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Nitric oxide contributes to oxygen demand-supply balance in hypoperfused right ventricle.

OBJECTIVE: The present study examined the role of nitric oxide (NO) in oxygen demand-supply balance in hypoperfused canine right ventricular myocardium. METHODS: The right coronary artery of anesthetized, open-chest dogs was perfused at pressures of 80, 60, and 40 mm Hg, and right ventricular myocardial oxygen consumption, right coronary blood flow and other hemodynamic and cardiac function variables were measured. Right ventricular mechanical function was indexed as the product of heart rate x peak right ventricular systolic pressure x right ventricular dP/dt(max). NO synthesis blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 150 mug/min) was infused into the right coronary artery to block NO synthesis. RESULTS: Neither hypoperfusion nor L-NAME altered right ventricular function. Right ventricular myocardial oxygen consumption fell with coronary perfusion pressure, but less steeply after L-NAME, and at all perfusion pressures was elevated above control. The increase in myocardial oxygen consumption in the absence of NO was met by increased oxygen extraction and by non-NO dependent vasodilation, but the relationship between flow and oxygen consumption was displaced downward after L-NAME. As right coronary perfusion pressure was reduced, the relationship between right ventricular oxygen consumption and right coronary venous PO(2) became steeper after L-NAME, and right coronary venous PO(2) was significantly reduced. CONCLUSIONS: During right coronary hypoperfusion, right ventricular function is well maintained, but myocardial oxygen consumption falls, reflecting an increase in oxygen utilization efficiency. NO contributes to this adaptation to hypoperfusion by restraining myocardial oxygen consumption, and by promoting coronary vasodilation with less severe reduction in myocardial PO(2). NO has an important role in right ventricular oxygen demand-supply balance when right coronary perfusion pressure is reduced.

Animals↗

The effect of some formulation and process variables on the surface roughness of film-coated tablets.

The effect of some formulation and process variables on the surface appearance of film-coated tablets has been examined by measuring the arithmetic mean roughness, Ra, values across the faces of tablets before and after they were coated with hydroxypropyl methyl-cellulose. For all tablet cores except those that were very porous, film coating resulted in an increasing surface roughness; for very porous cores a decrease was found. Tablets with rough surfaces were produced by coating with low molecular weight grades of the polymer; increasing the polymer molecular weight resulted in a smoother finish with a minimum roughness at intermediate molecular weight grades. Increasing the polymer concentration above 2% w/v caused an increase in roughness as did increasing film thickness to 140 micrometer. There was a minimum in roughness at film thickness of 20 micrometer. The addition of pigment in low concentrations (0--25% v/v) caused a marginal increase in surface roughness but at concentrations above the critical pigment volume concentration, the surfaces were very rough. The results illustrate the potential of the method in the optimization of film formulations and process conditions during product development.

Cellulose↗

Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses.

Because sensitivity of equine pulmonary vasculature to endogenous as well as exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous NO production plays a role in exercise-induced arterial hypoxemia. We hypothesized that inhibition of NO synthase may alter the distribution of ventilation-perfusion mismatching, which may affect the exercise-induced arterial hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound Thoroughbred horses at rest and during incremental exercise protocol leading to galloping at maximal heart rate without (control; placebo = saline) and with N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (20 mg/kg iv). The experiments were carried out in random order, 7 days apart. At rest, L-NAME administration caused systemic hypertension, pulmonary hypertension, and bradycardia. During 120 s of galloping at maximal heart rate, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and acidosis occurred in the control as well as in NO synthase inhibition experiments. However, statistically significant differences between the treatments were not found. In both treatments, exercise caused a significant rise in hemoglobin concentration, but the increment was significantly attenuated in the NO synthase inhibition experiments, and, therefore, arterial O(2) content (Ca(O(2))) increased to significantly lower values. These data suggest that, whereas L-NAME administration does not affect pulmonary gas exchange in exercising horses, it may affect splenic contraction, which via an attenuation of the rise in hemoglobin concentration and Ca(O(2)) may limit performance at higher workloads.

Animals↗

Trends in alkyl substituent effects on nucleophilic reactions of carbonyl compounds: gas phase reactions between amines and the methoxy methyl cation.

