1,721,381 research outputs found
Nitric oxide-releasing cyclodextrins as biodegradable antibacterial scaffolds: a patent evaluation of US2019343869(A1)
No full textIntroduction: Antimicrobial resistance is one of the major scourges for health care worldwide; therefore, novel investigational approaches are needed to potentiate and preserve the current antibacterial arsenal. Cyclodextrins are known to improve the formulability of several different therapeutic agents. When functionalized with nitric oxide (NO) releasing groups, and suitably loaded with an antibacterial or antitumoral agents, they can exert additive activity, especially toward certain bacterial strains and cell cancer lines. Areas covered: US2019343869 describes NO-releasing cyclodextrins, a method for their synthesis, a composition that is based on them, and their application as anticancer or antibacterial agents, especially toward planktonic P. aeruginosa and the biofilm resulting from infection. Anticancer activity is measured against A549 cells. The amount of NO released is in the range of 0.5 μmol to 2.5 μmol per milligram of functionalized cyclodextrin with a half-life for NO release in a range of between about 0.7–4.2 hours. Expert opinion: The results support the use of NO-releasing cyclodextrins as a matrix for the delivery of antibacterial and anticancer drugs in a suitable formulation. However, antibacterial activity seems to be weak, and more focused studies are needed
Antituberculosis agents: Beyond medicinal chemistry rules
No full textMycobacterial infections are among the most widespread infectious diseases worldwide. For instance, tuberculosis (TB) is one of the top 10 causes of death worldwide and it is the leading cause from a single infectious agent. Of particular concern is the growing number of drug-resistant mycobacterial strains, that requires therapy prolongation and the use of less effective and more toxic drugs. One of the challenges in the treatment of TB is represented by the peculiar structure of the mycobacterial cell wall, which represents an effective defense against external insults, since its poor accessibility. For these reasons, the treatment is based on the administration of a cocktail of antimycobacterial drugs that must be prolonged (6-month standard) promoting, in turn, the occurrence of resistance. The search for novel effective therapeutic regimens has led to a nourished TB pipeline that mostly includes new chemical entities characterized by high killing potency and innovative mechanism of action. Alongside, “non-antimicrobial” host- and pathogen-directed therapies are emerging as effective strategies to support the standard treatment. Analysis of the molecules in the pipeline demonstrates that antituberculosis agents, either antimicrobial or adjuvant, are rarely compliant with the most common medicinal chemistry rules and largely evade the boundaries of drug-likeness, resulting in a “stand-alone” pharmaceutical class. In this chapter, the structural characteristics of several molecules in the TB pipeline are critically reviewed, and useful suggestions for the design of the next-generation antituberculosis drugs, both antimicrobial and adjuvant, are provided
Letter regarding article by Abbate et al, "widespread myocardial inflammation and infarct-related artery patency
No full textLetter regarding article by Nanthakumar et al, "Electrophysiological findings in adolescents with atrial fibrillation who have structurally normal hearts".
