Non-pretreated Group Research Articles

Metabolic and Transcriptional Stress Memory in Sorbus pohuashanensis Suspension Cells Induced by Yeast Extract

Plant stress memory can provide the benefits of enhanced protection against additional stress exposure. Here, we aimed to explore the responses of recurrent and non-recurrent yeast extract (YE) stresses in Sorbus pohuashanensis suspension cells (SPSCs) at metabolomics and transcriptional levels. Biochemical analyses showed that the cell wall integrity and antioxidation capacity of SPSCs in the pretreated group were evidently improved. Metabolic analysis showed that there were 39 significantly altered metabolites in the pretreated group compared to the non-pretreated group. Based on the transcriptome analysis, 219 differentially expressed genes were obtained, which were highly enriched in plant-pathogen interaction, circadian rhythm-plant, oxidative phosphorylation, and phenylpropanoid biosynthesis. Furthermore, the correlation analysis of the transcriptome and metabolome data revealed that phenylpropanoid biosynthesis involved in the production of biphenyl phytoalexins may play a critical role in the memory response of SPSC to YE, and the key memory genes were also identified, including PAL1, BIS1, and BIS3. Collectively, the above results demonstrated that the memory responses of SPSC to YE were significant in almost all levels, which would be helpful for better understanding the adaptation mechanisms of medicinal plants in response to biotic stress, and laid a biotechnological foundation to accumulate favorable antimicrobial drug candidates from plant suspension cells.

Protective effects of coconut water against the intraperitoneal infused carbon tetrachloride-induced toxicity—evaluations of biochemical, haematological and histopathological profiles in rats

BackgroundCoconut water is a relished beverage traditionally used as a remedy for childhood diarrhoea and gastroenteritis. It can be given to an individual who has hangover or suspected to have ingested a toxic substance. In this study, we evaluated the protective effect of coconut water against carbon tetrachloride (CCl4)-induced toxicity in rats.ResultsAdministration of coconut water decreased significantly albumin, aspartate transaminase (AST), alanine transaminase (ALT), urea, creatinine, bicarbonate (HCO3−), total cholesterol, triglycerides, low-density lipoprotein, very low-density lipoprotein and malondialdehyde (MDA) levels compared to the non-pretreated group. Furthermore, high-density lipoprotein, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) increased significantly (p < 0.05) in coconut water-pretreated groups compared to the negative control. There were no observed pathological changes in the coconut water-pretreated groups, but slight enlargement of the central veins and tubules was evident when compared to the negative control.ConclusionsTherefore, intake of coconut water may be protective against toxicity induced by CCl4 as its pretreatment elevated antioxidant parameters (GSH, SOD and CAT) and did not alter biochemical parameters in rats.

THE EFFECTS OF LAVENDER ESSENTIAL OIL AND GALLIC ACID PRE-TREATMENT ON THE NEUROCOGNITIVE ASSESSMENT OF POST-STROKE WISTAR RATS

Stroke is a multifactorial, fatal and often disabling neurodegenerative disease in which neurons are degenerated leading to cognitive and muscular problems, there is no curative treatment for this disease; the drugs available on the market offer symptomatic relief with some improvement of daily functions. Thus, phytochemicals with multifactorial efficacy may be promising substances for the treatment of cerebral ischemia and its recurrences that would have been prevented by various plants and plant products. The aim of our study is to evaluate the effect of lavender oil and gallic acid administered orally at doses of 200 mg/kg and 100 mg/kg, respectively, prior to stroke induction by middle cerebral artery occlusion in Wistar rats. The aim is to evaluate their effects on post-stroke sequelae, such as anxiety, exploration and memory (spatial and working), which were quantified and compared between: the control, non- pretreated stroke and pretreated stroke batches. The results indicate a better cognitive-motor recovery on an anxious and exploratory level in the rats pretreated with GA and LEO, while memory capacities are superior in the latter compared to the non-pretreated stroke group. These findings reveal and support the neuroprotective effect of gallic acid and lavender essential oil taken separately or in combination.

