Search PubMed⌕ Search

Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 19 recordsLinked to original sources
PubMed2006

Recombinant human lactoferrin has a potential to suppresses uterine cervical ripening in preterm delivery in animal model.

OBJECTIVE: To investigate the effect of recombinant human lactoferrin (rhLF) on cervical ripening using a rabbit model in which preterm labor was induced by bacterial endotoxin lipopolysaccharide (LPS). STUDY DESIGN: Timed pregnant rabbits (New Zealand White, 3-4 kg, day 14) were randomly assigned to the following treatment groups: Group A, LPS + rhLF (n = 4); Group B, LPS (n = 4); and Group C, control (n = 4). Recombinant human lactoferrin (10 microg) was administrated to pregnant rabbits in Group A and not in Group B. Lipopolysaccharide (100 microg) was given to the rabbits in both groups for 3 days (days14-16). Drugs were administered as a vaginal suppository. On day 18, the rabbits were anesthetized with intramuscular ketamine hydrochloride (20 mg/kg) and diazepam (4 mg/kg). Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution for a histological study with standard hematoxylin-eosin staining. The other was used for an extension test to assess the grade of ripening. Extension was measured after a 5-mm length of cervical tissue was loaded with 5.8 g. RESULTS: The histological study showed remarkably loose and edematous connective tissue in Group B cervices. Cervical tissues in Group A was not different from those in Group C. Extension lengths were 2.2 +/- 0.2 mm in Group A, 7.0 +/- 2.7 mm in Group B, and 1.7 +/- 0.3 mm in Group C. CONCLUSION: These results suggest that rhLF inhibits cervical maturation induced by LPS in a rabbit model and may have a potential to prevent preterm delivery caused by cervical infection and ripening.

Administration, Intravaginal↗
PubMed2006

The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats.

In the present study, we have attempted to elucidate the effects of the intra-arterial injection of microglia on the global ischemia-induced functional and morphological deficits of hippocampal CA1 neurons. When PKH26-labeled immortalized microglial cells, GMIR1, were injected into the subclavian artery, these exogenous microglia were found to accumulate in the hippocampus at 24 h after ischemia. In hippocampal slices prepared from medium-injected rats subjected to ischemia 48 h earlier, synaptic dysfunctions including a significant reduction of synaptic responses and a marked reduction of long-term potentiation (LTP) of the CA3-CA1 Schaffer collateral synapses were observed. At this stage, however, neither significant neuronal degeneration nor gliosis was observed in the hippocampus. At 96 h after ischemia, there was a total loss of the synaptic activity and a marked neuronal death in the CA1 subfield. In contrast, the basal synaptic transmission and LTP of the CA3-CA1 synapses were well preserved after ischemia in the slices prepared from the microglia-injected animals. We also found the microglial-conditioned medium (MCM) to significantly increase the frequency of the spontaneous postsynaptic currents of CA1 neurons without affecting the amplitude, thus indicating that MCM increased the provability of the neurotransmitter release. The protective effect of the intra-arterial injected microglia against the ischemia-induced neuronal degeneration in the hippocampus was substantiated by immunohistochemical and immunoblot analyses. Furthermore, the arterial-injected microglia prevented the ischemia-induced decline of the brain-derived neurotrophic factor (BDNF) levels in CA1 neurons. These observations strongly suggest that the arterial-injection of microglia protected CA1 neurons against the ischemia-induced neuronal degeneration. The restoration of the ischemia-induced synaptic deficits and the resultant reduction of the BDNF levels in CA1 neurons, possibly by the release of diffusible factor(s), might thus contribute to the protective effect of the arterial-injection of microglia against ischemia-induced neuronal degeneration.

Animals↗
PubMed2006

Dependence of fragmentation behavior of colloidal aggregates on their fractal structure.

The fragmentation dynamics of aggregate of non-Brownian particles in shear flow is investigated numerically. The breakup behaviors of aggregates having the same connectivity but the different space-filling properties are examined. The Lagrangian particle simulation in a linear flow field is performed. The effect of surrounding fluid on the motion of multiple particles is estimated by Stokesian dynamics approach. The inter-particle force is calculated from the retarded van der Waals potential based on the Lifshitz theory. The results obtained in this work indicate that the fragmentation behavior of colloidal aggregates depends on their fractal structure. However, if the resultant aggregate size is smaller than the critical one, the fragmentation behavior shows the universality regardless of their original structure. Furthermore, the restructuring of aggregate in shear flow and its effect on the fragmentation process are also discussed.

