Wavefront-Guided versus Non-Wavefront-Guided Photorefractive Keratectomy for Myopia: Meta-Analysis of Randomized Controlled Trials

Purpose

To compare the efficacy, predictability, safety, and induced higher-order aberrations (HOAs) between wavefront-guided and non-wavefront-guided photorefractive keratectomy (PRK).

Methods

The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for randomized controlled trials. Trials meeting the selection criteria were quality appraised, and data was extracted by 2 independent authors. Measures of association were pooled quantitatively using meta-analytical methods. Comparisons between wavefront-guided and non-wavefront-guided ablations were made as pooled odds ratios (ORs) or weighted mean differences. The pooled ORs and 95% confidence intervals (CIs) were computed for efficacy, safety, and predictability. The weighted mean differences and 95% CIs were used to compare induced HOAs.

Results

The study covered five trials involving 298 eyes. After wavefront-guided PRK, the pooled OR of achieving an uncorrected distance visual acuity of 20/20 (efficacy) was 1.18 (95% CI, 0.53–2.60; p = 0.69), the pooled OR of achieving a result within ±0.50 diopter of the intended target (predictability) was 0.86 (95% CI, 0.40–1.84; p = 0.70). No study reported a loss of 2 or more lines of Snellen acuity (safety) with either modality. In eyes with wavefront-guided PRK, the postoperative trefoil aberrations (mean difference −0.02; 95% CI, −0.03 to −0.00; p = 0.03) were significantly lower. There were no significant differences between the two groups in the postoperative total HOAs (mean difference −0.04; 95% CI, −0.23 to 0.14; p = 0.63), spherical (mean difference 0.00; 95% CI, −0.08 to 0.09; p = 0.93), and coma (mean difference −0.06; 95% CI, −0.14 to 0.03; p = 0.20) aberrations.

Conclusions

According to the meta-analysis, wavefront-guided PRK offered no advantage in efficacy, predictability, or safety measures over non-wavefront-guided PRK, although it may have induced fewer trefoil aberrations.     

Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism

Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes in vitro and in vivo. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice in vivo. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes in vitro. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production.     

Thematic Review Series: Lysophospholipids and their Receptors: Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells

Cellular membranes are composed of numerous kinds of glycerophospholipids with different combinations of polar heads at the sn-3 position and acyl moieties at the sn-1 and sn-2 positions, respectively. The glycerophospholipid compositions of different cell types, organelles, and inner/outer plasma membrane leaflets are quite diverse. The acyl moieties of glycerophospholipids synthesized in the de novo pathway are subsequently remodeled by the action of phospholipases and lysophospholipid acyltransferases. This remodeling cycle contributes to the generation of membrane glycerophospholipid diversity and the production of lipid mediators such as fatty acid derivatives and lysophospholipids. Furthermore, specific glycerophospholipid transporters are also important to organize a unique glycerophospholipid composition in each organelle. Recent progress in this field contributes to understanding how and why membrane glycerophospholipid diversity is organized and maintained.     

Continuous infusion of substance P into rat striatum alleviates nociceptive behavior via phosphorylation of extracellular signal‐regulated kinase 1/2

Intraplantar injection of 0.4% formalin into the rat hind paw leads to a biphasic nociceptive response; an ‘acute’ phase (0–15 min) and ‘tonic’ phase (16–120 min), which is accompanied by significant phosphorylation of extracellular signal‐regulated kinase (ERK)1/2 in the contralateral striatum at 120 min post‐formalin injection. To uncover a possible relationship between the slow‐onset substance P (SP) release and increased ERK1/2 phosphorylation in the striatum, continuous infusion of SP into the striatum by reverse microdialysis (0.4 μg/mL in microdialysis fiber, 1 μL/min) was performed to mimic volume neurotransmission of SP. Continuous infusion for 3 h of SP reduced the duration of ‘tonic’ phase nociception, and this SP effect was mediated by neurokinin 1 (NK1) receptors since pre‐treatment with NK1 receptor antagonist CP96345 (10 μM) blocked the effect of SP infusion. However, formalin‐induced ‘tonic’ phase nociception was significantly prolonged following acute injection of the MAP/ERK kinase 1/2 inhibitor PD0325901 (100 pmol) by microinjection. The coinfusion of SP and PD0325901 significantly increased the ‘tonic’ phase of nociception. These data demonstrate that volume transmission of striatal SP triggered by peripheral nociceptive stimulation does not lead to pain facilitation but a significant decrease of tonic nociception by the activation of the SP‐NK1 receptor–ERK1/2 system.

     

Effects of intravenous cariporide on release of norepinephrine and myoglobin during myocardial ischemia/reperfusion in rabbits

Aims

To examine the effects of cariporide, a Na⁺/H⁺ exchanger-1 inhibitor, on cardiac norepinephrine (NE) and myoglobin release during myocardial ischemia/reperfusion by applying a microdialysis technique to the rabbit heart.

Main methods

In anesthetized rabbits, two dialysis probes were implanted into the left ventricular myocardium and were perfused with Ringer's solution. Cariporide (0.3 mg/kg) was injected intravenously, followed by occlusion of the left circumflex coronary artery. During 30-min coronary occlusion followed by 30-min reperfusion, four consecutive 15-min dialysate samples (two during ischemia and two during reperfusion) were collected in vehicle and cariporide-treated groups. Dialysate myoglobin and NE concentrations were measured by immunochemistry and high-performance liquid chromatography, respectively.

