Carriage of Clostridioides difficile in healthy infants in the community of Handan, China: A 1-year follow-up study.

OBJECTIVE: Clostridioides difficile may colonize healthy infants and young children asymptomatically and for the long-term. C. difficile genotypes and the rate and determinants of colonization differ substantially and vary among countries and regions. A 1-year follow-up study was performed to determine the incidence, kinetics and influencing factors of C. difficile intestinal colonization. METHODS: Twenty-nine healthy infants (14 girls and 15 boys) living at home with their parents in Handan City were followed by survey from birth to 1 year of age, specifically from October 2014 through December 2015. C. difficile isolates were typed by PCR ribotyping and analyzed for the presence of toxin genes. RESULTS: During the follow-up study period in the first year of life, 20 of the 29 total enrolled infants acquired C. difficile. A total of 437 fecal samples were obtained, and 111 (25.4%) samples contained C. difficile, including 79 (71.2%) toxigenic strains. The toxigenic isolates comprised six PCR ribotypes, and two PCR ribotypes were identified as nontoxigenic strains. CONCLUSION: Our study showed that C. difficile colonization increase with age during the 12-month period, and the dominant toxigenic types of C. difficile isolates in infants were those involved in long-term colonization. Feeding patterns may affect the dynamic progress of C. difficile colonization.

Epidemiological investigation of Clostridioides difficile colonization in Chinese community infants.

Clostridioides difficile is a colonizer of the human gut; asymptomatic colonization has been reported to be more common in infants and is highly variable across regions even with no symptoms of diarrhea or death. Antibiotic treatment strategies might increase the antibiotic resistance of C. difficile. We performed a one-point study involving 1098 healthy infants (0-36 months) to address the deficiency of reports on C. difficile colonization in Chinese community infants. The C. difficile colonization rate was 22.8% (250/1098), and more than half of the strains (55.2%) were toxigenic isolates. Among the 138 toxigenic isolates, 111 were of the A+B+CDT- genotype, 26 strains were A-B+CDT-, and one strain was A+B+CDT+. Fifteen different PCR ribotypes were found among the 250 isolates, and PCR-ribotype HB03 appeared to be dominant type, accounting for 19.6% (49/250). High levels of resistance to antimicrobial agents were observed. Our study showed that age and hospitalization before stool collection were positively correlated with the C. difficile colonization rate, whereas the delivery term was negatively related to the colonization rate. Particular attention should be paid to the increasing resistance of C. difficile to rifamycin.

Lead Induces Apoptosis and Histone Hyperacetylation in Rat Cardiovascular Tissues.

Acute and chronic lead (Pb) exposure might cause hypertension and cardiovascular diseases. The purpose of this study was to evaluate the effects of early acute exposure to Pb on the cellular morphology, apoptosis, and proliferation in rats and to elucidate the early mechanisms involved in the development of Pb-induced hypertension. Very young Sprague-Dawley rats were allowed to drink 1% Pb acetate for 12 and 40 days. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA) decreased in the tissues of the abdominal and thoracic aortas and increased in the cardiac tissue after 12 and 40 days of Pb exposure, respectively. Bax was upregulated and Bcl-2 was downregulated in vascular and cardiac tissues after 40 days of Pb exposure. In addition, an increase in caspase-3 activity was observed after 40 days of exposure to Pb. In terms of morphology, we found that the internal elastic lamina (IEL) of aorta lost the original curve and the diameter of cardiac cell was enlarged after 40 days. Furthermore, the exposure led to a marked increase in acetylated histone H3 levels in the aortas and cardiac tissue after 12 and 40 days, than that in the control group. These findings indicate that Pb might increase the level of histone acetylation and induce apoptosis in vascular and cardiac tissues. However, the mechanism involved need to be further investigated.

[The effects of low pre-pregnant lead exposure level on maternal bone turnover during gestation and lactation in mice].

