Sulfuric acid esters as ultimate electrophilic and carcinogenic metabolites of some alkenylbenzenes and aromatic amines in mouse liver.
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Biomedical subjects
Publications and source records attributed to C C Lai.
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The synthesis of [phenyl-U-14C]gentian violet from [U-14C]benzene is described. The 14C-labelled dye was administered by gavage to groups of male and female F344 rats which were killed at 2, 4, 14, 24 or 36 hr after the single dose. Radioactivity was measured in urine, and determined in faeces, liver, kidney, fatty tissue, gonads and muscle by combustion analysis. Residues were maximal at 4 hr in liver, kidney, muscle and gonads, and in fat they reached a plateau after 24 hr. Depletion half-lives for male and female livers were 14.5 and 17.0 hr, respectively. The 14C-labelled dye was also administered in multiple doses by gavage to both sexes of F344 rats and B6C3F1 hybrid mice for 7 days. The highest residue level was found in fatty tissue of females of both species, with a highly significant sex difference (P less than 0.01). Significant sex differences were also noted for residue levels in kidney and muscle tissue from both species and in mouse liver. Bile collected from cannulated rats contained 5.7-6.4% of a single oral dose of the dye. The results suggest that gentian violet is absorbed from the gastro-intestinal tract to a greater extent than has been reported for other triphenylmethane dyes.
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A fast and sensitive method for the determination of putrescine, spermidine, spermine and ammonia by high-performance liquid chromatography (HPLC) with dabsyl chloride is described. These compounds are converted to their chromophoric dabsyl derivatives and are separated by a normal-phase chromatographic column (mu Porasil, 10 microgram) with 2% acetone in chloroform as isocratic mobile phase. The sensitivity of the method is 20 pmoles. The present method was shown to be a straightforward procedure for estimating polyamines in various rat tissues. The chromophoric derivatives of polyamines are also well separated by thin-layer chromatography (TLC) on silica gel, and the combination of the HPLC and TL C procedures provides a reliable method for qualitative and quantitative analysis of polyamines.
No nitrite was detected in the tissues or contents of the gastro-intestinal tracts of normal rats but after 2 wk on a diet containing 0 . 5% sodium nitrate the levels of nitrite in the stomach, small intestine and large intestine contents were 0 . 83%, 1 . 64-2 . 07 and 0 . 83 micrograms/g of contents respectively. Concurrent administration of 2% Lactobacillus preparation and 0 . 5% sodium nitrate in the diet for 2 wk further increased the nitrite levels in the intestines and slightly increased the level in the stomach. The elevation of nitrite levels induced by sodium nitrate administration was potentiated considerably by combined treatment with sodium bicarbonate and hetacillin producing nitrite levels of 3 . 16, 2 . 93-5 . 18 and 1 . 96-2 . 34 micrograms/g of the contents of the stomach, small intestine and large intestine respectively. Like hetacillin, minomycin and thiamphenicol also potentiated the nitrite production whereas amikacin (another antibiotic) strongly inhibited the formation of nitrite in the stomach. The different effects of the antibiotics may be due to their selective activities on the various microbes. The results indicate that the levels of nitrite in the gastro-intestinal tract are regulated by the level of nitrate intake, the population of microflora and the gastric pH. The safety of combined medication with antacids, antibiotics and Lactobacillus preparations in man deserves further investigation.
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Levamisole, which has immunostimulant activity, is now being used to treat some forms of cancer. We report that the drug enhances granulocyte colony formation. The mechanism of action appears to be partly through modulation of molecules on cell membranes. The molecular content of colony-stimulating activity (CSA) released into leucocyte-conditioned medium by cells of leukaemic and some preleukaemic patients can be quantitatively altered by levamisole, both in vitro and in vivo, but the CSA produced is qualitatively similar to that released by normal cells. The demonstrated levamisole enhancement of colony formation, and altered CSA types detected in leucocyte-conditioned medium, makes this drug a promising candidate for treatment of selected leukaemic states and in preleukaemia.
A unique case of popliteal cyst apparently caused by a bullet that penetrated the knee joint 30 years previously was recently encountered. No similar case was found in the English-language literature (3, 9, 12). Removal of bullets adjacent to joints is recommended.
The effect of magnesium deficiency on phosphatase activity and bone composition was determined in the femora of young rats. In the right distal metaphysis the acid and alkaline phosphatase activities were decreased in magnesium-deficient rats, and the activity of bone alkaline phosphatase in the incubation mixture after adding magnesium was significantly greater in the magnesium-deficient than in the control rats. In the left distal metaphysis the water content was significantly lower in the magnesium-deficient rats at the fifth week but not at the third week. Conversely, the ash content of metaphyseal bone was significantly increased in magnesium-deficient rats at the fifth week, but not at the third week. The magnesium and phosphorus contents were abnormally low in the deficient bone at both periods. The calcium content was increased in the deficient bone at the third week, but not at the fifth week.
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The direct-acting mutagenicity in Salmonella typhimurium strains TA98 and TA100 and the half-wave reduction potentials of 6-nitrobenzo[a]pyrene (6-nitro-BaP), 7-nitrobenz[a]anthracene (7-nitro-BA), and a series of their derivatives were compared. The common structural feature of these compounds is that their nitro substituents, in order to minimize steric hindrance, preferentially adopt an orientation perpendicular or nearly perpendicular to the aromatic rings. All of the compounds, except 7-hydroxy-6-nitro-BaP and 7-acetoxy-6-nitro-BaP, were found to exhibit very weak or no direct-acting mutagenicity. 7-Acetoxy-6-nitro-BaP and 7-hydroxy-6-nitro-BaP were also found to have the lowest reduction potentials among the tested compounds. The results suggest that a combination of the orientation of the nitro substituent and the first half-wave reduction potential of the compound may correlate with the direct-acting bacterial mutagenicity of nitro-polycyclic aromatic hydrocarbons.
