32 research outputs found
Effect of Obstructive Jaundice and Nitric Oxide on the Profiles of Intestinal Bacterial Flora in Wild and iNOS−/− Mice
We previously reported that the plasma level of endotoxin and colonic expression of IgA in the mouse increased with obstructive jaundice induced by bile duct ligation (BDL). To elucidate the mechanism of the BDL-induced increase, we analyzed the effect of BDL on intestinal flora in wild type and inducible nitric oxide synthase (iNOS)-deficient mice (iNOS−/−) using the terminal restriction fragment length polymorphism analysis (T-RFLP) and 16S rDNA clone libraries. The amounts of bacterial DNA detected in fecal samples from both animal groups pretreated with antibiotics were extremely low as compared with untreated groups. We found that the profiles of enteric bacteria changed markedly after BDL. The bacterial composition is significantly different between not only wild type and iNOS−/− mice but also those before and after BDL, respectively. Among enteric bacteria examined, Lactobacillus murinus was found to increase markedly after BDL in rectum of both animal groups. However, Escherichia coli markedly increased after BDL in the iNOS−/− mice. These findings suggest that profiles of enteric flora change markedly in animals during obstructive jaundice by some mechanism that is affected by bile constituents and iNOS-derived NO
Fasting Differentially Modulates the Immunological System: Its Mechanism and Sex Difference
The immunological properties and hormonal metabolism in rodents are affected by physical and psychological stress more strongly in males than in females. To elucidate the mechanism and physiological significance of the sex difference in the susceptibility of animal to stresses, changes in the immunological system in plasma and intestine and hormonal status in plasma were compared among 8-week-old male and female ICR mice before and after fasting. During the fasting of animals, the expression of immunoglobulin A in intestinal mucosa, and cortisol, interleukin-10 and interferon-γ in plasma increased. These changes occurred more apparently in males than in females. Under identical conditions, the plasma levels of testosterone decreased markedly with concomitant occurrence of apoptosis in the testis, while the plasma levels of estradiol decreased calmly, and no appreciable apoptosis occurred in the ovary. These results indicate that testosterone enhances the stress-induced modulation of the immune system by some mechanism that was antagonized by estradiol
Development of Risk Prediction Equations for Incident Chronic Kidney Disease
IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease
could improve clinical care through enhanced surveillance and better management of underlying health
conditions.
OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney
disease, defined by reduced estimated glomerular filtration rate (eGFR).
DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from
the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first
analyzed individually and summarized overall using a weighted average. Since clinical variables were often differentially available by diabetes status, models were developed separately within participants
with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external
cohorts (N=2,253,540).
EXPOSURE Demographic and clinical factors.
MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.
RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were
660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants
with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean
follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR,
history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants
with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction
between the two. The risk equations had a median C statistic for the 5‐year predicted probability of
0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th
percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%)
study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was
similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18
(89%) had a slope of observed to predicted risk between 0.80 and 1.25.
CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease
developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and
variable calibration in diverse populations
Adverse Reaction of Dextran Sodium Sulfate-Induced Colitis in a Collagen-Induced Mouse Arthritis Model
Changes in the AGE/Macrophage/TNF-α Pathway Affect Skin Dryness during KK-Ay/Tajcl Mice Aging
Skin dryness associated with type 2 diabetes worsens with age; however, the underlying mechanisms remain unclear. Herein, we investigated the effects of aging on skin dryness using a type 2 diabetes mice model. Specific pathogen-free KK-Ay/TaJcl mice of different ages (10, 27, 40, and 50 weeks) were used in this study. The results confirmed that skin dryness worsens with age. Furthermore, increased levels of advanced glycation end products (AGE), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-α, along with an increased expression of the major AGE receptor (RAGE), an increased macrophage number, and decreased collagen expression were observed in the skin of aged KK-Ay/TaJcl mice. In conclusion, dry skin conditions worsen with age in diabetic mice, and the AGE/RAGE/PGE2 and TNF-α pathways play an important role in exacerbating skin dryness during aging in these mice
Anti-Inflammatory Activity of Orally Administered <i>Monostroma nitidum</i> Rhamnan Sulfate against Lipopolysaccharide-Induced Damage to Mouse Organs and Vascular Endothelium
We previously reported that rhamnan sulfate (RS) purified from Monostroma nitidum significantly suppressed lipopolysaccharide (LPS)-induced inflammation in cultured human vascular endothelial cells. Here, we analyzed the effect of orally administered RS on LPS-induced damage to mouse organs and vascular endothelium. RS (1 mg) was orally administered daily to BALB/c mice, 50 μg of LPS was intraperitoneally administered on day 8, and Evans blue was injected into the tail vein 6 h later. After 30 min, LPS-treated mice showed pulmonary Evans blue leakage and elevated plasma levels of liver damage markers, whereas this reaction was suppressed in LPS + RS-treated mice. Immunohistochemical and Western blot analysis of mouse organs 24 h after LPS treatment showed significant neutrophil infiltration into the lung, liver, and jejunum tissues of LPS-treated mice and high expression levels of inflammation-related factors in these tissues. Expression levels of these factors were significantly suppressed in LPS + RS-treated mice. Analysis of lung glycocalyx showed a significant reduction in glycocalyx in LPS-treated mice but not in LPS + RS-treated mice. Levels of syndecan-4, one of the glycocalyx components, decreased in LPS-treated mice and increased in LPS + RS-treated mice. The current results suggest that orally administered RS protects organs and vascular endothelium from LPS-induced inflammation and maintains blood circulation