Influence of clinical characteristics on maternal DHA and other polyunsaturated fatty acid status in pregnancy: A systematic review.

INTRODUCTION: Omega-3 DHA is important for the prevention of preterm birth, however there is limited knowledge of the determinants of omega-3 status during pregnancy. The primary objective of this systematic review was to synthesise data from existing studies assessing relationships between clinical factors and maternal DHA status. MATERIALS AND METHODS: The Medline, Embase, Amed, and CINAHL databases were searched for studies reporting measures of maternal omega-3 status and one or more clinical characteristics. RESULTS: Eighteen studies were included in the final analyses. Factors associated with a higher BMI (overweight, higher gestational weight gain, gestational diabetes), or lower parity were each associated with higher omega-3 status in the majority of studies, with mixed findings for other comparisons. DISCUSSION: Inconsistent findings between studies make it difficult to draw clear conclusions about the relationship between clinical factors and maternal omega-3 DHA status. However, maternal overweight and associated metabolic conditions may increase lipid metabolism.

Influence of sociodemographic, lifestyle and genetic characteristics on maternal DHA and other polyunsaturated fatty acid status in pregnancy: A systematic review.

INTRODUCTION: Omega-3 DHA is important for the prevention of preterm birth, however there is limited knowledge of the determinants of omega-3 status during pregnancy. The primary objective of this systematic review was to synthesise data from existing studies assessing relationships between sociodemographic, diet, lifestyle and genetic factors and maternal DHA status. MATERIALS AND METHODS: The Medline, Embase, Amed, and CINAHL databases were searched for studies reporting measures of maternal omega-3 status and a sociodemographic/lifestyle/genetic characteristic. RESULTS: Twenty-two studies were included in the final analyses. Higher dietary fish consumption/PUFA intake, higher education level and an older maternal age were associated with higher maternal omega-3 status. Higher alcohol intake, smoking and FADS genotype were each associated with lower maternal omega-3 status. DISCUSSION: Differences in findings between studies make it difficult to draw clear conclusions about the relationship between these factors and maternal omega-3 DHA status, although socioeconomic status may play a role.

Nox2 is a mediator of ischemia reperfusion injury.

Delayed graft function (DGF) results from ischemia-reperfusion injury (IRI) and the generation of reactive oxygen species. We hypothesized that NADPH oxidase 2 (Nox2) plays an important role in pathways leading to DGF. We tested this hypothesis in vitro, in an animal model of IRI using wild type and Nox2(-/-) mice, and in patients with DGF. Under hypoxic conditions, primary tubular epithelial cells from Nox2(-/-) mice had reduced expression of MMP2, vimentin, and HSP27. BUN and creatinine levels were significantly increased in both Nox2(-/-) and WT mice at 4 weeks and 6 months after IRI, suggesting the development of acute and chronic kidney injury. At 4 weeks, kidney fibrosis (α-SMA, picrosirius) and oxidative stress (dihydroethidine, HNE) were significantly reduced in Nox2(-/-) mice, confirming the oxidative and pro-fibrotic effects of Nox2. The molecular signature of IRI using genomic analyses demonstrated a significant decline in hypoxia reponse, oxidative stress, fibrosis, and inflammation in Nox2(-/-) mice. Immunohistochemical analyses of pre-implanatation kidney allograft biopsies from patients with subsequent DGF showed significantly greater Nox2 levels and vascular injury compared with patients without DGF. These studies demonstrate that Nox2 is a modulator of IRI and its absence is associated with reduced inflammation, OS, and fibrosis.

Characterization of transfusion-elicited acute antibody-mediated rejection in a rat model of kidney transplantation.

Animal models of antibody-mediated rejection (ABMR) may provide important evidence supporting proof of concept. We elicited donor-specific antibodies (DSA) by transfusion of donor blood (Brown Norway RT1(n) ) into a complete mismatch recipient (Lewis RT1(l) ) 3 weeks prior to kidney transplantation. Sensitized recipients had increased anti-donor splenocyte IgG1, IgG2b and IgG2c DSA 1 week after transplantation. Histopathology was consistent with ABMR characterized by diffuse peritubular capillary C4d and moderate microvascular inflammation with peritubular capillaritis + glomerulitis > 2. Immunofluorescence studies of kidney allograft tissue demonstrated a greater CD68/CD3 ratio in sensitized animals, primarily of the M1 (pro-inflammatory) phenotype, consistent with cytokine gene analyses that demonstrated a predominant T helper (TH )1 (interferon-γ, IL-2) profile. Immunoblot analyses confirmed the activation of the M1 macrophage phenotype as interferon regulatory factor 5, inducible nitric oxide synthase and phagocytic NADPH oxidase 2 were significantly up-regulated. Clinical biopsy samples in sensitized patients with acute ABMR confirmed the dominance of M1 macrophage phenotype in humans. Despite the absence of tubulitis, we were unable to exclude the effects of T cell-mediated rejection. These studies suggest that M1 macrophages and TH 1 cytokines play an important role in the pathogenesis of acute mixed rejection in sensitized allograft recipients.

