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PubMed1990

Effects of methanol on autonomic thermoregulation of rats at different ambient temperatures.

To measure the effect of methanol on autonomic thermoregulation, male Fischer rats were injected intraperitoneally with saline or 1 or 3 g/kg methanol (20% w/v in saline). The rats were then placed in a chamber, set at an ambient temperature (Ta) of 5, 15, 25, or 35 degrees C, for 60 min while total activity, metabolic rate (MR), evaporative water loss (EWL), and dry thermal conductance were measured. After 60 min, the rat was removed from the chamber and colonic temperature (Tc) was measured. The rats developed a significant hypothermia following the 3 g/kg dosage of methanol at Ta's from 5 to 25 degrees C, while the change in Tc at 35 degrees C was not significant. Total activity decreased following 3 g/kg methanol at Ta's from 15 to 35 degrees C. At a Ta of 25 degrees C, MR was at basal levels and methanol had no effect, but at the other Ta's, where MR was elevated, methanol caused a significant reduction in MR. EWL and thermal conductance were elevated at 35 degrees C in control rats, and methanol reduced EWL at this Ta while it had no effect on conductance at this or any other Ta. These data suggest that the methanol-induced hypothermia and its depressive effect on activity and MR were related. The effect of methanol on the heat loss effectors (EWL, conductance) was not significant or was in the direction of heat conservation. Thus, methanol exposure leads to a significant hypothermia in rats by an inhibitory action on heat production pathways.

Animals↗
PubMed1983

Methanol poisoning.

Methanol poisoning is an uncommon but an extremely hazardous intoxication. Since methanol is a versatile fuel and is having increasing usage in an energy-conscious society, a high index of suspicion and swift laboratory confirmation is essential in managing this poisoning. Methanol poisoning may occur in sporadic or epidemic circumstances. Chronic exposure may occur in the occupational setting. Man is uniquely susceptible to methanol toxicity, perhaps dependent upon folate metabolism. Classic symptoms of methanol toxicity can only occur in laboratory animals who are rendered folate deficient. Folate may be useful in humans enhancing removal of the toxic products of methanol poisoning. The enzyme responsible for metabolism of methanol is alcohol dehydrogenase. Ethanol has a higher affinity for this enzyme and is preferentially metabolized. Simultaneous ethanol and methanol administration may confuse the onset of the intoxication. Pyrazoles may also be used to inhibit alcohol dehydrogenase thus preventing the intoxication. The most important initial symptom of methanol poisoning is visual disturbance. The symptoms may be delayed up to 24 hours after ingestion due to simultaneous alcohol administration and metabolic processes. Laboratory evidence of severe metabolic acidosis with increased anion and osmolar gaps strongly suggest the clinical diagnosis. There may be an important association between mean corpuscular volume which is significantly higher in cases of severe methanol poisoning than in mild cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Effect of methanol on the interaction of monoclonal antibody with free and immobilized atrazine studied using the resonant mirror-based biosensor.

The interaction of monoclonal anti-atrazine antibody D6F3 with free and immobilized atrazine was studied using the resonant mirror-based optical biosensor system IAsys. The binding of antibody to atrazine immobilized on silanized surface through albumin spacer was studied in the presence of methanol. The highest affinity was observed in 10% methanol, the kinetic equilibrium association constant KA was 1.16 x 10(9) mol-1 l compared to 4.3 x 10(8) mol-1 l determined in water. The surface binding capacity was 2-fold lower in the presence of methanol compared to aqueous buffer solution. The kinetic rate constants were significantly improved with low contents of methanol; the fastest association and slowest dissociation occurred at 5 and 10% methanol, respectively. The formation of immunocomplexes was observed even in the presence of 50% methanol. To avoid possible disturbing effects resulting from the immobilization of atrazine, the interaction of free atrazine and antibody was studied using the competitive procedure. The determined values of KA were 9.35, 0.73 and 410 x 10(6) mol-1 l for interactions carried out in 10, 30 and 50% methanol, respectively. For practical determination of atrazine using this antibody, the content of 10% methanol in the assay mixture seems to be the best choice. Thirty percent methanol resulted in the lowest affinity; 50% methanol provides the highest affinity, but much smaller signal is measured. The affinity biosensor system IAsys appeared to be a suitable, rapid and convenient tool for studies of binding interactions in the presence of organic solvents.

Antibodies, Monoclonal↗
PubMedDate not supplied

Design of methanol Feed control in Pichia pastoris fermentations based upon a growth model.