Desensitization of Capsaicin-Sensitive Afferents Accelerates Early Tumor Growth via Increased Vascular Leakage in a Murine Model of Triple Negative Breast Cancer.

There is growing interest in the role of nerve-driven mechanisms in tumorigenesis and tumor growth. Capsaicin-sensitive afferents have been previously shown to possess antitumoral and immune-regulatory properties, the mechanism of which is currently poorly understood. In this study, we have assessed the role of these terminals in the triple negative 4T1 orthotopic mouse model of breast cancer. The ultrapotent capsaicin-analogue resiniferatoxin (RTX) was used for the selective, systemic desensitization of capsaicin-sensitive afferents. Growth and viability of orthotopically implanted 4T1 tumors were measured by caliper, in vivo MRI, and bioluminescence imaging, while tumor vascularity and protease enzyme activity were assessed using fluorescent in vivo imaging. The levels of the neuropeptides Calcitonin Gene-Related Peptide (CGRP), Substance P (SP), and somatostatin were measured from tumor tissue homogenates using radioimmunoassay, while tumor structure and peritumoral inflammation were evaluated by conventional use of CD31, CD45 and CD3 immunohistology. RTX-pretreated mice demonstrated facilitated tumor growth in the early phase measured using a caliper, which was coupled with increased tumor vascular leakage demonstrated using fluorescent vascular imaging. The tumor size difference dissipated by day seven. The MRI tumor volume was similar, while the intratumoral protease enzyme activity measured by fluorescence imaging was also comparable in RTX-pretreated and non-pretreated animals. Tumor viability or immunohistopathological profile was measured using CD3, CD31, and CD45 stains and did not differ significantly from the non-pretreated control group. Intratumoral somatostatin, CGRP, and SP levels were similar in both groups. Our results underscore the beneficial, antitumoral properties of capsaicin sensitive nerve terminals in this aggressive model of breast cancer, which is presumed to be due to the inhibition of tumor vascular bed disruption. The absence of any difference in intratumoral neuropeptide levels indicates non-neural sources playing a substantial part in their expression.

Simultaneous Pretreatment of Aspirin and Omega-3 Fatty Acid Attenuates Nuclear Factor-κB Activation in a Murine Model with Ventilator-Induced Lung Injury.

Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (p = 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (p = 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.

Pyrroloquinoline Quinine and LY294002 Changed Cell Cycle and Apoptosis by Regulating PI3K-AKT-GSK3β Pathway in SH-SY5Y Cells

To verify the role of PI3K-AKT-GSK3β pathway during manganese (Mn)-induced cell death, apoptosis, related indicators were investigated. SH-SY5Y cells were directly exposed to different concentrations of MnCl2. Then, cell viability, apoptosis, necrosis rate, and cell cycle were detected by MTT, FITC Annexin V Apoptosis Detection Kit with PI and PI staining. Then, in two intervention groups, cells were preconditioned with agonist (PQQ) and suppressant (LY294002). The cell viability decreased with a dose-response relationship (p < 0.05), while apoptosis and necrosis increased (p < 0.05). The ratio of G0/G1 and G2/M also decreased, but the percentage of S phase increased (p < 0.05). During above process, PI3K-AKT-GSK3β pathway was involved by regulating the expression of PI3K, AKT, p-AKT, and GSK3β (p < 0.05). For further research, cell cycle and apoptosis were detected pretreatment with PQQ and LY294002 before Mn exposure. The result showed cell ability, apoptosis, and necrosis rate changed obviously compared with non-pretreated group (p < 0.05). The variance of G0/G1 and G2/M ratio and percentage of S phase were also different, especially in 2.0mM (p < 0.05). Mn can cause apoptosis and necrosis, varying cell cycle of SH-SY5Y cells, which could be changed by PQQ and LY294002 by regulating PI3K-AKT-GSK3β pathway.

Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy.