Nox2 is a mediator of chronic CsA nephrotoxicity.

We hypothesized that Nox2, the classical phagocytic NADPH oxidase, plays an important role in calcineurin inhibitor (CNI)-induced renal fibrosis. We tested this hypothesis in vitro, in animal and in human studies. Cyclosporine A (CsA) and tacrolimus (TAC) were associated with greater levels of Nox2 mRNA and epithelial to mesenchymal transition (EMT) in NRK52E cells. CsA increased Nox2, α-SMA and phosphorylated-p38MAPK, Smad3 and NFκB proteins. Nox2 upregulation and EMT were inhibited in TGF-ß1 knockout cells suggesting that TGF-ß1 is required for Nox2 activation. Fisher344 rats treated with high dose CsA showed increased Nox2 in the tubulointerstitium and greater Nox2, α-SMA, phosphorylated Smad3 and nitrotyrosine by immunoblot analyses. Inhibition of Nox2 by coadministration of apocynin or diphenyleneiodonium was associated with reduced fibrogenesis. We validated these findings by treating wild type and Nox2 null (B6.129S-Cybb(Tm1Din)/J) mice with high dose CsA. Western blot analyses confirmed the absence of Nox2 and significantly lower levels of α-SMA and 4-hydroxynonenal (HNE) in CsA-treated knockout mice. These findings were clinically relevant since Nox2 and α-SMA were increased in the tubulointerstitium of kidneys from 15 liver transplant recipients with biopsy-confirmed chronic CsA or TAC nephrotoxicity. In conclusion, specific Nox2 inhibition strategies may improve chronic CNI nephrotoxicity in solid organ transplantation.

Is the major increase in notified campylobacteriosis in New Zealand real?

Notifications of campylobacteriosis by New Zealand medical practitioners have increased steadily in the last two decades. To determine if this increase is real, as opposed to a surveillance artefact, we examined both available notification (1980-2003) and hospitalization data (1995-2003). The similarity in the temporal pattern of increasing hospitalizations for campylobacteriosis, with that of notifications, is suggestive that this increase is indeed real. Although some risk factors for this disease have been identified (e.g. uncooked poultry consumption) it is unclear what the likely causes of the increasing rates are. The overall disease burden is also high compared with other developed countries (an annual notification rate of 396 cases per 100000 population in 2003), with highest rates in children aged 1-4 years, males, Europeans, and those living in urban areas. Given the large disease burden, further research and intervention studies should be public health priorities in this country.

Tobacco spending and children in low income households.

OBJECTIVE: To examine the role of tobacco use in creating financial hardship for New Zealand (NZ) low income households with children. DATA: The 1996 NZ census (smoking prevalence by household types), Statistics NZ (household spending surveys 1988-98), and NZ Customs (tobacco released from bond 1988-98). MAIN OUTCOME MEASURES: Proportion of children in households with smokers and < or = 15,000 NZ dollars gross income per adult. Proportion of spending on tobacco of second lowest equivalised household disposable income decile and of solo parent households. RESULTS: In < or = 15,000 NZ dollars gross income per adult households with both children and smokers, there were over 90,000 children, or 11% of the total population aged less than 15 years. Enabling second lowest income decile households with smokers to be smoker-free would on average allow an estimated 14% of the non-housing budgets of those households to be reallocated. CONCLUSIONS: The children in low income households with smokers need to be protected from the financial hardship caused by tobacco use. This protection could take the form of more comprehensive government support for such households and stronger tobacco control programmes. A reliance on tobacco price policy alone to deter smokers is likely to have mixed outcomes-for example, increased hardship among some of these households. The challenge for tobacco control is to move from a sole focus on "doing good" towards incorporating the principle of "doing no harm".

Invariant chain can bind MHC class II at a site other than the peptide binding groove.

Invariant chain binds to class II molecules and guides them to the cell surface via the endosomes. Class II-associated invariant chain peptide (CLIP), a conserved sequence in an unstructured region of invariant chain, binds in the peptide binding groove of class II and is thought to be the major contributor to the interaction between invariant chain and class II molecules. However, other interaction sites between the two proteins may exist. The published data on this subject are conflicting. We have studied the ability of invariant chain to interact with a class II molecule in which the peptide binding groove of the protein is already occupied by a covalently attached peptide. Precipitation of these class II/peptide complexes with an Ab specific for this particular combination also precipitates invariant chain. This binding between class II/peptide and invariant chain is weak, and coprecipitation is only apparent in mild detergents. Thus, when the class II peptide binding groove is occluded by peptide and is not free to interact with CLIP, invariant chain can still bind the class II molecule at other lower affinity sites.

Aspartic acid 26 in reduced Escherichia coli thioredoxin has a pKa > 9.

