Lower serum β-CrossLaps in male cardiac transplant recipients treated without prednisolone

Post-transplantation bone disease is a frequent problem after successful cardiac transplantation. We performed a cross-sectional analysis of male heart transplant recipients in the late post-transplantation period. Nine patients (group A) had received immunosuppressive therapy with cyclosporin A and mycophenolate mofetil (steroid-free treatment), and 12 patients (group B) remained on triple-drug therapy, which included glucocorticosteroids. Bone mineral density status was analyzed by osteodensitometry and by markers of bone turnover. Osteopenia was common in both groups (44.4% in group A and 50% in group B) as was osteoporosis (30% and 33.3% in groups A and B, respectively). beta-CrossLaps were significantly lower in sera of cardiac transplant recipients on double immunosuppressive (i.e., glucocorticosteroid-free) regimen than in sera of patients on triple-drug therapy (428.3+/-109.4 vs 661.7+/-337.0 pg/ml, P<0.05). Lower serum beta-CrossLaps levels in patients undergoing glucocorticosteroid-free treatment may indicate a lower risk of bone deterioration in the long term.     

Bioactivity of enoxaparin in critically ill patients with normal renal function

Aim

In critically ill patients, reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls.

Methods

A prospective, controlled, open label study was performed on a medical intensive care unit (ICU) and a general medical ward. Fifteen ICU patients (male = 12, median age 52 years [IQR 40−65], with a median Simplified Acute Physiology Score of 30 [IQR 18−52]) and sex- and age-matched medical ward patients were included. The anti-FXa plasma activity was measured after a single subcutaneous dose of 40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured.

Results

The anti-FXa plasma activity increased significantly after enoxaparin administration, with peak levels at 3 h after treatment, but was comparable between the ICU and medical ward groups (median 0.16 IU ml⁻¹[IQR 0−0.22 IU ml⁻¹]vs. 0.2 IU ml⁻¹[IQR 0.15−0.27 IU ml⁻¹], respectively, P= 0.13). The area under the anti-FXa activity curve from 0–12 h was similar between the groups (median 0.97 IU ml⁻¹ h [IQR 0.59−2.1] and 1.48 IU ml⁻¹ h¹[IQR 0.83−1.62], P= 0.42 for the ICU group compared with the control group, respectively). The ETP was lower in the ICU group (P < 0.05) at baseline, but it was comparable at 3 h between the groups. Thrombus size decreased at 3 h compared with predose (P= 0.029) and was not different between the groups.

Conclusion

Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patients with normal renal function.     

Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats

Background: There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats.

Methods and materials: Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD?+?vitamin D, HFD and HFD?+?vitamin D. Vitamin D was administered at 500?IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods.

Results: HFD significantly increased TNF-α (P?=?0.04) and NF-κB (P?=?0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD?+?vitamin D group (P?=?0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations.

Conclusion: Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms.     

Are Pregnant and Postpartum Women: At Increased Risk for Violent Death? Suicide and Homicide Findings from North Carolina

The purpose of this study is to estimate rates of suicide and homicide death among pregnant, postpartum and non-pregnant/non-postpartum women ages 14–44, and to determine comparative rates of violent death for pregnant and/or postpartum women compared to non-pregnant/non-postpartum women. North Carolina surveillance and vital statistics data from 2004 to 2006 were used to examine whether pregnant or postpartum women have higher (or lower) rates of suicide and homicide compared to other reproductive-aged women. The suicide rate for pregnant women was 27% of the rate for non-pregnant/non-postpartum women (rate ratio = 0.27, 95% CI = 0.11–0.66), and the suicide rate for postpartum women was 54% of the rate for non-pregnant/non-postpartum women (rate ratio = 0.54, 95% CI = 0.31–0.95). Homicide rates also were lower for pregnant and postpartum women, with the homicide rate for pregnant women being 73% of the rate for non-pregnant/non-postpartum women (rate ratio = 0.73, 95% CI = 0.39–1.37), and the homicide rate for postpartum women being half the rate for non-pregnant/non-postpartum women (rate ratio = 0.50, 95% CI = 0.26–0.98). Although pregnant and postpartum women are at risk for homicide and suicide death, the highest risk group is non-pregnant/non-postpartum women. Violence prevention efforts should target all women of reproductive age, and pay particular attention to non-pregnant/non-postpartum women, who may have less access to health care services than pregnant and postpartum women.     

