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<DIV><FONT face=Arial size=2>Just wanted everyone to know that I received my
Popular Science magazine today and the helmet that cools the head is in there
and should be available in the next few years. :-)</FONT></DIV>
<BLOCKQUOTE
style="PADDING-RIGHT: 0px; PADDING-LEFT: 5px; MARGIN-LEFT: 5px; BORDER-LEFT: #000000 2px solid; MARGIN-RIGHT: 0px">
<DIV style="FONT: 10pt arial">----- Original Message ----- </DIV>
<DIV
style="BACKGROUND: #e4e4e4; FONT: 10pt arial; font-color: black"><B>From:</B>
<A title=megao@sasktel.net href="mailto:megao@sasktel.net">Extropian
Agroforestry Ventures Inc.</A> </DIV>
<DIV style="FONT: 10pt arial"><B>To:</B> <A
title=extropy-chat@lists.extropy.org
href="mailto:extropy-chat@lists.extropy.org">ExI chat list</A> </DIV>
<DIV style="FONT: 10pt arial"><B>Sent:</B> Wednesday, December 15, 2004 7:56
AM</DIV>
<DIV style="FONT: 10pt arial"><B>Subject:</B> Re: [extropy-chat]
Re:Resuscitation: and ArmchairCryonicists-hypothermic liferaft</DIV>
<DIV><BR></DIV><BR>
<TABLE width="100%">
<TBODY>
<TR>
<TD align=left width="50%"><B>United States Patent Application</B></TD>
<TD align=right width="50%"><B>20040097534 </B></TD></TR>
<TR>
<TD vAlign=top align=left width="50%"><B>Kind Code</B> </TD>
<TD align=right width="50%"><B>A1 </B></TD></TR>
<TR>
<TD align=left width="50%"><B>Choi, Byung-Kil ; et al.</B> </TD>
<TD align=right width="50%"><B>May 20, 2004 </B></TD></TR></TBODY></TABLE>
<HR>
<FONT size=+1>Composition for the protection and regeneration of nerve cells
containing berberine derivatives </FONT><BR><BR>
<CENTER><B>Abstract</B></CENTER>
<P>Disclosed is a composition for protecting nerve cells, promoting nerve cell
growth and regenerating nerve cells comprising berberine, derivatives thereof
or pharmaceutically acceptable salts thereof. The composition has protective
effects against apoptosis of neuronal stem cells and differentiated neuronal
stem cells, an effect of inducing the regeneration of nerve cells, a
regenerative effect on neurites, a neuroregenerative effect on central nerves
and peripheral nerves, a reformation effect on neuromuscular junctions, and a
protective effect against apoptosis of nerve cells and a neuroregenerative
effect in animals suffering from dementia and brain ischemia. Therefore, the
composition can be used as a therapeutic agent for the prevention and
treatment of neurodegenerative diseases, ischemic nervous diseases or nerve
injuries, and for the improvement of learning capability.<BR></P>
<P>&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&<BR></P>
<P>[0150] Next, the head of the rat was fixed on a stereotaxic apparatus to
operate on the occiput, and then the tail was fixed so that it descended
downwardly at an angle of 30.degree.. After incising the occipital bone, an
electrocauterizing needle having a diameter of 1 mm or less was inserted into
the alar foramina positioned at lower part of the first cervical vertebra
under the occipital bone. At this time, this approach must be carefully done
so as not to damage the muscles in the alar foramina. Thereafter, the
vertebral artery was electrically cauterized by intermittently applying
current. After the complete electrocauterization of the vertebral artery was
confirmed, suturing was carried out using operating clips. After 24 hours, the
operating clips were removed. Finally, the common carotid arteries were
occluded using the silicone tube rings for 10 minutes to induce ischemia. If
light reflex did not disappear within 1 minute, the cervical portion was
further tightly sutured. Rats which did not show the complete disappearance of
light reflex were excluded from the experiment because they underwent no
damage to the CA1 region. After 10 minutes, the common carotid arteries were
loosened to reperfuse. For 20 minutes after the reperfusion, loss of
consciousness was observed. At this time, only rats which showed consciousness
loss period within 20.+-.5 minutes were selected for subsequent experiments.
<BR></P>
<P>&&&&&&&&&&&&&&&&&&&&&&&&&&&&&<BR></P>2)
Experimental Results <BR><BR>(1) Concentration of Berberine, Influence of Body
Temperature and Ischemia Inducing Time <BR><BR>[0157] The highest
concentration of berberine was set to 300 .mu.g/0.1 kg, and 600 .mu.l (1
mg/ml) of berberine was intraperitoneally injected to white rats weighing 200
g. In order to determine an optimal ischemia induction time, 2.about.3 rats
were selected and ischemia-induced over 5, 10, 20 and 30 minutes,
respectively. 1 week after reperfusion, they were sacrificed and their
hippocampal tissue sections were obtained to observe the number of damaged
nerve cells. 10 minutes after ischemia induction, damaged pyramidal cells in
the hippocampal CA1 region were found to be reduced to 1/4 of their original
numbers. The ischemia induction time of 10 minutes was determined to be most
optimal for evaluating the effects of berberine. <BR><BR>[0158] For
statistically analyzing the effects of berberine, a sham operated group having
undergone an operation in the same manner without ischemia induction was used.