OBJECTIVE: To study the effects of low pre-pregnant lead exposure level on the mobilization of lead and calcium in maternal skeleton during gestation and lactation in mice. METHODS: Seventy Kunming female mice were randomly divided into the lead exposure or control groups, 36 mice were exposed to lead by drinking water (50 mg/L) and 36 mice were exposed to deionized water for 4 weeks. The levels of calcium and lead in blood and femurs were measured on the 1st, 7th and 14th days during gestation and on the 1st,10th and 21st days during lactation with atomic absorption spectrophotometry using a heated graphite atomizer or flame atomic absorption spectrophotometry. RESULTS: As compared with the pre-pregnant, at the end of lactation in exposure group the levels of calcium in blood and bones significantly decreased 18.5% and 17.75%, respectively, the levels of lead in blood significantly increased 65.22% and the levels of lead in bones significantly decreased 28.45% (P < 0.05). There was a significant negative correlation between the blood lead level and the bone lead level during gestation and lactation in exposure group (r = -0.904, P < 0.01). There were significant differences of lead and calcium levels during the gestation and lactation between exposure group and control group (P < 0.05). CONCLUSION: The lead mobilization in maternal bone occurred during gestation and lactation in mice, which could be accelerated by the low pre-pregnant lead exposure.

Longitudinal increases in PCDD/F and dl-PCB concentrations in human milk in northern China.

There is a dearth of information on the temporal changes in polychlorinated dibenzodioxin/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) contamination, in both environmental and biological specimens, in China. We compared the concentrations of PCDD/Fs and dl-PCBs in human milk collected in Shijiazhuang, Hebei Province, in northern China in 2002 (n=30) and 2007 (n=20). The level of PCDD/Fs and dl-PCBs showed an increasing trend. The mean concentrations of PCDD/Fs plus dl-PCBs were 4.47 TEQ pg g(-1) fat and 6.24 TEQ pg g(-1) fat in human milk from Shijiazhuang in 2002 and in 2007, respectively. Based on statistical analysis of questionnaire data collected by in-person interviews with mothers, we found positive correlations between consumption of sea fish and PCDFs. The PCDDs, PCDFs, PCDD/Fs, and PCDD/Fs plus dl-PCBs levels in individuals consuming greater amounts of sea fish were higher than those consuming less sea fish, both with and without adjustments for potential confounding factors. Among 17 congeners of PCDD/Fs, the 2,3,7,8-TCDF, 1,2,3,7,8-PeCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 2,3,4,6,7,8-HxCDF congener concentrations in 2007 increased 134%, 55%, 53%, 57%, 65% and 130% when compared to 2002 levels, respectively. The 2007 dl-PCB congener levels were greater than those of the 2002 samples, with the exception of PCB81 and PCB77. Specifically, PCB105, PCB114, PCB118, PCB123 and PCB156 had increased greater than twofold from 2002 to 2007. Continuous surveillance of PCDD/F and dl-PCB levels in human milk is needed to accurately evaluate both environmental contamination and the human health risk to neonates in China.

High bone matrix turnover predicts blood levels of lead among perimenopausal women.

Skeletal bone is the primary endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as pregnancy and postmenopausal osteoporosis. We studied the influence of bone turnover rate on the release of lead from bone in 1225 female farmers from 5 districts in Japan. We collected peripheral blood and urine samples and medical nutritional information, and measured forearm bone mineral density (BMD). We found that blood lead levels in perimenopausal women were highest among all groups studied. Analysis of data for subjects grouped by level of markers of bone metabolism suggested that, in perimenopausal women, blood lead levels were higher in groups with high levels of N-telopeptide cross-linked collagen type I (NTx) and high levels of bone-specific alkaline phosphates (BALP) or osteocalcin (OC) compared with groups with low NTx and low BALP or OC levels. Linear multivariate models showed that markers of bone turnover were significantly positively related to blood lead levels. These results provide evidence that high bone turnover rates increase the release of lead stored in bone into the circulation. It is likely that markers of bone metabolism can be used to predict blood lead levels.