The methylotrophic yeast Pichia pastoris is an effective system for recombinant protein productions that utilizes methanol as an inducer, and also as carbon and energy source for a Mut(+) (methanol utilization plus) strain. Pichia fermentation is conducted in a fed-batch mode to obtain a high cell density for a high productivity. An accurate methanol control is required in the methanol fed-batch phase (induction phase) in the fermentation. A simple "on-off" control strategy is inadequate for precise control of methanol concentrations in the fermentor. In this paper we employed a PID (proportional, integral and derivative) control system for the methanol concentration control and designed the PID controller settings on the basis of a Pichia growth model. The closed-loop system was built with four components: PID controller, methanol feed pump, fermentation process, and methanol sensor. First, modeling and transfer functions for all components were derived, followed by frequency response analysis, a powerful method for calculating the optimal PID parameters K(c) (controller gain), tau(I) (controller integral time constant), and tau(D) (controller derivative time constant). Bode stability criteria were used to develop the stability diagram for evaluating the designed settings during the entire methanol fed-batch phase. Fermentations were conducted using four Pichia strains, each expressing a different protein, to verify the control performance with optimal PID settings. The results showed that the methanol concentration matched the set point very well with only small overshoot when the set point was switched, which indicated that a very good control performance was achieved. The method developed in this paper is robust and can serve as a framework for the design of other PID feedback control systems in biological processes.

Bioreactors↗
PubMed1991

Methanol oxidation and assimilation in Hansenula polymorpha. An analysis by 13C n.m.r. in vivo.

The metabolism of methanol was monitored in whole cells of the methylotrophic yeast Hansenula polymorpha by using [13C]methanol and n.m.r. in vivo. The main products observed under normal conditions were trehalose and glycerol, whereas cells that were starved before exposure to [13C]methanol also accumulated glutamate, glutamine and alanine; formate was also more prominent in spectra from starved cells. Cells exposed to high methanol concentration together with high oxygenation oxidized methanol extensively, leading to formaldehyde accumulation; label was not found in any subsequent metabolic products, indicating possible cell inactivation. [13C]Formate was incorporated into metabolic products in glucose-grown cells exposed to 150 mM-methanol for 3 h, but not in cells starved for 3 h, in which it was oxidized. At 21 degrees C such 3 h-starved cells showed a slower metabolism of [13C]methanol compared with those at 37 degrees C, and also converted methanol into formate rather than into assimilation products. The labelling pattern in trehalose from starved cells at 37 degrees C was consistent with methanol assimilation via the pentose phosphate pathway. Lack of appearance of labelled formaldehyde and formate during metabolism under normal conditions suggests that the linear oxidation pathway is not a major contributor to methanol oxidation; their appearance in extreme conditions suggests instead a more likely role in detoxification.

Carbon Isotopes↗
PubMed2006

Use of the osmolal gap to guide the start and duration of dialysis in methanol poisoning.

OBJECTIVE: Rapid diagnosis and treatment of methanol poisoning is mandatory. Dependence on serum methanol analysis in this situation may delay diagnosis and treatment. The anion and osmolal gaps have been recommended for use as diagnostic tools, but the use of these gaps to evaluate the length of hemodialysis treatment has only been emphasized in a few reports. We evaluated the usefulness of the osmolal gap in estimating the need for dialysis and the duration of this treatment in 17 methanol-poisoned subjects. MATERIAL AND METHODS: Patients were part of a recent outbreak of methanol poisoning, in which the diagnosis upon admission was mainly based on use of the anion and osmolal gaps. The duration of dialysis generally followed the standard recommendation of 8h. During dialysis, blood samples were frequently collected and analyzed to determine acid-base status and serum methanol and to calculate the osmolal gap. In nine patients, the duration of dialysis was compared with the duration necessary to normalize serum methanol and the osmolal gap. RESULTS: There was a good correlation between serum methanol and the osmolal gap during hemodialysis (y=1.09x+3.82; R(2)=0.92). The osmolal gap therefore gives a good estimate of the serum methanol level during hemodialysis, and could have saved a total of 23 h of dialysis treatment (34%) in nine patients had it been applied. CONCLUSIONS: In the absence of serum methanol analyses, the osmolal gap is useful to assess the indication for and duration of hemodialysis in methanol-poisoned patients. In mass poisoning situations, use of the osmolal gap makes it possible to reduce the duration of dialysis in a safe manner.

Acid-Base Equilibrium↗
PubMed1992

Methanol and ethanol oxidase respiratory chains of the methylotrophic acetic acid bacterium, Acetobacter methanolicus.

