapy. In addition, the durable action of these treatments facilitates combination therapy. Patients can receive these implants as foundational therapy, and then receive additional treatment with laser or intravitreal anti-VEGF agents as combination therapy, which may conceivably provide some synergistic benefit. While the FA implant lasts much longer than the DEX implant, potentially decreasing the visit and treatment burden on patients and their families, the FA implant appears to have a greater risk of inducing ocular hypertension and cataract. However, these modalities have not been directly compared in a clinical trial and there is insufficient evidence to draw more elaborate conclusions.     

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.     

Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia.

Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory.

Materials and methods Rats were pretreated with metformin (200?mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured.

Results Pretreatment with metformin (met) in the met?+?ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p?<?0.001) and increased latency time compared with the I/R group (p?<?0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R?+?met group (p?<?0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p?<?0.001) but increased that compared with the sham group (p?<?0.001). The level of pro-BDNF decreased in the met?+?CC?+?I/R group compared with the met?+?I/R group (p?<?0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p?<?0.001).

Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.     

Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model

Objective: In order to increase local drug concentration and reduce systemic side effects of liver cancer chemotherapy, it is desirable to develop novel non-invasive technologies for drug targeting, such as ultrasound-targeted microbubble destruction (UTMD).

Methods: H22 hepatocellular carcinoma (HCC) xenograft transplantation model was generated in UTMD study. BALB/c mice were randomly divided into six groups: doxorubicin HCl liposomal injection (DOX), DOX?+?US, UTMD, DOX?+?UTMD, H22 liver tumor control (CH control) and blank control group. The therapeutic schedule started on day 4 after tumor inoculation.

Results: Average survival time of the animal model was approximately 18?d. The UTMD therapy parameters were optimized in the H22 mouse model to be: microbubble (MB) diameter, 2.30?±?0.25?μm; MB density, 4.0?×?10⁹ bubbles/ml; treatment dose, 0.2?ml per 20?g mouse body weight; sonication frequency, 1.3?MHz; and sonication power, 2.06?W/cm². Mice treated with DOX?+?UTMD had the smallest tumor volume and weight (p?<?0.001), and the highest tumor inhibition rate (p?<?0.01), intratumoral DOX concentration (p?<?0.001) and survival rate among all tumor-burden groups (p?<?0.001). Cell viability in different treatment groups was also assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

Conclusion: An improved antitumor effect was observed with the combination therapy of DOX and UTMD, as compared with treatment with DOX, DOX?+?US or UTMD, which implicates a novel approach for HCC treatment.     

Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study

Purpose: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs.

Methods: Adult New Zealand albino rabbits (n?=?40) were divided into experimental and control groups. Experimental rabbits received a single 0.05?ml intravitreal injection of 1.25?mg bevacizumab (Avastin) into the right eye, and control rabbits (n?=?8) received no injection. Following injection, group 1 rabbits (n?=?8) were sacrificed on day 1, group 2 rabbits (n?=?8) on day 7, group 3 rabbits (n?=?8) on day 14, and group 4 rabbits (n?=?8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues.

Results: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p?p?Conclusions: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver.     

Role of innate immunity and oxidative stress in steroid-induced cataracts in developing chick embryos

Purpose: The exact etiopathogenesis of steroid-induced cataracts (SIC) is not known. Although oxidative stress is one of the most acceptable hypotheses, the exact molecular events in steroid-induced oxidative events in the lens need to be clarified. In addition, to the best of our knowledge, the innate immune system components in SIC formation have not been studied previously. The aim of the present study was to study the oxidative system and the innate immune system components in the cataractous lenses of a developing chick embryo SIC model.

Materials and methods: The study included 20 specific pathogen-free (SPF) fertilized eggs divided into two groups, with one hydrocortisone (HC)-treated group (G1) and one non-HC-treated control group (G2). On the 15th day of incubation, the SPF eggs in the two groups were removed from the incubator; HC was injected into G1, and phosphate-buffered saline (PBS) was injected into G2 using insulin injectors into the chorioallantoic membrane. On day 17, all of the chick embryos were removed from the eggs, and all lens and liver tissues were dissected from the embryos. Cataract formation was evaluated in all lenses, and total antioxidant status (TAS), total oxidant status (TOS), reduced glutathione (GSH), oxidized glutathione (GSSG), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels were measured in all lens and liver tissues.

Results: The lenses in the SIC group had lower levels of GSH, GSSG, TAS, and IL-6 (p?=?0.016, 0.022, 0.000, 0.000, respectively), and higher levels of TOS (p?=?0.000) than the control group. Furthermore, the liver tissues in the SIC group had decreased levels of TAS and IL-6, and increased levels of TOS compared to the control tissues (p?=?0.000). Although the IL-1β levels in the lens and liver tissues in the HC-induced cataract group were lower than in the control group, these differences were not statistically significant. In addition, the GSH levels in the liver tissues did not statistically differ between the two groups despite the significant GSH difference in the lens tissues.