[Effects of lead acetate on expression of brain-derived neurotropic factor and P75NTR in rat brain].

OBJECTIVE: To study the effects of lead acetate on the expression of brain-derived neurotropic factor (BDNF) and its receptor P75NTR in rat brain. METHODS: Lead acetate was given to SD rats by intraperitoneal injection (ip) for 5 days at the dosage of 25, 50 and 100mg/kg body weight respectively. The contents of lead in serum, cerebral cortex and hippocampus were measured by atomic absorption spectrophotochemistry. The levels of BDNF mRNA and protein expression in cerebral cortex and hippocampus were observed by RT-PCR and immunohistochemistry, respectively. The levels of P75NTR protein expression in rat brain were measured by immunohistochemistry. RESULTS: Compared with the control, the contents of lead were significantly increased in serum, cerebral cortex and hippocampus in the treatment groups respectively (P < 0.01, P < 0.05). The BDNF mRNA expression in the cerebral cortex (0.52 +/- 0.05, 0.33 +/- 0.03) and hippocampus (0.77 +/- 0.10, 0.92 +/- 0.08) of 50, 100 mg/kg treated groups was significantly higher than that of the control group (0.52 +/- 0.05, 0.33 +/- 0.03), respectively (P < 0.05). The results of immunohistochemistry showed that the area density of BDNF protein in cerebral cortex of every treatment group (0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040) was significantly increased whereas the average gray value (187.11 +/- 11.15, 180.53 +/- 5.82, 180.15 +/- 8.01) was significantly lower than that of the control (0.026 +/- 0.005, 204.98 +/- 3.45) (P < 0.05, P < 0.01). The area density of BDNF protein in hippocampus of every treatment group was 0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040, respectively, which was significantly increased compared with the control (0.045 +/- 0.019, P < 0.05). The average gray value of BDNF protein in hippocampus (181.03 +/- 5.16, 171.25 +/- 12.65) of 50, 100 mg/kg were significantly lower than that of the control (198.98 +/- 6.40, P < 0.01). There was no positive expression of P75NTR protein in the control and 25 mg/kg body weight groups. The positive expression of P75NTR protein was detected in 50 and 100 mg/kg body weight groups. CONCLUSION: Lead can increase the BDNF and P75NTR expression in rat brain which might play an important role in the neural damage and repair.

Dioxin concentration in human milk in Hebei province in China and Tokyo, Japan: potential dietary risk factors and determination of possible sources.

Very limited information is available on body burdens and environmental levels of dioxins and dioxin-like PCBs (dl-PCBs) in mainland China. In the current studies, human milk samples were collected from 30 breastfeeding mothers in Shijiazhuang city (industrialized) and 11 in the Tanshan countryside (agricultural) of Hebei Province in northern China. An additional 20 samples were obtained from mothers in Tokyo, Japan. PCDDs, PCDFs, and dl-PCBs in human milk were analyzed by high-resolution gas chromatography/high-resolution mass spectrometry. Our results show that arithmetic means for body burdens of PCDDs/Fs and dl-PCBs in Hebei were 3.6 and 1.9 pg TEQg(-1) fat, respectively, which were only about one fourth of the levels in Japan. In addition, no difference was found in the chemical levels except dl-PCBs between the urban and rural areas. Based on the results of an in-person interview of the Chinese mothers using a 59-item questionnaire, freshwater fish consumption was found to correlate with the body burden of dioxins. Principal component analysis of dioxin congeners revealed that the patterns of dioxins in the Hebei urban and rural areas are quite similar; however, they are clearly different from those in Japan. Collectively, our results suggest that the lower body burdens of dioxin in Hebei may be due in part to the relatively slow industrialization and a lower consumption of marine foods. Finally, the results indicate that comprehensive monitoring of dioxins and dl-PCBs in humans as well as in the environment and foods is necessary in China.

Oral administration of soy-derived genistin suppresses lipopolysaccharide-induced acute liver inflammation but does not induce thymic atrophy in the rat.

