EFFECTOFDIMETHYLGLYCINEONSPINALNEURONS
作者：Anitha Oommen,Shanthakumar Thomas Oommen Muddanna S Rao
单位：Anitha Oommen,Shanthakumar Thomas Oommen(Fr. Muller's Institute, Mangalore 575 002, India,)；Muddanna S Rao(Kasturba Medical College, Manipal 576 119,India)
关键词：
解剖学报000208
【Abstract】 N, N-dimethyl glycine(DMG),a food supplement, is claimed to be non
-toxic and is known for its immunoprotective and stamina building property. It improves CNS functions,mainly speech in autistic children, causes behavioral improv
, 百拇医药
ement and decreases seizures. To study its effect on the neurons on the ventral half of the cervical enlargement of the spinal cord, DMG dissolved in distilled water was given to 21 day old albino mice at a dose of 20mg/kg body weight per day for 30 days. The ventral half of the cervical enlargement of the spinal cord was studied morphologically. The results showed a significant decrease in the neuron count in the 15-25 micron range in the DMG-treated mice. No significant change was observed in the area of gray matter or white matter or total area. Neurons having a diameter of more than 25 microns showed no change in the cell count.These results suggest a cytotoxic damage caused by DMG.
, 百拇医药
【Key words】 Dimethyl glycine; Neuronal change; Spinal neurons
【 CLC number】R322.85 【Document code】A
【Article ID】0529-1356(2000)02-129
Introduction
N,N-dimethyl glycine, a nutrient[1],a methylated glycine, also known as pangamic acid and calcium pangamate, was once considered to be Vitamin B-15. However dietary deficiency of DMG does not cause any known disease[2]. DMG is present in low levels in meat, seeds and grains[3]. It is claimed to improve speech and behavioral patterns in mentally retarded and autistic children. It is claimed to be non-toxic and with no undesirable side effects[4]. It has been described as a new horizon in therapeutics[5].
, 百拇医药
DMG is known to improve immunity. It increases lymphocyte proliferation, stimulates interferon production and excites natural killer cell production[4]. It stimulates both antibody response and cellular immunity[6]. It also has anti-convulsant[7] and anti-cancer effects[2]. It is not mutagenic[1]. It also acts as an ergogenic nutrient, improving stamina and normalizing physical function[2]. It increases athletic performance though it has no effect on blood pressure, breathing pattern, blood chemistry and body weight[1]. DMG helps to improve oxygen utilization, causes increased tole rance to physical activity during strenuous exercise and faster recovery after such exercise, reducing lactic acid build-up and reducing muscle cram ping[3].
, 百拇医药
Since the effects of DMG on the spinal neurons which are concerned with motor functions have not been reported in literature so far, the present study was undertaken to determine the effect of DMG on the neurons of the cervical enlargement of the spinal cord.
Materials and Methods
Thirty albino mice of the BALB/c strain, of both sexes, aged 21 days, were randomly divided into three groups of ten each, namely normal control (NC), vehicle control(VC) and test group (DMG treated group). Mice in the NC group remained undisturbed in the home cage. Mice in the VC group were given a volume of distilled water equal to the amount of drug given orally. The mice in the test group received dimethyl glycine(DMG),20mg/(kg.day).The dose was extrapolated on the basis of the standard dose conversion table. The drug was administered as an aqueous solution which was prepared by dissolving 125 mg tablet in 12.5 ml of distilled water so that each ml of the solution contains 10 mg of the active ingredient. The dimethyl glycine was obtained from Vitamin World, Oakdale, New York(USA) through the India Christian Gospel Ministries, Chicago. The drug was given for 30 days. The body weight was taken before the commencement of the study and weekly thereafter. On the 31st day the mice were sacrificed. The cervical part of the spinal cord was dissected and a length of 5 mm from the middle of the cervical enlargement of the spinal cord was selected for the study. The tissue was processed and paraffin sections of 3 micron thickness were stained with cresyl violet. The slides were coded to avoid bias.
