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PubMed1981

[In vitro electrophysiological determination of an individual ouabain sensitivity of human ovarian tumors].

In the standardized ouabain test (10(-4) mol/l, 2 h) 10 different cell cultures react with cell kind specific transmembrane potential (TMP) changes. Primary cultures of human embryo cells and skin transmembrane potential (TMP) changes. Primary cultures of human embryo cells and skin fibroblasts revealed the highest sensitivity (approx. 60-70% TMP reduction), while smaller and relatively low sensitivities were observed for permanent cells (approx. 30-40% TMP reduction) and white blood cells (approx. 20% TMP reduction), respectively. Unlike these cells, 36 human ovarian tumors showed interindividually varied reactions within the range of TMP changes from -55% to +33%. Especially, the majority of malignant tumors exhibited only a weak reaction in the ouabain test or no reaction at all. Ovarian cysts or clinically benign tumors showed a normal ouabain effect. The striking reactions of the ovarian tumor cells are believed to demonstrate a defect of one or several transport enzymes, especially of the (Na+/K+)-activated membrane ATPases. Possible correlations between the disturbed transport mechanisms of the cell membrane and the control of the cell growth and cell division are discussed.

Animals↗
PubMed1981

Spectrophotometric and liquid-chromatographic studies of thymolphthalein monophosphate. Specifications for high-quality substrate for the measurement of prostatic acid phosphatase activity.

Fourteen lots of thymolphthalein monophosphate (TMP), disodium salt, obtained from 10 commercial suppliers were compared spectrophotometrically at 445 and 595 nm, liquid-chromatographically with monitoring at 254 nm, and enzymically by measurements of activity of prostatic acid phosphatase in human serum. Eight lots were classified as "unacceptable," six as "acceptable." Spectrophotometric testing revealed four lots with excessive thymolphthalein and three lots with grossly deficient amounts of TMP. In general, the chromatographic results paralleled those obtained by spectrophotometry, and both results correlated well with enzymic activity. Changing water content in this hygroscopic salt was a major problem, which resulted in great uncertainty as to the formula weight and therefore as to the moles of TMP actually taken. From these studies, specifications for high-quality TMP were determined. The critical importance of simultaneous enzymic activity measurements in comparisons with other "acceptable" lots in defining an adequate TMP substrate is stressed. Use of these specifications for selecting TMP for acid phosphatase activity measurements should improve intra- and inter-laboratory analytical performance.

Acid Phosphatase↗
PubMed1994

Protective effect of tetramethylpyrazine against damages of aortic endothelial cells elicited by low-density lipoproteins.

Effects of tetramethylpyrazine (TMP) on endothelial cells damaged by low-density lipoproteins (LDL) were investigated. When endothelial cells were incubated with LDL (1.5 mg protein.ml-1) the level of malondialdehyde (MDA) was increased and the activity of superoxide dismutase (SOD) was inhibited, and levels of cGMP and epoprostenol were decreased. TMP at concentrations of both 20 and 150 mg.L-1 nullified the inhibition of SOD activity and the reduction of cGMP and epoprostenol content elicited by LDL. However, the elevation of MDA content induced by LDL was negated by TMP only at 150 mg.L-1. TMP also caused a reduction in MDA content and an increase of epoprostenol level in normal endothelial cells. This study suggests that TMP protects endothelial cells against damages elicited by LDL and that the protection of TMP might be due to reduction in lipid peroxidation through stimulation of production and/or release of epoprostenol.

Animals↗
PubMedDate not supplied

Trimethoprim-sulfamethoxazole pharmacokinetics in trauma patients.

