Ml In Mice Research Articles

Inter and Intraserotype Variations of Streptococcus Pneumoniae Pathogenicity in Mice and Rabbits

The small mammalian labratory animals, the mice and the rabbits were tempted to be pathogenicity models for S. pneumoniae serotypes 1 and 6, the infecting doses were 0.3ml for mice and 0.5 ml for rabbits. These infectious doses were rated to a count of 1X 10 to 7 CFU/ml. The infection routes were intrapreritoneal for mice and intranasal for rabbits. The gold standard criteria for pathogenicity were the death end point DEP.DEP was up to 24hr for mice and ranged from four to 14 days in rabbits. Mice was more susciptable than rabbits for S. pneumoniae serotypes infections. Autopsy cultures of blood, lungs, liver and kideys were producing same infecting serotype both from mice and rabbits. This isolation profile was indicating bacterimic state induced by infection. Different serotypes have shown different death end points duration time. There were inter and intraserotype variations in DEP. Moderate to severe respiratory disease conditions RDC was noted in mice while mild RDC in rabbits. Both of the tested models were similar lung histology to man. The histological features of this experimental infections have shown that the infected mice and rabbits were of bronchopneumonia type. It appears that both mice and rabbits were standing as valid laboratory animal models for these local clinical isolates of S. pneumoniae serotypes.

4-Methoxylonchocarpin attenuates inflammation by inhibiting lipopolysaccharide binding to Toll-like receptor of macrophages and M1 macrophage polarization

The roots of Abrus precatorius (AP, Fabaceae) have traditionally been used in Vietnam and China for the treatment of inflammatory diseases such as stomatitis, asthma, bronchitis, and hepatitis. Therefore, in this study, we isolated 4-methoxylonchocarpin (ML), an anti-inflammatory compound present in AP, and studied its anti-inflammatory effects in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. In lipopolysaccharide (LPS)-stimulated macrophages, ML was found to inhibit nuclear factor (NF)-κB activation and tumor necrosis factor (TNF) and interleukin (IL)-6 expression by inhibiting LPS binding to Toll-like receptor 4 (TLR4) in vitro. Oral administration of ML in mice with TNBS-induced colitis suppressed colon shortening and colonic myeloperoxidase activity. ML treatment significantly inhibited the activation of nuclear factor (NF)-κB and phosphorylation of transforming growth factor β-activated kinase 1 in the colon. Treatment with ML also inhibited TNBS-induced expression of IL-1β, IL-17A, and TNF. While ML reduced the TNBS-induced expression of M1 macrophage markers such as arginase-2 and TNF, it was found to increase the expression of M2 macrophage markers such as arginase-1 and IL-10. In conclusion, oral administration of ML attenuated colitis in mice by inhibiting the binding of LPS to TLR4 on immune cells and increasing the polarization of M1 macrophages to M2 macrophages.

Dimethoxyflavone isolated from the stem bark of <i>Stereospermum kunthianum</i> possesses antidiarrhoeal activity in rodents

This study was undertaken to evaluate the antidiarrhoeal activity of 3, 7, 4'-trihydroxy-3'-(8″-acetoxy-7″-methyloctyl)-5, 6-dimethoxyflavone, a flavonoid isolated from the stem bark of Stereospermum kunthianum. The antidiarrhoeal activity was evaluated using rodent models with diarrhoea. The normal intestinal transit, castor oil-induced intestinal transit and castor oil-induced diarrhoea tests in mice as well as castor oil-induced intestinal fluid accumulation in rats were employed in the study. The animals were pretreated with distilled water (10 ml/kg for mice, 5 ml/kg for rats), dimethoxyflavone (25 mg/kg or 50 mg/kg), morphine (10 mg/kg), or indomethacin (10 mg/kg) before induction of diarrhoea with castor oil (0.2ml for mice and 2ml for rats). Dimethoxyflavone dose dependently and significantly reduced (P<0.05) castor oil-induced intestinal motility. Its antimotility effect at the dose of 50 mg/kg was higher compared to that of morphine (10 mg/kg). Dimethoxyflavone (25 mg/kg and 50 mg/kg) caused a delay in the onset of diarrhoea reduction in the number and weight of wet stools and total stools in mice with castor oil-induced diarrhoea compared to the distilled water treated mice. Treatment with dimethoxyflavone (25 mg/kg or 50 mg/kg) did not produce any remarkable effect on castor oil-induced intestinal fluid accumulation in rats and normal intestinal transit in mice. The results indicate that dimethoxyflavone possesses antidiarrhoeal activity due to its intestinal antimotility effect and inhibition of other diarrhoeal pathophysiological processes. In conclusion, dimethoxyflavone reduced the frequency and severity of diarrhoea in the diarrhoeal models studied.

Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments

To use rodent models effectively in in-vivo investigations on oral drug and vaccine delivery, the conditions in the gastrointestinal tract must be understood. Some fundamental information is currently unavailable or incomplete. We have investigated the pH, water content and lymphoid tissue distribution along the gastrointestinal tract, as well as the stomach volume, as these were critical to our investigations on pH-responsive drug delivery and colonic vaccination. The observed values were compared with those in man as an indication of the validity of the rodent model. The mouse stomach pH was 3.0 (fed) and 4.0 (fasted), and the corresponding values in the rat were 3.2 (fed) and 3.9 (fasted). The mean intestinal pH was lower than that in man (<pH 5.2 in the mouse; <pH 6.6 in the rat). This brings into question the use of rodents in investigations on enteric-coated drug carriers targeted to the large intestine/distal gut. The water content in the gastrointestinal tract in the fed and fasted mouse was 0.98+/-0.4 and 0.81+/-1.3 mL, respectively, and in the fed and fasted rat was 7.8+/-1.5 and 3.2+/-1.8 mL. When normalized for body weight, there was more water per kg body weight in the gastrointestinal tracts of the mouse and rat, than in man. The stomach capacity was found to be approximately 0.4 and 3.4 mL for mice and rats, respectively. The low fluid volume and stomach capacity have implications for the testing of solid dosage forms in these animal models. Substantial amounts of lymphoid tissue analogous to small intestinal Peyer's patches were measured in the rat and mouse colon, showing the feasibility of colonic vaccination, a route which might prove to have different applications to the more commonly studied oral vaccines. The existence of lymphoid tissue in the mouse and rat caecum has also been reported.

Regulation of Complement C3 Expression by the Bile Acid Receptor FXR

The farnesoid X receptor (FXR; NR1H4) is an intracellular bile acid-sensing transcription factor that plays a critical role in the regulation of synthesis and transport of bile acids as well as lipid metabolism. Although the reciprocal relationship between bile acid and triglyceride levels is well known, the mechanism underlying this link is not clearly defined. In this study, we demonstrate that FXR regulates the expression of at least two secreted factors, complement component C3 and FGF15, the rat ortholog of FGF19, known to influence lipid metabolism. The analysis of the human complement C3 gene reveals the presence of functional FXR response elements in the proximal promoter of C3. Furthermore, rats given a single dose of an FXR agonist exhibit an increase in the plasma concentration of complement C3 protein. These studies demonstrate a mechanism by which FXR, a nuclear receptor with a limited tissue expression pattern, regulates secretion of factors that ultimately can affect lipid metabolism in an endocrine or paracrine manner.

Influence of Stress on Gastric Emptying Depends on the Nature of Meals, Stressors, and Animal Species

This work evaluated the effects of 20‐minute exposures to acoustic stress, cold (10°C), or immobilization on gastric emptying of test meals containing 51Cr sodium chromate in rats and mice. Four diets were studied: one consisting of reconstituted cow's milk (diet A), a synthetic diet containing arabic gum, glucose, and casein (diet B), diet B with arachis oil (diet C), and a nonnutritive diet containing methylcellulose and saline (diet D). Test‐meal volumes were 0.5 ml in mice and 3 ml in rats. Gastric emptying, expressed as percentage of meal emptied, was measured 30 minutes after gavage with the test meal. Acoustic stress and cold, applied after gavage, increased (p &gt; .05) the rate of gastric emptying of diet A by 46.8% and 70.7%, respectively, in mice and by 13.4% and 22.0% in rats. Immobilization did not affect (p &gt; .05) the gastric emptying of diet A in either species. Cold significantly increased (p ≤ .05) the emptying rate of diets C and D in mice but not in rats. Gastric emptying of diet D was unaffected by the three stressors in mice but was increased (45.7%) by cold in rats. This study shows that the effects of stress on gastric emptying of a nutritive meal depend mainly on the type of stressor. Of the three tested, cold was the most powerful. These results also support the conclusion that stressor, diet, and species are all important in gastric emptying.

