Anti-HIV-1 Activity of CD4 Synthetic Oligopeptides Representative of the Putative gp120 Binding Site

Two CD4 oligopeptides, corresponding to residues (37–53) and (37–55) of the V1 domain of CD4, which recent structural studies propose as the most likely binding site of HIV-1 gp120, have been chemically synthesized by solid-phase techniques, modified by the addition of two side-chain protected cysteines at both termini and purified by HPLC. Their ability to inhibit the infectivity of human immunodeficiency virus type 1 (HIV-1) (HTLV-IIIB, RF and GB8 strains) in different cell lines was monitored by the production of progeny virus, p24 and reverse transcriptase activity in the culture supernatants and by electron microscopy. The results indicated that the peptides inhibited HIV-1 infectivity in a dose-dependent fashion without any detectable cytotoxicity

fluoroquinolone resistance and molecular characterization of gyra and parc quinolone resistance determining regions in escherichia coli isolated from poultry

Abstract Escherichia coli are a common inhabitant of the gastrointestinal tract of mammals and birds; nevertheless, they may be associated with a variety of severe and invasive infections. Whereas fluoroquinolones (FQ) have been banned in the United States for use in poultry production, the use of these antimicrobials in poultry husbandry is still possible in the European Union, although with some restrictions. The aim of this study was to investigate the FQ resistance of 235 E. coli isolates recovered from chickens and turkeys. Minimum inhibitory concentrations were determined by a microdilution method, whereas mutations in the quinolone resistance-determining regions of the target genes, gyrA and parC, were detected by a PCR-based method. High resistance rates (>60%) were observed for nalidixic acid, flumequine, and difloxacin, whereas resistance to ciprofloxacin, danofloxacin, enrofloxacin, marbofloxacin, and sarafloxacin was less frequently reported

Modular plastic chip for one-shot human papillomavirus diagnostic analysis.

In this article, we report the design and development of a plastic modular chip suitable for one-shot human papillomavirus (HPV) diagnostics, namely detection of the viral presence and relative genotyping, by two sequential steps performed directly on the same device. The device is composed of two modular and disposable plastic units that can be assembled or used separately. The first module is represented by a polydimethylsiloxane (PDMS) microreactor that is exploited for real-time polymerase chain reaction (PCR) and, thus, is suitable for detecting the presence of virus. The second unit is a PDMS microwell array that allows virus genotyping by a colorimetric assay, based on DNA hybridization technology developed on plastic, requiring simple inspection by the naked eye. The two modules can be easily coupled to reusable hardware, enabling the heating/cooling processes and the real-time detection of HPV. By coupling real-time assay and colorimetric genotyping on the same chip, the assembled device may provide a low-cost tool for HPV diagnostics, thereby favoring the prediction of cancer risk in patients

Novel highly potent and selective sigma1 receptor antagonists effectively block the binge eating episode in female rats

In this paper, the benzo-cracking approach was applied to the potent sigma1 (σ1) receptor antagonist 1 to afford the less conformationally constrained 1,3-dioxane derivatives 2 and 3. To evaluate the effect of the increase in the distance between the two hydrophobic structural elements that flank the basic function, the cis and trans diastereomers of 4 and 5 were also prepared and studied. Compounds 2 and 3 showed affinity values at the σ1 receptor significantly higher than that of the lead compound 1. In particular, 3 displayed unprecedented selectivity over the σ2 receptor, the phencyclidine site of the NMDA receptor, and opioid receptor subtypes, as well as over the dopamine transporter. Docking results supported the structure-activity relationship studies. Due to its interesting biological profile, derivative 3, selected for an in vivo study in a validated preclinical model of binge eating, was able to counteract the overeating of palatable food only in binging rats, without affecting palatable food intake in the control group and anxiety-like and depression-related behaviors in female rats. This result strengthened the involvement of the σ1 receptor in the compulsive-like eating behavior and supported the σ1 receptor as a promising target for the management of eating disorders

Role of the mucins in pathogenesis of COPD: implications for therapy.

Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different mucins present in the different compartments of the human lower airways. This occurs both in normal subjects and in COPD patients in different clinical phases and stages of severity.Areas covered: We review the known physiological mechanisms that regulate mucin production in human lower airways of normal subjects, the changes in mucin synthesis/secretion in COPD patients and the clinical efficacy of drugs that modulate mucin synthesis/secretion.Expert opinion: It is evident that the old simplistic concept that mucus hypersecretion in COPD patients is associated with negative clinical outcomes is not valid and that the therapeutic potential of 'mucolytic drugs' is under-appreciated due to the complexity of the associated molecular network(s). Likewise, our current knowledge of the effects of the drugs already available on the market that target mucin synthesis/secretion/structure in the lower airways is extremely limited and often indirect and more well-controlled clinical trials are needed in this area