, 百拇医药
From each animal 8-10 sections at intervals of 15-20 microns (total of 100 sections) were selected for analysis of the gray matter, white matter and total area measurement. The sections were viewed on a screen using a video camera attached to Biolux binocular microscope. The total area ventral to a line drawn across the central canal of the spinal cord was measured using a grid attached to the screen(Fig. 1a). Similarly the total area of the gray matter was measured in the same region(Fig.1a). The area of white matter was calculated by subtracting the area of gray matter from the total area.
, 百拇医药
Similarly, the neuron counts were done from the ventral halves of the spinal cord(right and left sides)using the same equipment. The interval between the two selected sections was 15-18 microns. The number of neurons in the range of 15-25 microns(maximum diameter) and above 25 microns were counted. Neurons below 15 microns and without a clear cell boundary and nucleus were excluded. The diameter was measured using a graduated transparent scale(Fig.1b). All the neurons without differentiating them into different classes of motor neurons and inter neurons were counted. The data was analyzed using the one-way ANOVA test.
, 百拇医药
Figure 1:(a) Video screen with grid to measure the area(each square=2500 sq. microns) and (b) scale to measure the diameter of the neuron
Results
All the three groups of mice were found to be healthy throughout the experiment. Though there was a slight increase in the body weight in the test group,it was not statistically significant(Fig.2). There was no significant difference in the gray matter area between the test and control groups(Table 1). There was also no significant difference in white matter area and the total area in the normal control and test groups(Table 1). There was a decrease in the neuronal count in the range of 15-25 microns in the test group as well as the vehicle control as compared to the normal control group (Table 2, Fig.3). However, only the data derived from the test group showed any statistically signifi-cant decrease in the neuronal count when compared with the control group. But there was no significant change in the number of neurons which had a diameter of more than 25 microns (Table 2).
, 百拇医药
Table 1 Area measurement(in mm2) Area
Normal
control
(Mean±SD)
Vehicle
control
(Mean±SD)
Test
(Mean±SD)
P-value
(Test vs.
, 百拇医药
normal control)
Gray
matter
0.418±0.059
0.404±0.066
0.380±0.154
>0.05
White
matter
0.640±0.086
0.620±0.119
0.645±0.248
, 百拇医药
>0.05
Total
1.058±0.122
1.028±0.157
1.030±0.400
>0.05
% Grey
matter
(of total
area)
39.56±3.58
39.44±4.91
, http://www.100md.com
36.93±3.89
>0.05
% White
matter
(of total
area)
60.43±3.58
60.55±4.91
63.56±4.12
>0.05
Table 2 Neuronal counts Neuronal size
, http://www.100md.com
(Microns)
Normal control
(Mean±SD)
Vehicle control
(Mean±SD)
Test
(Mean±SD)
15-25
27.67±6.03
21.98±4.74
19.31±7.5*
, 百拇医药
>25
2.85±1.38
3.09±1.57
1.91±1.60
*P<0.05(Compared to normal control)
Fig.2 Graph showing comparison of body weights between the three groups of animals.(NC=Normal control;VC=Vehicle control; DMG=DMG treated group).
, http://www.100md.com
Figure 3: Photomicrograph of sections of the cervical enlargement of the spinal cord, stained with cresyl violet. In photograph(a) the horizontal line passes through the central canal(cc)and the box indicates the area magnified in (b)normal control;(c)vehicle control and (d)test group(DMG-treated).Note that the number of neurons is significantly decreased in (d). Scale bar=400 microns in (a) and 50 microns in (b-d).
Discussion
, 百拇医药 N,N-dimethyl glycine is described as a natural simple compound[1] with no undesirable side effects[4]. It is claimed to improve speech in mentally retarded children. Roach and Carlin noticed a dramatic reduction in the seizure frequency in a patient with grand mal seizures[7]. It provides methyl groups which are essential in the formation of vitamins, hormones, enzymes, neurotransmitters and antibodies. It is reported to improve athletic performance and is known to be a stamina nutrient.
