Docosahexaenoic Acid Status in Pregnancy Determines the Maternal Docosahexaenoic Acid Status 3-, 6- and 12 Months Postpartum. Results from a Longitudinal Observational Study

Background

Essential fatty acid status as well as docosahexaenoic acid (DHA, 22:6n-3) declines during pregnancy and lactation. As a result, the DHA status may not be optimal for child development and may increase the risk for maternal postpartum depression. The objective of this study was to assess changes in the maternal fatty acid status from pregnancy to 12 months postpartum, and to study the impact of seafood consumption on the individual fatty acid status.

Methods

Blood samples and seafood consumption habits (gestation week 28, and three-, six- and 12 months postpartum) were collected in a longitudinal observational study of pregnant and postpartum women (n = 118). Multilevel linear modeling was used to assess both changes over time in the fatty acid status of red blood cells (RBC), and in the seafood consumption.

Results

Six fatty acids varied the most (>80%) across the four time points analyzed, including the derivative of the essential α-linoleic acid (ALA, 18:3n-3), DHA; the essential linoleic acid (LA, 18:2 n-6); and the LA derivative, arachidonic acid (AA, 20:4n-6). Over all, a large variation in individuals’ DHA- and AA status was observed; however, over the 15-month study period only small inter-individual differences in the longitudinal trajectory of DHA- and AA abundance in the RBC were detected. The median intake of seafood was lower than recommended. Regardless, the total weekly frequency of seafood and eicosapentaenoic acid (EPA, 20:5n-3)/DHA-supplement intake predicted the maternal level of DHA (μg/g RBC).

Conclusion

The period of depletion of the maternal DHA status during pregnancy and lactation, seem to turn to repletion from about six months postpartum towards one year after childbirth, irrespective of RBC concentration of DHA during pregnancy. Seafood and EPA/DHA-supplement intake predicted the DHA levels over time.

Trial Registration

www.helseforskning.etikkom.no 2009/570/REC, project number: 083.09     

Popliteal lymph node (PLN) assay to study adjuvant effects on respiratory allergy

Different variants of the popliteal lymph node (PLN) assay have been published. Here we describe the adjuvant popliteal lymph node assay, an immune response assay to study the adjuvant activity of soluble substances as well as particulate matter. The substance to be studied for adjuvant activity is injected into the hind footpad of mice or rats together with an antigen. Adjuvant activity is determined as the increase in PLN weight and cell numbers in animals receiving antigen together with the substance under study, compared with PLN weight and cell numbers in animals given the antigen without the substance in question, and animals given the putative adjuvant alone. Because lymph node weight and cell numbers are immunologically non-specific parameters, specific immune response assays like serum antibody responses or antibody-forming cell numbers should additionally be performed. Different antigens and immune response assays may be used, depending on the research question asked. In relation to respiratory (or food) allergy, the assays should as a minimum include determination of specific IgE in serum, and preferably also IgG1 (mouse). Serum specific IgG2a antibody determination may be added to get an indication of the Th1-Th2-balance of the response. The adjuvant PLN assay, with cellular response assays performed in the draining popliteal lymph node and antibody determinations in serum, requires small amounts of test material. The assay offers a practical, sensitive and reproducible method to determine the adjuvant activity of soluble substances as well as particulate material, with the possibility to also perform mechanistic studies.     

Abundance of actinobacteria and production of geosmin and 2-methylisoborneol in Danish streams and fish ponds

Occurrence of the odours geosmin and 2-methylisoborneol (MIB) in freshwater environments indicates that odour-producing organisms are commonly occurring. In the present study, we assumed actinomycetes to be a major source of the odours. Seasonal concentrations of odours and abundance of Actinobacteria, which includes actinomycetes and other G+ and high GC bacteria, were determined in one oligotrophic and two eutrophic freshwater streams, as well as in aquacultures connected to these streams, in Denmark. Concentrations of geosmin and MIB ranged from 2 to 9 ng l(-1) and were lowest in the winter. Passage of stream water in the aquacultures increased the amount of geosmin and MIB by up to 55% and 110%, respectively. Densities of actinobacteria were determined by fluorescence in situ hybridization with catalyzed reporter deposition (CARD-FISH) technique and were found to make up from 4 to 38 x 10(7) cells l(-1), corresponding to 3-9% of the total bacterial populations. The lowest densities of actinobacteria occurred in the winter. Filamentous bacteria targeted by the FISH probe made up about 2.7-38% (average was 22%) of the actinobacteria and were expected to be actinomycetes. Combined microautoradiography and CARD-FISH demonstrated that 10-38% (incorporation of 3H-thymidine) and 41-65% (incorporation of 3H-leucine) of the actinobacteria were metabolically active. The proportion of active actinobacteria increased up to 2-fold during passage of stream water in the aquacultures, and up to 98% of the cells became active. Sequencing of 16S rRNA genes in 8 bacterial isolates with typical actinomycete morphology from the streams and ponds demonstrated that most of them belonged to the genus Streptomyces. The isolated actinomycetes produced geosmin at rates from 0.1 to 35 aggeosmin bacterium(-1)h(-1). MIB was produced at similar rates in 5 isolates, whereas no MIB was produced by three of the isolates. Addition of the odours to stream water demonstrated that indigenous stream bacteria were capable of reducing the odours, and that enrichment with LB medium stimulated the degradation. Our study shows that bacterial communities in freshwater include geosmin- and MIB-producing actinobacteria. However, the mechanisms controlling production as well as degradation of the odours in natural waters appear complex and require further research.     

Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis: Exploratory Outcome from a Randomized Controlled Trial

Objective

To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA).