Acetobacter methanolicus is a unique acetic acid bacterium which has a methanol oxidase respiratory chain, as seen in methylotrophs, in addition to its ethanol oxidase respiratory chain. In this study, the relationship between methanol and ethanol oxidase respiratory chains was investigated. The organism is able to grow by oxidizing several carbon sources, including methanol, glycerol, and glucose. Cells grown on methanol exhibited a high methanol-oxidizing activity and contained large amounts of methanol dehydrogenase and soluble cytochromes c. Cells grown on glycerol showed higher oxygen uptake rate and dehydrogenase activity with ethanol but little methanol-oxidizing activity. Furthermore, two different terminal oxidases, cytochrome c and ubiquinol oxidases, have been shown to be involved in the respiratory chain; cytochrome c oxidase predominates in cells grown on methanol while ubiquinol oxidase predominates in cells grown on glycerol. Both terminal oxidases could be solubilized from the membranes and separated from each other. The cytochrome c oxidase and the ubiquinol oxidase have been shown to be a cytochrome co and a cytochrome bo, respectively. Methanol-oxidizing activity was diminished by several treatments that disrupt the integrity of the cells. The activity of the intact cells was inhibited with NaCl and/or EDTA, which disturbed the interaction between methanol dehydrogenase and cytochrome c. Ethanol-oxidizing activity in the membranes was inhibited with 2-heptyl-4-hydroxyquinoline N-oxide, which inhibited ubiquinol oxidase but not cytochrome c oxidase. Alcohol dehydrogenase has been purified from the membranes of glycerol-grown cells and shown to reduce ubiquinone-10 as well as a short side-chain homologue in detergent solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetobacter↗
PubMed2005

Uptake and disposition of inhaled methanol vapor in humans.

Methanol is a widely used solvent and a potential fuel for motor vehicles. Human kinetic data of methanol are sparse. As a basis for biological exposure monitoring and risk assessment, we studied the inhalation toxicokinetics of methanol vapor in four female and four male human volunteers during light physical exercise (50 W) in an exposure chamber. The relative uptake of methanol was about 50% (range 47-53%). Methanol in blood increased from a background level of about 20 to 116 and 244 microM after 2 h exposure at 0, 100 ppm (131 mg/m3) and 200 ppm (262 mg/m3), respectively. Saliva showed substantially higher levels than blood immediately after exposure. This difference disappeared in a few minutes; thereafter the concentrations and time courses in blood, urine, and saliva were similar, with half times of 1.4, 1.7, and 1.3 h, respectively. The postexposure decrease of methanol in exhaled air was faster, with a half time of 0.8 h. The methanol concentrations were approximately twice as high in all four types of biological samples at 200 compared to 100 ppm. No increase in urinary formic acid was seen in exposed subjects. Our study indicates non-saturated, dose-proportional kinetics of methanol up to 200 ppm for 2 h. No gender differences were detected. Similar, parallel patterns were seen with regard to the methanol time courses in blood, urine, and saliva, whereas the concentration in exhaled air decreased markedly faster. Thus, apart from blood and urine, saliva also seems suitable for biomonitoring of methanol exposure.

Adult↗
PubMed1996

Serum concentrations of methanol after inhalation at 200 ppm.

Methanol has been proposed as an alternative automotive fuel to reduce pollution in the urban environment. Utilization of methanol will increase exposure to low levels of methanol vapors for the general public and in occupational settings. Information on absorption by inhalation and serum concentrations after low-level exposure would be important in evaluating the health impact of generalized methanol exposure. During a randomized double-blind study of the potential neurobehavioral effects of inhaled methanol at 200 ppm for 4 hours, 15 timed specimens from 22 subjects were obtained for methanol analysis by head-space gas chromatography. Methanol was rapidly absorbed by inhalation (absorption rate constant = 0.87 +/- 0.60 hours-1). Serum methanol concentrations were increased by more than fourfold at the end of the exposure period (6.5 +/- 2.7 vs 0.9 +/- 0.6 mg/L), as were urinary methanol excretion rates, although formate concentrations were not increased over background concentrations. The overall (n = 22) elimination half-life was 3.2 +/- 2.3 hours. Elimination from plasma fit a monoexponential model for only half of the subjects during the 4-hour postexposure follow-up period (mean half-life = 2.2 hours). Subjects with poor fits either showed greater variability or apparent slow (nonsignificant) declines in serum methanol concentrations, possibly because of the offsetting contributions of dietary intake or endogenous production, but more likely as a result of the limited number of sampling times and limited follow-up period.