Comparative approach to analyse the effects of different surface treatments on CAD/CAM resin nanoceramics–resin composite repair bond strength

ABSTRACTLimited data are available on the repair bond strength between computer-aided design and manufacturing (CAD/CAM) resin nanoceramics and composite repair materials. Therefore, the purpose of this study was to test the influence of several different surface treatment modalities, intermediate agents and phosphoric acid on the shear bond strength (SBS) of repair composites with water-aged CAD/CAM resin nanoceramics. Three pretreatment and four conditioning methods comprised 12 different groups. A universal testing machine was used to test the SBS. Specimens were examined with a stereomicroscope and scanning electron microscope to determine the fracture mode. The results showed that a combination of the pretreatment and conditioning methods significantly enhanced the SBS of the resin nanoceramic (p:0.001; p < 0.01), while etching with phosphoric acid did not affect the SBS (p:0.841; p > 0.05). This study showed that surface pretreatment in combination with a conditioning method should be used in the repair of CAD/CAM nanoceramics. The highest SBS values were achieved by grinding the surface with a diamond bur followed by silane and adhesive application, whereas the lowest values were obtained in the non-conditioned non-pretreated group.

HYPOTENSIVE ACTIVITY OF THYMOQUINONE IN NORMOTENSIVE RATS AND ITS RECEPTOR MECHANISMS

Objective: The objectives of the current study were to confirm the blood pressure lowering effect of thymoquinone (TQ) and to investigate its mechanism through muscarinic and β-adrenergic receptors.Methods: Mean arterial blood pressure (MAP) was recorded using the non-invasive blood pressure tail-cuff technique. A dose-response relationship was obtained after using 3 TQ doses (2.5, 5 and 10 mg/kg) intraperitoneally to 3 different groups (n =5) of adult rats under pentobarbital anesthesia. MAP was then measured for another 2 animal groups pretreated either with atropine (P-at) or propranolol (P-pro) followed by 10 mg/kg TQ.Results: TQ produced a significant dose-dependent blood pressure and heart rate lowering effect. TQ-induced MAP reduction was significantly less pronounced in P-at (12±2.8 mmHg) than non-pretreated group (29±3.2 mmHg) with P&lt;0.01. Conversely, TQ-induced MAP reduction in P-pro (28±3.4 mmHg) did not demonstrate a significant difference from the non-pretreated group (29±3.2 mmHg) with P&gt;0.05.Conclusion: This study confirms the dose-related hypotensive effect of TQ and provides an evidence for the traditional use of Nigella sativa for the treatment of hypertension. The mechanism of TQ-induced hypotension involves at least in part activation of vascular muscarinic receptors, but not β-adrenergic receptors.

Enhancement of biogas production from microalgal biomass through cellulolytic bacterial pretreatment

Generation of bioenergy from microalgal biomass has been a focus of interest in recent years. The recalcitrant nature of microalgal biomass owing to its high cellulose content limits methane generation. Thus, the present study investigates the effect of bacterial-based biological pretreatment on liquefaction of the microalga Chlorella vulgaris prior to anaerobic biodegradation to gain insights into energy efficient biomethanation. Liquefaction of microalgae resulted in a higher biomass stress index of about 18% in the experimental (pretreated with cellulose-secreting bacteria) vs. 11.8% in the control (non-pretreated) group. Mathematical modelling of the biomethanation studies implied that bacterial pretreatment had a greater influence on sustainable methane recovery, with a methane yield of about 0.08 (g Chemical Oxygen Demand/g Chemical Oxygen Demand), than did control pretreatment, with a yield of 0.04 (g Chemical Oxygen Demand/g Chemical Oxygen Demand). Energetic analysis of the proposed method of pretreatment showed a positive energy ratio of 1.04.

SIRT1 attenuated oxidative stress induced by methyl tert-butyl ether in HT22 cells.