Journal Article↗
PubMed2006

Role of cytokines in inflammatory process in Parkinson's disease.

We investigated whether the cytokines produced in activated microglia in the substantia nigra (SN) and putamen in sporadic Parkinson's disease (PD) are neuroprotective or neurotoxic. In autopsy brains of PD, the number of MHC class II (CR3/43)-positive activated microglia, which were also ICAM-1 (CD 54)-, LFA-1 (CD 11a)-, TNF-alpha-, and IL-6-positive, increased in the SN and putamen during progress of PD. At the early stage activated microglia were mainly associated with tyrosine hydroxylase (TH)-positive neurites in the putamen, and at the advanced stage with damaged TH-positive neurons in the SN. The activated microglia in PD were observed not only in the nigro-striatal region, but also in various brain regions such as the hippocampus and cerebral cortex. We examined the distribution of activated microglia and the expression of cytokines and neurotrophins in the hippocampus of PD and Lewy body disease (LBD). The levels of IL-6 and TNF-alpha mRNAs increased both in PD and LBD, but those of BDNF mRNA and protein drastically decreased specifically in LBD, in which neuronal loss was observed not only in the nigro-striatum but also in the hippocampus. The results suggest activated microglia in the hippocampus to be probably neuroprotective in PD, but those to be neurotoxic in LBD. As an evidence supporting this hypothesis, two subsets of microglia were isolated from mouse brain by cell sorting: one subset with high production of reactive oxygen species (ROS) and the other with no production of ROS. When co-cultured with neuronal cells, one microglia clone with high ROS production was neurotoxic, but another clone with no ROS production neuroprotective. On the other hand, Sawada with coworkers found that a neuroprotective microglial clone in a culture experiment converted to a toxic microglial clone by transduction of the HIV-1 Nef protein with increasing NADPH oxidase activity. Taken together, all these results suggest that activated microglia may change in vivo from neuroprotective to neurotoxic subtsets as degeneration of dopamine neurons in the SN progresses in PD. We conclude that the cytokines from activated microglia in the SN and putamen may be initially neuroprotective, but may later become neurotoxic during the progress of PD. Toxic change of activated microglia may also occur in Alzheimer's disease and other neurodegenerative diseases in which inflammatory process is found.

Animals↗
PubMed2006

Endoscopic ultrasound-guided fine-needle aspiration biopsy for lymphadenopathy of unknown origin.

BACKGROUND AND STUDY AIMS: The diagnosis of mediastinal and intra-abdominal lymphadenopathy is sometimes difficult, especially in patients who have no other primary lesions. Lymphoma is one of the main causes of this condition. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and accurate diagnostic procedure for lesions surrounding the gastrointestinal tract. However, diagnosing lymphoma using the EUS-FNA technique remains a diagnostic challenge, due to limitations in the amount of material sampled. The aim of the present study was to evaluate the yield of EUS-FNA biopsy (EUS-FNAB) using a large-gauge needle in patients with mediastinal and intra-abdominal lymphadenopathy of unknown origin, especially in relation to subclassification of the lymphomas. PATIENTS AND METHODS: Consecutive patients with mediastinal and intra-abdominal lymphadenopathy of unknown origin who were referred between October 2003 and March 2005 were enrolled in the study. EUS-FNAB was carried out using a 19-gauge needle, passing through the esophageal, gastric, and duodenal walls. Pathological diagnoses were made on the basis of histological findings, including immunopathological staining. RESULTS: A total of 104 patients were included in the study. The locations of the lymph nodes were mediastinal in 50 patients, intra-abdominal in 48 patients, and both mediastinal and intra-abdominal in six patients. The diagnoses made using EUS-FNAB were lymphoma (n = 48), metastasis (n = 16), and benign/reactive (n = 40). The overall accuracy of EUS-FNAB for unknown lymphadenopathy was 98 %, and it was possible to classify the lymphomas in accordance with the World Health Organization classifications in 88 % of cases. No serious complications occurred with the procedure. CONCLUSIONS: Open thoracic surgery, laparotomy, and other invasive diagnostic procedures such as mediastinoscopy and laparoscopy can now be avoided, as EUS-FNAB is potentially a safe and accurate tool for diagnosing unknown lymphadenopathy, including lymphoma.