No full text“Hissing snake” left ventricle. Thrombotic phase of hypereosinophilic endomyocardial disease
No full textDetectability and parameter estimation of stellar origin black hole binaries with next generation gravitational wave detectors
No full textWe consider stellar-origin black hole binaries, which are among the main astrophysical sources for next generation gravitational wave (GW) detectors such as the Einstein Telescope (ET) and Cosmic Explorer (CE). Using population models calibrated with the most recent LIGO/Virgo results from O3b run, we show that ET and CE will be capable of detecting tens of thousands of such sources (and virtually all of those present in our past light cone up to z≲ 0.7 for ET and z≲ 1 for CE) with a signal-to-noise ratio up to several hundreds, irrespective of the detector design. When it comes to parameter estimation, we use a Fisher-matrix analysis to assess the impact of the design on the estimation of the intrinsic and extrinsic parameters. We find that the CE detector, consisting of two distinct L- shape interferometers, has better sky localization performance compared to ET in its triangular configuration. We also find that the network is typically capable of measuring the chirp mass, symmetric mass ratio and spins of the binary at order of 10 - 5, 10 - 4 and 10 - 4 fractional error respectively. While the fractional errors for the extrinsic parameters are of order 10 - 2 for the sky localization, luminosity distance and inclination
Cholinergic molecules and sperm functions
No full textMolecules acting on neurotransmitter systems are known to be present in sperms of several species: their presence was correlated to the regulation of sperm propulsion. To understand their function, a study was carried out on sperm activation, in the presence of cholinergic drugs (acetylcholine and drugs competitive at cholinergic receptors, agonist and antagonist, both muscarinic and nicotinic ones). The in vivo effects were also studied by demonstrating membrane depolarization with merocyanine, a potentiometric dye. Concentrated acetylcholine, up to 100 muM, inhibited both activation and membrane depolarization, while diluted to 10 muM, ACh enhanced it. The competitive drugs exerted on activation more or less the same effects as those on movement, reported in literature. 100 muM atropine reversibly prevented activation, while, more diluted, only delayed it. 1 muM nicotine and carbachol enhanced, and curare delayed activation and merocyanine staining. The results show the possibility that both nicotinic and muscarinic AChRs are involved in the mechanism of sperm activation. Further, the possibility that an ACh-like substance concentrated in the sperm liquid may be involved in maintaining the sperms in the quiescent state is discussed
Histologic findings in patients with clinical and instrumental diagnosis of arrhythmogenic right ventricular dysplasia
No full textImmunosuppressive treatment of chronic non-viral myocarditis.
No full textInflammatory cardiomyopathy defined as myocarditis associated with cardiac dysfunction, represents a main cause of heart failure. Despite the improvement 'of diagnostic techniques, a specific standardized treatment of myocarditis is not yet available. The immunohistochemical detection of myocardial HLA up-regulation has been demonstrated useful in the identification of a subgroup of autoimmune inflammatory dilated cardiomyopathy (DCM) in part susceptible to immunosuppression. Recently, in a retrospective study, we defined the virologic and immunologic profile of responders and non-responders to immunosuppressive therapy of active lymphocytic myocarditis and chronic heart failure in patients who had failed to benefit from conventional supportive treatment. Non-responders were characterized by high prevalence (85%) of viral genomes in the myocardium and no detectable cardiac autoantibodies in the serum. Conversely, 90% of responders were positive for autoantibodies, while only 3 (15%) of them presented viral particles at PCR analysis on frozen endomyocardial tissue. With regard to the type of virus involved in non-responders, enterovirus, adenovirus, or their combination was associated with the worst clinical outcome. Hepatitis C virus (HCV) was the only viral agent of our series associated with detectable cardiac autoantibodies, suggesting a relevant immunomediated mechanism of damage by HCV and explaining the relief of myocardial inflammation after immunosuppressive treatment. The assessment of virologic and immunologic features of patients with biopsy-proven inflammatory cardiomyopathy may allow us to identify a specific treatment leading to recovery of cardiac function
Measuring parity violation in the Stochastic Gravitational Wave Background with the LISA-Taiji network
Full text linkParity violation is a powerful observable to distinguish a cosmological background of Gravitational Waves (GWs) from an astrophysical one. Planar single GW interferometers, both on ground and in space, are unable to measure the net circular polarization of an isotropic Stochastic Gravitational Wave Background (SGWB). In this paper, we explore the possibility of detecting circular polarization of an isotropic SGWB by cross-correlating two space-based detectors planned to be launched around 2034: LISA and Taiji. We compute the response of such a network to chirality and we perform a Fisher forecast analysis on the I and V Stokes parameters for the SGWB. We find that a clear measurement of chirality can be claimed for a maximally chiral flat signal with amplitude h 2 ΩGW ≃ 10-12 at the frequency scales of LISA and Taiji
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