For comparing the effects of berberine, a control group administered with
physiological saline at the same dose as berberine was used. Berberine was
intraperitoneally injected into all experimental groups. <BR><BR>[0159] It is
well known that reduction in body temperature during ischemia induction
prevents damage to nerve cells in the hippocampus and thus exhibits
neuroprotective effects. Therefore, in order to evaluate the neuroprotective
effect of berberine, after ischemia induction and reperfusion, the body
temperature of all rats was maintained at a constant (37.+-.1.degree. C.) for
6 hours. <BR><BR>(2) Observation of Damaged Nerve Cells <BR><BR>[0160] When
ischemia was induced by 4-VO and then reperfusion was performed, nerve cells
in the neocortex, striatum, hippocampal CA1 region and cerebellum were
damaged. Among them, pyramidal nerve cells in the hippocampal CA1 region were
the most susceptible to the induced ischemia, and started to undergo cell
death 72 hours after reperfusion. In order to observe delayed neuronal death
in the hippocampal CA1 region, 1 week after reperfusion, the time when almost
all nerve cells were damaged, white rats were sacrificed and tissue sections
from the hippocampus were observed under an optical microscope. In a sham
operated group having undergone no ischemia, normal hippocampal nerve cells
were observed in the stratum pyramidale (490 .mu.m long)(see,A and B of FIG.
21). <BR><BR>[0161] C and D of FIG. 21 as control groups show apoptosis. When
cells are induced to undergo apoptosis by an external or an internal stimulus,
they shrink to lose their original shapes. This shrinkage breaks the junctions
with other adjacent cells so that the interaction between cells is disrupted.
When the shrinkage proceeds to some extent, the cell membranes form apoptotic
bodies like a bulla. In the hippocampal CA1 region of the control group
administered with physiological saline (D of FIG. 21), it was observed that
nerve cells underwent apoptotic morphological changes after ischemia
induction. In addition, it was observed that tissues was relaxed and separated
from adjacent cells, unlike B of FIG. 21. From these observations, it was
confirmed that the cell bodies of nerve cells lost their original pyramidal
shape and were condensed, thereby appearing to be single cells. Furthermore,
it was confirmed that subsequent nuclear chromatin condensation and nuclear
envelope collapse led to apoptosis of nerve cells. On the contrary, nerve
cells in the hippocampal CA1 region administered with berberine were similar
to normal cells in terms of their morphology (see, E and F of FIG. 21). At
this time, because necrotic nerve cells around the CA1 region were very
difficult to distinguish from microglias, only viable pyramidal nerve cells in
the CA1 region were counted. In F of FIG. 21, separated cells were observed
above and below the hippocampal region and cell bodies were condensed. This
demonstrates that the damage to nerve cells was great enough to induce
apoptosis. Nevertheless, it was observed that a great number of nerve cells
were protected from apoptosis and their original pyramidal morphology was
maintained. This suggests that berberine has a protective effect against
damages to nerve cells in the hippocampal CA1 region induced by 4-VO. Although
it was not confirmed what stage during apoptosis influences nerve cell
survival, it was certain that berberine has a significant protective effect
against apoptosis of nerve cells (see, E and F of FIG. 21). <BR><BR>(3)
Protective Effect of Berberine Against Damage to Nerve Cells <BR><BR>[0162] In
order to examine the neuroprotective effect of berberine after ischemia
induction, berberine was intraperitoneally injected 0 and 90 minutes after
ischemia induction. <BR><BR>[0163] In the sham groups, the density of viable
cells was measured to be 308.+-.6.6 cells/mm.sup.2 (at 37.degree. C.). In the
control groups administered with physiological saline, the density of viable
cells was measured to be 28.+-.3.8 cells/mm.sup.2 (at 37.degree. C.). There
was cell loss in these two groups. On the other hand, in the experimental
groups administered with berberine, the density of viable cells was measured
to be 257.+-.9.6 cell/mm.sup.2. In conclusion, berberine was determined to
have a significant neuroprotective effect (p<0.05). <BR><BR>[0164] As
described above, the composition according to the present invention
regenerates axons and dendrites of nerve cells, thereby having a protective
effect against nerve cell injuries, a positive effect on nerve cell growth and
a regenerative effect on nerve cells. In addition, the composition according
to the present invention can be used as a therapeutic agent for the prevention
and treatment of neurodegenerative diseases or nerve injuries, in particular,
dementia, Parkinson's disease, Alzheimer's disease, epilepsy, palsy, ischemic
brain diseases, trauma to the spinal cord and peripheral nerve injuries.
<BR><BR>[0165] Although the preferred embodiments of the present invention
have been disclosed for illustrative purposes, those skilled in the art will
appreciate that various modifications, additions and substitutions are
possible, without departing from the scope and spirit of the invention as
disclosed in the accompanying claims. <BR><BR>
<CENTER><B>* * * * *</B></CENTER>Aside from its carrier capacity DMSO was
chosen for its ability to inhibit damage from a light freeze<BR><BR>There are
a number of complementary chemistries besides from the ones cited readily
available.<BR><BR><BR><BR>Eugen Leitl wrote:<BR>
<BLOCKQUOTE cite=mid20041215104301.GT9221@leitl.org type="cite"><PRE wrap="">On Wed, Dec 15, 2004 at 03:01:49AM -0600, Extropian Agroforestry Ventures Inc. wrote:
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">The concept goes thusly:
The liferaft =
-sleeping /body bag like sack made so that no 2 arms or legs touch each
other or body
-zipper + ziplock seal
- control/RFID biomonitor keypad with on outside
-stage 1- evacuate liner to ensure good skin contact with sack
-person put inside without outer clothes , shoes etc
-put cooling hood or cap over all of head less face, face cover ziplock
cover after body cooled off
-start in 2 parts; activation of emergency cooling packs layer of sack
to quick cool body; hood cooling cycle
</PRE></BLOCKQUOTE><PRE wrap=""><!---->
Useless. This gives you no advatage over an ice bath.
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">co2 based for higher cooling rate
</PRE></BLOCKQUOTE><PRE wrap=""><!---->
More than useless. You can't go below 0 C, or you'll get freezing injury.
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">-infusion of adjuvants may include:
Caffeinol as neuroprotectant; berberine in DMSO solution as
neuroprotectant; cannabidiol in DMSO solution as neuroprotectant
-optional defib cycle to pump neuroprotectants into cooling body uniformly
</PRE></BLOCKQUOTE><PRE wrap=""><!---->
You have to maintain the circulation. Best do achieve this is life support.
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">The adjuvants are designed to allow the brain to survive a longer
cool-off time than the usual 3-5 minutes.
</PRE></BLOCKQUOTE><PRE wrap=""><!---->
Sorry, but your science is garbage. I'm being delibertely harsh here, because
otherwise you won't get the message.
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">as well as allow for easier re-start of body by hospital medical team
-once body temp is near 32F optional external hookups to maintain cooled
body during extended transport
Once the working prototype is designed and tested , the actual mfg
costs may be quite reasonable
</PRE></BLOCKQUOTE><PRE wrap=""><!---->
If you have to live in the sticks, you have to rely on people. No machinery
is going to help.
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">Morris Johnson
Hara Ra wrote:
</PRE>
<BLOCKQUOTE type="cite"><PRE wrap="">For Eugen:
Thanks for taking my point and clarifying it. If you read my sig
file, I don't think I am an "Armchair cryonicist". Please correct me
if you think so, and explain why.
</PRE></BLOCKQUOTE></BLOCKQUOTE><PRE wrap=""><!---->
Of course I wasn't commenting on what you wrote, but on periodical resurgence
of well-meaning-but-clueless armchair cryonicists.
</PRE>
<BLOCKQUOTE type="cite">
<BLOCKQUOTE type="cite"><PRE wrap="">PS We currently do no longer use the Thumper, which is an obscene
bastard of equipment fully capable of major injury to both patient and
rescue team. Respiratory support is no longer in the protocol, because
</PRE></BLOCKQUOTE></BLOCKQUOTE><PRE wrap=""><!---->
Oh yeah, if the cup breaks off you'll get a massive metal rod puncturing the
ribcage.
</PRE>
<BLOCKQUOTE type="cite">
<BLOCKQUOTE type="cite"><PRE wrap="">basically all patients are over the 4 minute limit, and restoring O2
is a bad idea. We use an Ambi product, a suction cup with handles, to
</PRE></BLOCKQUOTE></BLOCKQUOTE><PRE wrap=""><!---->
Not if you add neuroprotectants via IV push, and maintain artificial
circulation.
</PRE>
<BLOCKQUOTE type="cite">
<BLOCKQUOTE type="cite"><PRE wrap="">maintain circulation for the 3-5 minutes it takes to circulate the
medicines (a proprietary cocktail of anticoaguants, clot busters and
other stuff)
</PRE></BLOCKQUOTE></BLOCKQUOTE><PRE wrap=""><!---->
</PRE><PRE wrap=""><HR width="90%" SIZE=4>
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