Adult↗
PubMed1978

Growth and methanogenesis by Methanosarcina strain 227 on acetate and methanol.

Methanosarcina strain 227 exhibited exponential growth on sodium acetate in the absence of added H(2). Under these conditions, rates of methanogenesis were limited by concentrations of acetate below 0.05 M. One mole of methane was formed per mole of acetate consumed. Additional evidence from radioactive labeling studies indicated that sufficient energy for growth was obtained by the decarboxylation of acetate. Diauxic growth and sequential methanogenesis from methanol followed by acetate occurred in the presence of mixtures of methanol and acetate. Detailed studies showed that methanol-grown cells did not metabolize acetate in the presence of methanol, although acetate-grown cells did metabolize methanol and acetate simultaneously before shifting to methanol. Acetate catabolism appeared to be regulated in response to the presence of better metabolizable substrates such as methanol or H(2)-CO(2) by a mechanism resembling catabolite repression. Inhibition of methanogenesis from acetate by 2-bromoethanesulfonate, an analog of coenzyme M, was reversed by addition of coenzyme M. Labeling studies also showed that methanol may lie on the acetate pathway. These results suggested that methanogenesis from acetate, methanol, and H(2)-CO(2) may have some steps in common, as originally proposed by Barker. Studies with various inhibitors, together with molar growth yield data, suggest a role for electron transport mechanisms in energy metabolism during methanogenesis from methanol, acetate, and H(2)-CO(2).

Acetates↗
PubMedDate not supplied

Serum methanol levels in subjects with or without optic nerve head disease.

We evaluated serum methanol levels in subjects with or without optic nerve head disease. Serum methanol levels were determined using gas chromatography in 71 patients with optic nerve head disease and in 127 subjects without optic nerve head disease. Their ages ranged from 17 to 89 years. Serum methanol levels in 127 subjects without optic nerve head disease ranged from 0.12 to 3.86 microg/ml (mean +/- standard deviation, 1.72 +/- 0.86 microg/ml). In the subjects without optic nerve head disease, the differences in the levels between those with cataract versus retinal detachment, men versus women, and between each age-group (50-80 years) were not significant. The methanol levels in patients with optic neuritis (n = 2), Wolfram syndrome (n = 1), Leber hereditary optic neuropathy at the late stage (n = 2), retinitis pigmentosa (n = 23), and primary open-angle glaucoma (n = 16) were less than 3.86 microg/ml. Methanol levels in 1 patient with Leber hereditary optic neuropathy at the acute stage was 5.28 microg/ml. Of 10 patients with primary angle-closure glaucoma, 1 had a slightly elevated level and 9 had levels less than 3.86 microg/ml. Of 17 patients with normal tension glaucoma, 5 had methanol levels higher than 3.86 microg/ml, and 12 patients had levels less than 3.86 microg/ml. The present study shows that serum methanol levels in subjects without optic nerve head disease ranged from 0.12 to 3.86 microg/ml and were much lower than the levels that produce acute ocular symptoms of methanol intoxication. It is possible that high serum methanol levels may play a part in the acute stage of Leber hereditary optic neuropathy and normal tension glaucoma in certain patients. It is unlikely that increased serum methanol levels participate in primary angle-closure glaucoma.

Adolescent↗
PubMed2005

Fomepizole may change indication for hemodialysis in methanol poisoning: prospective study in seven cases.

BACKGROUND: Treatment of methanol poisoning includes administration of buffer, antidote and hemodialysis. The role of hemodialysis using the new antidote fomepizole has not been studied. We studied the kinetics of methanol and formate during hemodialysis, and the possibility for delayed hemodialysis in the methanol poisoned patients without severe metabolic acidosis or visual disturbances. PATIENTS AND METHODS: Prospective case series study on methanol, formate and dialysis kinetics in 7 cases of severe methanol poisoning treated with buffer, fomepizole and hemodialysis (average 7 hours, range 5 - 8). Four patients were dialyzed early after diagnosis was obtained, while three were dialyzed "electively" the next day. RESULTS: The median pH upon admission was 6.9 (range 6.6 - 7.5) and median base deficit 20.4 mmol/l (range 5.1 - 30.0). Their median S-methanol was 76.3 mmol/l (range 15.6 - 140.6) and S-formate 13.6 mmol/l (range 3.3 - 21). The median half-life of methanol during fomepizole treatment before dialysis was 71.2 hours (range 69.3 - 77); compared to 2.5 hours (range 1.7 - 3.3) during procedure. The median half-life of formate during dialysis was 1.7 hours (range 1.5 - 1.9). The median dialysis clearance of methanol was 222 ml/min (range 204 - 232) and for formate 225 ml/min (range 220 - 229) at a blood flow of 250 ml/min. One patient died and 2 were discharged with permanent visual and cerebral sequelae, whereas one died one year later. All three patients, in whom "elective" hemodialysis was performed, were discharged without sequelae. CONCLUSION: The efficacy and side effect profile of fomepizole may change the role of hemodialysis in methanol poisoning. More patients may be stabilized in local hospitals and transferred for "elective" dialysis, if methanol removal is still indicated after correction of metabolic acidosis.