Key findings

Dialysate myoglobin and NE concentrations increased significantly during myocardial ischemia/reperfusion in both vehicle and cariporide-treated groups (P < 0.01 vs. baseline). In cariporide-treated group, dialysate myoglobin concentrations were significantly lower than those in vehicle group throughout ischemia/reperfusion (P < 0.01 at 0–15 min of ischemia, P < 0.05 at 15–30 min of ischemia, P < 0.01 at 0–15 min of reperfusion, and P < 0.01 at 15–30 min of reperfusion). However, dialysate NE concentrations in cariporide-treated group were lower than those in vehicle group only during ischemia (P < 0.01 at 0–15 min of ischemia, and P < 0.05 at 15–30 min of ischemia).

Significance

When administered before ischemia, cariporide reduces myoglobin release during ischemia/reperfusion and decreases NE release during ischemia.     

Marine Hydroquinone Zonarol Prevents Inflammation and Apoptosis in Dextran Sulfate Sodium-Induced Mice Ulcerative Colitis

Background and Aim

We previously identified an anti-inflammatory compound, zonarol, a hydroquinone isolated from the brown algae Dictyopteris undulata as a marine natural product. To ascertain the in vivo functions of zonarol, we examined the pharmacological effects of zonarol administration on dextran sulfate sodium (DSS)-induced inflammation in a mouse model of ulcerative colitis (UC). Our goal is to establish a safe and effective cure for inflammatory bowel disease (IBD) using zonarol.

Methods and Results

We subjected Slc:ICR mice to the administration of 2% DSS in drinking water for 14 days. At the same time, 5-aminosalicylic acid (5-ASA) at a dose of 50 mg/kg (positive control) and zonarol at doses of 10 and 20 mg/kg, were given orally once a day. DSS-treated animals developed symptoms similar to those of human UC, such as severe bloody diarrhea, which were evaluated by the disease activity index (DAI). Treatment with 20 mg/kg of zonarol, as well as 5-ASA, significantly suppressed the DAI score, and also led to a reduced colonic ulcer length and/or mucosal inflammatory infiltration by various immune cells, especially macrophages. Zonarol treatment significantly reduced the expression of pro-inflammatory signaling molecules, and prevented the apoptosis of intestinal epithelial cells. Finally, zonarol protected against in vitro lipopolysaccharide (LPS)-induced activation in the RAW264.7 mouse macrophage cell line.

Conclusions

This is the first report that a marine bioproduct protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine, a well-known prodrug that releases 5-ASA. We believe that the oral administration of zonarol might offer a better treatment for human IBDs than 5-ASA, or may be useful as an alternative/additive therapeutic strategy against UC, without any evidence of side effects.     

Suppression of Microbial Metabolic Pathways Inhibits the Generation of the Human Body Odor Component Diacetyl by Staphylococcus spp

Diacetyl (2,3-butanedione) is a key contributor to unpleasant odors emanating from the axillae, feet, and head regions. To investigate the mechanism of diacetyl generation on human skin, resident skin bacteria were tested for the ability to produce diacetyl via metabolism of the main organic acids contained in human sweat. l-Lactate metabolism by Staphylococcus aureus and Staphylococcus epidermidis produced the highest amounts of diacetyl, as measured by high-performance liquid chromatography. Glycyrrhiza glabra root extract (GGR) and α-tocopheryl-l-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), a phosphate diester of α-tocopherol and ascorbic acid, effectively inhibited diacetyl formation without bactericidal effects. Moreover, a metabolic flux analysis revealed that GGR and EPC-K1 suppressed diacetyl formation by inhibiting extracellular bacterial conversion of l-lactate to pyruvate or by altering intracellular metabolic flow into the citrate cycle, respectively, highlighting fundamentally distinct mechanisms by GGR and EPC-K1 to suppress diacetyl formation. These results provide new insight into diacetyl metabolism by human skin bacteria and identify a regulatory mechanism of diacetyl formation that can facilitate the development of effective deodorant agents.     

Isolation of Tannin-Degrading Lactobacilli from Humans and Fermented Foods

Lactobacilli with tannase activity were isolated from human feces and fermented foods. A PCR-based taxonomic assay revealed that the isolates belong to Lactobacillus plantarum, L. paraplantarum, and L. pentosus. Additional studies on a range of Lactobacillus species from established culture collections confirmed that this enzymatic activity is a phenotypic property common to these three species.     

Hydrolysis of newspaper polysaccharides under sulfate reducing and methane producing conditions

The initial decomposition rates of cellulose and hemicellulose were measured using toluene to specifically inhibit the microbial uptake of hydrolysis products during the degradation of newspaper under sulfate reducing and methane producing conditions. The amount of glucose and xylose accumulation in the first 2 weeks of incubation period was higher in the sulfate reducing condition compared to the methane producing condition. It was estimated that 28 and 6% of initially loaded cellulose in the sulfate reducing condition and the methane producing condition was hydrolyzed, respectively. Accordingly, the newspaper-cellulose hydrolysis rate constant was estimated to be 6.7 times higher in sulfate reducing condition than in methane producing condition. Based on the glucose accumulation patterns, when sulfate reducing bacteria (SRB) were inhibited by anthraquinone and molybdate (Na₂MoO₄), it may be suggested that SRB might have contributed to the hydrolysis of cellulose, while their effect on the hydrolysis of hemicellulose could not be elucidated.