, 百拇医药
DMG is also considered to be very beneficial for children with autism as it improves speech and behavior. Although clinical trials of DMG have been carried out on patients with seizures and autism there is no available literature to suggest its effect on the brain or spinal cord. We therefore did a pilot study to determine its effects on the neurons of the ventral half of the spinal cord, which are concerned with motor functions, so that further studies on the more complex regions of the brain can be undertaken at a later stage. Mice of this age group were selected to compare with clinical reports of the efficacy of DMG in infants.
, http://www.100md.com
The mouse spinal cord consists of several different neuron populations clustered together in groups. Ten layers can be recognized in columns throughout the length of the spinal cord. Motor neurons are found in lamina Ⅸ. Lamina Ⅸ consists of columns of neurons located in the ventral horn and embedded in laminae Ⅶ and Ⅷ. The motor neurons supplying the axial musculature are located in the medial part of the ventral horn and those supplying the limb musculature are located laterally[8]. Retrograde labelling by horse radish peroxidase has identified motor neurons in the middle part of the gray matter and at the base of the dorsal horns[9].
, 百拇医药
The area of gray matter when compared to the total area of ventral half of the spinal cord did not show any significant difference between the groups. There was a decrease in the number of neurons of 15-25 microns range in the vehicle group when compared with the control group, which was not statistically significant. This decrease could be due to the stress experienced by the animals during vehicle administration, which is a well accepted phenomenon[10].
, http://www.100md.com
There was a statistically significant decrease in the number of neurons in the 15-25 micron range in the test group when compared to the control group, indicating a possibility of neuronal damage (Figure 3a-d). It is likely that the neurons may have shrunken and reduced in size as seen in degenerative diseases of the central nervous system[11,12]. Since there was no increase in the number of neurons of the size over 25 microns it was unlikely that there was any neuronal enlargement.
, 百拇医药
Glycine is the most abundant amino acid with inhibitory activity found in the ventral quadrant gray matter of the spinal cord. Our investigations showed that dimethyl glycine caused changes suggestive of neuronal atrophy.The exact mechanism by which DMG causes this neuronal damage is not clear. It is unlikely to be due to impurities since the DMG used was the same as is commercially available and was approved by the FDA and patients who have been on this substance have not shown any such toxicities. DMG is an aminoacid which has been found to have a very high margin of safety.The animal doses were administered based on the standard conversion table[13]. Therefore the neuronal changes seen are unlikely to have been dose-related.
, http://www.100md.com
Another possibility for the neuronal changes is that DMG enters the central nervous system and stimulates the strychnine-insensitive N-methyl D-aspartate(NMDA) receptors and opens the calcium channels which function effectively only in the presence of glycine[14]. When the concentration of glycine is increased the ability of glutamate to open the channel is also increased, thereby increasing the glutamate-mediated excitatory response. High concentrations of intracellular calcium may activate calcium dependent proteases and may produce free radicals that are toxic to the cell. Thus dimethyl glycine could predispose to excitotoxicity.
, 百拇医药
Acknowledgements
The authors wish to express their gratitude to Dr. Samson James, President of the India Christian Gospel Ministries, USA, for the generous supply of dimethyl glycine from Vitamin World, Oakdale, New York, USA and to the following staff of the Kasturba Medical College, Manipal:Dr. K. S. Karanth, Head of the Department of Pharmacology, for facilities of the animal house, Dr. P.Sreedevi, Head of the Department of Anatomy, for the availability of the video camera and Biolux microscope.
, 百拇医药
References
[1]Rimland B. Dimethyl Glycine(DMG):a non-toxic metabolite and autism[J]. Autism Res Rev Int, 1995,1:3.
[2]Lawson J, R A Passwater. Dimethyl glycine update-new studies confirm DMG improves health[J]. Let's Live, 1987:45-47.
[3]Walker M. Nutritional medicine:N,N-dimethyl glycine(DMG)[J]. Health Foods Business, 1994:26:92.
[4]Reap A E, J W Lawson. Stimulation of the immune response by dimethyl glycine, a nontoxic metabolite[J]. J Lab Clin Med, 1990,115:481-486.
, 百拇医药
[5]Oommen T. Dimethyl glycine:A new horizon in therapeutics[J]. Indian J Pharm Sci, 1998,49-52.
[6]Graber C D, J M Goost, A D Glassman, R Kendal and C B Loadholt. Immunomodulating properties of dimethyl glycine in humans[J]. J Infect Dis, 1981,143:101-105.
[7]Roach E S, L Carlin. N, N-dimethyl glycine for epilepsy[J]. N. Engl J Med, 1982,307：1081-1082.
[8]Weber U J, T Bock, K Buschard, D Pakkenberg. Total number and size distribution of motor neurons in the spinal cord of normal and EMC-virus infected mice-a stereological study[J]. J Anat,1997,191：347-353.
, http://www.100md.com
[9]Hashizume K, R E Burke, K Kanda. Medial gastrocnemius motor nucleus in the rat;age-related changes in the number and size of motonourons[J]. J Comp Neurol,1988,269：425-430.
[10]Uno H, Tarara R, Else JG. Suleman MA, Sapolsky RM. Hippocampal damage associated with prolonged and fatal stress in primates[J]. J Neurosci, 1989,9:1705-1711.
[11]Andrews J M, M B Gardner, F J Wolfgram, G W Ellison, D D Porter, W W Brandkamp. Studies on the murine form of spontaneous lower motoneuron degeneration-the Wobbler (Wr) mouse[J]. Am J Pathol,1974,76：63-78.
, http://www.100md.com
[12]Duchen L W, S J Strich. A hereditary motor neuron disease with progressive denervation of muscle in the mouse; the mutant“wobbler”[J]. J Neurol Neurosurg and Psychiatry, 1968,31：535-542.
[13]Paget GE, Barnes JM. Surface area ratios of some common laboratory animal species and man, In:Laurence DR, Bacharat AL, eds. Evaluation of Drug Actions:Pharmacometrics[M].New York: Academy Press,Vol.1,1964:161.
[14]Kandel E R, J H Schwartz. Directly gated transmission at the nerve-muscle synapse. In:Kendel ER, Schwartz JH, Jessel TM, eds. Principles of Neural Science[M]. London:Prentice Hall Int.Inc,3rd ed,1991:159-160.
【Received date】 1999-08-25, 百拇医药
单位：Anitha Oommen,Shanthakumar Thomas Oommen(Fr. Muller's Institute, Mangalore 575 002, India,)；Muddanna S Rao(Kasturba Medical College, Manipal 576 119,India)
关键词：
解剖学报000208
【Abstract】 N, N-dimethyl glycine(DMG),a food supplement, is claimed to be non
-toxic and is known for its immunoprotective and stamina building property. It improves CNS functions,mainly speech in autistic children, causes behavioral improv
, 百拇医药
ement and decreases seizures. To study its effect on the neurons on the ventral half of the cervical enlargement of the spinal cord, DMG dissolved in distilled water was given to 21 day old albino mice at a dose of 20mg/kg body weight per day for 30 days. The ventral half of the cervical enlargement of the spinal cord was studied morphologically. The results showed a significant decrease in the neuron count in the 15-25 micron range in the DMG-treated mice. No significant change was observed in the area of gray matter or white matter or total area. Neurons having a diameter of more than 25 microns showed no change in the cell count.These results suggest a cytotoxic damage caused by DMG.
, 百拇医药
【Key words】 Dimethyl glycine; Neuronal change; Spinal neurons
【 CLC number】R322.85 【Document code】A
【Article ID】0529-1356(2000)02-129
Introduction
N,N-dimethyl glycine, a nutrient[1],a methylated glycine, also known as pangamic acid and calcium pangamate, was once considered to be Vitamin B-15. However dietary deficiency of DMG does not cause any known disease[2]. DMG is present in low levels in meat, seeds and grains[3]. It is claimed to improve speech and behavioral patterns in mentally retarded and autistic children. It is claimed to be non-toxic and with no undesirable side effects[4]. It has been described as a new horizon in therapeutics[5].
