Azelastine Nasal Spray in Non-Hospitalized Subjects with Mild COVID-19 Infection: A Randomized Placebo-Controlled, Parallel-Group, Multicentric, Phase II Clinical Trial.

Nasal spray treatments that inhibit the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry into nose and nasopharynx at early stages can be an appropriate approach to stop or delay the progression of the disease. We performed a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicentric, phase II clinical trial comparing the rate of hospitalization due to COVID-19 infection between azelastine 0.1% nasal spray and placebo nasal spray treatment groups.

Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients.

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.

Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients.

The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine.

PF74 and Its Novel Derivatives Stabilize Hexameric Lattice of HIV-1 Mature-Like Particles.

A major structural retroviral protein, capsid protein (CA), is able to oligomerize into two different hexameric lattices, which makes this protein a key component for both the early and late stages of HIV-1 replication. During the late stage, the CA protein, as part of the Gag polyprotein precursor, facilitates protein-protein interactions that lead to the assembly of immature particles. Following protease activation and Gag polyprotein processing, CA also drives the assembly of the mature viral core.

Injection laser system for Advanced Radiographic Capability using chirped pulse amplification on the National Ignition Facility.

We report on the design, performance, and qualification of the injection laser system designed to deliver joule-level chirped pulse beamlets arranged in dual rectangular beam formats into two main laser amplifier beamlines of the National Ignition Facility. The system is designed to meet the requirements of the Advanced Radiographic Capability upgrade with features that deliver performance, adjustability, and long-term reliability.

A simple, high-throughput stabilization assay to test HIV-1 uncoating inhibitors.

Shortly after entering the cell, HIV-1 copies its genomic RNA into double-stranded DNA in a process known as reverse transcription. This process starts inside a core consisting of an enclosed lattice of capsid proteins that protect the viral RNA from cytosolic sensors and degradation pathways. To accomplish reverse transcription and integrate cDNA into the host cell genome, the capsid shell needs to be disassembled, or uncoated.

Stabilization of hyaluronan-based materials by peptide conjugation and its use as a cell-seeded scaffold in tissue engineering.

New materials based on molecules naturally occurred in body are assumed to be fully biocompatible and biodegradable. In our study, we used hyaluronic acid (HA) modified with peptides, which meet all this criterion and could be advantageously used in tissue engineering. Peptides with RGD, IKVAV or SIKVAV adhesive motif were attached to HA-based fiber or non-woven textile through ester bond in the term of solid phase peptide synthesis.

Electronic and vibrational optical activity of several peptides related to neurohypophyseal hormones: disulfide group conformation.

Electronic and vibrational optical activity of the set of neurohypophyseal hormones and their analogs was investigated to clarify the S-S bond solution conformation. The selected compounds include oxytocin (I), lysine vasopressin (II), arginine vasopressin (III), and their analogs (IV-IX), differing widely in their pharmacological properties. We have extended the already known electronic circular dichroism data by new information provided by vibrational circular dichroism (VCD) and Raman optical activity (ROA).

Step-length variability in minimally disabled women with multiple sclerosis or clinically isolated syndrome.

Gait is one of the most frequently impaired bodily functions in multiple sclerosis (MS). Determining abnormal parameters of gait in early MS could influence MS treatment and rehabilitation. The purpose of this study was to determine whether increased step-length variability could be detected in minimally disabled patients with MS or clinically isolated syndrome (CIS) using a sensored walkway gait analysis system.

Galanin modulating effect on restraint stress-induced short- and long-term behavioral changes in Wistar rats.

The neuropeptide galanin has been recognized as a possible neurotransmitter/neuromodulator, and in addition has been implicated in anxiety- and depression-related behaviors. The present study demonstrates increased locomotion and rearing after galanin (0.3mg/kg) that was given intraperitoneally (i.

The human cerebrospinal fluid metabolome.

With continuing improvements in analytical technology and an increased interest in comprehensive metabolic profiling of biofluids and tissues, there is a growing need to develop comprehensive reference resources for certain clinically important biofluids, such as blood, urine and cerebrospinal fluid (CSF). As part of our effort to systematically characterize the human metabolome we have chosen to characterize CSF as the first biofluid to be intensively scrutinized. In doing so, we combined comprehensive NMR, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) Fourier transform-mass spectrometry (FTMS) methods with computer-aided literature mining to identify and quantify essentially all of the metabolites that can be commonly detected (with today's technology) in the human CSF metabolome.

Crystal structure of LL-diaminopimelate aminotransferase from Arabidopsis thaliana: a recently discovered enzyme in the biosynthesis of L-lysine by plants and Chlamydia.

