A new mouse unilateral model of diffuse alveolar damage of the lung.

OBJECTIVE AND DESIGN: The existing biological models of diffuse alveolar damage (DAD) in mice have many shortcomings. To offset these shortcomings, we have proposed a simple, nonsurgical, and reproducible method of unilateral total damage of the left lung in ICR mice. This model is based on the intrabronchial administration of a mixture of bacterial lipopolysaccharide (LPS) from the cell wall of S. enterica and α-galactosylceramide (inducing substances) to the left lung. METHODS: Using computer tomography of the lungs with endobronchial administration of contrast material, we have been able to perform an operative intravital verification of the targeted delivery of the inducer. The model presented is characterized by more serious and homogeneous damage of the affected lung compared to the existing models of focal pneumonia; at the same time, our model is characterized by longer animal survival since the right lung remains intact. RESULTS: The model is also characterized by diffuse alveolar damage of the left lung, animal survival of 100%, abrupt increases in plasma levels of TNFa, INFg, and IL-6, and significant myocardial overload in the right heart. It can be used to assess the efficacy of innovative drugs for the treatment of DAD and ARDS as the clinical manifestations that are developed in patients infected with SARS-CoV-2. Morphological patterns of lungs in the noninfectious ("sterile") model of DAD induced by LPS simultaneously with α-galactosylceramide (presented here) and in the infectious model of DAD induced by SARS-CoV-2 have been compared. CONCLUSION: The DAD model we have proposed can be widely used for studying the efficacy of candidate molecules for the treatment of infectious respiratory diseases, such as viral pneumonias of different etiology, including SARS-CoV-2.

[In vitro activity of human recombinant alpha-2b interferon against SARS-CoV-2 virus].

INTRODUCTION: The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus. MATERIAL AND METHODS: The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies. RESULTS: The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102-106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated. DISCUSSION: IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000). CONCLUSION: Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.

Asymptotic decay of the pair correlation function in molecular fluids: application to hard rods.

We investigate the asymptotic decay of the total correlation function h (1,2) in molecular fluids. To this end, we expand the angular dependence of h (1,2) and the direct correlation function c (1,2) in the Ornstein-Zernike equation in a complete set of rotational invariants. We show that all the harmonic expansion coefficients h l1l2l) (r) are governed by a common exponential decay length and a common wavelength of oscillations in the isotropic phase. We determine the asymptotic decay of the total correlation functions by investigating the pole structure of the reciprocal ( q -space) harmonic expansion coefficients h l1l2l) (q) . The expansion coefficients in laboratory frame of reference h l1l2l) (r) are calculated in computer simulations for an isotropic fluid of hard spherocylinders. We find that the asymptotic decay of h (1,2) is exponentially damped oscillatory for hard spherocylinders with a length-to-diameter ratio L/D< or =10 for all statepoints in the isotropic fluid phase. We compare our results on the pole structure using different theoretical Ansätze for c (1,2) for hard ellipsoids. The theoretical results show that the asymptotic decay of h (1,2) is exponentially damped oscillatory for all elongations of the ellipsoids.

Sedimentation and multiphase equilibria in suspensions of colloidal hard rods.

Sedimentation and multiphase equilibria in a suspension of hard colloidal rods are explored by analyzing the (macroscopic) osmotic equilibrium conditions. We observe that gravity enables the system to explore a whole range of phases varying from the most dilute phase to the densest phase, i.e., from the isotropic (I), to the nematic (N), to the smectic (Sm), to the crystal (K) phase. We determine the phase diagrams for hard spherocylinders with a length-to-diameter ratio of 5 for a semi-infinite system and a system with fixed container height using a bulk equation of state obtained from simulations. Our results show that gravity leads to multiphase coexistence for the semi-infinite system, as we observe I, I+N, I+N+Sm , or I+N+Sm+K coexistence, while the finite system shows I, N, Sm, K, I+N, N+Sm, Sm+K, I+N+Sm, N+Sm+K , and I+N+Sm+K phase coexistence. In addition, we compare our theoretical predictions for the phase behavior and the density profiles with Monte Carlo simulations for the semi-infinite system and we find good agreement with our theoretical predictions.

Accuracy of measuring the nematic order from intensity scatter: a simulation study.

The determination of the nematic order parameter S and the orientational distribution function (ODF) from scattering data involve severe approximations. The validity of these are studied here using Monte-Carlo simulations of hard spherocylinders with an aspect ratio of 15 for varying densities in the isotropic and nematic phase. The "exact" ODF of the rods, the "exact" value of S, and the intensity scatter I(q) are determined directly in simulation. In addition, we determine the ODF and S from the simulated intensity scatter which includes spatial and orientational correlations of the particles. We investigate whether correlations present in the interparticle scatter influences the determination of the single particle orientational distribution function by comparing the results obtained from scattering with the "exact" results measured directly in our simulations. We find that the nematic order parameter determined from the intensity scatter underestimates the actual value by 2-9%. We also find that the values of S and the ODF are insensitive to the absolute value of the scattering vector for 1.2pi

Phase behavior of a suspension of colloidal hard rods and nonadsorbing polymer.

We study the phase behavior of a mixture of colloidal hard rods with a length-to-diameter ratio of L/sigma(c)=5 and nonadsorbing ideal polymer. We map our binary mixture onto an effective one-component system by integrating out the degrees of freedom of the polymer coils. We derive a formal expression for the exact effective Hamiltonian of the colloidal rods, i.e., it includes all effective many-body interactions and it is related to the exact free volume available for the polymer. We determine numerically on a grid the free volume available for the ideal polymer coils "on the fly" for each colloidal rod configuration during our Monte Carlo simulations. This allows us to go beyond first-order perturbation theory, which employs the pure hard-rod system as reference state. We perform free energy calculations for the isotropic, nematic, smectic, and crystal phase using thermodynamic integration and common tangent constructions are used at fixed polymer fugacities to map out the phase diagram. The phase behavior is determined for size ratios q=sigma(p)/sigma(c)=0.15, 0.5, and 1, where sigma(p) is the diameter of the polymer coils. The phase diagrams based on the full effective Hamiltonian are compared with those obtained from first-order perturbation theory, from simulations using the effective pair potential approximation to the effective Hamiltonian, and with those based on an empiric effective depletion potential for the rods. We find that the many-body character of the effective interactions stabilizes the nematic and smectic phases for large q, while the effective pair potential description overestimates the attractive interactions and favors, hence, a broad isotropic-crystal coexistence.