Ironjustic
Wed, Aug-09-06, 17:16
Last Updated: Monday, 7 August 2006, 23:14 GMT 00:14 UK
E-mail this to a friend Printable version
Drug 'treats depression in hours'
Ketamine proved effective in under two hours An anaesthetic
can treat depression within hours, US research suggests.
The study involving 17 patients found ketamine - used as an
anaesthetic but also taken as a recreational drug - relieved
symptoms of depression.
Most existing treatments for depression take weeks or even
months to relieve people's symptoms.
But the team, writing in Archives of General Psychiatry, said
ketamine would need to be altered so it lost its existing
hallucinatory side-effects.
This is the first report of any medication or other
treatment that results in such a pronounced, rapid,
prolonged response
Dr Thomas Insel, NIMH
Scientists from the National Institute of Mental Health (NIMH)
injected 17 patients with either a very low dose of ketamine
or a placebo of saline solution.
The participants were all depression sufferers who had tried
an average of six treatments that had failed.
The researchers then measured their levels of depression
minutes, hours and days after the dose was given.
Lead researcher Dr Carlos Zarate Junior, head of the mood and
anxiety disorders programme at NIMH, said: "Within 110
minutes, half of the patients given ketamine showed a 50%
decrease in symptoms."
By the end of day one, he added, 71% had responded to the
drug. And at this point the team found 29% of these patients
were nearly symptom free.
The researchers also discovered one dose lasted for at least a
week in more than one-third of the participants.
Brain pathways
Dr Thomas Insel, director of NIMH, commented: "To my
knowledge, this is the first report of any medication or other
treatment that results in such a pronounced, rapid, prolonged
response with a single dose.
"These were very treatment-resistant patients."
Many antidepressants target levels of brain chemicals, such as
serotonin and dopamine, and, over time, the accumulation of
these chemicals can affect a patient's mood. But this can take
several weeks.
But the team believes ketamine is having a faster effect
because it is targeting a different brain-protein, called the
NMDA receptor, which is thought to play a critical role in
learning and memory.
The team says ketamine, in its current form, would not be
appropriate for medication because of side-effects at higher
doses, which include hallucinations and euphoria.
Dr Zarate said: "This study is a tool to help us understand
what part of ketamine is causing this effect so we can refine
and develop better drugs.
"We are also looking at ways that we could use ketamine maybe
in lower doses or with drugs that block its perceptual effects
so we could perhaps use it clinically."
Professor John Henry, a clinical toxicologist at St Mary's
Hospital in London, said: "This is a very interesting piece of
work, very neatly done, with promising results.
"More studies need to be done to see if ketamine would work
over a longer period given in repeated doses.
"The benefit of having a fast-working drug would mean people
could return to work quickly, and it could reduce risk of
self-harm or suicide that could happen during the time-lag
that occurs with other drugs."
--------------------------------------------------------------
--------------=
----------
Exp Toxicol Pathol. 1998 Sep;50(4-6):501-6. Related
Articles, Links
Investigation on possible antioxidative properties of the
NMDA-receptor antagonists ketamine, memantine, and amantadine
in comparison to nicanartine in vitro.
Lupp A, Kerst S, Karge E, Quack G, Klinger W.
Institute of Pharmacology and Toxicology, Friedrich Schiller
University Jena, Germany.
Possible antioxidative properties of three
N-methyl-D-aspartate (NMDA)-receptor antagonists, the
anesthetic ketamine and the antiparkinson drugs memantine and
amantadine were investigated in vitro on the microsomal
cytochrome P450 (P450) system of rat livers and on rat whole
blood chemiluminescence in comparison to nicanartine, a
substance with known antiatherosclerotic, hypolipemic and
antioxidative capacity. For this purpose, the effects on
NADPH- and iron-stimulated lipid peroxidation (LPO), hydrogen
peroxide (H2O2) production, and NADPH- and iron-stimulated
lucigenin (LC) and luminol (LM) amplified chemiluminescence
(CL) were examined using rat liver microsomes. Additionally,
the influence on LM amplified whole blood chemiluminescence
after zymosan activation of polymorphonuclear leukocytes
(WB-CL) was investigated. Furthermore, binding to P450 and
effects on P450 mediated monooxygenase function, as measured
by the model reactions ethoxyresorufin O-deethylation (EROD),
ethoxycoumarin O-deethylation (ECOD), and ethylmorphine
N-demethylation (END), were assessed. Nicanartine
concentration dependently reduced LPO and H2O2 production
already at a concentration of 1 microM, whereas LC and LM
amplified CL and WB-CL were not affected. EROD and END were
concentration dependently diminished starting at 1 microM, and
ECOD already at 0.1 microM. Ketamine decreased LPO, H2O2
production and LM and LC amplified CL, starting at 100 microM.