, 百拇医药
DMG is known to improve immunity. It increases lymphocyte proliferation, stimulates interferon production and excites natural killer cell production[4]. It stimulates both antibody response and cellular immunity[6]. It also has anti-convulsant[7] and anti-cancer effects[2]. It is not mutagenic[1]. It also acts as an ergogenic nutrient, improving stamina and normalizing physical function[2]. It increases athletic performance though it has no effect on blood pressure, breathing pattern, blood chemistry and body weight[1]. DMG helps to improve oxygen utilization, causes increased tole rance to physical activity during strenuous exercise and faster recovery after such exercise, reducing lactic acid build-up and reducing muscle cram ping[3].
, 百拇医药
Since the effects of DMG on the spinal neurons which are concerned with motor functions have not been reported in literature so far, the present study was undertaken to determine the effect of DMG on the neurons of the cervical enlargement of the spinal cord.
Materials and Methods
Thirty albino mice of the BALB/c strain, of both sexes, aged 21 days, were randomly divided into three groups of ten each, namely normal control (NC), vehicle control(VC) and test group (DMG treated group). Mice in the NC group remained undisturbed in the home cage. Mice in the VC group were given a volume of distilled water equal to the amount of drug given orally. The mice in the test group received dimethyl glycine(DMG),20mg/(kg.day).The dose was extrapolated on the basis of the standard dose conversion table. The drug was administered as an aqueous solution which was prepared by dissolving 125 mg tablet in 12.5 ml of distilled water so that each ml of the solution contains 10 mg of the active ingredient. The dimethyl glycine was obtained from Vitamin World, Oakdale, New York(USA) through the India Christian Gospel Ministries, Chicago. The drug was given for 30 days. The body weight was taken before the commencement of the study and weekly thereafter. On the 31st day the mice were sacrificed. The cervical part of the spinal cord was dissected and a length of 5 mm from the middle of the cervical enlargement of the spinal cord was selected for the study. The tissue was processed and paraffin sections of 3 micron thickness were stained with cresyl violet. The slides were coded to avoid bias.
, 百拇医药
From each animal 8-10 sections at intervals of 15-20 microns (total of 100 sections) were selected for analysis of the gray matter, white matter and total area measurement. The sections were viewed on a screen using a video camera attached to Biolux binocular microscope. The total area ventral to a line drawn across the central canal of the spinal cord was measured using a grid attached to the screen(Fig. 1a). Similarly the total area of the gray matter was measured in the same region(Fig.1a). The area of white matter was calculated by subtracting the area of gray matter from the total area.
, 百拇医药
Similarly, the neuron counts were done from the ventral halves of the spinal cord(right and left sides)using the same equipment. The interval between the two selected sections was 15-18 microns. The number of neurons in the range of 15-25 microns(maximum diameter) and above 25 microns were counted. Neurons below 15 microns and without a clear cell boundary and nucleus were excluded. The diameter was measured using a graduated transparent scale(Fig.1b). All the neurons without differentiating them into different classes of motor neurons and inter neurons were counted. The data was analyzed using the one-way ANOVA test.
, 百拇医药
Figure 1:(a) Video screen with grid to measure the area(each square=2500 sq. microns) and (b) scale to measure the diameter of the neuron
Results
All the three groups of mice were found to be healthy throughout the experiment. Though there was a slight increase in the body weight in the test group,it was not statistically significant(Fig.2). There was no significant difference in the gray matter area between the test and control groups(Table 1). There was also no significant difference in white matter area and the total area in the normal control and test groups(Table 1). There was a decrease in the neuronal count in the range of 15-25 microns in the test group as well as the vehicle control as compared to the normal control group (Table 2, Fig.3). However, only the data derived from the test group showed any statistically signifi-cant decrease in the neuronal count when compared with the control group. But there was no significant change in the number of neurons which had a diameter of more than 25 microns (Table 2).
, 百拇医药
Table 1 Area measurement(in mm2) Area
Normal
control
(Mean±SD)
Vehicle
control
(Mean±SD)
Test
(Mean±SD)
P-value
(Test vs.
