Epidemiological and nonclinical studies investigating effects of iron in carcinogenesis-A critical review

The efficacy and tolerability of intravenous (i.v.) iron in managing cancer-related anemia and iron deficiency has been clinically evaluated and reviewed recently. However, long-term data in cancer patients are not available; yet, long-term i.v. iron treatment in hemodialysis patients is not associated with increased cancer risk. This review summarizes epidemiological and nonclinical data on the role of iron in carcinogenesis. In humans, epidemiological data suggest correlations between certain cancers and increased iron exposure or iron overload. Nonclinical models that investigated whether iron can enhance carcinogenesis provide only limited evidence relevant for cancer patients since they were typically based on high iron doses as well as injection routes and iron formulations which are not used in the clinical setting. Nevertheless, in the absence of long-term outcome data from prospectively defined trials in i.v. iron-treated cancer patients, iron supplementation should be limited to periods of concomitant anti-tumor treatment

Purification and partial characterization of draculin, the anticoagulant factor present in the saliva of vampire bats (<i>Desmodus rotundus</i>)

From the saliva of the vampire bat Desmodus rotundus, we isolated an unknown anticoagulant protein which we have named draculin. Its molecular mass as determined by non-reduced SDS-PAGE is about 83 kDa. The reduced polypeptide shows a slower migration. HPLC in a molecular sieve matrix yields a single, symmetrical peak corresponding to 88.5 kDa. Isoelectric focusing shows an acidic protein with pI = 4.1–4.2. Aminoacid analysis is compatible with a single chain polypeptide of about 80 kDa. Cyanogen bromide cleavage yields a single 16-aminoacid peptide, corresponding to the amino-terminus of the native molecule. Draculin inhibits the activated form of coagulation factors IX and X. It does not act on thrombin, trypsin, chymotrypsin and does not express fibrinolytic activity. The inhibition is immediate and not readily reversible, with a stoichiometry of about two molecules of draculin per molecule of factor IXa or Xa. Surprisingly, the inhibitory activity against either factor is not affected by the presence of the other. Draculin binds quantitatively to either immobilised factor Xa or factor IXa. Our preliminary interpretation is that there are two forms of draculin that hardly differ in structure. Both bind to factor Xa and to factor IXa but one form inhibits factor Xa and the other inhibits factor IXa. When added to plasma, draculin increases the lag phase as well as the height of the peak of thrombin generation

Feed-back on the development of a small scale Contact Erosion Test in the laboratory (characteristic size ~ 30 cm)

To determine the hydraulic load requested to initiate contact erosion process, tests are performed with an apparatus called the “Contact Erosion Test”. This device originally results from research carried out by Grenoble University, Électricité de France and Compagnie Nationale du Rhône, at the scale of ~60 cm. It has been adapted to a smaller scale in geophyConsult laboratory to conduct tests on samples extracted from core drilling. The instrumentation was improved to enable a better control of the hydraulic loading and avoid biases. The test protocol was modified, especially to better constrain the soil density at the interface. From the first series of test, we drew conclusions on the test repeatability and on the influence of parameters of the soil state. Discrepancies with previous results obtained at the scale of ~60 cm were identified. Therefore, a new erosion test campaign was planned to confirm and determine the reasons for these differences

Lattice worldline representation of correlators in a background field

We use a discrete worldline representation in order to study the continuum limit of the one-loop expectation value of dimension two and four local operators in a background field. We illustrate this technique in the case of a scalar field coupled to a non-Abelian background gauge field. The first two coefficients of the expansion in powers of the lattice spacing can be expressed as sums over random walks on a d-dimensional cubic lattice. Using combinatorial identities for the distribution of the areas of closed random walks on a lattice, these coefficients can be turned into simple integrals. Our results are valid for an anisotropic lattice, with arbitrary lattice spacings in each direction.Comment: 54 pages, 14 figure

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent ten-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted in chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and DLI (n=30), or isolated reinfusion of donor lymphocytes (DLI) (n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy = 385 d, second allograft = 391d, chemotherapy = 174d, DLI alone = 140d, palliative care = 43d. A second SCT or a combination of chemotherapy and donor lymphocytes infusion yielded similar outcome (HR=0.85, p=0.53) unlike chemotherapy alone (HR 1.43 p=0.04), palliative care (HR=4.24, p<0.0001) or isolated DLI (HR=1,94, p<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML

Cerebral toxoplasmosis following allogeneic hematopoietic peripheral blood stem cell transplantation with non-myeloablative conditioning

peer reviewedWe report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.Nous présentons le cas d'un patient ayant hbénéficié d'une mini-allogreffe de cellules souches hématopoïétiques dusang périphérique pour une leucémie myéloïde aiguë qui développa une toxoplasmose cérébrale 52 jours après sa greffe

Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam