Blood cell dynamics in P-selectin-deficient mice

P-selectin is expressed on the surfaces of activated platelets and endothelium where it mediates binding to leukocytes. P-selectin- deficient mice were shown to exhibit peripheral neutrophilia (Mayadas et al: Cell 74:541, 1993). We now show that this is not caused by changes in bone marrow precursors nor by a lack of neutrophil margination. Both P-selectin-positive and -negative animals displayed similar increases in peripheral blood neutrophil numbers after injection of epinephrine. However, clearance of 51Chromium-labeled neutrophils is delayed in mice deficient for P-selectin, indicating that the neutrophilia is at least in part the result of delayed removal. We detected no obvious alterations in lymphocyte differentiation, distribution, or adhesion to high endothelial venules in peripheral lymph nodes. Through intravital microscopy, we examined the impact of P-selectin deficiency on leukocyte/endothelial interaction beyond the initial stages of inflammation. Four hours after the administration of an inflammatory irritant, leukocyte rolling was observed even in the absence of P-selectin. There were significantly fewer rolling cells relative to wild-type mice, and their velocity was reduced. Moreover, in the peritonitis model, the number of peritoneal macrophages in wild-type mice increased threefold at 48 hours, whereas the macrophages in the mutant mice remained near baseline levels. Thus, whereas P-selectin is known to be involved in early stages of an inflammatory response, our results indicate that it is additionally responsible for leukocyte rolling and macrophage recruitment in more prolonged tissue injury.     

Chios mastic gum modulates serum biochemical parameters in a human population

INTRODUCTION: Current research suggests that Chios mastic (Pistacia lentiscus var. chia) possesses beneficial (antimicrobial, antioxidant, hepatoprotective) properties. This study aims to assess its effects on cardiologic and hepatic biochemical indices of human subjects. MATERIALS AND METHODS: Subjects (n=133, aged over 50) were randomly assigned to two groups, the first (high-dose group) ingesting daily 5g of mastic powder and the second receiving daily a Chios mastic solution (low-dose group). Serum biochemical parameters were determined on a monthly basis for an 18-month (high-dose group) and a 12-month (low-dose group) follow-up period. Generalized least squares random-effects linear regression was performed. RESULTS: The group ingesting Chios mastic powder (high-dose group) exhibited a decrease in serum total cholesterol, LDL, total cholesterol/HDL ratio, lipoprotein (a), apolipoprotein A-1, apolipoprotein B (apoB/apoA-1 ratio did not change), SGOT, SGPT and gamma-GT levels; in the second (low-dose) group, glucose levels decreased in males. DISCUSSION: Chios mastic powder could have a hepatoprotective/cardioprotective role in vivo in humans.     

Is birth weight associated with childhood lymphoma? A meta‐analysis

Several risk factors have been identified for childhood lymphomas. The purpose of this meta-analysis was to synthesize current evidence regarding the association between birth weight with primarily the risk for non-Hodgkin lymphoma (NHL), given its similarity to acute lymphoblastic leukemia, Hodgkin lymphoma (HL) and any category of lymphoma. Two cohort (278,751 children) and seven case-control studies (2,660 cases and 69,274 controls) were included. Effects estimates regarding NHL, HL and any lymphoma were appropriately pooled using fixed or random effects model in two separate analyses: specifically, high was compared to normal or any birth weight. Similarly, low was compared to normal or any birth weight. No statistically significant association was found between high birth weight, as compared to normal birth weight, and risk for NHL plus Burkitt lymphoma (OR = 1.17, 95% CI = 0.76-1.80, random effects), HL (OR = 0.94, 95% CI = 0.64-1.38, fixed effects) or any plus Burkitt lymphoma (OR = 1.09, 95% CI = 0.76-1.56, fixed effects). A null association emerged when low was compared with normal birth weight for NHL plus Burkitt lymphoma (OR = 1.07, 95% CI = 0.71-1.62, random effects), HL (OR = 0.94, 95% CI = 0.54-1.65, fixed effects) or any plus Burkitt lymphoma (OR = 1.02, 95% CI = 0.79-1.33, fixed effects). Accordingly, no association was found when high or low birth weight was compared to any birth weight. Although current evidence suggests no association, birth weight might be a too crude indicator to reveal a genuine association of fetal growth with specific lymphoma categories; hence, there is an emerging need for use of more elaborate proxies, at least those accounting for gestational week.     

XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis

Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy–Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808–1.078) for heterozygous and 0.819 (0.610–1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896–1.097) for heterozygous and 0.935 (0.729–1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906–1.019) for heterozygous and 0.984 (0.846–1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any.     

Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis

Cytochrome P450s are enzymes which catalyze Phase-I metabolism reactions; cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family and participates in the metabolism of a vast number of xenobiotics, as well as endogenous substrates. Four single nucleotide polymorphisms in CYP1A1 have been studied concerning their potential implication in terms of breast cancer risk: T3801C, T3205C, A2455G (Ile462Val), and C2453A (Thr461Asp); controversy exists regarding their role. This meta-analysis aims to examine whether the four aforementioned polymorphisms are associated with breast cancer risk. Separate analyses were performed on Caucasian, Chinese, and African populations, as well as on premenopausal and postmenopausal women. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to October 2009. Concerning T3801C, 32 studies were eligible (11,909 cases and 16,179 controls), 29 studies (12,257 cases and 20,379 controls) were eligible for A2455G, 11 studies (7,189 cases and 8,491 controls) were eligible for C2453A, and eight studies were eligible for T3205C (1,378 cases and 1,642 controls). Pooled odds ratios (OR) were appropriately derived from fixed- or random-effect models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy–Weinberg equilibrium was performed. Homozygous subjects of Caucasian origin carrying the A2455G G allele exhibited elevated breast cancer risk (pooled OR = 2.185, 95% CI 1.253–3.808, fixed effects), whereas heterozygous carriers did not (pooled OR = 1.062, 95% CI 0.852–1.323, random effects). A2455G polymorphism status was not associated with breast cancer risk in Chinese subjects or specifically in premenopausal/postmenopausal women. T3801C, T3205C, and C2453A status were not associated with breast cancer risk at any analysis. In conclusion, this meta-analysis points to the A2455G G allele as a risk factor for breast cancer among Caucasian subjects. On the contrary, T3801C, T3205C, and C2453A status does not seem capable of modifying breast cancer risk.