Effect of maternal diet rich in omega‐6 and omega‐9 fatty acids on the liver of LDL receptor‐deficient mouse offspring

BACKGROUND: Omega‐6 fatty acids are important to fetal development. However, during gestation/lactation, these fatty acids may contribute toward the development of fat tissue. Omega‐9 fatty acids are associated with a reduction in serum lipids and protection from liver disease. OBJECTIVES: The present study investigated the effect of the maternal intake of omega‐6 and omega‐9 in hypercholesterolemic mothers on the liver of the offspring. METHODS: LDL receptor–deficient mice were fed a diet rich in either omega‐6 (E6D) or omega‐9 (E9D) for 45 days prior to mating and until the birth of the offspring, evaluating the effect on the offspring liver in comparison to a standard diet (STD). RESULTS: Mothers fed with the E6D experienced an increase in total cholesterol (TC) and the offspring exhibited an increase in TC, hepatic triglycerides (TG), and CC‐chemokine ligand (CCL)2/monocyte chemoattractant protein (MCP)‐1 as well as a reduction in HDL. Histological analysis on this group revealed steatosis, leukocyte infiltrate, and increased CCL2/MCP‐1 expression. The ultrastructural analysis revealed hepatocytes with lipid droplets and myofibroblasts. The offspring of mothers fed the standard diet exhibited low serum TC, but microvesicular steatosis was observed. The offspring of mothers fed the E9D exhibited lower serum and hepatic TG as well as higher LDL in comparison to the other diets. The histological analyses revealed lower steatosis and leukocyte infiltrate. CONCLUSIONS: The findings suggest that hypercholesterolemic mothers with a diet rich in omega‐6 fatty acids predispose their offspring to steatohepatitis, whereas a diet rich in omega‐9 has a protective effect. Birth Defects Res (Part B) 89:164–170, 2010. © 2010 Wiley‐Liss, Inc.     

Nitrofen induces apoptosis independently of retinaldehyde dehydrogenase (RALDH) inhibition

BACKGROUND: Nitrofen is a diphenyl ether that induces congenital diaphragmatic hernia (CDH) in rodents. Its mechanism of action has been hypothesized as inhibition of the retinaldehyde dehydrogenase (RALDH) enzymes with consequent reduced retinoic acid signaling. METHODS: To determine if nitrofen inhibits RALDH enzymes, a reporter gene construct containing a retinoic acid response‐element (RARE) was transfected into HEK‐293 cells and treated with varying concentrations of nitrofen in the presence of retinaldehyde (retinal). Cell death was characterized by caspace‐cleavage microplate assays and terminal deoxynucleotidyl transferase dUTP nick end‐labeling (TUNEL) assays. Ex vivo analyses of cell viability were characterized in fetal rat lung explants using Live/Dead staining. Cell proliferation and apoptosis were assessed using fluorescent immunohistochemistry with phosphorylated histone and activated caspase antibodies on explant tissues. Nile red staining was used to identify intracellular lipid droplets. RESULTS: Nitrofen‐induced dose‐dependent declines in RARE‐reporter gene expression. However, similar reductions were observed in control‐reporter constructs suggesting that nitrofen compromised cell viability. These observed declines in cell viability resulted from increased cell death and were confirmed using two independent assays. Ex vivo analyses showed that mesenchymal cells were particularly susceptible to nitrofen‐induced apoptosis while epithelial cell proliferation was dramatically reduced in fetal rat lung explants. Nitrofen treatment of these explants also showed profound lipid redistribution, primarily to phagocytes. CONCLUSIONS: The observed declines in nitrofen‐associated retinoic acid signaling appear to be independent of RALDH inhibition and likely result from nitrofen induced cell death/apoptosis. These results support a cellular apoptotic mechanism of CDH development, independent of RALDH inhibition. Birth Defects Res (Part B) 89:223–232, 2010. © 2010 Wiley‐Liss, Inc.     

Relationship between Vehicle Emissions Laws and Incidence of Suicide by Motor Vehicle Exhaust Gas in Australia, 2001–06: An Ecological Analysis

Background

Globally, suicide accounts for 5.2% of deaths among persons aged 15 to 44 years and its incidence is rising. In Australia, suicide rates peaked in 1997 and have been declining since. A substantial part of that decline stems from a plunge in suicides by one particular method: asphyxiation by motor vehicle exhaust gas (MVEG). Although MVEG remains the second most common method of suicide in Australia, its incidence decreased by nearly 70% in the decade to 2006. The extent to which this phenomenon has been driven by national laws in 1986 and 1999 that lowered permissible levels of carbon monoxide (CO) emissions is unknown. The objective of this ecological study was to test the relationship by investigating whether areas of Australia with fewer noxious vehicles per capita experienced lower rates of MVEG suicide.

Methods and Findings

We merged data on MVEG suicides in Australia (2001–06) with data on the number and age of vehicles in the national fleet, as well as socio-demographic data from the national census. Poisson regression was used to analyse the relationship between the incidence of suicide within two levels of geographical area—postcodes and statistical subdivisions (SSDs)—and the population density of pre-1986 and pre-1999 passenger vehicles in those areas. (There was a mean population of 8,302 persons per postcode in the study dataset and 87,413 persons per SSD.) The annual incidence of MVEG suicides nationwide decreased by 57% (from 2.6 per 100,000 in 2001 to 1.1 in 2006) during the study period; the population density of pre-1986 and pre-1999 vehicles decreased by 55% (from 14.2 per 100 persons in 2001 to 6.4 in 2006) and 26% (from 44.5 per 100 persons in 2001 to 32.9 in 2006), respectively. Area-level regression analysis showed that the suicide rates were significantly and positively correlated with the presence of older vehicles. A percentage point decrease in the population density of pre-1986 vehicles was associated with a 6% decrease (rate ratio [RR] = 1.06; 95% confidence interval [CI] 1.05–1.08) in the incidence of MVEG suicide within postcode areas; a percentage point decrease in the population density of pre-1999 vehicles was associated with a 3% decrease (RR = 1.03; 95% CI 1.02–1.04) in the incidence of MVEG suicide.