Adult↗
PubMed2006

Expression of lactate dehydrogenase-A and -B messenger ribonucleic acids in chick glycogen body.

Glucose is a main metabolic substrate in the central nervous system (CNS). Recently, lactate has attracted renewed attention because it plays an important role in the CNS as a metabolic substrate between neurons and astrocytes. Lactate and lactate dehydrogenase (LDH), a key enzyme for lactate and pyruvate interconversion, have been investigated. The glycogen body (GB) is a gelatinous tissue in the dorsal area of the lumbosacral spinal cord in birds. It is composed of uniform cells with high glycogen storage and is thought to be in the astroglia lineage. In this article, we investigated the LDH enzyme activity in embryo GB (embryonic d 12, 14, 16, 17, and 18) and chickens. To detect the subtype of the LDH, mRNA expressions in GB were investigated and compared with those of cerebral cortex and spinal cord. By histochemical observations, LDH enzyme activity was detected in the cytoplasm of GB cells of all embryonic periods after embryonic d 12. In biochemical analysis, the enzymatic activities of the GB were higher than in the cerebral cortex. In the GB the subtype of LDH mRNA was LDM-B only, and in the cerebral cortex and spinal cord, the subtype of LDH mRNA was predominantly LDH-B, and a small amount of LDH-A was found in the chicken and embryo. The LDH-B mRNA expression in GB was detected during all periods of the study (after embryonic d 12). These observations suggest that GB expressed only LDH-B and that GB cells are not lactate-producing cells, like astrocyte, but rather are lactate-consuming cells, similar to neurons in CNS.

Animals↗
PubMed2005

Cervical inflammatory cytokines and other markers in the cervical mucus of pregnant women with lower genital tract infection.

OBJECTIVE: To evaluate concentrations of interleukin (IL)-6, IL-8, lactoferrin (LF), and alpha defencine (alpha-DF) in the cervical mucus of pregnant women and analyze their relation to cervicitis and bacterial vaginosis (BV). METHODS: Cervical mucus samples were obtained from August 2003 through May 2004 from 157 women who were between the 6th and 36th week of an uncomplicated singleton pregnancy. All women were delivered at term, 69 without BV or cervicitis, 9 with BV, and 79 with cervicitis. RESULTS: Interleukin 8, LF, and mu-DF concentrations were higher in women with cervicitis (0.81 +/- 0.36 pg/mL, 14.8+/-12.3 microg/mL, and 0.60 +/- 0.49 microg/mL) than in women without BV or cervicitis (0.35 +/- 0.34 pg/mL, 8.0 +/- 11.0 microg/mL, and 0.15 +/- 0.12 microg/mL). Interleukin 6 concentration was higher in women with BV (0.26 +/- 0.32 pg/mL) than in women without BV or cervicitis (0.09 +/- 0.15 pg/mL) or in women with cervicitis (0.12 +/- 0.18 pg/mL). CONCLUSIONS: Higher levels of inflammatory cytokines in the cervical mucus of pregnant women may lead to early detection of lower genital tract infection.

Adult↗
PubMed2005

Inhibition of inflammatory cytokine secretion from mouse microglia cells by DHMEQ, an NF-kappaB inhibitor.

Activation of microglia has been implicated in various neurodegenerative disorders, and thus the inhibition of microglial activity may suppress these disorders. Earlier we designed and synthesized an NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) that showed anti-inflammatory and anti-tumor activities in vivo. In the present research, we studied whether DHMEQ would inhibit the activation of mouse microglial cells. DHMEQ inhibited lipopolysaccharide (LPS)-induced activation of NF-kappaB in an electrophoresis mobility shift assay. It also inhibited LPS-induced secretions of TNF-alpha and IL-6 from mouse microglial cell line 6-1 cells.

