Cholesterol-induced alteration in liver mineral concentrations in corn oil and olive oil fed rats.

This study was undertaken to compare the effects of 1% cholesterol (Ch) on some liver mineral concentrations in rats fed with corn oil (C) or olive oil (O). Male Sprague-Dawley rats (n = 4 per group) were fed AIN76A semi-purified diets containing either 5% corn oil or 5% olive oil replacing corn oil with or without 1% cholesterol for 21 days. The analysis of minerals: Phosphorous (P), Potassium (K), Magnesium (Mg), and Sulfur (S), of liver were conducted by inductively coupled plasma (ICP) spectroscopic method. In the C fed rats addition of 1% cholesterol produced significant increase in P concentrations but not K, Mg, and S concentrations. In contrast, in O fed rats, 1% Ch significantly decreased Mg and S concentrations. There was no significant change in K and P concentrations. In conclusion, this study describes the interactions between dietary oils and cholesterol on certain mineral concentrations in liver of rats. The results obtained may have clinical significance and nutritional significance in cardiovascular health.

Antiviral efficacy of VP14637 against respiratory syncytial virus in vitro and in cotton rats following delivery by small droplet aerosol.

VP14637, the lead compound in a series of substituted bis-tetrazole-benzhydrylphenols developed by ViroPharma Incorporated, was evaluated for antiviral efficacy against respiratory syncytial virus (RSV) in vitro in cell culture and in vivo in cotton rats. A selective index of >3000 (> or =2000 times greater than that observed for ribavirin) was determined in the in vitro studies for this compound against both RSV A and B subtypes. In cotton rats, animals given as little as 126 microg drug/kg by small droplet aerosol in divided doses starting 1 day after experimental virus infection with either a RSV A or B subtype consistently had significantly lower mean pulmonary RSV titers and reduced histopathological findings than mock-treated animals or cotton rats given placebo (vehicle-treated animals). No cotton rat treated with aerosols of VP14637 during these studies manifested any evident untoward responses. Thus, VP14637 exhibited good selective antiviral efficacy both in vitro and in vivo.

Development of a cotton rat-human metapneumovirus (hMPV) model for identifying and evaluating potential hMPV antivirals and vaccines.

Hispid cotton rats were inoculated with two different human metapneumovirus (hMPV) subtype A strains and one subtype B hMPV. Although no overt disease was seen in any virus-inoculated animal, following an eclipse phase, significant pulmonary virus titers were observed in every hMPV-inoculated animal through day 7 post virus inoculation (p.i.) and in most through day 10. Peak virus titers occurred four days p.i., while virus-induced histopathology was most evident in lung sections obtained from animals 7 to 10 days p.i. The latter consisted primarily of desquamating and hypertrophic columnar epithelial cells lining the bronchi and bronchioles and the presence of large numbers of leukocytes in and around the bronchi and bronchioles. In fluorescent antibody studies, virus antigen-specific fluorescence was most evident in the desquamating tall columnar epithelial cells lining bronchi and bronchioles, in pneumocytes lining alveoli and in single or small groups of free cells, most probably leukocytes, present in the lumen of alveoli, bronchi and bronchioles. Virus was generally not detected in inoculated animals >10 days p.i. Although the pattern of virus replication in cotton rats was similar for all the three virus stains, the B subtype consistently grew to lower levels than the two A strains. Regardless, these findings indicate that hMPV replicates in cotton rats and that these animals may be used as a small animal model of hMPV infection and to facilitate the identification and development of vaccines and antivirals for preventing and/or ameliorating infections caused by this virus.

Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro.

Human metapneumovirus (hMPV) is a newly recognized pathogen that like its better-known relative, human respiratory syncytial virus (hRSV), appears to be ubiquitous and an important cause of respiratory disease in diverse subpopulations. No antivirals or vaccines are currently approved for the treatment or prevention of hMPV infections. However, ribavirin is licensed to treat serious hRSV-induced infections in children and immune globulin designed for intravenous administration (i.v.IG) and palivizumab (Synagis), a humanized monoclonal antibody preparation, have been utilized as alternatives to vaccines for preventing or reducing the severity of infections caused by this virus. Because both ribavirin and i.v.IG have broad viral specificities, studies were performed to compare the ability of these two agents to inhibit the replication of hRSV and hMPV in tissue culture-based assays. Two experimental chemotherapeutic agents (i.e. VP14637 and JNJ2408068) and different antibody preparations were included in this testing for comparison. Ribavirin and the i.v.IG utilized were found to have equivalent antiviral activity against hMPV and hRSV. In contrast, except for antisera specifically raised against hMPV, all of the other materials tested had marked activity only against hRSV.

