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The influence of different light irradiances on pineal N-acetyltransferase activity and melatonin levels in the cotton rat, Sigmodon hispidus.

Wild-captured cotton rats (Sigmodon hispidus) trapped and tested in September and October exhibited a rapid reduction in pineal N-acetyltransferase (NAT) activity and melatonin levels after exposure to a light irradiance of 300 microW/cm2 during the dark period. The half-time for the depression of both NAT and melatonin was on the order of 2 min. The exposure of cotton rats during darkness to much lower irradiances of light, i.e., 5.0, 0.04, 0.03 or 0.01 W/cm2, for 32 min also greatly diminished pineal NAT activity and radioimmunoassayable melatonin levels; however, a light irradiance of 0.005 microW/cm2 failed to significantly depress either the acetylating enzyme or the melatonin content of the pineal gland. The results show that the pineal gland of the wild-captured cotton rat, as judged by NAT activity and melatonin levels, is inhibited even by very low irradiances of light.

Acetyltransferases↗

Gingival response to silk, cotton, and nylon suture materials.

Silk, cotton, and nylon suture materials were implanted in the tunica propria of the gingiva in seven adult rhesus monkeys. The histologie study of twenty-four biopsy specimens indicated that there was neither an increase in the vascular permeability nor a leukocytic margination and migration into the tissues adjacent to the suture materials. However, there was a variable histiocytic reaction, with multinucleated cell formation. This reaction was quite intense with cotton, less intense with silk, and practically absent with nylon. The greater cellular response to cotton was probably due to its more active capacity for modifying the internal biologic medium of the gingvia.

Animals↗

An aerosol generator for the resuspension of cotton dust.

An aerosol generator, the Pitt 3 model, was designed, fabricated, and characterized for the resuspension of inhalable particles from bulk cotton dust. The generator was constructed around a loudspeaker whose energy is transferred into an air column through latex rubber dams. This action tumbles the bulk dust, and small particles are loosened which can then be carried out of the column with the air passing through it. Thirty to forty grams of bulk cotton dust produced a stable aerosol concentration for at least 90 min. The maximum output of about 100 mg/m3 can be reduced to lower concentrations by adding dilution air. In one application, the generator produced a stable aerosol cloud in the range of 2 to 30 mg/m3 with a mass median aerodynamic diameter (MMAD) of about 3 microns and a geometric standard deviation (sigma g) of about 1.5. In another application the concentration in an animal exposure chamber was kept at 20.8 mg/m3 with an MMAD = 2.5 microns and a sigma g = 1.8 for over 6 months. The Pitt 3 generator proved to be trouble-free and produced large amounts of inhalable particles from bulk cotton dust. The generator was also used to generate dust clouds from silica powder, fly ash, and cellulose dust. The only requirement for successful resuspension of any dust with this generator is the presence of small particles in the bulk feed dust.

Aerosols↗

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.

Animals↗

SP-303 small-particle aerosol treatment of influenza A virus infection in mice and respiratory syncytial virus infection in cotton rats.

A natural plant product, SP-303, was administered by small-particle aerosol to influenza A/HK virus-infected mice and RSV-infected cotton rats. Aqueous SP-303 at 2 mg/ml in the Collison nebulizer reservoir generated an aerosol with an output of 26 micrograms/l and a particle size distribution of 1.4 microns +/- 4.6 (MMAD +/- GSD). SP-303 at a dosage of 0.5-9.4 mg/kg per day administered for 3-4 days significantly increased both the rate and duration of survival of mice lethally infected with influenza A/HK virus. SP-303 was toxic to mice at 16 mg/kg per day as indicated by weight loss and a decrease in the duration of survival compared to control animals. From these data, a maximum therapeutic index (T.I.) of 12 was calculated. SP-303 given 3-4 days at dosages of 1.3-9.8 mg/kg per day was effective in reducing the pulmonary titer of RSV in infected cotton rats. However, at the 18.7 mg/kg per day dose a significant weight loss compared to control animals was observed; a T.I. of < or = 14 was estimated. These experiments demonstrate that aerosol administration of SP-303 was effective in the treatment of influenza A-infected mice and of RSV-infected cotton rats.

Administration, Inhalation↗

Evaluation of the antiviral activity of N-(phosphonoacetyl)-L-aspartate against paramyxoviruses in tissue culture and against respiratory syncytial virus in cotton rats.

