Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The measurement of carbon clearance in female BDF1 mice was used for the characterization of affinity of empty multilamellar (MLV) or small unilamellar vesicles (SUV) made from HEPC:CH:DCP 1:1:0,25 to the reticuloendothelial system (RES). Five mice each were treated i.v. with the corresponding liposomes or physiologic saline. At different times after treatment india ink was administered i.v. and its elimination over 15 minutes was determined by measuring the extinction in blood at 650 nm. MLV had a significant influence on the phagocytic function of RES, leading to a three-fold prolongation of elimination half time after 8h. At 48 hours the normal function of RES was restored. This effect was already seen with a dose of 0.05 ml MLV/mouse corresponding to 1.06 mg lipid. On the contrary, SUV caused no change of carbon clearance up to a dose of 0.8 ml/mouse. From these results we conclude that liposomes, especially MLV, can lead to a measurable but reversible impairment of RES function, while SUV are better suited for a by-pass of this tissue and a probable reaching of other targets, as, for example tumors.
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PMID:Measurement of carbon clearance in mice as toxicity parameter for liposomal preparations. 162 37

There is no major change in the indication of upper extremity fractures, although there is further refinement of plate design (LC-DCP), plate material (titanium), and operative technique ("biological osteosyntheses"). For lower extremity fractures, the external fixator has shown excellent results in the early phase of treatment, with some disadvantages the late phase. If a change to an intramedullary nail is planned, this should be performed in the early phase of treatment. The concept of the "pinless fixator" has shown great advantages for temporary stabilization, although further technical development is necessary. The claw interlocking nail allows easy distal locking without using X-rays. Unreamed nailing, with the advantage of less damage to the cortical blood supply and reduced pulmonary risk, will be of increasing importance, if the trend seen in current studies is confirmed.
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PMID:[New trends in the management of shaft fractures]. 179 49

Groups of 15 male and 15 female Sprague-Dawley rats were exposed to 1 of 3 chloropropene (2,3-Di = DCP; 1,2,3-Tri = TRCP; and 1,1,2,3-Tetra = TECP) vapors to provide information on repeated exposures and the potential for reproductive impairment by the most likely route of occupational exposure. Target exposure concentrations were 0, 1, 5, and 15 ppm, 6 h/d, 5 d/wk for 13 wk. The following parameters were evaluated: pharmacotoxic signs, survival, body weights, hematology, clinical blood chemistry, urine analysis, gross and histopathology (over 40 tissues/rat), organ weights, and selected weight ratios. Signs of nasal irritation were noted in rats exposed to 15 ppm of either DCP or TRCP but not TECP. Small decreases in overall body weight were observed in female rats exposed to 15 ppm TCP. An increase (approximately 15%) in spleen weight, with no corresponding histopathological or clinical findings, was observed in 15 ppm DCP-treated male rats. No other effects considered related to treatment were observed following exposure to any of the three chlorinated propenes. Additional groups of 10 male and 20 female Sprague-Dawley rats were exposed to DCP, TRCP, or TECP vapors at target concentrations of 0, 1, or 5 ppm for 6 h/d, 5 d/wk for a 10-wk premating period, a mating period, and the first 14 d (females only) of gestation. Females were allowed to deliver litters and the offspring were evaluated during a 21-d lactation period. Mating, pregnancy, and fertility indices were generally comparable among all test groups, although female mating and pregnancy indices of both DCP-treated females were lower than expected in the regular and postrecovery reproduction phase. No effects were seen on pup survival, sex distribution, body weights, organ weights, and ratios. A modest reduction in pup body weights was observed following TECP exposure but was attributed to large litter size. No treatment-related effects were seen following necropsy of adults or weanlings, nor were such effects noted following microscopic evaluation of gonads from parental animals.
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PMID:Subchronic inhalation toxicity and reproductive assessment in rats of three chlorinated propenes. 185 78