Animals↗
PubMed2005

Immunohistochemical and ultrastructural findings related to the blood--brain barrier in the blood vessels of the cerebral white matter in aged dogs.

Immunohistochemical and ultrastructural analysis of canine brain tissue was performed to determine whether cerebral capillaries, which form the blood--brain barrier (BBB), display age-related morphological changes in the white matter (WM). A slight decrease in laminin immunolabelling was detected in the basement membranes (BMs) of capillaries in the WM of old dogs, as compared with that in the brains of young dogs. The Prussian blue DAB post-DAB enhancement method detected iron present in macrophages and astrocytes in the WM. Copper/zinc superoxide dismutase, MT-I and -II and MT-III immunoreactivity was detected mainly in reactive astrocytes in the WM of aged dogs. Ultrastructurally, collagen-like fibrils were detected to a variable degree in the spaces between the BMs of capillary endothelial cells and astrocytes in the WM of some aged dogs. These results suggest that age-related morphological changes in capillaries of the WM are associated with BBB dysfunction, leading to the exudation of serum constituents, including harmful substances (e.g., iron), thereby causing tissue damage by oxidative injury. These factors may play a role in the pathogenesis of severe degenerative changes in the WM of aged dogs.

Aging↗
PubMed2005

Renal dysplasia with unilateral renal agenesis in a dog.

This report describes a renal dysplastic lesion associated with renal agenesis in a 3-year-old dog with chronic renal failure. Haematological examination revealed non-regenerative anaemia, azotaemia, increased creatinine and hyperphosphataemia. At necropsy, the right kidney and right ureter could not be identified. The left kidney was slightly enlarged, with a reduced cortico-medullary ratio. Histologically, the medulla of the left kidney had persistent mesenchyme and primitive tubules (tall pseudostratified columnar epithelium), dilated collecting ducts lined by flattened epithelium, and adenomatoid proliferation of cuboidal epithelium; fetal or immature glomeruli could not be identified. To our knowledge, this is the first report of a renal dysplastic lesion with unilateral agenesis in animals.

Animals↗
PubMed2005

Effect of MKC-733, a 5-HT receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study.

BACKGROUND: MKC-733, a 5-HT(3) receptor partial agonist, is a novel enteroprokinetic compound. OBJECTIVE: The aim of this study was to explore the effects of MKC-733 on bowel motility and symptoms in a small group of subjects with constipation. Tolerability was also examined. METHODS: The study was conducted in a single-blind and dose-escalation manner on 14 male and female subjects with constipation aged 22-67 years. After a 1 week run-in period, subjects were treated with placebo (b.i.d.) for 1 week, and 0.2 and 0.5 mg of MKC-733 (b.i.d.) for 2 weeks sequentially. Geometric mean and per cent elimination of surrogate markers of bowel motility were measured by a radio-opaque marker technique at the end of each treatment period. They were analysed on the whole group and subgroups with low (n = 6) and high (n = 8) bowel motility based upon the geometric mean value after placebo treatment. Subjects kept diaries of their bowel habits and gastrointestinal symptoms. RESULTS: Percent elimination increased after treatment with 0.5 mg MKC-733 compared with placebo treatment in the whole group (70.4 +/- 33.5% vs. 47.1 +/- 36.6%, mean +/- SD, P < 0.05). In the low bowel motility group, both geometric mean and percent elimination increased after treatment with 0.5 mg MKC-733 compared with placebo (7.1 +/- 0.9 vs. 5.9 +/- 0.5, P < 0.05; 60.0 +/- 35.8% vs. 13.3 +/- 19.4%, P < 0.05). Stool frequency increased after the first-week treatment with MKC-733 compared with placebo (P < 0.05). Numbers of sensation of incomplete evacuation and gastrointestinal symptoms decreased to half and less after the treatment with MKC-733. No serious adverse effect was noted. CONCLUSION: Multiple doses of 0.5 mg MKC-733 improve bowel motility, which was clearly demonstrated in the subjects with decreased bowel motility. MKC-733 at the doses studied might be effective in increasing stool frequency and reduce gastrointestinal symptoms related to constipation. MKC-733 was well tolerated. Further studies will be needed to clarify efficacy and safety of MKC-733 on a larger population.

