Interactions of herbicides 2,4-D and dinoseb with liver mitochondrial bioenergetics

The use of drugs for common pregnancy complications like premature labor, hypertensive diseases, and premature rupture of membranes with chorioamnionitis is reviewed. In addition, new publications on antiviral drugs in HIV-positive pregnant patients are also discussed. Among the drugs, suppressing premature labor side-effects of beta-mimetics are of growing concern. The effectiveness of other agents like magnesium, indomethacin, and sulindac are addressed. The various mechanisms explaining the beneficial effect of magnesium in pre-eclampsia are reviewed and new data on antihypertensives, such as labetalol, calcium channel blockers, and methyldopa are presented. The evidence from various clinical trials on the value of low-dose aspirin as a prophylactic agent against pregnancy-induced hypertension, pre-eclampsia, and intrauterine growth retardation in high-risk and low-risk patients is compared. Pharmacokinetic data including transplacental transfer of antibiotics and anti-HIV nucleosides are part of this review.     

Metabolic alterations in hepatocytes promoted by the herbicides paraquat, dinoseb and 2,4-D

The cytotoxic effects of the herbicides paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride), dinoseb (2-sec-butyl-4,6-dinitrophenol) and 2,4-D (2,4-dichlorophenoxyacetic acid) on freshly isolated rat hepatocytes were investigated. Paraquat and 2,4-D (1-10 mM) caused a dose and time dependent cell death accompanied by depletion of intracellular glutathione (GSH) and mirroring increase of oxidized glutathione (GSSG). Dinoseb, the most effective cytotoxic compound under study (used in concentrations 1000 fold lower than paraquat and 2,4-D), exhibited moderate effects upon the level of GSH and GSSG. These limited effects are at variance with significant effects upon the adenine and pyridine nucleotide contents. ATP and NADH levels are rapidly depleted by herbicide metabolism. This depletion is observed in the millimolar range for paraquat and 2,4-D and in the micromolar range for dinoseb. 2,4-D completely depletes cellular ATP, with subsequent cell death, as detected by LDH leakage. Paraquat rapidly depletes NADH, according to the redox cycling of the herbicide metabolism. The most effective compound is dinoseb since it exerts similar effects as described for paraquat and 2,4-D at concentrations 1000 fold lower. Simultaneously with NADH and ATP depletion, the levels of ADP, AMP and NAD+ increase in hepatocytes incubated in the presence of the herbicides. In contrast to NADH, the time course and extent of ATP depletion and fall in energy charge correlate reasonably with the time of onset and rate of cell death. It is concluded that the herbicides, paraquat and 2,4-D are hepatotoxic and initiate the process of cell death by decreasing cellular GSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enzyme immunoassay based survey of precipitation and surface water for the presence of atrazine, metolachlor and 2,4-D

The suitability of enzyme immunoassay (EIA) as a method of analysis for 2,4-D, atrazine and metolachlor contamination in water samples was determined by comparing EIA results to gas chromatography (GC) results. The comparison of EIA and GC results yielded a correlation coefficient of 0.92, 0.98 and 0.92 for 2,4-D, atrazine and metolachlor, respectively. EIA was used to monitor seasonal trends in the concentrations of 2,4-D, atrazine and metolachlor in surface water and precipitation throughout the province of Ontario, Canada. 2,4-D was detected in excess of 4 micrograms/L in urban creeks during the period of application. Concentrations of 43 and 9 micrograms/L of atrazine and metolachlor, respectively, were detected during the field application period in surface water samples from the Kintore Creek watershed. The levels of 2,4-D, atrazine and metolachlor detected exceeded the Canadian Water Quality Guidelines for the protection of fresh water aquatic life. Concentrations as high as 445 and 322 ng/L of atrazine and metolachlor, respectively, were detected in precipitation samples collected from 17 locations in Ontario during the herbicide application period. The EIA was shown to be qualitatively and quantitatively comparable to GC analysis.     

2,4-D and alkaloid accumulation in periwinkle cell suspensions

Omission of 2,4-D from culture medium during one subculture of Catharanthus roseus cells, strain C20, resulted in an increased alkaloid accumulation, without effect on growth. Alkaloid accumulation, rather than growth, seemed to be more sensitive to 2,4-D. 2,4-D inhibited alkaloid accumulation essentially during growth phase, but its inhibitory effect during this period was partially reversible. As this reversibility was underlined only during the stationary phase, this suggested that this action could be situated upstream in a terpenoid non-specific pathway. 2,4-D feeding showed that inhibition is weaker and weaker as the alkaloid accumulation period proceeds. Auxin action during this period could take place downstream in specific alkaloid pathways. The lower alkaloid accumulation obtained after loganic acid feeding compared to that obtained with secologanin and loganin could indicate that loganic acid methylation should be one of the 2,4-D target(s).     

