Serum Concentrations of Antibodies Against Vaccine Toxoids in Children Exposed Perinatally to Immunotoxicants

Background: Polychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose–response relationship and possible vulnerable time windows of exposure are uncertain. In this study we applied serum concentrations of specific antibodies against childhood vaccines as sentinels of immunotoxicity. Objectives: The main objective was to assess the possible dependence of antibody concentrations against diphtheria and tetanus toxoids in children with regard to prenatal and postnatal PCB exposures. Methods: From a cohort of 656 singleton births formed in the Faroe Islands during 1999–2001, children were invited for examination with assessment of serum antibody concentrations at 5 years (before and after a booster vaccination) and at 7 years of age. Total PCB concentrations were determined in serum from ages 5 and 7 years, and data were also available on PCB concentrations in maternal pregnancy serum, maternal milk, and, for a subgroup, the child’s serum at 18 months of age. Results: A total of 587 children participated in the examinations at ages 5 and/or 7 years. At age 5 years, before the booster vaccination, the antidiphtheria antibody concentration was inversely associated with PCB concentrations in milk and 18-month serum. Results obtained 2 years later showed an inverse association of concentrations of antibodies against both toxoids with PCB concentrations at 18 months of age. The strongest associations suggested a decrease in the antibody concentration by about 20% for each doubling in PCB exposure. At age 5 years, the odds of an antidiphtheria antibody concentration below a clinically protective level of 0.1 IU/L increased by about 30% for a doubling in PCB in milk and 18-month serum. Conclusions: Developmental PCB exposure is associated with immunotoxic effects on serum concentrations of specific antibodies against diphtheria and tetanus vaccinations. The immune system development during the first years of life appears to be particularly vulnerable to this exposure

Allergy and Sensitization during Childhood Associated with Prenatal and Lactational Exposure to Marine Pollutants

Background: Breast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region. Objectives: The objective was to assess whether sensitization and development of allergic disease is associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury. Methods: A cohort of 656 singleton births was formed in the Faroe Islands during 1999–2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at 5 and 7 years of age. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at 7 years of age was analyzed for total immunoglobulin E (IgE) and grass-specific IgE. Results: The total IgE concentration in serum at 7 years of age was positively associated both with the concomitant serum PCB concentration and with the duration of breast-feeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, although children with atopic dermatitis had lower prenatal PCB exposures than did nonallergic children. Conclusions: These findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants

Case Report First-in-Man Method Description: Left Ventricular Unloading With iVAC2L During Veno-Arterial Extracorporeal Membrane Oxygenation: From Veno-Arterial Extracorporeal Membrane Oxygenation to ECMELLA to EC-iVAC®

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly used in bi-ventricular failure with cardiogenic shock to maintain systemic perfusion. Nonetheless, it tends to increase left ventricular (LV) afterload and myocardial oxygen demand. In order to mitigate these negative effects on the myocardium, an Impella CP® (3.5 L/min Cardiac Output) can be used in conjunction with V-A ECMO (ECMELLA approach). We implemented this strategy in a patient with severe acute myocarditis complicated by cardiogenic shock. Due to a hemolysis crisis, Impella CP® had to be substituted with PulseCath iVAC2L®, which applies pulsatile flow to unload the LV. A subsequent improvement in LV systolic function was noted, with increased LV ejection fraction (LVEF), LV end-diastolic diameter (LVEDD) reduction, and a reduction in plasma free hemoglobin. This case documents the efficacy of iVAC2L in replacing Impella CP as a LV vent during V-A ECMO, with less hemolysis

Chimerism studies in HLA-identical nonmyeloablative hematopoietic stem cell transplantation point to the donor CD8+ T-cell count on day +14 as a predictor of acute graft-versus-host disease

AbstractChimerism analysis of hematopoietic cells has emerged as an essential tool in nonmyeloablative hematopoietic stem cell transplantation. We have investigated the development of donor chimerism in granulocytes and CD4+ and CD8+ T cells in blood and bone marrow of 24 patients with hematologic malignancies who received HLA-identical sibling peripheral blood stem cell grafts after conditioning with fludarabine and 2 Gy of total body irradiation. The T-cell chimerism of blood and bone marrow was tightly correlated. Complete donor chimerism was reached earlier in the granulocytes than in the T cells. Mixed T-cell chimerism was common at the time of onset of acute graft-versus-host disease (aGVHD), and both CD4+ and CD8+ donor T-cell chimerism increased with the occurrence of aGVHD grades II to IV (P = .0002 and P = .019, respectively). The rate of disappearance of recipient CD8+ T cells was faster in patients with aGVHD grades II to IV than in patients without clinically significant aGVHD (P = .016). This observation indicates a role of graft-versus-lymphohematopoietic tissue reactions in creating complete donor T-cell chimerism. A donor CD8+ T-cell count above the median on day +14 increased the risk of subsequent development of aGVHD grades II to IV (P = .003)

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review

Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Prenatal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19% to 29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding