The effects of 1st and 2nd generation biodiesel exhaust exposure on hematological and biochemical blood indices of Fisher344 male rats - The FuelHealth project.

Diesel exhaust emissions (DEE), being one of the main causes of ambient air pollution, exert a detrimental effect on human health and increase morbidity and mortality related to cardiovascular and pulmonary diseases. Therefore, the objective of the present study was to investigate potential adverse effects of exhausts emissions from B7 fuel, the first-generation biofuel containing 7% of fatty acid methyl esters (FAME), and SHB20 fuel, the second-generation biofuel containing 20% FAME/hydrotreated vegetable oil (HVO), after a whole-body exposure with and without diesel particle filter (DPF). The experiment was performed on 95 male Fischer 344 rats, divided into 10 groups (8 experimental, 2 control). Animals were exposed to DEE (diluted with charcoal-filtered room air to 2.1-2.2% (v/v)) for 7 or 28 days (6 h/day, 5 days/week) in an inhalation chamber. DEE originated from Euro 5 engine with or without DPF treatment, run on B7 or SHB20 fuel. Animals in the control groups were exposed to clean air. Our results showed that the majority of haematological and biochemical parameters examined in blood were at a similar level in the exposed and control animals. However, exposure to DEE from the SHB20 fuel caused an increase in the number of red blood cells (RBC) and haemoglobin concentration. Moreover, 7 days exposure to DEE from SHB20 fuel induced genotoxic effects manifested by increased levels of DNA single-strand breaks in peripheral blood lymphocytes. Furthermore, inhalation of both types of DEE induced oxidative stress and caused imbalance of anti-oxidant defence enzymes. In conclusion, exposure to DEE from B7, which was associated with higher exposure to polycyclic aromatic hydrocarbons, resulted in decreased number of T and NK lymphocytes, while DEE from SHB20 induced a higher level of DNA single-strand breaks, oxidative stress and increased red blood cells parameters. Additionally, DPF technology generated increased number of smaller PM and made the DEE more reactive and more harmful, manifested as deregulation of redox balance.

Relationship between lipophilicity of C6-10 hydrocarbon solvents and their ROS-inducing potency in rat cerebellar granule cells.

We have studied the effects of aliphatic, alicyclic, and aromatic C6-10 solvents on the formation of reactive oxygen species (ROS) in rat cerebellar granule cell cultures. ROS formation was assessed by monitoring oxidation of 2',7'-dichlorofluorescin (DCFH) to the fluorescent compound 2',7'-dichlorofluorescein (DCF). We found that aromatic solvents with C > 7, and aliphatic and alicyclic solvents with C > or = 7 induce ROS formation in rat cerebellar granule cells in vitro. The response increased with increasing solvent concentration. The potency of the compounds within each homologous group seemed to be correlated to their octanol water partition-coefficients. The aromatic solvents were generally less efficient in inducing ROS formation than the aliphatic and the alicyclic compounds.

Toxic effect of L-2-chloropropionate on cultured rat cerebellar granule cells is ameliorated after inhibition of reactive oxygen species formation.

Oral administration of rats to L-2-chloropropionate (L-CPA) causes selective necrosis to the granule cell layer of the cerebellum in vivo and to cultured rat cerebellar granule cells in vitro. The present study was conducted to characterize the involvement of reactive oxygen species (ROS) in cell death of L-CPA to rat cerebellar granule cells in vitro. Exposure to L-CPA (0.625-10 mM) produced a concentration dependent increase in formation of 2,7-dichlorofluorescein (DCF) as a measure of formation of ROS. The elevation of ROS was inhibited after incubation of the cells with the ERK-type of MAP kinases inhibitor U0126, the mitochondrial permeability transition pore inhibitor cyclosporin A (CSA), the antioxidant vitamin E, and the spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN). Measurements of nitrite (NO(2)) in the cell culture supernatant using the Griess reagent indicate generation of nitric oxide (NO) after exposure to L-CPA. Incubation with L-CPA (10 mM) for 48 hr lead to cell death (90%). When the granule cells were incubated with L-CPA in combination with the inhibitors of free radical production, the cell death was ameliorated. The results show that L-CPA is toxic to granular cells by production of ROS.

