[extropy-chat] Re:Resuscitation: and Armchair Cryonicists-hypothermic liferaft
Eugen Leitl
eugen at leitl.org
Wed Dec 15 14:31:38 UTC 2004
On Wed, Dec 15, 2004 at 07:56:05AM -0600, Extropian Agroforestry Ventures Inc. wrote:
>
> United States Patent Application 20040097534
> Kind Code A1
> Choi, Byung-Kil ; et al. May 20, 2004
>
> ------------------------------------------------------------------------
> Composition for the protection and regeneration of nerve cells
> containing berberine derivatives
Apoptosis is one of damage mechanisms, and is indeed initiated by ischaemic
damage. Most of it occurs days after damage, and requires a working
metabolism. There are lots of drugs to block it.
If you need drugs to block ischaemic damage as a cryonics patient there's
something ran terribly wrong. (Blocking brain activity when on life support
after flat EEG lacune due to ischemia is something else, and something
really really necessary).
> Abstract
>
> 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.
>
> &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
>
> [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.
>
> &&&&&&&&&&&&&&&&&&&&&&&&&&&&&
>
> 2) Experimental Results
>
> (1) Concentration of Berberine, Influence of Body Temperature and
> Ischemia Inducing Time
>
> [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.
>
> [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.
>
> [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.
>
> (2) Observation of Damaged Nerve Cells
>
> [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).
>
> [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).
>
> (3) Protective Effect of Berberine Against Damage to Nerve Cells
>
> [0162] In order to examine the neuroprotective effect of berberine after
> ischemia induction, berberine was intraperitoneally injected 0 and 90
> minutes after ischemia induction.
>
> [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).
>
> [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.
>
> [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.
>
> * * * * *
>
> Aside from its carrier capacity DMSO was chosen for its ability to
> inhibit damage from a light freeze
>
> There are a number of complementary chemistries besides from the ones
> cited readily available.
>
>
>
> Eugen Leitl wrote:
>
> >On Wed, Dec 15, 2004 at 03:01:49AM -0600, Extropian Agroforestry Ventures
> >Inc. wrote:
> >
> >
> >
> >>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
> >>
> >>
> >
> >Useless. This gives you no advatage over an ice bath.
> >
> >
> >
> >>co2 based for higher cooling rate
> >>
> >>
> >
> >More than useless. You can't go below 0 C, or you'll get freezing injury.
> >
> >
> >
> >>-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
> >>
> >>
> >
> >You have to maintain the circulation. Best do achieve this is life support.
> >
> >
> >
> >>The adjuvants are designed to allow the brain to survive a longer
> >>cool-off time than the usual 3-5 minutes.
> >>
> >>
> >
> >Sorry, but your science is garbage. I'm being delibertely harsh here,
> >because
> >otherwise you won't get the message.
> >
> >
> >
> >>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
> >>
> >>
> >
> >If you have to live in the sticks, you have to rely on people. No machinery
> >is going to help.
> >
> >
> >
> >>Morris Johnson
> >>
> >>Hara Ra wrote:
> >>
> >>
> >>>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.
> >>>
> >>>
> >
> >Of course I wasn't commenting on what you wrote, but on periodical
> >resurgence
> >of well-meaning-but-clueless armchair cryonicists.
> >
> >
> >
> >>>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
> >>>
> >>>
> >
> >Oh yeah, if the cup breaks off you'll get a massive metal rod puncturing
> >the
> >ribcage.
> >
> >
> >
> >>>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
> >>>
> >>>
> >
> >Not if you add neuroprotectants via IV push, and maintain artificial
> >circulation.
> >
> >
> >
> >>>maintain circulation for the 3-5 minutes it takes to circulate the
> >>>medicines (a proprietary cocktail of anticoaguants, clot busters and
> >>>other stuff)
> >>>
> >>>
> >
> >
> >
> >
> >------------------------------------------------------------------------
> >
> >_______________________________________________
> >extropy-chat mailing list
> >extropy-chat at lists.extropy.org
> >http://lists.extropy.org/mailman/listinfo/extropy-chat
> >
> >
>
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--
Eugen* Leitl <a href="http://leitl.org">leitl</a>
______________________________________________________________
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http://moleculardevices.org http://nanomachines.net
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