The reproductive geography of miscarriages. Social identities, places, and reproductive inequalities.

Increasing epidemiological evidence demonstrates the correlation between toxic contamination and miscarriages, and the disproportionate exposure of marginalised and racialised groups to environmental burdens. Yet, the debate on environmental reproductive health is still largely underpinned by a reductionist biomedical understanding of the health-place relationship that overlooks the interplay between social identities and places. In this article, I argue that understanding the role that places play in shaping reproductive inequalities, beyond the simplistic recognition of the environment as a factor of risk, is important to design a more inclusive reproductive health agenda that addresses the multiple scales across which reproductive inequalities unfold.

'Glocalizing' land-use and forest governance in the tropics: examining research partnerships and international forest policies affecting Brazil, DRC and Indonesia.

International and market forces are key drivers of deforestation and forest degradation, with transnational and market-based solutions in land-use and forest governance often missing economic, distributive, and environmental targets. This paper tackles both the framing and effectiveness of transnational initiatives affecting forest lands and peoples in the Global South, and the quality of relationships between institutions in the Global North and the Global South. Through more equitable research partnerships, this paper draws lessons from case studies in Indonesia (legality verification system in different forest property regimes), the Democratic Republic of the Congo (lifting of a moratorium on new logging concession), and Brazil (FSC in the Amazon region and the Amazon Fund).

The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways.

The prevalence of asthma has steadily increased during the last decade, probably as the result of changes in the environment, including reduced microbial exposure during infancy. Accordingly, experimental studies have shown that deliberate infections with live pathogens prevent the development of allergic airway diseases in mice. Bacterial extracts are currently used in children suffering from repeated upper respiratory tract infections.

Calcium dobesilate inhibits the alterations in tight junction proteins and leukocyte adhesion to retinal endothelial cells induced by diabetes.

Objective: Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy in the last decades, but its mechanisms of action are not elucidated. CaD is able to correct the excessive vascular permeability in the retina of diabetic patients and in experimental diabetes. We investigated the molecular and cellular mechanisms underlying the protective effects of CaD against the increase in blood-retinal barrier (BRB) permeability induced by diabetes.

A synthetic triacylated pseudo-dipeptide molecule promotes Th1/TReg immune responses and enhances tolerance induction via the sublingual route.

In this study, we tested two triacylated pseudo-dipeptidic molecules, OM-197-MP-AC and OM-294-BA-MP as candidate adjuvants for allergy vaccines. Both molecules induce human dendritic cell (h-DC) maturation and polarize naïve T cells toward the Th1 type with IFNgamma production. Only OM-294-BA-MP induces IL10 gene expression both in monocyte-derived DCs and CD4+ naïve T cells.

Cancer relapse under chemotherapy: why TLR2/4 receptor agonists can help.

Liver or lung metastases usually relapse under chemotherapy. Such life-threatening condition urgently needs new, systemic anticancer compounds, with original and efficient mechanisms of action. In B16 melanoma mice treated with cyclophosphamide, D'Agostini et al.

Synthetic triacylated lipid A derivative activates antigen presenting cells via the TLR4 pathway and promotes antigen-specific responses in vivo.

Triggering the maturation of dendritic cells (DC) with toll-like receptor (TLR) agonists is a favored strategy for the development of vaccine adjuvants. The triacyl pseudo-dipeptidic agent OM-197-MP-AC mimicking the lipid A structure of endotoxin induces the maturation of human monocyte-derived DC. In this study we investigated the signaling pathway by which this molecule activates DC.

The radiosensitizing effect of immunoadjuvant OM-174 requires cooperation between immune and tumor cells through interferon-gamma and inducible nitric oxide synthase.

Purpose: To explore whether antitumor immunoadjuvant OM-174 can stimulate immune cells to produce interferon-gamma (IFN-gamma) and thereby radiosensitize tumor cells.

Methods And Materials: Splenocytes from BALB/c mice were stimulated by OM-174 at plasma-achievable concentrations (0.03-3 mug/mL), and afterward analyzed for the expression and secretion of IFN-gamma by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent.

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. This review covers more than 40 years of intensive clinical and fundamental research with ethamsylate. First, we summarize the large medical literature concerning its clinical efficacy.

An hypothesis to link the opposing immunological effects induced by the bacterial lysate OM-89 in urinary tract infection and rheumatoid arthritis.

Extracts of lysed pathogenic bacteria were developed approximately 4 decades ago as oral vaccines in order to stimulate efficient specific immune and proinflammatory responses in patients experiencing recurrent infections, the ultimate aim being to rid the patient of the pathogen responsible for the infections. OM-89, a lysate of Escherichia coli, is clinically effective in patients who experience recurrent urinary tract infections by activating both innate and adaptive immunity. If immune activation is necessary to combat infectious pathogens, it may appear at first sight to be detrimental in patients with autoimmune diseases.

Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes.

The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-beta.

Calcium dobesilate in the treatment of diabetic retinopathy.

The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.

Antitumour effect of OM-174 and cyclophosphamide on murine B16 melanoma in different experimental conditions.

We report that OM-174, a purified water soluble diphosphorylated and triacetylated lipid A derived from E. coli, is able to reduce tumour progression and to prolong the survival of mice in the B16 melanoma experimental model. At the doses employed in our study OM-174 had an antitumour activity comparable to that of a single high dose of CY.

Inhibition of choroidal angiogenesis by calcium dobesilate in normal Wistar and diabetic GK rats.