Phosphatidylcholines are significant components of pulmonary surfactant in the alveolar region of the lung, where they play a major role in lung function due to their surface tension reducing properties. However, separation and the direct identification of many of the primary products of reaction of phosphatidylcholines with inhaled pollutant gases has not been possible until recently due to the lack of suitable analytical techniques, so that compounds such as fatty acid methyl esters generally have been used as analogues for the phospholipids. We report here the first isolation and identification of the products of reaction of ozone with one of the unsaturated components of lung surfactant, beta-oleoyl-gamma-palmitoyl-L-alpha-phosphatidylcholine (OPPC), using a combination of high-performance liquid chromatography, fast atom bombardment mass spectrometry, and Fourier transform infrared, ultraviolet absorption, and nuclear magnetic resonance spectrometry as well as gas chromatography. The products are shown to be the cis and trans secondary ozonides of the parent phosphatidylcholine, analogous to those previously observed by other researchers in the reactions of the simple fatty acid methyl esters with ozone. This also appears to be the first report of fast atom bombardment mass spectra of these phospholipid secondary ozonides. The implications of this work for the inhalation of ozone, formed in photochemical smog, are discussed.
A 59-year-old woman with diabetic vitreous hemorrhage and contracted anterior capsule opening received secondary capsulorhexis and trans pars plana vitrectomy in a single operation. The combined surgery was successful. In addition, the anterior capsule opening was enlarged by the procedure and no further vitreous hemorrhage occurred during the 6 month follow-up period in both eyes. When anterior capsule opening reduction is encountered in patients requiring vitreoretinal surgery, combining secondary capsulorhexis and vitreoretinal surgery together in a single operation maybe provide a good treatment alternative.
A case is reported of a traumatic macular hole caused by a high-energy Nd:YAG laser. The initial ocular examination revealed an explosive, crater-shaped, full-thickness macular hole surrounded by local edema and detachment. By the 12th day after the injury, the hole had shrunk progressively and was covered by a thin fibrin-like membrane. A thick epiretinal membrane covered the injured area 1 month after the injury. Nine months after the injury, the macular hole closed spontaneously with a partially detached epiretinal membrane. This case demonstrates one of the natural healing processes of a traumatic macular hole. Although the hole finally closed, the patient did not regain his vision because of the severe damage to the photoreceptors, retinal pigment epithelium, and choroid.
Amino acid and acylcarnitine profiling of dry blood specimens using electrospray tandem mass spectrometry (ESI/MS/MS) has been recognized as an useful tool for screening inherited metabolic defects of newborns. In this pilot study, we introduced this technology to screen 2100 newborns to establish the normal amino acid and acylcarnitine level. Based on the upper cutoff level (average + 4*SD), twenty-nine samples studied were considered as abnormal. After follow-up samples and urine GC/MS analysis, only two were confirmed as true inborn errors. One was identified as hyperphenylalaninemia, and the other as isovaleric acidemia. The positive rate of true inborn metabolic error was 0.09% (2/2100), and the false positive rate 1.28% (29/2100) in this study. ESI/MS/MS is proven to be an adequate tool for inborn metabolic error screening.
Trisomy 8 syndrome, with or without mosaicism, is characterized by the following clinical signs and symptoms: mental retardation, deformed skull, prominent forehad, high-arched palate, low-set and/or dysplastic ears, long and slender trunk, reduced joint mobility, and deep plantar furrows. The deep furrow or longitudinal crease of the sole may be pathognomonic for the syndrome. It should be noted that it has been seen in other rare syndromes. It is recommended that a child with mental retardation and associated multiple anomalies should be subjected to a cytogenetic study in order to define the incidence of this syndrome. Differnetial diagnosis should include: Fong's syndrome, arthrogryposis and otopalato-digital syndrome. It is interesting to note that there seem to be individuals who have had no physical abnormalities and have been identified during an evaluation for repeated abortions. The above described case of trisomy 8 mosaicism was seen and treated for many years by many different specialists without an accurate diagnosis.
To investigate the effects of intravenous immunoglobulin (IVIG) on patients of juvenile dermatomyositis (JDM), seven children with JDM were given monthly IVIG in conjunction with other treatments. The indications included disease exacerbation, inability to reduce dose of steroid, replacing cytotoxic drug because of complication and remission-induction for those with severe initial manifestations. Two patients were reported to improve slowly and maintained improved status while on a markedly reduced dose of steroid. One patient responded favorably to the first three courses only. Three patients had evident and quick responses, which could be seen as early as two or three days after the infusion. One patient failed to experience any beneficial effect by IVIG. Four initial responders had an aggravation some time after discontinuing the monthly regimen. The untoward reactions included only two occasions of fever, and another two occasions of fever associated with transient proteinuria. In conclusion, IVIG may be of value in terms of its quick, pulsatile effect and the adjuvant potential to reduce the side effect resulting from exposure to steroid or other immunosuppressive agents as well. However, its long-term efficacy is doubtful, based on this observation.