The reactions of various amines (RNH(2); R = H, CH(3), C(2)H(5) and i-C(3)H(7)) with the methoxy methyl cation (CH(2)OCH(3)(+)) have been investigated using an FT-ICR mass spectrometer, and the experimental results are supplied with ab initio calculations. The amines show clear trends in their reactivities with variable degree of: 1) nucleophilic substitution, 2) addition-elimination and 3) hydride abstraction. In all cases addition-elimination dominates over nucleophilic substitution, and for R not equal H the observed reactions occur at the collisional limit. The potential energy profiles for all three reaction types correlate with the basicities of the amines; the more basic amine-the more favourable is the reaction; in other words: nucleophilicity follows basicity in the gas phase.

Journal Article↗

[The acetylator polymorphism in a Khmer population: clinical consequences].

The great variability of slow acetylator (SA) and/or rapid acetylator (RA) frequency is mainly due to ethnic-racial origin. Using the urinary elimination ratio of three metabolites of caffeine--acetylamino formylamino methyluracil (AFMU) to AFMU + 1-methyl urate (1U) + 1-methyl xanthine (1X)--we settled the acetylation phenotype in 54 independent subjects of Khmer and 70 independent subjects of Caucasian origin. Using DNA from peripheral leucocytes, we determined by PCR, in 32 Khmer and 122 Caucasian subjects, the frequencies of wild-type alleles (NAT-2 *4) and of mutated alleles (NAT-2 *5A, *6A, *7A). The frequency of SA was respectively 28 per cent and 61 per cent in Khmer and Caucasian subjects. The antimode of the distribution of the ratio was different in the two populations: 0.07 in Khmers and 0.18 in Caucasians showing a reduced acetylation capacity in the Khmer population in spite of a higher frequency of RA. The frequencies of alleles were also different between the two populations. Between Khmers and Caucasians respectively: *4: 48.4-23.8 per cent *5A: 15.6-44.2 per cent. *6A: 29.7-32.0 per cent. *7A: 6.3-0 per cent. These differences might be taken into account to define a therapeutic strategy in the treatment of tuberculosis by isoniazide.

Acetylation↗

[Spontaneous and induced variability in Actinomyces rubiginosohelvolus, a new producer of the antibiotic rubomycin].

Mutants possessing 3 times higher activity as compared to the initial culture were obtained as a result of selection of active variants of Act. rubiginosonelvolus, a new organism producing rubomycin against the background of variation induced by N-methyl-N1-nitro-N-nitrozoguinidine, diethylsulphate and their combinations. Further selection among the mutants stable to 6-mercaptopurine and riboflavine resulted in obtaining an active culture No. 3912 at least 7 times more active with respect to rubomycin production than the initial soil culture.

Antibiotics, Antineoplastic↗

Effect of an anabolic steroid (metandienone) on central and peripheral blood flow in well-trained male athletes.

Several haemodynamic variables were measured in sixteen well-trained athletes at rest and during muscular exercise before and after two months of a daily oral dose of 15 mg of metandienone, an anabolic steroid (17alpha-methyl-17beta-hydroxy-1,4-androstadien-3-one). Their training programmes were the same as they had been for at least three years before the study. During metandienone treatment the total blood volume increased by about 15%, and the heart rate decreased significantly both at rest and during exercise. The resting values of cardiac index and stroke index did not differ significantly, while during muscular exercise cardiac index showed a tendency to increase, and stroke index increased by 20% during the treatment period. When treatment was discontinued, the haemodynamic values returned to pre-medication levels, and when a repetition of the treatment was carried out, exactly the same changes were seen. The resting forearm blood flow did not differ significantly during the treatment, while the peak flow during post-ischaemic hyperaemia increased by 27%. The pulmonary blood volume, peripheral resistance and mean arterial pressure did not differ significantly after metandienone treatment. The mean body weight increased significantly during the treatment period.

Administration, Oral↗

Improved method for the measurement of cimetidine in human serum by reverse-phase high-pressure liquid chromatography.