Relationship between glomerular filtration rate and the adipokines adiponectin, resistin and leptin in coronary patients with predominantly normal or mildly impaired renal function

BACKGROUND: Due to their molecular weight, it is possible that the adipokines adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR) is decreased. In reduced renal clearance, altered serum concentrations of these proteins might affect cardiovascular risk. The objective of the study was to investigate the relationship between adipokine concentrations and GFR. METHODS: The association between GFR, as determined by the abbreviated MDRD equation, and the concentrations of the adipokines adiponectin, resistin and leptin was assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After calculation of correlations between GFR and adipokine concentrations, the association was further assessed by analysis of covariance following adjustment for age, gender, BMI, presence of type 2 diabetes, presence of hypertension, history of smoking as well as for serum lipid concentrations. RESULTS: Mean GFR in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60 ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There were significant inverse correlations between adiponectin (r=-0.372; p<0.001), resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and GFR. After multivariate adjustment, the associations remained significant for adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73 m(2) showed a significant correlation between GFR and adiponectin as well as leptin concentrations. However, after adjustment, these associations no longer were significant. CONCLUSIONS: There is an independent association between GFR and the serum concentrations of adiponectin and resistin. However, this association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests that adipokine concentrations in mildly impaired and normal renal function are influenced by factors other than GFR.     

Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration

The role of nitric oxide (NO) in liver injury and fibrosis is unclear. The purpose of this study was to determine whether inducible NO synthase deficiency (iNOS(-/-)) affects liver injury and fibrosis produced in mice by chronic carbon tetrachloride (CCl(4)) administration. Wild-type (WT) or iNOS(-/-) mice were subjected to biweekly CCl(4) injections over 8 weeks, whereas controls were given isovolumetric injections of olive oil. Serum aminotransferases were lower after CCl(4) in the iNOS(-/-) than in the WT mice, which correlated with decreased necrosis on liver histology. There was increased apoptosis, a lower number of stellate cells, and a lesser degree of fibrosis after CCl(4) in the iNOS(-/-) as compared with the WT mice. alpha(1)(I) collagen messenger RNA (mRNA) was markedly increased after CCl(4) in the WT and to a significantly lesser extent in the iNOS(-/-) mice. Liver matrix metalloproteinase-9 (MMP-9) mRNA and MMP-2 mRNA were increased more in the WT than in the iNOS(-/-) mice after CCl(4). Also tissue inhibitor metalloproteinase 1 (TIMP-1) mRNA was increased to a much greater extent in the WT than in the iNOS(-/-) mice after CCl(4) (P < 0.05). However, MMP-9 and TIMP-1 protein, determined by western blot, were similarly increased after CCl(4) in both groups of mice. CONCLUSION: NO protects against CCl(4)-induced apoptosis. In the absence of iNOS, there is decreased necrosis, increased apoptosis, and reduced liver fibrosis.     

Family history and disease outcomes in patients with Crohn’s disease:A comparison between China and the United States

AIM To investigate the differences in family history of inflammatory bowel disease(IBD) and clinical outcomes among individuals with Crohn’s disease(CD) residing in China and the United States.METHODS We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States.We compared the prevalence of IBD family history and history of ileal involvement,CD-related surgeries and IBD medications in China and the United States,adjusting for potential confounders.RESULTS We recruited 49 participants from China and 145 from the United States.The prevalence of family history of IBD was significantly lower in China compared with the United States(China:4.1%,United States:39.3%).The three most commonly affected types of relatives were cousin,sibling,and parent in the United States compared with child and sibling in China.Ileal involvement(China:63.3%,United States:63.5%) and surgery for CD(China:51.0%,United States:49.7%) were nearly equivalent in the two countries.CONCLUSION The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States.Despite the potential difference in etiology,surgery and ileal involvement were similar in the two countries.Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.     

Intestinal microbiota and its association with colon cancer and red/processed meat consumption

The human colon harbors a high number of microorganisms that were reported to play a crucial role in colorectal carcinogenesis. In the recent decade, molecular detection and metabolomic techniques have expanded our knowledge on the role of specific microbial species in promoting tumorigenesis. In this study, we reviewed the association between microbial dysbiosis and colorectal carcinoma (CRC). Various microbial species and their association with colorectal tumorigenesis and red/processed meat consumption have been reviewed. The literature demonstrated a significant abundance of Fusobacterium nucleatum, Streptococcus bovis/gallolyticus, Escherichia coli, and Bacteroides fragilis in patients with adenoma or adenocarcinoma compared to healthy individuals. The mechanisms in which each organism was postulated to promote colon carcinogenesis were collated and summarized in this review. These include the microorganisms' ability to adhere to colon cells; modulate the inhibition of tumor suppressor genes, the activations of oncogenes, and genotoxicity; and activate downstream targets responsible for angiogenesis. The role of these microorganisms in conjugation with meat components including N‐nitroso compounds, heterocyclic amines, and heme was also evident in multiple studies. The outcome of this review supports the role of red meat consumption in modulating CRC progression and the possibility of gut microbiome influencing the relationship between CRC and diet. The study also demonstrates that microbiota analysis could potentially complement existing screening methods when detecting colonic lesions.