Conclusions: Steroid therapy causes a decrease in GSH, GSSG, and TAS levels and an increase in TOS levels in lens tissues, which means there is increased oxidative stress and decreased antioxidant defence. Furthermore, lenses with SIC have lower IL-6 levels compared to non-cataractous lenses. The interaction between lenticular IL-6 and antioxidant defence needs to be further studied.     

Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet

Context: High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties.

Objective: This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD.

Materials and methods: Forty male Wistar rats (200–250?g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD?+?extract. The extract (1?g/kg bw daily) was administered by oral gavage for 1?month. Animals were allowed free access to high-fat chow for 3?months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory.

Results: In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4?±?23.3) and HFD (150.3?±?25.2) groups were significantly lower than those of the control group (270.4?±?10.5) (respectively, p?p?p?p?Discussion and conclusion: Our results indicate that, while HFD or R. damascena extract alone leads to memory deficits, R. damascena extract exerted a positive effect on HFD-induced memory deficits. We hypothesize that the observed effects of R. damascena extract are likely due to its strong antioxidant properties.     

Effect of alpha lipoic acid on smoking-induced skin damage

Objective: Exposed to cigarette leads to the formation of reactive oxygen species and the generation of bioactive molecules that can damage skin cells. This investigation was carried out to study possible effects of Alpha Lipoic Acid (ALA) on smoking-induced rat skin injury.

Materials and methods: 28 Spraque–Dawley female rats were allocated into three groups: control group (n?=?8), smoking group (n?=?10; 12 cigarettes/day, 8 weeks) and smoking?+?ALA group (n?=?10; 12 cigarettes/day?+?100?mg/kg, 8 weeks). Experiment group animals were sacrificed under anaesthesia with 10%ketamine?+?2%xylasine at the end of second mounts and then skin examples were taken from the epigastric area. Histochemical (Haematoxylin–Eosin and Masson’s trichrome, immunohistochemical (TNF-α) and biochemical analysis (CAT, MDA and protein carbonylation) were performed on these skin tissues.

Results: Histologically, skin was distinguished normal structure in the control group. In the smoking group, collagen bundles and hair follicle degradation/reduction, sweat gland degeneration, mononuclear cell infiltration in dermis were encountered. In ALA-treated group, all of these changes were improved (p?<?0.05). Collagen bundles structures were appearance more regular than the smoking group . Immunohistologically, intense staining was observed in the smoking group, while very weak staining was observed in control group, weak staining was observed in the ALA-treated group. Biochemically; The CAT activity compared to cigarette group with control was raised high and in ALA group was higher compared to both groups, but not significant (p?>?0.05). MDA; which is indicator of lipid peroxidation was significantly higher in cigarette group than in control group (p?<?0.05) and was significantly lower in ALA group than cigarette (p?<?0.05). Protein carbonylation was higher in cigarette group than the control group but not in the non-significant (p?>?0.05). In the ALA it was significantly lower compared to the control group and cigarette (p?<?0.05).

Conclusions: Based on biochemical and histopathological determinations, the study showed that cigarette smoke can cause degenerative effects on skin tissues in rats. However, ALA has a curative effect on cigarette-induced injuries on the skin tissues by anti-oxidative and anti-inflammatory effects.     

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections

Background: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration.

Methods: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3?months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale.

Results: A total of 90 patients were included in the study. 43.3% n?=?39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n?=?11 amongst study eyes vs 4.4%, n?=?4 amongst control, fellow eyes (p?p?=?0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p?=?0.02).

Conclusion: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.     

Oxidative stress status in patients with melasma

Background: Melasma is an acquired skin disease characterized clinically by development of gray–brown macules or patches. The lesions have geographic borders and most often seen on face and less frequently on the neck and forearms. Pathogenesis has not been completely understood yet. Although the disease constitutes a very disturbing cosmetic problem, it has not obtained an efficient treatment. There were not any studies in the literature that evaluates the role of oxidative stress in melasma.

Objectives: The evaluation of the role of oxidative stress in melasma.

Methods: Fifty melasma patients and 50 healthy volunteers were included in the study. The diagnosis was made clinically and the patients were evaluated by Melasma Area Severity Index. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde, nitric oxide, protein carbonyl levels were measured both in the melasma group and the control group.

Results: SOD and GSH-Px enzyme activities were significantly higher in the patient group in comparison with the control group (p?p?Conclusion: The results show that the balance between oxidant and anti-oxidants was disrupted and the oxidative stress increased in melasma. These results improve the understanding of etiology–pathogenesis of the disease and its treatment.     

