Development of the lipolytic activity in isolated perfused perinatal rabbit lungs and the influence of maternal cigarette smoke exposure on it

The ability of the lungs to release fatty acids from circulating triglycerides or lipoproteins for its own phospholipid synthesis may be one of the factors which limit the rate of surfactant formation. Therefore, the development of the lipolytic activity of lungs obtained from late fetal and neonatal rabbits has been studied and the results correlated to the phospholipid content of lungs of similar ages. Isolated lungs were perfused with a medium which contained cold and radioactive triglyceride, and the release of fatty acids into the perfusion medium was analyzed by both colorimetric and radiochemical methods. The phospholipids of the postmitochondrial supernatant fractions of the lungs were extracted and quantified by measuring inorganic phosphorus. Finally, the influence of maternal cigarette smoke exposure on the lipolytic activity of the lungs of their litters were studied. A high lipolytic activity in the lungs of 28-day-old fetuses was detected. The activity decreased towards birth, and was lowest on the first day after birth (about 20% of that observed in 28-day-old fetuses). However, it increased again during the first week after birth. Exposure of the mothers to cigarette smoke during the last 10 days before delivery did not affect the pulmonary lipolytic activity of the offspring. Although the lung phospholipid content increased 3.6-fold from 28 days of fetal life to 1 week after birth, it remained unchanged on the days when the lung lipolytic activity was lowest. We conclude that changes in lung lipolytic activity influence lung phospholipid synthesis, and consequently influence also surfactant formation in the lungs.     

Identification of PKCalpha isoform-specific effects in cardiac myocytes using antisense phosphorothioate oligonucleotides

Members of the mammalian protein kinase C (PKC) superfamily play key regulatory roles in multiple cellular processes. In the heart, PKC signaling is involved in hypertrophic agonist-induced gene expression and hypertrophic growth. To investigate the specific function of PKC signaling in regulating cardiomyocyte growth, we used antisense oligonucleotides to inhibit PKC alpha, the major isozyme present in the neonatal heart. Transfection of cultured neonatal cardiomyocytes with antisense PKCalpha oligonucleotides resulted in a marked reduction in both PKCalpha mRNA and protein levels. PKCalpha antisense treatment also reduced phenylephrine (PE)-induced PKC activity and perinuclear translocation of PKCalpha. Antisense inhibition of PKCalpha led to reduction of PE-induced increase in skeletal alpha-actin mRNA levels and atrial natriuretic peptide (ANP) secretion but had no significant effects on PE-induced beta-myosin heavy chain, ANP, or B-type natriuretic peptide (BNP) gene expression. On the other hand, antisense PKCalpha treatment attenuated endothelin-1-induced increase in ANP and BNP peptide secretion, whereas endothelin-1-induced gene expression of ANP and BNP remained unchanged. The hypertrophic agonist-induced growth of cardiomyocytes, characterized by increased [(3)H]leucine incorporation, was not affected with antisense PKCalpha treatment. Furthermore, we found that PE-induced increase in extracellular signal-regulated kinase (ERK) activity was partially inhibited by antisense PKCalpha treatment, implicating ERK as a downstream mediator for PKCalpha signaling. These results indicate that PKCalpha isozyme is involved in hypertrophic signaling in cardiomyocytes and provide novel strategies for future studies to identify other cellular targets controlled selectively by PKCalpha or other PKC isozymes.     

Dense innervation in pseudocapsular tissue compared to aneural interface tissue in loose totally replaced hips

BACKGROUND: The function of many inflammatory cells is in part regulated by neuronal cells, which may lead to so-called neurogenic inflammation. Sensory nerves also mediate the pain sensation. METHODS: This immunohistochemical study focused on visualization of C-sensory and sympathetic innervation in the synovial membrane-like interface and pseudocapsular tissue around loosened total hip replacement. RESULTS: The synovial membrane-like interface did not contain C-sensory peptidergic or sympathetic neural structures. Only limited attempts to neural regeneration were detected. In contrast, pseudocapsule expressed dense innervation with strong CPON-ir sympathetic innervation and osteoarthritis also had C-sensory fibers. Intense neural regeneration was seen in these synovial membranes. Surprisingly, stellate and/or highly dendritic fibroblast-like cells in the fibrotic areas in the interface tissue expressed strong immunoreactivity to the neural marker PGP 9.5, ubiquitin carboxyterminal hydrolase. CONCLUSION: Pain related to aseptic loosening cannot arise in the aneural interface membrane. Inflammation in interface/aseptic loosening seems to be driven by non-neurogenic factors, such as foreign bodies and micromovement. Insufficient lysosomal degradation of denatured proteins causes accumulation of ubiquitinated conjugates and enzymes involved in the process. This leads to insufficient degradation of platelet derived growth factor (PDGF)-receptor complex and can contribute to the accumulation of connective tissue in the interface. Failure in ubiquitin mediated proteolysis might support overgrowth of interface tissue and aseptic loosening.     