Importance of soluble metals and reactive oxygen species for cytokine release induced by mineral particles.

The mechanisms for particle-induced health effects are not well understood, but inflammation seems to be of importance. Previously, we have shown that stone quarry particles with various mineral and metal content differed widely in potency to induce inflammatory cytokines (IL-6, IL-8 and TNF-alpha) in different types of lung cells. In this study we investigated if the observed cytokine responses were associated with the soluble or insoluble components of the stone particles and if there was a relationship between the differential cytokine release and generation of reactive oxygen species (ROS). Exposure of the human alveolar cell line A549 to the different particle leachates (pH 7.4 and 4.0) did not induce corresponding differential increases in the IL-8 release as observed with whole particles. Increase in ROS production, measured as dichlorofluorescein-fluorescence, was only demonstrated after exposure of A549 cells to the pH 4.0 extract from basalt. Furthermore, generation of ROS was found in neutrophils but not in A549 cells and primary macrophages after exposure to suspensions of the solid particles. However, no obvious differences in potency among the different particles were demonstrated. In summary, other mechanisms than particle-induced ROS formation seem to be responsible for the differential induction of IL-8. Furthermore, our findings indicate that the differential ability to induce IL-8 release in lung cells is attributed to the solid components of the stone particles.

The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: the involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A.

This study investigated the effects of C7 and C9 aliphatic (n-heptane, n-nonane), naphthenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)) and aromatic (toluene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat brain synaptosome fraction. Methyl mercury (MeHg) was included as a positive control. Exposure of the synaptosomes to the hydrocarbons produced a concentration-dependent linear increase in the formation of the fluorescence of 2',7'-dichlorofluorescein (DCF) as a measure of the production of ROS and RNS. Formation of RNS was demonstrated by preincubation of the synaptosome fraction with the neuronal nitric oxide synthase (nNOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), which reduced the MeHg and TMCH-stimulated fluorescence by 51% and 65%, respectively. The naphthenic hydrocarbon TMCH showed the strongest potential for ROS and RNS formation in rat brain synaptosomes, followed by TMB, toluene, n-nonane, n-heptane, and methylcyclohexane, respectively. TMCH was selected for mechanistic studies of the formation of ROS. Both MeHg and TMCH induced an increase in intracellular calcium concentration [Ca(2+)]i as measured with Fura-2. Blockade of voltage-dependent Ca(2+) channels with lanthanum prior to stimulation with MeHg and TMCH led to a reduction in the ROS/RNS formation of 72% and 70%, respectively. Furthermore, addition of cyclosporin A (CSA), a blocker of the mitochondrial permeability transition pore (MTP), lowered both the MeHg and TMCH-elevated DCF fluorescence by 72% and 59%. Preincubation of the synaptosome fraction with the protein tyrosine kinase inhibitor genistein lowered the MeHg and TMCH-stimulated fluorescence by 85% and 91%, respectively. Addition of the extracellular signal-regulated protein kinase (MEK)-1 and -2 inhibitor U0126 reduced the fluorescence stimulated by MeHg and TMCH by 62% and 63%. Furthermore, the protein kinase C inhibitor bisindolylmaleimide reduced the fluorescence stimulated by MeHg and TMCH by 52% and 56%. The compound 1-(6-[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]-aminohexyl)-1H-pyrrole-2,5-dione (U73122), which inhibits phospholipase C, was shown to decrease the ROS and RNS formation induced by MeHg and TMCH by 49% and 64%, respectively. The phospholipase A2 (PLA2) inhibitor 7,7-dimethyl eicosadienoic acid (DEDA) reduced fluorescence in response to MeHg and TMCH by 49% and 54%. Simultaneous addition of L-NAME, CSA, and DEDA to the synaptosome fraction totally abolished the DCF fluorescence. In conclusion, C7 and C9 aliphatic, naphthenic, and aromatic hydrocarbons stimulated formation of ROS and RNS in rat brain synaptosomes. The naphthenic hydrocarbon TMCH stimulated formation of ROS and RNS in the synaptosomes through Ca(2+)-dependent activation of PLA2 and nNOS, and through increased transition permeability of the MTP. Exposure of humans to the naphthenic hydrocarbon TMCH may stimulate formation of free radicals in the brain, which may be a key factor leading to neurotoxicity.