Calcium dobesilate reduces vascular endothelial growth factor (VEGF) over-expression in diabetic rat retina, but its effect on intraocular angiogenesis is unknown. Therefore, we tested calcium dobesilate for its in vitro and ex vivo effects on choroidal explant angiogenesis in spontaneously diabetic Goto-Kakizaki (GK) rats. Choroidal explants were cultured in gels of collagen.

OM-197-MP-AC adjuvant properties: the in vitro maturation of normal and leukemic dendritic cells in a serum-free culture model.

Dendritic cells (DC) play a pivotal role in linking innate and adaptive immunity. Only mature DC are able to initiate adaptive immune responses by sensitising naive antigen-specific T cells. For clinical immunotherapeutic applications, safe and efficient clinical grade maturation factors of DC are required.

The hemostatic agent ethamsylate promotes platelet/leukocyte aggregate formation in a model of vascular injury.

The hemostatic agent ethamsylate enhances membrane expression of P-selectin in human platelets, but whether this promotes platelet-leukocyte aggregate formation is unknown. Here we investigated this point by flow cytometry determination of human platelet-leukocyte aggregates under basal conditions and after whole-blood perfusion through a damaged rabbit aorta segment. Actions of ethamsylate on adhesive molecules of platelets and leukocytes were investigated in parallel.

Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in streptozotocin-diabetic rats.

Calcium dobesilate stabilizes blood-retinal barrier in patients with diabetic retinopathy and possesses antioxidant properties in the retinas of rats with streptozotocin-induced diabetes, exposed ex vivo to ischemia-reperfusion. Here we investigated the action of calcium dobesilate on retinal albumin leakage in streptozotocin-diabetic rats, together with relevant in vivo retinal antioxidant and permeability markers, i.e.

Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by ethamsylate.

The hemostatic agent, ethamsylate, inhibits arachidonic acid metabolism by a mechanism independent of cyclooxygenase activity and blocks carrageenan-induced rat paw edema. Here, ethamsylate was investigated for (i) in vivo actions on the free radical-dependent, permeabilizing responses to arachidonic acid and (ii) its antioxidant potential in vitro. Vascular permeability was equated to the extravasation rate of Evans blue from plasma into the rat peritoneal cavity.

Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by antioxidants.

Arachidonic acid was investigated for its vascular permeabilizing potential in the rat peritoneal cavity and for its mechanism of action. The antagonistic potential of antioxidants (vitamin E, vitamin C and troxerutin) was also evaluated. Vascular permeability was equated to the rate of extravasation of Evans blue dye from plasma into the peritoneal cavity.

The hemostatic agent ethamsylate enhances P-selectin membrane expression in human platelets and cultured endothelial cells.

Ethamsylate possesses antihemorrhagic properties, but whether or not it directly activates blood platelets is unclear. Here we investigated the platelet activation potential of ethamsylate, by measuring membrane P-selectin expression with flow cytometry in human whole blood and also by immunofluorescence imaging of isolated human platelets. Moreover, we measured membrane P-selectin expression in the SV40-transformed aortic rat endothelial cell line (SVAREC) and 14C-ethamsylate membrane binding and/or uptake in platelets and endothelial cells.

The adjuvant OM-174 induces both the migration and maturation of murine dendritic cells in vivo.

The aim of this study was to test the capacity of the novel adjuvant OM-174, a lipid A analog, to induce the migration and the maturation of murine dendritic cells (DC) in vivo, a step which is considered as the initiation of the adaptive immune response. BALB/c mice were injected intravenously or subcutaneously with OM-174. The spleen and popliteal lymph nodes were harvested, and analyzed for DC localization and phenotype.

Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina.

Calcium dobesilate possesses antioxidant properties and protects against capillary permeability by reactive oxygen species in the rat peritoneal cavity, but whether a similar action can take place in the diabetic rat retina is unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induced by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h of reperfusion). Streptozotocin-induced diabetic rats were orally treated with 50 and 100 mg/kg of calcium dobesilate for 10 days (n=12 in each group).

Delayed "all-or-none" activation of inositol 1,4,5-trisphosphate-dependent calcium signaling in single rat hepatocytes.

When single rat hepatocytes were stimulated with the phospholipase C-activating hormone, vasopressin (from 300 pM to 1 microM), the [Ca2+]i signals were always "all-or-none" responses. At low concentrations of vasopressin, Ca2+ release was maximal because liberation of additional inositol 1,4,5-trisphosphate (IP3) by photolysis of its caged precursor at the top of the [Ca2+]i spike failed to increase [Ca2+]i further. However, if IP3 was generated by photolysis of caged IP3 in previously unstimulated cells, [Ca2+]i increased immediately, and the magnitude of the response was a graded function of the quantity of IP3 released.

Cytosolic Ca2+ of excitable pituitary cells at resting potentials is controlled by steady state Ca2+ currents sensitive to dihydropyridines.

Different elements of voltage-gated Ca2+ influx and their role for cytosolic-free Ca2+, [Ca2+]i, were studied in cells of the pituitary line GH3B6. Single cell monitoring of [Ca2+]i with the fluorescent probe indo-1, as well as fast on-line ratio [Ca2+]i imaging with fura-2, were combined with electrophysiological recordings using the perforated patch configuration of the patch clamp technique. [Ca2+]i signals are generated by Ca2+ influx both during action potentials and in between.