Covalent Inhibitors of KEAP1 with Exquisite Selectivity.

The NRF2-KEAP1 interaction is central for cytoprotection against stresses, giving it high clinical significance. Covalent modification of KEAP1 is an efficient approach, but the covalent inhibitors used in the clinic carry undesired side effects originating in their moderate selectivity. Starting with a phenotypic screen, we identified a new covalent inhibitor chemotype that was optimized to deliver a series of potent and highly selective KEAP1 binders.

Targeting NOX2 via p47/phox-p22/phox Inhibition with Novel Triproline Mimetics.

On the basis of the knowledge that the proline-rich hot spot RPP region of P(151)PSNPPPRPP(160), an oligopeptide derived from the cytosolic portion of p22 (p22), binds to the single functional bis-SH3 domain of the regulatory protein p47 (p47), we designed a mimetic of the tripeptide based on NMR and X-ray crystallographic data for the p22(151-161) peptide PPSNRPPA with a peptide construct. Incorporation of the synthetic pseudo-triproline mimetic Pro-Pro-Cyp in a molecule derived from molecular modeling studies led to only a 7-fold diminution in activity in a surface plasmon resonance assay relative to the same molecule containing the natural Pro-Pro-Pro tripeptide. The alternative sequence corresponding to a Pro-Cyp-Pro insertion was inactive.

Keratitis Caused by Candida parapsilosis and Subsequent Corynebacterium macginleyi Infection: Case Report and Short Review.

Keratitis due to Candida parapsilosis or Corynebacterium macginleyi is uncommon. We present a patient with several risk factors who suffered two subsequent corneal infections caused by these pathogens and healed with topical conservative therapy. The important factor was the early detection of infection.

Lyme disease associated neuroretinitis - Case report.

We describe a rare case of Lyme disease complicated by unilateral neuroretinitis in the right eye. We report a case of a 27-year-old woman with blurred vision on her right eye. Because of the suspicion of optic neuritis (multiplex sclerosis) neurological examination was ordered.

Further Evidence for the Utility of Electrophysiological Methods for the Detection of Subclinical Stage Retinal and Optic Nerve Involvement in Diabetes.

Objective: To assess the utility of visual electrophysiological methods, visual evoked potentials (VEPs) and pattern electroretinograms (PERGs) were recorded for the detection of subclinical optic nerve and retinal involvement in patients with diabetes mellitus.

Subjects And Methods: The data of 63 patients (126 eyes) with no vascular retinopathy or optic neuropathy were retrospectively analyzed. The patients were divided into polyneuropathic/nonpolyneuropathic groups to differentiate between early and late subclinical stages.

Description of five dirofilariasis cases in South Hungary and review epidemiology of this disease for the country.

Background: Dirofilariasis is an emerging zoonosis (supported by climate change) in Central Europe. Human infections are usually caused by Dirofilaria repens and Dirofilaria immitis with mediation of mosquito vectors. Aims of this publication were to report our dirofilariasis cases, and to summarize Hungarian epidemiological data by reviewing literature.

Interocular amplitude and latency differences of pattern ERG and pattern VEP parameters.

Purpose: To determine the normal interocular differences in amplitudes and peak times of the pattern electroretinograms (PERGs) and pattern visual evoked potentials (PVEPs) and to investigate whether the PERG and PVEP parameters correspond in lateral dominance or whether the eye-side distributions of the functional parameters are similar.

Methods: The PERGs and PVEPs were recorded in healthy subjects (N = 77) according to the standards of the International Society for Clinical Electrophysiology of Vision, with the modification of the check size of the PERG to 0.5 degrees.

S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab.

Aberrant activity of the receptor tyrosine kinases MET, AXL, and FGFR1/2/3 has been associated with tumor progression in a wide variety of human malignancies, notably in instances of primary or acquired resistance to existing or emerging anticancer therapies. This study describes the preclinical characterization of S49076, a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo.

[Combined use of pattern electroretinography and pattern visual evoked potentials in neuroophthalmological practice].

Objective: To survey the role of pattern electroretinography (PERG) and pattern visual evoked potentials (VEPs) in the process of clinical evaluation of neuro-ophthalmological cases. The study is illustrated with the electrophysiological findings of 231 patients sent to our laboratory in 2005 because of the suspicion of damage in the optic pathway.

Methods: The RETIport program of the ROLAND equipment (Wiesbaden-Germany) was used to record PERGs and VEPs.

A boy or a girl? A Hungarian survey regarding gender selection.

Background: Infertile Hungarian couples were surveyed with regard to their opinion of preconception gender selection by the separation of X- and Y-bearing sperm populations.

Methods: Self-completion of a questionnaire. Group 1: subjects presenting for infertility examination; Group 2: presenting for homologous intrauterine insemination.

Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study.

A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P).