WB-CL was significantly diminished already at 10 microM. EROD
and ECOD were inhibited at 10 and 100 microM and END at 100
microM. With memantine a concentration dependent inhibition of
LPO and WB-CL was seen at 100 and 1000 microM and a reduction
of LC and LM amplified CL only at 1000 microM. H2O2 production
was not affected. EROD and ECOD were significantly diminished
by a concentration of 100 microM. No effect was observed on
END. Amantadine significantly reduced LPO and WB-CL, but only
at 1000 microM. H2O2 production and LC and LM amplified CL
were not affected. EROD was significantly diminished at 100
microM, whereas no influence was seen on ECOD and END.
Nicanartine displayed type II or reverse type I, ketamine,
memantine and amantadine type I substrate binding to P450. The
highest binding affinity to P450 was seen with nicanartine,
followed by ketamine, memantine and then amantadine. These
results demonstrate, that all four substances seem to act as
radical scavengers and/or as inhibitors of the oxidative
function of P450. All four substances seem to interfere with
the monooxygenase function of P450. This may result in a
possible influence on the biotransformation of endogenous as
well as of foreign compounds. The effects of nicanartine were
much more pronounced than those of ketamine, memantine, and
amantadine.
PMID: 9784030 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------=
-----
1: J Psychiatr Res. 2005 Nov;39(6):553-60. Epub 2005 Apr 26.
Related Articles, Links
Depression and possible cancer risk due to oxidative DNA
damage.
Irie M, Miyata M, Kasai H.
Second Department of Health Sciences (Clinical Science and
Psychology),
Institute of Health Science, Kyushu University, Kasuga,
Fukuoka 816-8580, Japan. i...@ihs.kyushu-u.ac.jp
The potential link between depression and cancer is an
important unsolved question. To clarify this, we compared a
cancer-related oxidative DNA damage, 8-hydroxydeoxyguanosine
(8-OH-dG), in peripheral leukocytes between 30 patients with
depression and 60 age- and gender-matched healthy controls,
and examined the 8-OH-dG-related factors. The degree of
depression was assessed by the scores of the Center for
Epidemiologic Studies Depression scale (CES-D) and the
Profile of Mood States (POMS). The patients showed
significantly higher
8-OH-dG levels than the controls. There was a significant
positive correlation between the CES-D scores and the 8-OH-dG
levels in depressive, particularly female, patients. Multiple
regression analysis
indicated that whether the subjects were patients or controls
was a significant predictor of the 8-OH-dG levels in male and
total subjects,
as was the CES-D score or the Depression-Rejection score of
the POMS in
female subjects. This study suggests that clinical
depression is a risk
factor for cancer initiation in view of oxidative DNA damage.
PMID: 16005897 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------= =AD-----
2: Ann N Y Acad Sci. 2005 May;1042:365-71. Related
Articles, Links
Alleviation of oxidative damage in multiple tissues in rats
with streptozotocin-induced diabetes by rice bran oil
supplementation. Hsieh RH, Lien LM, Lin SH, Chen CW, Cheng HJ,
Cheng HH. R-H.H. and L-M.L. contributed equally to this work.
School of Nutrition and Health Sciences, Taipei Medical
University, Taipei, Taiwan 110, Republic of China,
chen...@tmu.edu.tw.
The possibility of 8-hydroxy-2'-deoxyguanosine (8-OHdG)
serving as a sensitive biomarker of oxidative DNA damage and
oxidative stress was investigated. Reactive oxygen species
(ROS) have been reported to be a cause of diabetes induced by
chemicals such as streptozotocin (STZ) in experimental
animals. In this study, we examined oxidative DNA damage in
multiple tissues in rats with STZ-induced diabetes by
measuring the levels of 8-OHdG in the liver, kidney, pancreas,
brain, and heart. Levels of 8-OHdG in mitochondrial DNA
(mtDNA) and nuclear DNA (nDNA) were also determined in
multiple tissues of rats treated with rice bran
oil. Levels were 0.19 +/- 0.07, 0.88 +/- 0.30, 1.97 +/- 0.05,
and 9.79 +/- 3.09 (1/10(5) dG) in the liver of nDNA of normal
rats, nDNA of STZ-induced diabetic rats, mtDNA of normal rats,
and mtDNA of STZ-induced diabetic rats, respectively. Levels
of mtDNA of 8-OHdG were
10 times higher than those of nDNA in multiple tissues.
