The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis.

Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice.

Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS.

Domoic acid is an algal-derived seafood toxin that functions as a glutamate agonist and exerts excitotoxicity via overstimulation of glutamate receptors (AMPA, NMDA) in the central nervous system (CNS). At high (symptomatic) doses, domoic acid is well-known to cause seizures, brain lesions and memory loss; however, a significant knowledge gap exists regarding the health impacts of repeated low-level (asymptomatic) exposure. Here, we investigated the impacts of low-level repetitive domoic acid exposure on gene transcription and mitochondrial function in the vertebrate CNS using a zebrafish model in order to: (1) identify transcriptional biomarkers of exposure; and (2) examine potential pathophysiology that may occur in the absence of overt excitotoxic symptoms.

The glutathione synthesis gene Gclm modulates amphiphilic polymer-coated CdSe/ZnS quantum dot-induced lung inflammation in mice.

Quantum dots (QDs) are unique semi-conductor fluorescent nanoparticles with potential uses in a variety of biomedical applications. However, concerns exist regarding their potential toxicity, specifically their capacity to induce oxidative stress and inflammation. In this study we synthesized CdSe/ZnS core/shell QDs with a tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) (TOPO-PMAT) coating and assessed their effects on lung inflammation in mice.

A randomized cross-over study of inhalation of diesel exhaust, hematological indices, and endothelial markers in humans.

Background: Exposure to traffic-related air pollution (TRAP) is considered a trigger for acute cardiovascular events. Diesel Exhaust (DE) is a major contributor to TRAP in the world. We evaluated the effect of DE inhalation on circulating blood cell populations, hematological indices, and systemic inflammatory cytokines in humans using a specialized facility.

Mild passive focal cooling prevents epileptic seizures after head injury in rats.

Objective: Post-traumatic epilepsy is prevalent, often difficult to manage, and currently cannot be prevented. Although cooling is broadly neuroprotective, cooling-induced prevention of chronic spontaneous recurrent seizures has never been demonstrated. We examined the effect of mild passive focal cooling of the perilesional neocortex on the development of neocortical epileptic seizures after head injury in the rat.

A pilot study of the association between genetic polymorphisms involved in estrogen signaling and infant male genital phenotypes.

Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families.

Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice.

Context: Inhalation of ambient fine particulate matter (PM₂.₅) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM₂.

DIESEL particulate exposed macrophages alter endothelial cell expression of eNOS, iNOS, MCP1, and glutathione synthesis genes.

There is considerable debate regarding inhaled diesel exhaust particulate (DEP) causing impairments in vascular reactivity. Although there is evidence that inhaled particles can translocate from the lung into the systemic circulation, it has been suggested that inflammatory factors produced in the lung following macrophage particle engulfment also pass into the circulation. To investigate these differing hypotheses, we used in vitro systems to model each exposure.

The effect of progesterone dose on gene expression after traumatic brain injury.

Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10 mg/kg or 20 mg/kg given i.

Mammalian cytochrome CYP2E1 triggered differential gene regulation in response to trichloroethylene (TCE) in a transgenic poplar.

Trichloroethylene (TCE) is an important environmental contaminant of soil, groundwater, and air. Studies of the metabolism of TCE by poplar trees suggest that cytochrome P450 enzymes are involved. Using poplar genome microarrays, we report a number of putative genes that are differentially expressed in response to TCE.

Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk.

Background: This study investigated whether single nucleotide polymorphisms (SNP) in genes within the catechol estrogen metabolism pathway altered the risk of breast cancer alone or in combination, as well as whether menopausal hormone therapy modified the effect of these SNPs on breast cancer risk.

Methods: In a population-based case-control study of breast cancer, 891 cases and 878 controls were genotyped for six functional SNPs in the COMT, CYP1B1, GSTM1, GSTP1, and GSTT1 genes.

Results: Women homozygous with the T allele in CYP1B1*2 (Ser(119); rs1056827) were at 1.

Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC.

Cholecystokinin C-45T polymorphism and smoking cessation in women.

In view of the effect of cholecystokinin (CCK) on dopaminergic neurons in the mesolimbic "reward" pathway of the brain, its gene has been a focus in studies of dopamine-related conditions and behaviors, including smoking. We assessed the association between the CCK C-45T polymorphism and smoking cessation among women who participated in a randomized clinical trial of d,l-fenfluramine conducted in the Seattle area in 1993-1994. Several years later (Mdn = 3.

Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population.

Objective: To evaluate the association of VKORC1 genetic variants with warfarin dose requirements in a Hong Kong Chinese patient population.

Methods: A retrospective study of Hong Kong Chinese patients chronically maintained on warfarin was conducted. Single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 were genotyped.