Identification and characterization of a soluble suppressor factor(s) in the serum of AKR mice bearing lymphocytic leukemia

Leukemia in AKR mice was found to be associated with the presence of a serum factor(s) termed AKR leukemic suppressor factor (AKR-LSF). Suppression was quantitated by measuring the inhibition of PHA-stimulated [ 3H]thymidine incorporation by normal AKR spleen cells at various dilutions of leukemic mouse serum (LMS). AKR-LSF activity was expressed as units per milliliter, which is the reciprocal of the LMS dilution that inhibited [ 3H]thymidine uptake by 50% with respect to fetal calf serum control cultures. The amount of activity in the serum directly correlated to the rate of tumor cell growth. Mice receiving 10 7 BW5147 transplanted leukemia cells had 130 ± 12 units of AKR-LSF activity/ml of serum compared to 40 ± 8 units/ ml for mice with spontaneous leukemia. Normal mouse serum contained 33 ± 11 units/ml. The leukemic serum exhibited no strain specificity in either phytohemagglutinin or lipopolysaccharide assays, but was found to be twofold more inhibitory against mouse spleen cells than that against rat spleen cells. Human lymphocyte blastogenesis was not inhibited by the leukemic serum. LMS did not inhibit the growth of L929 fibroblasts or murine tumor cells in vitro. Further work is necessary to determine what role the suppressor factor may play in the regulation of antitumor cell immunity.

Metabolism of 3-deoxy-4-sulphohexosulose, a reaction product of sulphite in foods, by rat and mouse

The excretion of single intragastric doses of 14C-labelled 3-deoxy-4-sulphohexosulose (DSH) was studied in male CF1 mice and male and female Wistar albino rats. Urine and faeces were collected 6, 12, 24, (36), 48 and 72 hr after administration of 2100 mg [ 14C]DSH/kg body weight (to mice), 1700 mg/kg (to male rats) and 100 and 500 mg/kg (to male and female rats). After 72 hr, plasma and total carcass levels were determined in some experiments. In mice 29% of the administered radioactivity was excreted in the urine, 50% in the faeces and some 13% in cage washings. In rats, faecal excretion varied between 58.5 and 73%. Urinary excretion varied between 16.5 and 31% and was slightly higher in male than in female rats. No radioactivity was detected in expired air of rats, and carcass levels in rats and mice after 72 hr were less than 0.1% of the dose. TLC analysis of urine extracts revealed only unchanged [ 14C]DSH. In similar studies, male rats and mice were given 35S-labelled DSH in a dose of 6500 mg/kg or 10,700 mg/kg, respectively. Urinary activity accounted for 19.5% of the dose in rats and 27.5% in mice by 72 hr and no 35S-labelled sulphate was detectable in the urine. Organ analyses at nine intervals from 0.25 to 24 hr after intragastric administration of 1600 and 1800 mg [ 14C]DSH/kg to male rats and mice, respectively, showed that at all times most of the 14C activity was associated with the gastro-intestinal tract in both species. Maximum tissue levels were 2.16% of the dose in the rat liver 0.5 hr after dosing and 1.57% in the mouse kidney after 0.25 hr. Significant amounts of activity (>0.25% of the dose) occurred transiently also in the pancreas and lungs of both species, in the rat testes and in the mouse bladder. Maximum plasma levels were 0.09% of the dose/ml in rats 0.5 and 1 hr after dosing and 0.34%/ml in mice at 0.25 hr.

Serum diiodotyrosine.

Serum diiodotyrosine (DIT) was measured by radioimmunoassay in healthy subjects patients with thyroid disease and a variety of laboratorty animals. Ninety-two healthy adults had a mean level of 101 ng/100 ml. There was no sex difference in DIT levels but DIT fell with aging. There was no change with short term oral SSKI administration. Athyrotic subjects had measurable but reduced levels (mean = 52 ng/100 ml). Hyperthyroid subjects had levels slightly, but not significantly, higher than controls (mean = 149 ng/100 ml). Treatment of hyperthyroidism was followed by a small but significant fall in DIT levels, but there was no change in DIT levels with thyroid hormone therapy of hypothyroidism. A large species variation in serum DIT levels was found among laboratory animals with mean levels ranging from 17 ng/100 ml in mice to 428 ng/100 ml in dogs.