Blood pressure and glaucoma: At the crossroads between cardiology and ophthalmology

Glaucoma is an optic nerve neuropathy of undetermined cause. Although many mechanisms are thought to be involved in the development and progression of the disease, only an increased intraocular pressure has been established as a clinically significant modifiable risk factor. Nevertheless, up to 40% of patients develop glaucoma without evidence of increased intraocular pressure.  Ample evidence suggests that alterations in the control of arterial blood might negatively affect optic nerve function. However, evidence-based guidelines on the management of arterial blood pressure in glaucoma patients are lacking. Regrettably, intraocular pressure is generally not included as a secondary end-point in clinical trials on arterial hypertension. Considering the relative simplicity of intraocular pressure measurements and large number of patients included in hypertension studies, the benefits of including intraocular pressure as a secondary end-point could be of a great value for improving care for glaucoma patients. Therefore, closer collaboration between cardiologists and ophthalmologists is needed.

Dyslipidemia aterogenna w codziennej praktyce — interdyscyplinarny konsensus polskich ekspertów

Dyslipidemia is the most common risk factor for cardiovascular diseases in Poland. According to the latest guidelines of Scientific Societies, the primary goal of lipid-lowering therapy is to lower LDL-cholesterol, but we should not underestimate the impact of atherogenic dyslipidemia, defined as elevated levels of triglycerides (TG) and very-low-density lipoprotein (VLDL) and decreased HDL-cholesterol (HDL-C), on the progression of atherosclerosis. High TG and low HDL-C are independent risk factors for cardiovascular events, which can be effectively monitored and treated with statins and fenofibrate. The following consensus statement of Polish experts is an attempt to summarize the latest knowledge in the field of atherogenic dyslipidemia and to develop the recommendations for its treatment.Zaburzenia lipidowe są najbardziej rozpowszechnionym czynnikiem ryzyka chorób układu sercowo-naczyniowego w Polsce. Według najnowszych wytycznych towarzystw naukowych nadrzędnym celem terapii hipolipemizującej jest obniżenie stężenia cholesterolu frakcji LDL, niemniej jednak nie można nie doceniać wpływu, jaki na postęp zmian miażdżycowych w naczyniach tętniczych wywiera aterogenna dyslipidemia, czyli podwyższone stężenie triglicerydów (TG) i lipoprotein o bardzo małej gęstości (VLDL) zawierających TG oraz obniżone stężenie frakcji cholesterolu HDL (HDL-C). Wysokie stężenie TG i niskie stężenie HDL-C są niezależnymi czynnikami ryzyka zdarzeń sercowo-naczyniowych, które można skutecznie kontrolować i leczyć za pomocą statyn i fenofibratu. Poniższe stanowisko polskich ekspertów wielu dziedzin stanowi próbę podsumowania najnowszej wiedzy w dziedzinie dyslipidemii aterogennej i sformułowanie zaleceń dotyczących jej leczenia

Measurement of Production Properties of Positively Charged Kaons in Proton-Carbon Interactions at 31 GeV/c

Spectra of positively charged kaons in p+C interactions at 31 GeV/c were measured with the NA61/SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2007 with a graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections and charged pion spectra were already measured using the same set of data. These new measurements in combination with the published ones are required to improve predictions of the neutrino flux for the T2K long baseline neutrino oscillation experiment in Japan. In particular, the knowledge of kaon production is crucial for precisely predicting the intrinsic electron neutrino component and the high energy tail of the T2K beam. The results are presented as a function of laboratory momentum in 2 intervals of the laboratory polar angle covering the range from 20 up to 240 mrad. The kaon spectra are compared with predictions of several hadron production models. Using the published pion results and the new kaon data, the K+/\pi+ ratios are computed.Comment: 10 pages, 11 figure

Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase II multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase II study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 \u3bcg/ml, 20 \u3bcg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 \u3bcg/ml (+35.3%; 97.06% confidence interval [CI], 15.88\u201354.71; P < 0.001) and 58.0% receiving rhNGF 20 \u3bcg/ml (+38.4%; 97.06% CI, 18.96\u201357.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 \u3bcg/ml (+31.4%; 97.06% CI, 11.25\u201351.49; P = 0.001) and 74.0% receiving rhNGF 20 \u3bcg/ml (+30.9%; 97.06% CI, 10.60\u201351.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK

Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration

Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber–Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found (OR 3.40, 4.15, and 2.75). On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form (OR 0.23, 0.21, 0.26). Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD

2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action

Measurements of Cross Sections and Charged Pion Spectra in Proton-Carbon Interactions at 31 GeV/c

Interaction cross sections and charged pion spectra in p+C interactions at 31 GeV/c were measured with the large acceptance NA61/SHINE spectrometer at the CERN SPS. These data are required to improve predictions of the neutrino flux for the T2K long baseline neutrino oscillation experiment in Japan. A set of data collected during the first NA61/SHINE run in 2007 with an isotropic graphite target with a thickness of 4% of a nuclear interaction length was used for the analysis. The measured p+C inelastic and production cross sections are 257.2 +- 1.9 +- 8.9 mb and 229.3 +- 1.9 +- 9.0 mb, respectively. Inclusive production cross sections for negatively and positively charged pions are presented as a function of laboratory momentum in 10 intervals of the laboratory polar angle covering the range from 0 up to 420 mrad. The spectra are compared with predictions of several hadron production models.Comment: updated version; as published by Phys. Rev.