The impact of Aloe vera and licorice extracts on selected mechanisms of humoral and cell-mediated immunity in pigeons experimentally infected with PPMV-1.

BACKGROUND: The aim of the study was to evaluate the impact of herbal extracts on selected immunity mechanisms in clinically healthy pigeons and pigeons inoculated with the pigeon paramyxovirus type 1 (PPMV-1). For the first 7 days post-inoculation (dpi), an aqueous solution of Aloe vera or licorice extract was administered daily at 300 or 500 mg/kg body weight (BW). The birds were euthanized at 4, 7 and 14 dpi, and spleen samples were collected during necropsy. Mononuclear cells were isolated from spleen samples and divided into two parts: one part was used to determine the percentage of IgM+ B cells in a flow cytometric analysis, and the other was used to evaluate the expression of genes encoding IFN-γ and surface receptors on CD3+, CD4+ and CD8+ T cells. RESULTS: The expression of the IFN-γ gene increased in all birds inoculated with PPMV-1 and receiving both herbal extracts. The expression of the CD3 gene was lowest at 14 dpi in healthy birds and at 7 dpi in inoculated pigeons. The expression of the CD4 gene was higher in uninoculated pigeons receiving both herbal extracts than in the control group throughout nearly the entire experiment with a peak at 7 dpi. A reverse trend was observed in pigeons inoculated with PPMV-1 and receiving both herbal extracts. In uninoculated birds, increased expression of the CD8 gene was noted in the pigeons receiving a lower dose of the Aloe vera extract and both doses of licorice extracts. No significant differences in the expression of this gene were found between inoculated pigeons receiving both herbal extracts. The percentage of IgM+ B cells did not differ between any of the evaluated groups. CONCLUSIONS: This results indicate that Aloe vera and licorice extracts have immunomodulatory properties and can be used successfully to prevent viral diseases, enhance immunity and as supplementary treatment for viral diseases in pigeons.

Role of dietary antioxidants in human metapneumovirus infection.

Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important pathogenic mechanism(s) of hMPV infection. Here, we explored the potential protective role of dietary antioxidants in hMPV infection. Treatment of airway epithelial cells with resveratrol and quercetin during hMPV infection significantly reduced cellular oxidative damage, inflammatory mediator secretion and viral replication, without affecting viral gene transcription and protein synthesis, indicating that inhibition of viral replication occurred at the level of viral assembly and/or release. Modulation of proinflammatory mediator expression occurred through the inhibition of transcription factor nuclear factor (NF)-κB and interferon regulatory factor (IRF)-3 binding to their cognate site of endogenous gene promoters. Our results indicate the use of dietary antioxidants as an effective treatment approach for modulating hMPV induced lung oxidative damage and inflammation.

The effect of reduced treatment time and dosage of enrofloxacin on the course of respiratory disease caused by avian metapneumovirus and Ornithobacterium rhinotracheale.

A dose titration and reduced duration medication study were performed to evaluate the current enrofloxacin treatment schedule in growing turkeys experimentally infected with avian metapneumovirus and Ornithobacterium rhinotracheale. Experimental groups of 17 four-week-old turkeys were first infected with avian metapneumovirus and 3 d later with O. rhinotracheale. Enrofloxacin treatment in the drinking water was started 24 h after O. rhinotracheale inoculation. In the dose titration study, enrofloxacin doses of 5, 10, and 20 mg/kg of BW were administered for 5 successive days. In the reduced duration medication study, the following enrofloxacin regimens were compared: 25 mg/kg of BW per day on d 0 and 2; 15 mg/kg of BW per day on d 0, 2, and 4; and 10 mg/kg of BW for 5 successive days. In both studies, all enrofloxacin treatments were equally efficacious (i.e., equally capable of shortening the course of clinical disease), eliminating O. rhinotracheale from the respiratory tract and reducing gross lesions. Ornithobacterium rhinotracheale bacteria were not recovered from any of the birds on enrofloxacin-supplemented media, indicating that none of the used treatment regimens promoted the selection of bacterial clones with reduced susceptibility or resistance to this antimicrobial agent. In conclusion, none of the alternative enrofloxacin treatment regimens yielded better results than the current prescribed treatment (i.e., 10 mg/kg of BW for 5 successive days) of O. rhinotracheale infections in turkeys. However, the reduced duration of application would offer a less time-consuming and equally effective alternative.