Genistein, the principal isoflavone present in soy, has been identified as a protein tyrosine kinase (PTK) inhibitor that has in vitro anti-inflammatory effects. Whether genistein has in vivo anti-inflammatory effects remains unknown yet. Injecting or feeding rats with the unconjugated form of genistein (aglycone) results in decreased thymic weight and lymphocytopenia. However, 95-99% of genistein is present as the conjugated form genistin (genistein glycoside) in soy or soy-derived products. This study was undertaken to reveal whether genistin, as well as genistein, has anti-inflammatory effects in vivo. After oral administration of equimolar genistein (namely 7.4 or 74 micromol/dose) at daily doses of 2.0 or 20 mg/kg, or genistin at daily doses of 3.2 or 32 mg/kg for 3 days to male rats, both aglycone and glycoside suppressed the production of lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 in both from the liver and in the sera. Aglycone induced thymic atrophy while glycoside did not. In vitro preincubation of liver slices from naïve rat with genistein aglycone or glycoside suppressed LPS-induced TNF-alpha production in a dose-dependent manner. Taken together, both in vivo and in vitro administration of genistin and genistein suppressed LPS-induced liver pro-inflammatory cytokine production. However, equimolar oral administration of genistin did not induce thymus atrophy. Further investigation in long-term isoflavone intake is required especially among neonates. The results suggest that the safety evaluation of the consumption of isoflavone should be based on isoflavone glycoside but not aglycone.

Persistent organic pollutants in human milk in women from urban and rural areas in northern China.

Human milk specimens from 55 women in Shijiazhuang urban and Tangshan rural areas in Hebei Province in northern China were collected and analyzed for persistent organic pollutants, such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and dioxins. We administered a questionnaire to milk donors at collection time, asking about lifestyle factors that potentially influence organochlorine pesticide (OCP) levels in human milk. We found that the concentrations of p,p'-DDE and beta-HCH in human milk from the primiparous mothers in Shijiazhuang (3330 and 108.8 ng/g fat, respectively) were higher than in samples from mothers from Tangshan (1916 and 21.2 ng/g fat, respectively). In addition, we found the level of p,p'-DDE correlated positively with a dietary history of meat consumption or consumption of internal organs of pigs and sheep (r=0.38 and r=0.52, respectively), but not with intake frequencies of vegetables and fruits in primiparous mothers. The higher level for p,p'-DDE may be due to a greater intake of contaminated fatty foods in the industrialized areas. We also showed that the body burden of p,p'-DDE was higher in the urban group compared to the values in other regions in China after 1998. However, there was no difference in dioxin levels between the two regions. Comprehensive monitoring of persistent organic pollutants in human milk and food is needed in China.

A soy diet accelerates renal damage in autoimmune MRL/Mp-lpr/lpr mice.

Isoflavones, which are phytoestrogens present in large quantities in soy and soy-derived products, have estrogenic activity, inhibit protein tyrosine kinase, and exert other effects in the human body. Thus, the recent spread of soy consumption in Western populations emphasizes the need to more fully understand the potential effects in the body, especially in abnormal immune conditions. In the present study, the influence of a soy diet on lupus disease in MRL/Mp-lpr/lpr (MRL/lpr) mice was investigated. Weanling female MRL/lpr mice (4 weeks) were fed a soy diet (20% soybean protein and 5% soybean oil). The soy diet exacerbated renal damage; findings in this mouse strain included accelerated proteinuria, elevated serum creatinine concentrations, and reduced creatinine clearance. No effects were detected, however, in C3H/HeN mice, which have the same H-2(k) genetic background as MRL/lpr mice do. A tendency toward an increase in thymus weight and proliferation of T cells in spleen and B cells in lymph nodes were found at the age of 16 weeks. These findings indicate that a soy diet, in comparison with a casein diet, significantly exacerbates the clinical course of this autoimmune disease. Further research on the mechanism of this effect of soy-rich diets is needed, and isoflavone supplementation for systemic lupus erythematosus patients should be carefully reevaluated.