, 百拇医药
normal control)
Gray
matter
0.418±0.059
0.404±0.066
0.380±0.154
>0.05
White
matter
0.640±0.086
0.620±0.119
0.645±0.248
, 百拇医药
>0.05
Total
1.058±0.122
1.028±0.157
1.030±0.400
>0.05
% Grey
matter
(of total
area)
39.56±3.58
39.44±4.91
, http://www.100md.com
36.93±3.89
>0.05
% White
matter
(of total
area)
60.43±3.58
60.55±4.91
63.56±4.12
>0.05
Table 2 Neuronal counts Neuronal size
, http://www.100md.com
(Microns)
Normal control
(Mean±SD)
Vehicle control
(Mean±SD)
Test
(Mean±SD)
15-25
27.67±6.03
21.98±4.74
19.31±7.5*
, 百拇医药
>25
2.85±1.38
3.09±1.57
1.91±1.60
*P<0.05(Compared to normal control)
Fig.2 Graph showing comparison of body weights between the three groups of animals.(NC=Normal control;VC=Vehicle control; DMG=DMG treated group).
, http://www.100md.com
Figure 3: Photomicrograph of sections of the cervical enlargement of the spinal cord, stained with cresyl violet. In photograph(a) the horizontal line passes through the central canal(cc)and the box indicates the area magnified in (b)normal control;(c)vehicle control and (d)test group(DMG-treated).Note that the number of neurons is significantly decreased in (d). Scale bar=400 microns in (a) and 50 microns in (b-d).
Discussion
, 百拇医药 N,N-dimethyl glycine is described as a natural simple compound[1] with no undesirable side effects[4]. It is claimed to improve speech in mentally retarded children. Roach and Carlin noticed a dramatic reduction in the seizure frequency in a patient with grand mal seizures[7]. It provides methyl groups which are essential in the formation of vitamins, hormones, enzymes, neurotransmitters and antibodies. It is reported to improve athletic performance and is known to be a stamina nutrient.
, 百拇医药
DMG is also considered to be very beneficial for children with autism as it improves speech and behavior. Although clinical trials of DMG have been carried out on patients with seizures and autism there is no available literature to suggest its effect on the brain or spinal cord. We therefore did a pilot study to determine its effects on the neurons of the ventral half of the spinal cord, which are concerned with motor functions, so that further studies on the more complex regions of the brain can be undertaken at a later stage. Mice of this age group were selected to compare with clinical reports of the efficacy of DMG in infants.
, http://www.100md.com
The mouse spinal cord consists of several different neuron populations clustered together in groups. Ten layers can be recognized in columns throughout the length of the spinal cord. Motor neurons are found in lamina Ⅸ. Lamina Ⅸ consists of columns of neurons located in the ventral horn and embedded in laminae Ⅶ and Ⅷ. The motor neurons supplying the axial musculature are located in the medial part of the ventral horn and those supplying the limb musculature are located laterally[8]. Retrograde labelling by horse radish peroxidase has identified motor neurons in the middle part of the gray matter and at the base of the dorsal horns[9].
, 百拇医药
The area of gray matter when compared to the total area of ventral half of the spinal cord did not show any significant difference between the groups. There was a decrease in the number of neurons of 15-25 microns range in the vehicle group when compared with the control group, which was not statistically significant. This decrease could be due to the stress experienced by the animals during vehicle administration, which is a well accepted phenomenon[10].
, http://www.100md.com
There was a statistically significant decrease in the number of neurons in the 15-25 micron range in the test group when compared to the control group, indicating a possibility of neuronal damage (Figure 3a-d). It is likely that the neurons may have shrunken and reduced in size as seen in degenerative diseases of the central nervous system[11,12]. Since there was no increase in the number of neurons of the size over 25 microns it was unlikely that there was any neuronal enlargement.
, 百拇医药
Glycine is the most abundant amino acid with inhibitory activity found in the ventral quadrant gray matter of the spinal cord. Our investigations showed that dimethyl glycine caused changes suggestive of neuronal atrophy.The exact mechanism by which DMG causes this neuronal damage is not clear. It is unlikely to be due to impurities since the DMG used was the same as is commercially available and was approved by the FDA and patients who have been on this substance have not shown any such toxicities. DMG is an aminoacid which has been found to have a very high margin of safety.The animal doses were administered based on the standard conversion table[13]. Therefore the neuronal changes seen are unlikely to have been dose-related.