Efficacy of enrofloxacin, florfenicol and amoxicillin against Ornithobacterium rhinotracheale and Escherichia coli O2:K1 dual infection in turkeys following APV priming.

Experimental groups of 15 susceptible 3-week-old turkeys were inoculated oculonasally with avian metapneumovirus (APV) subtype A and susceptible Escherichia coli O2:K1 and Ornithobacterium rhinotracheale (ORT) bacteria, with a 3 days interval between viral and bacterial inoculation and approximately 8h between the two bacterial inoculations. The aims of the present study were to assess the efficacy of drinking-water administration of enrofloxacin for 3 and 5 days, amoxicillin for 5 days and florfenicol for 5 days for the treatment of the resulting respiratory disease, based on clinical and bacteriological examinations. Antimicrobial treatment started 1 day after dual bacterial inoculation. After infection, the birds were examined and scored for clinical signs daily, weighed at different times, and their tracheae swabbed daily. Five birds were euthanised and examined for macroscopic lesions at necropsy at 5 days post-bacterial inoculation (dpbi) and the remainder at 15dpbi. Samples of the turbinates, trachea, lungs, sinuses, air sacs, heart, pericardium and liver were collected for bacteriological examination. Recovery from respiratory disease caused by an APV/E. coli/ORT triple infection in 3-week-old turkey poults was overall most successful after enrofloxacin treatment, irrespective of treatment duration, followed by florfenicol treatment. Compared with the untreated group, clinical signs as well as ORT and E. coli multiplication in the respiratory tract were significantly reduced by both enrofloxacin treatments and the florfenicol treatment, with the enrofloxacin treatments showing significantly better reductions than the florfenicol treatment. Five-day treatment with amoxicillin, compared with the untreated group, did not cause a significant reduction in any of the aforementioned parameters.

[The use of gamma-interferon for the prevention and treatment of infectious diseases in piglets and calves]. / Vykorystannia hamma-interferonu dlia profilaktyky ta likuvannia infektsiinykh khvorob porosiat i teliat.

Administration of the homologous natural gamma-interferon for prophylaxis of infectious diseases showed that 2-3 injections of gamma-interferon prevented infectious morbidity of more than 90% of sucking pigs and new-born calves, sharply increased their preservation to 90% and above, increased their productivity by 1/3. In conditions of industrial growing of young animals therapy by this preparation of pigs and calves with colibacteriosis and parainfluenza in comparison with control significantly decreased mortality of morbid young animals, accelerated their recovery and promoted the weight gain in pigs and calves.

[The therapeutic effect of aprotinin inhalations in influenza and paramyxovirus infections in mice]. / Lechebnyi éffekt ingaliatsii aprotinina pri grippoznoi i paramiksovirusnoi infektsiiakh u myshei.

Mice infected with influenza A/Aichi/2/68 (H3N2) virus or Sendai/960 paramyxovirus were treated by inhalations of aerosol aprotinin, a broad spectrum inhibitor of proteinases. A course of inhalations of finely dispersed aerosol aprotinin including 4 exposures of 35-40 min each daily for 6 days provided respiratory administration of aprotinin in a dose about 100 kallikrein-inhibiting U/mouse per day. In mice treated by aprotinin inhalations, histological examinations showed decreased pulmonary pathology, and their body weights increased as much as in uninfected animals. In the placebo group, the weight decreased until the death of the animals. The protective effect of aprotinin inhalations was 40-80% with inoculation doses 10-100 MLD50/mouse. The treated animals died 2-4 days later than those in the placebo group. The results indicate the expedience of inhalation therapy with aerosol aprotinin in influenza and paramyxovirus respiratory infections.

[The antiviral activity of deitiforin in experimental para-influenza infection]. / Protivovirusnaia aktivnost' deitiforina pri éksperimental'noi paragrippoznoi infektsii.