MR perfusion, diffusion and BOLD imaging of methotrexate-exposed swine brain

PURPOSE: To evaluate the methotrexate (MTX)-exposed swine brain, functional magnetic resonance imaging (MRI), including perfusion, diffusion, and blood-oxygen-level-dependent (BOLD) contrast imaging, was used. MATERIAL AND METHODS: Juvenile pigs received either 2 x 5 g/m(2), or 5 x 2 g/m(2) MTX intravenously within one month. MRI was performed (sedative: propofol) before (14-17 kg, N = 6) and after (21-27 kg, N = 4) the MTX exposure. Also, age-matched controls (22-27 kg, N = 4) were imaged. RESULTS: After the MTX exposure, reduced (from 2%-4% to 0%-1%) or negative (-2% to -3%) BOLD responses were detected; apparent diffusion coefficient (ADC) or relative perfusion values did not change. CONCLUSION: This study suggests that MTX-related changes in the brain may be detected as changes in flow-metabolism coupling as reduced or negative response (for somatosensory activation) in the BOLD contrast MRI. The contrast agent perfusion MRI, without absolute quantification, may not show global damage in brain perfusion related to the MTX exposure in the swine model used. ADC (in one direction) may not indicate MTX-related changes in the brain.     

First report of saxitoxin in Finnish lakes and possible associated effects on human health

This study is the first report of saxitoxin in cyanobacterial blooms in Finland. Bloom samples (n = 50) were collected from Finnish freshwater sites during summer months of 2002 and 2003. These samples were screened for the presence of paralytic shellfish toxins (PSTs) using the Jellett rapid PSP screening test. Samples testing positive for PSTs (n = 7) were further analyzed with saxiphilin- and voltage-gated sodium channel [(3)H]-STX-binding radioreceptor assays and liquid chromatography using fluorescence and mass spectrometric analysis. The results indicated that saxitoxin (STX) was the only PST analogue in the samples and that it was present in high concentrations, as much as 1 mg L(-1). Microscopic analysis revealed that 95%-100% of the phytoplankton in the positive samples consisted of Anabaena lemmermannii. The trophic status of lakes in which STX-containing blooms were found varied from oligotrophic to hypertrophic. All the lakes had high nitrogen-to-phosphorus ratios. In some instances, samples had been collected from sites where swimmers had reported adverse health effects, and in three such cases, reported adverse health effects were associated with sites from which samples testing positive for STX had been received. Symptoms of fever, eye irritation, abdominal pains, and skin rash were reported in children aged 2-10 years after exposure to the water. These were not the adverse human symptoms typical of STX poisoning; rather, they represented acute effects often reported following recreational exposure to cyanobacterial blooms.     

Enhanced peroxisomal beta-oxidation of fatty acids and glutathione metabolism in rats exposed to phenoxyacetic acids

Peroxisomal beta-oxidation of fatty acids and the activities of glutathione-metabolizing enzymes in rat liver were measured after administration of 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), clofibrate [ethyl], 2-(p-chlorophenoxy)-2-methylpropionate], glyphosate (N-phosphonomethyl glycine, a herbicide not structurally related to phenoxy acids) or saline for 14 days. beta-Oxidation increased by 6-fold in the group given clofibrate, 3-fold in the 2,4-D-treated group, and 2-fold in the MCPA-treated group over the level in the controls (saline-treated). Glyphosate did not increase beta-oxidation. No significant change in reduced glutathione content from that in controls was found in any of the treated groups. Glutathione reductase activity increased by about 40% after administration of either 2,4-D or MCPA, and glutathione peroxidase activity increased by 30% in animals given MCPA. A slight decrease in glutathione S-transferase activity was found in the group treated with clofibrate. The marked increases in peroxisomal beta-oxidation of fatty acids were accompanied by only minor changes in the activities of enzymes involved in glutathione-dependent inactivation of organic hydroperoxides and other oxygen-centred reactive agents.     

Time-sharing strategies in driving after various cerebral lesions

Primary objective: To analyse time-sharing strategies in patients with cerebral lesions when they performed everyday in-car tasks in real-life highway driving. Research design: A case-control study. Methods and procedures: Thirteen male patients with brain damage and 11 healthy controls participated. The frequency and duration of glances at the in-car tasks, total time of eyes-off the road during tasks, speed and lateral displacement of the car were recorded. Main outcomes and results: Long glances away from the road and consequent large lateral displacements were characteristic for patients with anterior damage, while the patients with more posterior lesions used frequent short glances at the in-car task. Conclusion: Two different time-sharing strategies that appeared to be related to different aetiology were found in the patients, indicating different control of the driving task. It is proposed that standardized on-road dual tasks should be used for detecting problems in allocation of attention during driving.     

Biotransformational and neurophysiological changes in rabbits exposed to lead

Lead was administered to adult male rabbits in drinking water at a 0.1% concentration for four and five week periods. The lead contents were determined in the central and peripheral nervous tissues and in the liver, kidney, and intestinal mucosa. The conduction velocity of sciatic nerve and the activities of drug metabolizing enzymes in other tissues were determined. The lead concentration in the blood was at a steady state at four to five weeks of exposure. Lead accumulated in all tissues except the brain. The brain lead concentration was 40 to 50% of that in the blood, indicating the existence of a blood-brain barrier. However, the lead concentration in the sciatic nerve increased significantly from four to five weeks of exposure and exceeded that in the blood. This indicates the lack of a blood-nervous tissue barrier in the sciatic nerve allowing a continuous accumulation of lead. This accumulation affected the function of the sciatic nerve; motor nerve conduction velocity decreased from the control level (58.3±7.4 m/sec) to 43.8±6.3 m/sec after the four-week exposure and to 35.0 ± 1.3 m/sec at 5 weeks of exposure. After five weeks of exposure, no changes in the hepatic, intestinal, or renal drug metabolizing enzyme activites were found. These results suggest that motor nerve conduction velocity is affected by lead exposure prior to any influence on biotransformation enzymes.     

Lack of effect of central nervous system-active doses of nabilone on capsaicin-induced pain and hyperalgesia

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