The essential biosynthetic pathway to l-Lysine in bacteria and plants is an attractive target for the development of new antibiotics or herbicides because it is absent in humans, who must acquire this amino acid in their diet. Plants use a shortcut of a bacterial pathway to l-Lysine in which the pyridoxal-5'-phosphate (PLP)-dependent enzyme ll-diaminopimelate aminotransferase (LL-DAP-AT) transforms l-tetrahydrodipicolinic acid (L-THDP) directly to LL-DAP. In addition, LL-DAP-AT was recently found in Chlamydia sp.

Photoaddition of water and alcohols to the anthracene moiety of 9-(2'-hydroxyphenyl)anthracene via formal excited state intramolecular proton transfer.

The title compound undergoes efficient photoaddition of a molecule of a hydroxylic solvent (H(2)O, MeOH, (Me)(2)CHOH) across the 9- and 10-positions of the anthracene moiety to give isolable triphenylmethanol or triphenylmethyl ether type products. The reaction is believed to proceed via a mechanism involving water-mediated formal excited state intramolecular proton transfer (ESIPT) from the phenolic OH to the 10-position of the anthracene ring, generating an o-quinone methide intermediate that is observable by nanosecond laser flash photolysis, and is trappable with nucleophiles. A "water-relay" mechanism for proton transfer seems plausible but cannot be proven directly with the data available.

Chiral analysis of biogenic D,L-amino acids derivatized by N-fluorenylmethoxycarbonyl-L-alanyl N-carboxyanhydride using high-performance liquid chromatography.

Nineteen biogenic D,L-amino acids are derivatized with highly reactive N-fluorenylmethoxycarbonyl-L-alanyl N-carboxyanhydride. Using a 0.5M borate buffer at pH 7.

Chiral analysis of biogenic DL-amino acids derivatized by urethane - protected alpha-amino acid N-carboxyanhydride using capillary zone electrophoresis and micellar electrokinetic chromatography.

A new analytical method for enantioselective separation of DL-amino acids derivatized by N-fluorenylmethoxycarbonyl-L-alanyl N-carboxyanhydride (FMOC-L-Ala-NCA) using capillary electrophoresis was developed. Separation parameters, such as composition and pH of the background electrolyte, and concentration of gamma-cyclodextrin (in capillary zone electrophoresis) and sodium dodecyl sulfate (in micellar electrokinetic chromatography) were optimized. The separation method was validated and it suits well for purity analysis.

Large-scale synthesis of peptides.

Recent advances in the areas of formulation and delivery have rekindled the interest of the pharmaceutical community in peptides as drug candidates, which, in turn, has provided a challenge to the peptide industry to develop efficient methods for the manufacture of relatively complex peptides on scales of up to metric tons per year. This article focuses on chemical synthesis approaches for peptides, and presents an overview of the methods available and in use currently, together with a discussion of scale-up strategies. Examples of the different methods are discussed, together with solutions to some specific problems encountered during scale-up development.

An assessment of lower back pain in young adults: implications for college health education.

A convenience sample of 243 undergraduates completed a 36-item questionnaire on their knowledge about back care and exercise patterns before they attended lectures and a workshop on back mechanics. At the workshop, the students were individually evaluated for posture, hamstring flexibility, hip flexor flexibility, back and abdominal strength, and lifting technique. Twenty-nine percent of the students reported that they experienced no back pain; 71% experienced lower back pain 1 to 5 days a week.

T-cell-dependent immunobiological activity of a desmuramyl analog of muramyl dipeptide, adamantylamide dipeptide (AdDP), and D-isoglutamine.

The present experiments demonstrate that, similar to immunomodulatory muramyl dipeptide, its desmuramyl analog adamantylamide dipeptide is able to induce mild and fully reversible paw edema in mice. This effect is an immune-related phenomenon depending on the activation of T-cell/macrophage interactions and on production of prostaglandins. Possible involvement of certain immunoregulatory/inflammatory cytokines (e.

Pharmacokinetic profile of the immunomodulating compound adamantylamide dipeptide (AdDP), a muramyl dipeptide derivative in mice.

A pharmacokinetic profile of 14C-AdDP with uniformly labelled alanine was investigated. It was shown that the distribution phase after an i.v.

Synthesis of inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli.

In order to obtain inhibitors of the meso-diaminopimelate-adding enzyme, which participates in the biosynthesis of bacterial peptidoglycan, several N alpha-propionyl-dipeptides of the general formula Pr-L-Ala-ambo-Xaa-OH were synthesized. Xaa represented methionine S,S-dioxide, methionine S-oxide, methionine sulfoximine, and 2-amino-4-phosphonobutyric acid, i.e.

Solid-phase synthesis of a nonadecapeptide coded for by the v-myb oncogene.

A nonadecapeptide comprising a predicted B-cell determinant from the v-myb oncoprotein was synthesized by Merrifield's solid-phase method. Hydrogen chloride in dichloromethane was used for protective t-butyloxycarbonyl group removal; the deprotection was monitored using a new qualitative deprotection test. The nonadecapeptide coupled to a carrier elicited a high titre of protein-reactive antipeptide antibodies.