Acidosis↗
PubMed1997

Methanol as an alternative fixative for cytological smears.

Ninety-five percent (95%) ethanol is the standard cytological fixative used in many laboratories. Commercially available ethanol is expensive and not freely available in some institutions. Methanol, a tissue dehydrant, is also known to be a cytological fixative. However its efficacy has not been assessed or documented in the literature. One hundred and eight consecutive fine needle aspiration biopsies (FNAB) of thyroid performed at the Department of Pathology, Faculty of Medicine, Colombo were included in a study to assess the efficacy of methanol as a cytological fixative. Aspirated material was smeared on at least 2 slides, one fixed in ethanol and the other in methanol, and stained with haematoxylin and eosin (H&E). The 2 smears were separately assessed for preservation of colloid and cells (nuclei and cytoplasm), as determined by the staining quality with the H&E stain. A score was given for each smear and the final scores for ethanol and methanol were statistically compared. The evaporation rates for ethanol and methanol were calculated. The total score for preservation of colloid was 294/300 (98%) for methanol and 291/300 (97%) for ethanol (p = 0.4). The total score for preservation of cells (nuclear and cytoplasmic) was 276/279 (98.9%) for methanol and 274/279 (98.2%) for ethanol (p = 0.7). The evaporation rates per 100 ml when the bottles used for fixation were kept closed and open per 24 hours were 1 and 37 for methanol and 0 and 17 for ethanol. Literature search did not show inhalational side effects of methanol in humans under standard laboratory conditions. We conclude that methanol is as effective as ethanol for fixation of smears and cheaper.

Biopsy, Needle↗
PubMed1991

Effects of methanol vapor on human neurobehavioral measures.

Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three-choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand steadiness; visual search task; Gamberale reaction time task; visual tracking task; Sternberg memory task; interval production task; and speeded addition task. Two dual tasks were also included in the task batteries. These endpoints were selected from those indicated in the literature to be sensitive to solvents, and from those that are widely used in other neurobehavioral test batteries to identify the effects of environmental pollutants. Because the number of endpoints examined was large and the number of subjects was small, procedures designed to reduce the number of statistical tests performed were used. Mean methanol concentration in the exposure room during methanol exposures was 249 mg/m3 (SD +/- 7 mg/m3). Exposure produced significant increases in blood and urine methanol concentration. As expected, no changes in plasma formate were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Effects of methanol cryosolvents on the structural and catalytic properties of bovine trypsin.

The effect of aqueous methanol cryosolvents on the catalytic and structural properties of bovine trypsin has been investigated. The low freezing points and low viscosities of methanol-based cryosolvents are desirable for a variety of cryoenzymological experiments. Increasing concentrations of methanol caused increases in the values of kcat and Km for the hydrolysis of N alpha-benzyloxycarbonyl-L-lysine p-nitrophenyl ester at 0 degrees C and a small increase in Ki for inhibition by benzamidine. Based on product analysis the increase in kcat with increasing methanol concentration at pH* 4.0 and 6.5 can be completely accounted for by nucleophilic competition of methanol for the acyl enzyme intermediate. This observation indicates that deacylation is the rate-limiting step under these conditions. The effect of increasing methanol concentration on kcat/Km for the above ester substrate and N alpha-benzoyl-L-arginine p-nitroanilide was similar. Incubation experiments indicated that trypsin was quite stable in 70% methanol at 0 degrees C and below. The Arrhenius plot for the catalytic reaction in 70% methanol was linear over the 0 to -40 degrees C range, indicating no change in rate-determining step nor temperature-induced structural perturbation. No evidence for structural effects induced by methanol or temperature were detected by monitoring the intrinsic fluorescence and absorbance. We conclude that aqueous methanol cryosolvents are satisfactory for cryosolvent studies of trypsin.