Methyl tertiary-butyl ether (MTBE), an unleaded gasoline additive, can lead to oxidative stress, thus injuring the nervous system after long-term exposure. SIRT1, a NAD+-dependent histone deacetylase, can play a neuroprotective role in brain injury. However, the mechanism is unclear. This present study intended to define the role of SIRT1 during the process of MTBE-induced oxidative stress in mouse hippocampal neurons (HT22 cells). Our data showed that MTBE could directly trigger oxidative stress in HT22 cells by decreasing the activity of superoxide dismutase (SOD) and GSH/T-GSH level while increasing ROS, lipid peroxidation product malondialdehyde (MDA) and GSSG level. Similarly, the expression of SIRT1, an antioxidant, decreased in a dose-dependent manner. To further explore whether SIRT1 plays a key role during the process of oxidative stress, HT22 cells were transfected with siRNA-SIRT1 and preconditioned with the agonist of SIRT1 (SRT1720) for 2 h. The levels of oxidative stress (ROS, SOD, MDA, GSH/GSSG) were detected again after siRNA-SIRT1 HT22 cells and SRT1720 HT22 cells were exposed to MTBE for 6 h. In contrast to the non-pretreated group, levels of oxidative stress were tonic in siRNA-SIRT1 HT22 cells and attenuated in SRT1720 HT22 cells. Our results indicate that MTBE could directly cause oxidative stress in HT-22 cells, and SIRT1 might be an important antioxidant during MTBE-induced oxidative stress.

The Probiotic Lactobacillus Prevents Citrobacter rodentium-Induced Murine Colitis in a TLR2-Dependent Manner.

The main objective of this study was to investigate whether Lactobacillus rhamnosus GG (LGG) ameliorated the effects of Citrobactor rodentium infection in Toll-like receptor 2 (TLR2) knockout (KO) and TLR4 KO mice, as well as in wild-type C57BL/6 (B6) mice. TLR2 KO, TLR4 KO, and B6 mice were divided into three groups per each strain. Each group had an uninfected control group (n = 5), C. rodentium-infected group (n = 8), and LGG-pretreated C. rodentium-infected group (n = 8). The survival rate of B6 mice infected with C. rodentium was higher when pretreated with LGG. Pretreatment with LGG ameliorated C. rodentium-induced mucosal hyperplasia in B6 and TLR4 KO mice. However, in C-rodentium-infected TLR2 KO mice, mucosal hyperplasia persisted, regardless of pretreatment with LGG. In addition, LGG-pretreated B6 and TLR4 KO mice showed a decrease in spleen weight and downregulation of tumor necrosis factor alpha, interferon gamma, and monocyte chemotactic protein 1 mRNA expression compared with the non-pretreated group. In contrast, such changes were not observed in TLR2 KO mice, regardless of pretreatment with LGG. From the above results, we conclude that pretreatment with LGG ameliorates C. rodentium-induced colitis in B6 and TLR4 KO mice, but not in TLR2 KO mice. Therefore, LGG protects mice from C. rodentium-induced colitis in a TLR2-dependent manner.

Antioxidant effects and mechanism of thiopental and propofol on the rabbit abdominal aortic endothelial dependent vasorelaxation against reactive oxygen species

Antioxidant effects and mechanism of thiopental and propofol on the rabbit abdominal aortic endothelial dependent vasorelaxation against reactive oxygen species

Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line

Besides their prominent function in cellular energy metabolism, the central role of mitochondria has been focused on control of cellular death in last decades. The mitochondrial permeability transition pore (PTP) is involved in the intrinsic pathway of apoptosis via the release of cytochrome c into cytosol. Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome c release. The modulation of PTP is still unknown, but calcium is certainly the most important known inducer. In the present study, the preventive effects of metformin on gentamicin ototoxicity were investigated through the changes of intracellular calcium concentrations using calcium imaging in HEI-OC1 cells. Calcium imaging traced the changes of intracellular calcium concentration after the application of 50 mM of gentamicin in both 100 uM of metformin pretreated group and non-pretreated group. These calcium reactions were compared and analyzed with the results of cell viability test, Hoechst staining, intracellular reactive oxygen species level and expression of caspase-3, and poly-ADP-ribose polymerase (PARP). Continuous increase of intracellular calcium concentration (increase of 380/340 ratio) occurred after application of 50 mM of gentamicin. However, there was no change of intracellular calcium concentration in 100 uM metformin pretreated group. Cell viability was significantly higher in 100 uM metformin pretreated group and also, metformin pretreated HEI-OC1 cells produced less ROS that gentamicin alone treated group. Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP. This study demonstrated that metformin prevented gentamicin induced apoptosis through the calcium modulating and ROS reducing anti-apoptotic effects.

Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema

Editor, We read with interest the article ‘Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema’ by Fang et al. (2008). We would like to make an observation regarding the same topic. The optical coherence tomography (OCT) image of one of the eyes with diabetic macular oedema (DMO) in the non-pretreated group (Fig. 3) shows the presence of serous macular detachment (SMD), which decreased in height after intravitreal bevacizumab and was almost negligible by the end of 12 weeks. DMO associated with SMD is a recently recognized entity present in up to 15% of patients with DMO (Otani et al. 1999). Gaucher et al. (2008) showed that SMD may appear before central neuroretinal thickening and disappear before or after its regression; SMD does not seem to be related either to the severity of DMO or to its resorption. Because of poor laser uptake in such cases, there is no established treatment modality for this condition, although there are isolated reports of resolution of SMD in response to intravitreal triamcinolone acetonide (Ozdemir et al. 2005). The resolution of SMD in this particular case may point towards the efficacy of intravitreal bevacizumab for this condition. Were there more such cases in the series where SMD was present with DMO and, if so, did they respond similarly to intravitreal bevacizumab?

THE RELATIONSHIP BETWEEN SOME SOLUBLE OSTEOGENIC MARKERS, ANGIOGENIC CYTOKINES/OTHER BIOLOGICAL PARAMETERS AND THE STAGES OF MULTIPLE MYELOMA EVALUATED ACCORDING TO THE DURIE-SALMON AND INTERNATIONAL PROGNOSTIC INDEX STRATIFICATION SYSTEMS

The aim of the present paper was to examine the correlation between serum concentrations of 12 soluble biological markers and stages of myeloma evaluated according to the Durie-Salmon (D-S) and International Prognostic Index (IPI) stratification systems. We analyzed a non-pretreated group of 179 patients with MM stratified according to D-S and IPI. Serum levels of soluble biological markers were evaluated using ELISA, REA and quantitative sandwich enzymatic immunoassays. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. The staging system according to D-S revealed a highly significant relationship between all stages (I-III) in case of beta(2)-m (p<0.0001) and sTK (p<0.001), in sICTP a significant difference was found only in stages II vs III (p<0.001) and I vs III (p<0.001), in case of sCD(138) (syndecan-1) in stages I vs II (p = 0.006) and I vs III (p<0.001), in sVEGF only in stages I vs III (p = 0.006). In substages A vs B we found a significant difference in case of beta2-m (p<0.0001), sTK (p = 0.041), sICTP (p 0.0001), sOSP (p = 0.008), sHGF (p<0.001), sCD138 (p = 0.001) and sFas (p= 0.001). The relationship between other factors and stages and substages according to D-S appeared nonsignificant. The IPI system showed a highly significant relationship between all 3 categories (1-3) in case of beta(2)-m (p<0.001), sTK (p<0.0001) and sICTP (p<0.0001), while in sHGF only in stages 2 vs 3 (p<0.0001) and 1 vs 3 (p<0.0001). In 4 parameters there were only discrete differences in 1 vs 3: sPINP (p= 0.036), sOSP (p= 0.002), sCD(138) (p = 0.03) and sFas (p=0.012), in the remaining markers the analysis was negative. A highly convincing relationship between myeloma stages and serum levels was found only in beta(2)-m, sTK, sICTP and partly also in sCD(138) (syndecan-1) and sHGF. More favourable was the IPI stratification system.