STUDY OBJECTIVES: To characterize the pharmacokinetic profile of trimethoprim-sulfamethoxazole (TMP-SMX) in trauma patients and to compare these parameter estimates with those obtained in nontrauma patients. DESIGN: Open-label, multidose, pharmacokinetic study. SETTING: Trauma intensive care unit of a level 1 trauma center located within a regional medical center. PATIENTS: Fifteen adult trauma patients with serious gram-negative infections. All patients were studied on day 1 of treatment, nine on day 3, three on day 5, and two on day 7. One patient was discontinued from the study because of a possible drug-induced rash. INTERVENTIONS: Study patients received TMP 4 mg/kg and SMX 20 mg/kg intravenously every 12 hours. Serial blood sampling was performed up to 4 times per patient between treatment days 1 and 7. Serum was assayed for TMP-SMX using high-performance liquid chromatography. A one-compartment model was fit to the data using maximum likelihood estimation. MEASUREMENTS AND MAIN RESULTS: Mean (SD) baseline parameter estimates for TMP were volume 2.1 (0.65) L/kg, half-life 9.7 (3.0) hours, and clearance 2.6 (0.80) ml/min/kg. Estimates for SMX were volume 0.51 (0.10) L/kg, half-life 7.8 (2.0) hours, and clearance 0.80 (0.29) ml/min/kg. Both volume (p < 0.01) and clearance (p < 0.001) for SMX were significantly higher and half-life (p < 0.05) significantly shorter than previously reported estimates in nontrauma patients. No significant differences in TMP parameter estimates were found. Neither TMP nor SMX clearance was significantly correlated with estimated creatinine clearance (p > 0.05). CONCLUSION: The results indicate that the pharmacokinetics of SMX in trauma patients differ significantly from nontrauma patients, which may result in lower than expected concentrations using standard dosing guidelines.

Accidents↗
PubMedDate not supplied

Oral absorption of trimethoprim-sulfamethoxazole in patients with AIDS.

STUDY OBJECTIVE: To determine the bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) in patients infected with the human immunodeficiency virus (HIV). DESIGN: Open-label, randomized, two-way crossover trial. SETTING: Outpatient clinical research center affiliated with a community-based teaching hospital. PATIENTS: Ten individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) with CD4+ counts less than 200 cells/mm3, receiving TMP-SMX one double-strength tablet 3 times/week as prophylaxis for Pneumocystis carinii pneumonia (PCP), and without documented gastroenteropathy or diarrhea agreed to participate in the trial. One patient withdrew from the study secondary to development of symptomatic PCP. Data were available for analysis from the remaining nine subjects. INTERVENTIONS: Participants received TMP 160 mg and SMX 800 mg orally or intravenously during two study periods. Following dose administration, blood samples were collected at predetermined time points over 36 hours. MEASUREMENTS AND MAIN RESULTS: Analysis of TMP-SMX pharmacokinetic parameters (half-life, total body clearance, area under the serum concentration versus time curve, and peak concentration) failed to reveal any significant differences between intravenous and oral preparations. The calculated bioavailabilities of oral TMP and SMX (mean +/- SD) were 102.7% +/- 19.8% and 109.4% +/- 19.4%, respectively. CONCLUSION: The absorption of TMP-SMX is not adversely affected by HIV infection in the absence of HIV-induced gastroenteropathy or diarrhea.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Fluorescence properties of quinacrine- and spin-labelled oligodeoxynucleotide.

Oligodeoxynucleotides involving a stable nitroxide radical, 5-(2,2,5,5-tetramethyl-3-ethynylpyrroline-1-oxyl)-2-deoxyuridine residue (TMP), and a fluorescence dye, quinacrine (Qu), on each complementary strand and those on the same strand in the duplexes were prepared. Three base-pair units locate between TMP and Qu. The interaction between TMP and the excited singlet Qu has been studied by picosecond transient absorption spectroscopy and fluorometry. From the biphasic fluorescence decay profile, it was suggested that there exist two sites of the dye in the oligodeoxynucleotide with the modifiers in the different complementary strands. In addition, no effective fluorescence quenching was observed for this oigodeoxynucleotide. On the other hand, the triphasic fluorescence decay profile was observed for the oligodeoxynucleotide having Qu and TMP in the same strand and the fluorescence was slightly quenched. Picosecond transient absorption spectroscopy revealed that the enhanced intersystem-crossing by TMP was responsible for the quenching of the fluorescent state of the dye. From these results, it has been concluded that the role of the DNA duplex in the quenching process of the dye by TMP was rather small.

Fluorescent Dyes↗
PubMed1997

Which method of flicker perimetry is most effective for detection of glaucomatous visual field loss?