An improved method for the measurement of cimetidine in human serum by reverse-phase HPLC has been developed. The assay involves the addition of the following to 1.0 ml serum: 5 ml of ethyl acetate/isopropanol (96:4 by volume); 0.1 ml of 5N NaOH; and 0.1 ml of the internal standard, N-cyano-N'-methyl-N"-[3-(4-imidazolyl)propyl]-guanidine, which is a close structural analog of cimetidine. The extracted cimetidine is quantitated with high-pressure liquid chromatograph containing a reverse-phase column and a variable-wavelength UV detector (228 nm). The mobile phase consists of methanol in 5 mM K2HPO4 (adjusted to pH 2.8) as a 10:90 mixture by volume. At a flow rate of 2 ml/min, the retention times for the internal standard and cimetidine are 2.8 and 6.2 min, respectively. The standard curve for cimetidine is linear from 0.1 at least 4.0 micrograms/ml in serum. The CV of this assay for cimetidine, obtained from analysis of six replicate samples of a 1.0 microgram/ml serum pool, is 2%. The CV of this method obtained from the daily analysis (N = 12) of the 1.0 microgram/ml cimetidine standard, is 3%, and that from the 0.5 microgram/ml standard is 5%. Cimetidine was found to be stable in refrigerated or frozen serum for 1 month and in whole blood for 24 hr either at room temperature or refrigerated. In the serum from 13 patients receiving cimetidine therapy, the trough cimetidine levels varied from less than 0.1 to 2.7 mg/ml.

Blood Specimen Collection↗

Bone-methyl methacrylate interfacial shear strength: an experimental study of dogs.

Bone-methyl methacrylate interfacial shear strength at failure in chronically implanted hip prostheses was studied. Gorman total hip prostheses fixed with methyl methacrylate bone cement were implanted in 6 large dogs. Interface shear strength studies were performed at 8, 16, and 24 weeks. Mechanical testing determined that the mean interfacial shear strength was 15.2 +/- 13.0 kg/cm2. Variability of the data was too great to allow conclusions to be drawn from statistical analysis, but trends in the data were observed. It was concluded that the interfacial bond had sufficient strength to withstand axial loads 3 to 6 times greater than those applied under normal physiologic conditions.

Animals↗

Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation.

The metabolism of the synthetic glucocorticoid dexamethasone in human liver microsomal incubations has been studied. Metabolites were analyzed by radiometric high-performance liquid chromatography and were identified by liquid-chromatography-mass spectrometry; in addition, the major metabolite 6beta-hydroxydexamethasone was identified by cochromatography with a chemically synthesized standard. A total of 17 human livers were used in this study and the following metabolites were identified: 6beta-hydroxydexamethasone, 6 alpha-hydroxydexamethasone, 6-hydroxy-9 alpha-fluoro-androsta-1,4-diene-11 beta-hydroxy-16 alpha-methyl-3,17-dione (6-hydroxy-9 alpha-F-A) and 9 alpha-fluoro-androsta-1,4-diene-11 beta-hydroxy-16 alpha-methyl-3,17-dione (9 alpha-F-A). Dexamethasone underwent side-chain cleavage to form 9 alpha-F-A. This metabolite was then a substrate for 6-hydroxylation. There was considerable interindividual variability in metabolic profiles. Mean (+/-S.D.) K(m) values for 6 beta- and 6 alpha-hydroxydexamethasone formation were 23.2 +/- 3.8 and 25.6 +/- 1.6 microM (n = 4), respectively. The corresponding V max values were 14.3 +/- 9.9 and 4.6 +/- 3.1 pmol x min(-1) mg protein (-1). Ketoconazole (3 microM) completely inhibited 6 alpha- and 6 beta-hydroxylation, indicating that formation of both metabolites was catalyzed by CYP3A4. This was confirmed in studies of correlations between the rate of metabolite formation and the relative expression of CYP3A4: r = 0.74 for 6 beta-hydroxydexamethasone, P = .003; r = 0.70 for 6 alpha-hydroxydexamethasone, P = .006. In addition to ketoconazole, both ellipticine and gestodene caused marked inhibition of 6-hydroxylation. Ellipticine is clearly not a selective CYP1A inhibitor as has been stated previously. However, furafylline (CYP1A inhibitor), tolbutamide (CYP2C substrate), and sulfaphenazole (CYP2C inhibitor) were essentially noninhibitory. The relatively simple metabolic profile of dexamethasone compared to other steroids may point to this being a potentially useful in vivo probe for CYP3A4 in humans.

Cytochrome P-450 Enzyme System↗

Spontaneous silencing of humanized green fluorescent protein (hGFP) gene expression from a retroviral vector by DNA methylation.