Apparent pKa values of active site residues Asp26, Cys32, and Cys35 in reduced thioredoxin have been characterized. Both wild-type thioredoxin and mutant D26A thioredoxin were selectively 13C-enriched on cysteine beta-carbons. In both proteins, the variation with pH of 1HB1, 1HB2, and 13CB NMR chemical shifts has been measured. In wild-type reduced thioredoxin, for both cysteines, the pH versus chemical shift plots of HB1 protons can be fit to one titration with pKa values of 7.0-7.1. In contrast, the HB2 protons and beta-carbons give pH--chemical shift plots that clearly reflect more than one titration; fits to the data give apparent pKa values of 7.0-7.3 and 9.5 for HB2 protons and 7.5-7.9 and 9.2-10.2 for CB carbons. In reduced D26A, all three probe chemical shifts have a pH dependence that is fit by one titration with pKa of 7.4-7.9. The absence of a titration with pKa > 9 in D26A, taken together with cysteine thiol pKa values of 7.1 and 7.9 determined by Raman spectroscopy [Li et al. (1993) Biochemistry 32, 5800-5808], indicates that the pKa > 9 in reduced thioredoxin is that of Asp26. This is highly significant in view of the previous observation that, in oxidized thioredoxin, Asp26 pKa is 7.5 [Langsetmo et al. (1991) Biochemistry 30, 7603-7609]. The very high pKa values of these carboxyls is consistent with their local environment in the three-dimensional structure; the Asp26 side chain in oxidized thioredoxin is almost but not completely buried, and in reduced thioredoxin it may be even more buried.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of instrumentation on human spinal fusion mass.

STUDY DESIGN: This study is a prospective histomorphometric evaluation of human spinal fusion bone using video dimensional analysis. OBJECTIVES: Little information exists regarding the biology of fusion mass (FM) and the effect that instrumentation has on FM quality. Concerns regarding potential for "stress shielding" of FM with rigid implants have arisen. The goal of this study was to determine what effect spinal implants have on the quality and metabolism of FM bone. METHODS: Fifty-six patients underwent surgeries to remove spinal implants or extend a fusion after pulse-dose labeling with fluorochrome. Twelve patients had undergone fusions without instrumentation. Duplicate biopsies of FM and iliac crest (IC) were obtained and evaluated blindly for mineralized volume, trabecular thickness, mineralization rate, and bone formation rate. Iliac crest, instrumented FM, and noninstrumented FM were compared. RESULTS: Instrumental FM had superior material properties relative to noninstrumented FM or IC. No significant difference in metabolic activity was present. CONCLUSION: Instrumentation does not lead to FM "stress-shielding."

Ectoparasites of a population of urban gray squirrels in northern Florida.

Ectoparasites infesting a population of urban gray squirrels (Sciurus carolinensis Gmelin) in northern Florida were collected monthly during 1974. Eleven species were identified: one flea (Orchopeas howardi (Baker], three suckling lice (Enderleinellus longiceps Kellogg & Ferris, Hoplopleura sciuricola Ferris, and Neohaematopinus sciuri Jancke), one tick (Dermacentor variabilis Say), two mesostigmatid (gamasid) mites (Androlaelaps casalis (Berlese) and A. fahrenholzi (Berlese], and four chiggers (Eutrombicula alfreddugesi (Oudemans), E. splendens (Ewing), Leptotrombidium peromysci Vercammen-Grandjean & Langston, and Parasecia gurneyi (Ewing]. The flea and three suckling lice represent core species of ectoparasites for the gray squirrel; the remainder are probably satellite species. Only E. longiceps varied significantly in prevalence or intensity of infestation among host age groups; subadult squirrels had higher intensities than adults. Peak prevalence of O. howardi occurred in January and attained maximum intensity in March, whereas both prevalance and intensity were minimum in August. Prevalence of H. sciuricola was maximum in November and remained at similar levels through June. It then declined significantly to its minimum in September-October. Intensity of infestation, however, was greatest in August, September, and January. Maximum prevalence of N. sciuri occurred from January to March and was minimum in September; intensity of infestation reached maxima in January, June, and August.

Reservoirs for human campylobacteriosis.

The epidemiology of human enteric infection due to Campylobacter fetus subspecies jejuni is not well understood. To determine whether an endogenous human reservoir is present, the rate of isolation of C. fetus subspecies jejuni from several populations of diarrheal and asymptomatic adults and children were compared. C. fetus subspecies jejuni was recovered from 4.1% of patients with diarrhea and 66.7% of household contacts of the index patients who themselves had diarrhea. Carriage of organisms in most untreated patients lasted less than three weeks from onset of symptoms. C. fetus subspecies jejuni was rarely recovered from the feces of asymptomatic individuals and not at all from the vaginal flora of 272 women. Domestic animals, especially puppies with diarrhea, were frequently infected with Campylobacter and may represent a significant reservoir for human infection.