N-(phosphonoacetyl)-L-aspartate (PALA), a potent inhibitor of L-aspartic acid transcarbamoylase, was evaluated for cytotoxicity and antiviral activity against three different paramyxoviruses in tissue culture, and for antiviral efficacy and toxicity in vivo using a cotton rat-respiratory syncytial virus (RSV) model. Significant in vitro cytotoxicity was observed in proliferating cultures of HEp-2 (IC50 = 250 micrograms/ml) and Vero cells (IC50 = 32 micrograms/ml), but was less evident in cultures containing confluent monolayers (i.e., stationary cells) of these cells, or in cultures of Madin Darby canine kidney (MDCK) cells (these IC50 values were all > or = 750 micrograms/ml, with 1000 micrograms/ml being the maximum concentration tested). Mean selective indices (ratio of the median cytotoxic dose: median efficacious dose) of 1, 72 and 146 were obtained against parainfluenza virus type 3, RSV and measles virus, respectively, when PALA was tested against these viruses using confluent HEp-2 and Vero cell monolayers. In cotton rats, significant reductions in pulmonary titers (0.8-1.4 log10/g lung) compared to pulmonary viral titers in placebo-treated control animals, were consistently seen in cotton rats given > or = 10 mg of PALA/kg/day (b.i.d.) intraperitoneally on days 1-3 postinfection with either subtype A or B RSV. No toxic effects were noted even in animals given 100 mg of PALA/kg/day for 7 consecutive days.

Animals↗

Recombinant superoxide dismutase (SOD) administered by aerosol inhibits respiratory syncytial virus infection in cotton rats.

Recombinant (r) human (hu) manganese (Mn) and copper-zinc (CuZn) superoxide dismutase (SOD) were evaluated for their cytotoxicity and antiviral activity against respiratory syncytial virus (RSV) in tissue culture and in cotton rats. No apparent cytotoxicity or inhibition of RSV was observed in the tissue culture studies (both compounds had IC50 and EC50 values > or = 1000 micrograms/ml and a selective index = 1). However, significant reductions in mean pulmonary RSV titers (ranging between 0.5 and 1.9 log10/g of lung compared with the mean pulmonary viral titers detected in similarly inoculated, placebo-treated control animals) were seen in most of the experiments, in which experimentally infected cotton rats were exposed to continuous small-particle aerosols (reservoir concentrations > or = 20 mg/ml) containing either rhuMnSOD or rhuCuZnSOD. This protective effect was dose dependent and not observed when either rSOD compound was administered parenterally (intraperitoneally) or intranasally. No toxic effects were noted in any of the cotton rats exposed to aerosols of either rhuMn or CuZnSOD; nor was any evidence of drug-induced histopathology observed in sections of lung prepared from these animals.

Aerosols↗

Characterization of a cDNA clone encoding the complete amino acid sequence of cotton isocitrate lyase.

A cDNA clone encoding the glyoxysomal enzyme isocitrate lyase (ICL) (EC 4.1.3.1) was isolated from a library prepared from cotton (Gossypium hirsutum L.) cotyledon poly(A)+ RNA. The clone is 1893 basepairs (bp) in length and contains a 1728 bp open reading frame encoding a polypeptide of 576 residues (Mr = 64,741). The deduced amino acid sequence of cotton ICL is 85.2%, 90.3% and 41.1% identical to ICL from rapeseed, castor bean and E. coli, respectively. Cotton ICL has a C-terminal tripeptide of A-R-M which is a putative trafficking signal for peroxisome (glyoxysome) proteins.

Amino Acid Sequence↗

Studies on the bacterial permeability of non-woven fabrics and cotton fabrics.

The permeability of cotton and non-woven fabrics to bacteria, air and water was studied. Non-woven fabrics, even when wet, showed low resistance to air, and high resistance to permeation of water and bacteria. Water-repellent cotton fabrics were resistant to permeation of water, air and bacteria, but these properties decreased on washing. Non-water-repellent cotton fabrics were poor bacterial barriers even when new.

Bacteria↗

Comparison of lung histopathology and bronchoalveolar lavage cytology in mice and cotton rats infected with respiratory syncytial virus.

Lung histology as well as cell number and size distribution in bronchoalveolar lavage (BAL) were compared in Balb/c mice and in cotton rats, of various immune status regarding the respiratory syncytial virus (RSV), when subjected to challenge with RSV. In mock-immunized animals, RSV infection typically caused microscopic inflammatory lesions of the lungs and the presence of inflammatory cells in the BAL. Immunization with a formalin inactivated vaccine prior to challenge increased the severity of the lung lesions and the number of cells recovered in the BAL. We observed that cotton rats are more convenient to study primary RSV infections, inasmuch naive subjects show more pronounced lesions than do naive mice. Conversely, the changes in lung histopathology and in BAL cytology associated with exposure to formalin inactivated vaccine prior to challenge were more apparent in mice, making them a more suitable model for potentiation studies. Moreover, mice showed less individual fluctuations than cotton rats. The reading of the lung sections could be made less tedious by use of computer image analysis, which results paralleled those of conventional examination. In mice, cytological analysis of the BAL could be used in place of lung histology for some potentiation studies since the number of cells recovered in BAL reflected the intensity of the lung lesions and size distribution profiles typical of potentiation were recognized.