Conclusions

Areas of Australia with fewer vehicles predating stringent CO emission laws experience lower rates of MVEG suicide. Although those emission laws were introduced primarily for environmental reasons, countries that lack them may miss the benefits of a serendipitous suicide prevention strategy. Please see later in the article for the Editors'' Summary     

Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study

Background

There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.

Methods and Findings

A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.

Conclusions

The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous. Please see later in the article for the Editors'' Summary     

Western diet leads to aging-related tumorigenesis via activation of the inflammatory,UPR, and EMT pathways

Among the principal causative factors for the development of complications related to aging is a diet rich in fats and sugars, also known as the Western diet. This diet advocates numerous changes that might increase the susceptibility to initiate cancer and/or to create a tissue microenvironment more conducive to the growth of malignant cells, thus favoring the progression of cancer and metastasis. Hypercaloric diets in general lead to oxidative stress generating reactive oxygen species and induce endoplasmic reticulum stress. Our results demonstrate that mice bearing tumors fed with a Western diet presented bigger tumor mass with increased insulin sensitivity in these tissues. Several markers of insulin signaling, such as AKT phosphorylation and mTOR pathway, are promoted in tumors of Western diet-fed animals. This process is associated with increased macrophage infiltration, activation of unfolded protein response pathway, and initiation of epithelial–mesenchymal transition (EMT) process in these tumor tissues. Summing up, we propose that the Western diet accelerates the aging-related processes favoring tumor development.Subject terms: Melanoma, TOR signalling, Mechanisms of disease, Ageing     

Studies on parasitic castration: Aminopeptidase activity levels and protein concentrations in Ilyanassa obsoleta (mollusca) parasitized by larval trematodes

Specimens of the estuarine prosobranch Ilyanassa obsoleta collected in the vicinity of Charleston, South Carolina, during June, July, and August 1981, were found to be parasitized by larvae of the digeneans Cercaria dipterocerca, Himasthla quissetensis, Lepocreadium setiferoides, Microbilharzia variglandis, Microphalloides nassicola, Stephanostomum tenue, and Zoogonus lasius. The aminopeptidase activity levels and the total protein concentrations of the hemocytes and sera of these infected snails were determined. It was ascertained that snails parasitized by larvae of L. setiferoides had significantly higher levels of hemocytic aminopeptidase activity and hemocytic total protein concentrations than noninfected snails. Furthermore, snails parasitized by L. setiferoides larvae had significantly higher hemocytic levels of aminopeptidase activity than snails parasitized by larvae of S. tenue, Z. lasius, M. nassicola, and H. quissetensis.     

Rare extra-pair fertilizations in the semi-colonially breeding linnet Carduelis cannabina

Microsatellite analysis was used to analyse the level of extra-pair paternity (EPP) in the semi-colonially breeding linnet Carduelis cannabina in Denmark. During the breeding seasons of 1998 and 1999 EPP accounted for only 3.8% of young (4/106, 95% CL=1–13%). These extra-pair young were found in 9.1% of the broods (2/22, 95% CL=1–29%). We hypothesize that this low level of EPP is due to an efficient use of both mate guarding and frequent copulations as paternity guards. However, experimental tests with temporary detainment of males would be needed to establish whether there is a causal relationship between the low EPP level and the double paternity guard.     

Criteria for Patient Selection and Multidisciplinary Evaluation and Treatment of the Weight Loss Surgery Patient

Objective: To provide evidence‐based guidelines for patient selection and to recommend the medical and nutritional aspects of multidisciplinary care required to minimize perioperative and postoperative risks in patients with severe obesity who undergo weight loss surgery (WLS). Research Methods and Procedures: Members of the Multidisciplinary Care Task Group conducted searches of MEDLINE and PubMed for articles related to WLS in general and medical and nutritional care in particular. Pertinent abstracts and literature were reviewed for references. Multiple searches were carried out for various aspects of multidisciplinary care published between 1980 and 2004. A total of 3000 abstracts were identified; 242 were reviewed in detail. Results: We recommended multidisciplinary screening of WLS patients to ensure appropriate selection; preoperative assessment for cardiovascular, pulmonary, gastrointestinal, endocrine, and other obesity‐related diseases associated with increased risk for complications or mortality; preoperative weight loss and cessation of smoking; perioperative prophylaxis for deep vein thrombosis and pulmonary embolism (PE); preoperative and postoperative education and counseling by a registered dietitian; and a well‐defined postsurgical diet progression. Discussion: Obesity‐related diseases are often undiagnosed before WLS, putting patients at increased risk for complications and/or early mortality. Multidisciplinary assessment and care to minimize short‐ and long‐term risks include: comprehensive medical screening; appropriate pre‐, peri‐, and postoperative preparation; collaboration with multiple patient care disciplines (e.g., anesthesiology, pulmonary medicine, cardiology, and psychology); and long‐term nutrition education/counseling.