Deitiforin in HEp-2 cell culture was shown to inhibit replication of the reference PIV-3 strain when administered 1 hour before virus inoculation. The most marked effect of the drug was observed in the first 4 days of observation. In experimental newborn mice infected with parainfluenza virus 3 deitiforin protected the animals from developing the infection. In humans given deitiforin reaction to vaccination was found to develop 5-6 times more rarely than in the control group, PIV-3 could be isolated twice as rarely, and a diagnostically significant rise of specific antibody levels was observed less frequently.

Evaluation of the toxicity and antiviral activity of carbocyclic 3-deazaadenosine against respiratory syncytial and parainfluenza type 3 viruses in tissue culture and in cotton rats.

The toxicity and antiviral efficacy of carbocyclic 3-deazaadenosine (Cc3Ado) against respiratory syncytial (RSV) and parainfluenza type 3 (PIV3) virus infections were tested in tissue culture and in cotton rats. The mean median efficacious dose (ED50) of Cc3Ado in HEp2 cells against RSV and PIV3 was 9 and 14 micrograms/ml, respectively. These values were 85- and 55-fold less than the median inhibitory (toxic) dose (ID50) of Cc3Ado in this cell line (750 micrograms/ml), and similar to values obtained for ribavirin. Cc3Ado exhibited no significant antiviral activity against influenza A, influenza B, adeno type 5 or adeno type 7 viruses (all ED50 were greater than 1000 micrograms/ml). In cotton rats, animals given greater than or equal to 1 mg/kg/day Cc3Ado intraperitoneally on days 1, 2 and 3 after experimental challenge with virus, consistently had significant reductions in pulmonary RSV and PIV3 titers compared to pulmonary virus titers in comparably treated control animals. The minimum efficacious dose of ribavirin given under the same conditions was 30 mg/kg/day. Cc3Ado was also efficacious in cotton rats when given orally by gavage, or when different administration schedules were used. The median efficacious dose of Cc3Ado when given orally was 10 mg/kg/day. No significant toxic effects were noted in cotton rats, even in animals given 20 mg/kg daily for eight consecutive days.

Toxicity and antiviral activity of LY253963 against respiratory syncytial and parainfluenza type 3 viruses in tissue culture and in cotton rats.

LY253963, the sodium salt of 1,3,4-thiadiazol-2-ylcyanamide, was evaluated in tissue culture and in cotton rats for toxicity and antiviral efficacy against respiratory syncytial (RSV) and parainfluenza type 3 (PIV3) viruses. The selective index (ratio of the median toxic dose: median efficacious dose) of LY253963 in HEp2 tissue culture cells was greater than 100 against both RSV and PIV3. When given intraperitoneally to cotton rats, the minimum protective dose of LY253963 against both of these viruses was between 1 and 3 mg/kg/day. In contrast, doses of LY253963 as high as 30 mg/kg/day, administered orally after experimental inoculation of virus, did not significantly reduce pulmonary virus titers in treated animals compared to control animals given placebo. No toxic effects were noted in cotton rats, even in those given 20 mg/kg/day for eight consecutive days.

[Antiviral and interferon-inducing effect of fang-gan mixture].

The present study was carried out by using the plaque formation test, microdosage cytopathic effect (CPE) method, and mice nasal-cavity-attacking method to observe the antiviral and interferon-inducing effect of Fang-Gan mixture (FGM). The results showed that FGM has direct respiratory syncytia virus (RSV) inactivation effect, and protection effect after mice infected by RSV. FGM could also decrease mice death rate (P less than 0.01) in the experimentation of using parainfluenza virus to attack them, and work in coordination with interferon induced by Newcastle disease virus. After 8, 16, 24, 32 hours of injecting FGM into mice abdominal cavity, the authors used CPE method to determine interferon titer of L929 cells, and found that the highest interferon titer was 98.23 mu/m at the 24th hour. The interferon induced by FGM was in keeping with the nature of Type I interferon. The results suggested that FGM might have strong antiviral effect which is achieved by inducing interferon.