Significant reductions in mtDNA 8-OHdG levels were seen in the
liver, kidney, and pancreas of diabetic rats treated with rice
bran oil compared with diabetic rats without intervention. Our
study demonstrated that oxidative mtDNA damage may occur in
multiple tissues of STZ-induced diabetics rats. Intervention
with rice bran oil treatment may reverse the increase in the
frequency of 8-OHdG.
PMID: 15965082 [PubMed - in process] -------------------------
---------------------------------------------------= =AD-----
--------------------------------------------------------------
--------------= =AD-----
Lipids. 2000 Dec;35(12):1411-3. Related Articles, Links
Protective effect of phytic acid hydrolysis products on
iron-induced lipid peroxidation of liposomal membranes.
Miyamoto S, Kuwata G, Imai M, Nagao A, Terao J.
Department of Nutrition, School of Medicine, The University of
Tokushima, Japan.
Beneficial effects of dietary phytic acid (myo-inositol
hexaphosphate;
IP6) have often been explained by its strong iron
ion-chelating ability, which possibly suppresses iron
ion-induced oxidative damage in
the gastrointestinal tract. Because phytic acid is hydrolyzed
during digestion, this work aimed to know whether its
hydrolysis products (IP2, IP3, IP4, and IP5) could still
prevent iron ion-induced lipid peroxidation. Studies using
liposomal membranes demonstrated that hydrolysis products
containing three or more phosphate groups are able to inhibit
iron ion-induced lipid peroxidation although their
effectiveness decreased with dephosphorylation. Similarly,
they also prevented iron ion-induced decomposition of
phosphatidylcholine hydroperoxide. These results demonstrate
that intermediate products of phytic acid hydrolysis still
possess iron ion-chelating ability, and thus they can
probably prevent iron ion-induced lipid peroxidation in
biological systems.
PMID: 11202004 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------= =AD-----
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING=20 http://tinyurl.com/zk9fk
E-mail this to a friend Printable version
Drug 'treats depression in hours'
Ketamine proved effective in under two hours An anaesthetic
can treat depression within hours, US research suggests.
The study involving 17 patients found ketamine - used as an
anaesthetic but also taken as a recreational drug - relieved
symptoms of depression.
Most existing treatments for depression take weeks or even
months to relieve people's symptoms.
But the team, writing in Archives of General Psychiatry, said
ketamine would need to be altered so it lost its existing
hallucinatory side-effects.
This is the first report of any medication or other
treatment that results in such a pronounced, rapid,
prolonged response
Dr Thomas Insel, NIMH
Scientists from the National Institute of Mental Health (NIMH)
injected 17 patients with either a very low dose of ketamine
or a placebo of saline solution.
The participants were all depression sufferers who had tried
an average of six treatments that had failed.
The researchers then measured their levels of depression
minutes, hours and days after the dose was given.
Lead researcher Dr Carlos Zarate Junior, head of the mood and
anxiety disorders programme at NIMH, said: "Within 110
minutes, half of the patients given ketamine showed a 50%
decrease in symptoms."
By the end of day one, he added, 71% had responded to the
drug. And at this point the team found 29% of these patients
were nearly symptom free.
The researchers also discovered one dose lasted for at least a
week in more than one-third of the participants.
Brain pathways
Dr Thomas Insel, director of NIMH, commented: "To my
knowledge, this is the first report of any medication or other
treatment that results in such a pronounced, rapid, prolonged
response with a single dose.
"These were very treatment-resistant patients."
Many antidepressants target levels of brain chemicals, such as
serotonin and dopamine, and, over time, the accumulation of
these chemicals can affect a patient's mood. But this can take
several weeks.
But the team believes ketamine is having a faster effect
because it is targeting a different brain-protein, called the
NMDA receptor, which is thought to play a critical role in
learning and memory.
The team says ketamine, in its current form, would not be
appropriate for medication because of side-effects at higher
doses, which include hallucinations and euphoria.
Dr Zarate said: "This study is a tool to help us understand
what part of ketamine is causing this effect so we can refine
and develop better drugs.