We have constructed a functional murine leukemia virus (MLV)-derived retroviral vector transducing two genes encoding the autofluorescent humanized green fluorescent protein (hGFP) and neomycin phosphotransferase (Neo). This was done to determine whether hGFP could function as a marker gene in a retroviral vector and to investigate the expression of genes in a retroviral vector. Surprisingly, clonal vector packaging cell lines showed variable levels of hGFP expression, and expression was detected in as few as 49% of the cells in a clonally derived culture. This indicated that hGFP expression was silenced in individual cells. This silencing could be diminished by selective culturing of the vector packaging cells with the neomycin analog G418 and was reduced by a 3-day treatment with the demethylating agent 5-azacytidine. The 5-azacytidine effect was transient, and hGFP expression in the vector packaging cells returned to untreated control levels within 2 weeks. Using flow cytometric analysis, hGFP expression was detected in up to 15% of transduced MT4 cells (a CD4+ lymphocytic cell line) after coculturing with packaging cells for 4 days. A 3-day postcoculture treatment with 5-azacytidine was shown to increase the hGFP-expressing MT4 cells from either 10.4% to 11.6% or 3.7% to 4.8%, corresponding to an increase in observed transduction efficiencies of 12% and 30%, respectively. These results indicate that silencing of gene expression from a retroviral vector may result from DNA methylation and occurs rapidly after transduction.

Animals↗

Successful correction of the human Cooley's anemia beta-thalassemia major phenotype using a lentiviral vector flanked by the chicken hypersensitive site 4 chromatin insulator.

beta-Thalassemias are the most common single-gene disorders and are potentially amenable to gene therapy. While retroviral vectors carrying the human beta-globin cassette were notoriously unstable and expressed poorly, considerable progress has now been made using lentiviral vectors (LVs), which stably transmit the beta-globin expression cassette. Mouse studies using LVs have shown correction of the beta-thalassemia-intermedia phenotype and a partial, variable correction of the mouse beta-thalassemia major phenotype, despite the use of beta-globin-hypersensitive sites that are known to result in position-independent effects. Our group used the alpha-globin-hypersensitive site in self-inactivating (SIN) LVs with long-term expression in secondary mice that resisted methylation-associated proviral silencing. However, these vectors also suffered from chromatin position effects. We therefore flanked a SIN-lentiviral vector carrying the human beta-globin expression cassette with a chromatin insulator and studied expression in bone marrow from four patients with transfusion-dependent human thalassemia major. We demonstrated normal levels of human beta-globin expression in erythroid cells produced in in vitro cultures for unilineage erythroid differentiation. There was restoration of effective erythropoiesis and reversal of the abnormally elevated apoptosis that characterizes beta-thalassemia. The gene-corrected human beta-thalassemia progenitor cells were transplanted into immune-deficient mice, where they underwent normal erythroid differentiation, expressed normal levels of human beta-globin, and displayed normal effective erythropoiesis 3-4 months after xenotransplantation. Variability of beta-globin expression in erythroid colonies derived in vitro or from xenograft bone marrow was similar to that seen in normal control subjects. Results show genetic correction of primitive human progenitor cells and normalization of the human thalassemia major phenotype.

Animals↗

Staurosporine impairs both short-term and long-term potentiation in the dentate gyrus in vitro.

The present study shows that the protein kinase inhibitor staurosporine impairs the transient (< 60 min) potentiation (short-term potentiation) evoked by a weak tetanus to about the same extent as the more stable potentiation (long-term potentiation) evoked by a strong tetanus. This effect on short-term and long-term potentiation was seen both as a reduced magnitude and an increased decay rate, the latter being increased by about 50% compared to that seen under normal conditions. Comparison with potentiations evoked at different strengths in control solution suggested that much, but not all, of the increased decay rate observed in the presence of staurosporine could be explained by an impared induction. Staurosporine did not affect the N-methyl-D-aspartate-mediated field excitatory postsynaptic potential evoked by low-frequency stimulation or the magnitude of N-methyl-D-aspartate-mediated currents during high-frequency tetanization. This result suggests that the induction is impaired at a stage not related to the N-methyl-D-aspartate-mediated calcium influx. The present results suggest that short-term and long-term potentiation cannot be separated on the basis of protein kinase dependence. They do not support the common notion that short-term and long-term potentiation are mechanistically separate entities. Instead, the results support the view that long-term potentiation has a variable duration/stability dependent on the induction conditions and that protein kinase activation, via an action on induction mechanisms, contributes to its stabilization.