PURPOSE: The authors compared the efficacy of two different forms of flicker perimetry: temporal modulation perimetry (TMP), which measures contrast thresholds for a fixed temporal frequency, and critical flicker frequency (CFF), which measures the highest frequency for which flicker is detected at a fixed contrast. METHODS: The authors compared 16 patients with early to moderate glaucomatous visual field loss with 16 age-matched normal controls. Flicker stimuli consisted of 2 degrees diameter targets of 2 seconds in duration, presented in 44 locations throughout the central 30 degrees visual field. Flicker was presented within a cosine envelope to avoid temporal transients. For TMP, contrast sensitivity thresholds were measured for 8-Hz sinusoidal flicker; CFF thresholds were measured for a stimulus of 100% contrast. RESULTS: The results indicate that TMP and CFF produced similar test-retest reliability in normals. CFF had slightly better reliability in glaucoma patients. Receiver operating characteristic analysis revealed that TMP could provide better separation of normals and glaucoma patients than did CFF. Similar findings were obtained when the thresholds for both procedures were converted to Z scores. CONCLUSIONS: Both methods of flicker perimetry testing provide acceptable test-retest reliability, and both can distinguish normal subjects from glaucoma patients. However, TMP is more effective in separating normal subjects from glaucoma patients than CFF, suggesting that TMP is the method of choice for detecting glaucomatous damage using flicker perimetry.

Aged↗
PubMed1993

Flow cytometric analysis of altered mononuclear cell transmembrane potential induced by cyclosporin.

Immunosuppression by the fungal metabolite cyclosporin A (CsA) is characterized by functional inhibition, rather than destruction of cells. Because activation of immune cells involves intracellular signalling events associated with modulations of cell transmembrane potential (TMP), we tested the ability of cyclosporin A (CsA) to modulate immune mononuclear cell TMP in vitro using a TMP sensitive cationic dye, dihexyloxacarbocyanine (DIOC6(3)). All analyses were performed by flow cytometry. CsA increased TMP in monocytes and lymphocytes isolated from the blood of healthy human volunteers. CsA-induced hyperpolarization was time and concentration dependent in monocytes while the lymphocyte hyperpolarization, although time dependent, was evident over the entire range of CsA concentrations tested. CsA-induced hyperpolarization of lymphocytes was dependent on potassium ion (K+) efflux as indicated by the absence of hyperpolarization in 154 mM KCl or with pretreatment with 100 microM quinine (an inhibitor of K+ channels). Monocyte hyperpolarization by CsA was not inhibited in either system. Dihydrocyclosporin C (DH-CsC), an immunosuppressive analog of CsA, also hyperpolarized mononuclear cells. The anionic TMP sensitive dye bis oxonal (diBA-C4) indicated that CsA treatment depolarized mononuclear cell plasma membranes. The mitochondrial poison carbonyl cyanide p-trifluoromethoxy-phenyl-hydrazine (FCCP) eliminated CsA induced hyperpolarization and also indicated that CsA caused plasma membrane depolarization. We conclude that brief in vitro exposure to cyclosporin alters the transmembrane electrical potential of human lymphocytes and monocytes.

Cyclosporine↗
PubMed2001

The aquatic fate of triclopyr in whole-pond treatments.

The aquatic fate of the triethylamine salt formulation of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) was determined in whole-pond applications in closed (no water exchange) systems in California, Missouri and Texas in two studies conducted in 1995 and 1996. These studies determined dissipation rates of triclopyr and its principal metabolites, 3,5,6-trichloropyridinol (TCP) and 3,5,6-trichloro-2-methoxypridine (TMP) in water, sediment and finfish. Ponds at each site containing a healthy biological community were treated at 2.5 mg AE litre-1 triclopyr. Water and sediment samples were collected through 12 weeks post-treatment, and non-target animals were collected through 4 weeks post-treatment. Dissipation rates for triclopyr, TCP and TMP were similar at each of the study sites, despite differences in weather, water quality, biotic community, light transmission and geographic location. Half-lives of triclopyr in water ranged from 5.9 to 7.5 days, while those of TCP and TMP ranged from 4 to 8.8 and 4 to 10 days, respectively. Levels of triclopyr and TCP declined in sediments at half-lives ranging from 2.8 to 4.6 days and 3.8 to 13.3 days, respectively. No TMP was detected in sediment. Triclopyr and TCP cleared from fish in relation to concentrations found in the water column. TMP levels in fish were generally an order of magnitude higher than levels of triclopyr and TCP, particularly in the visceral portion of the animals. No adverse effects on water quality or on the non-target biotic community were found following triclopyr applications. Results of these studies were comparable to those of triclopyr dissipation studies conducted in reservoirs, lakes and riverine systems in Georgia, Florida, Minnesota and Washington, indicating that the degradation and dissipation of triclopyr and its metabolites are similar in representative systems throughout the USA.