Adult↗
PubMed2005

Inflammatory process in Parkinson's disease: role for cytokines.

Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and decreased levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the nigrostriatal region of postmortem brains and/or in the ventricular or lumbar cerebrospinal fluid (CSF) from patients with sporadic PD, and in animal models, such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)- and 6-hydroxydopamine (6-OHDA)-induced PD. These changes in cytokine and neurotrophin levels may be initiated by activated microglia, which may then promote apoptotic cell death and subsequent phagocytosis of DA neurons. Cytokines as pleiotropic factors, promote signals that either lead to cell death or exert neuroprotective effects. The discovery of toxic changes in trophic microglia by M. Sawada and co-workers is important to this point. Ultimately, microglial cells may regulate cellular changes that cause either harm or benefit by producing cytokines or neurotrophins depending upon the primary cause and the circumstances during the inflammatory process of PD.

Animals↗
PubMed2004

Determination of the orbital polarization in YTiO3 by using soft X-ray linear dichroism.

We report measurements of linear dichroism in x-ray absorption at Ti L(2,3) edges of a Mott-insulating ferromagnet YTiO3, where orbital ordering occurs in the triply degenerate Ti 3d t(2g) states. Dichroic spectra and their integrated intensities are obtained for the incident electric field with polarizations parallel to a, b, and c axes. The comparison of the spectra with atomic multiplet calculations removes the ambiguity about the orbital polarization, i.e., the relative weights of |xy>, |yz>, and |zx> orbits, which are crucial for the origin of ferromagnetism. The result is consistent with the previous analysis of nuclear magnetic resonance in the Mizokawa-Fujimori scheme.

Journal Article↗
PubMed2004

Mercury accumulation and its distribution to metallothionein in mouse brain after sub-chronic pulse exposure to mercury vapor.

Previously we found that exposure to mercury vapor effectively induced metallothionein (MT) biosynthesis in rat brain. Although the induction of not only MT-I/II but also MT-III was evident, the induction rate of the latter was much lower than that of the former. The brain of an MT-null mouse lacks MT-I/II, but has MT-III. Here we examined the effects of sub-chronic pulse exposure to mercury vapor on the brain MT in MT-null mice and their wild type controls. MT-null and wild type mice were preliminarily exposed to mercury vapor for 2 weeks at 0.1 mg Hg/m(3) for 1 h/day for 3 days a week, and then exposed for 11 weeks at 4.1 mg Hg/m(3) for 30 min/day for 3 days a week. This exposure caused no toxic signs such as abnormal behavior or loss of body weight gain in the mice of either strain throughout the experimental period. Twenty-four hours after the termination of the exposure, mice were sacrificed and brain samples were subjected to mercury analysis, MT assay, and pathological examination. The MT-null mice showed lower accumulation of mercury in the brain than the wild type mice. Mercury exposure resulted in a 70% increase of brain MT in the wild type mice, which was mostly accounted for by the increase in MT-I/II. On the other hand, the brain MT in the MT-null mice increased by 19%, suggesting less reactivity of the MT-III gene to mercury vapor. Although histochemical examination revealed silver-mercury grains in the cytoplasm of nerve cells and glial cells throughout the brains of both strains, no significant difference was observed between the two strains.

Administration, Inhalation↗
PubMed2004

p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis.