Short duration aerosols of JNJ 2408068 (R170591) administered prophylactically or therapeutically protect cotton rats from experimental respiratory syncytial virus infection.

Cotton rats exposed to continuous small droplet aerosols of 2[[2-[[1-(2-aminoethyl)-4-piperidinyl]amino]-4-methyl-1H-benzimidazol-1-yl]methyl]-6-methyl-3-pyridinol (JNJ 2408068) or its hydrochloric salt for only 15 min, one day prior to virus inoculation or one day after, were significantly protected from pulmonary respiratory syncytial virus (RSV) infection compared to control animals similarly infected but exposed to aerosols of placebo at these times. No evidence of toxicity was seen in any of these animals or in cotton rats administered 10 times the minimum cotton rat efficacious dose (i.e. 10x0.39 mg of active compound per kilogram of body weight) for four continuous days. The marked selective antiviral activity observed in the cotton rats mirrored that seen for these compounds in cytotoxicity and antiviral assays performed against RSV in vitro. Plasma kinetics and tissue distribution of JNJ 2408068 in cotton rats following inhalation were determined in separate experiments performed using conditions similar to those utilized in the in vivo efficacy studies. The data from these experiments indicated that significant levels of the test compound were delivered to the lungs of exposed animals, but that extrapulmonary distribution was limited.

Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by NMSO3 in tissue culture assays.

Human metapneumovirus (hMPV) is a recently elucidated respiratory virus pathogen for which there are no agents currently licensed to prevent or treat infections caused by it. However, NMSO3 has been reported to inhibit replication of human respiratory syncytial virus (hRSV), a virus that is closely related to hMPV, both in vitro in tissue culture cells and in vivo in cotton rats. For this reason, experiments were performed to compare the antiviral activity of NMSO3 against both hRSV and hMPV in tissue culture-based assays. Heparin and ribavirin, two other compounds known to inhibit hRSV, and two other paramyxoviruses, human parainfluenza virus type 3 (PIV3) and measles virus (MV), were included in these tests for comparison. All three compounds significantly inhibited the replication of subtype A and B strains of hRSV and serotypes 1 and 2 hMPV. However, unlike ribavirin, NMSO3 and heparin inhibited only hMPV and hRSV and not PIV3 or MV. Also unlike ribavirin, the activity of the two sulfated molecules was most effective if these materials were present during virus attachment and penetration of host cells. Interestingly, NMSO3, but not heparin, was able to limit secondary infection and spread of both viruses.

Garlic induced alteration in liver mineral concentrations in corn oil and olive oil fed rats.

This study was undertaken to compare the effects of 2% garlic (G) on liver mineral concentrations in rats fed with corn oil (C) or olive oil (O). Male Sprague-Dawley rats (n = 4 per group) were fed AIN76A semi-purified diets containing either 5% corn oil or 5% olive oil replacing corn oil with or without 2% garlic for 21 days. The analysis of minerals calcium (Ca), phosphorous (P), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), Sulfur (S), copper (Cu), iron (Fe) and zinc (Zn) of liver were conducted by inductively coupled plasma (ICP) spectroscopic method. In the C fed rats addition of 2% garlic produced significant increase in liver Ca, P, Mg, S, Mn, Cu, and Zn. There was no significant change in Fe, Na and K. In contrast, in olive oil fed rats, 2% garlic diets did not affect Ca, Mg, S, Mn, Na and K concentrations. However, there was significant decrease in liver Cu and Zn concentrations. Also, in O fed control rats liver, Ca, P, Mg, S, Fe, Mn, Cu, and Zn concentrations were significantly increased as compared to C fed control rats. In conclusion, this study describes the interactions between dietary oils and garlic on liver mineral concentrations in rats.