"We are also looking at ways that we could use ketamine maybe
in lower doses or with drugs that block its perceptual effects
so we could perhaps use it clinically."
Professor John Henry, a clinical toxicologist at St Mary's
Hospital in London, said: "This is a very interesting piece of
work, very neatly done, with promising results.
"More studies need to be done to see if ketamine would work
over a longer period given in repeated doses.
"The benefit of having a fast-working drug would mean people
could return to work quickly, and it could reduce risk of
self-harm or suicide that could happen during the time-lag
that occurs with other drugs."
--------------------------------------------------------------
--------------=
----------
Exp Toxicol Pathol. 1998 Sep;50(4-6):501-6. Related
Articles, Links
Investigation on possible antioxidative properties of the
NMDA-receptor antagonists ketamine, memantine, and amantadine
in comparison to nicanartine in vitro.
Lupp A, Kerst S, Karge E, Quack G, Klinger W.
Institute of Pharmacology and Toxicology, Friedrich Schiller
University Jena, Germany.
Possible antioxidative properties of three
N-methyl-D-aspartate (NMDA)-receptor antagonists, the
anesthetic ketamine and the antiparkinson drugs memantine and
amantadine were investigated in vitro on the microsomal
cytochrome P450 (P450) system of rat livers and on rat whole
blood chemiluminescence in comparison to nicanartine, a
substance with known antiatherosclerotic, hypolipemic and
antioxidative capacity. For this purpose, the effects on
NADPH- and iron-stimulated lipid peroxidation (LPO), hydrogen
peroxide (H2O2) production, and NADPH- and iron-stimulated
lucigenin (LC) and luminol (LM) amplified chemiluminescence
(CL) were examined using rat liver microsomes. Additionally,
the influence on LM amplified whole blood chemiluminescence
after zymosan activation of polymorphonuclear leukocytes
(WB-CL) was investigated. Furthermore, binding to P450 and
effects on P450 mediated monooxygenase function, as measured
by the model reactions ethoxyresorufin O-deethylation (EROD),
ethoxycoumarin O-deethylation (ECOD), and ethylmorphine
N-demethylation (END), were assessed. Nicanartine
concentration dependently reduced LPO and H2O2 production
already at a concentration of 1 microM, whereas LC and LM
amplified CL and WB-CL were not affected. EROD and END were
concentration dependently diminished starting at 1 microM, and
ECOD already at 0.1 microM. Ketamine decreased LPO, H2O2
production and LM and LC amplified CL, starting at 100 microM.
WB-CL was significantly diminished already at 10 microM. EROD
and ECOD were inhibited at 10 and 100 microM and END at 100
microM. With memantine a concentration dependent inhibition of
LPO and WB-CL was seen at 100 and 1000 microM and a reduction
of LC and LM amplified CL only at 1000 microM. H2O2 production
was not affected. EROD and ECOD were significantly diminished
by a concentration of 100 microM. No effect was observed on
END. Amantadine significantly reduced LPO and WB-CL, but only
at 1000 microM. H2O2 production and LC and LM amplified CL
were not affected. EROD was significantly diminished at 100
microM, whereas no influence was seen on ECOD and END.
Nicanartine displayed type II or reverse type I, ketamine,
memantine and amantadine type I substrate binding to P450. The
highest binding affinity to P450 was seen with nicanartine,
followed by ketamine, memantine and then amantadine. These
results demonstrate, that all four substances seem to act as
radical scavengers and/or as inhibitors of the oxidative
function of P450. All four substances seem to interfere with
the monooxygenase function of P450. This may result in a
possible influence on the biotransformation of endogenous as
well as of foreign compounds. The effects of nicanartine were
much more pronounced than those of ketamine, memantine, and
amantadine.
PMID: 9784030 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------=
-----
1: J Psychiatr Res. 2005 Nov;39(6):553-60. Epub 2005 Apr 26.
Related Articles, Links
Depression and possible cancer risk due to oxidative DNA
damage.
Irie M, Miyata M, Kasai H.