Design

Randomized, masked, parallel, placebo-controlled trial involving 100 participants with clinical and radiographic knee OA that were randomized to one intra-articular injection on the knee with either 1 ml of 40 mg/ml methylprednisolone (corticosteroid) dissolved in 4 ml lidocaine (10 mg/ml) or 1 ml isotonic saline (placebo) mixed with 4 ml lidocaine (10 mg/ml). Two weeks after the injections all participants undertook a 12-week supervised exercise program. Main outcomes were changes from baseline in pressure-pain sensitivity (pressure-pain threshold [PPT] and temporal summation [TS]) assessed using cuff pressure algometry on the calf. These were exploratory outcomes from a randomized controlled trial.

Results

A total of 100 patients were randomized to receive either corticosteroid (n = 50) or placebo (n = 50); 45 and 44, respectively, completed the trial. Four participants had missing values for PPT and one for TS at baseline; thus modified intention-to-treat populations were analyzed. The mean group difference in changes from baseline at week 14 was 0.6 kPa (95% CI: -1.7 to 2.8; P = 0.626) for PPT and 384 mm×sec (95% CI: -2980 to 3750; P = 0.821) for TS.

Conclusions

These results suggest that adding intra-articular corticosteroid injection 2 weeks prior to an exercise program does not provide additional benefits compared to placebo in reducing pain sensitivity in patients with knee OA.

Trial Registration

EU clinical trials (EudraCT): 2012-002607-18     

Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study

Introduction  

Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration.     

Antibody to CCDC104 is associated with a paraneoplastic antibody to CDR2 (anti-Yo)

Patients with cancer may develop paraneoplastic neurological syndromes (PNS) in which onconeural antibodies are important diagnostic findings. As the functional role of onconeural antibodies is largely unknown, insight gained by identifying associated antibodies may help to clarify the pathogenesis of the PNS. In this study, we identified patients with Yo antibodies who also had antibodies to an uncharacterized protein called coiled-coil domain-containing protein 104 (CCDC104). We found a significant association between CCDC104 and Yo antibodies (4 of 38, 10.5%), but not other onconeural antibodies (0 of 158) (P = 0.007, Fisher’s exact test). The prevalence of CCDC104 antibodies was approximately similar in patients with cancer (8 of 756, 1.1%) and in healthy blood donors (2 of 300, 0.7%). CCDC104 antibodies were not associated with PNS, as this was found in only two of the ten CCDC104-positive patients. The CCDC104 protein, whose function is unknown, is expressed in various human tissues, including the brain, and is localized mainly to the nucleus, but is also found in the cytoplasm. The association between Yo and CCDC104 antibodies may indicate functional similarities.     

Exophiala angulospora causes systemic inflammation in atlantic cod Gadus morhua

Species of Exophiala are opportunistic fungal pathogens that may infect a broad range of warm- and cold-blooded animals, including salmonids and Atlantic cod. In the present study, we observed abnormal swimming behaviour and skin pigmentation and increased mortality in cod kept in an indoor tank. Necropsy revealed foci of different sizes with a greyish to brownish colour in internal organs of diseased fish. The foci consisted of ramifying darkly pigmented fungal hyphae surrounded by distinct layers of inflammatory cells, including macrophage-like cells. In the inner layer with many hyphae, the macrophage-like cells were dead. We observed no apparent restriction of fungal growth by the inflammatory response. A darkly pigmented fungus was repeatedly isolated in pure culture from foci of diseased fish and identified as Exophiala angulospora using morphological and molecular characters. This species has not been previously reported to cause disease in cod, but has been reported as an opportunistic pathogen of both marine and freshwater fish. Based on the morphology and sequence analysis presented here, we conclude that E. angulospora caused the observed chronic multifocal inflammation in internal organs of cod, leading to severe disease and mortality.     

Francisella noatunensis in Atlantic cod (Gadus morhua L.); waterborne transmission and immune responses

This is the first report that confirms waterborne transmission of francisellosis in Atlantic cod. To investigate the transmission of disease, particle reduced water was transferred from a tank with intraperitoneally infected cod to a tank with healthy cod. Waterborne transmission of Francisella noatunensis was confirmed in the effluent group using immunohistochemistry and real-time quantitative PCR (RT-qPCR). The bacteria were located inside the accumulated macrophage-like cells. Specific and high antibody responses against live and inactivated bacteria were observed. Oil adjuvant had no effect on the antibody responses against inactivated F.?noatunensis compared to saline formulation. The antigen epitope was a 20-25?kDa component of F.?noatunensis suggested to be lipopolysaccharide detected by Western blot, Sypro Ruby and Silver staining. Systemic immune reactions were investigated by measuring the expression of IFN-γ, IL-1β and IL-10 genes with RT-qPCR. After i.p. injection of live bacteria, a significant up-regulation of IFN-γ and IL-1β expression was observed from 15 to 60 days post infection in spleen and head kidney. In intestine, IFN-γ was significantly up-regulated after 30 days whereas rectum showed no significant differences in expression. Elevated expression of IL-10 was observed in all the organs tested but was only significantly up-regulated at 60 days post infection in intestine from i.p. infected fish. For the cohabitant group, IL-1β and IFN-γ was up-regulated in spleen whereas intestine and rectum showed a down-regulation after 60 days. IL-10 was up-regulated in intestine of cohabitant fish from day 30 to day 60. These results indicate that F.?noatunensis infection provokes both specific antibody responses and long term inflammatory responses in cod. The present study provides new knowledge about infection routes and shows that both humoral and cellular defence mechanisms are triggered by F.?noatunensis in cod.