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Biomedical subjects

M H Li

Publications and source records attributed to M H Li.

At least 55 records · Page 3Linked to original sources

Toxicokinetics of 2,2',4,4'- and 3,3',4,4'-tetrachlorobiphenyl congeners in the house cricket.

Recently, investigators have reported bioaccumulation of polychlorinated biphenyls (PCBs) in insects collected at hazardous waste sites. Little is known about differences in bioaccumulation of particular PCB congeners in insects. The authors report on the toxicokinetics of a non-coplanar ortho substituted congener, 2,2',4,4'-tetrachlorobiphenyl (PCB-47) and a coplanar non-ortho substituted PCB, 3,3',4,4'-tetrachlorobiphenyl (PCB-77) in topically treated house crickets. Penetration and excretion were more rapid for PCB-47 than for PCB-77. PCB-47 demonstrated a high affinity for abdomen, gut, and gonads, whereas, PCB-77 had a greater affinity for the head and thorax. Sex differences were observed in excretion and distribution. Females had an increased excretion of PCBs and increased accumulation in gut and gonads compared to males. Differences in lipophilicity can explain differences in distribution between sexes and of compounds within sexes. However, to explain the observed difference in penetration, it is necessary to invoke explanations based on stearic factors associated with coplanarity of the molecules. Differences in excretion are likely related to sex differences in mixed-function oxidase activities. These toxicokinetic data suggest that the more toxic coplanar congener, PCB-77, is likely to be more persistent in crickets compared to PCB-47, despite its lower lipophilicity.

Abdomen↗

Dimethylthiourea ameliorates acute lung injury induced by phorbol myristate acetate in dogs.

BACKGROUND AND METHODS: The protective effects of dimethylthiourea, a potent scavenger of hydroxy radical (.OH) and hydrogen peroxide, in experimental lung injury in large animals remain controversial. The present study was designed to determine whether dimethylthiourea can ameliorate the acute lung injury produced in dogs by phorbol myristate acetate. Six dogs were infused with dimethylthiourea (0.75 g/kg in saline) for 1.5 hrs, beginning 1 hr before an i.v. bolus injection of phorbol myristate acetate (17 micrograms/kg); six dogs received phorbol myristate acetate (17 micrograms/kg) alone; and six dogs were infused with saline alone. Hemodynamic changes, arterial oxygenation, and the development of lung edema were monitored for 4 hrs after phorbol myristate acetate injection to assess the extent of lung damage. RESULTS: As compared with the dogs that received phorbol myristate acetate alone, the edematous lung damage was significantly reduced in those dogs that received dimethylthiourea as well as phorbol myristate acetate. In the dimethylthiourea-treated dogs, the lung wet/dry weight ratios were smaller (p less than .01); protein concentrations in lung lavage fluid were lower (p less than .01); the decrease in PaO2 was significantly reduced (p less than .01); and there were significant reductions in the alveolar-arterial oxygen tension difference (P[A-a]O2) (p less than .01) and shunt (Qsp/Qt) (p less than .05). Also, dimethylthiourea significantly lowered the increased mean pulmonary arterial pressure levels during the second half of the experiment. CONCLUSIONS: These experimental data suggest that dimethylthiourea is capable of reducing the neutrophil-mediated lung injury produced by the release of hydroxy radical and/or hydrogen peroxide in dogs exposed to phorbol myristate acetate.

Acute Disease↗

Air embolism-induced lung injury in isolated rat lungs.

Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10-0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5-8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O-1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

MR imaging of intradural extramedullary tumors.

Thirty-one consecutive intradural extramedullary spinal tumors examined with MR at 0.3 T were reviewed. In 13 of the patients myelography had been performed. There were 11 patients with meningeoma, 14 with neuroma, one ependymoma, 3 metastases, and 2 lipomas. All tumors were surgically removed and verified by histology. The intradural extramedullary location of the tumors was accurately assessed by MR imaging in all patients and by myelography in 10 of 13. The MR diagnoses were in accordance with the histologic findings in 74% of cases. Compression of the spinal cord or cauda equina with widening of the subarachnoid space above and below the mass or outward displacement of epidural fat was characteristic of the intradural extramedullary tumors. The signal intensity of meningeoma as well as of neuroma was slightly lower or equal to that of the cord on T1-weighted images, and equal to or higher than cord signal on T2-weighted images. Neuroma had a lower signal intensity on T1-weighted images and a higher signal intensity on T2-weighted images than meningeoma. Meningeoma appeared more homogeneous than neuroma and had a broad base towards the dura.