Animals↗
PubMed1998

Interactions of hypochlorous acid with pyrimidine nucleotides, and secondary reactions of chlorinated pyrimidines with GSH, NADH, and other substrates.

HOCl-induced chlorination of pyrimidine nucleotides, PyNH, strikingly depends on the nature of the available chlorine acceptor group. For CMP, with an -NH2 group as acceptor, the reaction is slow and involves predominantly the acid [k(CMP + HOCl) approximately 100 M-1 s-1 at pH 6]; apparent rate constants of the reaction decrease around the pK alpha (HOCl), to 0 in alkaline solution. For TMP and UMP, with a heterocyclic > NH group (at 3N) as acceptor, the reaction is faster and involves mainly the conjugated CIO- anion [e.g., k(UMP + ClO-) approximately 3 x 10(4) M-1 s-1 and k(UMP + HOCl) approximately 200 M-1 s-1]. The 3-N-methylthymidine derivative is inert toward HOCl. Reactions of ClO- with TMP, UMP, and poly(U) are shown to be reversible, PyNH + ClO- = PyNCl + OH-; an increase in pH due to this reaction was confirmed, and equilibrium constants have been estimated. The chlorinated derivatives of TMP and UMP are very reactive toward GSH, disulfide, aliphatic amines, and NADH. In contrast, the PyNCl derivative of CMP is unreactive, except with GSH. Rate constants of reactions of PyNCl species with various substrates are presented. Oxidation of NADH, by both HOCl and PyNCl derivatives, leads to a stable product (not NAD+) which is irreversibly degraded by reaction with excess HOCl, but inert toward acsorbate, GSH, and H2O2. Thiols (GSH) and disulfides (DTPA) were previously found capable of scavenging up to four HOCl molecules (Prütz, W. A., Arch. Biochem. Biophys. 332, 110-120, 1996). In the present study it was established that reactions of GSH or DTPA with excess HOCl give rise to a rapid drop in the pH by release of up to four HCl molecules per GSH or DTPA, as expected for a sequence of consecutive sulfoxidations. Reactions of GSH and DTPA with PyNCl efficiently regenerate PyNH, namely up to four molecules per GSH or DTPA in the case of TMP and UMP, but only one molecule per GSH in the case of CMP. The PyNCl derivatives of TMP and UMP transfer chlorine slowly but completely to CMP or AMP. Such chlorine transfer between nucleic acid bases is likely to occur also in DNA; it is shown that HOCl in fact induces a complex series of reactions on interaction with native DNA.

Animals↗
PubMed2001

The effects of singlet oxygen produced by photodynamic action on the mitochondrial permeability transition differ in accordance with the localization of the sensitizer.

We have examined whether the effects of singlet oxygen (1O2) produced by photodynamic action on the mitochondrial permeability transition (PT) can be modulated by the localization of photosensitizers in irradiated mitochondria. We have previously shown that oxidation due to 1O2 photogenerated in hematoporphyrin (HP)-loaded mitochondria can prevent opening of the PT pores, likely after degradation of some critical histidines (Salet et al, 1997, J. Biol. Chem. 272, 21938-21943). Equally, in the present study we have irradiated mitochondria in the presence of a structurally different photosensitizer producing 1O2, namely 4,5',8-trimethylpsoralen (TMP). Fluorescence studies show that TMP binds to protein sites which differ from those of HP. In sharp contrast with HP, TMP-driven photodynamic action triggers per se pore opening. Interestingly, this inducing effect is inhibited when TMP-treated mitochondria are irradiated after addition of mersalyl, a specific reagent protecting thiol groups of the inner mitochondrial membrane that are oriented toward the external hydrophilic phase. This fact suggests that 1O2-mediated thiol oxidation is responsible for TMP-photoinduced pore opening. Taken together, these findings suggest that 1O2 can activate or inactivate a cellular function such as mitochondrial PT depending on the site where it is produced in the mitochondrial membrane.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Mutational analysis of two structural genes of the temperate lactococcal bacteriophage TP901-1 involved in tail length determination and baseplate assembly.

