Effect of dietary (n-3) and (n-6) fatty acids on in vivo pulmonary bacterial clearance by neonatal rabbits.

Intrapulmonary bacterial clearance, lung inflammatory cell recruitment and macrophage superoxide generating capacity were studied in newborn rabbits nursed by their mother and given a supplement of either high [5 g/(kg.d)] or low [0.22 g/(kg.d)] doses of fish oil, safflower oil or saline for 7 d after birth. The high dose fish and safflower oil regimens diminished lung clearance of inspired Staphylococcus aureus by approximately 50% compared with the saline controls, but they did not alter lung neutrophil recruitment or alveolar macrophage bacterial phagocytosis. Only high dose fish oil decreased macrophage superoxide anion generation (by 30%). With high dose fish or safflower oil supplementation, the fatty acid content of lung parenchyma, bronchoalveolar lavage effluent and alveolar macrophages increased significantly. Low dose supplementation did not have this effect. We conclude that pharmacologic dietary (n-6) and (n-3) fatty acid supplementation impairs the ability of the neonatal rabbit lung to kill intrapulmonary S. aureus. It has been proposed that human infant formula be supplemented with fatty acids either to alleviate dietary deficiencies or to treat pulmonary inflammatory disorders. Based on our findings, the effects of such supplementation should be monitored relative to the possible heightened risk of bacterial infection.     

Inhibition of human lymphocyte reactivity by plasma fibronectin in vitro

The effect of purified human plasma fibronectin (FN) on the reactivity of human lymphocyte-rich mononuclear cells to mitogens and allogeneic cell interactions was studied. Concentrations of FN from 25 to 100 micrograms per 250 microL of culture consistently depressed phytohemagglutinin (PHA) responses. To exert an inhibitory effect, FN must be present within 20 hours after the addition of PHA to cells, and, therefore, it appears to interfere with early events in the transformation process. Increasing the concentration of PHA failed to reduce the inhibitory effect of FN, which suggests that the depressed response was not the result of FN-PHA complex formation, which would reduce the amount of mitogen available for stimulation. This possibility was supported by the finding that FN also inhibited the mixed lymphocyte response (MLR), in a reaction that was not dependent on the activity of soluble antigen or mitogen. In contrast, the stimulation of lymphocytes to undergo transformation that is induced by the nonlectin mitogen, sodium periodate, was unaffected by FN. Periodate-treated cells are, however, already stimulated to undergo transformation, prior to their exposure to FN. FN did not interfere with the activity of interleukin-2, nor did it indirectly regulate lymphocyte responses by modifying the production and/or effect of humoral regulatory factors released from the adherent accessory cells (macrophages). These studies show that FN is a potent immunosuppressive agent in vitro.     

Neonatal Injury Results in Sex-Dependent Nociceptive Hypersensitivity and Social Behavioral Deficits During Adolescence,Without Altering Morphine Response

Neonatal injury is associated with persistent changes in sensory function and altered nociceptive thresholds that give rise to aberrant pain sensitivity in later life. Although these changes are well documented in adult rodents, little is known about the consequences of neonatal injury during adolescence. Because adolescence is a critical developmental period during which persistent pain conditions can arise, we examined the effect of neonatal injury on nociception, social behavior, and response to morphine in adolescent Sprague Dawley rats. Male and female rats exposed to plantar incision injury at postnatal day 3 displayed mechanical hypersensitivity that resolved by 24 hours after incision. When these animals reached adolescence (postnatal day 28–40), neonatally-injured male rats showed ipsilaterally restricted mechanical, heat, and cold hypersensitivity, as well as social behavioral deficits. In contrast, these effects were not seen in female rats. Neonatal injury did not alter acute morphine antinociception or the development of analgesic tolerance in either sex. Morphine-induced conditioned place preference, behavioral sensitization, and physical withdrawal were also not affected by neonatal incision. Thus, early-life injury results in sex-dependent pain-related hypersensitivity and social behavior deficits during adolescence, without altering the response to opioids.