The effects of aliphatic (n-nonane), naphtenic (1,2, 4-trimethylcyclohexane), and aromatic (1,2,4-trimethylbenzene) hydrocarbons on respiratory burst in human neutrophil granulocytes.

This study investigates the effects of aliphatic (n-heptane, n-nonane), naphtenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)), and aromatic (methylbenzene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on respiratory burst in human granulocytes. The free radical formation was measured as 2,7-dichlorofluorescein diacetate-amplified (DCF) fluorescence, by electron paramagnetic resonance (EPR) spectroscopy and by hydroxylation of 4-hydroxybenzoate. The chemotactic peptide N-formyl-met-leu-phe (fMLP) and phorbol 12-myristate 13-acetate (PMA), a diacylglycerol analogue, were included as positive controls. DCF fluorescence was elevated in a concentration-dependent manner by C9 hydrocarbons. The C7 hydrocarbons did not stimulate respiratory burst in the concentration range examined. The naphtenic hydrocarbon TMCH showed the strongest effect on respiratory burst and was therefore selected for mechanistic studies of this free radical formation. In the absence of extracellular Ca(2+), fluorescence in response to TMCH and fMLP was reduced by 77 and 90%, respectively. Preincubation of the granulocytes with the protein kinase C inhibitor bisindolylmaleimide reduced the DCF fluorescence stimulated with TMCH, fMLP, and PMA by 82, 56, and 90%, respectively. The phospholipase C inhibitor U73122 lowered the TMCH- and fMLP-activated DCF fluorescence by 87 and 76%. In addition, the TMCH- and fMLP-induced DCF fluorescence, after the preincubation with the phospholipase D modulator n-butanol, was lowered by 83 and 52%, respectively. The importance of protein kinase C, phospholipase C, and phospholipase D for elevation of respiratory burst was also demonstrated by the EPR experiments using the spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). Preincubation with the NADPH oxidase inhibitor diphenyleneiodonium and diethyldithiocarbamate, which inhibits superoxide dismutase, led to an almost complete reduction of DCF fluorescence in response to TMCH, fMLP, and PMA. Preincubation with diethyldithiocarbamate led to the elevation of superoxide adducts of DEPMPO. The hydrocarbons stimulated formation of mainly the superoxide (O(*-)(2)) adduct of DEPMPO (DEPMPO-OOH) but also small amounts of the hydroxyl adduct ((*)OH) (DEPMPO-OH). Using 4-hydroxybenzoate as a hydroxyl radical trap confirmed formation of (*)OH after stimulation with the hydrocarbons. In conclusion, our findings indicate that TMCH-activated respiratory burst is dependent on the Ca(2+)-dependent phospholipase C, phospholipase D, and protein kinase C prior to activation of the NADPH oxidase.

Percutaneous drainage of tuberculous abscess of the psoas muscle.

Two cases of tuberculous abscess of the psoas muscle are reported which did not improve with antituberculosis chemotherapy. They were treated by sonographically guided percutaneous drainage through a pigtail catheter, with a successful result.

Squamous cell papilloma of the esophagus: a case report and review of the literature.

Squamous cell papilloma of the esophagus is exceedingly rare. This is the seventh case to be presented since histological verification began in 1959. Clinical, radiographic and microphotographic evidence are presented, together with a survey of the literature.

Mechanical problems in the use of the intra-aortic balloon.

Although there are many complications in the use of the intraortic balloon (IAB) support device, they are relatively benign compared to the benefits of the device. The purpose of this paper is, firstly, to review a protocol in the safe use of this device, and secondly to remind enthusiastic users of the IAB that the use of this method is not always as benign as we would like it to be. Rarely reported findings at postmortem examination in two patients who died in cardiogenic shock are described. The aorta of one of the two cases in this report had a longitudinal tear which involved only the intima and extended from the common femoral artery to well above the renal arteries. In the second case, the balloon tip had entered at the bifurcation of the aorta in a subintimal manner and had re-entered well below the renal arteries, to be relocated in the proper site in the descending aorta.