Two putative structural genes, orf tmp (tape measure protein) and orf bpp (baseplate protein), of the temperate lactococcal phage TP901-1 were examined by introduction of specific mutations in the prophage strain Lactococcus lactic ssp. cremoris 901-1. The adsorption efficiencies of the mutated phages to the indicator strain L. lactic ssp. cremoris 3107 were determined and electron micrographs were obtained. Specific mutations in orf tmp resulted in the production of mostly phage head structures without tails and a few wild-type looking phages. Furthermore, construction of an inframe deletion or duplication of 29% in orf tmp was shown to shorten or lengthen the phage tail by approximately 30%, respectively. The orf tmp is proposed to function as a tape measure protein, TMP, important for assembly of the TP901-1 phage tail and involved in tail length determination. Specific mutations in orf bpp produced phages which were unable to adsorb to the indicator strain and electron microscopy revealed particles lacking the baseplate structure. The orf bpp is proposed to encode a highly immunogenic structural baseplate protein, BPP, important for assembly of the baseplate. Finally, an assembly pathway of the TP901-1 tail and baseplate structure is presented.

Adsorption↗
PubMed1980

The effect of trimethylpsoralen--crosslinks on entry of donor DNA in transformation and transfection of Bacillus subtilis.

Transforming chromosomal DNA, irradiated with long-wave UV light in the presence of 4,5',8-trimethylpsoralen (TMP) binds to competent B. subtilis cells as effectively as non-treated DNA, but its transforming activity is strongly reduced. Uptake studies show that the entry of transforming DNA, after some stimulation by short periods of irradiation in the presence of TMP, decreases proportionally with the dose of irradiation. Crosslinking was quantitated by electron microscopy. Since the number of crosslinks increases proportionally with the dose of irradiation, it is suggested that entry of donor DNA is prevented by crosslinks. The inhibition of entry of DNA is paralleled both by decreased breakdown of crosslinked DNA interacting with competent cells, and decreased breakdown by nuclease activity liberated during protoplasting of competent cultures. These data support the model of Lacks et al. (1976) which postulates that a membrane-bound deoxyribonuclease is engaged in the entry of donor DNA into the competent cell. The transforming activity of the chloramphenicol-resistance carrying plasmid pC194, originally obtained from Staphylococcus aureus, is also destroyed by TMP crosslinks. Contrary to chromosomal DNA, its association with the cells is stimulated by long-wave UV irradiation in the presence of TMP, but experiments are presented suggesting that the DNA is still vulnerable to the action of exogenous pancreatic deoxyribonuclease. Transfecting SPP1 DNA is also inactivated by TMP crosslinks. Marker rescue of transfecting DNA containing crosslinks occurs; the extent of rescue of one marker is considerably in excess of that of linked markers.

Bacillus subtilis↗
PubMed1980

Protective effect of trimethylpsoralen against UV-B erythema.

Vitiliginous patients undergoing photochemotherapy with TMP were less susceptible to a sun burn. To investigate this point, the MED for UV-B was measured before, 2 h, and 24 h after oral intake of TMP in 10 healthy volunteers. There was an increase of MED when UV exposure had taken place 2 h after TMP intake (P < 0.01). This was no longer detectable when the exposure had taken place 24 h after intake. MED increase was 11.8% for 0.19 mg/kg TMP, 21.0% for 0.37 mg/kg, and 23.7% for 0.74 mg/kg. This dose-dependence was significant (P < 0.01). The protective effect of TMP against UV-B erythema seemed related to UV absorption by the drug while it was in the blood stream.

Adolescent↗
PubMed1992

Modified cell proliferation due to electrical currents.

In view of the evidence that electrical currents may enhance healing of chronic wounds and retard tumour growth it is suggested that these currents normalise cell proliferation. Additional support to this contention is given by two reports: one on healing of pressure sores in man and one on tumour growth retardation in mice. The effect of an ionic environment on the cell cycle is analysed. Finally a hypothesis attempting to explain the normalising effect of electrical currents on cell proliferation is proposed. It is known that non-dividing cells, e.g. mature neurons, have high transmembrane potential (TMP) whereas fast-dividing cells, e.g. cancerous cells, have low TMP. When a cell is exposed to an electrical field, one side of the cell becomes hyperpolarised while the opposite side is depolarised. Assuming a nonlinear relationship between TMP and the transmembrane ionic currents, it can be shown that in non-dividing cells their high TMP is lowered; whereas in cells with a high division rate, their low TMP is raised due to cell exposure to the external electrical field. These alterations in transmembrane potential could contribute to the normalisation of abnormal cell proliferation.