Adolescent↗

MR imaging of spinal lymphoma.

Fourteen patients with spinal lymphoma examined by MR imaging were reviewed. Thirteen of them also had extraspinal lymphoma. Vertebral involvement was found in 12 patients, epidural in 10, and paraspinal in 8 patients. On the basis of MR imaging at 0.3 T, spinal lymphoma may be divided into three types of growth pattern according to the main location: paraspinal, vertebral, and epidural. Most frequently, all three locations were found simultaneously on MR (7/14). In one patient the location was vertebral with epidural extension, in one paraspinal with vertebral extension, in 3 it was entirely vertebral, and in 2 entirely epidural. Multiple plane T1-weighted imaging gave complete information about the extent of spinal lymphoma. The signal intensity was lower than or equal to muscle and lower than bone marrow in paraspinal and vertebral lesions on T1-weighted images and high on T2-weighted images. Epidural lesions showed a hypo- or isointense signal relative to the cord on T1-weighted images except in one case and a hyperintense signal on T2-weighted images. Compression of the cord and cauda equina due to bulging of diseased vertebral bodies and epidural lesions was well demonstrated. MR imaging was also found useful in the follow-up of treatment.

Adult↗

MR imaging of spinal intramedullary tumors.

The MR examinations in 25 patients with intramedullary tumors were analyzed. Seven patients were diagnosed with astrocytoma, 6 ependymoma, 2 unspecified glioma, 3 medulloblastoma, 2 metastasis, one neurinoma, and one teratoma. In 3 patients the diagnosis was uncertain. The tumors frequently involved a large portion of the cord and were often accompanied by intratumor necrosis, cystic degeneration, and edema, which was well demonstrated on MR. Gd-DTPA was used in 6 patients and was helpful in separating solid tumor components from cysts and edema. It was difficult to separate different kind of tumors based on morphologic and signal characteristics on MR. Some prominent features could, however, be distinguished. Complete cystic degeneration was more common in astrocytomas than in other tumors, and ependymomas frequently had a heterogeneous signal pattern on both T1- and T2-weighted sequences. The single teratoma had a characteristic content of fat and calcification, and the melanoma had a signal pattern consistent with blood. CSF pathway spread in cases of medulloblastoma was demonstrated by ill-defined contour of the cord and CSF or tumor nodules on the surface of cord and nerve roots.

Adolescent↗

MR imaging of spinal neurofibromatosis.

The MR findings in 7 patients with neurofibromatosis involving the spine were evaluated. Six patients had paraspinal tumors at multiple levels. In 4 they were bilateral. Five patients had multiple intraspinal lesions, frequently with growth through the neural foramen. In one patient paraspinal tumors were found in the lumbar sacral plexus and in another bony dysplasia and meningoceles but no tumors were disclosed. In 2 patients the lesions were associated with bilateral acoustic neuromas and multiple intracranial meningeomas. In one of these a spinal meningeoma with signal characteristics close to spinal cord was found. The other tumors had a signal that was equal to or slightly lower than the spinal cord and slightly higher than muscle on T1-weighted images. On T2-weighted images the tumors had a markedly increased signal compared to surrounding tissue. In 3 patients with tumors larger than 4 cm the signal intensity was inhomogeneous with decreased signal in the center on T2-weighted images, indicating the presence of increased fibrous tissue. Gadolinium-DTPA was given to one patient with marked increase in intensity of small tumors on T1-weighted images. The study shows that MR imaging is the modality of choice for evaluating most aspects of spinal and paraspinal neurofibromatosis.

Adolescent↗

[Isolation and identification of two new pyrone compounds from the culture of Herictum erinaceus].

Four crystalline and one liquid compounds were isolated from the solid cultured extract of Hericium erinaceus, Two of them are new, named herein III and IV. Their chemical structures were determined as 6-methyl-2,5-dihydroxymethyl-gamma-pyranone (III) and 2-hydroxymethyl-5-alpha-hydroxy-ethyl-gamma-pyranone (IV). The others are 4-chloro-3,5-dimethoxybenzoic-O-arabitol ester, 4-chloro-3,5-dimethoxybenzoic methyl ester and 4-chloro-3,5-dimethoxybenzoic acid. In addition, a mixture of palmic and stearic acid, a mixture of behenic acid and tetracosanic acid and a mixture of 5 alpha-ergostan-3-one, 5 alpha-stigmasten-22-en-3-one and 5 alpha-stigmastan-3-one were also isolated.

Basidiomycota↗

Dimethylthiourea decreases acute pulmonary edema induced by phorbol myristate acetate in isolated blood-perfused lung of the rat.

Acute pulmonary edema can be induced by phorbol myristate acetate (PMA). Oxygen radicals released from the neutrophils have been considered to play an important role in the pathogenesis of PMA-induced pulmonary edema. In the present experiment, we studied the effect of dimethylthiourea (DMTU) on PMA-induced pulmonary injuries in isolated perfused lungs of rats. DMTU is a potent scavenger of the hydroxyl radical and hydrogen peroxide. PMA infusion into the isolated lung increased pulmonary arterial pressure (delta PAP) by 37.8 +/- 3.9 mmHg. The lung weight gain (LWG) and lavage albumin concentration (LAC) amounted to 6.2 +/- 1.2 g and 102.0 +/- 22.9 mg/dl, respectively. DMTU (100 mM) pretreatment significantly reduced the PAP increase (delta PAP = 4.6 +/- 0.8 mmHg, p less than 0.001), LWG (0.3 +/- 0.1 g, p less than 0.01) and LAC (25.3 +/- 1.7 mg/dl, p less than 0.01). Additional in vitro experiments demonstrated that DMTU depressed the chemiluminescence released from neutrophils activated by PMA (17.9 +/- 2.6 mV.min to 2.6 +/- 0.5 mV.min, p less than 0.01). The results suggest that DMTU, a scavenger of toxic radicals, decreases the lung edema through both attenuation of pulmonary hypertension and protection of vascular permeability from PMA injury.

Acute Disease↗

Metabolism of fusarin C by rat liver microsomes. Role of esterase and cytochrome P-450 enzymes with respect to the mutagenicity of fusarin C in Salmonella typhimurium.

Fusarin C (FC) is a potent mutagen present on Fusarium moniliforme contaminated corn. This compound requires metabolic activation for which microsomes from phenobarbital-induced rats are most effective. Inhibition of the simultaneously induced esterase activity, which produced a less mutagenic metabolite, doubled the mutagenicity of FC. Carbon monoxide inhibited the mutagenicity of FC, suggesting the involvement of a heme containing enzyme. However, monoclonal antibodies specific for the phenobarbital-induced cytochrome P-450 enzymes PB-4 and PB-5, while inhibiting O-demethylation of p-nitroanisole and aflatoxin B1 mutagenicity, had not effect on FC mutagenicity. This implies that either these enzymes are not involved in the activation of FC or FC competes well with the antibodies for binding to the cytochrome P-450 enzymes. Two additional metabolites of FC were detected. One had an ultraviolet spectrum similar to FC: the other had a lambda max at 326 nm, and its retention time on reverse phase HPLC was very sensitive to changes in pH.

Aflatoxin B1↗

Roussin red methyl ester, a tumor promoter isolated from pickled vegetables.

Roussin red methyl ester [RRME; Fe2(SMe)2(NO)4], has recently been isolated from pickled vegetables consumed in Linxian, China. In the present studies, the tumor-promoting effect of RRME was found in rats treated first with nitrosodiethylamine. A two-stage experiment was also carried out by application of RRME on BALB/c mouse skin subsequent to 7,12-dimethylbenz[a]anthracene treatment, and induction of ornithine decarboxylase (ODC) activity was observed in epidermal cells. After 37-week treatments with 150, 300 or 450 nmol of RRME, the skin developed precancerous lesions and squamous cell carcinomas. The epidermal ODC activity was increased rapidly following a single application of RRME, and the level of its activation was in proportion to the doses used, although the promoting effect of RRME was weaker than that of 12-O-tetradecanoyl-phorbol-13-acetate. Since pickled vegetables are staple food in high-risk areas for esophageal cancer, RRME, as a tumor promoter, may therefore play a role in the development of this malignant disease.

9,10-Dimethyl-1,2-benzanthracene↗

[Synthesis of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins].