The effect of enzymatic pretreatments on subsequent octenyl succinic anhydride modifications of cornstarch

Cornstarch granules were allowed to react with α-amylase and then esterified with octenyl succinic anhydride (OSA). The paste properties and the distribution of octenyl succinate (OS) groups of OS-starch granule were studied. Results show that the α-amylase pretreatments significantly decreased the degree of substitution (DS) of OS-starch compare with a non-pretreated control group, while the retrogradation properties, freeze-thaw stability and shearing resistant stability of α-amylase pretreated OS-starch didn't change markedly. Enzymatic pretreatment appears to influence the distribution of the OS groups from being mostly on the surface and amorphous part of the starch granules to being in the inner amorphous and crystalline regions of the granules, as shown by X-ray photoelectron spectroscopy (XPS) and lintnerisation studies.

Arecoline and oral keratinocytes may affect the collagen metabolism of fibroblasts

The characteristic of oral submucous fibrosis (OSF) is related with the disturbance of synthesis and degradation of extracellular matrix. Arecoline, the areca nut (betel nut) component of betel quid, plays a major role in pathogenesis of OSF. But the exact mechanism how arecoline influences the collagen metabolism is unclear. Oral keratinocytes and fibroblasts were cocultured and keratinocytes were pre-treated by arecoline. Fibroblasts alone, fibroblasts stimulated by arecoline, fibroblasts cocultured with keratinocytes and fibroblasts cocultured with keratinocyte pre-treated by arecoline were included as the four groups in the present study. The concentration of collagen, the content and activity of matrix metalloproteinase (MMP) and the concentration of tissue inhibitor of metalloproteinase (TIMP) were assessed. The collagen production of fibroblasts decreased when cocultured with keratinocytes; when cocultured with keratinocytes pre-treated by arecoline, fibroblasts produced more soluble collagen than non-pretreated coculture group. MMP-9 was produced only in coculture groups. There was no significant difference in the two coculture groups. The activation ratio of pro-MMP-2 in arecoline pre-treated keratinocytes-fibroblasts coculture group was significantly higher than that of non-coculture groups, but no significant difference existed in the two coculture groups. TIMP-1 produced by arecoline pre-treated keratinocytes-fibroblasts coculture group was significantly higher than those by the other three groups. TIMP-1 and the interaction of oral keratinocytes and fibroblasts play important role in pathogenesis of OSF.

Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema

To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups. In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up. One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

Effects of simvastatin on neuroprotection and modulation of Bcl-2 and BAX in the rat quinolinic acid model of Huntington's disease

A possible neuroprotective role has been recently suggested for 3H3MGCoA reductase inhibitors. Here, we sought to determine whether simvastatin exerts a neuroprotective effect in our rat model of HD. Rats were surgically administered quinolinic acid and treated with simvastatin 1mg/kg intraperitoneally (i.p.) once daily up to 2 or 8 weeks. Two more groups of animals received a pretreatment with 1mg/kg simvastatin i.p. for 2 weeks before the QA lesion and then were treated with simvastatin for the following 2 weeks or 8 weeks, respectively. In the simvastatin treated groups (both pretreated and non-pretreated), striatal lesion size was about 36% smaller while neuronal counts where higher than in the vehicle treated ones at 2 weeks. The neuroprotective effects of simvastatin was still evident at 8 weeks post lesion, where the non-pretreated group had a 8% smaller lesion size than the saline group, and the pretreated group had an 11% smaller lesion size than the saline group. Simvastatin also induced immunoreactivity for Bcl-2, an anti-apoptotic factor, on one hand, and down-regulated immunoreactivity for Bax, a proapoptotic factor. Bcl-2/Bax modulation can account, at least partly, for the beneficial effect of simvastatin in our rodent model of striatal degeneration. Our findings show that statins could be explored as possible neuroprotective agents for neurodegenerative disorders such as HD.