Influence of fibronectin-containing blood products on lymphocyte reactivity

Two fibronectin (FN)-containing blood products, human peripheral blood plasma and cryoprecipitate, were examined for their effect on mitogen-induced lymphocyte transformation in vitro. Responses of human peripheral blood lymphocytes to phytohemagglutinin (PHA) were depressed in the presence of a plasma concentration above that required for maximum DNA synthesis, and this concentration must be present in cultures prior to lymphocyte activation. The removal from the plasma of heparin-induced cryoprecipitate, a complex consisting of FN, heparin, and fibrinogen, resulted in a significant reduction in the inhibitory effect of the plasma on the PHA response. Plasma specifically depleted of FN by affinity chromatography on gelatin-agarose beads was 32 percent less inhibitory to the PHA-induced stimulation of cells than untreated plasma; the remaining inhibitory activity in the FN-depleted plasma samples was attributed to the presence of other normal immunosuppressive factors. The inhibitory capacity of FN in plasma was similar to that obtained with purified FN alone, which indicates that, unlike that of other known plasma inhibitors, the immunosuppressive activity of FN was not altered by the presence of other components of plasma. Cryoprecipitate used in the treatment of hemophilia contains high levels of FN, and, as anticipated, PHA-induced lymphocyte transformation was markedly depressed in the presence of solubilized cryoprecipitate. The contribution of FN to the T-cell abnormalities in patients chronically receiving cryoprecipitate and/or factor VIII concentrates derived from cryoprecipitate warrants further investigation.     

Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality

G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding protein (CREB1) are involved in synaptic plasticity and their genes have been implicated depression and memory processing. Excessive rumination is a core cognitive feature of depression which is also present in remission. High scores on the Ruminative Response Scale (RRS) questionnaire are predictive of relapse and recurrence. Since rumination involves memory, we tested the hypothesis that variation in the genes encoding GIRK2 (KCNJ6) and CREB1 mechanisms would influence RRS scores. GIRK2 and CREB1 polymorphisms were studied in two independent samples (n = 651 and n = 1174) from the general population. Strongly significant interaction between the TT genotype of rs2070995 (located in KCNJ6) and the GG genotype of rs2253206 (located in CREB1) on RRS were found in both samples. These results were validated in an independent third sample (n = 565; individuals with personality disorders) showing significant main effect of the variants mentioned as well as significant interaction on a categorical diagnosis of Cluster C personality disorder (obsessional-compulsive, avoidant and dependent) in which rumination is a prominent feature. Our results suggest that genetic epistasis in post-receptor signaling pathways in memory systems may have relevance for depression and its treatment.     

Genetic polymorphisms in AS3MT and arsenic metabolism in residents of the Red River Delta, Vietnam

To elucidate the role of genetic factors in arsenic (As) metabolism, we studied associations of single nucleotide polymorphisms (SNPs) in As (+ 3 oxidation state) methyltransferase (AS3MT) with the As concentrations in hair and urine, and urinary As profile in residents in the Red River Delta, Vietnam. Concentrations of total As in groundwater were 0.7-502 μg/l. Total As levels in groundwater drastically decreased by using sand filter, indicating that the filter could be effective to remove As from raw groundwater. Concentrations of inorganic As (IAs) in urine and total As in hair of males were higher than those of females. A significant positive correlation between monomethylarsonic acid (MMA)/IAs and age in females indicates that older females have higher methylation capacity from IAs to MMA. Body mass index negatively correlated with urinary As concentrations in males. Homozygote for SNPs 4602AA, 35991GG, and 37853GG, which showed strong linkage disequilibrium (LD), had higher percentage (%) of dimethylarsinic acid (DMA) in urine. SNPs 4740 and 12590 had strong LD and associated with urinary %DMA. Although SNPs 6144, 12390, 14215, and 35587 comprised LD cluster, homozygotes in SNPs 12390GG and 35587CC had lower DMA/MMA in urine, suggesting low methylation capacity from MMA to DMA in homo types for these SNPs. SNPs 5913 and 8973 correlated with %MMA and %DMA, respectively. Heterozygote for SNP 14458TC had higher MMA/IAs in urine than TT homozygote, indicating that the heterozygote may have stronger methylation ability of IAs. To our knowledge, this is the first study on the association of genetic factors with As metabolism in Vietnamese.     

Heavy Metals in the Farming Environment and in some Selected Aquaculture Species in the Van Phong Bay and Nha Trang Bay of the Khanh Hoa Province in Vietnam

Aquaculture is currently one of the most rapidly growing production sectors in Vietnam. This publication describes the concentrations of heavy metals in the farming environment and some aquaculture species in the Khanh Hoa Province in Vietnam. The concentration of total As in the sediments ranged from 0.07 to 0.64 mg/kg, whereas the concentration of Hg varied from <0.0005 to 0.56 mg/kg. The corresponding concentration span for Cd and Pb, were 0.001–0.069 and 0.016–0.078 mg/kg, respectively. The concentrations of As in the aquaculture organisms spanned from 0.14 to 1.03 mg/kg. For Hg the concentrations varied from 0.1 to 0.45 mg/kg, for Cd from 0.02 to 0.10 mg/kg and for Pb from 0.07 to 0.37 mg/kg.