Animals↗
PubMedDate not supplied

Changes of pharmacokinetics of trimethoprim after pretreatment with streptococcal peptidoglycan.

Trimethoprim (TMP) 10 mg.kg-1 was given orally to calves and rabbits. Two to three weeks later the animals were pretreated by i.v. Peptidoglycan (Pt) 20 micrograms.kg-1. One hour later TMP was administered as above. To other animals under otherwise identical conditions TMP was injected intravenously. The pretreatment with Peptidoglycan induced in both species a significant increase of TMP serum levels positively correlated with temperature elevation. Peptidoglycan pretreatment increased the bioavailability of TMP.

Administration, Oral↗
PubMed1984

Nervous tissue thiamine metabolism in vivo. II. Thiamine and its phosphoesters dynamics in different brain regions and sciatic nerve of the rat.

Different steps of the metabolism of thiamine (T), thiamine mono- (TMP), pyro- (TPP) and triphosphate (TTP) in the cerebellum, brainstem, cerebral cortex and the sciatic nerve were evaluated in the rat in vivo. The radioactivity of T and its phosphoesters was determined at fixed time intervals (0.5-240 h) after an intraperitoneal injection of [14C]T (30 micrograms:1.25 muCi), under steady state conditions. The dynamics of thiamine compounds was evaluated using a compartmental mathematical model that allowed the fractional rate constants (FRC), turnover rates (TR) and turnover times to be calculated. The phosphorylation of T to TPP and the dephosphorylations of TPP to TMP and TMP to T could be estimated in all the structures investigated. Their turnover rates were found to be ordered in the sequence: cerebellum greater than brainstem greater than cerebral cortex greater than sciatic nerve. The transphosphorylation of TPP to TTP was so small that it could not be determined in a reliable way. Regional differences were found both the rate and in the composition of T and TMP mixture released from nervous structures. The shortest turnover time of TPP was found in the cerebellum, while the sciatic nerve exhibited the fastest renewal of T and TMP. In all the structures investigated TPP had a rather short turnover time, suggesting that its function might be associated to a rapid conversion into chemically different forms. The possible relationships between the rates of turnover of T compounds are the sensitivity of the nervous structures to T deficiency are discussed.

Animals↗
PubMed1987

Nervous tissue thiamine metabolism in vivo. III. Influence of ethanol intake on the dynamics of thiamine and its phosphoesters in different brain regions and sciatic nerve of the rat.

The effects of chronic ethanol administration on different steps of the metabolism of thiamine (T), thiamine mono- (TMP) and thiamine pyrophosphate (TPP) in the cerebellum, brainstem, cerebral cortex and sciatic nerve were evaluated in vivo. The radioactivity of T and its phosphoesters was determined in plasma and in the selected nervous structures under steady-state conditions and at fixed time intervals (0.5-192 h) after an i.p. injection of [14C]T (30 micrograms: 1.25 microCi) to rats chronically (35 days) ethanol-treated (daily dose of 4.7 g X kg-1 b.wt. by gastric gavage) and pair-fed controls similarly treated with a sucrose solution isoenergetic with ethanol. All rats were given a nutritionally adequate diet supplying an excess of thiamine, which produced a virtually steady content of thiamine compounds in the tissues. By using a compartmental mathematical model, fractional rate constants, turnover rates and turnover times were calculated. Ethanol caused a reduction of the rate of thiamine compound enzymatic transformations (T phosphorylation to TPP, TPP dephosphorylation to TMP and TMP to T), and a facilitation of the regional uptake of T and TMP, associated to a less relevant influence on their release. Isoenergetic sucrose prevailingly caused an increased rate of thiamine metabolic steps (except phosphorylation in the brainstem and cerebral cortex), with negligible modifications of T and TMP uptake and release. Thus the changes induced by ethanol were virtually opposite to those caused by sucrose.

Animals↗