Sex differences in inflammatory cytokine production in hepatic ischemia-reperfusion

BACKGROUND: The inflammatory response to hepatic ischemia-reperfusion (I/R) is associated with an increase in cytokine production. Studies have documented that sex hormones modulate both the innate and adaptive immune responses, and that females are more robust than males. The aim of this study was to determine whether a sex difference in cytokine response to hepatic I/R exists under normal pathophysiologic condition without hormone intervention. METHODS: Adult C57BL/6 mice underwent 90 min of hepatic ischemia followed by various reperfusion periods (0, 1.5, 3, 6 hr). Plasma cytokine TNF-α, IL-6, MIP-2, and KC were measured. Liver injury was assessed by plasma alanine transaminase (ALT) levels and liver histopathology. RESULTS: A reperfusion time-dependent increase in hepatocellular injury was observed in both males and females, as indicated by increasing levels of plasma ALT and liver histopathology. The plasma cytokines were significantly increased in both female and male I/R groups compared to their respective sham counterparts. However, there was a significant difference in cytokine kinetics between the female and male I/R groups. Female mice initially had a higher level of IL-6, KC, and MIP-2 in response to I/R, which began to decline after 3 hr of reperfusion and were significantly lower than the male I/R counterparts by 6 hr of reperfusion. In contrast, the hepatocellular injury and TNF production were only moderately lower in female IR than male IR. CONCLUSION: The study underscores role of the gender in differential inflammatory cytokine expression in response to hepatic I/R, which may reflect the host response outcome

Gene deletion of P-Selectin and ICAM-1 does not inhibit neutrophil infiltration into peritoneal cavity following cecal ligation-puncture

BACKGROUND: Neutrophil infiltration is one of the critical cellular components of an inflammatory response during peritonitis. The adhesion molecules, P-selectin and intercellular adhesion molecule (ICAM)-1, mediate neutrophil-endothelial cell interactions and the subsequent neutrophil transendothelial migration during the inflammatory response. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy, suggesting that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the objective of this study was to determine the role of P-selectin and ICAM-1 in neutrophil infiltration into the peritoneal cavity during early and late phases of peritonitis. METHODS: Peritonitis was induced in both male wild-type and P-selectin/ICAM-1 double deficient (P/I null) mice by cecal ligation-puncture (CLP). Peripheral blood and peritoneal lavage were collected at 6 and 24 hours after CLP. The total leukocyte and neutrophil contents were determined, and neutrophils were identified with the aid of in situ immunohistochemical staining. Comparisons between groups were made by applying ANOVA and student t-test analysis. RESULTS: CLP induced a severe inflammatory response associated with a significant leukopenia in both wild-type and P/I null mice. Additionally, CLP caused a significant neutrophil infiltration into the peritoneal cavity that was detected in both groups of mice. However, neutrophil infiltration in the P/I null mice at 6 hours of CLP was significantly lower than the corresponding wild-type mice, which reached a similar magnitude at 24 hours of CLP. In contrast, in peritonitis induced by intraperitoneal inoculation of 2% glycogen, no significant difference in neutrophil infiltration was observed between the P/I null and wild-type mice at 6 hours of peritonitis. CONCLUSIONS: The data suggest that alternative adhesion pathway(s) independent of P-selectin and ICAM-1 can participate in neutrophil migration during peritonitis and that the mode of stimuli and duration of the injury modulate the neutrophil infiltration

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

BACKGROUND: Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury. METHODS: Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine) or saline-vehicle were administered i.p. before ischemia. Plasma cytokine tumor necrosis factor (TNF)-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT) and liver histopathology. RESULTS: A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR. CONCLUSION: Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury

Nutritional health attitudes and behaviors and their associations with the risk of overweight/obesity among child care providers in Michigan Migrant and Seasonal Head Start centers

Abstract Background Children enrolled in Migrant and Seasonal Head Start (MSHS) programs are at high risks of health problems. Although non-family child care providers play important roles on children’s health status as role models, educators, program deliverers, and information mediators, little is known about their nutritional health attitudes and behaviors, and weight status. Therefore, we investigated nutritional health attitudes and behaviors and their associations with overweight/obesity among child care providers in Michigan MSHS centers. Methods A total of 307 child care providers aged ≥ 18 years working in 17 Michigan MSHS centers were included in this cross-sectional study conducted in 2013. An online survey questionnaire was used to collect data on nutritional health attitudes and behaviors of child care providers. Weight status was categorized into normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obese (BMI ≥ 30 kg/m2) based on child care providers’ self-reported height and weight. Factor analysis was performed to investigate patterns of nutritional health attitudes and behaviors. Multivariate logistic regression was conducted to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) of overweight/obesity across tertiles of pattern scores taking the lowest tertile group as the reference group after adjustment for potential confounding variables. Results Three patterns of nutritional health attitudes and behaviors were identified: pattern 1) “weight loss practices with weight dissatisfaction”, pattern 2) “healthy eating behaviors”, and pattern 3) “better knowledge of nutrition and health”. The pattern 1 scores were positively associated with overweight/obesity (Tertile 2 vs. Tertile 1: OR = 5.81, 95 % CI = 2.81–12.05; Tertile 3 vs. Tertile 1: OR = 14.89, 95 % CI = 6.18–35.92). Within the pattern 2, the OR for overweight/obesity in individuals with the highest scores was 0.37 (95 % CI = 0.19–0.75) compared with those with the lowest scores. However, the pattern 3 was not associated with the risk of overweight/obesity. Conclusions Our findings support that nutrition education or health interventions targeting MSHS child care providers are urgently necessary. These efforts might be an efficient and effective approach for improving the nutritional health status of young children enrolled in MSHS programs

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists-2

<p><b>Copyright information:</b></p><p>Taken from "Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists"</p><p>BMC Clinical Pathology 2006;6():3-3.</p><p>Published online 15 Feb 2006</p><p>PMCID:PMC1382240.</p><p>Copyright © 2006 Crockett et al; licensee BioMed Central Ltd.</p>, prior to the onset of ischemia (90 min), followed by various reperfusion times (IR). Sham animals received the same pretreatment as the IR group, followed by sham operation. The ischemic liver sections were prepared and stained with H&E. The top row images represent the sham mice, which show normal hepatic histology. The following rows represent mice that were subjected to I/R. A pattern of reperfusion damage is evident by necrosis of hepatocytes in the pericentral and midzonal regions, with relative sparing of the periportal areas. Note the presence of neutrophils in the midzonal region around the central vein. Images are representative of n = 13 mice per saline or DMPP, and n = 8 per nicotine group

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists-1

<p><b>Copyright information:</b></p><p>Taken from "Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists"</p><p>BMC Clinical Pathology 2006;6():3-3.</p><p>Published online 15 Feb 2006</p><p>PMCID:PMC1382240.</p><p>Copyright © 2006 Crockett et al; licensee BioMed Central Ltd.</p> mg/kg), prior to the onset of ischemia (90 min), followed by 3, 6, and 24 h of reperfusion (IR). Nicotine or DMPP treatment was administered 15 min prior to the onset of ischemia and repeated after 3 and 6 h of reperfusion. Sham animals received the same pretreatment as the IR group, followed by sham operation (n = 3 mice each group). "Control" group represents mice that received no drug treatment, and no surgical operation of IR/sham protocol was performed (n = 3 mice). Values are expressed as means ± SEM of = 8 to 13 mice per saline or DMPP group, and n = 4–8 per nicotine group.< 0.05, IR group vs. sham-operated group. < 0.05, Saline-treated IR group vs. DMPP-or nicotine-treated IR group