Intraocular corticosteroids for posterior segment disease: 2012 update

Introduction: Diabetic macular edema (DME), cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO) and uveitis are responsible for severe visual impairment worldwide. In some patients with these conditions, treatment with intraocular corticosteroids may be beneficial. Although off-label use of these agents has occurred for many years, novel agents including preservative-free and sustained-release intravitreal implants are currently being studied in clinical trials (CTs).

Areas covered: This paper reviews the use of CTs for vitreoretinal (VR) diseases including choroidal neovascularization, CME, DME, RVO and posterior uveitis. It also discusses the use of corticosteroids for treating VR disease, including dexamethasone, fluocinolone acetonide, intravitreal implants and triamcinolone acetonide.

Expert opinion: Used alone, intravitreal corticosteroids may benefit disorders such as DME, RVO and uveitis compared with standard therapy. Cases of exudative AMD non-responsive to standard treatment may benefit from combination therapy, including usage of intravitreal corticosteroid injections. Intraoperative use of these agents may aid visualization of retinal structures. Sustained-release intraocular implants have been approved for posterior uveitis and RVO associated with macular edema. In spite of this, most intraocular corticosteroids have a limited duration of action along with significant side effects, including cataract and glaucoma. Currently, intravitreal corticosteroid usage for DME is considered off-label.     

Assessment of the therapeutic activity of a combination of almitrine and raubasine on functional rehabilitation following ischaemic stroke

Background and objectives: Stroke is a major cause of disability. Certain experimental studies have suggested that a combination of almitrine?+?raubasine (Duxil) increases the supply of oxygen to cerebral tissues and may be beneficial in post-stroke rehabilitation. This multicentre clinical study was carried out in order to assess the efficacy of this combination on post-stroke rehabilitation.

Methods: The trial was a randomised, double-blind, placebo-controlled study. Patients that had experienced an ischaemic cerebrovascular accident (confirmed by CT scan) were included 4-6 weeks after the acute onset and received randomised treatment of either almitrine?+?raubasine or placebo 2 tablets daily for 3 months. Before treatment, there was a 2-week washout period for stopping all other drugs, except for antihypertensive and antidiabetic drugs. We assessed the patients by Barthel Index (BI), Neurological Functional Deficit Scores (NFDS), and Hasagawa Dementia Scales (HDS) each month after treatment.

Results: A total of 83 patients were entered into the study and data were available for 74. Of these, 38 patients received almitrine?+?raubasine and 36 received placebo. The baseline characteristics were comparable between both groups. Almitrine?+?raubasine was significantly more effective than placebo at increasing BI at 1, 2 or 3 months (14.6?±?13.8 versus 3.3?±?13.2, p?=?0.01; 19.3?±?13.6 versus 8.8?±?14.0, p?=?0.02; 22.6?±?14.7 versus 10.7?±?17.0, p?=?0.02 respectively) and reducing NFDS at 1 month (3.6?±?3.2 versus 1.9?±?3.5, p?=?0.034) after treatment. More almitrine?+?raubasine-treated patients' NFDS had improved compared with placebo-treated patients at 2 and 3 months (97 versus 78%, p?=?0.013; 100 versus 86%, p?=?0.023 respectively). Compared with pre-treatment, there was a strong tendency towards an improvement of HDS with almitrine + raubasine. The number of adverse events reported was low for the almitrine + raubasine-treated group and the placebo group and all events were mild, of short duration and resolved without treatment. Almitrine + raubasine had no clinically significant effect on blood pressure, heart rate or other laboratory tests.

Conclusion:The results indicate that almitrine + raubasine can accelerate neurological function recovery after stroke to some degree and is well tolerated.     

The effect of aqueous extract of Rosa damascena on formaldehyde-induced toxicity in mice testes

Context: Rosa damascena L. (Rosaceae) (RD) essential oil and extracts are commonly used as a flavour in herbal medicine which increase libido. Previous studies have shown inhalation of RD flower’s oil increases libido and causes protective effects in formaldehyde (FA)-induced testicular damage.

Objective: The protective effects of aqueous extract of RD on the male reproductive system of mice were examined following FA-induced damage.

Materials and methods: Forty-eight adult NMRI male mice were randomly assigned to six groups (n?=?8): control (normal saline, 10?mg/kg); RD40 (40?mg/kg, p.o.); FA treated (10?mg/kg of 10%, i.p.) and FA?+?RD treated at 10, 20 and 40?mg/kg (FA?+?RD10), (FA?+?RD20) and (FA?+?RD40), respectively, for 40 days. At the end of treatment regimes, serum testosterone (T) level and the reproductive activity, viz. body/organ weights, testicular structure and sperm characteristics were studied.

Results: Formaldehyde administration significantly decreased serum T level (p?p?p?Discussion and conclusions: We may conclude that RD flower extract can withstand effects of FA in the male reproductive system of mice possibly due to its antioxidative properties.