Animals↗

Enhanced pulmonary histopathology is observed in cotton rats immunized with formalin-inactivated respiratory syncytial virus (RSV) or purified F glycoprotein and challenged with RSV 3-6 months after immunization.

Formalin-inactivated (FI) RSV, purified F glycoprotein in alum, and RSV infection (intranasal) were compared for their immunogenicity, efficacy, and ability to enhance pulmonary histopathology during RSV infection 3 and 6 months following immunization by the intramuscular route. Purified influenza virus in alum was used as a control immunogen. At 1 month following immunization with one dose of purified F glycoprotein (5 micrograms), cotton rats developed levels of F antibodies (ELISA) higher than the other groups, but these antibodies had the lowest level of neutralizing activity, Little increase in antibody titre was seen following a second dose of FI-RSV or purified F vaccine given at 1 month. Animals that received 5 micrograms F, 0.5 microgram F, or were almost completely resistant to pulmonary RSV infection following challenge at 3 months, but were susceptible by 6 months. Animals immunized with 5 micrograms of purified F glycoprotein developed alveolar and bronchiolar histopathology following RSV challenge at 3 or 6 months which was comparable to that of animals immunized with FI-RSV. These levels significantly exceeded those in animals previously immunized with influenza A virus vaccine which exhibited little histopathology. Animals previously infected with RSV also developed bronchiolar, but not alveolar, histopathology suggesting that the bronchiolar histopathology seen in RSV challenged cotton rats is a normal component of the immune resolution of RSV infection. These results suggest that the immune response of cotton rats to immunoaffinity purified F glycoprotein can result in enhanced bronchiolar and alveolar histopathology following RSV challenge. Thus, caution should be exercised in studies in humans using a purified F glycoprotein subunit vaccine.

Animals↗

Parainfluenza virus type 3 (PIV3)-specific and non-virus-specific delayed type hypersensitivity responses in cotton rats given different PIV3 antigen preparations.

Virus-specific, T-lymphocyte-mediated delayed type hypersensitivity (DTH) responses were studied in cotton rats using replicating (wild-type parainfluenza virus type 3 (PIV3) and recombinant vaccinia virus expressing PIV3 haemagglutinin-neuraminidase (HN) or fusion (F) glycoproteins), and non-replicating (detergent-solubilized, affinity chromatography purified HN and F glycoproteins or inactivated whole PIV3) virus preparations. Significant virus-specific DTH responses were observed in all test groups 1-2 weeks after a single antigen inoculation or 5 days after two inoculations given 3 weeks apart. Peak swelling of ear pinnas in these animals generally occurred 24 h after elicitation and was marked by a cellular infiltration consisting of mono- and polymorphonuclear leucocytes. A considerable non-virus-specific inflammatory response, presumably due to tissue culture or media components in the priming antigen preparations, was observed 3 weeks after priming. No significant differences in DTH responses were observed in cotton rats primed with any of the PIV3 preparations. The possible roles and significance of both the virus-specific and non-virus-specific DTH responses in paramyxovirus-induced disease in humans and cotton rats are discussed.

Animals↗

Morphological, biochemical, and histopathological indices and contaminant burdens of cotton rats (Sigmodon hispidus) at three hazardous waste sites near Houston, Texas, USA.

Male cotton rats (Sigmodon hispidus) were studied at three industrial waste sites near Houston, Texas, to determine whether various morphological, biochemical, and histopathological indices provided evidence of contaminant exposure and toxic insult. Only modest changes were detected in cotton rats residing at waste sites compared with reference sites. No single parameter was consistently altered, except hepatic cytochrome P-450 concentration which was lower ( [Formula: see text] ) at two waste sites, and tended to be lower ( [Formula: see text] ) at a third waste site. Elevated petroleum hydrocarbon concentrations were detected in rats at one waste site, but contaminant burdens of rats from the other sites were unremarkable. Unlike rats captured in summer, those trapped in winter exhibited hepatocellular hypertrophy and up to a 65% increase in liver: body weight ratio, cytochrome P-450 concentration, and activities of aniline hydroxylase, aryl hydrocarbon hydroxylase, and glutathione S-transferase. Although genotoxicity has been previously documented in cotton rats residing at two of the waste sites, biomarkers in the present study provided little evidence of exposure and damage.

Journal Article↗

Selected immune responses of adult cotton rats (Sigmodon hispidus) to dietary restriction.