The objective of this study was to compare the disposition and metabolism of [14C]1,2-dichloropropane [( 14C]DCP) following oral and inhalation exposure since these two routes are of interest with regards to occupational and accidental exposure. [14C]DCP was administered orally to groups of four rats of each sex as a single dose of 1 or 100 mg/kg and as a multiple 1 mg/kg nonradiolabeled dose for 7 days followed by a single 1 mg [14C]DCP/kg dose on day 8. In addition, four rats of each sex were exposed to [14C]DCP vapors for a 6-h period in a head-only inhalation chamber at target concentrations of 5, 50 and 100 ppm. [14C]DCP was readily absorbed, metabolized and excreted after oral or inhalation exposure. For all treatment groups the principal routes of elimination were via the urine (37-65%) and expired air (18-40%). The tissues, carcass, feces and cage wash contained less than 11, 9.7 and 3.8% of the dose, respectively. The major urinary metabolites, as a group, from the oral and inhalation exposures were identified as three N-acetylcysteine conjugates of DCP, N-acetyl-S-(2-hydroxypropyl)-L-cysteine, N-acetyl-S-(2-oxopropyl)-L-cysteine and N-acetyl-S-(1-carboxyethyl)-L-cysteine. The majority (61-87%) of the expired volatile organic material was found to be parent DCP in all samples analyzed. Increasing the dose/concentration of [14C]DCP resulted in an increase in the amount of exhaled [14C]-volatile organics. The peak DCP blood concentrations (inhalation exposure) were not proportional to dose, indicating a dose-dependency in the blood clearance of DCP. Nonetheless, upon termination of exposure, DCP was rapidly eliminated from the blood. In all treatment groups, following oral and inhalation exposure the majority of the radioactivity was eliminated by 24 h postdosing and no differences were noted between sexes. Therefore, it can be concluded that in the rat the pharmacokinetics and metabolism of [14C]DCP are similar regardless of route of exposure or sex.
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PMID:Disposition and metabolism of [14C]1,2-dichloropropane following oral and inhalation exposure in Fischer 344 rats. 189

2,4-Dichlorophenol hydroxylase, a flavoprotein monooxygenase from Pseudomonas cepacia grown on 2,4-dichlorophenoxyacetic acid (2,4-D) as the sole source of carbon, was purified to homogeneity by a single-step affinity chromatography on 2,4-DCP-Sepharose CL-4B. The enzyme was eluted from the affinity matrix with the substrate 2,4-dichlorophenol. The enzyme has a molecular weight of 275,000 consisting of four identical subunits of molecular weight 69,000 and requires exogenous addition of FAD for its complete catalytic activity. The enzyme required an external electron donor NADPH for hydroxylation of 2,4-dichlorophenol to 3,5-dichlorocatechol. NADPH was preferred over NADH. The enzyme had Km value of 14 microM for 2,4-dichlorophenol, and 100 microM for NADPH. The enzyme activity was significantly inhibited by heavy metal ions like Hg2+ and Zn2+ and showed marked inhibition with thiol reagents. Trichlorophenols inhibited the enzyme competitively. The hydroxylase activity decreased as a function of increasing concentrations of Cibacron blue and Procion red dyes. The apoenzyme prepared showed complete loss of FAD when monitored spectrophotometrically and had no enzymatic activity. The inactive apoenzyme was reconstituted with exogenous FAD which completely restored the enzyme activity.
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PMID:Affinity purification and characterization of 2,4-dichlorophenol hydroxylase from Pseudomonas cepacia. 189 14

1,3-Dichloro-2-propanol (1,3-DCP-OH, glycerol dichlorohydrin) is of great importance in many industrial processes and has been detected in foodstuffs, in particular in soup spices and instant soups. It has been shown to be carcinogenic, genotoxic and mutagenic. Its genotoxic mechanisms are, however, not yet entirely understood. We have investigated whether alcohol dehydrogenase (ADH) catalysed activation to the highly mutagenic and carcinogenic 1,3-dichloroacetone or formation of epichlorohydrin or other genotoxic compounds play a role for mutagenicity and genotoxicity. In our studies, no indications of ADH catalysed formation of 1,3-dichloropropane could be found, although we could demonstrate a clear activation by ADH in the case of 2-chloropropenol. Formation of allyl chloride could also be excluded. We found, however, clear evidence that epichlorohydrin formed chemically in the buffer and medium used in the test is responsible for genotoxicity. No indication was found that enzymatic formation of epichlorohydrin plays a role. Additional mutagenicity and genotoxicity studies with epichlorohydrin also confirmed the hypothesis that genotoxic effects of 1,3-DCP-OH depend on the chemical formation of epichlorohydrin.
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PMID:Genotoxicity of 1,3-dichloro-2-propanol in the SOS chromotest and in the Ames test. Elucidation of the genotoxic mechanism. 191 79