, http://www.100md.com
Another possibility for the neuronal changes is that DMG enters the central nervous system and stimulates the strychnine-insensitive N-methyl D-aspartate(NMDA) receptors and opens the calcium channels which function effectively only in the presence of glycine[14]. When the concentration of glycine is increased the ability of glutamate to open the channel is also increased, thereby increasing the glutamate-mediated excitatory response. High concentrations of intracellular calcium may activate calcium dependent proteases and may produce free radicals that are toxic to the cell. Thus dimethyl glycine could predispose to excitotoxicity.
, 百拇医药
Acknowledgements
The authors wish to express their gratitude to Dr. Samson James, President of the India Christian Gospel Ministries, USA, for the generous supply of dimethyl glycine from Vitamin World, Oakdale, New York, USA and to the following staff of the Kasturba Medical College, Manipal:Dr. K. S. Karanth, Head of the Department of Pharmacology, for facilities of the animal house, Dr. P.Sreedevi, Head of the Department of Anatomy, for the availability of the video camera and Biolux microscope.
, 百拇医药
References
[1]Rimland B. Dimethyl Glycine(DMG):a non-toxic metabolite and autism[J]. Autism Res Rev Int, 1995,1:3.
[2]Lawson J, R A Passwater. Dimethyl glycine update-new studies confirm DMG improves health[J]. Let's Live, 1987:45-47.
[3]Walker M. Nutritional medicine:N,N-dimethyl glycine(DMG)[J]. Health Foods Business, 1994:26:92.
[4]Reap A E, J W Lawson. Stimulation of the immune response by dimethyl glycine, a nontoxic metabolite[J]. J Lab Clin Med, 1990,115:481-486.
, 百拇医药
[5]Oommen T. Dimethyl glycine:A new horizon in therapeutics[J]. Indian J Pharm Sci, 1998,49-52.
[6]Graber C D, J M Goost, A D Glassman, R Kendal and C B Loadholt. Immunomodulating properties of dimethyl glycine in humans[J]. J Infect Dis, 1981,143:101-105.
[7]Roach E S, L Carlin. N, N-dimethyl glycine for epilepsy[J]. N. Engl J Med, 1982,307：1081-1082.
[8]Weber U J, T Bock, K Buschard, D Pakkenberg. Total number and size distribution of motor neurons in the spinal cord of normal and EMC-virus infected mice-a stereological study[J]. J Anat,1997,191：347-353.
, http://www.100md.com
[9]Hashizume K, R E Burke, K Kanda. Medial gastrocnemius motor nucleus in the rat;age-related changes in the number and size of motonourons[J]. J Comp Neurol,1988,269：425-430.
[10]Uno H, Tarara R, Else JG. Suleman MA, Sapolsky RM. Hippocampal damage associated with prolonged and fatal stress in primates[J]. J Neurosci, 1989,9:1705-1711.
[11]Andrews J M, M B Gardner, F J Wolfgram, G W Ellison, D D Porter, W W Brandkamp. Studies on the murine form of spontaneous lower motoneuron degeneration-the Wobbler (Wr) mouse[J]. Am J Pathol,1974,76：63-78.
, http://www.100md.com
[12]Duchen L W, S J Strich. A hereditary motor neuron disease with progressive denervation of muscle in the mouse; the mutant“wobbler”[J]. J Neurol Neurosurg and Psychiatry, 1968,31：535-542.
[13]Paget GE, Barnes JM. Surface area ratios of some common laboratory animal species and man, In:Laurence DR, Bacharat AL, eds. Evaluation of Drug Actions:Pharmacometrics[M].New York: Academy Press,Vol.1,1964:161.
[14]Kandel E R, J H Schwartz. Directly gated transmission at the nerve-muscle synapse. In:Kendel ER, Schwartz JH, Jessel TM, eds. Principles of Neural Science[M]. London:Prentice Hall Int.Inc,3rd ed,1991:159-160.
【Received date】 1999-08-25, 百拇医药