1. We examined the influence of moderate to severe dietary restriction on immune system function in adult cotton rats. Animals (N = 80) were fed ad lib. (controls) or restricted [moderate = 80% ad lib. for 1 or 2 weeks; severe = 80% ad lib. for 1 or 2 weeks followed by 40% ad lib. for one (week 3) or two (week 4) additional weeks] amounts of food for 1-4 weeks. 2. Average body weight loss for severely restricted animals in week 4 was 17%; dietary treatments had no measurable effect on hematological parameters (hematocrit, white blood cell count), lymphoid organ weights (thymus gland, spleen, popliteal lymph nodes), and mononuclear cell yields from lymphoid organs. 3. Cell-mediated immune function was assessed in vitro by a lymphoproliferative response assay and in vivo by a delayed-type hypersensitivity response assay. 4. Proliferative responses of spleen cell cultures stimulated with concanavalin A (Con A, Canavalia ensiformis) and pokeweed (PWM, Phytolacca americana) were normal or significantly greater among moderately restricted than control cotton rats during week 1 and week 2. 5. Lymphoproliferative responses of severely restricted animals were normal or reduced during week 3 and week 4. 6. Delayed-type hypersensitivity responses to the contact antigen oxazolone were significantly depressed among severely restricted animals in week 4 compared to controls. 7. In comparison with laboratory rodent strains, our initial results indicate that immune system function in adult cotton rats is not as sensitive to short term (1-4 weeks) periods of dietary restriction. 8. Immune system function was related to changes in body weight as a result of feed restriction.

Animals↗

The properties of forms of Ruminococcus flavefaciens which differ in their ability to degrade cotton cellulose.

Two mutant strains of Ruminococcus flavefaciens strain 007 that differ in their ability to hydrolyse cotton fibres have been shown also to differ in their cell-surface topology, in that the cotton degrading form possessed larger and more protuberant cell surface structures. The strains had similar CMCase, cellobiosidase and beta-glucosidase activities. The results indicate the importance of cell-surface properties in cotton degradation by R. flavefaciens.

Animals↗

Hypoglycemic effect of cotton seed aqueous extract in alloxan-induced diabetes mellitus in rats.

The aqueous extract of cotton seed is able to reduce blood sugar in alloxan-induced diabetes mellitus in rats. A dose of 1000 mg/kg was found to be an effective dose. Cotton seed extract was able to enhance the liver glycogen, like glibenclamid, and was also able to reduce blood cholesterol which was found raised in the diabetic state. Further it was able to normalize the altered level in the liver lipid peroxide content. The role of cotton seed aqueous extract is suggested in the lipid metabolism which is altered during diabetes mellitus.

Animals↗

Diseases associated with exposure to plant dusts: focus on cotton dust.

Research during recent years has made clear that pulmonary disease and certain general symptoms caused by organic dusts are far more common than previously suspected. To the traditional environments of cotton dust and moldy hay has been added a series of environments, such as swine confinement buildings, sewage treatment stations and industrial fermentation plants. It has been suggested that, rather than linking clinical disease with a specific environment (farmer's lung, byssinosis, etc), symptoms should be related to the relevant pulmonary cellular reactions, particularly inflammation. In so doing, a more homogenous picture of the various clinical entities has emerged. It is now understood that symptoms once considered to be unique to one particular environment, such as chest tightness in cotton mills, are also present in other organic dust environments. New models for organic dust-induced disease have been established using the criteria developed for disease among workers in cotton mills and swine confinements buildings. This has led to uniform methods for diagnosis, description of symptomatology and understanding of pathogenesis. Employing this experience on an international basis, provides an important background for dealing with new problems in this important area of occupational health and is a prerequisite for the establishment of treatment and prevention programs.

Byssinosis↗

The cotton rat model for adenovirus ocular infection: antiviral activity of cidofovir.

To determine the antiviral effects of compounds against ocular adenovirus (AdV) infection, we established an animal model of AdV infection in cotton rat eyes. Cotton rat eyes were inoculated intrastromally and topically with four AdV serotypes 4, 5, 8, and 37, and treated topically with 1% HPMPC (cidofovir) eye drops twice a day. The infected corneas were extracted and homogenized, and virus titers in the cornea specimens were determined by a plaque assay. The virus titer in AdV type 5-inoculated eyes peaked on days 0 through 3 after inoculation and virus shedding was detected for 18.0+/-2.8 days. AdV 5 antigen in the infected corneas was demonstrated in the corneal epithelial cells by immunofluorescence stain. However, for AdV serotypes 4, 8, and 37, no evidence of continued virus replication in cotton rat eyes was noted. Specimens from cidofovir-treated eyes infected with AdV 5 demonstrated a statistically significant reduction in the mean virus titer (days 3-15) (P=0.028) and virus shedding duration (P=0.0014), as compared with those of the control group.

Adenoviridae Infections↗