Seventeen derivatives of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins were synthesized with acid chloride method, Vilsmeier reagent method and mixed anhydride method. Isolation and purification were fulfilled with Sephadex LH-20 column chromatography and centrifugal-TLC technique. Their chemical structures were identified by elemental analysis, IR and 1HNMR spectrum. The preliminary antibacterial activity tests showed that these cephalosporin derivatives exhibited good activity against Gram-positive bacteria and individual Gram-negative bacteria. Further experiments in pharmacology will be made.

Cephalosporins↗

Fusarium moniliforme metabolites: genotoxicity of culture extracts.

Fusarin C (FC) is a potent mutagen which has been isolated from Fusarium moniliforme culture extracts (FME). We have confirmed that the mutagenicity of these extracts is enhanced by phenobarbital- or Aroclor-induced microsomes and shown that: (i) additional, direct-acting, mutagens are present in crude extracts from F. moniliforme cultures; (ii) Salmonella typhimurium TA 100 exposed to FME in the presence of S9 mixtures shows an increased number of DNA strand breaks as detected by intercalation of ethidium bromide; (iii) exposure of polyoma-transformed rat fibroblast cells to HPLC-purified FC induced asynchronous replication of polyoma DNA sequences, a phenomenon also observed when these cells were exposed to a variety of other carcinogens; (iv) FME can alkylate 4-(p-nitrobenzyl)pyridine in the absence of S9 mix, although less efficiently than styrene oxide; and (v) these additional direct-acting mutagens, present in crude extracts from F. moniliforme cultures, may be responsible for the DNA adducts formed by reaction with calf thymus DNA in the absence of metabolic activation and detected by the 32P-postlabeling assay. All of these observations suggest that significant health effects may be associated with human exposure to F. moniliforme and that further studies on its metabolites are needed.

Animals↗

Occurrence of nitroso compounds in fungi-contaminated foods: a review.

Dimethylnitrosamine (NDMA), diethylnitrosamine (NDEA), methylbenzylnitrosamine, and a new N-nitroso compound, N-3-methylbutyl-N-1-methylacetonylnitrosamine (NMAMBA), were found in cornbread that was inoculated with Fusarium moniliforme and underwent an incubation and the addition of a small amount of NaNO2. The carcinogenicity of NMAMBA was shown by the induction of forestomach carcinomas and liver tumors in mice and rats. Another new nitrosamine, N-2-methylpropyl-N-methylacetonyl nitrosamine, was isolated in millet and wheat flour after similar treatment. Some species of fungi not only can reduce nitrates to nitrites but also can increase the amount of secondary amines in the moldy foods and provide favorable conditions for the synthesis of nitrosamines. Some fungi may utilize primary amines to synthesize nitrosamines in appropriate culture mediums. Furthermore, the cornmeal may naturally contain trace amounts of nitrosamines, as detected by a gas chromatography/thermoenergy analyzer. Prolonged feeding of F. moniliforme-inoculated cornbread alone also induced the development of forestomach carcinoma in rats. This indicates the occurrence of potential carcinogens, perhaps certain Fusarium mycotoxins, in the moldy cornbread in addition to the carcinogenic nitrosamines. Another nitroso compound, Roussin red methylester (di-mu-methanethiolatotetranitrosodiiron) was found in pickled vegetables that are eaten daily in the Linxian (China) area. Roussin Red may provide NO-2 ions, which would react readily with secondary amines to form nitrosamines. Possibly this compound is a natural tumor promoter and is able to induce epithelial hyperplasia of the upper digestive tract and forestomach papilloma in treated mice. Also, trace amounts of NDMA, NDEA, and some other nitrosamines were found in the extract of pickled vegetables.

Animals↗

Synthesis of nitrosomethylisoamylamine from isoamylamine and sodium nitrite by fungi.

Nitrosomethylisoamylamine (NMIA), a carcinogenic N-nitroso compound was synthesized from isoamylamine (IAA) in a glucose-ammonium nitrate medium after several days' incubation with fungi and subsequent nitrosation with sodium nitrate. The nitrosamine was not produced by control reactions which lacked either IAA or fungi. The yield of NMIA varied with the length of incubation after inoculation with the fungi, and with the concentrations of IAA and NaNO2, the duration of nitrosation, the pH of the medium and the species of the fungi. The optimum conditions for the formation of the nitrosamine are reported.

Amines↗