Voluntary bystanders, simulating a situation of non-occupational exposure to Z- and E-1,3-dichloropropene (Z- and E-DCP), were exposed during field application of this nematocide in the Dutch flower-bulb culture. Environmental monitoring revealed that mean respiratory exposure concentrations of Z- and E-DCP varied from non-detectable levels to 1.12 mg/m3 8-h time-weighted average (TWA) for Z-DCP and to 0.91 mg/m3 8-h TWA for E-DCP. Biological monitoring was executed by determining urinary mercapturic acid metabolites of Z- and E-DCP according to a method recently validated in occupationally exposed applicators. A linear relationship between respiratory exposure to Z- and E-DCP and the urinary excretion of both mercapturic acids was observed in bystanders. Dermal uptake did not contribute significantly to the internal dose of Z- or E-DCP. The urinary mercapturic acid of Z-DCP was a more sensitive parameter for the detection of exposure than was respiratory air monitoring. In future studies it would be worthwhile to determine the extent of exposure of real bystanders to DCP on the basis of urinary mercapturic acid excretion.
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PMID:Environmental and biological monitoring of non-occupational exposure to 1,3-dichloropropene. 191 66

The thermal behavior of water in liposome dispersions and in liposome dispersions containing mannitol at subzero temperatures was investigated with differential scanning calorimetry (DSC). The cooling curves from 20 down to -60 degrees C for a liposome dispersion (bilayer composition PL100H/DCP), monitored at cooling rates of 5 and 10 degrees C/min, showed several heat flows related to water crystallization. All lipid-containing dispersions showed water crystallization at temperatures below -40 degrees C. The magnitude of this heat flow strongly depended on the experimental variables. Cooling rate, particle size, lipid concentration, and location and nature of the cryoprotectant all influenced the water crystallization behavior as shown in the DSC cooling curve. Different fractions of water--presumably related to their location in the dispersion--could be distinguished. It is concluded that DSC provides a valuable tool for the detection of changes in the physical state of water in liposome dispersions during freezing/thawing. The insights gained from these DSC studies may make it possible to select--on the basis of rational considerations rather than by trial and error--optimum conditions for the cryopreservation of liposomes containing water-soluble drugs.
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PMID:The cryopreservation of liposomes. 1. A differential scanning calorimetry study of the thermal behavior of a liposome dispersion containing mannitol during freezing/thawing. 192 54

This is a study of 84 patients with upper arm fractures who were treated by plate osteosynthesis. The indication was mandatory in 9 patients with open fractures, 23 patients with primary radial nerve palsy on admission, 5 patients with radial nerve palsy after the initial treatment, 22 patients with pseudarthrosis and 7 patients who were polytraumatised. The operation was also indicated in 15 patients, because of the form of the fracture, in 3 patients with brachial plexus lesion, in 3 patients because it involved both upper arms and in 3 patients with segmental fractures. The 4.5 DCP was used in all these cases. All the cases of pseudarthrosis progressed to achieve bony union after the operation. There was no incidence of postoperative pseudarthrosis. We did encounter two cases (2.4%) of radial nerve palsy that required exploration. All the preoperative primary and secondary cases of radial nerve palsy recovered postoperatively. After an average follow-up period of 2.4 years (1-10 years) 90% of the patients could be classified as having very good or good results.
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PMID:[The surgical treatment of humeral shaft fractures]. 197 84

A biological monitoring study was carried out in the Dutch flower-bulb culture to determine the relationship between respiratory occupational exposure to Z- and E-1,3-dichloropropene (Z- and E-DCP) and urinary excretion of two mercapturic acid metabolites, N-acetyl-S-(Z- and E-3-chloropropenyl-2)-L- cysteine (Z- and E-DCP-MA). Urinary excretion of Z- and E-DCP-MA, either based on excretion rates or on creatinine excretion, followed first order elimination kinetics after exposure. Urinary half-lives of elimination were 5.0 +/- 1.2 hr for Z-DCP-MA and 4.7 +/- 1.3 hr for E-DCP-MA and were not statistically significantly different. Calculated coefficients of variation indicated that the half-lives of elimination of Z- and E-DCP-MA were quite consistent inter- and intra-individually. Strong correlations (r greater than or equal to 0.93) were observed between respiratory 8-hr time weighted average (TWA) exposure to Z- and E-DCP and complete cumulative urinary excretion of Z- and E-DCP-MA. Z-DCP yielded three times more mercapturic acid than E-DCP, probably due to differences in metabolism. Z- and E-DCP were excreted 45 and 14% as their respective mercapturic acid metabolites. A respiratory 8-hr TWA exposure to the Dutch occupational exposure limit of 5 mg.m-3 DCP would result in a complete cumulative excretion of 14.4 mg (95% confidence interval: 11.7-17.0 mg) Z-DCP-MA and 3.2 mg (95% confidence interval: 2.3-4.1 mg) E-DCP-MA.
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PMID:Inhalation exposure to 1,3-dichloropropene in the Dutch flower-bulb culture. Part II. Biological monitoring by measurement of urinary excretion of two mercapturic acid metabolites. 199 11


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