Interaction of 2,4-dichlorophenoxyacetic acid (2,4-D) with cell and model membranes

2,4-dichlorophenoxyacetic acid (2,4-D), a widely used herbicide, is a component of the "agent orange' whose toxicity has been extensively studied without definite conclusions. In order to evaluate its perturbing effect upon cell membranes, 2,4-D was made to interact with human erythrocytes and molecular models. These studies were performed by scanning electron microscopy on red cells, fluorescence spectroscopy on dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles and X-ray diffraction on multilayers of DMPC and dimyristoylphosphatidylethanolamine (DMPE). It was observed that 2,4-D induced a pronounced shape change to the erythrocytes. This effect is explained by the herbicide interaction with the outer monolayer of the red cell membrane.     

Genetic and phenotypic diversity of 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacteria isolated from 2,4-D-treated field soils

Forty-seven numerically dominant 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacteria were isolated at different times from 1989 through 1992 from eight agricultural plots (3.6 by 9.1 m) which were either not treated with 2,4-D or treated with 2,4-D at three different concentrations. Isolates were obtained from the most dilute positive most-probable-number tubes inoculated with soil samples from the different plots on seven sampling dates over the 3-year period. The isolates were compared by using fatty acid methyl ester (FAME) profiles, chromosomal patterns obtained by PCR amplification of repetitive extragenic palindromic (REP) sequences, and hybridization patterns obtained with probes for the tfd genes of plasmid pJP4 and a probe (Spa probe) that detects a distinctly different 2,4-D-degrading isolate, Sphingomonas paucimobilis (formerly Pseudomonas paucimobilis). A total of 57% of the isolates were identified to the species level by the FAME analysis, and these isolates were strains of Sphingomonas, Pseudomonas, or Alcaligenes species. Hybridization analysis revealed four groups. Group I strains, which exhibited sequence homology with tfdA, -B, -C, and -D genes, were rather diverse, as determined by both the FAME analysis and the REP-PCR analysis. Group II, which exhibited homology only with the tfdA gene, was a small group and was probably a subset of group I. All group I and II strains had plasmids. Hybridization analysis revealed that the tfd genes were located on plasmids in 75% of these strains and on the chromosome or a large plasmid in the other 25% of the strains. One strain exhibited tfdA and -B hybridization associated with a plasmid band, while tfdC and -D hybridized with the chromosomal band area. The group III strains exhibited no detectable homology to tfd genes but hybridized to the Spa probe. The members of this group were tightly clustered as determined by both the FAME analysis and the REP-PCR analysis, were distinctly different from group I strains as determined by the FAME analysis, and had very few plasmids; this group contained more of the 47 isolates than any other group. The group III strains were identified as S. paucimobilis. The group IV strains, which hybridized to neither the tft prove nor the Spa probe, were as diverse as the group I strains as determined by the FAME and REP-PCR analyses. Most of group IV strains could not be identified by the FAME analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of the degradation of phenoxyacid herbicides at different sites in a limestone aquifer

The biodegradation of three phenoxyalkanoic acid herbicides, viz. MCPA, dichlorprop and mecoprop, under aerobic and anaerobic conditions was investigated using microcosm techniques. The field studies were conducted in a limestone aquifer that had suffered contamination from leaking landfill sites in which phenoxyalkanoic acid herbicides (mostly mecoprop) had undergone disposal. The results from in situ field and laboratory microcosms indicated that under microbially active aerobic conditions the biotransformation of all three herbicides was rapid and that lag phases were short. Under fully aerobic conditions the concentration of each of the three herbicides was reduced from 2,000 micrograms/l to below the detection limit (approx. 10 micrograms/l) of the HPLC system, used for their analysis, within 14 days. However, under microbially active anaerobic conditions no degradation of the herbicides could be discerned over the 100-200 day duration of the experiments. This finding has significant implications for the disposal of phenoxyalkanoic acid herbicides particularly in situations where any resulting leachate may find its way into underlying water resources.     

Pollution of the agricultural lands of Bashkortostan by the herbicide 2,4-D and dioxins]

Market forces present the nursing profession with an urgency to prepare gerontological nurses to assume significant roles in the managed care industry. An understanding of the current managed care environment underscores the need for training. Nurses require a "managed care" skill-set encompassing a firm grasp of the organization, financing, delivery, and policy implications of managed care as well as advanced practice clinical skills and a sound business orientation. The importance of the consumer as a significant player in managed care is highlighted.     