Although the p53 tumor-suppressor gene product plays a critical role in apoptotic cell death induced by DNA-damaging chemotherapeutic agents, human glioma cells with functional p53 were more resistant to gamma-radiation than those with mutant p53. U-87 MG cells with wild-type p53 were resistant to gamma-radiation. U87-W E6 cells that lost functional p53, by the expression of type 16 human papillomavirus E6 oncoprotein, became susceptible to radiation-induced apoptosis. The formation of ceramide by acid sphingomyelinase (A-SMase), but not by neutral sphingomyelinase, was associated with p53-independent apoptosis. SR33557 (2-isopropyl-1-(4-[3-N-methyl-N-(3,4-dimethoxybphenethyl)amino]propyloxy)benzene-sulfonyl) indolizine, an inhibitor of A-SMase, suppressed radiation-induced apoptotic cell death. In contrast, radiation-induced A-SMase activation was blocked in glioma cells with endogenous functional p53. The expression of acid ceramidase was induced by gamma-radiation, and was more evident in cells with functional p53. N-oleoylethanolamine, which is known to inhibit ceramidase activity, unexpectedly downregulated acid ceramidase and accelerated radiation-induced apoptosis in U87-W E6 cells. Moreover, cells with functional p53 could be sensitized to gamma-radiation by N-oleoylethanolamine, which suppressed radiation-induced acid ceramidase expression and then enhanced ceramide formation. Sensitization to gamma-radiation was also observed in U87-MG cells depleted of functional p53 by retroviral expression of small interfering RNA. These results indicate that ceramide may function as a mediator of p53-independent apoptosis in human glioma cells in response to gamma-radiation, and suggest that p53-dependent expression of acid ceramidase and blockage of A-SMase activation play pivotal roles in protection from gamma-radiation of cells with endogenous functional p53.

Apoptosis↗
PubMed2004

Molecular mechanisms of TNF-alpha-induced ceramide formation in human glioma cells: P53-mediated oxidant stress-dependent and -independent pathways.

The present study was designed to examine the roles of p53, reactive oxygen species (ROS), and ceramide, and to determine their mutual relationships during tumor necrosis factor (TNF)-alpha-induced apoptosis of human glioma cells. In cells possessing wild-type p53, TNF-alpha stimulated ceramide formation via the activation of both neutral and acid sphingomyelinases (SMases), accompanied by superoxide anion (O2-*) production, and induced mitochondrial depolarization and cytochrome c release, whereas p53-deficient cells were partially resistant to TNF-alpha and lacked O2-* generation and neutral SMase activation. Restoration of functional p53 sensitized glioma cells expressing mutant p53 to TNF-alpha by accumulation of O2-*. z-IETD-fmk (benzyloxycarbonyl-Ile-Glu-Thr-Asp fluoromethyl ketone), but not z-DEVD-fmk (benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethyl ketone), blocked TNF-alpha-induced ceramide formation through both SMases as well as O2-* generation. Caspase-8 was processed by TNF-alpha regardless of p53 status of cells or the presence of antioxidants. Two separate signaling cascades, p53-mediated ROS-dependent and -independent pathways, both of which are initiated by caspase-8 activation, thus contribute to ceramide formation in TNF-alpha-induced apoptosis of human glioma cells.

Apoptosis↗
PubMed2004

Protective role of metallothionein in acute lung injury induced by bacterial endotoxin.

BACKGROUND: Metallothionein (MT) is a protein that can be induced by inflammatory mediators and participate in cytoprotection. However, its role in inflammation remains to be established. A study was undertaken to determine whether intrinsic MT protects against acute inflammatory lung injury induced by bacterial endotoxin in MT-I/II knock out (-/-) and wild type (WT) mice. METHODS: MT (-/-) and WT mice were given vehicle or lipopolysaccharide (LPS, 125 microg/kg) intratracheally and the cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema, lung histology, expression of proinflammatory molecules, and nuclear localisation of nuclear factor-kappaB (NF-kappaB) in the lung were evaluated. RESULTS: MT (-/-) mice were more susceptible than WT mice to lung inflammation, especially to lung oedema induced by intratracheal challenge with LPS. After LPS challenge, MT deficiency enhanced vacuolar degeneration of pulmonary endothelial cells and type I alveolar epithelial cells and caused focal loss of the basement membrane. LPS treatment caused no significant differences in the enhanced expression of proinflammatory cytokines and chemokines nor in the activation of the NF-kappaB pathway in the lung between the two genotypes. Lipid peroxide levels in the lungs were significantly higher in LPS treated MT (-/-) mice than in LPS treated WT mice. CONCLUSIONS: Endogenous MT protects against acute lung injury related to LPS. The effects are possibly mediated by the enhancement of pulmonary endothelial and epithelial integrity, not by the inhibition of the NF-kappaB pathway.

Animals↗