Intra-articular therapy with infliximab in psoriatic arthritis: efficacy and safety in refractory monoarthritis

Objective: To evaluate efficacy and safety of intra-articular therapy (IA) with infliximab (IFX), in patients with psoriatic arthritis (PsA) and refractory monoarthritis. Methods: Four male and 1 female aged from 25 to 71 years and disease duration from 1 to 25 years, affected by PsA (CASPAR criteria) were observed . All patients were treated with immunomodulators (methotrexate, leflunomide, cyclosporin A), 3/5 with concomitant steroids, 4/5 with NSAID’s. Only 1 patient were treated with IFX 5 mg/kg IV every 6 weeks. Before the IFX injection an amount of synovial fluid was aspired from the inflamed site and the anti-TNF injection was echographic guided. Patients were evaluated at regular intervals through clinical and echographic examination and retreated in case of flare. Results: At follow-up visit after 7 days, in all patients treated with the first injection was detected total regression of the inflammation and no new inflamed synovial fluid was observed; power doppler examination shows reduction of local vascularization. Two patients experienced full remission after 6 months and only one injection, 1 patient (arthritis of the wrist) was in remission after 2 injections (3 months of interval). In 2 patients with knee arthritis and important synovial hypertrophy good results obtained after the first injection were not maintained afterwards and second injection was ineffective: these patients were evaluated for surgical intervention. Conclusions: Local injections of IFX were safe and well tolerated in all patients. The efficacy in short term was observed in all cases; our supposition is that presence of synovial hypertrophy is cause of worsening

A 50 ps resolution monolithic active pixel sensor without internal gain in SiGe BiCMOS technology

A monolithic pixelated silicon detector designed for high time resolution has been produced in the SG13G2 130 nm SiGe BiCMOS technology of IHP. This proof-of-concept chip contains hexagonal pixels of 65 µm and 130 µm side. The SiGe front-end electronics implemented provides an equivalent noise charge of 90 and 160 e- for a pixel capacitance of 70 and 220 fF, respectively, and a total time walk of less than 1 ns. Lab measurements with a 90Sr source show a time resolution of the order of 50 ps. This result is competitive with silicon technologies that integrate an avalanche gain mechanism. © 2019 CERN

Severe Aortic Stenosis and Myocardial Function: Diagnostic and Prognostic Usefulness of Ultrasonic Integrated Backscatter Analysis

Background— The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology. Methods and Results— Thirty-five subjects (AS: valve orifice ≤1 cm2; 12 female; mean age, 71.8±6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy). Conclusions— One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15\u201320 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801\u20133). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E \u3b3 \u2009\u2009>\u2009\u2009200\u2009keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7\u201319.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc

Significant changes in the magma dynamics of Stromboli steady-state volcano recorded by clinopyroxene crystals.

&amp;lt;p&amp;gt;Steady-state volcanic activity implies equilibrium between the rate of magma replenishment and eruption of compositionally homogeneous magmas, lasting for tens to thousands of years in an open conduit system. The Present-day activity of Stromboli volcano (Aeolian Islands, Southern Italy) has long been recognised as typical of a steady-state volcano, with a shallow magmatic reservoir (highly porphyritic or hp-magma) continuously refilled by more mafic magma (with low phenocryst content or lp-magma) at a constant rate and accompanied by mixing, crystallisation and eruption. The lp-magma is erupted only during more violent explosive events (paroxysms), which usually occur at intervals of a few years. However, the two most recent paroxysms occurred at very short timescales on 3 July and 28 August 2019 offering the unique opportunity of obtaining crucial information on the current magma dynamics of Stromboli.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Albeit the plumbing system shows such uniformity, clinopyroxene phenocrysts exhibit marked chemical heterogeneities and complex textures caused by continuous lp-hp magma mixing as well as antecryst recycling from different mush portions. The compositional zoning in clinopyroxene provides essential information on pre-eruptive magma dynamics, indicating multi-stage crystallization across the lp-hp-reservoirs, where diopsidic compositions are markers of more primitive, high-T magmas injecting into shallow, low-T domains of the plumbing system. By comparing clinopyroxene texture, chemistry and residence times from the Present-day eruptions with the previous Post-Pizzo activity, we conclude that a distinct phase in the life of Stromboli volcano commenced after the violent 2003 paroxysm. Our observations suggest there are more efficient mechanisms of mush disruption and cannibalization, in which old diopsidic antecrysts are continuously remobilized and transported by the lp-magmas permeating the mush. The disappearance of diopsidic recharge bands within augitic overgrowths indicates that over time, magmatic injections feeding the persistent Present-day activity are more intensively mixed and homogenized prior to eruption.&amp;lt;/p&amp;gt; </jats:p