The effects of antioxidants on a porcine model of liver hemorrhage.

PURPOSE: The aim of this study is to assess the efficacy of the combination of N-acetylcysteine (NAC) and deferoxamine (DFO) in the resuscitation from hemorrhagic shock in a porcine model of bleeding during hepatectomy. METHODS: Twenty-one pigs were divided randomly to three groups: Sham (S) group, n = 5; fluid (F) resuscitation group, n = 8; and fluid plus NAC plus DFO (NAC&DFO) resuscitation group, n = 8. The animals of groups F and NAC&DFO were subjected to left hepatectomy and controlled hemorrhage from the traumatic liver surface. Shock was established within 10 minutes and maintained for 30 minutes at mean arterial pressure (MAP) of 30 to 40 mm Hg. Resuscitation followed the shock period with crystalloids and colloids. Group NAC&DFO received additionally NAC and DFO in doses of 200 mg/kg and 65 mg/kg, respectively. The total time of the experiment was 6 hours. RESULTS: Animal weight, blood loss, excised liver mass, and MAP at the end of the shock period were comparable between experimental groups. Group NAC&DFO received significantly lower volume of both crystalloids and colloids (35% and 42% less, respectively) compared to group F. Hepatocellular proliferation (proliferating cell nuclear antigen) was higher in the antioxidant group. Apoptosis, measured by caspase-3, was restored to sham group levels when NAC and DFO were administered. CONCLUSIONS: Our experimental study showed that coadministration of NAC and DFO during liver hemorrhage can decrease the amounts of fluids needed for resuscitation. Moreover, the antioxidant combination restores the energy dependent apoptosis and proliferation of the hepatocytes.

Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males.

OBJECTIVE: We aimed to determine the prevalence of 25(OH)D (D2 and D3 independently) inadequacy in healthy young/middle-aged men and to investigate its relationship with BMD, bone markers, demographic and lifestyle parameters such as age, BMI, smoking, alcohol consumption and dietary calcium intake. DESIGN: We determined 25(OH)D levels using LC-MS/MS, a robust method for measurement of both 25(OH)D3 and 25(OH)D2, iPTH, osteocalcin, beta C terminal cross-linked telopeptides of type I collagen (b-CTXs), procollagen type 1 amino-terminal propeptide (PINP), BMD at L2-L4 and proximal femur, smoking habits, daily dietary calcium intake and alcohol consumption in 181 randomly selected healthy men aged 20-50y. RESULTS: The prevalence of vitamin D deficiency (25(OH)D < 20 ng/ml) was 50.3%. Only 8.8% of the participants had vitamin D sufficiency (25(OH)D ≥ 30 ng/ml). We found a strong correlation between 25(OH)D and smoking in the totality of participants (p<0.001). 25(OH)D level was lower by approximately 4.3 ng/dl (p<0.001) in a smoker compared to a non-smoker among the totality of participants, while this value increased to 9.2 ng/ml in the 40-50y subgroup (p=0.003). A multinomial logistic regression model demonstrated that a young smoker (20-29y) had 58% increased likelihood of having vitamin D deficiency compared to a non-smoker of the same age group (p=0.041). CONCLUSIONS: A high prevalence of vitamin D deficiency was identified in a young and middle-aged male population. Smoking is a significant determinant of serum 25(OH)D, while it increases significantly the likelihood of having vitamin D deficiency. In our hands, vitamin D levels are not a determinant of bone turnover and BMD in this population.

Smoking cessation increases serum adiponectin levels in an apparently healthy Greek population.

BACKGROUND: Smoking has been associated with low serum levels of adiponectin, an adipocytokine with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. The objective of this study was to assess the early effect on adiponectin levels of smoking cessation supported by bupropion. METHODS: Apparently healthy smokers of both sexes with no additional cardiovascular risk factors were administered 150mg sustained-release bupropion twice daily for 9 weeks. Quitters constituted the active group and non-quitters the control group. Sandwich enzyme-linked immunosorbent assays were employed for the measurement of serum adiponectin and cotinine, the latter used for validation of self-reported abstinence. RESULTS: Among the 106 participants (mean age 44.5+/-11.3 years, 57 females, Brinkman index 512.2+/-98.4, basal adiponectin 7.2+/-1.5mg/L), 45 (42.5%) had quitted smoking at week 9. Quitters' post-cessation adiponectin levels were significantly increased (mean difference with baseline 1.9+/-0.8mg/L, 95% CI 1.2, 2.3; p<0.001), while non-quitters' adiponectin remained unaltered. A multiple regression model including female gender (standardized beta coefficient=0.480, p=0.002), age (0.355, p=0.003), body mass index (BMI) (-0.308, p=0.005), waist circumference (-0.276, p=0.008), smoking status (-0.255, p=0.010), and cotinine levels (-0.233, p=0.021) explained about two thirds of the variation in adiponectin levels (adjusted R(2)=0.656). CONCLUSIONS: Serum adiponectin levels appear to increase considerably within 2 months after smoking cessation. This finding may provide further insight into the mechanisms related to the detrimental effects of smoking and the benefits of quitting.

Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study.

Accumulating evidence supports a role for obesity in the etiology of multiple myeloma (MM). The distinct possibility exists that obesity may be linked to MM through altered adipokine secretion and circulating levels, one of which, adiponectin, has a protective role in several malignancies, including leukemia. In this case-control study, we investigated the role of serum adiponectin, resistin, and leptin levels in the etiopathogenesis of MM and we explored their association with several established prognostic factors. Seventy three patients with incident, histologically confirmed MM and 73 controls matched on gender and age were studied between 2001 and 2007, and blood samples were collected. Serum adiponectin, leptin, resistin, as well as MM prognostic parameters were determined. Statistical analysis of the data was performed using univariate and multivariate analyses. Lower serum adiponectin and resistin levels were associated with higher risk of MM by bivariate analysis and after adjusting for age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a protective role in MM, whereas leptin was not associated with risk for MM at a comparable level of significance and resistin levels may be decreased via a compensatory mechanism. Further studies are needed to confirm these associations and to explore the mechanisms underlying adiponectin's role in MM and plasma cell dyscrasias.

Effect of exogenous catecholamines on tumor necrosis factor alpha, interleukin-6, interleukin-10 and beta-endorphin levels following severe trauma.

Cytokines and endogenous opioids are mediators of the post traumatic inflammatory response. The aim of this study was to determine the effect of exogenous catecholamines on tumor necrosis factor alpha (TNFa), interleukin-6 (IL-6), interleukin-10 (IL-10) and beta(beta)-endorphin levels in patients with severe trauma, during the first 24 h after injury. Forty four traumatized patients with haemorrhage class III and IV were included in the study. Patients were divided in two groups: Group 1 (adrenergic, n=22) and Group 2 (non adrenergic, n=22), depending on the use of exogenous catecholamines. Blood samples were collected at 0, 2, 4 and 24 h time points. Baseline values were different between the two groups, but an altered pattern of release was observed for TNFa, IL-6, IL-10 and beta-endorphin levels in patients treated with catecholamines. ICU stay was longer for the adrenergic group, while survival after 1 month was significantly lower. Findings support an altered pattern of cytokine release during the early phase after trauma, probably due to catecholamine presence.

Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker.

Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.