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.

Not first-line antihypertensive agents, but still effective-The efficacy and safety of imidazoline receptor agonists: A network meta-analysis.

Cardiovascular disorders are the leading cause of death in the world. Many organ diseases (kidney, heart, and brain) are substantially more prone to develop in people with hypertension. In the treatment of hypertension, first-line medications are recommended, while imidazoline receptor agonists are not first-line antihypertensives.

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.

The effect of an exam period as a stress situation on baroreflex sensitivity among healthy university students.

Authors investigated the effect of a university exam period on blood pressure (BP) and baroreflex-sensitivity (BRS) among healthy students. Fifty-three healthy normotensive university students participated in the test. BP values and BRS were recorded once during a 14-week long semester and once during a 6-week long exam period with a Finometer device.

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.

Observations of changes of blood pressure before and after neurosurgical decompression in hypertensive patients with different types of neurovascular compression of brain stem.

Aims: The neurovascular pulsatile compression of the rostral ventrolateral medulla can be divided into different subtypes. The posterior inferior cerebellar artery and/or vertebral artery can compress either the rostral ventrolateral medulla or the cranial nerves IX and X or both and on left, right or both sides.

Methods: It was retrospectively investigated whether the types of neurovascular compression can influence blood pressure values.

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.

Investigation of cardiac autonomic and peripheral sensory neuropathy in diabetic and nondiabetic patients with hypertension.

Peripheral sensory function and cardiac autonomic neuropathy were studied in 18 nondiabetic and 10 type-2 diabetic hypertensives compared with 11 healthy controls. All the patients were treated with antihypertensive drugs. Cardiac autonomic neuropathy using Ewing method was detected in all patient groups.

BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis.

BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis.

Clostridium septicum gas gangrene in the orbit: a case report.

Our report presents a case of Clostridium septicum gas gangrene in an unusual, orbital localization. The predisposing factors are typical: colon tumour and lymphatic malignancy. Most probably bacteria from the intestinal flora entered the bloodstream through the compromised intestinal wall and settled in the orbit resulting in the development of an abscess containing gas.

Interocular amplitude differences of multifocal electroretinograms obtained under monocular and binocular stimulation conditions.

Purpose: To compare the interocular amplitude differences of the multifocal electroretinograms (mfERGs) evoked by either monocular or binocular stimulation in healthy subjects with good vision.

Methods: Thirty-five subjects were included in the study. A Roland Consult RETIscan system was used.

[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.

Characterization of subsoil heterogeneity, estimation of grain size distribution and hydraulic conductivity at the Krauthausen test site using Cone Penetration Test.

A Cone Penetration Test (CPT) survey with a high spatial resolution was performed in order to investigate the stratigraphy as well as the spatial variability of various soil properties of the Krauthausen test site. Analyses of the CPT measurements showed the subsurface to be dominated by a planar layered structure. Variogram analysis of the various CPT parameters disclosed that within each layer the soil properties have an anisotropic spatial correlation structure.

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.

Absolute and relative-rate kinetics experiments and direct dynamics computations for the reaction of Br atoms with CH2ClBr.

Kinetics of the reaction Br + CH2ClBr <--> CHClBr + HBr (1, -1) were studied experimentally in the forward direction. The absolute reaction kinetics method of laser flash photolysis coupled with Br atom resonance fluorescence detection and three different relative-rate methods with gas-chromatographic analysis were applied to carry out the experiments. The rate constants determined were found to obey the Arrhenius law in the wide temperature range of T = 293-785 K providing the kinetic expression k1 = (2.

Effect of body weight on testosterone/estradiol ratio in oligozoospermic patients.

To evaluate the effect of body mass on the hormonal and semen profiles of subfertile men with oligozoospemia, sperm concentration and reproductive hormone levels were compared in two body mass index (BMI) groups: underweight or normal weight patients (BMI = 25 kg/m2) vs. overweight or obese patients (BMI > 25 kg/m2). The mean BMI was 27 +/- 4.