Second Department of Health Sciences (Clinical Science and
Psychology),
Institute of Health Science, Kyushu University, Kasuga,
Fukuoka 816-8580, Japan. i...@ihs.kyushu-u.ac.jp
The potential link between depression and cancer is an
important unsolved question. To clarify this, we compared a
cancer-related oxidative DNA damage, 8-hydroxydeoxyguanosine
(8-OH-dG), in peripheral leukocytes between 30 patients with
depression and 60 age- and gender-matched healthy controls,
and examined the 8-OH-dG-related factors. The degree of
depression was assessed by the scores of the Center for
Epidemiologic Studies Depression scale (CES-D) and the
Profile of Mood States (POMS). The patients showed
significantly higher
8-OH-dG levels than the controls. There was a significant
positive correlation between the CES-D scores and the 8-OH-dG
levels in depressive, particularly female, patients. Multiple
regression analysis
indicated that whether the subjects were patients or controls
was a significant predictor of the 8-OH-dG levels in male and
total subjects,
as was the CES-D score or the Depression-Rejection score of
the POMS in
female subjects. This study suggests that clinical
depression is a risk
factor for cancer initiation in view of oxidative DNA damage.
PMID: 16005897 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------= =AD-----
2: Ann N Y Acad Sci. 2005 May;1042:365-71. Related
Articles, Links
Alleviation of oxidative damage in multiple tissues in rats
with streptozotocin-induced diabetes by rice bran oil
supplementation. Hsieh RH, Lien LM, Lin SH, Chen CW, Cheng HJ,
Cheng HH. R-H.H. and L-M.L. contributed equally to this work.
School of Nutrition and Health Sciences, Taipei Medical
University, Taipei, Taiwan 110, Republic of China,
chen...@tmu.edu.tw.
The possibility of 8-hydroxy-2'-deoxyguanosine (8-OHdG)
serving as a sensitive biomarker of oxidative DNA damage and
oxidative stress was investigated. Reactive oxygen species
(ROS) have been reported to be a cause of diabetes induced by
chemicals such as streptozotocin (STZ) in experimental
animals. In this study, we examined oxidative DNA damage in
multiple tissues in rats with STZ-induced diabetes by
measuring the levels of 8-OHdG in the liver, kidney, pancreas,
brain, and heart. Levels of 8-OHdG in mitochondrial DNA
(mtDNA) and nuclear DNA (nDNA) were also determined in
multiple tissues of rats treated with rice bran
oil. Levels were 0.19 +/- 0.07, 0.88 +/- 0.30, 1.97 +/- 0.05,
and 9.79 +/- 3.09 (1/10(5) dG) in the liver of nDNA of normal
rats, nDNA of STZ-induced diabetic rats, mtDNA of normal rats,
and mtDNA of STZ-induced diabetic rats, respectively. Levels
of mtDNA of 8-OHdG were
10 times higher than those of nDNA in multiple tissues.
Significant reductions in mtDNA 8-OHdG levels were seen in the
liver, kidney, and pancreas of diabetic rats treated with rice
bran oil compared with diabetic rats without intervention. Our
study demonstrated that oxidative mtDNA damage may occur in
multiple tissues of STZ-induced diabetics rats. Intervention
with rice bran oil treatment may reverse the increase in the
frequency of 8-OHdG.
PMID: 15965082 [PubMed - in process] -------------------------
---------------------------------------------------= =AD-----
--------------------------------------------------------------
--------------= =AD-----
Lipids. 2000 Dec;35(12):1411-3. Related Articles, Links
Protective effect of phytic acid hydrolysis products on
iron-induced lipid peroxidation of liposomal membranes.
Miyamoto S, Kuwata G, Imai M, Nagao A, Terao J.
Department of Nutrition, School of Medicine, The University of
Tokushima, Japan.
Beneficial effects of dietary phytic acid (myo-inositol
hexaphosphate;
IP6) have often been explained by its strong iron
ion-chelating ability, which possibly suppresses iron
ion-induced oxidative damage in
the gastrointestinal tract. Because phytic acid is hydrolyzed
during digestion, this work aimed to know whether its
hydrolysis products (IP2, IP3, IP4, and IP5) could still
prevent iron ion-induced lipid peroxidation. Studies using
liposomal membranes demonstrated that hydrolysis products
containing three or more phosphate groups are able to inhibit
iron ion-induced lipid peroxidation although their
effectiveness decreased with dephosphorylation. Similarly,
they also prevented iron ion-induced decomposition of
phosphatidylcholine hydroperoxide. These results demonstrate
that intermediate products of phytic acid hydrolysis still
possess iron ion-chelating ability, and thus they can
probably prevent iron ion-induced lipid peroxidation in
biological systems.
PMID: 11202004 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
--------------= =AD-----
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING=20 http://tinyurl.com/zk9fk