Dimethyl Sulfoxide↗
PubMed1997

Perinatal methanol exposure in the rat. II. Behavioral effects in neonates and adults.

The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PND 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.

Administration, Inhalation↗
PubMed2006

Impact of methanol concentration on secreted protein production in oxygen-limited cultures of recombinant Pichia pastoris.

The methylotrophic yeast Pichia pastoris is a powerful system for production of recombinant proteins, showing high ability to secrete properly folded proteins. A major plus is the strong AOX1 promoter highly induced by methanol. During growth on methanol, however, oxygen readily becomes limiting. In oxygen-limited cultivations of recombinant Pichia pastoris, the methanol concentration had a strong impact on the production of a single-chain antibody fragment (scFv). High methanol concentrations were required to compensate the lack of oxygen and fully induce recombinant protein production, at the same time reducing gratuitous biomass formation due to a lower biomass yield. Product concentrations of 60, 150, and 350 mg/L were obtained with methanol concentrations of 0.3, 1, and 3% (v/v). Moreover, accumulation of a putative product fragment that cannot be removed during affinity purification was prevented at high methanol concentrations. Cell vitality after 100 h was maintained above 98% and 96% of the culture with 0.3% and 3% methanol, respectively. In cultivations supplemented with oxygen, in contrast, methanol concentration between 0.3% and 3% did not influence the product yield of 300-400 mg/L. Thus, efficient recombinant protein production under oxygen-limitation seems to require high methanol concentrations, enabling product concentration as high as otherwise obtained only with expensive supply of pure oxygen.

Animals↗
PubMed1993

Evidence that catalase is a major pathway of ethanol oxidation in vivo: dose-response studies in deer mice using methanol as a selective substrate.

Recently, it was demonstrated that 4-methylpyrazole was not only an inhibitor of alcohol dehydrogenase but also caused competitive inhibition of fatty acyl-CoA synthetase, the enzyme which activates fatty acids (B. U. Bradford, D. T. Forman, and R. G. Thurman, 1993, Mol. Pharmacol. 43, 115-119). Rates of catalase-dependent alcohol metabolism were decreased in alcohol dehydrogenase-negative (ADH-) deer mice because the H2O2 supply for catalase via peroxisomal fatty acid oxidation was inhibited due to substrate limitation. In light of these findings it became necessary to reevaluate the role of catalase and alcohol dehydrogenase in alcohol metabolism. In this study, methanol, a selective substrate for catalase in rodents, was compared with ethanol. Rates of ethanol and methanol metabolism were studied in vivo at blood alcohol levels ranging from 50 to 500 mg/dl. In the ADH- deer mouse, rates of methanol and ethanol metabolism increased when alcohol was elevated from 0 to 100 mg/dl and were maximal at values around 6-8 mmol/kg/h (half-maximal rates were observed at blood alcohol levels around 50 mg/dl). In the ADH+ deer mouse, rates of ethanol metabolism increased to values around 9 mmol/kg/h at 100 mg/dl and remained constant at blood levels up to 500 mg/dl. In contrast, rates of methanol metabolism increased to values of only 5 mmol/kg/h at levels of 100 mg/dl (the half-maximal rate was about 2.5 mmol/kg/h at 50 mg/dl) followed by a steady increase to 9 mmol/kg/h as the blood level was increased from 100 to 500 mg/dl (the half-maximal rate for this second component was around 6 mmol/kg/h at 300 mg/dl). Rates of methanol uptake were 50 +/- 4 nmol/min/mg protein in 10,000g pellets from ADH- deer mouse livers; however, methanol was not metabolized by isolated microsomes. The catalase inhibitor aminotriazole decreased ethanol and methanol metabolism 75% in ADH- deer mice. Further, olive oil, which is rich in oleate, increased methanol metabolism from 7 to 11.5 mmol/kg/h. This stimulation was blocked by fructose, which diminishes ATP and decreases H2O2 supply. In the ADH+ deer mouse, fructose (2 g/kg) stimulated ethanol metabolism as expected; however, inhibition of both ethanol and methanol metabolism was observed with higher doses of fructose (10 g/kg). Taken together, these data support the hypothesis that catalase is the predominant pathway for alcohol metabolism in the ADH- deer mouse. The contribution of catalase was about 50% in the ADH+ mutant at low doses of ethanol and approached 100% as the alcohol concentration was elevated.

Alcohol Dehydrogenase↗