Alkaloids↗

K-ras and p16 aberrations confer poor prognosis in human colorectal cancer.

PURPOSE: Mutations in the K-ras gene are frequent in human cancer. ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16. At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways. PATIENTS AND METHODS: We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas. p53 mutations and p14 alternative reading frame methylation status were also assessed. Associations with survival were investigated. RESULTS: K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases. p53 mutations were detected in 50% (56 of 115) and p14 methylation in 29% (32 of 112) of cases. K-ras and p16 alterations were independent genetic events. Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant. Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras. Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis. Differences were maintained when cases undergoing radical surgery and without distant metastases were considered. CONCLUSION: These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer.

Adenocarcinoma↗

Epigenetic mechanisms in sexual differentiation of the brain and behaviour.

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

Animals↗

Multivariate statistics of the pyrolysis products of high molecular components in pulping wastewaters to explain their toxicity.

BACKGROUND, AIM AND SCOPE: At present, large-scale paper manufacture involves delignification and bleaching by elemental chlorine free (ECF), or totally chlorine free (TCF) processes. The wastewater is purified by secondary treatment (mechanical, chemical and biological) which removes most of the toxic substances from the discharge. However, we found residual toxicity in the high molecular (> 1000 D) matter (HMWM) of the discharge by test of the RET (reverse electronic transfer) inhibition. This fraction consists mainly of polydispersed lignin (LIG) and carbohydrate (CH) macromolecules. Structural units in these molecules are studied by pyrolysis gas chromatography/mass spectrometry (Pyr-GC/MS). In the present work, our aim was to find out those structural units which could explain the RET toxicity of LIG or CH molecules. We compared statistically RET toxicity values of the HMWM samples from treated wastewaters of pilot pulping experiments and intensity variation of the pyrolysis product gas chromatograms of these samples. This application is a novel study procedure. METHODS: Pyrolysis products (Py-GC/MS results) and inhibition of RET (reverse electronic transport toxicity) as TU50 and TU20 of HMWM (High Molecular Weight Material; Mw > 1000 D) were compared by multivariate statistics. The samples were from laboratory pilot stages of TCF (Totally Chlorine Free) and ECF (Elemental Chlorine Free) manufacture of softwood pulp. Py-GC/MS was done without and with the addition of TMAH (Tetra Methyl Ammonium Hydroxide). The name and structure of each abundant fragment compound was identified from its retention time and mass spectrum compared to authentic reference compounds or literature. Four sets of Toxicity Units (TUs) and GC peak areas of the pyrolysis fragments were obtained. The data were normalized by division with LIG (lignin content of each sample). TU values were dependent and the fragment values independent (explanatory) variables in statistical treatments by SPSS system. Separate analyses of correlations, principal components (PCA) and stepwise multiple linear regression (SMLR) were performed from the four sample sets TCF and ECF with and without TMAH. RESULTS AND DISCUSSION: From the CH fragments, 2-furfural in TCF, and from the LIG fragments, styrene in ECF showed the highest probabilities of originating from source structures of toxicity. Other possible compounds in concern were indicated to be CH fragment 2-methyl-2-cyclopenten-1-one in ECF and LIG fragments 2-methoxy-4-methylphenol, 4,5-dimethoxy-2-methylphenol and 2-methylphenol in TCF.

Alkylating Agents↗

X-chromosome inactivation patterns are unbalanced and affect the phenotypic outcome in a mouse model of rett syndrome.