Determination of arylphenoxypropionic herbicides in water by liquid chromatography-electrospray mass spectrometry

The study described here investigates the replicability of gender-specific risk profiles for gonorrhea based on an Alaskan sample compared to a U.S. national sample of drug users at risk for HIV infection. The Alaska sample (interviewed at a field station in Anchorage, Alaska; N=1,049) and the national sample (interviewed at 18 sites other than Alaska; N=17,619) consisted of cocaine smokers and injection drug users not in drug treatment. A history of gonorrhea infection was self-reported and coded as ever or never. The Anchorage and national risk profile for men included the following factors: (a) history of intranasal or parenteral cocaine use, (b) being black versus nonblack, (c) being older, (d) income from illegal activity, and (e) history of amphetamine use. The Anchorage and national risk profiles for women included the following factors: (a) trading sex for money, (b) being Native American versus non-Native American, and (c) trading sex for drugs. The Anchorage model for women included perceived homelessness as a factor, but it was not retained in the national model. The extent of the replicability of these models illustrates the generalizability of Alaskan findings to other U.S. drug-using populations. The authors also discuss the implications of these findings for disease prevention.     

Molecular genetic analysis of the response of three soil microbial communities to the application of 2,4-D

The responses of three different soil microbial communities to the experimental application of 2,4-dichlorophenoxyacetic acid (2,4-D) were evaluated with a variety of molecular genetic techniques. Two of the three soil communities had histories of prior direct exposure to 2,4-D, and one had no prior direct application of any herbicide. Dominant 2,4-D degrading strains isolated from these soils the previous year were screened for hybridization with three catabolic genes (tfdA, tfdAII, and tfdB) cloned from the well-studied 2,4-D degradative plasmid, pJP4, revealing varying degrees of similarity with the three genes. Hybridization of total community DNA from the three soils with the tfd gene probes also indicated that pJP4-like tfd genes were not harboured by a significant percentage of the community. Community level response was evaluated by the comparison of different treatments by Random Amplified Polymorphic DNA (RAPD) fingerprints and by community DNA cross-hybridization. No differences between treatments within the same soil were detected in any of the RAPD fingerprints generated with 17 primers. Community DNA cross-hybridization also indicated that the application of 2,4-D at the applied rates did not quantitatively affect the structure of the soil microbial communities present in the three soils during the time-frame studied.     

Use of solid phase extraction disks for the GC-MS analysis of acidic and neutral herbicides in drinking water

An analytical procedure was developed in which thirteen herbicides (10 acidic and 3 neutral compounds) may be extracted from drinking water samples using solid phase extraction disks and subsequently analyzed by gas chromatography-mass spectrometry. Using 8 replicate samples consisting of reagent water fortified with nanogram quantities of each herbicide, the average percent recoveries and method detection limits were determined for each analyte. The method was found to be suitable for the determination of individual herbicides in drinking water at concentrations of approximately 10 ng/L.     

Microbiologic/hygienic evaluation of the risk potential of bacteria from soil and water sources in combination with biotechnologic risks of soil restoration

Biological cleanup-processes removing contaminations from soil and ground-water can be carried out "ex-situ" or "in situ". The pollutants are mineralized (totally or partly) by microorganisms. The successful application of bioremediation techniques often leads to an increase of aerobic and facultatively anaerobic bacteria in soil and/or groundwater, a fact that triggered discussions about a potential biological risk originating from these microorganisms. In this study the identification results of 10,200 microorganisms isolated from 109 ground-water- and 152 soil-samples of different sites contaminated with mineral oil or chlorinated aromatics are evaluated with respect to a possible biological risks originating from these microorganisms. According to their biological risk potential, 19.2% (1958) of the isolated organisms can be grouped into risk-groups II, that means they they are able o cause human disease but it is unlikely that they are spread to the community and there is effective prophylaxis or treatment available. The majority of isolates (81.8%) are grouped into risk group I, meaning that it is very unlikely that they cause a human disease. All these microorganisms are either adsorbed to the soil-matrix or within a closed system of a water-treatment-plant, so that the risk of infection is very unlikely for healthy individuals (regarding possible pathways of infection). The risk potential in waste-water-treatment-plants is regarded to be significantly higher than in biological soil-cleanup processes, because of the specific origin of the bacteria and the possible formation of aerosols.