Rett syndrome (RTT), a neurodevelopmental disorder affecting mostly females, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Although the majority of girls with classic RTT have a random pattern of X-chromosome inactivation (XCI), nonbalanced patterns have been observed in patients carrying mutant MECP2 and, in some cases, account for variability of phenotypic manifestations. We have generated an RTT mouse model that recapitulates all major aspects of the human disease, but we found that females exhibit a high degree of phenotypic variability beyond what is observed in human patients with similar mutations. To evaluate whether XCI influences the phenotypic outcome of Mecp2 mutation in the mouse, we studied the pattern of XCI at the single-cell level in brains of heterozygous females. We found that XCI patterns were unbalanced, favoring expression of the wild-type allele, in most mutant females. It is notable that none of the animals had nonrandom XCI favoring the mutant allele. To explore why the XCI patterns favored expression of the wild-type allele, we studied primary neuronal cultures from Mecp2-mutant mice and found selective survival of neurons in which the wild-type X chromosome was active. Quantitative analysis indicated that fewer phenotypes are observed when a large percentage of neurons have the mutant X chromosome inactivated. The study of neuronal XCI patterns in a large number of female mice carrying a mutant Mecp2 allele highlights the importance of MeCP2 for neuronal viability. These findings also raise the possibility that there are human females who carry mutant MECP2 alleles but are not recognized because their phenotypes are subdued owing to favorable XCI patterns.

Animals↗

Environmental fate of methyl bromide as a soil fumigant.

The great variation among results of recent experiments measuring the total emission of MeBr from fields implies that many factors influence MeBr transport and transformation in the soil-water-air system and its ultimate loss from the soil surface. It has been demonstrated that variables related to application methods (e.g., injection depth, use and type of surface tarp), soil properties (e.g., water content, bulk density, soil organic matter), and climatic conditions (e.g.. air temperature, wind speed, barometric pressure) have pronounced effects on MeBr volatilization following soil injection. The following conclusions can be drawn from this experimental information. Tarping consistently, increased the residence time and concentration of MeBr residing in the soil. Prolonged retention of MeBr in the soil resulted in more extensive degradation and reduced cumulative emissions. Research indicates that the polyethylene film typically used for the surface cover is relatively permeable to MeBr and allows significant emissions compared to virtually impermeable plastic films. This effect is more pronounced during periods of high temperature. Soil type, soil water content, and bulk density are important factors affecting MeBr transport and transformation in soil, which ultimately affect volatilization. The total volatilization from a soil with high organic matter content may be drastically reduced relative to that from a low organic matter soil. Amendment of the surface soil with organic matter or nucleophilic compounds that promote increased degradation may offer another method for reducing volatilization. MeBr volatilization may also be decreased by increasing soil water content and bulk density, mainly because of the reduced gas-phase diffusion resulting from reduced soil air-filled porosity. To minimize volatilization, MeBr should be applied during periods of cool temperature, injected relatively deep in organic-rich, moist soil, and the soil surface packed and tarped immediately after the application. Depending on site-specific conditions, a new high-barrier plastic should be used. Injecting MeBr during periods of warm temperature, at a shallow depth in dry, loose soil without the use of low-permeability plastic barriers, will likely result in maximum volatilization rates and therefore should be discouraged. Before adopting any new emission reduction technology, the pest control characteristics of the new methodology should be assessed under soil and environmental conditions typical of the region to optimize efficacy while minimizing environmental contamination. There is considerable current scientific evidence indicating that eliminating MeBr use for soil fumigation may not have a significant impact on stratospheric ozone depletion. Management practices can and have been developed that essentially eliminate atmospheric emissions of MeBr and other fumigant compounds following soil application. Some scientists have suggested that there are natural buffers and various unknown sources of MeBr that make it impossible to ascertain that eliminating soil fumigation with MeBr will significantly improve stratospheric ozone levels. It is quite certain, however, that the phase-out will make it much more difficult for growers to economically provide an adequate and healthful food supply in the U.S. and elsewhere in the world. As the phase-out date approaches, there remains a great need for information about MeBr and stratospheric ozone depletion. Stratospheric ozone must be protected, but recent experiments suggest that it can be protected while still allowing MeBr to be used for soil fumigation. A new approach may be warranted in which state and federal regulations recognize that every chemical is a potential environmental contaminant, depending on the properties of the chemical and the environmental conditions prevailing following its application. Ideally, regulations should incorporate incentives to develop technology that minimizes the likelihood that a chemical becomes an environmental and/or public health problem. Rather than instituting an irrevocable ban, allowing for a suspension of chemical use until the appropriate technology is developed to control the undesirable characteristic(s) of the chemical use would provide much more flexibility to growers and may enhance environmental protection by adopting a proactive approach in which growers, chemical manufacturers, regulators, and the public can have confidence.

Adsorption↗